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Zieve syndrome is a rare condition which occurs in patients with severe alcohol abuse. It is typically characterised by the triad of jaundice, haemolytic anaemia and transient hyperlipidaemia. In the following report, we present the case of a man in his 30s who was admitted to our emergency department with severe epigastric pain and signs of alcohol intoxication. Blood samples showed signs of severe hyperlipidaemia and jaundice. Due to massive hyperlipidaemia, laboratory measurements of triglycerides were impaired and the blood samples had a ‘yellowish’ and ‘creamy’ texture. In order to prevent pancreatitis, plasmapheresis was performed. Subsequently, triglyceride concentration dropped and the patient was discharged a few days later in significantly improved physical condition. In the following case report, we discuss plasmapheresis as a possible treatment for patients with severe Zieve syndrome in addition to conventional symptomatic therapy.

Immunologically mediated diseases can lead to severe courses that have to be treated in an intensive care unit. The use of extracorporeal organ support systems (ventilation, ECMO) is common. A therapeutic principle for these diseases is the removal of disease-causing antibodies. This can be done nonspecifically by plasmapheresis or specifically by immune adsorption. While most intensive care units have the facilities for plasmapheresis (membrane plasma filtration), immunoadsorption is much less common. Over a period of 10 years, the numbers of immunoadsorption and plasmapheresis treatments performed in a single center intensive care unit are shown according to their indication (IA: 18 Pts, 58 treatments. PA: 54 Pts, 148 treatments). A case study of a patient with granulomatosis with polyangiitis shows the successful treatment with immunoadsorption. The advantages of immunoadsorption in patients with complex coagulation disorders and a critical clinical picture in terms of SIRS and ARDS are shown.

We present here the second documented case of severe immune checkpoint inhibitor-induced myocarditis successfully treated with abatacept. The patient was started on pembrolizumab for stage IIIA malignant melanoma, and after the first dose was admitted for worsening shortness of breath and weakness. Her symptoms were refractory to high-dose steroids and she decompensated rapidly necessitating cardiopulmonary resuscitation and subsequent intubation and mechanical ventilation. Intravenous immunoglobulin and plasmapheresis did not invoke significant improvement, so abatacept was then initiated. She began to show improvement and was eventually discharged to a skilled nursing facility. This case highlights a severe adverse reaction to an immunomodulator class steadily growing in its application. Providers of all specialties should be aware of the side effects and treatment options. Our case demonstrates that continued investigation into the utilisation of CTLA-4 agonists in the treatment of severe adverse reactions like myocarditis caused by pembrolizumab is required.

Granulomatosis with polyangiitis (GPA) is a rare disorder characterised by inflammation of small-sized and medium-sized blood vessels that result in damage to various organ systems, but it most commonly affects the respiratory tract and kidneys. It is one of the few entities that can present with ocular inflammation as well as renal impairment at the same time. We describe a case of a 38-year-old man with conjunctivitis, episcleritis, anterior uveitis as a first manifestation of GPA. His presentation with red eye and anterior uveitis prompted further workup, which revealed acute renal failure (creatinine 442 mmol/L), elevated inflammatory markers (erythrocyte sedimentation rate of 85 mmol/hour and C reactive protein of 72 mg/L), and a c-antineutrophil cytoplasmic antibody titre >8. An urgent renal biopsy was performed demonstrating necrotising crescentic glomerulonephritis, which led to the final diagnosis of GPA. Treatment induction with intravenous methylprednisolone and plasmapheresis followed by an oral prednisone taper and intravenous rituximab infusions leading to resolution of all symptoms and normalisation of kidney function. This report highlights conditions that can present with both ocular inflammation and renal dysfunction with a focus on GPA and its ocular manifestations.

Wunderlich syndrome is a rare condition characterised by acute spontaneous non-traumatic renal haemorrhage into the subcapsular and perirenal spaces. Our case of anti-GAD65-associated autoimmune encephalitis (AE), aged 30 years, developed this complication following use of enoxaparin and was managed by selective glue embolisation of subsegmental branches of right renal cortical arteries. Our case had opsoclonus as one of the clinical manifestations, which has till now been described in only two patients of this AE. This patient received all forms of induction therapies (steroids, plasmapheresis, intravenous immunoglobulin and rituximab) following which she had good improvement in her clinical condition. The good response to immunotherapy is also a point of discussion as this has been rarely associated with anti-GAD65 AE.

This study evaluates the efficacy and safety of plasmapheresis without plasma transfusion tandem with chemotherapy in treating multiple myeloma (MM).This retrospective study involves seventy-two patients, newly diagnosed with multiple myeloma, divided into two groups; one with plasmapheresis without plasma transfusion tandem with the chemotherapy group (Trial group), while the second was chemotherapy group (Control group). The levels of Plasma Globulin, β2-microglobulin, Creatinine, Vascular endothelial growth factor (VEGF), and IL-6 were monitored after plasmapheresis, at initial diagnosis, and after four chemotherapy courses. Overall response rate of groups after four courses of chemotherapy was analyzed, and the adverse events were recorded.The baseline data showed that sixty-seven percent of patients were at the ISS III stage and showed more severe renal insufficiency in the Trial group. The Plasma Globulin, β2-microglobulin, VEGF and IL-6 levels were significantly different between the two groups during the initial diagnosis. After three times plasmapheresis, Plasma Globulin, β2-microglobulin, VEGF, and IL-6 were significantly reduced in the plasmapheresis group. The Creatinine levels were also lowered, but the differences were not statistically significant. After four courses of chemotherapy, the levels of VEGF and IL-6 in the two groups were significantly reduced than the initial diagnosis; the differences were statistically considerable. No adverse events were found in the trial group as compared to the control group.Plasmapheresis reduces Globulin, β2-microglobulin, serum VEGF and IL-6 levels in MM, improves renal functions, and releases some patients from dialysis dependence.

The purpose of our research was to evaluate the effects of saline infusion to counteract incidents of severe hypotension during donor plasmapheresis (DP; synonym with plasma donation), and on immunoglobulin G (IgG) content in collected plasma, and on donor hematological values. It examines the clearance (Cl) of IgG during DP without saline to calculate the distribution of citrate and citrate infusion rate (CIR) during DP. It is based on three studies: an observation of saline infusion in donors with severe drops in blood pressure at DP, and two crossover trials of 32 repeat plasma donors each on saline infusion during DP. We observed 50 cases with a significant drop of mean systolic blood pressure ≤90 mm Hg in 1 year, predominantly in young, female first-time donors. In trial 1, there was a reduction of IgG concentration in collected plasma related to the average IgG serum concentration without saline to 85.5% vs to 80.5% with saline (P .001). In trial 2, there was an important 11%-12% increase of the donor hematological values without saline during DP. An average of 84.6% of citrate was removed in retained plasma; our calculated minimal CIR of 0.16 ± 0.17 mg/kg/min was confirmed by other empirical studies. Our research has led to significant improvements in the practice of DP: (a) Saline should be infused at DP as clinically indicated in agreement with the donor. (b) Young, female first-time donors require special care. (c) The long-time effects of minimal amounts of citrate on bone metabolism are improbable.

Diagnosing uncommon diseases in individuals with underlying medical conditions can be challenging. Cognitive bias can lead to delayed or missed disease management. We present a case of Shiga-toxin mediated hemolytic uremic syndrome (ST-HUS) in a 46-year-old man with ulcerative colitis and alcohol use disorder who presented with acute alcohol intoxication, non-bloody diarrhoea and coffee ground emesis. He was admitted to the hospital for alcoholic ketoacidosis, alcohol withdrawal and possible upper gastrointestinal bleed, but ultimately, he developed severe thrombocytopaenia, hemolytic anaemia, acute renal failure and prolonged altered mentation. Given that ST-HUS is uncommon in adults, his initial report of diarrhoea was attributed to alcohol use or underlying active ulcerative colitis and not connected to his haematologic abnormalities. He was initially started on plasmapheresis; however, thrombotic microangiopathy work up revealed Shiga-toxin in his stool and ADAMST13 levels within normal limits. Subsequently, he was transitioned to supportive care for management of ST-HUS.

Antibody-mediated rejection (AMR) has emerged as the leading cause of late graft loss in kidney transplant recipients. Donor-specific antibodies are an independent risk factor for AMR and graft loss. However, not all donor-specific antibodies are pathogenic. AMR treatment is heterogeneous due to the lack of robust trials to support clinical decisions. This review provides an overview and comments on practical but relevant dilemmas physicians experience in managing kidney transplant recipients with AMR.Active AMR with donor-specific antibodies may be treated with plasmapheresis, intravenous immunoglobulin and corticosteroids with additional therapies considered on a case-by-case basis. On the contrary, no treatment has been shown to be effective against chronic active AMR. Various biomarkers and prediction models to assess the individual risk of graft failure and response to rejection treatment show promise.The ability to personalize management for a given kidney transplant recipient and identify treatments that will improve their long-term outcome remains a critical unmet need. Earlier identification of AMR with noninvasive biomarkers and prediction models to assess the individual risk of graft failure should be considered. Enrolling patients with AMR in clinical trials to assess novel therapeutic agents is highly encouraged.

Anti-glomerular basement membrane (anti-GBM) disease is a rare but severe autoantibody-mediated immune disorder. The typical clinical presentation includes rapidly progressive glomerulonephritis and often concurrent pulmonary hemorrhage. The present study is aimed to investigate the therapeutic effects of rituximab either used alone or with other immunosuppressants.Eight patients diagnosed with anti-GBM disease and treated with rituximab from 2014 to 2020 were retrospectively reviewed.Eight patients included 5 males and 3 females with a median age of 58.5 years. They all presented severe kidney injuries and 1 patient had lung hemorrhage. At diagnosis, the median of serum creatinine was 246 µmol/L (ranging from 91 to 850 µmol/L), with 3 patients requiring dialysis. All of them received corticosteroids and plasmapheresis. Rituximab was given as either standard four weekly doses or one pulse ranging from 100 to 600 mg. After a median follow-up of 34.5 months, kidney function was partially recovered or stabilized in 5/8 (62.5%) patients, free of dialysis. Anti-GBM antibodies remained undetected in all patients during follow-up. No severe adverse effect associated with rituximab was observed.Rituximab may be an alternative therapy in the treatment of patient with severe or refractory anti-GBM disease.

Plasmapheresis is a frequently used procedure that removes the pathogenic components from circulation. We aimed to evaluate the relationship between plasmapheresis, neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) and mortality in the intensive care unit (ICU) between 2014 and 2021.Forty-nine patients (27 females and 22 males) were included. Demographic characteristics, laboratory values of the day of admittance to the ICU, APACHE II scores, and length of stay were recorded.The mean age was 52.73 ± 16.93. APACHE II value (p = 0.003; p 0.01), NLR ratio (p = 0.001; p 0.01) and PLR ratio (p = 0.001; p 0.01) of the surviving group were lower than those of the deceased group, which was statistically significant.As high PLR and NLR levels suggest increased mortality in the ICU population, attention should be paid for increased NLR and PLR when plasmapheresis is decided on in the ICU.

Sinusoidal obstruction syndrome/venoocclusive disease is a significant complication of hematopoietic stem cell transplantation. Due to high mortality rates, new treatment strategies have been investigated. Here, we have presented outcomes of therapeutic plasma exchange performed on patients with sinusoidal obstruction syndrome/veno-occlusive disease.Our study included 70 pediatric patients diagnosed with sinusoidal obstruction syndrome/veno-occlusive disease. Therapeutic plasma exchange procedures in patients were evaluated retrospectively.There were 9 mild (12.9%), 9 moderate (12.9%), 21 severe (30%), and 31 very severe (44.2%) cases of sinusoidal obstruction syndrome/venoocclusive disease. Therapeutic plasma exchange was performed in 31 of the 70 study patients (59.6%). Moreover, 10/21 patients with severe (47.6%) and 21/31 patients with very severe (67.7%) disease underwent plasma exchange. Mean time from diagnosis of sinusoidal obstruction syndrome/venoocclusive disease to therapeutic plasma exchange initiation was 2.3 days. The 31 patients who received therapeutic plasma exchange had a total of 146 sessions. Overall survival rates at 100 days were 87.1% and 92.3% for patients who did and did not undergo therapeutic plasma exchange, respectively. When patients with mild and moderate disease who were not expected to undergo plasma exchange were excluded (n = 52), 100-day overall survival rates were 87.1% and 90.5% for those who did and did not undergo plasma exchange, respectively. When we compared severe versus very severe groups, no significant difference was found.Plasmapheresis had no positive effect on survival. However, overall survival in all groups was higher than that in the literature, despite the high number of patients with severe and very severe disease. Interpretation of the results is limited by the retrospective nature of the study. Thus, prospective, randomized controlled trials with larger numbers of patients are necessary to investigate the role of therapeutic plasma exchange in patients with sinusoidal obstruction syndrome/veno-occlusive disease.

Severe gestational hypertriglyceridemia can lead to acute pancreatitis, with maternal mortality rate of approximately 20%. The recent National Lipid Association part 2 expert panel recommendations provide guidance on monitoring pregnant women at high risk for hyperlipidemia. We suggest that high-risk women have triglyceride levels checked once every trimester. Fasting triglycerides250 mg/dL should prompt monthly triglyceride levels, screening for gestational diabetes, and implementing a strict low-carbohydrate, low-fat diet, exercise. Fasting triglycerides500 mg/dL, despite a strict dietary and lifestyle modifications, should prompt treatment with omega-3-fatty acids and continue a fat-restricted diet (20 g total fat/d or15% total calories) under the guidance of a registered dietician. The use of fibrates should be considered as a second-line therapy due to their unclear risk versus benefit and potential teratogenic effects. Plasmapheresis should be considered early in asymptomatic pregnant women with fasting triglyceride levels1000 mg/dL or in pregnant women with clinical signs and symptoms of pancreatitis and triglyceride levels500 mg/dL despite maximal lifestyle changes and pharmacologic therapy.

Bilateral diffuse uveal melanocytic proliferation (BDUMP) is a rare paraneoplastic syndrome. Diagnosis can be difficult and treatment guidelines are ill-defined. A 73-year-old man with poorly differentiated high grade urothelial carcinoma of the ureter metastatic to the liver, lungs, lymph nodes, and pelvis treated with chemotherapy and immunotherapy reported gradual vision loss. Optical coherence tomography (OCT) demonstrated intraretinal and subretinal fluid with hyperreflective subretinal deposits and focal, deeply pigmented choroidal lesions. Irregular hyperpigmentation of the retinal pigment epithelium (RPE) with a “leopard spot” pattern on fundus autofluorescence (FAF) supported the diagnosis of BDUMP. Multiple plasmapheresis sessions did not result in sustained clinical improvement. [ Ophthalmic Surg Lasers Imaging Retina 2022;53(6): 350–353.]

Cryoglobulinemia is defined as the presence of an abnormal immunoglobulin that may be responsible for vasculitis of small-caliber vessels. Apheresis can be used in order to temporarily eliminate circulating cryoglobulins. The aim of this study was to assess the effectiveness of apheresis (double-filtration plasmapheresis-DFPP-) in symptomatic and/or severe cryoglobulinemias.Four male patients presenting cryoglobulinemic vasculitis and who received DFPP sessions were included.Their mean age was 57 ± 15 years. One patient had hepatitis-C virus (HCV)-related cryoglobulinemia and the other three patients were carriers of an IgM Kappa monoclonal gammopathy. Mean duration of follow-up was 15 ± 2 months. DFPP allowed healing of ulcerative skin lesions in the first patient and remission of nephrotic syndrome in the other patients after a median of 6(5-10) sessions.DFPP can be used safely in cryoglobulinemic-vasculitis and can be considered early to achieve a faster and sustained clinical-biological response.

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.

Therapeutic plasma exchange (TPE) is a conventional second-line treatment for patients with multiple sclerosis (MS) or clinically isolated syndrome with steroid-refractory relapses.MS and clinically isolated syndrome patients with a steroid-refractory relapse, who fulfilled the indications for TPE were enrolled in this study. An expert nurse recorded the data comprising age, sex, type of MS, disease modifying therapy, disease duration, relapse rate, vital signs at the beginning, during and at the end of each plasma exchange session, plasma exchange volume, normal saline volume, and TPE complications. Ultimately, the statistical association was estimated amongst the variables.A total of 122 cases were assessed. Twelve cases (9.8%) received plasmapheresis for the second time. The mean age was 32.2±8.7 years and 107 (87.7%) were female. In total, 609 plasma exchange sessions were completed. Hypotension and skin reaction were the most clinical complications. Hemoglobin loss and hypokalemia were the most laboratory complications. Fifty-four cases (44.3%) had no complications, 40 (32.8%) had 1 complication, 21 (17.2%) 2 complications, 6 (4.9%) had 3 complications, and 1 (0.8%) disclosed 4 complications. The relapse rate in the past 12 months and the mean plasma volume exchange were significantly different between the groups.We revealed that TPE could be considered as a safe second-line therapy in MS relapses. Hypotension, skin reaction, hemoglobin loss, and hypokalemia were the most complications of TPE in our patients.

Systemic vasculitides include a variety of, and numerous diseases. In 2012, the International CHAPEL HILL Consensus Conference (CHCC2012) led to a major reorganization of the classification of vasculitis, and this is still in wide use today. Although the results of plasmapheresis for individual diseases have been sometimes shown, there are few systematic reviews that discuss the effects along with vasculitis classification. Therefore, we will discuss the efficacy and the latest evidence for each vasculitis according to the CHCC 2012 classification in this review. This review provides a comprehensive overview of the estimation of plasmapheresis in each of the vasculitides, with a particular focus on small vasculitides, which have recently discussed frequently. For some time now, plasma exchange therapy (PEX) has been frequently used and is expected to be effective in some diseases, most of which are included in small vessel vasculitides. In particular, data showing efficacy have been accumulated for immune complex vasculitis, and the recommendation seems to be high. For instance, anti-GBM nephritis, concomitant use of PEX is essential and strongly recommended. On the other hand, for ANCA-related vasculitis among small vessel vasculitis, RCTs have recently shown negative results. In particular, the PEXIVAS trial statistically showed that PEX has no potential to reduce the mortality and renal death in AAV, but the ASFA, ACR, and KDIGO guidelines following this trial all regard PEX as salvage therapy or selective treatment for severe cases. As plasmapheresis is often performed in combination with other therapies, it is difficult to evaluate to clarify its efficacy on its own, and this predisposition may be pronounced in vasculitis, a rare disease. Although statistically significant differences are not apparent, the diseases that show a trend toward efficacy may possibly include treatment-sensitive subgroups. Further analysis is expected in the future.

Therapeutic plasmapheresis is a therapeutic procedure in which the patient's blood is passed through a medical device which separates out plasma from other components of blood. The plasma is removed and replaced with a replacement solution. Studies on the use of plasmapheresis in critically ill patients are scarce. The aim of this study was to review all therapeutic plasmapheresis sessions carried out in the Hospital Beatriz Ângelo intensive care unit.An observational retrospective study was conducted between April 2012 and March 2019. All patients who underwent therapeutic plasmapheresis in the intensive care unit were included, and plasmapheresis sessions held outside the intensive care unit were excluded.Of 46 patients, 63% were men (n = 29), with a median age of 53 years. The most frequent diagnoses were hypertriglyceridemia-induced pancreatitis, vasculitis, autoimmune haemolytic anaemia, and atypical haemolytic-uremic syndrome. A total of 198 plasmapheresis sessions were carried out in the intensive care unit. Most of the used replacement solutions were fresh frozen plasma (34.4%), albumin/crystalloid (24.2%), and albumin/fresh frozen plasma (19.2%). The most common complications were hydroelectrolytic changes (84; 42.4%) and coagulation disorders/thrombocytopenia (65; 32.8%). There was no need to interrupt any plasmapheresis session due to complications related to the patient.Therapeutic plasmapheresis is an urgent procedure that can reduce morbidity and mortality in critically ill patients. This justifies that 37% of patients started the technique before the diagnostic confirmation. The indications for plasmapheresis and the choice of replacement solution were in agreement with the guidelines. Despite the risk of bleeding, no haemorrhagic complications were recorded.Therapeutic plasmapheresis is a complex technique that requires specific training. The indications are diverse, and some are not consensual. Complications were frequent, but they did not increase morbidity.Introdução: A plasmaferese terapêutica é um procedimento em que o sangue passa por um circuito extracorpóreo que separa o plasma dos outros componentes do sangue. O plasma removido é substituído por soluções de reposição. Os estudos sobre a utilização de plasmaferese terapêutica no doente crítico são escassos. O objetivo do estudo foi rever todas as sessões de plasmaferese realizadas no serviço de Medicina Intensiva do Hospital Beatriz Ângelo. Material e Métodos: Estudo observacional retrospetivo de todos os doentes admitidos no serviço de Medicina Intensiva entre abril de 2012 e março de 2019. Foram selecionados os doentes submetidos a plasmaferese e excluídas as sessões realizadas fora do serviço de Medicina Intensiva. Resultados: No período de estudo foram incluídos 46 doentes. A maioria eram homens (n = 29; 63%) com uma idade mediana de 53 anos. Os diagnósticos mais frequentes foram pancreatite secundária a hipertrigliceridemia, vasculite, anemia hemolítica autoimune e síndrome hemolítica urémica atípica. Foram realizadas 198 sessões de plasmaferese no serviço de Medicina Intensiva. As soluções de substituição mais utilizadas foram plasma fresco congelado (34,4%), albumina/cristalóide (24,2%) e albumina/plasma (19,2%). As complicações mais comuns foram alterações hidroeletrolíticas (84; 42,4%), e distúrbios da coagulação/plaquetas (65; 32,8%). Em nenhum dos casos a técnica teve que ser interrompida por complicações relacionadas com o doente. Discussão: A plasmaferese terapêutica é um procedimento urgente capaz de reduzir a morbilidade e mortalidade no doente crítico. Isto justifica que 37% dos doentes tenham iniciado a técnica antes da confirmação diagnóstica. As indicações e soluto de reposição escolhido foram de acordo com as recomendações. Apesar do risco hemorrágico, nenhuma complicação desta natureza foi reportada. Conclusão: A plasmafere terapêutica é uma técnica complexa que requer treino específico. As indicações são diversas e algumas não consensuais. As complicações foram frequentes, mas não condicionaram morbilidade associada.

ABO-incompatible kidney transplantation (KTP) is effective for avoiding transplantation-related issues. It is a viable alternative to ABO-compatible KTP, as both techniques have similar patient and graft survival rates. However, anti-A/B antibody-mediated rejection (AMR) can occur, resulting in poor long-term graft survival.A 45-year-old man with end-stage renal disease presented with a serum creatinine level of 10.2 mg/dL. We decided to perform KTP with spousal donation. He had panel-reactive antibody class I and II and cross matching test negativity, a 3/6 mismatch on human leukocyte antigen typing, an ABO antibody titer of 1:256, and no donor-specific antibodies. The patient and donor blood types were O+ and A+, respectively. The anti-A/B antibody titer was reduced preoperatively with rituximab (200 mg/body), plasmapheresis, and intravenous immunoglobulin (0.2 mg/kg). Basiliximab and methylprednisolone were used for induction immunosuppression, and tacrolimus, mycophenolate mofetil, and prednisolone were used for maintenance immunosuppression. KTP was successful, and graft function was initially normal. On postoperative day (POD) 5, the serum creatinine level and anti-A/B antibody titer increased from 0.9 mg/dL to 1.9 mg/dL and 1:16 to 1:64, respectively. Graft biopsy revealed acute AMR and tubular injury. We started steroid pulse therapy, plasmapheresis, and subcutaneous bortezomib (2.6 mg, twice a day, every 3 days) with no side effects. The serum creatinine level decreased from 5.7 mg/dL to 1.5 mg/dL on POD 28. Graft biopsy showed no rejection, and normal function was maintained for 40 months.Acute, early anti-A/B AMR was successfully treated with plasmapheresis and bortezomib.

Calciphylaxis is commonly associated with end-stage renal disease (ESRD) and renal transplant. We present a rare case of early onset calciphylaxis in a patient presenting with acute kidney injury (AKI) secondary to anti-glomerular basement membrane (anti-GBM) antibody disease. A 65-year-old obese Caucasian woman with type 2 diabetes mellitus and hypertension presented with a 1-month history of painless gross haematuria and worsening lower extremity oedema. Laboratory results indicated AKI and nephrotic-range proteinuria. Anti-glomerular antibodies were elevated. Renal biopsy revealed focal crescentic glomerulonephritis with linear capillary immunoglobulin G staining consistent with anti-GBM antibody disease. She was treated with haemodialysis, plasmapheresis, steroids, bumetanide and cyclophosphamide. Two months later, she developed necrotic lesions on bilateral thighs. Wound biopsy was consistent with calciphylaxis. This case highlights that calciphylaxis, usually seen in patients with chronic kidney disease or ESRD, can manifest in patients with AKI as well.

Double filtration plasmapheresis (DFPP) is an apheretic technique that selectively removes high molecular weight substances using a plasma component filter. DFPP has been used to treat positive-sense RNA virus infections, mainly chronic hepatitis C virus (HCV) infection, because of its ability to directly eliminate viral particles from blood plasma from 2008 to about 2015, before direct-acting antiviral agents was marketed. This effect has been termed virus removal and eradication by DFPP. HCV is a positive-sense RNA virus similar to West Nile virus, dengue virus and the SARS and Middle East respiratory syndrome coronaviruses. SARS-CoV-2 is classified same viral species. These viruses are all classified in Family Flaviviridae which are family of single-stranded plus-stranded RNA viruses. Viral particles are 40–60 nm in diameter, enveloped and spherical in shape. We present a rare case of HCV removal where an RNA virus infection that copresented with virus-associated autoimmune hepatitis was eliminated using DFPP. Our results indicate that DFPP may facilitate prompt viraemia reduction and may have novel treatment applications for SARS-CoV-2, that is, use of therapeutic plasma exchange for fulminant COVID-19.

BACKGROUND: Data from the PEXIVAS trial challenged the role of plasma exchange (PLEX) in ANCA-associated vasculitides (AAV). We aimed to describe kidney biopsy from patients with AAV treated with PLEX, evaluate whether histopathologic findings could predict kidney function, and identify which patients would most benefit from PLEX. METHODS: We performed a multicenter, retrospective study on 188 patients with AAV and AKI treated with PLEX and 237 not treated with PLEX. The primary outcome was mortality or KRT at 12 months (M12). RESULTS: No significant benefit of PLEX for the primary outcome was found. To identify patients benefitting from PLEX, we developed a model predicting the average treatment effect of PLEX for an individual depending on covariables. Using the prediction model, 223 patients had a better predicted outcome with PLEX than without PLEX, and 177 of them had >5% increased predicted probability with PLEX compared with without PLEX of being alive and free from KRT at M12, which defined the PLEX-recommended group. Risk difference for death or KRT at M12 was significantly lower with PLEX in the PLEX-recommended group (−15.9%; 95% CI, −29.4 to −2.5) compared with the PLEX not recommended group (−4.8%; 95% CI, 14.9 to 5.3). Microscopic polyangiitis, MPO-ANCA, higher serum creatinine, crescentic and sclerotic classes, and higher Brix score were more frequent in the PLEX-recommended group. An easy to use score identified patients who would benefit from PLEX. The average treatment effect of PLEX for those with recommended treatment corresponded to an absolute risk reduction for death or KRT at M12 of 24.6%. CONCLUSIONS: PLEX was not associated with a better primary outcome in the whole study population, but we identified a subset of patients who could benefit from PLEX. However, these findings must be validated before utilized in clinical decision making.

There are two conventional modalities used to perform therapeutic plasma exchange (TPE): centrifuge TPE (cTPE) or membrane TPE (mTPE). There is limited data on complications with mTPE.We sought to better understand the patient and machine complications of mTPE compared to cTPE. We hypothesize that our protocol for mTPE using heparin anticoagulation is well-tolerated.In this retrospective cohort study of children21 years of age, we evaluated differences in patient and machine characteristics and complications between cTPE (with citrate anticoagulation) vs mTPE (with heparin anticoagulation).Of the 105 patients who met inclusion/exclusion criteria, 63 received cTPE and 42 mTPE via Prismaflex. Those who used mTPE were younger (4.8 ± 2.8 years vs 15.2 ± 3.7 years, P = .0001) and weighed less (19.5 ± 10.6 vs 71.7 ± 28.5 kg, P = .0001). There were no significant differences in patient-related complications or indications for TPE between the two modalities. Of the 1031 therapies performed,1003 therapies were analyzed (646 using cTPE and 357 using mTPE) due to exclusion criteria. No significant difference in patient complications were detected between groups. Machine-related complications were infrequent in both approaches. More circuits clotted during mTPE than during cTPE (6.7% [24/357] vs 0% [0/646]; P 0.001).Although we use mTPE in smaller children, we showed low rates of complications that were not statistically different from cTPE performed in older children. While the overall rate of circuit clotting using mTPE was low, it occurred more commonly than with cTPE.

Antibody-mediated rejection (AMR) following orthotopic heart transplant (OHT) causes significant morbidity and mortality. There are limited data on antibodies to the angiotensin II type 1 receptor antibody (AT1R-Ab) causing rejection following OHT.This is a retrospective, single-center study that presents our 2-y experience with a series of 11 patients with evidence of nonspecific graft dysfunction and pathologic levels of AT1R-Ab. The clinical outcomes and treatments were compared to a group of 10 patients, also with evidence of nonspecific graft dysfunction, but who had nonsignificant AT1R-Ab titers.The mean age of the AT1R-Ab cohort was 52% and 73% were bridged to transplant with an left ventricular assist device. The average left ventricular ejection fraction at presentation was 45%, and most were not on an angiotensin receptor blocker (ARB). Endomyocardial biopsies in those with elevated AT1R-Ab levels frequently showed reactive endothelium/endocardium without C4d or intravascular CD68 staining. Ten patients (91%) were started on an ARB. Other therapies included plasmapheresis and IVIg (64%), with 4 patients also receiving rituximab. Most patients had symptom improvement, but minimal change in graft function at an average 6 mo of follow-up.The role of AT1R-Ab-mediated rejection in OHT recipients remains poorly understood. More than half of patients at our center who presented with graft dysfunction in the absence of acute cellular rejection or AMR were found to have elevated AT1R-Ab titers. Empiric AMR treatment in conjunction with ARB therapy may improve patient outcomes. Future studies are needed to better define the optimal treatment modalities for ATR1-Ab-mediated AMR.

Introduction: Recurrence of focal segmental glomerulosclerosis (FSGS) after kidney transplantation (KTx) develops in 40% of patients, leading to graft loss in half of cases. Extracorporeal apheretic treatments, combined with immunosuppressive drugs, seem to be the most promising therapies, but at now limited reports are available, mainly in pediatric patients. Objective: We aimed to assess the efficacy of immunoadsorption (IA) to treat recurrent FSGS in pediatric patients. Methods: We report a case series of 4 pediatric patients (aged 4–12 years) followed at our institution for early recurrent FSGS after KTx. FSGS recurrence was treated with early and intensive apheretic treatments IA. Results: After IA initiation, a partial remission (PR) of proteinuria at 24-month follow-up was achieved only in 1 patient. The others showed a mild reduction of nephrotic proteinuria, without PR, but gained a significant improvement in clinical signs of nephrotic syndrome (reduction of edema, increased serum albumin, and total protein levels). After a median follow-up of 38 (22–48) months, renal function was almost stable over time in all patients, except one who returned to hemodialysis after 22 months. No severe IA-related complications occurred. Conclusions: According to our clinical experience, IA revealed as a safe and effective therapy to treat patients with recurrent FSGS after KTx and it could maintain stable renal function in 75% of patients.

Key Points IPF has a typical clinical presentation with involvement of the lower limbs corresponding to vascular territories.The antithrombin level and platelet count at diagnosis seemed to be associated with severe complications in IPF., Visual Abstract, Idiopathic purpura fulminans (IPF) is a rare but severe prothrombotic coagulation disorder that can occur after chickenpox or human herpesvirus 6 (HHV-6) infection. IPF leads to an autoantibody-mediated decrease in the plasma concentration of protein S. We conducted a retrospective multicenter study involving patients with IPF from 13 French pediatric centers and a systematic review of cases in published literature. Eighteen patients were included in our case series, and 34 patients were included as literature review cases. The median age was 4.9 years, and the diagnostic delay after the first signs of viral infection was 7 days. The lower limbs were involved in 49 patients (94%) with typical lesions. In all, 41 patients (78%) had a recent history of varicella-zoster virus infection, and 7 patients (14%) had been infected by HHV-6. Most of the patients received heparin (n = 51; 98%) and fresh frozen plasma transfusions (n = 41; 79%); other treatment options were immunoglobulin infusion, platelet transfusion, corticosteroid therapy, plasmapheresis, and coagulation regulator concentrate infusion. The antithrombin level and platelet count at diagnosis seemed to be associated with severe complications. Given the rarity of this disease, the creation of a prospective international registry is required to consolidate these findings.

Background There are no systematic reviews yet that evaluated the effects of PE/IA in patients with optic neuritis (ON) in demyelinating diseases. A meta-analysis of available study is needed to further explore the value of plasma exchange (PE) or immunoadsorption (IA) in treating ON in demyelinating diseases. Methods All relevant articles published on PubMed, Web of Science, Cochrane Library, Embase, China National Knowledge Infrastructure (CNKI), VIP Database, Wanfang, Sinomed and ophthalmology professional websites were searched. Study characteristics, demographic characteristics, clinical features and outcome measures were extracted. Response rate, adverse events (AE) rate, serious adverse event (SAE) rate, the log of the minimum angle of resolution (logMAR), visual outcome scale (VOS) and expanded disability status scales (EDSS) were evaluated using a random-effects model. Results 35 studies were included between 1985 and 2020, containing 1191 patients. The response rates of PE and IA in acute attack of ON were 68% and 82% respectively. LogMAR (−0.60 to − 1.42) and VOS (−1.10 to −1.82) had been significantly improved from within 1 month to more than 1 month after PE treatment. Besides, we found that logMAR improved 1.78, 0.95 and 0.38, respectively ,when the time from symptom onset to the first PE/IA was less than 21 days, 21–28 days, and more than 28 days. The pooled mean difference of EDSS was −1.14.Adverse effects rate in patients with PE or IA were 0.20 and 0.06, respectively. Conclusion The meta-analysis provided evidence that PE/IA treatment was an effective and safe intervention, and it is recommended that early initiation of PE/IA treatment is critical.

Therapeutic plasma exchange (TPE) and immunoadsorption (IA) are first or second line treatment options in patients with neurological autoimmune diseases, including multiple sclerosis, neuromyelitis optica spectrum disorders (NMSOD), chronic inflammatory demyelinating polyneuropathy, acute inflammatory demyelinating polyradiculoneuropathy (Guillain-Barré syndrome), and autoimmune encephalitis.In this prospective randomized controlled monocentric study, we assessed safety and efficacy of therapy with IA or TPE in patients with neurological autoimmune diseases. Treatment response was assessed using various neurological scores as well by measuring immunoglobulin and cytokine concentrations. Clinical outcome was evaluated by application of specific scores for the underlying diseases.A total of 32 patients were analyzed. Among these, 19 patients were treated with TPE and 13 patients with IA. IA and TPE therapy showed a comparable significant treatment response. In patients with MS and NMOSD, mean EDSS before and after treatment showed a significant reduction after treatment with IA. We observed a significant reduction of the pro-inflammatory cytokines IL-12, lL-17, IL-6, INF-γ, and tumor necrosis factor alpha during IA treatment, whereas this reduction was not seen in patients treated with TPE.In summary, both IA and TPE were effective and safe procedures for treating neurological autoimmune diseases. However, there was a trend towards longer therapy response in patients treated with IA compared to TPE, possibly related to a reduction in plasma levels of pro-inflammatory cytokines seen only in the IA-treated group.

The prevalence of intracardiac thrombus (ICT) is gradually increasing, though it is rare among children. Data related to the occurrence of ICT among children are limited, and treatment recommendations have been made utilizing adult guidelines. The primary objective of this study is to determine associated factors, management, and outcomes of intracardiac thrombosis in children. Between January 2013 and January 2020, patients diagnosed with ICT at the Pediatric Hematology-Oncology and Pediatric Cardiology departments in our hospital were included in the study. Demographic characteristics, clinical and laboratory findings, treatment protocols, and outcomes were analyzed retrospectively. The median age at diagnosis was 10.5 months (2 days to 14.5 years), and the median follow-up period was 6.5 months (1 month to 3.1 years). The most common primary diagnoses of the patients, in order of frequency, were heart disease (n: 8), metabolic disease (n: 3), prematurity and RDS (n: 3), burns (n: 2), pneumonia (n: 2), and asphyxia (n: 2). CVC was present in 19/23 of the patients. The reasons for CVC insertion were the need for plasmapheresis in one patient with a diagnosis of HUS and the need for well tolerated vascular access because of long-term hospitalization in others. LMWH was administered to all patients as first-line therapy. Complete response was achieved in 19 (79%) of 24 patients and 4 patients (16.6%) were unresponsive to medical treatment. It was found out that the thrombus location, type, sepsis, and hemoculture positivity, as well as the presence of CVC, had no impact on treatment response (chi-square P = 0.16, 0.12, 0.3, 0.49, 0.56). Moreover, no correlation was determined between thrombus size and treatment response (Mann Whitney U test P = 0.47). The mortality rate was determined to be 12.5% (3/24). Spontaneous occurrence of ICT is rare in childhood, without any underlying primary disease or associated factor. The presence of CVC, sepsis, and heart disease are factors associated with ICT. The success rate is increased with medical treatment. There was no significant difference in treatment response between the newborn and 1 month to 18-year-old patient group. It has been demonstrated that thrombus size, type, localization; sepsis, and hemoculture positivity had no impact on the treatment response.

Introduction Autoimmune neuropathies have diverse presentations and underlying immune mechanisms. Demonstration of efficacy of therapeutic agents that inhibit the complement cascade would confirm the role of complement activation. D A review of the pathophysiology of the autoimmune neuropathies, to identify those that are likely to be complement mediated. Expert opinion Complement mediated mechanisms are implicated in the acute and chronic neuropathies associated with IgG or IgM antibodies that target the Myelin Associated Glycoprotein (MAG) or gangliosides in the peripheral nerves. Antibody and complement mechanisms are also suspected in the Guillain-Barre syndrome and chronic inflammatory demyelinating neuropathy, given the therapeutic response to plasmapheresis or intravenous immunoglobulins, even in the absence of an identifiable target antigen. Complement is unlikely to play a role in paraneoplastic sensory neuropathy associated with antibodies to HU/ANNA-1 given its intracellular localization. In chronic demyelinating neuropathy with anti-nodal/paranodal CNTN1, NFS-155, and CASPR1 antibodies, myotonia with anti-VGKC LGI1 or CASPR2 antibodies, or autoimmune autonomic neuropathy with anti-gAChR antibodies, the response to complement inhibitory agents would depend on the extent to which the antibodies exert their effects through complement dependent or independent mechanisms. Complement is also likely to play a role in Sjogren's, vasculitic, and cryoglobulinemic neuropathies.

Introduction We report the effects of plasma exchange (PE) with albumin replacement on neuropsychological, neuropsychiatric, and quality-of-life (QoL) outcomes in mild-to-moderate Alzheimer's disease (AD) patients in a phase 2b/3 trial (Alzheimer's Management by Albumin Replacement [AMBAR] study). Methods Three hundred forty-seven patients were randomized into placebo (sham-PE) and three PE-treatment arms with low/high doses of albumin, with/without intravenous immunoglobulin (IVIG). Specific test measurements were performed at baseline; month 2 (weekly conventional PE); months 6, 9, and 12 (monthly low-volume PE [LVPE]); and month 14. Results The PE-treated mild-AD cohort improved their language fluency and processing speed versus placebo at month 14 (effect sizes: >100%; P-values: .03 to .001). The moderate-AD cohort significantly improved short-term verbal memory (effect sizes: 94% to >100%; P-values: .02 to .003). The progression of the neuropsychiatric symptoms of PE-treated was similar to placebo. Mild-AD patients showed improved QoL (P-values: .04 to .008). Discussion PE-treated AD patients showed improvement in memory, language abilities, processing speed, and QoL-AD. No worsening of their psychoaffective status was observed.

Background Acute disseminated encephalomyelitis (ADEM) is an inflammatory demyelinating disorder of the central nervous system. Little information is available about the clinical and neuroradiological profile or the follow-up of this disease in Tunisian children. Aim To determine the clinical, laboratory, and radiological features and the outcome of ADEM in children admitted to the pediatrics department of a university hospital in Tunisia. Methods All children ≤ 18 years old presenting with ADEM and admitted to the tertiary referral center for pediatrics at Sahloul University Hospital from January 2000 to December 2020 were included in the study. The diagnosis of ADEM was confirmed according to the international pediatric multiple sclerosis study group criteria. Results A total of 20 patients (13 girls and 7 boys) fulfilled the diagnostic criteria for ADEM. The mean age at diagnosis was 5.6 years. The clinical presentation included polyfocal neurological signs such as cranial hypertension (45%), seizures (35%), and motor weaknesses (55%). Pyramidal tract signs and cranial nerve palsies were noted in 55% of cases. Brain magnetic resonance imaging showed particular features, namely, a relapsing tumor-like form in one case, and optic neuritis and demyelinating lesions of the white matter in the brain and the spinal cord with gadolinium cerebral ring-like enhancement in another case. The treatment consisted of intravenous immunoglobulin in 16 cases (80%) and corticosteroid in 19 cases (95%). Plasmapheresis was used for one patient. Complete recovery was observed in 12 patients (60%); 19 patients (95%) had a monophasic course of the disease while only one patient developed multiphasic ADEM. Conclusions ADEM remains a difficult diagnosis in children. Nevertheless, after prompt diagnosis and adequate treatment, most children with ADEM have a favorable outcome with restitutio ad integrum.

Introduction In highly sensitized patients who have panel reactive antibodies (PRAs) before hematopoietic stem cell transplantation, primary graft failure risk may increase. In this study, we aimed to determine the association of PRA with engraftment, and graft versus host disease (GVHD) in pediatric patients. Materials and methods Forty-three PRA-positive and 42 PRA-negative patients were taken into study. Both groups were compared in terms of graft failure, acute GVHD, viral infection and survival rates. PRA-positive group was also divided into 2 according to treatment modality (steroid-only group/combination therapy) and compared for the same parameters. Results There was no difference in PRA-positive and negative patients in terms of graft failure, acute GVHD and viral infections. Analysis of the PRA-positive group in itself showed that there was also no difference in terms of graft failure and viral infection frequency. The only difference is that acute grade 3 to 4 GVHD was higher in the steroid-only group. The 100-day overall survival was 90.2% and 90.4% for the PRA-positive and negative groups, respectively. Conclusions Different treatment strategies like plasmapheresis, steroid, rituximab, or combination therapies can be used for the desensitization of PRA-positive patients before hematopoietic stem cell transplantation. Patient-specific treatment modality for sensitized patients before transplant can increase the success rate.

Desensitization therapy for heart transplantation (HT) candidates can shorten transplant wait times and broaden the donor pool. Specific evidence-based recommendations on both protocols and indications are lacking. We retrospectively assessed left ventricular assist devices-bridged candidates who received pre-HT desensitization therapy. The therapeutic protocol consisted of intravenous immunoglobulin and rituximab followed by bortezomib and plasmapheresis if an insufficient response was achieved. Desensitization was attempted in 10 patients; only 7 tolerated therapy and underwent transplant. For those patients, median decrease in unacceptable calculated panel reactive antibody was 11%; there was no significant decrease for 3 patients. Post-desensitization adverse events were observed in all patients which included coagulopathy, bone marrow suppression, and infection. Median time to first infection was 16 days. One patient had clinically significant rejection and 3 patients had uptrending donor-specific antibodies. Decisions to proceed with desensitization should be individualized understanding potential risks and benefits.

Background Positive crossmatch (XM+) combined liver–kidney transplantation due to preformed donor-specific human leukocyte antigen antibodies has produced mixed results. We sought to understand the role of delayed kidney transplant approach in XM+ combined liver–kidney transplantations. Methods XM+ combined liver–kidney transplantations were retrospectively reviewed. T- and B-cell XM, complement-dependent cytotoxic crossmatch, and flow cytometric crossmatch were performed prospectively. Results Of 183 combined liver-kidney transplantations performed (2002–2019), 114 (62%) were with “delayed” kidney transplant approach and 19 (19 of 183, 10%) were XM+. Of 19 XM+ combined liver–kidney transplantations, kidney transplant was “delayed” in 14 by an average of 47 hours (range 24–64 hours) from liver transplant. There was a significant reduction in both class I (mean pre–liver transplant mean fluorescence intensity (MFI) 26,230 versus mean post–liver transplant and pre–delayed kidney transplant MFI 3,272, P = .01) and total MFI (mean pre–liver transplant MFI 27,233 vs mean post liver transplant and predelayed kidney transplant MFI 11,469, P = .01). However, there was no significant change in the MFI of class II donor-specific antibodies (mean pre–liver transplant MFI 17,899 versus post-liver transplant and pre–delayed kidney transplant MFI 14,341, P = .19). None of XM+ delayed kidney transplants had delayed graft function, and there was no antibody-mediated rejection. One-year patient survival for the XM+ combined liver–kidney transplantation with delayed kidney transplant approach was 92.9%, which is comparable to patient survival of XM– combined liver–kidney transplantation. Whereas patient survival in recipients before “delayed” approach (“simultaneous”; n = 5) was 40% when liver–kidney transplants were performed simultaneously (P = .06). Conclusion In sensitized combined liver-kidney transplantation recipients, the “delayed” kidney transplant approach is associated with a significant reduction in total and class I donor-specific antibodies after liver transplant before kidney transplant, enabling therapeutic interventions such as plasmapheresis, if needed, providing optimal outcomes similar to crossmatch recipients.

Objective To evaluate the results of isolated liver and combined liver and kidney transplantation in a retrospective series of 32 patients with hepatorenal liver and kidney disease. Patients and methods A retrospective observational study that enrolled patients with polycystic liver disease (PLD) and polycystic liver and kidney disease (PLKD) who were evaluated for transplantation between January 1999 and December 2019 at Hospital Clinic de Barcelona [Clinical Hospital of Barcelona]. Results Of 53 patients enrolled, 32 (60.3%) had an indication for transplantation, 12 received a single liver transplant and 20 received a double liver and kidney transplant. The mean age was 52 years and 83.9% of the recipients were women. The main indication for liver transplantation was disabling symptomatic hepatomegaly (93.5%). Among the postoperative complications, in the combined liver and kidney transplant group, hepatic artery thrombosis and renal artery thrombosis were detected. In both groups there was an inferior vena cava lesion. Three patients presented acute cellular rejection responding to corticosteroids and one presented humoral rejection which was treated with plasmapheresis. During the follow-up period of 80 (27–121) months, the liver transplant survival rate was 100% and the kidney transplant survival rate was 90%. Two patients in the combined liver and kidney transplant group died (one due to cardiovascular causes and the other due to intestinal adenocarcinoma). Conclusions Isolated liver transplantation or combined liver and kidney transplantation in selected patients with polycystic disease yields excellent results, with few complications, very good transplant survival and excellent patient survival (93.8%).