Apheresis Therapy Research Articles

S1447 Treatment of Severe Hypertriglyceridemia-Induced Pancreatitis With Insulin Drip

INTRODUCTION: Severe elevation of serum triglycerides (TG) is associated with a high morbidity and mortality, worldwide. TG levels greater than 1000 mg/dl predispose to the development of acute pancreatitis and require urgent treatment. The breakdown of TG by pancreatic enzymes releases free fatty acids, activates trypsinogen resulting in inflammation of the pancreas. Treatment with IV insulin promotes synthesis of lipoprotein lipase leading to rapid reduction of TG levels. We present a case of severe hypertriglyceridemia induced pancreatitis treated with IV insulin despite meeting criteria for apheresis therapy. CASE DESCRIPTION/METHODS: /Methods 30 years old male with history of diabetes presented with abdominal pain and vomiting. Physical exam was remarkable for tenderness in the epigastric. Labs revealed metabolic acidosis due to beta-hydroxybutyrate and elevated lipase. CT abdomen confirmed the diagnosis of pancreatitis. No history of alcohol abuse and abdominal ultrasound was unremarkable. Serum triglyceride level was >4425 mg/dl. The patient did not have lactic acidosis, hypocalcemia, however he did have >2 signs of inflammation. IV insulin was started to treat diabetic ketoacidosis as well as hypertriglyceridemia. Over the course of three days, the triglyceride level dropped to 579 mg/dl and IV insulin was switched to subcutaneous insulin. The triglyceride reduction rate was maxed at 118 mg/dL/h at the beginning of insulin therapy and slowest at 51 mg/dL/h at the end of treatment. The patient was started on Fenofibrate and Atorvastatin therapy prior to discharge. He was instructed to test for primary causes of severe hypertriglyceridemia. DISCUSSION: The indications for lipid apheresis include TG >1000 mg/dl, serum lipase greater than three times the upper limit, severe hypocalcemia, lactic acidosis, worsening inflammation, or organ dysfunction. Despite meeting criteria for apheresis therapy, the patient’s serum TG were safely and effectively lowered below 500 with insulin drip over the course of three days, without any adverse effects. In current guidelines there is no consensus on first line therapy. Observational studies have compared the efficacy as well as risks vs benefits of both therapies, showing promising results for insulin. However, more research is required in large scale centers. Insulin drip should be considered as an effective treatment of HTG induced pancreatitis in select patients to minimize invasive procedures and the risks associated with them.Figure 1.: A trend of serum triglyceride level while receiving IV insulin drip.

Current state of therapeutic apheresis and cellular therapy education for transfusion medicine fellows in the United States.

Numerous conditions are responsive to therapeutic apheresis (TA) and cellular therapy (CT) treatments. Both TA and CT are two broad and diverse knowledge fields within transfusion medicine (TM). We therefore sought to survey all the TM fellowship program directors (PDs) in the United States to examine the current fellow state education in TA and CT. A 37-question survey was sent to all PDs to collect details of TA and CT training for TM fellows. Responses from 29/51 (56.9%) surveyed programs were received. Most PDs considered TA and CT training for their fellows more than adequate. Two PDs from programs that did not directly oversee TA and CT services at their training sites stated that their program's training in these two areas were only "slightly adequate" or "moderately inadequate." Detailed analysis of training in TA, cell collection, and CT suggests that trainees from programs with direct oversight of these services had longer training and more learning experiences compared to those in which outside rotations were required. Transfusion medicine fellowship training in TA and CT varies. Most respondents, and particularly those from programs directly overseeing TA services, reported their fellows were adequately prepared in TA. Cellular therapy collections and laboratory operations, however, are less consistent areas of training despite the rapid expansion of these fields. Our survey suggests that a greater emphasis in CT training is needed.

Case Report: Overwhelming Babesia Parasitemia Successfully Treated Promptly With RBC Apheresis and Triple Therapy With Clindamycin, Azithromycin, and Atovaquone

Babesiosis with high-grade parasitemia is life-threatening, especially in asplenic hosts. We report an asplenic patient with parasitemia >50% who was successfully treated with prompt red blood cell apheresis and triple therapy with clindamycin + azithromycin + atovaquone. This regimen may be an alternative to poorly tolerated clindamycin + quinine in severe cases.

Do modern therapies change natural history of Neuromyelitis optica?

Neuromyelitis optica spectrum disorder (NMOSD) is an uncommon antibody-mediated disease of the central nervous system. Approximately 75% of patients have antibodies against aquaporin-4, a water channel expressed on astrocytes. Untreated, approximately 50% of NMOSD patients will be wheelchair users and blind, and a third will have died within 5 years of their first attack. Unlike multiple sclerosis, a progressive clinical course is very unusual and the accrual of disability is related to relapses. Aggressive treatment of attacks and highly efficient maintenance therapies to prevent attacks are therefore crucial to prevent residual disability. In this article, we review how high dose steroids and most importantly apheresis and modern therapies implicating B cell depletion, inhibition of complement and IL-6 reception are effective to change its natural history. We will emphasize the results of three recent double blind randomized controlled studies using monoclonal antibodies allowing strong hope to modify natural history of NMOSD.

Plaque Regression and Endothelial Progenitor Cell Mobilization With Intensive Lipid Elimination Regimen (PREMIER).

Low-density lipoproteins (LDLs) are removed by extracorporeal filtration during LDL apheresis. It is mainly used in familial hyperlipidemia. The PREMIER trial (Plaque Regression and Progenitor Cell Mobilization With Intensive Lipid Elimination Regimen) evaluated LDL apheresis in nonfamilial hyperlipidemia acute coronary syndrome patients treated with percutaneous coronary intervention. We randomized 160 acute coronary syndrome patients at 4 Veterans Affairs centers within 72 hours of percutaneous coronary intervention to intensive lipid-lowering therapy (ILLT) comprising single LDL apheresis and statins versus standard medical therapy (SMT) with no LDL apheresis and statin therapy alone. Trial objectives constituted primary safety and primary efficacy end points and endothelial progenitor cell colony-forming unit mobilization in peripheral blood. Mean LDL reduction at discharge was 53% in ILLT and 17% in SMT groups (P<0.0001) from baseline levels of 116.3±34.3 and 110.7±32 mg/dL (P=0.2979), respectively. The incidence of the primary safety end point of major peri-percutaneous coronary intervention adverse events was similar in both groups (ILLT, 3; SMT, 0). The primary efficacy end point, percentage change in total plaque volume at 90 days by intravascular ultrasound, on average decreased by 4.81% in the ILLT group and increased by 2.31% in the SMT group (difference of means, -7.13 [95% CI, -14.59 to 0.34]; P=0.0611). The raw change in total plaque volume on average decreased more in the ILLT group than in the SMT group (-6.01 versus -0.95 mm3; difference of means, -5.06 [95% CI, -11.61 to 1.48]; P=0.1286). Similar results were obtained after adjusting for participating sites, age, preexisting coronary artery disease, diabetes mellitus, baseline LDL levels, and baseline plaque burden. There was robust endothelial progenitor cell colony-forming unit mobilization from baseline to 90 days in the ILLT group (P=0.0015) but not in SMT (P=0.0844). PREMIER is the first randomized clinical trial to demonstrate safety and a trend for early coronary plaque regression with LDL apheresis in nonfamilial hyperlipidemia acute coronary syndrome patients treated with percutaneous coronary intervention. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01004406 and NCT02347098.

Why Some Patients Undergoing Lipoprotein Apheresis Therapy Develop New Cardiovascular Events?

Lipoprotein apheresis (LA) is an effective tool to reduce cardiovascular events (CVEs) in high-risk patients with elevations of low density lipoprotein-cholesterol (LDL-C) and/or Lipoprotein(a) (Lp(a)). All patients included into this retrospective analysis had experienced CVEs before the start of the LA therapy. We compared personal and lab data in two groups: CVEx/0 (n 60) with no new events during LA therapy, CVEx/1+ (n 48) with at least one new event. Patients of Group CVEx/1+ were about 5 years older when they had started the extracorporeal therapy, and they experienced more CVEs prior to that timepoint. There was a positive correlation between the number of CVEs before and during LA therapy. No differences were seen with respect to lipid concentrations, even after a correction of LDL-C concentrations for the LDL-C transported with Lp(a) particles. LA sessions effectively reduced both LDL-C and Lp(a). Lp(a) levels measured before LA sessions were lower than those measured initially. It appeared difficult to reach the target values for LDL-C published in the ESC/EAS Guideline in 2019, although all patients were maximally treated including drugs when tolerated. In conclusion, it will be important to initiate an LA therapy earlier, at least after a second CVE and at a younger age.

Therapeutic Apheresis in Pediatrics with Neurological and Hematological Diseases

The advantages of therapeutic apheresis (TA) with hollow fiber membranes are a complete separation of the corpuscular components from the plasma and due to increased blood flow rate higher efficacy [1]. The use of therapeutic apheresis in pediatric patients, which increasing more and more, has always been restricted by technical difficulties and the low incidence of diseases requiring this kind of treatment. The development of new, more sophisticated membranes and new adsorption technologies allow the most selective separation of plasma components. TA has been successfully introduced in a variety of autoantibody-mediated diseases [2]. The updated information on immunology and molecular biology of different neurological and hematological diseases are discussed in relation to the rationale for apheresis therapy and its place in combination with other modern treatments. The different diseases can be treated by various apheresis methods. Pathogenetical aspects are demonstrated in these diseases, in which they are clarified. TA has been shown to effectively remove the autoantibodies from blood and lead to rapid clinical improvement. For the neurological and hematological diseases, which can be treated with TA, the guidelines of the Apheresis Application Committee (AAC) of the American Society for Apheresis (ASFA) are cited [3, 4].

Dual-chambered venous access port as alternative access for extracorporeal apheresis therapy.

To evaluate the use of a dual-chambered venous access port for extracorporeal apheresis therapy. This was a single-center retrospective analysis of all patients who received a dual-chambered venous access port for apheresis therapy over a 36-month period. Clinical success was defined as successful completion of at least one round of apheresis via the venous access port. Major complications were defined as any event requiring elevation of patient care and/or venous access port removal or repositioning. Minor complications were defined as venous access port issues resolved with clinical intervention. Forty-four patients had a venous access port placed at the time of this study. Patients underwent red cell exchange (n = 33), therapeutic plasma exchange (n = 6) or extracorporeal photopheresis (n = 5). Forty (90%) patients had autoimmune diseases and four (10%) had neoplastic processes. Clinical success was achieved in 42 (95.5%) patients. Average venous access port dwell time was 632 days (range = 42-1191 days). All therapies through the venous access ports were well tolerated and no patients reported pain or discomfort. Major complications were seen in nine (20.5%) patients-the majority (n = 7) of which were due to venous access port malfunction-and resolved with catheter revision. One (2.27%) major complication involved an infected venous access port, and one involved a large hematoma at the venous access port site. Minor complications were seen in eight (18.2%) patients, where simple flushing of the catheter with saline or tissue plasminogen activator resolved the issue. The dual-chambered venous access port was successfully used for sustained blood flow in apheresis therapy with a moderate, yet correctable complication rate.

The effect of DALI lipid apheresis in the prognosis of homozygous familial hypercholesterolemia: Seven patients' experience at a DALI apheresis center.

Introduction:Familial hypercholesterolemia (FH) is characterized by severe hypercholesterolemia that can result in coronary artery disease occurring at an early age. If patients are not cured with lipid-lowering drugs and diets, lipid apheresis may be an effective treatment option in these cases. Here, we evaluate the efficacy, selectivity and safety of the DALI apheresis technique.Materials and Methods:Seven pediatric patients (2 girls; 5 boys) with ages between 7 and 14 years (mean age: 6.5±2.1 years) with HFH were included in this study. We restrospectively evaluated clinical and laboratory findings. We used the DALI system for lipid apheresis concomitant with medical treatment and diet for hyperlipidemia.Results:The cohort's mean T.cholesterol level prior to apheresis was 700.57±136.36 mg/dl,the mean LDL-C value was 526.86±131.56 mg and the mean HDL-C level was 36.57±4.58 mg/dl.The mean cholesterol levels after apheresis were consecutively 317.57±93.70 /257.29±90.38 / 33.36±4.78 mg/dl.We noted a 51.1% reduction in LDL-C level and an 8.7% reduction in HDL-C level in our apheresis sessions.The reduction in LDL-C was statistically significant (p<0.05). During 1025 apheresis therapy, the most frequent mild and moderate adverse events were deviceaccess problems and hypotension (in all patients);severe adverse events were mainly due to cardiac problems(myocardial infarct and arrhythmia) and hypotension.Conclusion:Lipid apheresis is an inevitable alternative treatment for HFH. Despite all of its application problems, DALI system is an effective therapy for decreasing atherogenic lipids from circulation.

Essential updates 2018/2019: Colorectal (benign): Recent updates (2018-2019) in the surgical treatment of benign colorectal diseases.

This review outlines current topics on the surgical treatment of benign colorectal diseases, with a focus on inflammatory bowel disease (IBD) and diverticulitis. Treatment options for IBD and diverticulitis have evolved in the last few years as a result of medical advances in technology and new clinical trials. Therefore, treatment options and strategies need to be updated to provide optimal care for patients. The purpose of this review is to elucidate recent global trends and update the surgical treatment strategy for IBD and diverticulitis based on literature published in the past 2 years. Prevalence of IBD, including ulcerative colitis and Crohn's disease, has increased over the last few decades. During this period, many new medical therapies were introduced for the treatment of IBD, including biological therapy, immunomodulators, and leukocyte apheresis therapy. As a result, new surgical strategies for IBD are required. In order to improve surgical outcomes in IBD patients, the influence of preoperative treatment on postoperative complications needs to be considered. The incidence of diverticulitis is also increasing with lifestyle changes and increasing numbers of older people. For diverticulitis with perforation and generalized peritonitis, surgery is the gold standard. Elective surgery after conservative treatment of diverticulitis is also an option because of high recurrence rates. With an increase in diverticulitis, systematic strategies are essential for an appropriate approach to diverticulitis, taking into account various factors, including the patient's background.

Efficacy of apheresis as maintenance therapy for patients with ulcerative colitis in an open-label prospective multicenter randomised controlled trial.

Apheresis therapy involves the selective removal of leukocytes and is used to induce remission in ulcerative colitis (UC) patients. The aim of this study was to demonstrate the efficacy and safety of apheresis therapy for maintaining UC remission. We conducted a multicenter, prospective, randomised-control trial of patients with remitting UC induced by granulocyte and monocyte adsorption apheresis or leukocytapheresis. Patients were randomly assigned to the apheresis group (twice per month for 12months) or the control group (no apheresis treatment) using a 1:1 allocation ratio. The primary endpoint was the rate of cumulative clinical remission (Mayo score≤2) at 12months. The secondary endpoints were the rates of clinical remission, endoscopic remission, and complete endoscopic remission at 12months. Between March 2013 and March 2017, 164 patients were enrolled. The cumulative remission rate at 12months was 46.6% in the apheresis group and 36.4% in the control group (p = 0.1621). The rate of endoscopic remission at 12months was significantly higher in the apheresis group than in the control group (42.5% vs. 25.9%)p = 0.0480). The rate of clinical remission (47.5% vs.32.1%, p = 0.0540) and complete endoscopic remission (33.8% vs.19.8%, p = 0.0513) tended to be higher in the apheresis than in the control group; however, the difference was not significant. No severe adverse events were observed in either group. Apheresis was well tolerated as maintenance therapy for UC although the cumulative clinical remission rate at 12months was comparable between the apheresis and control groups.

Extracorporeal apheresis therapy for Alzheimer disease-targeting lipids, stress, and inflammation.

Current therapeutic approaches to Alzheimer disease (AD) remain disappointing and, hence, there is an urgent need for effective treatments. Here, we provide a perspective review on the emerging role of "metabolic inflammation" and stress as a key factor in the pathogenesis of AD and propose a novel rationale for correction of metabolic inflammation, increase resilience and potentially slow-down or halt the progression of the neurodegenerative process. Based on recent evidence and observations of an early pilot trial, we posit a potential use of extracorporeal apheresis in the prevention and treatment of AD. Apolipoprotein E, lipoprotein(a), oxidized LDL (low density lipoprotein)'s and large LDL particles, as well as other proinflammatory lipids and stress hormones such as cortisol, have been recognized as key factors in amyloid plaque formation and aggravation of AD. Extracorporeal lipoprotein apheresis systems employ well-established, powerful methods to provide an acute, reliable 60-80% reduction in the circulating concentration of these lipid classes and reduce acute cortisol levels. Following a double-membrane extracorporeal apheresis in patients with AD, there was a significant reduction of proinflammatory lipids, circulating cytokines, immune complexes, proinflammatory metals and toxic chaperones in patients with AD. On the basis of the above, we suggest designing clinical trials to assess the promising potential of such "cerebropheresis" treatment in patients with AD and, possibly, other neurodegenerative diseases.

Lipoprotein apheresis for lipoprotein(a) and cardiovascular disease

Elevated lipoprotein(a) [Lp(a)] is an independent risk factor for cardiovascular disease (CVD). In the United States, lipoprotein apheresis (LA) therapy is approved for patients with familial hypercholesterolemia. Germany uses LA therapy for patients with an Lp(a)>60mg/dL, normal low-density lipoprotein cholesterol (LDL-C) levels, and CVD. LA therapy in this population demonstrated a >70% reduction in CVD events. In the United States, LA is only approved for patients with elevated LDL-C levels, regardless of Lp(a) level. The objective of the study was to evaluate clinical significance of Lp(a) reduction with LA therapy in the United States. A retrospective cohort study at one LA site in the United States evaluated 14 CVD patients with elevated Lp(a) and near normal LDL-C levels. Patient data was analyzed to demonstrate possible clinical benefit in reducing Lp(a) levels with LA to mitigate risk of major adverse cardiovascular events. Pre-LA patients' mean LDL-C and Lp(a) were 80mg/dL and 138mg/dL, respectively. LA therapy demonstrated a reduction of mean LDL-C to 29mg/dL and Lp(a) to 51mg/dL. These represent a percent reduction of 64% and 63% for LDL-C and Lp(a), respectively. There was a 94% reduction in major adverse cardiovascular events over a mean treatment period of 48months. The treatment of CVD patients with an elevated Lp(a) and near normal LDL-C with LA in a U.S. treatment center demonstrated a significant reduction in future CVD events. LA should be considered for patients in the United States suffering from an elevated Lp(a) and progressive CVD.

Implementation and 2‐year outcomes of the first FDA‐approved implantable apheresis vascular access device

Patients requiring chronic apheresis treatments typically lack sufficient peripheral venous access to support long-term therapy. Historically, central venous tunneled catheters, septum-bearing subcutaneous ports, and fistulas were used to obtain required blood flow rates for apheresis procedures. In 2017, the US Food and Drug Administration approved the first intravascular device specifically designed for apheresis therapy, the PowerFlow Implantable Apheresis IV Port. Several preimplementation meetings with key hospital stakeholders were held to determine the most efficient and safest strategy for integrating the PowerFlow device into our practice. Interventional radiologists implanted the apheresis port in patients meeting specified criteria. Performance metrics and adverse events were evaluated over a 2-year period, July 2017 through June 2019. Eighteen patients underwent apheresis therapy using the PowerFlow port. The most common apheresis therapy provided was extracorporeal photopheresis, followed by therapeutic plasma exchange and low-density lipoprotein apheresis. Flow rates up to 90 mL/min were obtained; the rates were limited by patient tolerance for the apheresis procedure. Complications included infection, obstruction due to fibroblastic sleeve, and migration of the vascular device. The estimated risk of PowerFlow-associated bloodstream infection in the study population was 0.18 per 1000 intravascular device days. The PowerFlow Implantable Apheresis IV Port can achieve flow rates necessary for all apheresis therapies and is a promising alternative vascular access device for patients undergoing apheresis.

SAT-084 DIFFERENCE IN RATE OF DECLINE OF ISOAGGLUTININ TITERS BETWEEN SELECTIVE PLASMA EXCHANGE WITH AND WUTHOUT FRESH FROZEN PLASMA BEFORE ABO-INCOMPATIBLE KIDNEY TRANSPLANTATION

Isoagglutinins removal by apheresis and immunosuppressive therapy are generally performed at pre-transplant desensitization of ABO-incompatible kidney transplantation. Selective plasma exchange (SePE) is a new simple plasma exchange (PE) modality that enables removal of small and medium-sized molecules without removing larger molecules, such as coagulation factors. Since 2015, we have always performed SePE using albumin solution in patients with a low isoagglutinin titers, or we added this approach in patients in whom the isoagglutinin titers was sufficiently decreased by double-filtration plasmapheresis (DFPP) and/or simple PE. However, although this procedure is advantageous in that it has fewer adverse effects, it also removes about 30% of coagulation factors, such as fibrinogen and factor XIII, and this is problematic in the perioperative period. Thus, we currently perform SePE using fresh frozen plasma (FFP) as part of the replacement fluid in patients with a decline of coagulation factors. We have had a favorable impression clinically with regard to the decline of the antibody titer with use of FFP. In this study, we examined if this impression was supported by a significant difference in outcomes.

Familial Hypercholesterolemia and Lipoprotein Apheresis.

Lipoprotein apheresis has been developed as the treatment for refractory familial hypercholesterolemia (FH) to remove low-density lipoprotein (LDL), which is the main pathogenic factor. Currently, three procedures are available in Japan, including the plasma exchange, double-membrane filtration, and selective LDL adsorption. Selective LDL adsorption, which was developed in Japan, has been one of the most common treatment methods in the world. Lipoprotein apheresis enabled the prevention of atherosclerosis progression even in homozygous FH (HoFH) patients. However, in our observational study, HoFH patients who started lipoprotein apheresis in adulthood had a poorer prognosis than those who started in childhood. Therefore, HoFH patients need to start lipoprotein apheresis as early as possible. Although the indication for lipoprotein apheresis in heterozygous FH (HeFH) patients has been decreasing with the advent of strong statins, our observational study showed that HeFH patients who discontinued lipoprotein apheresis had a poorer prognosis than patients who continued apheresis therapy. These results suggest that it is beneficial for very-high-risk HeFH patients to be treated by lipoprotein apheresis even if their LDL cholesterol is controlled well by lipid-lowering agents. Since launching a new class of lipid-lowering agents, proprotein convertase subtilisin/kexin type 9 (PCSK9) antibody and microsome triglyceride transfer protein inhibitors, the indication for lipoprotein apheresis in FH has been changing. However, despite the development of these drugs, lipoprotein apheresis is still an option with a high therapeutic effect for FH patients with severe atherosclerotic cardiovascular disease.

Critical developments of 2018: A review of the literature from selected topics in transfusion. A committee report from the AABB's Clinical Transfusion Medicine Committee.

The AABB compiles an annual synopsis of the published literature covering important developments in the field of transfusion medicine. An abridged version of this work is being made available in TRANSFUSION, with the full-length report available as Appendix S1 (available as supporting information in the online version of this paper). Papers published in late 2017 and 2018 are included, as well as earlier papers cited for background. Although this synopsis is comprehensive, it is not exhaustive, and some papers may have been excluded or missed. The following topics are covered: "big data" and "omics" studies, emerging infections and testing, platelet transfusion and pathogen reduction, transfusion therapy and coagulation, transfusion approach to hemorrhagic shock and mass casualties, therapeutic apheresis, and chimeric antigen receptor T-cell therapy. This synopsis may be a useful educational tool.

A cross-national investigation of cardiovascular survival in homozygous familial hypercholesterolemia: The Sino-Roman Study

Homozygous familial hypercholesterolemia (hoFH) is a rare inherited disorder characterized by extreme elevation of low-density lipoprotein (LDL) cholesterol, accelerated coronary artery disease, and premature death. Aggressive LDL-lowering therapies are important for survival, but these are not available worldwide. The aim of the study was to compare and contrast cardiovascular outcomes and mortality of hoFH patients in 2 countries with disparate use of lipoprotein apheresis (LA) and modern therapies for lowering LDL cholesterol. A retrospective study was undertaken comparing cardiovascular disease (CVD)-free survival and mortality in 44 hoFH patients who were treated with statins but not LA, from a center in Beijing, China, and 18 hoFH patients who were treated with LA and novel therapies from an early age, from a center in Rome, Italy. CVD-free survival and survival were significantly reduced in Chinese patients compared with the Italian patients after 30years of follow-up (log-rank P<.01). In a pooled analysis, cardiovascular survival was significantly increased with earlier age at treatment, longer duration of treatment, and lower on-treatment LDL cholesterol concentrations (P<.05). In addition, the probability of a CVD event and death were increased in patients that carried a null mutation in the LDLR or had elevated lipoprotein(a). We show that coronary artery disease outcomes in patients with hoFH can be significantly improved with earlier and potent LDL cholesterol lowering with pharmacotherapies and LA. This has major implications for countries, such as China, where the models of care for hoFH remains underdeveloped.

Clearance of Intra-graft Donor Specific Anti-HLA Antibodies in the Early Stage of Antibody-Mediated Rejection Following Rituximab and Apheresis Therapy in Renal Transplantation

BackgroundThe management of acute or, in particular, chronic antibody-mediated rejection (AMR) resulting from donor-specific HLA antibodies (DSA) is a critical barrier to obtaining better long-term graft survival. To ascertain the efficacy of anti-AMR therapies, the transition of intra-graft DSA (g-DSA) was assessed. MethodsAllograft biopsy specimens were analyzed by graft immunocomplex capture fluorescence analysis, as previously described. One hundred recipients who underwent graft biopsies between April 2016 and December 2017 were enrolled for this study. Fifteen recipients diagnosed with g-DSA positive (+) received anti-humoral treatments and underwent follow-up biopsies. g-DSA levels were assessed again by a follow-up biopsy at 6–12 months following the treatments. ResultsWith anti-humoral treatments, 9 out of 15 recipients comprised a g-DSA negative (-) (3.59 ± 2.82-.58 ± .25): g-DSA6-12- group, while the remaining 6 recipients comprised a g-DSA +(20.6 ± 17.0-14.9 ± 14.1): g-DSA6-12+ group. The initial g-DSA scores were significantly higher in the g-DSA6-12+ group (P = .01). All samples were diagnosed as chronic AMR in the g-DSA+ groups, whereas there were 3 chronic AMR, 4 acute AMR, and 2 incomplete AMR samples in the g-DSA- group. Interestingly, the frequency of responsible DSA belonging to class II tended to be higher in the g-DSA6-12+ group (4/6) compared to the g-DSA6-12- group (2/9) (P = .14). ConclusionThese results imply that chronic exposure to DSA causes significant and irreversible damage to the allograft. Timely and adequate anti-humoral intervention might reverse the early phase of AMR with complete clearance of g-DSA.

Tu1846 – Higher TNFα and Mip-1β Expression in Pretreatment Colonic Mucosa Have Potential to Predict of Achieving Mucosal Healing by Granulocyte and Monocyte Adsorptive Apheresis Therapy in Ulcerative Colitis Patients

Tu1846 – Higher TNFα and Mip-1β Expression in Pretreatment Colonic Mucosa Have Potential to Predict of Achieving Mucosal Healing by Granulocyte and Monocyte Adsorptive Apheresis Therapy in Ulcerative Colitis Patients