LDL apheresis in the treatment of familial hypercholesterolemia: Experience of Hospital Santo António, Porto | Revista Portuguesa de Cardiologia (English edition)

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=> "f" "identificador" => "aff0030" ] ] ] 8 => array:3 [ "nombre" => "Maria Helena" "apellidos" => "Ramos" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] ] "afiliaciones" => array:6 [ 0 => array:3 [ "entidad" => "Serviço de Endocrinologia, Hospital Santo António – Centro Hospitalar do Porto, Porto, Portugal" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Serviço de Nefrologia, Hospital Santo António – Centro Hospitalar do Porto, Porto, Portugal" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Serviço de Química Clínica, Hospital Santo António – Centro Hospitalar do Porto, Porto, Portugal" "etiqueta" => "d" "identificador" => "aff0020" ] 4 => array:3 [ "entidad" => "Serviço de Cardiologia, Hospital Santo António – Centro Hospitalar do Porto, Porto, Portugal" "etiqueta" => "e" "identificador" => "aff0025" ] 5 => array:3 [ "entidad" => "Serviço de Neurologia, Hospital Santo António – Centro Hospitalar do Porto, Porto, Portugal" "etiqueta" => "f" "identificador" => "aff0030" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "pt" => array:1 [ "titulo" => "LDL-aférese no tratamento de hipercolesterolemia familiar: experiência do Hospital Santo António" ] ] "textoCompleto" => "IntroductionHypercholesterolemia in the form of elevated low-density lipoprotein cholesterol (LDL-C) is a major risk factor for the development and progression of coronary artery disease.<a class="elsevierStyleCrossRef" href="#bib0135">1</a>Familial hypercholesterolemia (FH) is a genetic disease of lipoprotein metabolism with autosomal dominant transmission in which affected individuals present very high LDL-C levels, tendon xanthomas and premature coronary artery disease.<a class="elsevierStyleCrossRef" href="#bib0140">2</a>FH is usually due to loss-of-function mutations in the gene encoding the LDL receptor (LDLR), although loss-of-function mutations in the gene encoding apolipoprotein B (ApoB) and gain-of-function mutations in the gene encoding proprotein convertase subtilisin/kexin type 9 (PCSK9) can also cause FH, albeit more rarely.<a class="elsevierStyleCrossRef" href="#bib0145">3</a>Mutations in the LDLR gene lead to absent or reduced production of the protein depending on the type of mutation; mutations in the APOB gene encode mutant ApoB 100 molecules, which have less affinity for LDLR, thus blocking or reducing the binding of ApoB to LDLR, while gain-of-function missense mutations in the PCSK9 gene enhance LDLR catabolism.<a class="elsevierStyleCrossRefs" href="#bib0150">4–7</a>Homozygous FH is extremely rare, with a prevalence of 1/1000000. Most cases of homozygosity involve either the same functional mutation in both alleles (true homozygotes) or different functional mutations in each allele (compound heterozygotes).Another rare condition that presents the same phenotype as homozygous FH is autosomal recessive hypercholesterolemia (ARH), which is caused by mutations in the gene encoding LDLR adaptor protein 1 (LDLRAP1) and the parents do not usually present dyslipidemia.<a class="elsevierStyleCrossRef" href="#bib0170">8</a>There are also rare cases of double heterozygosity, which present a more severe phenotype than patients with heterozygous FH but less severe than those with homozygous FH.<a class="elsevierStyleCrossRefs" href="#bib0175">9–11</a>Heterozygous FH is much more frequent than homozygous FH, with a prevalence of 1/300–500 individuals; it is thus one of the most common severe genetic diseases and is recognized as a public health problem by the World Health Organization (WHO),<a class="elsevierStyleCrossRefs" href="#bib0190">12,13</a> who estimate that over 10000000 individuals worldwide have FH. However, less than 10% are diagnosed and of these, less than 25% receive lipid-lowering therapy.<a class="elsevierStyleCrossRef" href="#bib0195">13</a>Treatment of dyslipidemia, for both primary and secondary prevention, focuses on reducing LDL-C. Numerous clinical trials have demonstrated the benefits of statin therapy in reducing LDL-C and cardiovascular (CV) morbidity and mortality.<a class="elsevierStyleCrossRefs" href="#bib0135">1,14</a>Among the non-pharmacological treatment options for severely hypercholesterolemic patients who are intolerant or refractory to lipid-lowering therapy is LDL apheresis. There are various techniques, all of which lead to significant and acute reduction in plasma LDL-C levels.<a class="elsevierStyleCrossRef" href="#bib0205">15</a> At Hospital Santo António, Porto, we use the technique of direct adsorption of lipoproteins (DALI).ObjectiveWe describe the experience of the multidisciplinary clinic for lipid disorders assessing severely hypercholesterolemic patients refractory to lipid-lowering therapy who underwent DALI LDL apheresis.MethodsSince 1993 the endocrinology department of Hospital Santo António has had a multidisciplinary clinic for lipid disorders, which includes specialists in endocrinology and nutrition and has a joint working protocol with the cardiology, neurology, clinical chemistry and nephrology departments. There is a weekly clinic whose main function is the study and treatment of severe lipid disorders, and DALI LDL apheresis has been available there since 2008.Direct adsorption of lipoproteinsIn this technique, whole blood is passed through an adsorber containing polyacrylamide gel. This consists of polyanions with negatively charged carboxylate groups that interact selectively with the cationic groups of Apo B found in very low density lipoprotein (VLDL), intermediate density lipoprotein (IDL), LDL and lipoprotein(a) (Lp(a)). Each of these lipoproteins contains a single molecule of Apo B, by which the lipoproteins are immobilized in the adsorber through electrochemical interactions.High-density lipoproteins (HDL) do not interact with the polyanions in the adsorber since they are coated with Apo A1, and are thus not eliminated by the technique.After passing through the adsorber, the blood depleted of all Apo B-containing lipoproteins is returned to the patient. Reductions in LDL-C of over 60% have been observed.<a class="elsevierStyleCrossRefs" href="#bib0210">16,17</a>The apheresis sessions were performed using the following equipment from Fresenius Medical Care, Germany: 4008 ADS monitor, DALI adsorbers, priming solution and acid citrate dextrose formula A (ACD-A). According to the German clinical guidelines, the aim of LDL apheresis is to achieve a reduction in LDL-C of ≥60% per session. Two configurations are available: DALI 750 and DALI 1000.<a class="elsevierStyleCrossRef" href="#bib0220">18</a>In patients indicated for prolonged or chronic treatment, the creation of an arteriovenous fistula is recommended in order to facilitate vascular access.The volume of blood processed per session is tailored to the patient's gender and weight, and flow rate varies between 60 and 100 ml/min.A patient is referred for LDL apheresis following agreement by the multidisciplinary team based on the criteria recommended by the US Food and Drug Administration (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).<a class="elsevierStyleCrossRef" href="#bib0225">19</a><elsevierMultimedia ident="tbl0005"></elsevierMultimedia>LDL apheresis is recommended for these patients if they have not attained therapeutic targets after six months of non-pharmacological or pharmacological therapy at the maximum tolerated dose.Laboratory testsLaboratory tests are performed by the clinical chemistry department of Hospital Santo António using a Cobas Integra 800 analyzer (Roche Diagnostics) and appropriate reagents.Blood samples are obtained directly via the afferent line immediately before the start of each session. Samples are collected via the same line at the end of treatment before the extracorporeal circuit is rinsed with saline.Measurement of lipid parametersAcute percentage reductions in lipid parameters in a single treatment are calculated according to the following formula: 100×(pre-session value−post-session value)/pre-session value.Long-term reductions in each lipid parameter are calculated from the baseline value prior to the first session, the mean value after the antepenultimate session (post-session n-2), before the penultimate session (pre-session n-1), after the penultimate session (post-session n-1) and before the last session (pre-session n),<a class="elsevierStyleCrossRefs" href="#bib0215">17,20</a> according to the following formulas:<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005">•Long-term percentage reduction in lipid parameters: 100×(baseline value−mean value)/baseline value</li><li class="elsevierStyleListItem" id="lsti0010">•Mean value of lipid parameters: (post-session value n-2+pre-session value n-1+post-session value n-1+pre-session value n)/4.n-2, n-1 and n refer to the last three sessions in chronological order from the earliest to the last, respectively.The same formulas were used for all lipid parameters: LDL-C, triglycerides (TG), total cholesterol (TC), HDL-C and non-HDL-C, the latter being calculated as the difference between TC and HDL-C.</li></ul>ResultsPatientsAll patients underwent fortnightly sessions of DALI LDL apheresis lasting an average of 90 min while maintaining previous pharmacological therapy.Patient 1A 55-year-old man had been diagnosed with asymptomatic ischemic heart disease on exercise testing at age 37, followed by stenting in 1995 for critical stenosis of the right coronary artery and placement of two further stents in 2010 due to restenosis of the same artery.He had no CV risk factors including smoking, diabetes mellitus (DM), hypertension, family history of premature ischemic heart disease or dyslipidemia and was not overweight (body mass index [BMI] 23.8 kg/m2).His pre-treatment lipid profile was TC 390 mg/dl, TG 140 mg/dl, HDL-C 50 mg/dl, LDL-C 312 mg/dl, Apo A1 109 mg/dl and Apo B 186 mg/dl, with no other abnormalities on laboratory tests.Since the patient presented sustained elevation of transaminases under therapy with rosuvastatin 40 mg/day, intolerance to resins manifested as constipation and severe flushing with nicotinic acid, he was medicated with rosuvastatin 20 mg/day (maximum tolerated dose) and ezetimibe 10 mg/day. He was also taking diltiazem 120 mg, clopidogrel 75 mg and aspirin 100 mg. However, his dyslipidemia was refractory to maximum tolerated pharmacological therapy.Genetic study showed a heterozygous functional mutation in the PCSK9 gene.He began LDL apheresis as adjuvant therapy in December 2008 using the DALI 750 filter, while maintaining his usual lipid-lowering therapy.Four years after beginning LDL apheresis, carotid Doppler ultrasound showed diffuse carotid atherosclerosis with mild stenosis (<20%) of the right and left internal carotid arteries; myocardial perfusion study revealed no evidence of ischemia, a mild fixed inferolateral defect and good left ventricular global systolic function.Patient 2A 59-year-old man had been diagnosed with severe dyslipidemia in routine laboratory tests at the age of 36. He had xanthelasmas and tendon xanthomas and asymptomatic carotid atherosclerosis, with >70% stenosis of the right internal carotid artery and 50–70% stenosis of the left internal carotid artery. He underwent elective endarterectomy of the right internal carotid artery in March 2007.He was a former smoker, of normal weight (BMI 22.8 kg/m2), and had a family history of dyslipidemia (mother, siblings and daughter with hypercholesterolemia) and no other CV risk factors.His pre-treatment lipid profile was TC 378 mg/dl, TG 75 mg/dl, HDL-C 112 mg/dl, LDL-C 251 mg/dl, Apo A1 223 mg/dl and Apo B 176 mg/dl, with no other abnormalities on laboratory tests.Since the patient experienced myalgia on rosuvastatin 40 mg/day, intolerance to resins at the maximum recommended dose and worsening gastric disease (peptic ulcer) with nicotinic acid, he was medicated with cholestyramine 8 g/day, rosuvastatin 20 mg/day and ezetimibe 10 mg/day, as well as aspirin 325 mg, valsartan 160 mg and esomeprazole 40 mg.Genetic study showed a heterozygous functional mutation in the LDLR gene.He began LDL apheresis in March 2009 using the DALI 750 configuration, while maintaining his previous lipid-lowering therapy.Fours years after beginning LDL apheresis, carotid Doppler ultrasound showed diffuse atherosclerosis with mild stenosis (<20%) of the right internal carotid artery and moderate stenosis of the left internal carotid artery, with an echogenic, partially calcified atheromatous plaque causing 30–50% stenosis but with normal carotid flow. Myocardial perfusion study was suggestive of mild ischemia in the territory of the anterior descending artery, but with good left ventricular global systolic function.Patient 3A 62-year-old woman with severe symptomatic aortic stenosis underwent aortic valve replacement with a mechanical prosthesis in July 2010. She also had asymptomatic carotid arteriosclerosis, atheromas in the common carotid arteries and proximal internal carotid arteries with <30% stenosis.She had a family history of dyslipidemia (daughter and grandson with hypercholesterolemia), was of normal weight (BMI 22.7 kg/m2) and had no other CV risk factors (non-smoker, no hypertension or DM and no family history of premature CV disease).Her pre-treatment lipid profile was TC 379 mg/dl, TG 71 mg/dl, HDL-C 67 mg/dl, LDL-C 298 mg/dl, Apo A1 120 mg/dl and Apo B 184 mg/dl, with no other abnormalities on laboratory tests.Since the patient was intolerant to rosuvastatin 40 mg and resins, she was medicated with rosuvastatin 20 mg, nicotinic acid 1 g (maximum tolerated), ezetimibe 10 mg, warfarin 5 mg, aspirin 100 mg and diazepam 5 mg.Genetic study showed a heterozygous functional mutation in the LDLR gene and another mutation of unknown significance in the same gene; functional studies are in progress to assess the pathogenicity of this alteration, and if confirmed, the patient will be classified as a compound heterozygote.She began LDL apheresis in March 2009, while maintaining her usual lipid-lowering therapy. Due to the lack of adequate response to the DALI 750 configuration, the DALI 1000 filter was subsequently used.<a class="elsevierStyleCrossRef" href="#bib0220">18</a>Four years after beginning LDL apheresis, carotid Doppler ultrasound showed an atheroma with regular contours in the right internal carotid artery with <30% stenosis and <20% stenosis in the left internal carotid artery; myocardial perfusion study was within normal limits, with good left ventricular global systolic function.ComplicationsBetween December 2008 and January 2013, 308 treatments were performed (<a class="elsevierStyleCrossRefs" href="#tbl0010">Tables 2–6</a>), during which there were 11 complications – 10 minor and one major – including six episodes of chest pain, three of hypotension (one accompanied by an anaphylactic reaction) and one of clotting of the extracorporeal circuit.<elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><elsevierMultimedia ident="tbl0025"></elsevierMultimedia><elsevierMultimedia ident="tbl0030"></elsevierMultimedia>DiscussionSimilar to reports in the literature, 96.4% of the sessions were uneventful.<a class="elsevierStyleCrossRef" href="#bib0235">21</a> The overall incidence of adverse events was 3.6%, also similar to that reported by other authors, and treatment had to be suspended in only one case.<a class="elsevierStyleCrossRef" href="#bib0235">21</a> No prolonged or irreversible adverse effects were seen in any patient.Comparing the adverse effects in our patients with those observed by Bosch et al.,<a class="elsevierStyleCrossRef" href="#bib0235">21</a> the most common adverse effect in our population was angina (1.95% vs. 0.09%), followed by hypotension (0.97% vs. 0.97%), clotting of the extracorporeal circuit (0.32% vs. 0.03%) and anaphylactic reaction (0.32% vs. 0%).There were six episodes of angina during the 308 LDL apheresis sessions, a higher percentage than that reported in the literature.<a class="elsevierStyleCrossRef" href="#bib0235">21</a> These all occurred in the same patient, who had critical aortic valve stenosis, and were reversed by reducing flow rate and administering fluids, oxygen and nitrates. The etiology of the angina was probably multifactorial but we believe the underlying aortic stenosis was the main factor, since following surgical treatment, there were no further episodes of angina.Hypotension is reported as the most common complication of LDL apheresis.<a class="elsevierStyleCrossRefs" href="#bib0210">16,20,21</a> This may be due to hypovolemia, vasodilation or vasovagal reaction. In the DALI technique, the negatively charged surfaces of the adsorber increase concentrations of factor XII, kallikrein and bradykinin. Bradykinin can cause hypotension, flushing and Quincke's edema. Although it is generated in the adsorber and reinfused into the patient, it is rapidly degraded by angiotensin-converting enzyme (ACE), so levels in the pre-adsorber afferent line are negligible.<a class="elsevierStyleCrossRefs" href="#bib0210">16,22</a>The main cause of hypovolemia during DALI apheresis appears to be the initial transfer of blood to the extracorporeal circuit. Like other authors, we replace part of the initial blood volume with saline solution in the contralateral vein while the extracorporeal circuit is filling in order to minimize this effect and prevent hypotension.<a class="elsevierStyleCrossRef" href="#bib0210">16</a>One of the three cases of hypotension was more severe and accompanied by pallor, dyspnea and a feeling of imminent death. This was in a patient who had been prescribed ramipril for the first time and took it inadvertently on the day of the LDL apheresis session. This episode was interpreted as an anaphylactic reaction. The DALI technique can cause severe hypotension in patients taking ACE inhibitors due to decreased bradykinin catabolism through ACE inhibition and the increased bradykinin production associated with the procedure. Drugs that inhibit degradation of bradykinin into inactive metabolites are thus contraindicated in patients undergoing DALI LDL apheresis.<a class="elsevierStyleCrossRefs" href="#bib0235">21,23</a>In order to avoid the risk of hypotension in patients undergoing DALI apheresis, ACE inhibitors should be suspended 24 hours before treatment and whenever possible replaced by other antihypertensive drugs, such as angiotensin receptor blockers, that do not inhibit ACE.Of the three cases of hypotension, two were resolved with intravenous fluid therapy and reduction of flow rate; in the more severe case, LDL apheresis was suspended and oxygen, fluid and intravenous corticosteroid therapy were required.As described in the literature, 1 ml of ACD-A per 20–40 ml of blood was used to prevent clotting of the extracorporeal circuit, which proved adequate for anticoagulation.<a class="elsevierStyleCrossRefs" href="#bib0230">20,21</a> In 308 sessions, there was only one episode of clotting of the extracorporeal circuit (0.32% vs. 0.17%).<a class="elsevierStyleCrossRef" href="#bib0230">20</a>Besides lipoproteins, the DALI column also adsorbs positively charged ions such as calcium and magnesium. We observed no hypocalcemia or hypomagnesemia in our experience, but like other authors we used a priming solution that contains these electrolytes, saturating the column with these cations and thus preventing hypocalcemia and hypomagnesemia during treatment; in addition, an ampoule of calcium gluconate was used prophylactically at the end of each session.<a class="elsevierStyleCrossRef" href="#bib0250">24</a>Iron deficiency, leading to microcytic anemia, has also been reported in patients under chronic LDL apheresis. This may be due to frequent laboratory tests and residual blood loss in the extracorporeal system after each session. No iron deficiency or anemia was observed in our patients.We used the methodology previously described by us and other authors<a class="elsevierStyleCrossRefs" href="#bib0215">17,20</a> to assess the technique's efficacy in terms of lipid parameters.Mean acute reductions in LDL-C of 63.3% (57.3–69.6%) were obtained, which are similar to those described by other authors and meet the objectives stated in the German clinical guidelines for LDL apheresis.<a class="elsevierStyleCrossRefs" href="#bib0220">18,21</a>With regard to long-term reductions in LDL-C, we achieved a mean reduction of 36.0% (25.6–44.2%), slightly lower than reported in the literature<a class="elsevierStyleCrossRef" href="#bib0235">21</a>; however, we believe that the difference may be explained by the longer treatment time and larger number of patients, as well as better patient compliance with drug therapy, in these studies.We obtained a mean acute reduction in non-HDL-C of 62.3% (55.1–68.4%) and a mean long-term reduction of 35.5% (23.9–45.4%), comparable to those seen for LDL-C. We believe that this was due to the characteristics of our patients’ dyslipidemia: hypercholesterolemia but no DM, obesity or metabolic syndrome criteria, and hence no factors that promote the production of VLDL or IDL. On the other hand, it may have been due to TG values of <400, as reflected in a low error rate in calculating LDL-C by the Friedewald formula.<a class="elsevierStyleCrossRef" href="#bib0255">25</a>Acute reductions in HDL-C were similar to those obtained by other authors and are related to low TG levels, which in turn depend heavily on the food ingested prior to treatment sessions. No significant long-term changes in HDL-C were observed, which demonstrates the selectivity of DALI LDL apheresis.ConclusionThe results reflect the efficacy and selectivity of DALI LDL apheresis and are comparable to those obtained in previous studies of the technique.<a class="elsevierStyleCrossRefs" href="#bib0230">20,21</a>In 308 sessions over a 49-month period the technique was shown to be safe, effective and selective for LDL-C, with acute reductions of over 60% and no significant changes in other lipoproteins. The main objective of LDL-C reduction is to prevent the development and progression of atherosclerosis, and the improvement seen in our patients’ lipid profiles was reflected in the absence of disease progression. The selective elimination of LDL-C by DALI apheresis is an important advance in the treatment of hypercholesterolemic patients with high CV risk.<a class="elsevierStyleCrossRef" href="#bib0260">26</a>LDL apheresis in conjunction with lipid-lowering therapy prevented the development of atherosclerosis in patients with severe dyslipidemia and high CV risk.The low incidence of complications means that LDL apheresis is well tolerated by patients, which is reflected in the high rate of adhesion to the treatment.DALI LDL apheresis was shown to be a simple, safe and effective treatment in patients with FH refractory to diet modification and pharmacological therapy and should be considered as an adjuvant therapy for hypercholesterolemic patients who are intolerant or refractory to statin therapy and for those with contraindications to drug therapy.Ethical disclosuresProtection of human and animal subjectsThe authors declare that no experiments were performed on humans or animals for this study.Confidentiality of dataThe authors declare that they have followed the protocols of their work center on the publication of patient data.Right to privacy and informed consentThe authors have obtained the written informed consent of the patients or subjects mentioned in the article. The corresponding author is in possession of this document.Conflicts of interestThe authors have no conflicts of interest to declare." "textoCompletoSecciones" => array:1 [ "secciones" => array:14 [ 0 => array:3 [ "identificador" => "xres469290" "titulo" => "Abstract" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Objective" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Methods" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Results" ] 4 => array:2 [ "identificador" => "abst0025" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec491902" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres469291" "titulo" => "Resumo" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0030" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec491903" "titulo" => "Palavras-chave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Objective" ] 6 => array:3 [ "identificador" => "sec0015" "titulo" => "Methods" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0020" "titulo" => "Direct adsorption of lipoproteins" ] 1 => array:2 [ "identificador" => "sec0025" "titulo" => "Laboratory tests" ] 2 => array:2 [ "identificador" => "sec0030" "titulo" => "Measurement of lipid parameters" ] ] ] 7 => array:3 [ "identificador" => "sec0035" "titulo" => "Results" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "sec0040" "titulo" => "Patients" ] 1 => array:2 [ "identificador" => "sec0045" "titulo" => "Patient 1" ] 2 => array:2 [ "identificador" => "sec0050" "titulo" => "Patient 2" ] 3 => array:2 [ "identificador" => "sec0055" "titulo" => "Patient 3" ] 4 => array:2 [ "identificador" => "sec0060" "titulo" => "Complications" ] ] ] 8 => array:2 [ "identificador" => "sec0065" "titulo" => "Discussion" ] 9 => array:2 [ "identificador" => "sec0070" "titulo" => "Conclusion" ] 10 => array:3 [ "identificador" => "sec0075" "titulo" => "Ethical disclosures" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0080" "titulo" => "Protection of human and animal subjects" ] 1 => array:2 [ "identificador" => "sec0085" "titulo" => "Confidentiality of data" ] 2 => array:2 [ "identificador" => "sec0090" "titulo" => "Right to privacy and informed consent" ] ] ] 11 => array:2 [ "identificador" => "sec0095" "titulo" => "Conflicts of interest" ] 12 => array:2 [ "identificador" => "xack141264" "titulo" => "Acknowledgments" ] 13 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2013-05-29" "fechaAceptado" => "2014-07-31" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec491902" "palabras" => array:5 [ 0 => "Direct adsorption of lipoprotein apheresis" 1 => "Low-density lipoprotein apheresis" 2 => "Cardiovascular disease" 3 => "Elevated serum lipoprotein(a)" 4 => "Familial hypercholesterolemia" ] ] ] "pt" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palavras-chave" "identificador" => "xpalclavsec491903" "palabras" => array:5 [ 0 => "DALI aférese" 1 => "LDL-aférese" 2 => "Doença cardiovascular" 3 => "Lipoproteína (a) elevada" 4 => "Hipercolesterolemia familiar" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "IntroductionHigh plasma levels of low-density lipoprotein (LDL) cholesterol are a risk factor for the development of premature atherosclerosis. Direct adsorption of lipoproteins (DALI) is an apheresis technique by which LDL cholesterol is selectively removed from whole blood. ObjectiveThe present study describes our experience with DALI LDL apheresis in severely hypercholesterolemic patients. MethodsThree hypercholesterolemic patients suffering from atherosclerotic complications were treated fortnightly by DALI apheresis, in a total of 308 sessions between December 2008 and January 2013. All patients were on the highest tolerated dose of statins and other lipid-lowering drugs. ResultsThe sessions were essentially uneventful, adverse events being recorded in only 3.6% of them. A mean 63.3% acute reduction in LDL cholesterol was obtained. ConclusionsDALI apheresis proved to be a simple, safe and efficient method of lipid apheresis in hypercholesterolemic patients refractory to conservative lipid-lowering therapy." "secciones" => array:5 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Objective" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Methods" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Results" ] 4 => array:2 [ "identificador" => "abst0025" "titulo" => "Conclusions" ] ] ] "pt" => array:2 [ "titulo" => "Resumo" "resumen" => "A hipercolesterolemia manifestada pelos níveis elevados de colesterol das lipoproteínas de baixa densidade constitui um fator de risco major para o desenvolvimento e progressão da doença aterosclerótica prematura.A adsorção direta de lipoproteínas é uma técnica de LDL-aférese na qual o LDL-c pode ser seletivamente removido do sangue total.Este trabalho partilha a experiência da LDL-aférese pela técnica de adsorção direta de lipoproteínas no tratamento de doentes com hipercolesterolemia severa.Três doentes com hipercolesterolemia e doença aterosclerótica documentada foram tratados quinzenalmente com LDL-aférese pela técnica de adsorção direta de lipoproteínas, realizando no total 308 sessões entre dezembro de 2008 e janeiro de 2013. Todos os doentes estavam medicados com estatinas e outros fármacos hipolipemiantes na dose máxima tolerada.As sessões decorreram na generalidade sem intercorrências. A incidência global de efeitos adversos reportados durante as sessões foi de 3,6%. Em relação aos parâmetros lipídicos obtivemos reduções agudas do colesterol das lipoproteínas de baixa densidade da ordem dos 63,3% (mínimo de 57,3% e máximo de 69,6%).Em resumo, a LDL-aférese pela técnica de adsorção direta de lipoproteínas demonstrou ser um procedimento simples, seguro e eficaz em doentes com hipercolesterolemia resistentes ao tratamento instituído." ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Palma I, Caldas AR, Palma IM, Queirós JA, Madureira A, Oliveira JC, et al. LDL-aférese no tratamento de hipercolesterolemia familiar: experiência do Hospital Santo António – CHP. Rev Port Cardiol. 2015;34:163–172." ] ] "nomenclatura" => array:1 [ 0 => array:3 [ "identificador" => "nom0005" "titulo" => "List of abbreviations" "listaDefinicion" => array:1 [ 0 => array:1 [ "definicion" => array:23 [ 0 => array:2 [ "termino" => "ACD-A" "descripcion" => "acid citrate dextrose formula A" ] 1 => array:2 [ "termino" => "ACE" "descripcion" => "angiotensin-converting enzyme" ] 2 => array:2 [ "termino" => "Apo A1" "descripcion" => "apolipoprotein A1" ] 3 => array:2 [ "termino" => "Apo B" "descripcion" => "apolipoprotein B 100" ] 4 => array:2 [ "termino" => "ARH" "descripcion" => "autosomal recessive hypercholesterolemia" ] 5 => array:2 [ "termino" => "BMI" "descripcion" => "body mass index" ] 6 => array:2 [ "termino" => "CV" "descripcion" => "cardiovascular" ] 7 => array:2 [ "termino" => "DALI" "descripcion" => "direct adsorption of lipoproteins" ] 8 => array:2 [ "termino" => "DM" "descripcion" => "diabetes mellitus" ] 9 => array:2 [ "termino" => "FH" "descripcion" => "familial hypercholesterolemia" ] 10 => array:2 [ "termino" => "HDL" "descripcion" => "high-density lipoprotein" ] 11 => array:2 [ "termino" => "HDL-C" "descripcion" => "high-density lipoprotein cholesterol" ] 12 => array:2 [ "termino" => "IDL" "descripcion" => "intermediate density lipoprotein" ] 13 => array:2 [ "termino" => "LDL" "descripcion" => "low-density lipoprotein" ] 14 => array:2 [ "termino" => "LDL-C" "descripcion" => "low-density lipoprotein cholesterol" ] 15 => array:2 [ "termino" => "LDLR" "descripcion" => "low-density lipoprotein receptor" ] 16 => array:2 [ "termino" => "LDLRAP1" "descripcion" => "low-density lipoprotein receptor adaptor protein 1" ] 17 => array:2 [ "termino" => "Lp(a)" "descripcion" => "lipoprotein(a)" ] 18 => array:2 [ "termino" => "PCSK9" "descripcion" => "proprotein convertase subtilisin/kexin type 9" ] 19 => array:2 [ "termino" => "TC" "descripcion" => "total cholesterol" ] 20 => array:2 [ "termino" => "TG" "descripcion" => "triglycerides" ] 21 => array:2 [ "termino" => "VLDL" "descripcion" => "very-low-density lipoprotein" ] 22 => array:2 [ "termino" => "WHO" "descripcion" => "World Health Organization" ] ] ] ] ] ] "multimedia" => array:6 [ 0 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "DM: diabetes mellitus; CV: cardiovascular; FH: familial hypercholesterolemia; HDL-C: high-density lipoprotein cholesterol; LDL-C: low-density lipoprotein cholesterol; Lp(a): lipoprotein(a)." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Patients with homozygous FH, LDL-C ≥300 mg/dl or non-HDL-C ≥330 mg/dl \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Patients with heterozygous FH, LDL-C ≥300 mg/dl or non-HDL-C ≥330 mg/dl and 0–1 risk factors \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Patients with heterozygous FH, LDL-C ≥200 mg/dl or non-HDL-C ≥230 mg/dl and high risk, characterized by ≥2 risk factors or Lp(a) ≥50 mg/dl \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Patients with heterozygous FH, with LDL-C ≥60 or non-HDL-C ≥190 and very high CV risk (established CAD or other CV disease or DM) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab726701.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Selection criteria for LDL apheresis recommended by the US Food and Drug Administration." ] ] 1 => array:7 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "LDL-C: low-density lipoprotein cholesterol. n-2, n-1 and n refer to the last three sessions; pre and post: values before and after treatment sessions; ↓Acute: acute reduction; ↓Long-term: long-term reduction." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col">Patient \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col">Baseline LDL-C(mg/dl) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " colspan="3" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Session n-2</th><th class="td" title="table-head " colspan="3" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Session n-1</th><th class="td" title="table-head " colspan="3" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Session n</th><th class="td" title="table-head " align="left" valign="top" scope="col">Mean LDL-C(mg/dl) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col">↓Long-term(%) \t\t\t\t\t\t\n \t\t\t\t</th></tr><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Pre(mg/dl) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Post(mg/dl) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">↓Acute(%) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Pre(mg/dl) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Post(mg/dl) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">↓Acute(%) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Pre(mg/dl) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Post(mg/dl) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">↓Acute(%) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">312 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">239 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">101 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">57.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">245 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">91 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">62.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">259 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">102 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">60.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">174 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">44.2 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">251 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">344 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">147 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">57.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">259 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">93 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">64.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">248 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">98 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">60.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">187 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">25.6 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">298 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">287 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">88 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">69.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">280 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">85 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">69.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">285 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">90 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">68.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">185 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">38.1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Mean \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">61.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">65.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">63.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">36.0 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab726704.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Acute and long-term reductions in low-density lipoprotein cholesterol by direct adsorption of lipoprotein LDL apheresis." ] ] 2 => array:7 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "HDL-C: high-density lipoprotein cholesterol. n-2, n-1 and n refer to the last three sessions; pre and post: values before and after treatment sessions; ↓Acute: acute reduction; ↓Long-term: long-term reduction." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col">Patient \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col">Baseline HDL-C(mg/dl) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " colspan="3" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Session n-2</th><th class="td" title="table-head " colspan="3" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Session n-1</th><th class="td" title="table-head " colspan="3" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Session n</th><th class="td" title="table-head " align="left" valign="top" scope="col">Mean HDL-C(mg/dl) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col">↓Long-term(%) \t\t\t\t\t\t\n \t\t\t\t</th></tr><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Pre(mg/dl) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Post(mg/dl) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">↓Acute(%) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Pre(mg/dl) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Post(mg/dl) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">↓Acute(%) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Pre(mg/dl) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Post(mg/dl) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">↓Acute(%) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">50 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">52 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">48 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">51 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">44 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">13.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">53 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">48 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">9.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">49 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.0 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">112 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">101 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">94 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">132 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">118 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">10.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">118 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">103 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">12.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">116 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−3.1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">67 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">59 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">64 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−8.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">75 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">67 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">10.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">76 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">64 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">15.8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">71 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−5.2 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Mean \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">11.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">12.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−2.1 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab726703.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Acute and long-term reductions in high-density lipoprotein cholesterol by direct adsorption of lipoprotein LDL apheresis." ] ] 3 => array:7 [ "identificador" => "tbl0020" "etiqueta" => "Table 4" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "TG: triglycerides. n-2, n-1 and n refer to the last three sessions; pre and post: values before and after treatment sessions; ↓Acute: acute reduction; ↓Long-term: long-term reduction." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col">Patient \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col">Baseline TG(mg/dl) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " colspan="3" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Session n-2</th><th class="td" title="table-head " colspan="3" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Session n-1</th><th class="td" title="table-head " colspan="3" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Session n</th><th class="td" title="table-head " align="left" valign="top" scope="col">Mean TG(mg/dl) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col">↓Long-term(%) \t\t\t\t\t\t\n \t\t\t\t</th></tr><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Pre(mg/dl) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Post(mg/dl) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">↓Acute(%) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Pre(mg/dl) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Post(mg/dl) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">↓Acute(%) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Pre(mg/dl) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Post(mg/dl) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">↓Acute(%) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">140 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">92 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">36 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">60.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">74 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">24 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">67.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">98 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">39 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">60.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">58 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">58.6 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">75 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">158 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">111 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">29.8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">67 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">31 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">53.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">109 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">103 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">80 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−6.0 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">71 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">108 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">37 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">65.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">72 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">38 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">47.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">74 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">37 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">50.0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">55 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">22.2 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Mean \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">52.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">56.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">38.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">24.9 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab726706.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Acute and long-term reductions in triglycerides by direct adsorption of lipoprotein LDL apheresis." ] ] 4 => array:7 [ "identificador" => "tbl0025" "etiqueta" => "Table 5" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "TC: total cholesterol. n-2, n-1 and n refer to the last three sessions; pre and post: values before and after treatment sessions; ↓Acute: acute reduction; ↓Long-term: long-term reduction." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col">Patient \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col">Baseline TC(mg/dl) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " colspan="3" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Session n-2</th><th class="td" title="table-head " colspan="3" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Session n-1</th><th class="td" title="table-head " colspan="3" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Session n</th><th class="td" title="table-head " align="left" valign="top" scope="col">Mean TC(mg/dl) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col">↓Long-term(%) \t\t\t\t\t\t\n \t\t\t\t</th></tr><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Pre(mg/dl) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Post(mg/dl) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">↓Acute(%) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Pre(mg/dl) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Post(mg/dl) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">↓Acute(%) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Pre(mg/dl) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Post(mg/dl) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">↓Acute(%) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">390 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">309 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">156 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">49.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">311 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">140 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">55.0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">332 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">158 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">52.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">235 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">39.8 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">378 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">477 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">263 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">44.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">404 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">217 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">46.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">388 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">222 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">42.8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">318 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">15.9 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">379 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">360 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">159 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">55.8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">369 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">160 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">56.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">376 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">161 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">57.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">266 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">29.8 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Mean \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">50.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">52.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">50.8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">28.5 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab726702.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Acute and long-term reductions in total cholesterol by direct adsorption of lipoprotein LDL apheresis." ] ] 5 => array:7 [ "identificador" => "tbl0030" "etiqueta" => "Table 6" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "HDL-C: high-density lipoprotein cholesterol. n-2, n-1 and n refer to the last three sessions; pre and post: values before and after treatment sessions; ↓Acute: acute reduction; ↓Long-term: long-term reduction." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col">Patient \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col">Baseline non-HDL-C(mg/dl) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " colspan="3" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Session n-2</th><th class="td" title="table-head " colspan="3" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Session n-1</th><th class="td" title="table-head " colspan="3" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Session n</th><th class="td" title="table-head " align="left" valign="top" scope="col">Mean non-HDL-C(mg/dl) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col">↓Long-term(%) \t\t\t\t\t\t\n \t\t\t\t</th></tr><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Pre(mg/dl) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Post(mg/dl) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">↓Acute(%) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Pre(mg/dl) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Post(mg/dl) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">↓Acute(%) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Pre(mg/dl) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Post(mg/dl) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">↓Acute(%) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">340 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">257 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">108 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">58.0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">260 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">96 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">63.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">279 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">110 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">60.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">186 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">45.4 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">266 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">376 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">169 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">55.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">272 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">99 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">63.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">270 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">119 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">55.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">203 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">23.9 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">312 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">301 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">95 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">68.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">294 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">93 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">68.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">300 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">97 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">67.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">196 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">37.3 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Mean \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">60.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">65.0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">61.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">35.5 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab726705.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Acute and long-term reductions in non-high-density lipoprotein cholesterol by direct adsorption of lipoprotein LDL apheresis." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:26 [ 0 => array:3 [ "identificador" => "bib0135" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:1 [ "titulo" => "Expert panel on detection, evaluation, and treatment of high blood cholesterol in adults: third report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III) final report" ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Circulation" 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Original Article

LDL apheresis in the treatment of familial hypercholesterolemia: Experience of Hospital Santo António, Porto

LDL-aférese no tratamento de hipercolesterolemia familiar: experiência do Hospital Santo António

Isabel Palmaa,

Corresponding author

isabel.m.mangas@gmail.com

Corresponding author.

, Ana Rita Caldasa, Isabel Mangas Palmab, José Alexandre Queirósc, Anselmo Madureirac, José Carlos Oliveirad, Paulo Palmae, Carlos Correiaf, Maria Helena Ramosa

a Serviço de Endocrinologia, Hospital Santo António – Centro Hospitalar do Porto, Porto, Portugal

b Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal

c Serviço de Nefrologia, Hospital Santo António – Centro Hospitalar do Porto, Porto, Portugal

d Serviço de Química Clínica, Hospital Santo António – Centro Hospitalar do Porto, Porto, Portugal

e Serviço de Cardiologia, Hospital Santo António – Centro Hospitalar do Porto, Porto, Portugal

f Serviço de Neurologia, Hospital Santo António – Centro Hospitalar do Porto, Porto, Portugal

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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Introduction</span><p id="par0120" class="elsevierStylePara elsevierViewall">Hypercholesterolemia in the form of elevated low-density lipoprotein cholesterol &#40;LDL-C&#41; is a major risk factor for the development and progression of coronary artery disease&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">1</span></a></p><p id="par0125" class="elsevierStylePara elsevierViewall">Familial hypercholesterolemia &#40;FH&#41; is a genetic disease of lipoprotein metabolism with autosomal dominant transmission in which affected individuals present very high LDL-C levels&#44; tendon xanthomas and premature coronary artery disease&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">2</span></a></p><p id="par0130" class="elsevierStylePara elsevierViewall">FH is usually due to loss-of-function mutations in the gene encoding the LDL receptor &#40;LDLR&#41;&#44; although loss-of-function mutations in the gene encoding apolipoprotein B &#40;ApoB&#41; and gain-of-function mutations in the gene encoding proprotein convertase subtilisin&#47;kexin type 9 &#40;PCSK9&#41; can also cause FH&#44; albeit more rarely&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">3</span></a></p><p id="par0135" class="elsevierStylePara elsevierViewall">Mutations in the <span class="elsevierStyleItalic">LDLR</span> gene lead to absent or reduced production of the protein depending on the type of mutation&#59; mutations in the <span class="elsevierStyleItalic">APOB</span> gene encode mutant ApoB 100 molecules&#44; which have less affinity for LDLR&#44; thus blocking or reducing the binding of ApoB to LDLR&#44; while gain-of-function missense mutations in the <span class="elsevierStyleItalic">PCSK9</span> gene enhance LDLR catabolism&#46;<a class="elsevierStyleCrossRefs" href="#bib0150"><span class="elsevierStyleSup">4&#8211;7</span></a></p><p id="par0140" class="elsevierStylePara elsevierViewall">Homozygous FH is extremely rare&#44; with a prevalence of 1&#47;1<span class="elsevierStyleHsp" style=""></span>000<span class="elsevierStyleHsp" style=""></span>000&#46; Most cases of homozygosity involve either the same functional mutation in both alleles &#40;true homozygotes&#41; or different functional mutations in each allele &#40;compound heterozygotes&#41;&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">Another rare condition that presents the same phenotype as homozygous FH is autosomal recessive hypercholesterolemia &#40;ARH&#41;&#44; which is caused by mutations in the gene encoding LDLR adaptor protein 1 &#40;LDLRAP1&#41; and the parents do not usually present dyslipidemia&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">8</span></a></p><p id="par0150" class="elsevierStylePara elsevierViewall">There are also rare cases of double heterozygosity&#44; which present a more severe phenotype than patients with heterozygous FH but less severe than those with homozygous FH&#46;<a class="elsevierStyleCrossRefs" href="#bib0175"><span class="elsevierStyleSup">9&#8211;11</span></a></p><p id="par0155" class="elsevierStylePara elsevierViewall">Heterozygous FH is much more frequent than homozygous FH&#44; with a prevalence of 1&#47;300&#8211;500 individuals&#59; it is thus one of the most common severe genetic diseases and is recognized as a public health problem by the World Health Organization &#40;WHO&#41;&#44;<a class="elsevierStyleCrossRefs" href="#bib0190"><span class="elsevierStyleSup">12&#44;13</span></a> who estimate that over 10<span class="elsevierStyleHsp" style=""></span>000<span class="elsevierStyleHsp" style=""></span>000 individuals worldwide have FH&#46; However&#44; less than 10&#37; are diagnosed and of these&#44; less than 25&#37; receive lipid-lowering therapy&#46;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">13</span></a></p><p id="par0160" class="elsevierStylePara elsevierViewall">Treatment of dyslipidemia&#44; for both primary and secondary prevention&#44; focuses on reducing LDL-C&#46; Numerous clinical trials have demonstrated the benefits of statin therapy in reducing LDL-C and cardiovascular &#40;CV&#41; morbidity and mortality&#46;<a class="elsevierStyleCrossRefs" href="#bib0135"><span class="elsevierStyleSup">1&#44;14</span></a></p><p id="par0165" class="elsevierStylePara elsevierViewall">Among the non-pharmacological treatment options for severely hypercholesterolemic patients who are intolerant or refractory to lipid-lowering therapy is LDL apheresis&#46; There are various techniques&#44; all of which lead to significant and acute reduction in plasma LDL-C levels&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">15</span></a> At Hospital Santo Ant&#243;nio&#44; Porto&#44; we use the technique of direct adsorption of lipoproteins &#40;DALI&#41;&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Objective</span><p id="par0170" class="elsevierStylePara elsevierViewall">We describe the experience of the multidisciplinary clinic for lipid disorders assessing severely hypercholesterolemic patients refractory to lipid-lowering therapy who underwent DALI LDL apheresis&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Methods</span><p id="par0175" class="elsevierStylePara elsevierViewall">Since 1993 the endocrinology department of Hospital Santo Ant&#243;nio has had a multidisciplinary clinic for lipid disorders&#44; which includes specialists in endocrinology and nutrition and has a joint working protocol with the cardiology&#44; neurology&#44; clinical chemistry and nephrology departments&#46; There is a weekly clinic whose main function is the study and treatment of severe lipid disorders&#44; and DALI LDL apheresis has been available there since 2008&#46;</p><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Direct adsorption of lipoproteins</span><p id="par0180" class="elsevierStylePara elsevierViewall">In this technique&#44; whole blood is passed through an adsorber containing polyacrylamide gel&#46; This consists of polyanions with negatively charged carboxylate groups that interact selectively with the cationic groups of Apo B found in very low density lipoprotein &#40;VLDL&#41;&#44; intermediate density lipoprotein &#40;IDL&#41;&#44; LDL and lipoprotein&#40;a&#41; &#40;Lp&#40;a&#41;&#41;&#46; Each of these lipoproteins contains a single molecule of Apo B&#44; by which the lipoproteins are immobilized in the adsorber through electrochemical interactions&#46;</p><p id="par0185" class="elsevierStylePara elsevierViewall">High-density lipoproteins &#40;HDL&#41; do not interact with the polyanions in the adsorber since they are coated with Apo A1&#44; and are thus not eliminated by the technique&#46;</p><p id="par0190" class="elsevierStylePara elsevierViewall">After passing through the adsorber&#44; the blood depleted of all Apo B-containing lipoproteins is returned to the patient&#46; Reductions in LDL-C of over 60&#37; have been observed&#46;<a class="elsevierStyleCrossRefs" href="#bib0210"><span class="elsevierStyleSup">16&#44;17</span></a></p><p id="par0195" class="elsevierStylePara elsevierViewall">The apheresis sessions were performed using the following equipment from Fresenius Medical Care&#44; Germany&#58; 4008 ADS monitor&#44; DALI adsorbers&#44; priming solution and acid citrate dextrose formula A &#40;ACD-A&#41;&#46; According to the German clinical guidelines&#44; the aim of LDL apheresis is to achieve a reduction in LDL-C of &#8805;60&#37; per session&#46; Two configurations are available&#58; DALI 750 and DALI 1000&#46;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">18</span></a></p><p id="par0200" class="elsevierStylePara elsevierViewall">In patients indicated for prolonged or chronic treatment&#44; the creation of an arteriovenous fistula is recommended in order to facilitate vascular access&#46;</p><p id="par0205" class="elsevierStylePara elsevierViewall">The volume of blood processed per session is tailored to the patient&#39;s gender and weight&#44; and flow rate varies between 60 and 100 ml&#47;min&#46;</p><p id="par0210" class="elsevierStylePara elsevierViewall">A patient is referred for LDL apheresis following agreement by the multidisciplinary team based on the criteria recommended by the US Food and Drug Administration &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">19</span></a></p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0215" class="elsevierStylePara elsevierViewall">LDL apheresis is recommended for these patients if they have not attained therapeutic targets after six months of non-pharmacological or pharmacological therapy at the maximum tolerated dose&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Laboratory tests</span><p id="par0220" class="elsevierStylePara elsevierViewall">Laboratory tests are performed by the clinical chemistry department of Hospital Santo Ant&#243;nio using a Cobas Integra 800 analyzer &#40;Roche Diagnostics&#41; and appropriate reagents&#46;</p><p id="par0225" class="elsevierStylePara elsevierViewall">Blood samples are obtained directly via the afferent line immediately before the start of each session&#46; Samples are collected via the same line at the end of treatment before the extracorporeal circuit is rinsed with saline&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Measurement of lipid parameters</span><p id="par0230" class="elsevierStylePara elsevierViewall">Acute percentage reductions in lipid parameters in a single treatment are calculated according to the following formula&#58; 100&#215;&#40;pre-session value&#8722;post-session value&#41;&#47;pre-session value&#46;</p><p id="par0235" class="elsevierStylePara elsevierViewall">Long-term reductions in each lipid parameter are calculated from the baseline value prior to the first session&#44; the mean value after the antepenultimate session &#40;post-session n-2&#41;&#44; before the penultimate session &#40;pre-session n-1&#41;&#44; after the penultimate session &#40;post-session n-1&#41; and before the last session &#40;pre-session n&#41;&#44;<a class="elsevierStyleCrossRefs" href="#bib0215"><span class="elsevierStyleSup">17&#44;20</span></a> according to the following formulas&#58;<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">&#8226;</span><p id="par0240" class="elsevierStylePara elsevierViewall">Long-term percentage reduction in lipid parameters&#58; 100&#215;&#40;baseline value&#8722;mean value&#41;&#47;baseline value</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">&#8226;</span><p id="par0245" class="elsevierStylePara elsevierViewall">Mean value of lipid parameters&#58; &#40;post-session value n-2&#43;pre-session value n-1&#43;post-session value n-1&#43;pre-session value n&#41;&#47;4&#46;</p><p id="par0250" class="elsevierStylePara elsevierViewall">n-2&#44; n-1 and n refer to the last three sessions in chronological order from the earliest to the last&#44; respectively&#46;</p><p id="par0255" class="elsevierStylePara elsevierViewall">The same formulas were used for all lipid parameters&#58; LDL-C&#44; triglycerides &#40;TG&#41;&#44; total cholesterol &#40;TC&#41;&#44; HDL-C and non-HDL-C&#44; the latter being calculated as the difference between TC and HDL-C&#46;</p></li></ul></p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Results</span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Patients</span><p id="par0260" class="elsevierStylePara elsevierViewall">All patients underwent fortnightly sessions of DALI LDL apheresis lasting an average of 90 min while maintaining previous pharmacological therapy&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Patient 1</span><p id="par0265" class="elsevierStylePara elsevierViewall">A 55-year-old man had been diagnosed with asymptomatic ischemic heart disease on exercise testing at age 37&#44; followed by stenting in 1995 for critical stenosis of the right coronary artery and placement of two further stents in 2010 due to restenosis of the same artery&#46;</p><p id="par0270" class="elsevierStylePara elsevierViewall">He had no CV risk factors including smoking&#44; diabetes mellitus &#40;DM&#41;&#44; hypertension&#44; family history of premature ischemic heart disease or dyslipidemia and was not overweight &#40;body mass index &#91;BMI&#93; 23&#46;8 kg&#47;m<span class="elsevierStyleSup">2</span>&#41;&#46;</p><p id="par0275" class="elsevierStylePara elsevierViewall">His pre-treatment lipid profile was TC 390 mg&#47;dl&#44; TG 140 mg&#47;dl&#44; HDL-C 50 mg&#47;dl&#44; LDL-C 312 mg&#47;dl&#44; Apo A1 109 mg&#47;dl and Apo B 186 mg&#47;dl&#44; with no other abnormalities on laboratory tests&#46;</p><p id="par0280" class="elsevierStylePara elsevierViewall">Since the patient presented sustained elevation of transaminases under therapy with rosuvastatin 40 mg&#47;day&#44; intolerance to resins manifested as constipation and severe flushing with nicotinic acid&#44; he was medicated with rosuvastatin 20 mg&#47;day &#40;maximum tolerated dose&#41; and ezetimibe 10 mg&#47;day&#46; He was also taking diltiazem 120 mg&#44; clopidogrel 75 mg and aspirin 100 mg&#46; However&#44; his dyslipidemia was refractory to maximum tolerated pharmacological therapy&#46;</p><p id="par0285" class="elsevierStylePara elsevierViewall">Genetic study showed a heterozygous functional mutation in the <span class="elsevierStyleItalic">PCSK9</span> gene&#46;</p><p id="par0290" class="elsevierStylePara elsevierViewall">He began LDL apheresis as adjuvant therapy in December 2008 using the DALI 750 filter&#44; while maintaining his usual lipid-lowering therapy&#46;</p><p id="par0295" class="elsevierStylePara elsevierViewall">Four years after beginning LDL apheresis&#44; carotid Doppler ultrasound showed diffuse carotid atherosclerosis with mild stenosis &#40;&#60;20&#37;&#41; of the right and left internal carotid arteries&#59; myocardial perfusion study revealed no evidence of ischemia&#44; a mild fixed inferolateral defect and good left ventricular global systolic function&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Patient 2</span><p id="par0300" class="elsevierStylePara elsevierViewall">A 59-year-old man had been diagnosed with severe dyslipidemia in routine laboratory tests at the age of 36&#46; He had xanthelasmas and tendon xanthomas and asymptomatic carotid atherosclerosis&#44; with &#62;70&#37; stenosis of the right internal carotid artery and 50&#8211;70&#37; stenosis of the left internal carotid artery&#46; He underwent elective endarterectomy of the right internal carotid artery in March 2007&#46;</p><p id="par0305" class="elsevierStylePara elsevierViewall">He was a former smoker&#44; of normal weight &#40;BMI 22&#46;8 kg&#47;m<span class="elsevierStyleSup">2</span>&#41;&#44; and had a family history of dyslipidemia &#40;mother&#44; siblings and daughter with hypercholesterolemia&#41; and no other CV risk factors&#46;</p><p id="par0310" class="elsevierStylePara elsevierViewall">His pre-treatment lipid profile was TC 378 mg&#47;dl&#44; TG 75 mg&#47;dl&#44; HDL-C 112 mg&#47;dl&#44; LDL-C 251 mg&#47;dl&#44; Apo A1 223 mg&#47;dl and Apo B 176 mg&#47;dl&#44; with no other abnormalities on laboratory tests&#46;</p><p id="par0315" class="elsevierStylePara elsevierViewall">Since the patient experienced myalgia on rosuvastatin 40 mg&#47;day&#44; intolerance to resins at the maximum recommended dose and worsening gastric disease &#40;peptic ulcer&#41; with nicotinic acid&#44; he was medicated with cholestyramine 8 g&#47;day&#44; rosuvastatin 20 mg&#47;day and ezetimibe 10 mg&#47;day&#44; as well as aspirin 325 mg&#44; valsartan 160 mg and esomeprazole 40 mg&#46;</p><p id="par0320" class="elsevierStylePara elsevierViewall">Genetic study showed a heterozygous functional mutation in the <span class="elsevierStyleItalic">LDLR</span> gene&#46;</p><p id="par0325" class="elsevierStylePara elsevierViewall">He began LDL apheresis in March 2009 using the DALI 750 configuration&#44; while maintaining his previous lipid-lowering therapy&#46;</p><p id="par0330" class="elsevierStylePara elsevierViewall">Fours years after beginning LDL apheresis&#44; carotid Doppler ultrasound showed diffuse atherosclerosis with mild stenosis &#40;&#60;20&#37;&#41; of the right internal carotid artery and moderate stenosis of the left internal carotid artery&#44; with an echogenic&#44; partially calcified atheromatous plaque causing 30&#8211;50&#37; stenosis but with normal carotid flow&#46; Myocardial perfusion study was suggestive of mild ischemia in the territory of the anterior descending artery&#44; but with good left ventricular global systolic function&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Patient 3</span><p id="par0335" class="elsevierStylePara elsevierViewall">A 62-year-old woman with severe symptomatic aortic stenosis underwent aortic valve replacement with a mechanical prosthesis in July 2010&#46; She also had asymptomatic carotid arteriosclerosis&#44; atheromas in the common carotid arteries and proximal internal carotid arteries with &#60;30&#37; stenosis&#46;</p><p id="par0340" class="elsevierStylePara elsevierViewall">She had a family history of dyslipidemia &#40;daughter and grandson with hypercholesterolemia&#41;&#44; was of normal weight &#40;BMI 22&#46;7 kg&#47;m<span class="elsevierStyleSup">2</span>&#41; and had no other CV risk factors &#40;non-smoker&#44; no hypertension or DM and no family history of premature CV disease&#41;&#46;</p><p id="par0345" class="elsevierStylePara elsevierViewall">Her pre-treatment lipid profile was TC 379 mg&#47;dl&#44; TG 71 mg&#47;dl&#44; HDL-C 67 mg&#47;dl&#44; LDL-C 298 mg&#47;dl&#44; Apo A1 120 mg&#47;dl and Apo B 184 mg&#47;dl&#44; with no other abnormalities on laboratory tests&#46;</p><p id="par0350" class="elsevierStylePara elsevierViewall">Since the patient was intolerant to rosuvastatin 40 mg and resins&#44; she was medicated with rosuvastatin 20 mg&#44; nicotinic acid 1 g &#40;maximum tolerated&#41;&#44; ezetimibe 10 mg&#44; warfarin 5 mg&#44; aspirin 100 mg and diazepam 5 mg&#46;</p><p id="par0355" class="elsevierStylePara elsevierViewall">Genetic study showed a heterozygous functional mutation in the <span class="elsevierStyleItalic">LDLR</span> gene and another mutation of unknown significance in the same gene&#59; functional studies are in progress to assess the pathogenicity of this alteration&#44; and if confirmed&#44; the patient will be classified as a compound heterozygote&#46;</p><p id="par0360" class="elsevierStylePara elsevierViewall">She began LDL apheresis in March 2009&#44; while maintaining her usual lipid-lowering therapy&#46; Due to the lack of adequate response to the DALI 750 configuration&#44; the DALI 1000 filter was subsequently used&#46;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">18</span></a></p><p id="par0365" class="elsevierStylePara elsevierViewall">Four years after beginning LDL apheresis&#44; carotid Doppler ultrasound showed an atheroma with regular contours in the right internal carotid artery with &#60;30&#37; stenosis and &#60;20&#37; stenosis in the left internal carotid artery&#59; myocardial perfusion study was within normal limits&#44; with good left ventricular global systolic function&#46;</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Complications</span><p id="par0370" class="elsevierStylePara elsevierViewall">Between December 2008 and January 2013&#44; 308 treatments were performed &#40;<a class="elsevierStyleCrossRefs" href="#tbl0010">Tables 2&#8211;6</a>&#41;&#44; during which there were 11 complications &#8211; 10 minor and one major &#8211; including six episodes of chest pain&#44; three of hypotension &#40;one accompanied by an anaphylactic reaction&#41; and one of clotting of the extracorporeal circuit&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><elsevierMultimedia ident="tbl0025"></elsevierMultimedia><elsevierMultimedia ident="tbl0030"></elsevierMultimedia></span></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Discussion</span><p id="par0375" class="elsevierStylePara elsevierViewall">Similar to reports in the literature&#44; 96&#46;4&#37; of the sessions were uneventful&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">21</span></a> The overall incidence of adverse events was 3&#46;6&#37;&#44; also similar to that reported by other authors&#44; and treatment had to be suspended in only one case&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">21</span></a> No prolonged or irreversible adverse effects were seen in any patient&#46;</p><p id="par0380" class="elsevierStylePara elsevierViewall">Comparing the adverse effects in our patients with those observed by Bosch et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">21</span></a> the most common adverse effect in our population was angina &#40;1&#46;95&#37; vs&#46; 0&#46;09&#37;&#41;&#44; followed by hypotension &#40;0&#46;97&#37; vs&#46; 0&#46;97&#37;&#41;&#44; clotting of the extracorporeal circuit &#40;0&#46;32&#37; vs&#46; 0&#46;03&#37;&#41; and anaphylactic reaction &#40;0&#46;32&#37; vs&#46; 0&#37;&#41;&#46;</p><p id="par0385" class="elsevierStylePara elsevierViewall">There were six episodes of angina during the 308 LDL apheresis sessions&#44; a higher percentage than that reported in the literature&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">21</span></a> These all occurred in the same patient&#44; who had critical aortic valve stenosis&#44; and were reversed by reducing flow rate and administering fluids&#44; oxygen and nitrates&#46; The etiology of the angina was probably multifactorial but we believe the underlying aortic stenosis was the main factor&#44; since following surgical treatment&#44; there were no further episodes of angina&#46;</p><p id="par0390" class="elsevierStylePara elsevierViewall">Hypotension is reported as the most common complication of LDL apheresis&#46;<a class="elsevierStyleCrossRefs" href="#bib0210"><span class="elsevierStyleSup">16&#44;20&#44;21</span></a> This may be due to hypovolemia&#44; vasodilation or vasovagal reaction&#46; In the DALI technique&#44; the negatively charged surfaces of the adsorber increase concentrations of factor XII&#44; kallikrein and bradykinin&#46; Bradykinin can cause hypotension&#44; flushing and Quincke&#39;s edema&#46; Although it is generated in the adsorber and reinfused into the patient&#44; it is rapidly degraded by angiotensin-converting enzyme &#40;ACE&#41;&#44; so levels in the pre-adsorber afferent line are negligible&#46;<a class="elsevierStyleCrossRefs" href="#bib0210"><span class="elsevierStyleSup">16&#44;22</span></a></p><p id="par0395" class="elsevierStylePara elsevierViewall">The main cause of hypovolemia during DALI apheresis appears to be the initial transfer of blood to the extracorporeal circuit&#46; Like other authors&#44; we replace part of the initial blood volume with saline solution in the contralateral vein while the extracorporeal circuit is filling in order to minimize this effect and prevent hypotension&#46;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">16</span></a></p><p id="par0400" class="elsevierStylePara elsevierViewall">One of the three cases of hypotension was more severe and accompanied by pallor&#44; dyspnea and a feeling of imminent death&#46; This was in a patient who had been prescribed ramipril for the first time and took it inadvertently on the day of the LDL apheresis session&#46; This episode was interpreted as an anaphylactic reaction&#46; The DALI technique can cause severe hypotension in patients taking ACE inhibitors due to decreased bradykinin catabolism through ACE inhibition and the increased bradykinin production associated with the procedure&#46; Drugs that inhibit degradation of bradykinin into inactive metabolites are thus contraindicated in patients undergoing DALI LDL apheresis&#46;<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">21&#44;23</span></a></p><p id="par0405" class="elsevierStylePara elsevierViewall">In order to avoid the risk of hypotension in patients undergoing DALI apheresis&#44; ACE inhibitors should be suspended 24 hours before treatment and whenever possible replaced by other antihypertensive drugs&#44; such as angiotensin receptor blockers&#44; that do not inhibit ACE&#46;</p><p id="par0410" class="elsevierStylePara elsevierViewall">Of the three cases of hypotension&#44; two were resolved with intravenous fluid therapy and reduction of flow rate&#59; in the more severe case&#44; LDL apheresis was suspended and oxygen&#44; fluid and intravenous corticosteroid therapy were required&#46;</p><p id="par0415" class="elsevierStylePara elsevierViewall">As described in the literature&#44; 1 ml of ACD-A per 20&#8211;40 ml of blood was used to prevent clotting of the extracorporeal circuit&#44; which proved adequate for anticoagulation&#46;<a class="elsevierStyleCrossRefs" href="#bib0230"><span class="elsevierStyleSup">20&#44;21</span></a> In 308 sessions&#44; there was only one episode of clotting of the extracorporeal circuit &#40;0&#46;32&#37; vs&#46; 0&#46;17&#37;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">20</span></a></p><p id="par0420" class="elsevierStylePara elsevierViewall">Besides lipoproteins&#44; the DALI column also adsorbs positively charged ions such as calcium and magnesium&#46; We observed no hypocalcemia or hypomagnesemia in our experience&#44; but like other authors we used a priming solution that contains these electrolytes&#44; saturating the column with these cations and thus preventing hypocalcemia and hypomagnesemia during treatment&#59; in addition&#44; an ampoule of calcium gluconate was used prophylactically at the end of each session&#46;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">24</span></a></p><p id="par0425" class="elsevierStylePara elsevierViewall">Iron deficiency&#44; leading to microcytic anemia&#44; has also been reported in patients under chronic LDL apheresis&#46; This may be due to frequent laboratory tests and residual blood loss in the extracorporeal system after each session&#46; No iron deficiency or anemia was observed in our patients&#46;</p><p id="par0430" class="elsevierStylePara elsevierViewall">We used the methodology previously described by us and other authors<a class="elsevierStyleCrossRefs" href="#bib0215"><span class="elsevierStyleSup">17&#44;20</span></a> to assess the technique&#39;s efficacy in terms of lipid parameters&#46;</p><p id="par0435" class="elsevierStylePara elsevierViewall">Mean acute reductions in LDL-C of 63&#46;3&#37; &#40;57&#46;3&#8211;69&#46;6&#37;&#41; were obtained&#44; which are similar to those described by other authors and meet the objectives stated in the German clinical guidelines for LDL apheresis&#46;<a class="elsevierStyleCrossRefs" href="#bib0220"><span class="elsevierStyleSup">18&#44;21</span></a></p><p id="par0440" class="elsevierStylePara elsevierViewall">With regard to long-term reductions in LDL-C&#44; we achieved a mean reduction of 36&#46;0&#37; &#40;25&#46;6&#8211;44&#46;2&#37;&#41;&#44; slightly lower than reported in the literature<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">21</span></a>&#59; however&#44; we believe that the difference may be explained by the longer treatment time and larger number of patients&#44; as well as better patient compliance with drug therapy&#44; in these studies&#46;</p><p id="par0445" class="elsevierStylePara elsevierViewall">We obtained a mean acute reduction in non-HDL-C of 62&#46;3&#37; &#40;55&#46;1&#8211;68&#46;4&#37;&#41; and a mean long-term reduction of 35&#46;5&#37; &#40;23&#46;9&#8211;45&#46;4&#37;&#41;&#44; comparable to those seen for LDL-C&#46; We believe that this was due to the characteristics of our patients&#8217; dyslipidemia&#58; hypercholesterolemia but no DM&#44; obesity or metabolic syndrome criteria&#44; and hence no factors that promote the production of VLDL or IDL&#46; On the other hand&#44; it may have been due to TG values of &#60;400&#44; as reflected in a low error rate in calculating LDL-C by the Friedewald formula&#46;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">25</span></a></p><p id="par0450" class="elsevierStylePara elsevierViewall">Acute reductions in HDL-C were similar to those obtained by other authors and are related to low TG levels&#44; which in turn depend heavily on the food ingested prior to treatment sessions&#46; No significant long-term changes in HDL-C were observed&#44; which demonstrates the selectivity of DALI LDL apheresis&#46;</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Conclusion</span><p id="par0455" class="elsevierStylePara elsevierViewall">The results reflect the efficacy and selectivity of DALI LDL apheresis and are comparable to those obtained in previous studies of the technique&#46;<a class="elsevierStyleCrossRefs" href="#bib0230"><span class="elsevierStyleSup">20&#44;21</span></a></p><p id="par0460" class="elsevierStylePara elsevierViewall">In 308 sessions over a 49-month period the technique was shown to be safe&#44; effective and selective for LDL-C&#44; with acute reductions of over 60&#37; and no significant changes in other lipoproteins&#46; The main objective of LDL-C reduction is to prevent the development and progression of atherosclerosis&#44; and the improvement seen in our patients&#8217; lipid profiles was reflected in the absence of disease progression&#46; The selective elimination of LDL-C by DALI apheresis is an important advance in the treatment of hypercholesterolemic patients with high CV risk&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">26</span></a></p><p id="par0465" class="elsevierStylePara elsevierViewall">LDL apheresis in conjunction with lipid-lowering therapy prevented the development of atherosclerosis in patients with severe dyslipidemia and high CV risk&#46;</p><p id="par0470" class="elsevierStylePara elsevierViewall">The low incidence of complications means that LDL apheresis is well tolerated by patients&#44; which is reflected in the high rate of adhesion to the treatment&#46;</p><p id="par0475" class="elsevierStylePara elsevierViewall">DALI LDL apheresis was shown to be a simple&#44; safe and effective treatment in patients with FH refractory to diet modification and pharmacological therapy and should be considered as an adjuvant therapy for hypercholesterolemic patients who are intolerant or refractory to statin therapy and for those with contraindications to drug therapy&#46;</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Ethical disclosures</span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Protection of human and animal subjects</span><p id="par0480" class="elsevierStylePara elsevierViewall">The authors declare that no experiments were performed on humans or animals for this study&#46;</p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Confidentiality of data</span><p id="par0485" class="elsevierStylePara elsevierViewall">The authors declare that they have followed the protocols of their work center on the publication of patient data&#46;</p></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Right to privacy and informed consent</span><p id="par0490" class="elsevierStylePara elsevierViewall">The authors have obtained the written informed consent of the patients or subjects mentioned in the article&#46; The corresponding author is in possession of this document&#46;</p></span></span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Conflicts of interest</span><p id="par0495" class="elsevierStylePara elsevierViewall">The authors have no conflicts of interest to declare&#46;</p></span></span>"
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    "fechaRecibido" => "2013-05-29"
    "fechaAceptado" => "2014-07-31"
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          "clase" => "keyword"
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          "identificador" => "xpalclavsec491902"
          "palabras" => array:5 [
            0 => "Direct adsorption of lipoprotein apheresis"
            1 => "Low-density lipoprotein apheresis"
            2 => "Cardiovascular disease"
            3 => "Elevated serum lipoprotein&#40;a&#41;"
            4 => "Familial hypercholesterolemia"
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          "palabras" => array:5 [
            0 => "DALI af&#233;rese"
            1 => "LDL-af&#233;rese"
            2 => "Doen&#231;a cardiovascular"
            3 => "Lipoprote&#237;na &#40;a&#41; elevada"
            4 => "Hipercolesterolemia familiar"
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">High plasma levels of low-density lipoprotein &#40;LDL&#41; cholesterol are a risk factor for the development of premature atherosclerosis&#46; Direct adsorption of lipoproteins &#40;DALI&#41; is an apheresis technique by which LDL cholesterol is selectively removed from whole blood&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Objective</span><p id="spar0130" class="elsevierStyleSimplePara elsevierViewall">The present study describes our experience with DALI LDL apheresis in severely hypercholesterolemic patients&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Three hypercholesterolemic patients suffering from atherosclerotic complications were treated fortnightly by DALI apheresis&#44; in a total of 308 sessions between December 2008 and January 2013&#46; All patients were on the highest tolerated dose of statins and other lipid-lowering drugs&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">The sessions were essentially uneventful&#44; adverse events being recorded in only 3&#46;6&#37; of them&#46; A mean 63&#46;3&#37; acute reduction in LDL cholesterol was obtained&#46;</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">DALI apheresis proved to be a simple&#44; safe and efficient method of lipid apheresis in hypercholesterolemic patients refractory to conservative lipid-lowering therapy&#46;</p></span>"
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            "titulo" => "Introduction"
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          1 => array:2 [
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        "resumen" => "<span id="abst0030" class="elsevierStyleSection elsevierViewall"><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">A hipercolesterolemia manifestada pelos n&#237;veis elevados de colesterol das lipoprote&#237;nas de baixa densidade constitui um fator de risco <span class="elsevierStyleItalic">major</span> para o desenvolvimento e progress&#227;o da doen&#231;a ateroscler&#243;tica prematura&#46;</p><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">A adsor&#231;&#227;o direta de lipoprote&#237;nas &#233; uma t&#233;cnica de LDL-af&#233;rese na qual o LDL-c pode ser seletivamente removido do sangue total&#46;</p><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Este trabalho partilha a experi&#234;ncia da LDL-af&#233;rese pela t&#233;cnica de adsor&#231;&#227;o direta de lipoprote&#237;nas no tratamento de doentes com hipercolesterolemia severa&#46;</p><p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Tr&#234;s doentes com hipercolesterolemia e doen&#231;a ateroscler&#243;tica documentada foram tratados quinzenalmente com LDL-af&#233;rese pela t&#233;cnica de adsor&#231;&#227;o direta de lipoprote&#237;nas&#44; realizando no total 308 sess&#245;es entre dezembro de 2008 e janeiro de 2013&#46; Todos os doentes estavam medicados com estatinas e outros f&#225;rmacos hipolipemiantes na dose m&#225;xima tolerada&#46;</p><p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">As sess&#245;es decorreram na generalidade sem intercorr&#234;ncias&#46; A incid&#234;ncia global de efeitos adversos reportados durante as sess&#245;es foi de 3&#44;6&#37;&#46; Em rela&#231;&#227;o aos par&#226;metros lip&#237;dicos obtivemos redu&#231;&#245;es agudas do colesterol das lipoprote&#237;nas de baixa densidade da ordem dos 63&#44;3&#37; &#40;m&#237;nimo de 57&#44;3&#37; e m&#225;ximo de 69&#44;6&#37;&#41;&#46;</p><p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Em resumo&#44; a LDL-af&#233;rese pela t&#233;cnica de adsor&#231;&#227;o direta de lipoprote&#237;nas demonstrou ser um procedimento simples&#44; seguro e eficaz em doentes com hipercolesterolemia resistentes ao tratamento institu&#237;do&#46;</p></span>"
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        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Palma I&#44; Caldas AR&#44; Palma IM&#44; Queir&#243;s JA&#44; Madureira A&#44; Oliveira JC&#44; et al&#46; LDL-af&#233;rese no tratamento de hipercolesterolemia familiar&#58; experi&#234;ncia do Hospital Santo Ant&#243;nio &#8211; CHP&#46; Rev Port Cardiol&#46; 2015&#59;34&#58;163&#8211;172&#46;</p>"
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                "termino" => "ACD-A"
                "descripcion" => "<p id="par0005" class="elsevierStylePara elsevierViewall">acid citrate dextrose formula A</p>"
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              2 => array:2 [
                "termino" => "Apo A1"
                "descripcion" => "<p id="par0015" class="elsevierStylePara elsevierViewall">apolipoprotein A1</p>"
              ]
              3 => array:2 [
                "termino" => "Apo B"
                "descripcion" => "<p id="par0020" class="elsevierStylePara elsevierViewall">apolipoprotein B 100</p>"
              ]
              4 => array:2 [
                "termino" => "ARH"
                "descripcion" => "<p id="par0025" class="elsevierStylePara elsevierViewall">autosomal recessive hypercholesterolemia</p>"
              ]
              5 => array:2 [
                "termino" => "BMI"
                "descripcion" => "<p id="par0030" class="elsevierStylePara elsevierViewall">body mass index</p>"
              ]
              6 => array:2 [
                "termino" => "CV"
                "descripcion" => "<p id="par0035" class="elsevierStylePara elsevierViewall">cardiovascular</p>"
              ]
              7 => array:2 [
                "termino" => "DALI"
                "descripcion" => "<p id="par0040" class="elsevierStylePara elsevierViewall">direct adsorption of lipoproteins</p>"
              ]
              8 => array:2 [
                "termino" => "DM"
                "descripcion" => "<p id="par0045" class="elsevierStylePara elsevierViewall">diabetes mellitus</p>"
              ]
              9 => array:2 [
                "termino" => "FH"
                "descripcion" => "<p id="par0050" class="elsevierStylePara elsevierViewall">familial hypercholesterolemia</p>"
              ]
              10 => array:2 [
                "termino" => "HDL"
                "descripcion" => "<p id="par0055" class="elsevierStylePara elsevierViewall">high-density lipoprotein</p>"
              ]
              11 => array:2 [
                "termino" => "HDL-C"
                "descripcion" => "<p id="par0060" class="elsevierStylePara elsevierViewall">high-density lipoprotein cholesterol</p>"
              ]
              12 => array:2 [
                "termino" => "IDL"
                "descripcion" => "<p id="par0065" class="elsevierStylePara elsevierViewall">intermediate density lipoprotein</p>"
              ]
              13 => array:2 [
                "termino" => "LDL"
                "descripcion" => "<p id="par0070" class="elsevierStylePara elsevierViewall">low-density lipoprotein</p>"
              ]
              14 => array:2 [
                "termino" => "LDL-C"
                "descripcion" => "<p id="par0075" class="elsevierStylePara elsevierViewall">low-density lipoprotein cholesterol</p>"
              ]
              15 => array:2 [
                "termino" => "LDLR"
                "descripcion" => "<p id="par0080" class="elsevierStylePara elsevierViewall">low-density lipoprotein receptor</p>"
              ]
              16 => array:2 [
                "termino" => "LDLRAP1"
                "descripcion" => "<p id="par0085" class="elsevierStylePara elsevierViewall">low-density lipoprotein receptor adaptor protein 1</p>"
              ]
              17 => array:2 [
                "termino" => "Lp&#40;a&#41;"
                "descripcion" => "<p id="par0090" class="elsevierStylePara elsevierViewall">lipoprotein&#40;a&#41;</p>"
              ]
              18 => array:2 [
                "termino" => "PCSK9"
                "descripcion" => "<p id="par0095" class="elsevierStylePara elsevierViewall">proprotein convertase subtilisin&#47;kexin type 9</p>"
              ]
              19 => array:2 [
                "termino" => "TC"
                "descripcion" => "<p id="par0100" class="elsevierStylePara elsevierViewall">total cholesterol</p>"
              ]
              20 => array:2 [
                "termino" => "TG"
                "descripcion" => "<p id="par0105" class="elsevierStylePara elsevierViewall">triglycerides</p>"
              ]
              21 => array:2 [
                "termino" => "VLDL"
                "descripcion" => "<p id="par0110" class="elsevierStylePara elsevierViewall">very-low-density lipoprotein</p>"
              ]
              22 => array:2 [
                "termino" => "WHO"
                "descripcion" => "<p id="par0115" class="elsevierStylePara elsevierViewall">World Health Organization</p>"
              ]
            ]
          ]
        ]
      ]
    ]
    "multimedia" => array:6 [
      0 => array:7 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">DM&#58; diabetes mellitus&#59; CV&#58; cardiovascular&#59; FH&#58; familial hypercholesterolemia&#59; HDL-C&#58; high-density lipoprotein cholesterol&#59; LDL-C&#58; low-density lipoprotein cholesterol&#59; Lp&#40;a&#41;&#58; lipoprotein&#40;a&#41;&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Patients with homozygous FH&#44; LDL-C &#8805;300 mg&#47;dl or non-HDL-C &#8805;330 mg&#47;dl&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Patients with heterozygous FH&#44; LDL-C &#8805;300 mg&#47;dl or non-HDL-C &#8805;330 mg&#47;dl and 0&#8211;1 risk factors&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Patients with heterozygous FH&#44; LDL-C &#8805;200 mg&#47;dl or non-HDL-C &#8805;230 mg&#47;dl and high risk&#44; characterized by &#8805;2 risk factors or Lp&#40;a&#41; &#8805;50 mg&#47;dl&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Patients with heterozygous FH&#44; with LDL-C &#8805;60 or non-HDL-C &#8805;190 and very high CV risk &#40;established CAD or other CV disease or DM&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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                0 => "xTab726701.png"
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        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Selection criteria for LDL apheresis recommended by the US Food and Drug Administration&#46;</p>"
        ]
      ]
      1 => array:7 [
        "identificador" => "tbl0010"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">LDL-C&#58; low-density lipoprotein cholesterol&#46; n-2&#44; n-1 and n refer to the last three sessions&#59; pre and post&#58; values before and after treatment sessions&#59; &#8595;Acute&#58; acute reduction&#59; &#8595;Long-term&#58; long-term reduction&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col">Patient&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col">Baseline LDL-C&#40;mg&#47;dl&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " colspan="3" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Session n-2</th><th class="td" title="table-head  " colspan="3" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Session n-1</th><th class="td" title="table-head  " colspan="3" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Session n</th><th class="td" title="table-head  " align="left" valign="top" scope="col">Mean LDL-C&#40;mg&#47;dl&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col">&#8595;Long-term&#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Pre&#40;mg&#47;dl&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Post&#40;mg&#47;dl&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">&#8595;Acute&#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Pre&#40;mg&#47;dl&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Post&#40;mg&#47;dl&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">&#8595;Acute&#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Pre&#40;mg&#47;dl&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Post&#40;mg&#47;dl&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">&#8595;Acute&#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">312&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">239&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">101&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">57&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">245&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">91&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">62&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">259&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">102&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">60&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">174&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">44&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">251&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">344&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">147&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">57&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">259&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">93&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">64&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">248&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">98&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">60&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">187&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">25&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">298&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">287&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">88&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">69&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">280&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">85&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">69&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">285&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">90&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">68&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">185&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">38&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Mean&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">61&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">65&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">63&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">36&#46;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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                0 => "xTab726704.png"
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        "descripcion" => array:1 [
          "en" => "<p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">Acute and long-term reductions in low-density lipoprotein cholesterol by direct adsorption of lipoprotein LDL apheresis&#46;</p>"
        ]
      ]
      2 => array:7 [
        "identificador" => "tbl0015"
        "etiqueta" => "Table 3"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0095" class="elsevierStyleSimplePara elsevierViewall">HDL-C&#58; high-density lipoprotein cholesterol&#46; n-2&#44; n-1 and n refer to the last three sessions&#59; pre and post&#58; values before and after treatment sessions&#59; &#8595;Acute&#58; acute reduction&#59; &#8595;Long-term&#58; long-term reduction&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col">Patient&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col">Baseline HDL-C&#40;mg&#47;dl&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " colspan="3" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Session n-2</th><th class="td" title="table-head  " colspan="3" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Session n-1</th><th class="td" title="table-head  " colspan="3" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Session n</th><th class="td" title="table-head  " align="left" valign="top" scope="col">Mean HDL-C&#40;mg&#47;dl&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col">&#8595;Long-term&#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Pre&#40;mg&#47;dl&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Post&#40;mg&#47;dl&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">&#8595;Acute&#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Pre&#40;mg&#47;dl&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Post&#40;mg&#47;dl&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">&#8595;Acute&#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Pre&#40;mg&#47;dl&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Post&#40;mg&#47;dl&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">&#8595;Acute&#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">50&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">52&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">48&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">7&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">51&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">44&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">13&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">53&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">48&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">9&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">49&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&#46;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">112&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">101&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">94&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">7&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">132&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">118&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">10&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">118&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">103&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">12&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">116&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8722;3&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">67&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">59&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">64&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8722;8&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">75&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">67&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">10&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">76&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">64&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">15&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">71&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8722;5&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Mean&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">11&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">12&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8722;2&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab726703.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0090" class="elsevierStyleSimplePara elsevierViewall">Acute and long-term reductions in high-density lipoprotein cholesterol by direct adsorption of lipoprotein LDL apheresis&#46;</p>"
        ]
      ]
      3 => array:7 [
        "identificador" => "tbl0020"
        "etiqueta" => "Table 4"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0105" class="elsevierStyleSimplePara elsevierViewall">TG&#58; triglycerides&#46; n-2&#44; n-1 and n refer to the last three sessions&#59; pre and post&#58; values before and after treatment sessions&#59; &#8595;Acute&#58; acute reduction&#59; &#8595;Long-term&#58; long-term reduction&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col">Patient&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col">Baseline TG&#40;mg&#47;dl&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " colspan="3" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Session n-2</th><th class="td" title="table-head  " colspan="3" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Session n-1</th><th class="td" title="table-head  " colspan="3" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Session n</th><th class="td" title="table-head  " align="left" valign="top" scope="col">Mean TG&#40;mg&#47;dl&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col">&#8595;Long-term&#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Pre&#40;mg&#47;dl&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Post&#40;mg&#47;dl&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">&#8595;Acute&#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Pre&#40;mg&#47;dl&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Post&#40;mg&#47;dl&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">&#8595;Acute&#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Pre&#40;mg&#47;dl&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Post&#40;mg&#47;dl&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">&#8595;Acute&#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">140&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">92&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">36&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">60&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">74&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">24&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">67&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">98&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">39&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">60&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">58&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">58&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">75&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">158&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">111&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">29&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">67&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">31&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">53&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">109&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">103&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">80&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8722;6&#46;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">71&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">108&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">37&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">65&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">72&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">38&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">47&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">74&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">37&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">50&#46;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">55&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">22&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Mean&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">52&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">56&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">38&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">24&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab726706.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0100" class="elsevierStyleSimplePara elsevierViewall">Acute and long-term reductions in triglycerides by direct adsorption of lipoprotein LDL apheresis&#46;</p>"
        ]
      ]
      4 => array:7 [
        "identificador" => "tbl0025"
        "etiqueta" => "Table 5"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0115" class="elsevierStyleSimplePara elsevierViewall">TC&#58; total cholesterol&#46; n-2&#44; n-1 and n refer to the last three sessions&#59; pre and post&#58; values before and after treatment sessions&#59; &#8595;Acute&#58; acute reduction&#59; &#8595;Long-term&#58; long-term reduction&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col">Patient&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col">Baseline TC&#40;mg&#47;dl&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " colspan="3" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Session n-2</th><th class="td" title="table-head  " colspan="3" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Session n-1</th><th class="td" title="table-head  " colspan="3" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Session n</th><th class="td" title="table-head  " align="left" valign="top" scope="col">Mean TC&#40;mg&#47;dl&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col">&#8595;Long-term&#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Pre&#40;mg&#47;dl&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Post&#40;mg&#47;dl&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">&#8595;Acute&#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Pre&#40;mg&#47;dl&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Post&#40;mg&#47;dl&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">&#8595;Acute&#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Pre&#40;mg&#47;dl&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Post&#40;mg&#47;dl&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">&#8595;Acute&#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">390&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">309&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">156&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">49&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">311&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">140&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">55&#46;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">332&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">158&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">52&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">235&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">39&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">378&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">477&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">263&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">44&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">404&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">217&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">46&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">388&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">222&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">42&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">318&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">15&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">379&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">360&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">159&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">55&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">369&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">160&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">56&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">376&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">161&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">57&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">266&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">29&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Mean&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">50&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">52&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">50&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">28&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab726702.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0110" class="elsevierStyleSimplePara elsevierViewall">Acute and long-term reductions in total cholesterol by direct adsorption of lipoprotein LDL apheresis&#46;</p>"
        ]
      ]
      5 => array:7 [
        "identificador" => "tbl0030"
        "etiqueta" => "Table 6"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0125" class="elsevierStyleSimplePara elsevierViewall">HDL-C&#58; high-density lipoprotein cholesterol&#46; n-2&#44; n-1 and n refer to the last three sessions&#59; pre and post&#58; values before and after treatment sessions&#59; &#8595;Acute&#58; acute reduction&#59; &#8595;Long-term&#58; long-term reduction&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col">Patient&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col">Baseline non-HDL-C&#40;mg&#47;dl&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " colspan="3" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Session n-2</th><th class="td" title="table-head  " colspan="3" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Session n-1</th><th class="td" title="table-head  " colspan="3" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Session n</th><th class="td" title="table-head  " align="left" valign="top" scope="col">Mean non-HDL-C&#40;mg&#47;dl&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col">&#8595;Long-term&#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Pre&#40;mg&#47;dl&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Post&#40;mg&#47;dl&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">&#8595;Acute&#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Pre&#40;mg&#47;dl&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Post&#40;mg&#47;dl&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">&#8595;Acute&#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Pre&#40;mg&#47;dl&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Post&#40;mg&#47;dl&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">&#8595;Acute&#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">340&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">257&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">108&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">58&#46;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">260&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">96&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">63&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">279&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">110&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">60&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">186&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">45&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">266&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">376&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">169&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">55&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">272&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">99&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">63&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">270&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">119&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">55&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">203&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">23&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">312&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">301&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">95&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">68&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">294&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">93&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">68&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">300&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">97&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">67&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">196&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">37&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Mean&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">60&#46;5&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
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Article information

ISSN: 21742049
Original language: English

DOI:10.1016/j.repce.2014.07.010

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Year/Month	Html	Pdf	Total

2024 November	8	4	12
2024 October	42	31	73
2024 September	51	23	74
2024 August	43	29	72
2024 July	41	27	68
2024 June	34	22	56
2024 May	50	26	76
2024 April	29	29	58
2024 March	31	15	46
2024 February	31	22	53
2024 January	23	34	57
2023 December	22	28	50
2023 November	32	18	50
2023 October	26	29	55
2023 September	17	24	41
2023 August	37	16	53
2023 July	27	8	35
2023 June	35	8	43
2023 May	35	24	59
2023 April	15	7	22
2023 March	48	16	64
2023 February	36	23	59
2023 January	34	21	55
2022 December	46	18	64
2022 November	43	22	65
2022 October	60	28	88
2022 September	29	35	64
2022 August	29	34	63
2022 July	60	25	85
2022 June	26	22	48
2022 May	29	29	58
2022 April	37	30	67
2022 March	28	40	68
2022 February	28	27	55
2022 January	31	25	56
2021 December	23	29	52
2021 November	35	26	61
2021 October	40	38	78
2021 September	35	30	65
2021 August	35	28	63
2021 July	21	33	54
2021 June	29	17	46
2021 May	56	29	85
2021 April	82	64	146
2021 March	94	14	108
2021 February	61	9	70
2021 January	35	20	55
2020 December	46	12	58
2020 November	42	12	54
2020 October	20	13	33
2020 September	63	10	73
2020 August	37	12	49
2020 July	56	4	60
2020 June	56	21	77
2020 May	54	9	63
2020 April	36	22	58
2020 March	57	8	65
2020 February	114	43	157
2020 January	44	6	50
2019 December	52	5	57
2019 November	40	13	53
2019 October	62	23	85
2019 September	33	8	41
2019 August	42	3	45
2019 July	60	15	75
2019 June	45	9	54
2019 May	49	13	62
2019 April	33	23	56
2019 March	104	12	116
2019 February	105	15	120
2019 January	72	8	80
2018 December	77	9	86
2018 November	101	8	109
2018 October	287	16	303
2018 September	93	18	111
2018 August	30	14	44
2018 July	26	7	33
2018 June	35	6	41
2018 May	60	9	69
2018 April	55	18	73
2018 March	89	7	96
2018 February	52	8	60
2018 January	85	6	91
2017 December	130	6	136
2017 November	54	10	64
2017 October	48	11	59
2017 September	50	7	57
2017 August	48	14	62
2017 July	37	8	45
2017 June	45	13	58
2017 May	59	23	82
2017 April	73	18	91
2017 March	63	67	130
2017 February	34	3	37
2017 January	51	5	56
2016 December	50	15	65
2016 November	49	16	65
2016 October	41	8	49
2016 September	37	8	45
2016 August	10	1	11
2016 July	29	7	36
2016 June	6	10	16
2016 May	17	5	22
2016 April	81	22	103
2016 March	97	24	121
2016 February	125	33	158
2016 January	100	34	134
2015 December	88	18	106
2015 November	71	15	86
2015 October	76	25	101
2015 September	63	18	81
2015 August	48	15	63
2015 July	42	10	52
2015 June	50	7	57
2015 May	85	24	109
2015 April	140	61	201

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