LDL-apheresis Research Articles

#4772 DOUBLE FILTRATION PLASMAPHERESIS DURING HETEROLOGOUS FERTILIZATION PREGNANCY FOR THE TREATMENT OF HETEROZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA

Abstract Background and Aims Pregnancy in women affected by familial hypercholesterolemia is rare. Estrogen and progesterone fluctuations, featuring pregnancy, adversely influence lipid metabolism, causing considerable increase of LDL-C, triglyceride and lipoprotein A levels. These changes in fatty metabolism, essential for embryonic development, might be critical for placental circulation and for mother's health. Indeed, high lipoprotein amount can raise uteroplacental vascular resistance and it is associated with intrauterine growth restriction because of oxidative stress, whereas hypertriglyceridemia and hypercholesterolemia might cause an increased risk of cardiovascular accidents and pancreatitis. Lipid-lowering drugs, such as statins, ezetimibe or PCSK9 inhibitors are discontinued due to possible teratogen effects. Thus, LDL apheresis is the only available therapy for severe hypercholesterolemia during pregnancy. Method A 46 years old woman affected by heterozygous familial hypercholesterolemia in treatment with PCSK9 inhibitors and statins, decided to undergo an heterologous in vitro fertilization with oocyte donation. Hence, pharmacological therapy was stopped to avoid teratogen effects. We started a 10-months apheresis program with double filtration plasmapheresis (DFPP). The treatment was performed by a temporary double lumen central venous catheter. Initially, she underwent apheresis twice a month with an average exchange volume of 1.2, low blood flow (≤ 90 ml/min) and incremental plasma flow (from 5 to 30 ml/min every 10 minutes of treatment), to ensure a physiological procedure. We gradually modulated the exchange volume monitoring blood levels of LDL-C, Lp(a) and triglycerides before and after each procedure. We aimed to keep mean LDL-C level < 200 mg/dl. We did not use anti-coagulation during the procedure, monitoring TMP values and arterial-venous pressure. Results LDL-C levels remained about 227.2 ± SD 91 mg/dl, with a median of 186.8 mg/dl, complying with the target range (Figure 1). Mean triglycerides and Lp(a) values were, respectively, 180.3±94 mg/dl (median 146 mg/dl) and 77.3±36.3 mg/dl (median 55.7 mg/dl) (Figure 1). Our patient did not face any complications related to pregnancy or to the procedure, and gave birth at 38th gestational week to an healthy full-term male baby of 52 centimeters and 3.34 kilograms. Conclusion Although there is a widespread hesitation in performing extracorporeal blood purification treatment in pregnancy, this case underlines the essential role of LDL apheresis in in this setting, giving spark to standardize the procedure and to encourage its use also in pregnancy.

Homozygous Familial Hypercholesterolemia in Canada: An Observational Study

BackgroundHomozygous familial hypercholesterolemia (HoFH) is a rare genetic disease characterized by very high levels of low-density lipoprotein cholesterol (LDL-C). Untreated patients present with extensive xanthomas and premature atherosclerosis. Lipid-lowering therapy is highly efficacious and has dramatically increased life expectancy of patients with HoFH. ObjectivesThe aim of the study was to obtain a comprehensive registry of HoFH in Canada, known to have several founder effect regions, and describe the clinical characteristics and cardiovascular outcomes of this population over time. MethodsClinical and genetic data on patients with HoFH were collected via a standardized questionnaire sent to academic sites participating in the Familial Hypercholesterolemia Canada network. ResultsA total of 48 patients with HoFH were enrolled. The median age at diagnosis was 12 years (interquartile range [IQR]: 5-24) and untreated LDL-C levels were 15.0 mmol/L (IQR: 10.5-18.6 mmol/L; 580 mg/dL IQR: 404-717 mg/dL). At last follow-up visit, median age was 40 years (IQR: 26-54 years). Treated LDL-C levels were 6.75 mmol/L (IQR: 4.73-9.51 mmol/L; 261 mg/dL IQR: 183-368 mg/dL) with 95.5% of patients on statins, 88.6% on ezetimibe, 34.1% on proprotein convertase subtilisin/kexin type 9 inhibitors, 27.3% on lomitapide, 13.6% on evinacumab, and 56.8% were treated with low-density lipoprotein apheresis or plasmapheresis. Deaths were reported in 7 (14.5%) and major adverse cardiovascular events were observed in 14.6% of patients with the average onset at 30 years (IQR: 20-36 years). Aortic stenosis was reported in one-half the patients (47.9%) and 10 (20.8%) underwent aortic valve replacement. ConclusionsThis HoFH patient registry in Canada will provide important new health-related knowledge about the phenotypic manifestations and determinants of cardiovascular risk in this population, allowing for closer examination of quality of life and burden to the health care system.

LDL Apheresis And/or Human Monoclonal Antibodies as Treatment in Se-vere Dyslipoproteinemia

LDL Apheresis And/or Human Monoclonal Antibodies as Treatment in Se-vere Dyslipoproteinemia

Long‐term prognosis of focal segmental glomerulosclerosis treated with therapeutic low‐density lipoprotein‐apheresis in patients with severe kidney dysfunction and proteinuria

AbstractBackgroundThe prognosis of focal segmental glomerulosclerosis patients with nephrotic syndrome is estimated to be 10%–20% in 5 years and 30%–50% in 10 years, leading to end‐stage kidney disease. The response rate with steroid therapy is 40%–60%. Therapeutic low‐density lipoprotein‐apheresis (LDL‐A) may be effective in patients with steroid resistance. Information regarding the long‐term prognosis of patients with focal segmental glomerulosclerosis receiving this therapy is scarce.MethodsWe investigated the effectiveness of treatment in 50 patients with primary focal segmental glomerulosclerosis diagnosed between 1961 and 2017 at Kanazawa University Hospital and related facilities. The patients were observed at least 12 months after biopsy or until end‐stage kidney disease occurrence or death.ResultsLDL‐A was performed in four patients who presented with steroid‐resistant nephrotic syndrome (two patients had concurrent acute renal failure for which hemodialysis was performed). In comparison with 17 patients who did not receive LDL‐A after 1989, the LDL‐A group had higher urinary protein excretion (13.7 vs. 5.2 g/day, P = 0.053) and serum creatinine (4.11 vs. 1.65 mg/dL) levels at onset, and a numerically higher remission rate (75.0% vs. 58.7%) compared with the nonlipoprotein‐apheresis group.ConclusionTherapeutic LDL‐A can be performed for critical cases and may improve the remission rate.

Gene and cell therapy approaches for familial hypercholesterolemia: An update.

Familial hypercholesterolemia (FH) is a common autosomal codominant hereditary illness marked by the heightened risk of early atherosclerotic cardiovascular disease and high blood levels of low-density lipoprotein cholesterol (LDL-C). FH patients can have homozygous or heterozygous variants. This condition has been linked to variations in the genes for the LDL receptor (LDLR), apolipoprotein B, proprotein convertase subtilisin/Kexin 9 (PCSK9), and LDLR adaptor protein 1. Drugs such as statins, ezetimibe, and PCSK9 inhibitors are currently widely available, allowing for the theoretical normalization of plasma LDL-C levels mostly in patients with heterozygous FH. However, homozygous FH patients usually have a poor response to traditional lipid-lowering therapy and may have a poor prognosis at a young age. LDL apheresis and novel pharmacological therapies such as microsomal transfer protein inhibitors or anti-angiopoietin-like protein 3 monoclonal antibodies are extremely expensive and unavailable in most regions of the world. Therefore, the unmet need persists for these patients. In this review, we discuss the numerous gene delivery, gene editing, and stem cell manipulation techniques used in this study to correct FH-causing LDLR gene variations in vitro, ex vivo, and in vivo. Finally, we looked at a variety of studies that corrected genetic defects that caused FH using the ground-breaking clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) gene editing technology.

Efficacy of extracorporeal plasma therapy for adult native kidney patients with Primary FSGS: a Systematic review

Purpose This study aimed to assess efficacy of extracorporeal plasma therapy (EPT), including plasmapheresis (PE), immunoadsorption (IA), low-density lipoprotein apheresis (LDL-A), and lymphocytapheresis (LCAP) for adult native kidney patients with primary focal segmental glomerulosclerosis (FSGS). Methods A literature search was conducted using MEDLINE, EMBASE and Cochrane Databases through August 2022. Studies that reported outcomes of EPT in adult native kidneys with primary FSGS were enrolled. Results 18 studies with 104 therapy-resistant or refractory primary native FSGS patients were identified. Overall EPT response rate was 56%, with long-term benefit of 46%. Of the 101 non-hemodialysis (HD) patients, 54% achieved remission, with 30% complete remission (CR) and 23% partial remission (PR). Of 31 patients with PE, response rate was 65%; CR and PR rates were 27% and 37% in 30 non-HD patients. Of 61 patients with LDL-A, the response rate was 54%; CR and PR rates were 41% and 3% in 29 non-HD patients. Of 10 patients with IA, response rate was 40%. Of 2 patients with LCAP, 1 achieved CR, and one developed renal failure. All 3 HD patients showed increase in urine output and gradual decrease in urine protein excretion following PE (n = 1) or LDL-A (n = 2). 2 of 3 HD patients ultimately discontinued dialysis. Conclusion EPT with immunosuppressive therapy showed benefit in some patients with refractory primary FSGS, and PE appeared to have a higher response rate.

Design, Rationale, and Preliminary Results of the Canadian Homozygous Familial Hypercholesterolemia Registry: 2008 to 2022 Update


 Homozygous familial hypercholesterolemia (HoFH) is an orphan disease characterized by extreme elevations of low-density lipoprotein cholesterol (LDL-C) in the blood and premature atherosclerotic cardiovascular disease.
 Untreated, survival beyond 30 years is rare.
 The Canadian HoFH Registry was created by clinicians from across Canada to understand the burden of disease, current treatments, outcomes, and costs to society.
 The registry will be used to inform decisions for access to specialized therapies, such as LDL apheresis and orphan medications.
 To date, 79 cases of HoFH have been identified across the country, and 52 patients from 5 provinces have been enrolled.

Management and clinical outcomes of patients with homozygous familial hypercholesteremia in Saudi Arabia.

We report the incidence, patient characteristic with clinical outcomes in patients with homozygous familial hypercholesterolemia (HoFH) in Saudi Arabia. This is a retrospective and prospective, single center study which included 37 patients 14 years and older enrolled and followed up between 2018-2021 for three years. 46% were females, 78% were offspring of consanguineous marriage. LDLR mutation was in 78% and LDL-C/LDLRAP in 3% of patients. Mean LDL-C at the first presentation was 14.2±3.7 mmol/L, average Dutch lipid score was 20.9±6.24. LDL apheresis was performed on 70% of patients. Most patients were on ezetimibe (92%), high-dose statins ( 84%) and PCSK9 inhibitors (32%). 48.6% had aortic stenosis, out of which 30% had severe aortic stenosis. Ten underwent aortic valve surgery (5 mechanical valve, 3 Ross procedure, 1 aortic valve repair, 1 bioprosthetic valve) and one had transcatheter aortic valve implantation (TAVI). Coronary artery bypass surgery (CABG) was performed on 32% and percutaneous intervention (PCI) on 11% of patients. HoFH patients have complex diseases with high morbidity and mortality, and benefit from a highly specialized multidisciplinary clinic to address their clinical needs. Although there are several therapeutic agents on the horizon, early diagnosis, and treatment of HoFH remain critical to optimize patient outcomes.

Invasive aspergillosis in the patient with focal segmental glomerulosclerosis initiating hemodialysis: a case report and mini-review

BackgroundInvasive aspergillosis (IA) is a severe form of fungal infection caused by the genus Aspergillus in immunocompromised hosts and has a high mortality rate. End-stage kidney disease (ESKD) is one of the risk factors for developing fungal infection; however, the detailed clinical and treatment course of ESKD patients with IA has been scarcely reported, especially for the patient initiating hemodialysis (HD). Here, we experienced a patient under immunosuppressive therapy for focal segmental glomerulosclerosis (FSGS) who suffered from IA involving lung and brain and resulted in initiating HD.Case presentationA 66-year-old male patient with a history of suspected non-tuberculosis mycobacterial lung disease was initially admitted to the hospital with minimal change disease and subsequently diagnosed as FSGS with worsening urinary protein levels. The combined treatment including immunosuppressive treatments of cyclosporin and glucocorticoids and low-density lipoprotein apheresis was initiated, and then, he experienced the symptoms of dry cough, somnolence, and disorientation, which were subsequently diagnosed as IA involving lung and brain. The patient required renal replacement therapy, and maintenance HD was continued. Despite the intensive treatment with multiple antifungals of liposomal amphotericin B, voriconazole, micafungin, and amphotericin B, the pneumonia of the patient did not improve, and he subsequently passed away.ConclusionsWe report the case of the IA under immunosuppressive treatment, who was subsequently initiated maintenance HD. The detailed clinical course of medications used to treat the patient is presented with the literature review of IA in ESKD and HD patients and those with past acid-fast bacterial infections. The careful determination of the intensity of immunosuppression and monitoring of the patient’s symptoms and early definitive diagnosis is crucial in treating IA in immunocompromised hosts with ESKD or in HD under immunosuppressive treatment, as the mortality for these patients is suspected to be high despite the intensive treatment.

Effect of Low-Density Lipoprotein Apheresis on Quality of Life in Patients with Diabetes, Proteinuria, and Hypercholesterolemia

Introduction: Treating diabetic nephropathy with low-density lipoprotein (LDL) apheresis reduces proteinuria and improves prognosis. However, its impact on patients’ quality of life (QoL) is unclear. This study evaluated the effect of LDL apheresis on QoL in patients with diabetes, proteinuria, and hypercholesterolemia. Methods: In this nationwide multicenter prospective study, we enrolled 40 patients with diabetes. Inclusion criteria were proteinuria (defined as an albumin/creatinine ratio ≥3 g/g), serum creatinine levels <2 mg/dL, and serum LDL ≥120 mg/dL despite drug treatment. LDL apheresis was performed 6–12 times within 12 weeks. The 36-item Short Form Health Survey (SF-36) was used to analyze QoL. Results: The study enrolled 35 patients (27 men and 8 women; mean age 58.9 ± 11.9 years). A comparison of baseline SF-36 values with those at the end of the course of apheresis found an improvement in the mean physical component summary (37.9 ± 11.4 vs. 40.6 ± 10.5, p = 0.051) and a significant increase in the mean mental component summary (MCS) (49.4 ± 8.4 vs. 52.5 ± 10.9, p = 0.026). A multivariable linear regression analysis revealed a history of coronary heart disease negatively correlated with the MCS increase at the end of the course of apheresis (β coefficient −6.935, 95% confidence interval, 13.313 to−0.556, p = 0.034). Conclusion: Our results suggest that LDL apheresis may improve the mental and physical QoL in patients with diabetes, proteinuria, and hypercholesterolemia.

Induction of vascular endothelial growth factor-A165a in human retinal and endothelial cells in response to glyoxal.

Low-density lipoprotein (LDL) apheresis is effective and safe for patients with diabetes, proteinuria, and dyslipidemia. Diabetes mellitus is accompanied by ocular microvascular complications like retinal neovascularization or diabetic macular edema. These are leading causes of blindness and can be mediated by abnormal vessel growth and increased vascular permeability due to elevated levels of vascular endothelial growth factor (VEGF) in diabetic patients. In this study, we established methods to study the expression of different VEGF isoforms in human retinal and endothelial cells. The VEGF-A165a isoform is much higher expressed in retinal cells, compared to endothelial cells. Stimulation with glyoxal as a model of oxidative stress under diabetic conditions lead to a pronounced induction of VEGF-A165a in human retinal and endothelial cells. These data suggest that diabetes and oxidative stress induce VEGF-A isoforms which could be relevant in regulating the ingrowths of novel blood vessels into the retina in diabetic patients.

Familial Hypercholesterolemia and Its Current Diagnostics and Treatment Possibilities: A Literature Analysis.

Familial hypercholesterolemia (FH) is a common, inherited disorder of cholesterol metabolism. This pathology is usually an autosomal dominant disorder and is caused by inherited mutations in the APOB, LDLR, and PCSK9 genes. Patients can have a homozygous or a heterozygous genotype, which determines the severity of the disease and the onset age of cardiovascular disease (CVD) manifestations. The incidence of heterozygous FH is 1: 200-250, whereas that of homozygous FH is 1: 100.000-160.000. Unfortunately, FH is often diagnosed too late and after the occurrence of a major coronary event. FH may be suspected in patients with elevated blood low-density lipoprotein cholesterol (LDL-C) levels. Moreover, there are other criteria that help to diagnose FH. For instance, the Dutch Lipid Clinical Criteria are a helpful diagnostic tool that is used to diagnose FH. FH often leads to the development of early cardiovascular disease and increases the risk of sudden cardiac death. Therefore, early diagnosis and treatment of this disease is very important. Statins, ezetimibe, bile acid sequestrants, niacin, PCSK9 inhibitors (evolocumab and alirocumab), small-interfering-RNA-based therapeutics (inclisiran), lomitapide, mipomersen, and LDL apheresis are several of the available treatment possibilities that lower LDL-C levels. It is important to say that the timeous lowering of LDL-C levels can reduce the risk of cardiovascular events and mortality in patients with FH. Therefore, it is essential to increase awareness of FH in order to reduce the burden of acute coronary syndrome (ACS).

The fluctuation of skin perfusion pressure in hemodialysis patients treated with LDL apheresis therapy: A comparison of LDL adsorption and double filtration plasmapheresis.

There have been a number of reports suggesting that LDL apheresis, including LDL adsorption and double filtration plasmapheresis (DFPP), can be applied for the treatment of lower extremity peripheral arterial disease (PAD) in hemodialysis patients, whereas there is no definitive recommendation for the use of LDL apheresis. The change of skin perfusion pressure (SPP) during LDL apheresis was measured in every single treatment to determine the effect of LDL adsorption and DFPP on improving blood flow in lower extremity PAD hemodialysis patients. Eleven hemodialysis patients treated with more than two series of LDL apheresis were involved in the study. "One series" included 10 treatments of LDL apheresis according to the Japanese health care insurance system. In total, 320 treatments (32 series) of LDL apheresis were performed utilizing either LDL adsorption or DFPP treatment in 11 patients. The SPP values pre- and post-apheresis were recorded in 315 treatments (228 LDL adsorption and 87 DFPP). The SPP was significantly improved after both LDL adsorption (P < .001) and DFPP (P=.002) treatment. The median change of SPP was significantly larger in the LDL adsorption group (12.6 mm Hg, range: -48.5, 77.0 mm Hg) than in the DFPP group (6.7 mm Hg, range: -42.0, 72.5 mm Hg) (P=.003). The LDL adsorption consistently offered a significant increase in the SPP, whereas DFPP treatment seemed to have modest effects on the improvement of SPP compared to the LDL adsorption. These data indicate that LDL adsorption should be considered the primary LDL apheresis therapy for lower extremity PAD in hemodialysis patients to achieve improvement of blood flow.

Abstract 10882: Homozygous Familial Hypercholesterolemia: Luck Meets Opportunity Meets Knowledge

Introduction: Homozygous familial hypercholesterolemia (HoFH) is an inherited autosomal co-dominant disorder characterized by severely elevated circulating low-density lipoprotein (LDL). Monoclonal antibodies are now a treatment focus. Inhibition of proprotein convertase subtilisin kexin type 9 (PCSK9) increases the number of LDL receptors. Inhibition of angiopoietin-like 3 (ANGPTL3) inhibitor is associated with hypolipidemia and reduced risk of cardiovascular disease. We present the case of one of the oldest living patients with HoFH. Case Description: The patient is a 67-year-old black woman diagnosed with corneal arcus senilis and xanthomas at the age of 11, with total cholesterol (TC) levels &amp;gt;1000 mg/dL. At age 12, she underwent a partial ileal bypass (PIB) that lowered her TC by 39%. At age 32, she began statin therapy (Lovastatin, intensified to Atorvastatin at age 43). Despite concomitant dietary changes, her LDL levels remained elevated (&amp;gt;400 mg/dL). At age 34, multivessel coronary artery disease was detected and she initiated lipoprotein apheresis. Her LDL-C was reasonably well-controlled over the 20 years on LDL apheresis and high intensity statin therapy. Combined therapy with PCSK9 inhibitors (Evolocumab at age 61, replaced by Alirocumab at age 67) and ANGPTL3 inhibitor Evinacumab (age 67) lowered her LDL-C significantly. Genetic analysis confirmed two LDLR mutations: c.1846-1G&amp;gt;A and c.907C&amp;gt;T. Conclusion: Elevated cholesterol levels are linked to a higher risk of premature myocardial infarction and stroke. We report a case of HoFH with successful lowering of LDL levels on dual antibody and high intensity statin therapy along with PIB. Unlike PCSK9 inhibitors, ANGPTL3 inhibitors work independently of LDLRs by stimulating lipoprotein &amp; endothelial lipase. This case offers insight into early surgical and combination drug therapy in HoFH and describes one of the longest living patients with HoFH illustrating treatment evolution.

Abstract 12279: Cardiovascular Disease Progression in Children With Homozygous Familial Hypercholesterolemia Despite Early Diagnosis on a Genetic Cascade Screening Program

Introduction: Homozygous familial hypercholesterolemia (HoFH) is a rare genetic disorder characterized by extremely elevated low-density lipoprotein cholesterol (LDL-c) and very high risk of premature atherosclerotic cardiovascular (ASCVD) and aortic/supraortic valve heart diseases (VHD). The study aim was to examine clinical and biochemical trajectories of a cohort of HoFH patients since childhood. Methods: In this longitudinal study we assessed the incidence of manifest or subclinical ASCVD (coronary or carotid) and VHD as well as plasma lipids in a cohort of HoFH subjects during a 12.9 ± 9.6 years follow-up. Results: From the 868 individuals ≤19 y-old (at baseline) that were genotyped on a genetic cascade screening program, 420 (48.4%) had an FH mutation. From children bearing mutations, 12 were true homozygotes and 1 was compound heterozygote (53.8% females, mean age 7.5 ± 4.1 years at the first visit). During follow-up all were on statin and ezetimibe therapies, and the mean final dose of atorvastatin was 56 ± 27 mg/d (n=10); and rosuvastatin, 26 ± 17 mg/d (n=3). Initial and on treatment LDL-c were 655 ± 177 mg/dL and 399 ± 150 mg/dL, respectively, with a mean 39.1% reduction (-256 mg/dL). None were under LDL apheresis; 2 patients used mipomersen, 2 lomitapide, and 2 are currently using PCSK9 inhibitors. Subclinical cardiovascular disease, either coronary, carotid or in aortic valve, was identified in 38.5% (n=5; mean age 16.4 ± 9.8 years), whereas 30.8% had a clinical cardiovascular event (n=4; mean age 22.8 ± 6.8 years), with 2 deaths. Therefore, 69.3% had either subclinical or manifest cardiovascular disease. Conclusion: Despite early diagnosis and LDL-c reduction HoFH is still marked by an adverse and premature cardiovascular disease progression. Conventional lipid lowering therapies are not adequate to prevent ASCVD and VHD disease course.

SUCCESSFUL USE OF ICATIBANT PRE-TREATMENT TO PREVENT SYSTEMIC REACTION DURING LDL APHERESIS

<h3>Introduction</h3> Familial hyperlipidemia(FH) is a hereditary condition characterized by elevated low-density lipoprotein (LDL) levels, treated by medications and possibly apheresis when refractory. There's a rare risk of anaphylactoid reactions in 0.2-0.4%. Current literature reports apheresis reactions could be mediated by complement, bradykinin, or cytokine activation. <h3>Case Description</h3> A 62-year-old man with FH and coronary artery disease, not taking ACE-inhibitors/ARBs, developed recurrent systemic reactions during apheresis after COVID-19 infection 1 month prior. Reactions consisted of headache, facial/tongue swelling, and oral tingling. For 7 years before his COVID-19 infection, he tolerated apheresis with a pre-medication routine of solumedrol and diphenhydramine. After the COVID-19 infection, reactions subsided after stopping the procedure. For his subsequent procedure, prednisone prior was unsuccessful at preventing reactions. For the following infusion, adjunctive prednisone, cetirizine, aspirin, montelukast administered the night prior and morning of the infusion and slowing the infusion rate to the lowest settings were unsuccessful. Complement and tryptase levels were all normal at baseline and following symptomatic treatments (Table 1) suggesting no predisposition to angioedema. Given elevated bradykinin levels are associated with LDL apheresis and these reactions, Icatibant was administered before infusion along with his routine pre-medications, and the apheresis procedure was completed without incident. <h3>Discussion</h3> Limited documented cases of these reactions during LDL apheresis respond to bradykinin antagonists and none of which began after COVID-19 infection. COVID-19 is associated with significant inflammation, but rarely angioedema. Further investigation is needed as to why this FH patient is more sensitive to the effects of bradykinin after COVID-19 infection.

SARS-CoV-2 IgG spike protein antibody response in mRNA-1273 Moderna® vaccinated patients on maintenance immunoapheresis - a cohort study.

BackgroundThe SARS-CoV-2 pandemic increased mortality and morbidity among immunocompromised populations. Vaccination is the most important preventive measure, however, its effectiveness among patients depending on maintenance immunoglobulin G (IgG) apheresis to control autoimmune disease activity is unknown. We aimed to examine the humoral immune response after mRNA-1273 Moderna® vaccination in immunoapheresis patients.MethodsWe prospectively monitored SARS-CoV-2 IgG spike (S) protein antibody levels before and after each IgG (exposure) or lipid (LDL) apheresis (controls) over 12 weeks and once after 24 weeks. Primary outcome was the difference of change of SARS-CoV-2 IgG S antibody levels from vaccination until week 12, secondary outcome was the difference of change of SARS-CoV-2 IgG S antibody levels by apheresis treatments across groups.ResultsWe included 6 IgG and 18 LDL apheresis patients. After 12 weeks the median SARS-CoV-2 IgG S antibody level was 115 (IQR: 0.74, 258) in the IgG and 1216 (IQR: 788, 2178) in the LDL group (p=0.03). Median SARS-CoV-2 IgG S antibody reduction by apheresis was 76.4 vs. 23.7% in the IgG and LDL group (p=0.04). The average post- vs. pre-treatment SARS-CoV-2 IgG S antibody rebound in the IgG group vs. the LDL group was 46.1 and 6.44%/week from prior until week 12 visit.ConclusionsIgG apheresis patients had lower SARS-CoV-2 IgG S antibody levels compared to LDL apheresis patients, but recovered appropriately between treatment sessions. We believe that IgG apheresis itself probably has less effect on maintaining the immune response compared to concomitant immunosuppressive drugs. Immunization is recommended independent of apheresis treatment.

Unusual reaction to PCSK9 inhibitors and lipoprotein apheresis: A mind-boggler clinical case

Background and Aims : Heterozygous familial hypercholesterolemia is one of the most common genetic disorders and patients often require PCSK9 inhibitors to reach LDL-c target values. When these medications are not effective enough or not well-tolerated, treatment with LDL apheresis should be implemented.

妊娠21週で高トリグリセリド血症による重症急性膵炎を発症し血漿交換療法とLDL（low density lipoprotein）吸着療法を施行した1例(A case of plasma exchange and LDL apheresis during the second trimester in a pregnant woman with hypertriglyceridemia–induced severe acute pancreatitis)

要旨症例は38歳，妊娠21週の女性。発熱，腹痛を主訴に絨毛膜羊膜炎の診断で入院加療していたが，改善に乏しく，血液検査と造影CTで高トリグリセリド血症（triglyceride: TG，TG値 9,922mg/dL）による急性膵炎と診断した。高TG血症に対して，薬物療法を行ったが奏功せず，血漿交換療法を施行した。その後，呼吸不全と代謝性アシドーシスが進行したため，帝王切開により妊娠を終結させた。経過中，LDL吸着療法を2回施行し，TG値は690mg/dLまで低下した。膵炎の保存的加療を継続し，第29病日に退院した。高TG血症による重症膵炎では，膵炎治療に加えて高TG血症への治療併施が重要だが，TG値に応じて異なる血液浄化療法を選択し，病態改善に寄与したと考えられた。

The Importance of Arterial Stiffness Assessment in Patients with Familial Hypercholesterolemia.

Cardiovascular diseases are still the leading cause of mortality due to increased atherosclerosis worldwide. In the background of accelerated atherosclerosis, the most important risk factors include hypertension, age, male gender, hereditary predisposition, diabetes, obesity, smoking and lipid metabolism disorder. Arterial stiffness is a firmly established, independent predictor of cardiovascular risk. Patients with familial hypercholesterolemia are at very high cardiovascular risk. Non-invasive measurement of arterial stiffness is suitable for screening vascular dysfunction at subclinical stage in this severe inherited disorder. Some former studies found stiffer arteries in patients with familial hypercholesterolemia compared to healthy controls, while statin treatment has a beneficial effect on it. If conventional drug therapy fails in patients with severe familial hypercholesterolemia, PCSK9 inhibitor therapy should be administered; if these agents are not available, performing selective LDL apheresis could be considered. The impact of recent therapeutic approaches on vascular stiffness is not widely studied yet, even though the degree of accelerated athero and arteriosclerosis correlates with cardiovascular risk. The authors provide an overview of the diagnosis of familial hypercholesterolemia and the findings of studies on arterial dysfunction in patients with familial hypercholesterolemia, in addition to presenting the latest therapeutic options and their effects on arterial elasticity parameters.