Plasma Exchange Therapy Research Articles

Short-term efficiency of plasma exchange in combination with immunosuppressants and/or biologics in the treatment of idiopathic inflammatory myopathy with rapidly progressive interstitial lung disease: a systematic review and meta-analysis

Objective Rapidly progressive interstitial lung disease (RP-ILD) is a frequent and serious manifestation of idiopathic inflammatory myopathy (IIM) associated with poor outcomes. Plasma exchange (PE) can quickly remove pathogenic substances from the blood. Therefore, PE may be efficacious in IIM patients who have elevated levels of autoantibodies, cytokines and chemokines, fighting for time for immunosuppressive therapy. However, the value of adding PE to immunosuppressants remains unclear. The purpose of this study was to determine the short-term outcomes, including the survival rate at 6 months and change of the laboratory data, of PE in combination with immunosuppressants and/or biologics in the treatment of IIM-RP-ILD. Methods We searched PubMed, Embase and Cochrane Library to find reports of interest published from inception to March 4, 2024. STATA 15.1 was used for data analysis. A fixed or random-effects model with inverse-variance weighting was used to estimate the pooled risk ratio (RR) and 95% confidence interval (CI). Results Two hundred and thirty studies were identified. Eleven studies, including five retrospective cohort studies, four case-control studies and two case series, were included. PE was performed on 114 patients. The survival rate at 6 months was 80% (95%CI = 64%–92%), with moderate heterogeneity (I 2=63.45%, p < 0.05). Moreover, the 6-month survival rate was significantly better in the PE group than in the non-PE group (RR, 1.34; 95% CI = 1.05–1.71, I 2=30.7%; p = 0.194). ILD-related serum markers, including ferritin, KL-6 and anti-MDA-5 antibody titres, were significantly suppressed by a series of PE treatments (p < 0.05). Conclusion The application of PE therapy plus treatment with corticosteroids, immunosuppressants and/or biologics was effective for patients with IIM-RP-ILD. PE may have additional supportive effect in intractable disease.

Successful treatment of Anti-melanoma differentiation-associated gene 5 (MDA-5) antibody-positive dermatomyositis with rapidly progressive interstitial lung disease complicated by bilateral breast cancer following the additional tofacitinib: A case report.

Anti-melanoma differentiation-associated gene 5 (MDA-5) antibody-positive dermatomyositis (MDA5-DM) is known to cause rapidly progressive interstitial lung disease (RP-ILD). Cancer complications in MDA5-DM are less frequently reported compared to other forms of DM, though they do occur. The treatment strategy for DM with aspects of paraneoplastic syndrome is usually to treat the cancer first, if possible. However, surgery is difficult in the setting of respiratory failure and carries the risk of acute exacerbation of interstitial lung disease, as does chemotherapy and radiotherapy. The prognosis of MDA5-DM with RP-ILD has improved with initial immunosuppressive combination therapy, but certain cases remain refractory to treatment. Recently, the efficacy of janus kinase (JAK) inhibitors in refractory MDA5-DM cases has been reported. However, immunosuppressive therapies, including JAK inhibitors, may have negative effect on cancer progression. Here, we report a 48-year-old woman suffering from MDA5-DM with RP-ILD complicated by bilateral breast cancer. Due to respiratory failure, radical breast cancer surgery and chemotherapy could not be performed, so endocrine therapy and combined immunosuppressive therapy were first administered. However, the patient's condition was refractory to this initial treatment. Therefore, tofacitinib in combination with plasma exchange therapy was initiated, leading to an improvement in ILD, and bilateral mastectomy could be performed. One year later, MDA-5 antibody titers became negative, and glucocorticoid was successfully discontinued after two years. To date, three years have passed without recurrence of either MDA5-DM or breast cancer. To our knowledge, this is the first report of MDA5-DM complicated by breast cancer, as well as the first case of JAK inhibitor use for MDA5-DM with cancer. For curative treatment of MD5-DM with RP-ILD, if comorbid cancers are found, collaboration with oncologists to balance the efficacy and adverse events of MDA5-DM with RP-ILD therapy is essential in determining the appropriate type and timing of treatment, which could lead to a favorable outcome.

Outcomes of therapeutic plasma exchange for the treatment of patients with multiple myeloma cast nephropathy.

Current treatment guidelines of myeloma cast nephropathy (MCN) recommend the institution of plasma cell-directed therapy and consideration of therapeutic plasma exchange (TPE), with the goal of rapid reduction of the serum free light chain (sFLC). However, the role of TPE continues to remain a subject of debate. The goal of this retrospective bi-institutional study was to evaluate the clinical outcomes of TPE in combination with systemic therapy. Eighty patients were included in this analysis, of whom 72.5% had ≥50% drop in their initial involved sFLC. At 3months from TPE initiation, the overall hematologic response rate (ORR) was 67.5% with a very good partial response or better (≥VGPR) rate of 40%. At 6months, ORR was 57.5%, with ≥VGPR rate of 49%. The renal response rate at 3 and 6months was 47.5% and 43.75%, respectively; the overall renal response rate was 48.75%. On multivariable analysis, every one unit increase in baseline creatinine (odds ratio [OR] 0.76, p=0.006), and achievement of ≥VGPR (OR 21.7 p<0.0001) were significantly associated with renal response. Also, a ≥50% drop in sFLC was favorably associated with renal response (OR 3.39, p=0.09). With a median follow-up of 36.4months, the median overall survival (OS) was 11months. On multivariable analysis, achievement of renal response (hazard ratio [HR]0.3, p<0.0001) and newly diagnosed disease (NDMM; HR 0.43, p=0.0055) were associated with improved OS. Among NDMM patients, those treated with daratumumab-based regimens had a trend for better OS (p=0.15), compared to other regimens, but the difference was not significant. At the end of follow-up, an estimated 40.4% of patients who were on dialysis were able to become dialysis independent. In conclusion, our study highlights the poor survival of patients with MCN. Achievement of early renal response is crucial for prolonged OS, with daratumumab-based therapies showing promise.

Plasma-exchange therapy in acute immune-mediated neuropathy: Effects on muscle strength and functional outcomes

Background and objectives. This study explores the impact of plasma exchange therapy (TPE) on muscle strength and functional outcomes in patients with acute immune-mediated neuropathy. Materials and methods. We retrospectively analyzed clinical data from patients diagnosed with acute immune-mediated neuropathy at the Department of Neurology, Bolan University of Medical Sciences, Baluchistan, from January 2016 to December 2021. Results. The study, comprising 141 patients with various neurological disorders, underscores the efficacy of plasma exchange therapy in improving muscle strength and functional outcomes, particularly in Guillain-Barré Syndrome (GBS). Notably, after four weeks of treatment, a significant proportion of patients demonstrated improved mobility, with 51.8% able to walk without assistance. However, despite the positive response to therapy, a small percentage (2.8%) experienced unfavorable outcomes marked by expiration. Additionally, the study identifies significant associations between treatment outcomes and patient characteristics, such as the number of plasma exchange cycles and diagnosis (p &lt;0.05), emphasizing the importance of personalized treatment approaches in managing neurological disorders. Conclusions. Our findings underscore the effectiveness of plasma exchange in enhancing muscle strength and functional outcomes in acute immune-mediated neuropathy, particularly GBS.

Clinical Course of Nonresponders With Recurrent Focal Segmental Glomerulosclerosis After Pediatric Kidney Transplantation: A Retrospective Multicenter Study.

Primary focal segmental glomerulosclerosis (FSGS) frequently recurs after kidney transplantation and is associated with poor graft survival. Patients who do not achieve remission (nonresponders) have an especially poor graft survival. However, the characteristics that may affect graft survival in nonresponders are unknown. This study aimed to determine the clinical characteristics associated with graft survival in nonresponders. We retrospectively collected the clinical records of patients with FSGS and an age at onset <16 years who experienced posttransplant recurrence of FSGS at six hospitals in Japan from 1993 to 2018. Eight nonresponders with recurrent FSGS were enrolled in this study. The median time to recurrence after kidney transplantation was 1 day (interquartile range, 1-2 days). All patients received therapeutic plasma exchange and methylprednisolone pulse therapy. Rituximab was used as an add-on therapy in three patients. Five patients lost their graft within 2 years after kidney transplantation (rapid group). In contrast, three patients had much longer graft survival (nonrapid group). We compared the clinical characteristics of the rapid and nonrapid groups. Proteinuria tended to be lower in the nonrapid group at the third and subsequent months of therapy. The rapid group had persistent nephrotic syndrome. The rate of reduction in proteinuria was lower in the rapid group than in the nonrapid group. Our study suggests that persistent nephrotic syndrome and a low rate of reduction in proteinuria may predict rapid progression to graft failure in nonresponders.

Terapia de recambio plasmático en el paciente críticamente enfermo.

Introduction: Plasmapheresis has been used with different levels of evidence in neurology, nephrology, and rheumatology. Management guidelines have evolved with the development of randomized clinical trials; however, the low prevalence of some conditions that can benefit from this intervention is a limitation. Objective of the review: This article is a narrative review that reviews the basic principles of plasma exchange therapy, establishes the levels of evidence, and identifies entities that may benefit from this treatment. Essential points of the review: In category I, the conditions are established where the therapy is first-line; in category II, plasmapheresis is the second treatment option; in category III, the optimal role has yet to be established; and in category IV, it is an ineffective treatment. Among the category I renal indications are Goodpasture syndrome with diffuse alveolar hemorrhage, recurrent focal and segmental glomerulosclerosis in kidney transplant, vasculitis associated with ANCA, rapidly progressive, ABO incompatible kidney transplant. Conclusion: Due to the lack of clinical studies, some pathologies remain with indications category II to IV. Due to the low prevalence and incidence in intensive care, the collective work of the scientific community is required.

Early plasma exchange and continuous renal replacement therapy improve puerperal prognosis in hepatitis B virus-related acute-on-chronic liver failure in pregnancy

Background and aimHepatitis B virus (HBV)-related gestational acute-on-chronic liver failure (ACLF) is a severe condition with limited treatment options. This study aimed to evaluate the efficacy and ideal timing of plasma exchange and continuous renal replacement therapy (CRRT) in managing pregnant women with HBV-related ACLF. MethodsThis study retrospectively analyzed 51 eligible patients with HBV-related gestational ACLF between 2009 and 2020. Patients admitted to the study were divided into a conventional treatment group and a new treatment group according to whether they received the new management protocol, which included more aggressive plasma exchange (PE) and CRRT strategies. All 19 pregnant women with hepatic encephalopathy (HE) were divided into an early treatment group and a non-early treatment group according to whether PE therapy was initiated within three days. Our study had two primary objectives. Firstly, we aimed to evaluate the impact of PE and CRRT on puerperal survival. Secondly, we sought to assess the effects of early PE and CRRT regimens on puerperal survival in women with HE. ResultsThe levels of total bilirubin on the second day postpartum (D3), the third day postpartum (D4), and the fifth day postpartum (D6) were significantly lower in the new treatment group compared to the conventional treatment group (P = 0.02, 0.01, and 0.02, respectively). The ALT of D3 was significantly elevated in the new treatment group compared to the conventional treatment group (P = 0.02). The incidence of HE overall increased from prenatal to postpartum D4, peaked on D4, and then gradually decreased from the fourth day postpartum (D5) （P = 0.027）. The first week after delivery revealed a significant difference in survival rate between the two groups, the conventional treatment group had statistically higher mortality rates compared to the new treatment group (P = 0.002). Similarly, the entire puerperal period mortality rate of the conventional treatment group was statistically higher than the new treatment group (P = 0.002). Moreover, among all patients with HE, the non-early treatment group showed significantly higher puerperal mortality rates compared to the early treatment group (P = 0.006). ConclusionsEarly PE and CRRT conducted within three days post-childbirth, enhance puerperal prognosis for HBV-related gestational ACLF.

Rapidly progressive seronegative immune-mediated neuropathies responded to “Remove and suppress” therapy with plasma exchange and B-cell suppression therapy

Immune-mediated peripheral neuropathies are heterogeneous group of disorders due to the present of autoantibodies against peripheral nerve molecules located in node of Ranvier such as gangliosides and cell adhesion proteins or myelin components of peripheral nerves. Although the exact aetiology and pathophysiological mechanisms involved are not fully understood, both humoral and cellular immunity are likely playing a role in their pathogenesis. A proportion of patients present with clinical phenotype of rapidly progressive neuropathy refractory to conventional therapies but are lacking in identifiable or detectable antibodies. This makes diagnosis and treatment decision challenging.We illustrate a patient with rapidly progressive seronegative immune-mediated neuropathy resembling autoimmune nodopathy (AN) associated with atypical features (prominent ataxia) and cranial involvement (facial and oropharyngeal weakness, dysgeusia), refractory to conventional therapies (IV immunoglobulin and corticosteroids) but responded to ‘remove and suppress’ treatment regime using therapeutic plasma exchange (TPE), followed by long-term B-cell suppressive therapy.

#3006 Therapeutic apheresis in Fabry disease

Abstract Background and Aims Fabry's disease (FD) is a rare lysosomal disorder linked to the X chromosome due to a mutation in the gene encoding alpha-galactosidase A (alpha-Gal A). This mutation leads to a defect in the metabolism of glycosphingolipids, causing the progressive accumulation of globotriaacylceramide (GB3) or LysoGB3 in cells, tissues, and organs. In the treatment of FD, we have enzyme replacement therapy (ERT) with Agalsidase-alfa (Replagal®), Agalsidase-beta (Fabrazyme®), and chaperones (Migalastat®). However, there are limitations such as disease progression and morbimortality. Regarding ERT, the development of circulating immunoglobulin G (IgG) antibodies against agalsidase (aGAL) in the long term appears to be associated with a loss of effectiveness. The use of Therapeutic Apheresis (TA), such as plasma exchange therapy (PE) and low-density lipoprotein apheresis (LDL-apheresis), is employed in the treatment of various pathologies due to its ability to eliminate plasma, antibodies, low-density lipoproteins, apolipoproteins, and the adaptability of therapy to the molecule to be removed. The aim was to demonstrate that LDL-apheresis and PE favor Lyso-Gb3 elimination, and PE also eliminates IgG-aGAL as an adjunctive treatment in FD and conducted a proof-of-concept study. Method Two branches of intervention were established, where patients were classified into two groups based on the presence or absence of anti-agalsidase IgG antibodies. If they have the presence of antibodies, they would be eligible for plasma exchanges with two objectives: removing pre-formed antibodies and eliminating Lyso-Gb3. Conversely, in the absence of pre-formed antibodies, LDL-apheresis is performed with the aim of eliminating Lyso-Gb3. The proof-of-concept study was done with two FD patients undergoing ERT were identified, one with IgG-aGAL and the other with very low levels. PE was performed on the first patient, and LDL-apheresis on the second. Lyso-Gb3 levels were titrated in blood before and after LDL-apheresis, and in the washout bag of the column. For antibodies, titration was done in pre and post PE blood and in the extracted plasma from PE. Results After applying TA techniques, we observed that PE reduces IgG-aGAL by 85%, and in the case of LDL-apheresis, there was a 28% reduction in IgG-aGAL. While the ability to eliminate LysoGb3 showed a reduction of 25.5% in PE and 39.7% for LDL-apheresis. To eliminate a potential confounding factor, LysoGb3 determination in albumin was within normal limits. Conclusion With these results, we confirm that PE is more efficient in removing IgG-aGAL but also eliminates LysoGb3, whereas LDL-apheresis is a very effective technique for removing Lyso-Gb3 but also contributes to antibody removal. Based on these findings, we consider TA to be an effective adjunctive tool for FD treatment, even as a standalone treatment. However, these are very preliminary results and should be reproduced with a larger number of patients.

Enhancing Survival in Septic Shock: A Systematic Review and Meta-Analysis of the Efficacy of Plasma Exchange Therapy.

Sepsis is a life-threatening condition that occurs when the body's immune response to infection becomes unregulated, causing organ dysfunction and a heightened risk of mortality. Despite increased awareness campaigns, its prevalence escalates, annually afflicting over 1.7 million adults in the United States. This research explores the potential of therapeutic plasma exchange (TPE) in septic shock management, aiming to highlight its capacity to improve patient outcomes and reduce mortality. Adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, our comprehensive search across 51,534 studies, using keywords such as plasmapheresis, plasma exchange therapy, therapeutic plasma exchange, septic shock, and reduction in mortality integrated with medical subject headings terms, led to the meticulous selection of six pivotal studies. Through rigorous evaluation with tools such as the revised Cochrane Risk-of-Bias tool, Newcastle-Ottawa Scale, and Assessment of Methodological Quality of Systematic Reviews, we extracted strong evidence supporting TPE's significant impact on decreasing mortality in septic shock patients compared to standard care, as demonstrated in three randomized controlled trials and one cohort study, with an odds ratio (OR) of 0.43 (95% confidence interval (CI) = 0.26-0.72). Additionally, two meta-analyses further validate TPE's effectiveness, showing a mortality reduction with an OR of 0.30 (95% CI = 0.20-0.46). This advantage also extends to critically ill COVID-19 patients, underscoring TPE's crucial role in modulating the coagulation cascade, decreasing sepsis-related complications, and reducing the risk of bleeding and organ failure. Nevertheless, the benefits of TPE must be carefully balanced against potential risks such as hypocalcemia, hypotension, and citrate toxicity, especially in patients with underlying renal or liver issues, emphasizing the importance of shared decision-making. While TPE emerges as a promising therapy, its formal integration into standard care protocols awaits further confirmation, highlighting the critical need for more in-depth research to conclusively determine its efficacy and safety in septic shock management.

#1475 Anti-neutrophil cytoplasmic antibodies (ANCA) associated vasculitis (AAV) with glomerulonephritis (AAV-GN) in real world life

Abstract Background and Aims Anti-neutrophil cytoplasmic antibodies (ANCA) associated vasculitis (AAV) with glomerulonephritis (AAV-GN) is a rare disease and the different treatment with plasma exchange are still controversial. We evaluate the AAV-GN outcomes of the last ten years in our centre. Method We retrospectively reviewed the clinical presentations and outcomes of AAV-GN patients in our centre between 2013-2022. We compared the presentation and prognosis according to the type of ANCA, serum creatinine (SCr) and the use of plasma exchange (PLEX). We included patients with AAV and kidney biopsy with at least 6 months of follow-up. Patients with positivity for both MPO and PR3, anti-GBM antibodies or did not meet inclusion criteria were excluded. Results Of 64 patients reviewed, 13 were excluded: 3 lack of follow-up, 3 absence of renal biopsy, 3 ANCA negative, and 4 concomitant anti-GBM antibodies. A total of 51 patients were included in the analysis (Table 1): 28 women (54.9%), age 66.75 ± 15.24 years, (64.7% over 65 years) and 44 (86.3%) with ANCA-MPO (+). Results comparing ANCA-MPO and PR3 in Table 1. The most frequent form of presentation was anaemia with haemoglobin 9.87 ± 2.04 mg/dL, acute kidney injury (AKI) AKIN III (39.2%), median SCr 2.78 (1.58-5.22) mg/dL, 41 (80.4%) with microhematuria, proteinuria 2.62 ± 2.7g/g, and 8 (15.7%) alveolar haemorrhage. 18 patients (25.3%) required hemodialysis, and 7 (13.5%) were transient (4 requiring &amp;lt;1 month). Rituximab was more used than cyclophosphamide (p &amp;lt; 0.001). Of the patients treated with plasma exchange (PLEX, n = 11), 6 (54.5%) had alveolar haemorrhage and/or 7 (63.6%) SCr&amp;gt;5.6 mg/dL, with no further infections or mortality at one year. Of the patients diagnosed with SCr&amp;gt;5.6 mg/dL, 9 (81.8%) were men (p = 0.008), 7 (63.6%) received PLEX (p &amp;lt; 0.001) and 6 (54.4%) died (p = 0.003). As expected, in the multivariate binary logistic regression SCr&amp;gt;5.6 at diagnosis was identified as independent risk factor for PLEX (p = 0.02, OR = 15.6 (95% CI 3.16-76.92). There were 13 deaths (25.5%), 6 in the first year after diagnosis. The most used maintenance treatment was MMF (52.9%), SCr and glomerular filtration rates at 2 years were 1.5 mg/dL and 45.36 mL/min/1.72 m² respectively. Conclusion The most common AAV-GN in our centre are ANCA-MPO+, and mainly affect people over 65 years of age, with rituximab being the most used treatment. ANCA-MPO+ patients have worse renal function at 18 months of follow-up. Mortality is higher in AAV-GN with serum creatinine greater than 5.6 mg/dL at diagnosis and in ANCA-MPO+. PLEX therapy is more used in cases of alveolar hemorrhage or severe renal involvement, without presenting an impact in our cohort in the incidence of infections or mortality at one year of follow-up.

#3076 A UK parallel cohort study on renal ANCA associated vasculitis outcomes for avacopan exposed and matched unexposed cohorts

Abstract Background and Aims Avacopan was approved in the UK for severe ANCA associated vasculitis (AAV) in December 2022. The ADVOCATE trial found the differential effect of avacopan on kidney function was greatest in patients with the lowest estimated glomerular filtration rate (eGFR), at highest risk of progression to end stage kidney disease (ESKD). Patients with an eGFR &amp;lt;15 ml/min/1.73 m2, pulmonary haemorrhage requiring invasive ventilation, under 12 months prognosis, use of plasma exchange and dual therapy with cyclophosphamide (CYC) and rituximab (RTX) were excluded from ADVOCATE; all common scenarios in real life practice. We aim to provide further information on these subgroups and evaluate 6 month renal outcome data in the UK. Method Parallel cohort study on renal AAV outcomes for avacopan exposed and matched unexposed cohorts, with severe, active GPA or MPA. 120 patients on avacopan from 7 UK centres have been recruited to date. Controls matched by renal function and age will be presented. Comparisons of ESKD, delta eGFR, eGFR recovery, reduction in proteinuria/haematuria, remission, relapse and mortality will be presented, with subgroup analyses for eGFR&amp;lt;15 ml/min/1.73 m2. Steroid exposure will be presented. Results Baseline characteristics of the avacopan cohort are below. Most received oral prednisolone at avacopan initiation (89%, n = 107) and 54% received intravenous methylprednisolone (n = 65). The majority received RTX alone (44%, n = 53) or RTX and CYC combination therapy (43%, n = 52). Fewer received CYC alone (9%, n = 11) and 3% were initiated on alternative immunosuppression (n = 4). 26% (n = 31) underwent plasma exchange and 13% required haemodialysis (n=16). 3% of patients have died. Excluding dialysis dependent patients at presentation, median eGFR was 22ml/min/1.73 m2 (IQR 10-36). eGFR at the time of avacopan initiation was 21ml/min/1.73 m2 (IQR 11-34). Conclusion Avacopan is commonly being used to treat nephritis in patients with a low eGFR, including haemodialysis dependent and elderly patients. Avacopan is frequently used with RTX and CYC combination therapy. 6 month outcome data will provide new data on important patient subgroups excluded from the ADVOCATE trial.

Outcomes of patients with thrombotic thrombocytopenic purpura treated in an intensive care unit.

Background Thrombotic thrombocytopenic purpura (TTP) is a multisystem disorder characterized by widespread microthrombosis that can predispose to multiple organ failure. The literature is sparse on the outcomes of critically ill patients with TTP managed in intensive care units (ICUs). We aimed to determine the mortality of ICU patients admitted with TTP and evaluate the predictors of survival. We also compared the incidence of nosocomial infection among those who did or did not receive plasma exchange (PE). Methods We conducted a retrospective study in a tertiary ICU. Two authors screened patients for eligibility from the hospital information system based on peripheral smear reports. Adult critically ill TTP patients managed in ICU were included. Patients with a diagnosis of haemolytic uraemic syndrome, autoimmune causes of haemolysis and pregnancy-related conditions, etc. were excluded. Two authors extracted data from medical charts. No imputation of missing variables was done. Non-parametric statistics were used to report data. Statistical analyses were performed using Stata version 16. Results Of the 535 records that were screened, 33 patients were deemed eligible. Mortality among TTP patients was 14 (42%). The women to men ratio was 7:3. At admission, greater degree of anaemia, thrombocytopenia, and higher lactate dehydrogenase levels were observed in non-survivors compared to survivors (5.4 g/dl [4.8-7.1] v. 7.6 g/dl [6.1-8.9], p=0.05; 17x103 μl v. 21x103 μl, p=0.63; and 2987 (1904-3614) U/L v. 2126 U/L (1941-3319), p=0.71; respectively]. Nineteen (57%) patients had acute kidney injury (AKI), of which 11 survived: 6 recovered completely from renal failure and 5 progressed to end-stage renal disease. Nosocomial infection rates were not different among those receiving and not receiving PE therapy (7 [33%] v. 3 [25%], respectively). Conclusion TTP is more common in women and has a high mortality. Older age, low haemoglobin and higher platelet transfusions are predictors of poor survival. Nosocomial infection rates were similar irrespective of receiving PE therapy.

Management of pediatric liver failure with therapeutic plasma exchange and continuous renal replacement therapy: A retrospective observational study.

Liver failure represents a critical medical condition, marked by the rapid decline of hepatic functions. Emerging therapies, notably therapeutic plasma exchange (TPE) and continuous venovenous hemodiafiltration (CVVHDF), have demonstrated potential in mitigating these conditions through their roles in detoxification and hepatic support. The utility of these treatments, whether applied individually or in tandem, constitutes a significant area of research concerning the management of liver failure in pediatric patients. This study aims to evaluate the role and efficacy of TPE or TPE combined with CVVHDF in the treatment of liver failure among children. This retrospective study was conducted in a LTICU by reviewing the medical history of pediatric patients aged 1 month to 18 years. Patients were admitted between January 1, 2021 and December 1, 2023 due to acute liver failure or acute-chronic liver failure. The study evaluated those who received TPE or continuous renal replacement therapy combined with TPE. In statistical analyses, a P-value of <.05 was considered statistically significant. The study involved 24 patients with liver failure, comprising 13 males and 11 females. Sixteen patients (66.6%) received only TPE, while 8 patients (33.4%) were treated with TPE and CVVHDF. For patients treated only with TPE, the median INR reduced from 3.1 to 1.26, alanine aminotransferase from 1255 to 148, and aspartate aminotransferase from 2189 to 62. Similar significant reductions were observed in the TPE and CVVHDF group: INR from 3.9 to 1.26, alanine aminotransferase from 1749 to 1148, and aspartate aminotransferase from 1489 to 62. These changes were statistically significant with P-values of .01 for each parameter in both groups. Overall, 14 patients survived without requiring a liver transplant, while 4 patients underwent liver transplantation. Our study on pediatric liver failure treatment shows that both standalone TPE and its combination with CVVHDF are effective, especially as a bridge to transplantation. With 58% transplant-free survival, these therapies demonstrate significant clinical improvements. Future multicentric studies are needed for broader validation of these findings in liver failure management.

Critical Care in Guillain–Barré Syndrome

AbstractGuillain–Barré syndrome (GBS) is an autoimmune polyneuropathy characterized by hyporeflexic neuromuscular paralysis and albuminocytologic dissociation in the cerebrospinal fluid. It is a postinfectious disorder. The most common antecedent illnesses are respiratory tract infection and Campylobacter jejuni infection. After the antecedent infection, specific antibodies are generated that cross-react with gangliosides in the host culminating in demyelination of the peripheral nerves or nerve roots. Complement activation also contributes to nerve degeneration. Bilateral symmetrical progression of the limb weakness occurs over a period of a few days followed by a plateau phase, after which a recovery phase follows. Generalized hypotonia and hyporeflexia characterize the limb weakness. Cerebrospinal fluid analysis shows albuminocytologic dissociation. About one-third of patients develop respiratory failure. Neuropathic pain is a disturbing symptom in GBS. Dysautonomia is very characteristic of GBS. Erasmus GBS respiratory insufficiency score predicts the need for mechanical ventilation. The weaning process from mechanical ventilation mainly depends on the recovery of vital capacity and inspiratory force. The definitive treatment for GBS consists of plasma exchange or intravenous immunoglobulin therapy both of which are equally efficacious. Seasonal variation has been observed in the occurrence and recovery of GBS. Prognosis of GBS varies widely. Erasmus GBS outcome scale scoring system predicts the ability of the patient to walk independently after 6 months. Several GBS cases have been reported globally during recent pandemic of coronavirus disease 2019. Though GBS is a self-limiting disease, there are quite a few research questions that still remain to be answered.

Management of Fetal Hemolytic Disease Due to Anti-Rh17 With the D−Phenotype [ID 2683500

INTRODUCTION: The rare blood D− haplotype produces multiple Rh antibodies against red blood cell antigens such as anti-Rh17 or anti-Hr0 antibodies if a patient is sensitized to Rh antigens. METHODS: This report discusses successful management of a pregnancy in a 28-year-old woman with high anti-Rh17 titers leading to hemolytic disease of the fetus (HDFN). The combination of a D− allele and the weak D 45 allele has not been reported previously, and it may be that the hybrid allele expresses D antigen epitopes such that the D antigen is not weakened. During the studied pregnancy, the patient received plasmapheresis and intravenous immunoglobulin (IVIG) infusions along with intrauterine transfusions (IUTs) when absolutely necessary. She underwent uncomplicated repeat cesarean delivery at 32 5/7 weeks of gestation resulting in a female infant weighing 2,020 g. Patient informed consent was obtained for this case report. CONCLUSION: This patient with the D−/D− blood phenotype leading to anti-Rh17 antibodies after her first pregnancy was managed successfully. Her baby with HDFN and several instances of hydrops fetalis, was successfully managed and treated. The patient’s blood donations for IUTs and maternal plasma exchange therapies promoted efficiency and favorable outcomes for the baby, but did put the mother in an anemic blood range.

Visual Function Improvement after Plasma Exchange Therapy for Acute Optic Neuritis in Neuromyelitis Optica Spectrum Disorders: Case Series and Review.

Neuromyelitis optica (NMO) and neuromyelitis optica spectrum disorder (NMOSD) are autoimmune-mediated central nervous system disorders distinguished by the presence of serum aquaporine-4 IgG antibody (AQP4-Ab). The clinical panel comprises severe optic neuritis (ON) and transverse myelitis, which can result in incomplete recovery and a high risk of recurrence. This study aimed to evaluate the visual outcomes of three patients with severe acute ON in NMOSD that was non-responsive to intravenous methylprednisolone (IVMP), who received plasma exchange therapy (PLEX). We included three patients (P1, P2 and P3) with severe acute ON who had no improvement after IVMP treatment and were admitted to the ophthalmology department at the Emergency University Hospital Bucharest from January 2022 to September 2023. All three patients with ON were diagnosed in accordance with the criteria described by the Optic Neuritis Treatment Trial. All the subjects were experiencing their first attack. The mean recruitment age was 35.3 ± 7.71. All patients were seropositive for the AQP4 antibody. All patients were tested for serum myelin oligodendrocyte glycoprotein (MOG) antibody but only one showed a positive test (P3). Lesions visible in orbital MRI indicated the involvement of retrobulbar, canalicular and/or intracranial segments. All three subjects had no response or incomplete remission after an IVMP protocol (5 days of 1000 mg intravenous methylprednisolone in sodium chloride 0.9%). The mean time from onset of optic neuritis to PLEX was 37.6 days. The PLEX treatment protocol comprised five cycles of plasma exchange treatment over 10 days, with a plasma exchange session every other day. An amount of 1 to 1.5 volumes of circulating plasma were dialyzed for 2-4 h. At 1 month after the completion of PLEX therapy, BCVA and VF parameters were improved in all three patients. The treatment of ON remains subject to debate and is somewhat controversial. Plasma exchange must be considered as a rescue therapy when IVMP is insufficient for AQP4-ON patients. This study revealed that PLEX treatment effectively improves the visual outcomes of patients experiencing their first attack of severe acute isolated ON after high-dose IVMP treatment. This study suggests that PLEX may be associated with improved visual outcomes in NMOSD acute optic neuritis.

Comparison of estimated blood loss during living kidney transplantation according to the number of double-filtration plasmapheresis

BackgroundPlasmapheresis is an important preoperative desensitization treatment for ABO-incompatible living kidney transplantation. However, in cases with plasma exchange therapy (PET), it is necessary to consider the risks of perioperative bleeding and healthcare economic costs. This study investigated the association between intraoperative blood loss and the frequency of preoperative double-filtration plasmapheresis (DFPP) and explored the correlation between DFPP frequency and coagulation factors. Furthermore, the study examined the incidence of perioperative bleeding complications.MethodsWe enrolled 294 patients (205 men and 89 women) who underwent living kidney transplantation at our institution between January 2020 and March 2023, without PET or with only DFPP performed as PET. A single dose of rituximab (200 mg) was administered to ABO-incompatible living kidney transplant patients within 7 days before transplantation. In these patients, PET was performed until anti-blood group IgG and IgM antibody titers were reduced to 32 times or less.ResultsThe intraoperative blood loss increased in accordance with the DFPP sessions. The amount of bleeding significantly increased when DFPP was performed ≥ 2 sessions. Considering this, we initiated serum fibrinogen level measurements from the middle of the study and observed that serum fibrinogen levels decreased in correlation with the number of DFPP sessions. Fibrinogen levels dropped to critical levels (< 100 mg/dL) after three sessions of DFPP. Within the entire cohort, four patients (1.4%) underwent post-transplantation hematoma removal surgery, and among them, three had received DFPP before transplantation.ConclusionsThe number of DFPP procedures was associated with the amount of bleeding and serum fibrinogen levels during living kidney transplantation.

A Clinicopathological study of Guillain-Barrḗ Syndrome in a Tertiary Level Hospital

Background: Guillain-Barre syndrome (GBS) stands out as the most prevalent autoimmune neurological disorder. This investigation involves a comparative analysis of clinical observations, neurophysiological assessments, and cerebrospinal fluid examination, outcomes among patients with GBS. Method: A retrospective review of medical records constituted the methodology for this study, spanning from July 1, 2023, to December 31, 2023. Sociodemographic traits, antecedent illnesses, clinical progression, laboratory results, therapeutic interventions, and ultimate outcomes were assessed and compared among the study participants. Results: The study encompassed 8 patients, with an average age of 42.75 years. Respiratory complications were evident in 87.5% of the patients. In CSF analysis, 62.50% exhibited a normal cell count, while 37.50% displayed an elevated count. Elevated CSF protein levels were observed in 50% of patients, with a corresponding 50% revealing normal CSF protein levels. Increased CSF protein was associated with delayed lumbar puncture, demyelinating nerve conduction study subtype, and sensory motor variant. Regarding treatment modalities, 37.5% received intravenous immunoglobulin, and 25% underwent plasma exchange therapy. The acute phase of the disease resulted in a 25% mortality rate among patients. Conclusion: Guillain-Barre syndrome manifests diverse clinical presentations and laboratory findings. Notably, a high cerebrospinal fluid cell count challenges the widely accepted Brighton criteria for GBS diagnosis. Further investigations are warranted to elucidate the correlation between elevated CSF cell count and other factors influencing pathogenesis and outcomes in GBS patients. Bangladesh Crit Care J March 2024; 12 (1): 25-28

Trends in Plasma Exchange Use in Optic Neuritis Hospitalizations in the United States

To report use trends of plasma exchange (PLEX) as well as sociodemographic and medical comorbidities associated with PLEX in the United States. Retrospective cross-sectional study. Adult patients (≥ 18 years) admitted for inpatient hospitalization with a primary diagnosis of optic neuritis (ON). Data from the National Inpatient Sample database was compiled to assess PLEX use rates between 2000 and 2020. The cohorts of patients receiving PLEX versus not receiving PLEX were analyzed between quarter 4 of 2015 through 2020 (International Classification of Diseases, Tenth Revision [ICD-10], only) for patient sociodemographic variables, medical diagnoses, insurance types, hospital characteristics, cause of disease, time to therapy, length of stay (LOS), and total charges incurred. Incidence of ON, incidence of PLEX, demographics, diagnoses associated with PLEX therapy, total charges, and LOS. From 2000 through 2020, 11 209 patients hospitalized with a primary diagnosis of ON were identified, with a significant majority managed at urban teaching hospitals. Use of PLEX increased steadily over 2 decades from 0.63% to 5.46%. Use was greatest in the western United States and least in the eastern United States. In the subset of ICD-10 cases, 3215 patients were identified. The median time to therapy of PLEX was 1 day after admission, and PLEX use was highest in patients with neuromyelitis optica spectrum disorder (NMOSD) (21.21%) and lowest in multiple sclerosis-associated ON (3.80%). Use of PLEX was associated with significantly longer LOS and higher total charges incurred. Medical comorbidities associated with PLEX included adverse reaction to glucocorticoids (adjusted odds ratio [aOR], 31.50), hemiplegia (aOR, 28.48), neuralgia (aOR, 4.81), optic atrophy (aOR, 3.74), paralytic strabismus (aOR, 2.36), and psoriasis (aOR, 1.76). Over the last 2 decades in the United States, PLEX therapy for ON has increased, with the highest use in the western United States and for patients with the diagnosis NMOSD ON. The author(s) have no proprietary or commercial interest in any materials discussed in this article.