Combination Of Plasmapheresis Research Articles

#3105 Tocilizumab for treatment of antibody mediated rejection in kidney transplant patients

Abstract Background and Aims Chronic active antibody-mediated rejection (caABMR) causes 40% of long-term graft failure after kidney transplantation (KT). Early treatment is of great importance, however, hard clinical evidence is still lacking. Currently the combination of plasmapheresis (PF), rituximab and intravenous immunoglobulin is used as standard treatment. Tocilizumab (TCZ) is a monoclonal antibody, IL-6 receptor antagonist, and it inhibits the production of donor-specific antibodies (DSA). We hypothesized that tocilizumab administration has an additional effect on graft survival and non-inferior to standard therapy in KT patients with ABMR. Method Retrospective single-center noninferiority case-control study was performed by involving 73 KT patients (43.5 ± 14.3 years, females 31, eGFR 19.5 ± 13.4) with biopsy proven ABMR diagnosed between June 2017 and May 2022. 19 patients received 8 mg/kg intravenous TCZ therapy for 6 months (12 aABMR, 7 caABMR, 38.6 ± 12.8 years, females 6). In the control group (C, n=54, 10 aABMR, 44 caABMR, 45.2 ± 14.5 years, females 25), 20 patients received plasmapheresis treatment, the rest stayed on optimized maintenance therapy (tacrolimus, mycophenolic acid, prednisolone). Baseline demographic data, standard laboratory data, proteinuria and DSA level were also monitored and analyzed. Results Graft loss occurred in 13 cases (6 aABMR, 7 caABMR) in KT on TCZ therapy and 43 (6 aABMR, 37 caABMR) in C group, meaning significantly lower risk of graft loss in the TCZ group (RR 0.69, p=0.036) during the median follow-up of 11.3 (IQR 2.5-23.1) months. In TCZ group, all caABMR patients lost their graft during the observation. In TCZ group, 1 year after the TCZ treatment, DSA (pooled) was lower (7028 (575-17782) versus 1605 (551-16903), p<0.05). Conclusion Early administration of TCZ seems to be noninferior to standard therapy and effective to prevent early graft loss as part of standard therapy in aABMR. Further clinical studies are needed to clarify clinical indications of TCZ and its long-term effects on the course of chronic active ABMR.

Principles of treatment of intrahepatic cholestasis of pregnant women

BACKGROUND:Intrahepatic cholestasis of pregnancy occupies a leading place in the structure of hepatoses associated with pregnancy. As with many other diseases that debut during gestation, all the symptoms of intrahepatic cholestasis of pregnancy disappear after delivery and have no consequences for the mother, unlike, for example, acute fatty degeneration of the liver. However, the fetal prognosis remains serious due to the high incidence of preterm birth and the toxic effect of bile components on the developing fetus, which both lead to perinatal complications. Especially fatal is the situation when intrahepatic cholestasis of pregnancy is combined with intrauterine infection, placental insufficiency, severe preeclampsia, diabetes mellitus, or other extragenital pathology. Until recently, it was believed that the only correct solution for intrahepatic cholestasis of pregnancy development was early delivery. Only in recent decades, attempts have been made to therapeutic correction of this pathology in order to prolong pregnancy to full term and reduce the frequency of perinatal complications. So far, tangible results have been achieved with the use of ursodeoxycholic acid preparations and the introduction of efferent methods of therapy into obstetric practice.
 AIM:The aim of this study was to develop optimal schemes for pathogenetic therapy of intrahepatic cholestasis of pregnancy using hepatoprotectors from the ursodeoxycholic acid group, as well as ademetionine, essential phospholipids, and membrane plasmapheresis.
 MATERIALS AND METHODS:This study included 150 pregnant women with intrahepatic cholestasis of pregnancy. Group I (n= 50) comprised patients who were treated only with ursodeoxycholic acid. Group II (n= 50) included individuals who were given combined drug therapy with ursodeoxycholic acid, ademetionine, and essential phospholipids. Group III (n= 50) consisted of women whose treatment included efferent therapies (membrane plasmapheresis) in combination with ursodeoxycholic acid or ademetionine preparations. All pregnant women before the start of therapy were determined the blood levels of bile acids, total and direct bilirubin, and transaminases (alanine aminotransferase, aspartate aminotransferase). Blood parameters were monitored once every seven days. All the patients were also monitored for the condition of the fetus (fetometry, dopplerometry, cardiotocography).
 RESULTS:The use of ursodeoxycholic acid not combined with other hepatoprotectors (group I) was possible only in cases of increased blood levels of bile acids of not more than 40 mmol/L, preparations of ademetionine and essential phospholipids as monotherapy being ineffective. With an increase in the blood levels of bile acids of more than 40 mmol/L and transaminases by two to three or more times from the upper limit of the norm (group II), the most effective was the combined use of ursodeoxycholic acid, ademetionine and essential phospholipid preparations. The most significant decrease in the blood levels of bile acids and hepatic cytolysis parameters (transaminases) was observed when plasmapheresis was used in combination with ursodeoxycholic acid or ademetionine (group III).
 CONCLUSIONS:The choice of treatment regimen depends on the level of increase in bile acids and the severity of cytolytic syndrome. With an increase in the level of bile acids to 40 mmol/L, ursodeoxycholic acid preparations can be used only. With an increase in bile acid level of more than 40 mmol/L, the complex use of the above hepatoprotectors is necessary. The most effective treatment regimen is the use of membrane plasmapheresis in combination with ursodeoxycholic acid or ademetionine.

A randomized controlled trial of preemptive rituximab to prevent recurrent focal segmental glomerulosclerosis post-kidney transplant (PRI-VENT FSGS): protocol and study design.

Focal segmental glomerulosclerosis (FSGS) is a common cause of end-stage kidney disease requiring kidney transplantation and can recur in the allograft in 30-80% of recipients resulting in reduced graft survival. Plasmapheresis has shown efficacy in treating some cases of recurrent FSGS but isolated plasmapheresis has not demonstrated efficacy in preventing recurrent FSGS. Rituximab has had anecdotal success in preventing recurrence in a single center study but has not been studied in combination with plasmapheresis for preventing FSGS recurrence. We are conducting a randomized, controlled, multicenter clinical trial of adult and pediatric kidney transplant recipients with primary FSGS to assess whether plasmapheresis in combination with rituximab prevents recurrent disease post-transplantation. Rituximab combined with plasmapheresis is a promising, novel therapy to prevent recurrent FSGS, a disease with limited therapeutic options and no consensus guidelines for prevention or treatment. https://clinicaltrials.gov/ct2/show/NCT03763643, identifier NCT03763643.

Multidisciplinary Treatment in Toxic Epidermal Necrolysis.

Toxic epidermal necrolysis, Leyll's syndrome (TEN), is a rare mucocutaneous blistering disease burdened with high mortality rates. The diagnosis of TEN is based on clinical symptoms and histopathological findings. In approximately 90% of cases, it is a severe adverse reaction to drugs. In TEN, not only is the skin affected, but also mucosa and organs' epithelium. There are no unequivocal recommendations in regard to systemic and topical treatment of the patients. The aim of this paper is to review available literature and propose unified protocols to be discussed. Early management and multidisciplinary treatment are necessary to improve patients' outcome. Treatment of patients with TEN suspicions should be initiated with early drug withdrawal. TEN patients, like patients with burns, require intensive care and multidisciplinary management. Each patient with TEN should be provided with adequate fluid resuscitation, respiratory support, nutritional treatment, pain control, infection prophylaxis, anticoagulant therapy, and gastric ulcer prophylaxis. The key to local treatment of patients with TEN is the use of nonadherent dressings that do not damage the epidermis during the change. The aim of the systemic treatment is purification of the blood stream from the causative agent. The most efficient way to clarify serum of TEN patients' is the combination of plasmapheresis and IVIG. Immunomodulatory therapy can reduce the mortality five times in comparison with the patients with immunosuppression or lack of full protocol.

P8.148: HLA Desensitization in Kidney Transplantation

Introduction: In the last decade, organ transplantation has been developing fast in Kazakhstan. 1892 transplants have been performed since 2012. Patients often need kidney (91.5%), heart (4.4%), liver (4%) transplantations. Nearly 100 kidney transplantations from living donors and 30 ones from deceased donors are performed annually. The most important factor hindering the long-term survival of recipients is HLA sensitization. The formation of specific antibodies to HLA may develop as a result of previous transplantation, blood transfusion or pregnancy. There are 3.5% highly sensitized patients among 3012 patients on the waiting list for kidney transplantation. This study aimed to review an effectiveness of desensitizing therapy during the preparation of patients for transplantation. Methods: This study included 13 patients with end-stage chronic kidney disease (CKD). The participants underwent a general clinical examination, a specialized immunological study to determine the level of antibodies to leukocyte antigens (anti-HLA) before and after the desensitization stages. Microsoft Excel was used to perform statistical analyses. Qualitative variables were summarized in the form of absolute frequency and percentages. Results: The proportion of male and female was 38.5% (5) and 61.5% (8), respectively. The average age of the participants was 44.8 years, ranging from 25 to 58 years. 30.8% (4) of patients had a decrease in the level of leukocyte antibodies after rituximab administration and three sessions of citrate plasmapheresis. In 23.1% (3) of patients, the level of sensitization remained same. An increase in the level of leukocyte antibodies was observed in 15.4% (2) of participants. 15.4% (2) of patients are currently at the second stage of desensitization. In 53.8% (7) of patients, a positive cross-match test is observed, which leads to the impossibility of kidney transplantation from living donor. A significant decrease in leukocyte antibodies was revealed in 53.8% (7) patients after repeated plasmapheresis sessions, despite the absence of differences in the level of antibodies after administration of rituximab and one plasmapheresis session. 46.2% (6) of the participants underwent only the first stage (rituximab) and one plasmapheresis session. 37.5% (3) of female had 5 or more pregnancies, which affects the increased immunological risk in CKD. 62.5% (5) of women had one pregnancy each and they had a decrease in the level of antibodies after rituximab and one plasmapheresis session. One patient has a significant decrease in the level of leukocyte antibodies after several sessions of plasmapheresis. 25% (2) undergo the first stage of desensitizing therapy. Conclusion: According to preliminary data, the combination of plasmapheresis and rituximab was insufficient to achieve a negative cross-match test and kidney transplantation. In this regard, we recommend adding the introduction of human immunoglobulin to desensitizing therapy. This study is ongoing.

Characteristics of expression of cancer stem cell markers in various approaches to cervical cancer treatment.

e17516 Background: Cancer stem cells (CSCs) are being actively studied as a possible origin of malignant neoplasms. Research of the properties of CSCs and mechanisms of their regulation holds the promise of the development of new approaches to antitumor therapy. The most frequently detected CSC markers in different tumors are CD44 and CD133. In this regard, the aim of our study was to identify characteristics of expression of CSC markers in cervical cancer treatment and their possible predictive value. Methods: The study included 237 patients with locally advanced cervical cancer T2a-2bNx-1M0. Patients were divided depending on the treatment: neoadjuvant chemotherapy with cisplatin and bleomycin (NACT, n = 84); plasmapheresis (PA) in combination with NACT (PA+NACT, n = 60); PA+NACT with nonspecific immunotherapy with an interferon inducer (PA+NACT+IT, n = 93). Immunohistochemical study was performed on sections from paraffin blocks of tumors using anti-CD44 monoclonal mouse antibodies (156-3C11, Thermo Scientific) at a dilution of 1:2500 and anti-CD133 polyclonal rabbit antibodies (AF5120, Affinity Biosciences) at a dilution of 1:400 (Thermo autostainer Scientific 480S). Membrane staining and staining intensity were evaluated: 0, 1+ weak, 2+ moderate, 3+ strong staining. Protein expression was defined as positive when staining was detected in ≥10% of all tumor cells with a staining intensity ≥2. Statistical analysis of the results was performed with the STATISTICA 13.0 program (StatSoftInc., USA) using the Mann-Whitney U-test. Results: Tumors with positive CD133 and CD44 expression were observed in all groups of patients. However, only PA+NACT+IT patients had CD133- (57%) and CD44- (43%) tumors. Median expression of CD133: in NACT - 70 [60;80]; PA+NACT - 60 [37;70], PA+NACT+IT - 25 [5;60]. Median expression of CD44: in NACT - 30 [10;40]; PA+NACT - 30 [13;65], PA+NACT+IT - 20 [2; 40]. CD133 expression in PA+NACT+IT patients was significantly lower than in PA+NACT and NACT patients by 2.4 times (*p = 0.009) and 2.8 times (*p = 0.002), respectively. CD44 expression in tumors of patients with PA+NACT+IT was 1.5 times lower (statistically non-significant). Differences in tumors of NACT and PA+NACT patients were not found. Conclusions: The immunohistochemical study revealed a decline in the expression of CSC markers (CD133 and CD44) in tumors of patients who received PA+NAPCT+IT. The results obtained for the CD133 marker show its possible value as a predictive factor in the treatment of cervical cancer.

Immunomodulatory Treatment of Lyell's Syndrome: A Simultaneous Plasmapheresis and Intravenous Immunoglobulins Therapy.

Lyell's syndrome, or toxic epidermal necrolysis (TEN) is a rare but life-threatening condition. It manifests with blistering of skin and mucous due to subepidermal bullae and keratinocyte necrosis. In most cases, it is an immune response to drugs or their metabolites. The mortality in TEN is high despite optimal infection and wound control. There are no unequivocal treatment guidelines in TEN. Immunosuppressive treatment may increase the wound infection risk and mortality. The aim of the study was to evaluate a 10-year experience with immunomodulatory therapy in TEN. We perform a combination of plasmapheresis and intravenous immunoglobulins to control the disease. There were 35 patients in the group and we performed a post hoc evaluation. Twenty-eight patients received the full protocol and there were seven patients who did not complete the treatment (single therapy group). The mortality in the test group was 14.29%, and the difference reached statistical significance in comparison with the single therapy group (P < .05). Our protocol reduced the mortality risk five times. Our study proved that simultaneous plasmaphereses with intravenous immunoglobulins administration were safe and improved patients' outcome in TEN.

ANTIBACTERIAL THERAPY IN INFECTED FORMS OF NECROTIC PANCREATITIS

Summary: Evaluation of the effectiveness of antibacterial therapy at different stages of necrotic pancreatitis (NP) is the most important area of ​​scientific and practical research on the course of necrotic pancreatitis and the development of sepsis. The work is based on the results of a comprehensive examination and treatment of 54 patients with necrotic pancreatitis in the intensive care unit of city Hospital № 3, Zaporizhia in 2017-2019 pp.
 Objective: Optimize the use of antibacterial therapy in the complex treatment of infected forms of NP depending on the microbial spectrum of infection, the course of the disease and the development of sepsis.
 Material and methods of research. The study included 54 patients with infected forms of NP who were treated in the Department of Anesthesiology and Intensive Care of the 3rd City Hospital. Research results and their discussion. Thus, the analysis of antibiotic sensitivity showed that high activity against pathogens, based on the perception of the main pathogens characteristic of infected forms of NP, is observed in meropenem, taigecycline and tobramycin. When studying the species composition of microorganisms, it was found that the NP is dominated by gram-negative flora: Pseudomonas aeruginosa - 26.5%, Acinetobacter spp. - 21.2%, family Enterobacteriaceae: Klebsiella pneumoniae - 10.2% and Escherichia coli - 15.6%. Resistant strains of Ps were found in 22% of patients. Aeruginosa. The use of detoxification therapy with the inclusion of extracorporeal detoxification methods (discrete plasmapheresis) in combination with two-component antibacterial therapy (meropenem + linezolid) led to a positive trend in the course of the disease.
 Conclusions. Analyzing the course of the disease in patients with infected NP and its complications on the basis of constant monitoring of bacterial flora with optimal antibacterial therapy, prevention of nosocomial infection and modern strategy of surgical interventions, especially minimally invasive, noted a positive trend in the course of sepsis and sepsis.

POS-808 "Renal allograft cortical necrosis" - Disappearing entity in live renal transplant over two decades - A Single centre experience

Renal graft cortical necrosis (GCN) is a catastrophic cause of graft failure. The literature is very scarce on this entity. We evaluated the incidence, causes, management, and outcome of allograft cortical necrosis in two decades from our center. This is a retrospective analysis of transplant patients who had biopsy-proven allograft cortical necrosis, transplanted between 2000 and 2020. Demographic details, immunological workup, induction, and maintenance regimen, cause of cortical necrosis, the outcome was analyzed. Data were analyzed using SPSS version 20. Continuous data were presented in mean ± standard deviation, for non-normal data, the median (interquartile range) was used. Among 1975 transplant recipients, 37 (1.87%) patients had GCN. Of which 35 patients (2.87/100 transplant/year) were between 2000-2010; 2 patients (0.086/100 live transplants/year) between 2011-2020. All had CDC crossmatch XM negative. None had flow crossmatch testing before 2011 whereas all were tested with FXM after 2012. Mean days to GCN was 8. 28 had early rejection (19 had vascular rejection); 7 had graft vessel thrombosis,1 had mucormycosis. 60% had diffuse; 40% had partial GCN. 60% received ATG; 11% received combined plasmapheresis and ATG as anti-rejection therapy. 25 patients had no recovery, 9 had partial recovery and 3 had a complete recovery.15 patients underwent nephrectomy within 24 days (median); 11 patients died of sepsis; median days to death from transplant was 56 days. 4 underwent a second renal transplant. The dramatic decrease in the incidence of graft cortical necrosis after 2011 could be attributed to use of improved DSA detection methods, crossmatching techniques, adoption of better desensitization protocols in our institute.

A Young Woman with Anemia and Thrombocytopenia

<p>本文描述一位32歲女性病患，罹患全身性紅斑性狼瘡已有11年，規則於門診追蹤，因發燒、關節痛、胸痛，實驗室檢查發現貧血、血小板低下、補體（C3）低下、高效價之抗雙股去氧核糖核酸抗體（anti-dsDNA > 379 IU／mL）、尿液呈現蛋白尿，初步診斷懷疑全身性紅斑性狼瘡復發。靜脈注射高劑量methylprednisolone七天，血小板仍偏低，治療反應差。本個案實驗室檢查顯示溶血性貧血、血小板低下、週邊血液抹片顯示碎裂紅血球，確定微血管性溶血性貧血證據，且血液中ADAMTS 13嚴重缺乏其血中活性為0%，因此診斷為血栓性血小板低下紫斑症。緊急接受血漿置換術，同時持續高劑量類固醇與靜脈注射Rituximab治療，因而血小板上升、乳酸脫氫脢大幅下降、貧血改善，達到治療的成效。全身性紅斑性狼瘡同時出現血栓性血小板低下紫斑症，經緊急啟動血漿置換，會降低病人的死亡率。</p> <p> </p><p>A 32-year-old female patient in this study, who suffered from systemic lupus erythematosus (SLE) for 11 years. Upon a regular rheumatology outpatient follow-up, she presented not only with fever,arthralgia and chest pain, but also with anemia, low platelets, low complement (C3), and high titer anti-double-strand deoxyribonucleic acid antibody (anti-dsDNA > 379 IU/mL) on laboratory test report,as well as proteinuria on urinalysis. Accordingly, her condition was suspected to be a relapse of SLE. Unfortunately, after treatment with high-dose intravenous methylprednisolone, the response was poor with persistent low platelet level. Besides, hemolytic anemia and thrombocytopenia were noted and peripheral blood smear examination also showed fragmented red blood cells, supporting the diagnosis of microangiopathic hemolytic anemia. Moreover, there was severe ADAMTS13 deficiency in the blood, even with 0% of activity. Therefore, the patient was finally diagnosed with thrombotic thrombocytopenic purpura and then received urgent plasmapheresis in combination with high-dose glucocorticoid and of intravenous rituximab treatment. After the treatment, the platelet level increased, lactate dehydrogenase level remarkably decreased, and anemia gradually improved. Taken together, urgent initiation of plasma exchange together with glucocorticoid and rituximab treatment for SLE patient with thrombotic thrombocytopenic purpura could lower the mortality rate.</p> <p> </p>

Plasma cell–directed therapies in monoclonal gammopathy–associated scleromyxedema

AbstractScleromyxedema is a rare skin and systemic mucinosis that is usually associated with monoclonal gammopathy (MG). In this French multicenter retrospective study of 33 patients, we investigated the clinical and therapeutic features of MG-associated scleromyxedema. Skin molecular signatures were analyzed using a transcriptomic approach. Skin symptoms included papular eruptions (100%), sclerodermoid features (91%), and leonine facies (39%). MG involved an immunoglobulin G isotype in all patients, with a predominant λ light chain (73%). Associated hematologic malignancies were diagnosed in 4 of 33 patients (12%) (smoldering myeloma, n = 2; chronic lymphoid leukemia, n = 1; and refractory cytopenia with multilineage dysplasia, n = 1). Carpal tunnel syndrome (33%), arthralgia (25%), and dermato-neuro syndrome (DNS) (18%) were the most common systemic complications. One patient with mucinous cardiopathy died of acute heart failure. High-dose IV immunoglobulin (HDIVig), alone or in combination with steroids, appeared to be quite effective in nonsevere cases (clinical complete response achieved in 13/31 patients). Plasma cell–directed therapies using lenalidomide and/or bortezomib with dexamethasone and HDIVig led to a significant improvement in severe cases (HDIVig refractory or cases with central nervous system or cardiac involvement). The emergency treatment of DNS with combined plasmapheresis, HDIVig, and high-dose corticosteroids induced the complete remission of neurological symptoms in 4 of 5 patients. Quantitative reverse-transcriptase polymerase chain reaction analysis of 6 scleromyxedema skin samples showed significantly higher profibrotic pathway levels (transforming growth factor β and collagen-1) than in healthy skin. Prospective studies targeting plasma cell clones and/or fibrotic pathways are warranted for long-term scleromyxedema management.

Whole exome sequencing identifies three novel gene mutations in patients with the triad of diabetic ketoacidosis, hypertriglyceridemia, and acute pancreatitis.

This study aimed to analyze the genetics and treatments of the patients with the triad of diabetic ketoacidosis (DKA), hypertriglyceridemia, and acute pancreatitis (AP). We conducted a retrospective study of six patients with the triad of AP, hypertriglyceridemia, and DKA at our hospital. All patients underwent plasmapheresis as part of their treatment. The clinical characteristics of the patients were obtained from the hospital information system and analyzed. Whole exome sequencing was performed using samples of one patient (case 6) and his family members. The average triglyceride level before plasmapheresis was 3282.17 ± 2975.43 mg/dL (range: 1646-9332 mg/dL). The triglyceride levels dropped by approximately 80% after plasmapheresis. None of the patients developed complications related from plasmapheresis. During follow-up, patients 5 and 6 developed recurrent pancreatitis for several times and showed the formation of pancreatic pseudocysts. We identified three novel heterozygous missense mutations in the family of patient 6, including c.12614C > T (p.Pro4205Leu) in APOB, c.160G > C (p.Glu54Gln) in CILP2, and c.1199C > A (p.Ala400Glu) in PEPD. Three novel heterozygous missense mutations, including c.12614C > T (p.Pro4205Leu) in APOB, c.160G > C (p.Glu54Gln) in CILP2, and c.1199C > A (p.Ala400Glu) in PEPD were first identified in a patient with the triad of DKA, hypertriglyceridemia, and AP. The combination of plasmapheresis, hydration, and insulin therapy may have the greatest clinical benefits for these patients.

MO010TREATMENT STRATEGIES OF ANTIBODY MEDIATED REJECTION IN KIDNEY TRANSPLANTATION: A SYSTEMATIC REVIEW AND META-ANALYSIS

Abstract Background and Aims Antibody mediated rejection (AMR) remains accountable for the majority of death-censored graft failure following the first year of kidney transplantation. Despite significant advances in transplant immunology and immunosuppressive agents, long-term graft survival has not improved significantly. The objective of this systematic review and meta-analysis is to determine the optimal treatment strategy for AMR by investigating the effect on kidney function, proteinuria, donor specific antibody (DSA), histopathology, graft survival, adverse events and patient survival. Method MEDLINE (PubMed), Scopus, Cochrane Central Register of Controlled Trials and ClinicalTrials.gov databases were systematically searched following the PRISMA guidelines. Any kidney transplant study conducted between 1997-2018, which investigated treatment strategies for biopsy-proven AMR, and reported at least one of the following outcomes; serum creatinine, glomerular filtration rate (GFR), proteinuria, DSA, histopathology scores, graft survival, adverse events and/or patient survival were eligible for inclusion. Risk of bias was evaluated using the Cochrane Risk of Bias Tool for randomised controlled trials (RCTs) and the ROBINS-I tool for non-randomised controlled studies. Results Our analysis identified a total of 27 studies consisting of 6 RCTs and 21 non-randomised controlled studies. Together these studies included 1,237 transplant recipients; 748 patients with acute AMR (AAMR) and 489 with chronic AMR (CAMR). Meta-analysis identified significantly better 1-year graft survival in patients with AAMR when treated with Rituximab in addition to plasmapheresis and intravenous immunoglobulin (IVIG) compared to plasmapheresis and IVIG alone [risk ratio (RR): 0.48, 95% confidence interval (CI): 0.27-0.86, Z=2.46, P=0.01, I2=0%] (Fig-1A). Pooled analysis of GFR in the AAMR group was not possible due to insufficient data. There was no significant difference in the GFR at 6-12 months after treatment of CAMR with IVIG plus Rituximab compared to no treatment [mean difference: 0.36, 95% CI: -11.80-12.52, Z=0.06, P=0.95, I2=89%] (Fig-1B). Similarly, there was no significant difference in the 1-year graft survival after treatment of CAMR with IVIG plus Rituximab compared to no treatment [RR: 0.77, 95% CI: 0.42-1.40, Z=0.86, P=0.39, I2=9%] (Fig-1C). Late diagnosis of AMR and established transplant glomerulopathy seem associated with graft dysfunction and poor prognosis. Additionally, declining GFR and proteinuria seem to impact considerably on the overall outcome of the graft. Pooled analysis of proteinuria, DSA titres, and histopathology scores was not possible due to insufficient data. Similarly, pooled analysis of adverse events was not possible; however, these therapeutic strategies were generally well tolerated and associated with excellent patient survival throughout the included studies. Novel therapeutic approaches seem promising, but currently there is insufficient evidence for their routine use in AMR. The risk of bias ranged between low-risk to high-risk throughout the included RCTs and between moderate-risk to critical-risk amongst the non-randomised controlled studies. Conclusion This systematic review and meta-analysis outlines the treatment of AMR in kidney transplantation using the current best available evidence. We identified low-quality evidence in favour of treatment with combined plasmapheresis, IVIG and Rituximab in AAMR. Treatment of established CAMR does not seem advantageous in terms of graft function and survival. Additionally, the treatment of AMR is particularly heterogeneous between transplant centres, reflecting the lack of good quality evidence to guide practice. RCTs conducted via multicentre collaboration are urgently required to establish the optimal therapeutic strategies and validate models for predicting therapeutic response in AMR.

Anti-lipid therapy and risk factor management for triglyceridaemia-induced acute pancreatitis.

Pancreatitis secondary to hypertriglyceridaemia is rare, accounting for less than 5% of pancreatitis presentations. We reviewed our institutional experience with triglyceridaemia induced acute pancreatitis to report the clinical presentation, patient demographics and clinical management. The Acute Surgical Unit database at a high-volume general surgical referral centre was queried to identify cases of acute pancreatitis secondary to hypertriglyceridaemia between 2016 and 2019. Patient demographics, clinical manifestations, biochemical derangements and treatment regimens were analysed. Current related literature was reviewed. There were 496 presentations for acute pancreatitis of which 14 presentations (2.8%), amongst 12 patients were due to hypertriglyceridaemia. The mean triglyceride level at presentation was 92.46 (standard deviation 46.9) mmol/L. Ten patients (83%) had poorly controlled type 2 diabetes. All patients were managed using conservative therapy combined with a restricted fat diet and commenced on long-term anti-lipid therapy to manage associated risk factors. In addition, 10 patients received an insulin infusion and one patient received insulin infusion, plasmapheresis and heparin infusion in combination. The median length of hospital stay was 5.5 (range 3-13) days. Two patients (16%) developed a recurrent episode related to non-compliance to medical therapy. Hypertriglyceridaemia is a rare cause of acute pancreatitis. Successful management involves the treatment of acute pancreatitis in conjunction with long-term anti-lipid therapy and optimisation of associated risk factors.

Induction of Accommodation by Anti-complement Component 5 Antibody-based Immunosuppression in ABO-incompatible Heart Transplantation.

Plasmapheresis in combination with immunoglobulin and rituximab is often used to induce accommodation in ABO-incompatible (ABOi) living-donor transplantation; however, this regimen cannot be applied to cases of ABOi deceased-donor transplantation. Here, we investigated whether an anti-complement component 5 (C5) antibody-based regimen can induce accommodation in ABOi heart transplantation. Both IgM and IgG anti-blood type A antibodies were induced in wild-type mice by sensitization using human blood type A antigen. Heterotopic ABOi heart transplantation was performed from human blood type A-transgenic C57BL/6J mice to sensitized wild-type DBA/2 mice. Either anti-C5 antibody or conventional triple immunosuppressants (corticosteroid, tacrolimus, mycophenolate mofetil) alone did not induce accommodation in majority of ABOi heart allografts, whereas their combination induced accommodation in more than 70% of cases despite the presence of anti-A antibodies. The combination therapy markedly suppressed the infiltration of T cells and macrophages into ABOi allografts, despite mild deposition of IgG and C4d. T-cell activation and differentiation into Th1, Th2, and Th17 cells were suppressed along with CD49dCD4 T and follicular helper T cells in the combination treatment group. CD24 B cells, including both CD24CD23 marginal zone B cells and CD24CD23 T2-marginal zone B cells, were increased in the accommodation group. C5 inhibitor-based immunosuppression induced accommodation in murine ABOi heart transplantation, presenting a promising strategy for ABOi deceased-donor transplantation.

Microbial spectrum and rational antibacterial therapy in treatment of infected forms of necrotic pancreatitis

The most significant areas of scientific and practical research in urgent pancreatology of the last decade are the study of the course of necrotic pancreatitis with the evaluation of the effectiveness of antibiotic therapy at different stages of the disease according to microbiological studies, nosocomial infection and the development of sepsis.
 Purposw of the study. To study the effectiveness of antibacterial therapy in complex treatment of infected forms of necrotizing pancreatitis, depending on the species composition of the infection, the severity of the pathology and the development of sepsis.
 Materials and methods. The study included 48 patients with infected forms of necrotic pancreatitis over the past two years undergoing treatment at the Department of Anesthesiology and Intensive Care of Zaporizhzhia 3rd City Clinical Hospital in 2017–2018.
 Results. Research of the species composition of microorganisms showed that there is predominant gram-negative flora in pancreatogenic infection such as: Pseudomonas aeruginosa – 26,3%, Acinetobacter spp. – 21,1%, the Enterobacteriaceae family: Klebsiella pneumoniae – 10,5% and Escherichia coli – 15,8%. The detected spectrum of microorganisms gives an idea of the main pathogens characteristic of infected forms of necrotizing pancreatitis. Antibiotic sensibility analysis showed that high activity against pathogens was observed in meropenem, taygecycline and tobramycin. In 21% of patients, resistant strains of Ps. Aeruginosa were detected, but in 3 patients there was a positive dynamics in the use of detoxication therapy with inclusion of extracorporal methods (discrete plasmapheresis) in combination with two-component antibiotic therapy (meropenem + linezolid).
 Conclusion. The analysis of treatment of patients with infected necrotizing pancreatitis and its complication sonthebasis of continuous monitoring of bacterial flora with the provision of adequate antibiotic therapy, prevention of nosocominal infectionand a modern strategy for the use of surgical interventions, especiallynoninvasive, contributes to the reduction of sepsis and, as a result, reduction in mortality and severe postoperative complications.

Comparative Clinical Study the Effectiveness of Plasmapheresis with Ozone Therapy in the Prevention of Ocular Herpes Recurrence

The purpose. To study the clinical efficacy of plasmapheresis in combination with ozone therapy in the prevention of ocular herpes recurrence.Patients and methods. There were 108 patients with relapsing forms of eye herpes (herpes keratitis, keratouveitis, uveitis) under our observation. 56 men and 52 women, aged between 37 and 62 old (47,6 ± 11,5) were involved into the research. The number of patients included into the main group were 54 (54 eyes), and also 54 patients (54 eyes) were in the comparison group. Results. In the main group, the patients undergone a course of anti — relapse therapy with plasmapheresis in combination with therapeutic ozone in combination with traditional treatment from 54 persons — the expressed therapeutic effect was registered in 48-and (88.8 %) patients, the partial therapeutic effect (decrease in the frequency of relapses) was observed in 6 (11.1 %) patients, the absence of effect was not registered in any patient. In the control group, consisting of 54 patients, which undergone anti-relapse therapy with plasmapheresis in combination with traditional treatment, expressed therapeutic effect (no exacerbations) was observed in 31 (57.4 %) patients, a partial therapeutic effect (decrease in the frequency of relapses) was observed in 17 (31.5 %) patients, and the absence of effect — in 6 (11.1 %) patients.Conclusions. For prevention of ophthalmic herpes recurrence and optimal results of anti-relapse therapy of patients with recurrent ophthalmic herpes were shown concurrently with the beginning of the standard antiherpetic treatment courses of plasmapheresis with ozone therapy and spend it as monotherapy at the end of treatment.

Role of Plasmapheresis in the Management of Acute Kidney Injury in Patients With Multiple Myeloma: Should We Abandon It?

The aim of the current study was to determine whether plasmapheresis in combination with chemotherapy could significantly remove free light chains (FLC) in multiple myeloma (MM) patients with acute kidney injury (AKI) and therefore improve renal recovery and patient survival. During the study period, 29 patients with MM and AKI presented to our unit and were treated with two different therapy modalities (plasmapheresis with chemotherapy or bortezomib). At the end of treatment, a significant decrease of FLCs was present in the group treated with plasmapheresis compared to the bortezomib group. Patients treated with plasmapheresis had similar survival compared to patients treated with bortezomib. There was a significantly higher decrease of FLCs and longer survival in patients treated with three or more plasmapheresis sessions than in patients treated with two plasmapheresis sessions. Plasmapheresis therapy still remains a useful and effective method in the treatment of AKI in MM patients. Plasmapheresis significantly reduces FLCs compared to bortezomib especially with higher number of plasma exchange sessions but it must be combined with other chemotherapy agents in order to prolong renal recovery and therefore patient survival.

A Rare Case of Calcific Rheumatoid Constrictive Pericarditis Complicated by Diffuse Alveolar Hemorrhage and MPO-ANCA-Associated Systemic Vasculitis With Pauci-Immune Glomerulonephritis

SESSION TITLE: Pulmonary Manifestations of Systemic Disease 4 SESSION TYPE: Affiliate Case Report Poster PRESENTED ON: Tuesday, October 31, 2017 at 01:30 PM - 02:30 PM INTRODUCTION: Diffuse alveolar hemorrhage(DAH) is a rare complication in patients with Rheumatoid arthritis(RA). The added calcific constrictive pericarditis, systemic vasculitis and pauci-immune glomerulonephritis(PIGN) in the same patient poses a unique diagnostic and therapeutic dilemma CASE PRESENTATION: A 60-year-old male with a history of RA, calcific constrictive pericarditis was admitted with fever, chills, dry cough and worsening exertional dyspena. He had diminished breath sounds in bilateral lower lung fields on exam. Computed tomography of the chest revealed patchy nodular infiltrate in the left lung and confluent ground glass infiltrate in the right lung with persistent pericardial calcifications. He developed worsening hemoglobin drop and severe hypoxemic respiratory failure worsening and was intubated. Bronchoscopy with sequential bronchoalveolar lavage was progressively more hemorrhagic and hemosiderin laden macrophages confirmed the diagnosis of DAH. He was started on intravenous methylprednisolone. A workup revealed high titers of antibodies (Table1). Due to severity of his illness he had serial plasmapheresis followed by treatment with intravenous cyclophosphamide. Renal biopsy showed PIGN. By hospital day 20 his respiratory and renal function improved and was successfully extubated DISCUSSION: We report for the first time to the best of our knowledge a rare case with chronic rheumatoid constrictive pericarditis complicated by DAH in the setting of MPO-ANCA associated vasculitis and PIGN. One of the rare cardiac complications of RA is constrictive pericarditis confirmed here by cardiac catheterization with equalization of diastolic pressures and discordant right and left ventricular pressures and pericardial calcifications on imaging. DAH complicates 40% of cases of MPO-ANCA vasculitis however, limited data is available in adults with concurrent RA and is associated with higher mortality. The incidence of ANCA in RA is around 40% and both p- and c-ANCA staining patterns are expressed. one study described three RA patients with renal manifestations who improved with a combination of plasmapheresis and cyclophosphamide with or without methylprednisolone such as in our patient. CONCLUSIONS: A high index of suspicion, careful analysis and early detection is essential to improve chances of recovery in these patients Reference #1: Gauhar UA et al. Pulmonary manifestations of rheumatoid arthritis.Semin RespirCrit Care Med 2007;28:430-40. Reference #2: Kurita N et al. MPO-ANCA glomerulonephritis with RA.ClinExpNephrol.2010Aug;14(4):325-32. DISCLOSURE: The following authors have nothing to disclose: Kavitha Gopalratnam, Despina Michailidou, Ashley Rosario-Durchhalter, Paul Cohen, Armand Wolff No Product/Research Disclosure Information

P199 A successful lung transplantation in two patients with positive donor specific antibodies and positive crossmatch

Introduction Sensitization to HLA antibodies has been associated with worse outcome in lung transplant recipients. Many lung transplant centers avoid transplanting patients with positive flow cytometry crossmatch (FCXM). However, delaying the transplant in these patients may increase their mortality on the waiting list. We are reporting two cases of crossmatch positive lung transplantation. Case scenario A 37-year old lady diagnosed with pulmonary fibrosis. Patient sensitized to HLA class I and II at time of transplant.The FCXM was positive T-cell (+78 MCS) and B-cell (+165 MCS). She had multiple DSA: Anti A2 (2795 MFI), Anti DR51 (2215 MFI), Anti DR52 (2088 MFI), Anti DQB1:05:02 (655 MFI), Anti DR14 (1411 MFI), anti DP2 (813 MFI). Second case is a 58-year old lady with pulmonary fibrosis secondary to Sjogren’s syndrome. Patient sensitized to HLA class II only at the time of transplant. The T-cell crossmatch was negative while, B-cell was positive (+318 MCS). She had multiple DSA: Anti DRB1∗10:01(14776 MFI), Anti-DR53 (4796 MFI), Anti-DP1 (1942 MFI), Anti- DQB1∗05:01(3384 MFI), Anti-DP2 (790 MFI). In view of patients’ deterioration, lung transplantation was preceded despite of positive crossmatch results, using combination of plasmapheresis, Intravenous immunoglobulin (IVIG) and Thymoglobulin. Both patients did well with no evidence of graft rejection. However, the repeated HLA antibodies screening during follow up showed persistent DSA. in the first patient: Anti-A2(1377 MFI), Anti-DRB1∗14 (4864 MFI), Anti-DR52 (3044 MFI), Anti-DR51 (1708 MFI), Anti-DP2 (1993 MFI). In the second patient: Anti-A1 (3561 MFI), AntiA24 (712 MFI), Anti-DQB1∗05:01(5837 MFI), Anti-DP1 (692 MFI), Anti-DRB1∗10:01 (643 I). Conclusion Lung transplantation is possible in patients with crossmatch positive, using perioperative desensitization protocol. Desensitization treatment did neither eliminate DSA nor prevent de novo DSA formation. However, follow up of these patients showed no evidence of graft rejection. Long-term data is needed.