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Background Sepsis remains a common condition with high mortality when multiple organ failure develops. The evidence for therapeutic plasma exchange (TPE) in this setting is promising but inconclusive. Our study aims to evaluate the efficacy of adjunct TPE for septic shock with multiple organ failure compared to standard therapy alone. Methods A retrospective, observational chart review was performed, evaluating outcomes of patients with catecholamine-resistant septic shock and multiple organ failure in intensive care units at a tertiary care hospital in Winston-Salem, NC, from August 2015 to March 2019. Adult patients with catecholamine-resistant septic shock (≥ 2 vasopressors) and evidence of multiple organ failure were included. Patients who received adjunct TPE were identified and compared to patients who received standard care alone. A propensity score using age, gender, chronic co-morbidities (HTN, DM, CKD, COPD), APACHE II score, SOFA score, lactate level, and number of vasopressors was used to match patients, resulting in 40 patients in each arm. Results The mean baseline APACHE II and SOFA scores were 32.5 and 14.3 in TPE patients versus 32.7 and 13.8 in control patients, respectively. The 28-day mortality rate was 40% in the TPE group versus 65% in the standard care group ( p  = 0.043). Improvements in baseline SOFA scores at 48 h were greater in the TPE group compared to standard care alone ( p  = 0.001), and patients receiving adjunct TPE had a more favorable fluid balance at 48 h ( p  = 0.01). Patients receiving adjunct TPE had longer ICU and hospital lengths of stay ( p  = 0.003 and p  = 0.006, respectively). Conclusions Our retrospective, observational study in adult patients with septic shock and multiple organ failure demonstrated improved 28-day survival with adjunct TPE compared to standard care alone. Hemodynamics, organ dysfunction, and fluid balance all improved with adjunct TPE, while lengths of stay were increased in survivors. The study design does not allow for a generalized statement of support for TPE in all cases of sepsis with multiple organ failure but offers valuable information for a prospective, randomized clinical trial.

Background Amatoxin-related acute liver failure (AT-ALF) carries high mortality without liver transplantation (LTX). While therapeutic plasma exchange (PEX) might improve LTX-free survival in other ALF cases, its role in AT-ALF is unclear. Clinical practice varies, and, given the rarity of this ALF entity, the feasibility of conducting a randomized controlled trial to investigate PEX in AT-ALF is more or less impossible. Methods The Amanita-PEX study is a multi-center, international, retrospective study analyzing patients with AT-ALF from 2013 to 2024. The primary outcome was 28-day LTX-free survival (composite endpoint: death or LTX) after ALF diagnosis. Results The study included 111 patients from 25 centers: 82 received standard-of-care (SOC), and 29 received at least one PEX-session. PEX and SOC-groups were comparable at baseline, but 76% of PEX- vs. 58% of SOC-patients developed hepatic-encephalopathy (HE) grade ≥ 2 ( p  = 0.021). While the primary outcome of 28-day LTX-free survival in all patients was not different between the SOC and PEX-groups, in the subgroup of patients with maximal HE grade ≥ 2, LTX-free survival was 19.1% ( n  = 8/42) in the SOC group, while it was 36.4% ( n  = 8/22) in patients receiving adjunctive PEX (Gehan-Breslow-Wilcoxon- p  = 0.041, Log-Rank- p  = 0.060). PEX was independently associated with reduced risk of the combined endpoint death or liver transplantation within 28 days from inclusion in patients with HE grade ≥ 2 (HR 0.37, 95%-CI 0.19–0.73, p  = 0.004). After propensity-score-matching, LTX-free survival was 28% in the SOC- and 52% in the PEX group (Gehan-Breslow- p  = 0.036; Log-Rank- p  = 0.035). Conclusions In this real-world study, adjunctive use of PEX was associated with increased LTX-free-survival in patients with AT-ALF and HE grade ≥ 2. Highlights Acute liver failure due to ingestion of mushrooms containing amatoxins has a poor prognosis when higher grade hepatic encephalopathy develops. Adjunctive use of therapeutic plasma exchange was independently associated with increased liver transplant-free-survival in patients with amatoxin associated acute liver failure and maximum hepatic encephalopathy grade ≥ 2. Therapeutic plasma exchange was not associated with increased liver transplant-free-survival in patients with hepatic encephalopathy grade 1 and did not improve overall-survival or other secondary endpoints such as shorter length of hospital stay or lower incidence of acute kidney injury, need for renal-replacement therapy, invasive ventilation or vasopressor support. Impact and Implications Therapeutic plasma exchange is frequently used in the management of patients with acute liver failure but its effect on improving liver transplant-free-survival has recently been questioned. Amatoxin-associated acute liver failure is a rare entity of acute liver failure and solid data concerning clinical outcomes are scarce. This multi-national, multi-center, real-world, retrospective study suggests that therapeutic plasma exchange is significantly associated with improved liver transplant-free survival only in patients with amatoxin-associated acute liver failure and higher-grade hepatic encephalopathy. These results might help to guide the future use of therapeutic plasma exchange in this specific patient population. Graphical abstract

Background Autoimmune hemolytic anemia (AIHA) is a rare but potentially life-threatening condition requiring intensive care unit (ICU) admission in severe cases. While corticosteroids and immunosuppressants are standard treatments, their delayed efficacy limits their utility in critical settings requiring rapid hemolysis control. Plasma exchange (PlEx) may offer a rapid intervention, but its effectiveness in severe AIHA remains uncertain. This study aims to assess the clinical characteristics, outcomes, and the potential benefit of PlEx in ICU cases with severe AIHA. Methods We conducted a multicenter retrospective cohort study including patients with severe AIHA admitted to 15 ICUs within the Assistance Publique–Hôpitaux de Paris (AP-HP) network between 2017 and 2024. Clinical, biological, and therapeutic data were collected. A multivariate logistic regression model, an analysis adjusted on a propensity score (PS) and on inverse probability of treatment weighting (IPTW) were used to identify predictors of in-ICU mortality and evaluate the association between PlEx and in-ICU mortality. Results One hundred forty-eight ICU stays involving severe AIHA hemolytic crises were analyzed. The median age at ICU admission was 61 {48–71} years, with a balanced sex ratio (51% male). Admission median hemoglobin was 5.2 g/dL {4.2–7.2} and in-ICU mortality was 17.6%. Risk factors for in-ICU mortality included age > 60 years, renal replacement therapy, mechanical ventilation, and high-dose intravenous methylprednisolone (HDIM). Therefore, ICU mortality was mainly driven by organ dysfunction rather than anemia severity. Standard corticosteroid therapy (1–2 mg/kg) (OR:0.19 [0.03–0.94], P  = 0.05) and PlEx (OR:0.04 [0.004–0.4], P  = 0.008) were associated with improved survival. The association between PlEx and outcome persisted after PS (OR: 0.04 [0.001–0.39]; P  = 0.012) and IPTW (OR: 0.13 [0.02–0.55]; P  = 0.011) adjustment. Conclusion In this large ICU cohort, severe AIHA was associated with high mortality, driven by organ failure rather than anemia severity. PlEx are associated with survival, suggesting its potential role as a bridge to immunosuppressive therapy in selected cases. Prospective studies are needed to confirm these findings.

: This study investigated and compared the efficacy of therapeutic plasma exchange (PEX) between antineutrophil cytoplasmic antibody (ANCA)-positive and ANCA-negative patients with microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) presenting with diffuse alveolar haemorrhage (DAH) and rapidly progressive glomerulonephritis (RPGN). : A total of 336 patients with ANCA-associated vasculitis were screened, and 34 patients with MPA/GPA receiving PEX for DAH or RPGN were included. PEX was performed a total of 5-6 times consecutively (three times a week × 2 weeks) in all 34 patients. All-cause mortality (ACM) and end-stage kidney disease (ESKD) were evaluated as poor outcomes of MPA/GPA. Clinical data and poor outcomes were compared between ANCA-positive and ANCA-negative MPA/GPA patients receiving PEX. : The median age of the 34 MPA/GPA patients was 67 years (15 men and 19 women), of whom two were diagnosed with ANCA-negative vasculitis. Among the 34 patients, 28 (82.4%) received PEX owing to RPGN, and 6 (17.6%) due to DAH. During follow-up, 13 patients (38.2%) died, and 15 (44.1%) progressed to ESKD. Serum protein and C-reactive protein levels at AAV diagnosis were higher in ANCA-positive MPA/GPA patients than in ANCA-negative patients, although the difference was not statistically significant. Similarly, there were no differences in ACM or ESKD between the two groups during follow-up. Survival analysis showed that ANCA-positive MPA/GPA patients did not have significantly different cumulative patient or ESKD-free survival rates compared to ANCA-negative patients. : This pilot study is the first to demonstrate the clinical feasibility of PEX in managing severe and refractory ANCA-negative MPA and GPA.

Background Therapeutic plasma exchange (TPE) is increasingly used throughout the world. Although the procedure itself is fairly standardized, it is yet unknown how the underlying disease entities influence the key coordinates of the treatment. Methods Retrospective chart review. The treatment indications were clustered into four categories. Data are presented as median and interquartile (25–75%) range [IQR]. Results Within 1 year, 912 TPE treatments were performed in 185 patients (90 female, 48.6%). The distribution of the treatment numbers to the pre-specified disease categories were as follows: transplantation (35.7%), neurology (31.9%), vasculitis and immunological disease (17.3%), and others including thrombotic microangiopathy (8.1%), critical care related diseases (5.4%), hematology [multiple myeloma] (1.1%), and endocrine disorders (0.5%). The calculated plasma volume was significantly higher in patients with vasculitis and immunological diseases (3984 [3433–4439] ml) as compared to patients treated for transplant related indications (3194 [2545–3658] ml; p  = 0.0003) and neurological diseases (3058 [2533–3359] ml; p  < 0.0001). This was mainly due to the differences in the hematocrit which was 30.5 [27.0–33.6] % in the vasculitis/immunological disease patients and 40.2 [37.5–42.9] % in the neurological patients; p  < 0.0001. Interestingly, treatment time using a membrane based technology was significantly longer than TPE using a centrifugal device 135.0 [125.0–140.0] min vs. 120.0 [112.5–135.0] min. Furthermore, the relative exchanged plasma volume was significantly lower in the treatment of vasculitis and immunological diseases as compared to treatments of transplant related indications and neurological diseases. Conclusion Patients with low hematocrit and high body weight do not receive the minimum recommended dose of exchange volume. Centrifugal TPE allowed faster plasma exchange than membrane TPE.

Background and objective: Severe sepsis and septic shock are life-threatening organ dysfunctions and causes of death in critically ill patients. The therapeutic goal of the management of sepsis is restoring balance to the immune system and fluid balance. Continuous renal replacement therapy (CRRT) is recommended in septic patients, and it may improve outcomes in patients with severe sepsis or septic shock. Therapeutic plasma exchange (TPE) is another extracorporeal procedure that can improve organ function by decreasing inflammatory and anti-fibrinolytic mediators and correcting haemostasis by replenishing anticoagulant proteins. However, research about sepsis and CRRT and TPE in children has been insufficient and incomplete. Therefore, we investigated the reliability and efficacy of extracorporeal therapies in paediatric patients with severe sepsis or septic shock. Materials and methods: We performed a multicentre retrospective study using data from all patients aged <18 years who were admitted to two paediatric intensive care units. Demographic data and reason for hospitalization were recorded. In addition, vital signs, haemogram parameters, and biochemistry results were recorded at 0 h and after 24 h of CRRT. Patients were compared according to whether they underwent CRRT or TPE; mortality between the two treatment groups was also compared. Results: Between January 2014 and April 2019, 168 septic patients were enrolled in the present study. Of them, 47 (27.9%) patients underwent CRRT and 24 underwent TPE. In patients with severe sepsis, the requirement for CRRT was statistically associated with mortality (p < 0.001). In contrast, the requirement for TPE was not associated with mortality (p = 0.124). Conclusion: Our findings revealed that the requirement for CRRT in patients with severe sepsis is predictive of increased mortality. CRRT and TPE can be useful techniques in critically ill children with severe sepsis. However, our results did not show a decrease of mortality with CRRT and TPE.

Guillain–Barré syndrome (GBS) outbreaks associated with endemic and epidemic infections have increased in recent decades, and the need for standard treatment guidelines is compelling. A new study presents data from a worldwide prospective observational registry, providing insights into current treatment practices and laying the foundations for future clinical trials.

Background/Objectives: Acute liver failure (ALF) is a life-threatening condition with high mortality in nontransplant candidates. Therapeutic plasma exchange (TPE) has emerged as a promising intervention for removing inflammatory mediators and toxic metabolites. In Latin America, data on the efficacy of TPE in ALF patients are limited. This real-world study aimed to compare 30-day survival outcomes between patients receiving standard medical treatment (SMT) and those receiving SMT plus TPE. Methods: We analyzed 25 ALF patients admitted to the tertiary intensive care unit (ICU) of Hospital Juárez of Mexico City, Mexico, from 2018 to 2024. Patients received either standard medical treatment (SMT group, n = 12) or SMT with TPE (TPE group, n = 13), including high-volume TPE (n = 8) and standard-volume TPE (n = 5). Survival analysis was performed via Kaplan–Meier estimates, and binomial regression analysis was run to estimate the mortality probability stratified by the hepatic encephalopathy grade. Results: At 30 days, survival was significantly greater in the TPE group (92%) than in the SMT group (50%) (p = 0.02). The greatest survival benefit was observed in patients with Grade 4 encephalopathy. The ICU stay was longer in the TPE group, reflecting the complexity of ALF management. Conclusions: TPE significantly improves 30-day survival in ALF patients compared with SMT alone, supporting its role as an adjunct therapy. Further studies are needed to refine patient selection and optimize treatment protocols.

Steroids have been beneficial in the treatment of demyelinating diseases with features similar to those of Guillain-Barré syndrome (GBS). However, steroid treatment of GBS has been disappointing; in an earlier trial oral prednisolone was ineffective, although the dose was low and the sample small. We assessed the benefit of a high-dose steroid regimen in a large sample of patients with GBS in a multicentre, randomised, double-blind trial. 242 adult patients were randomised to receive intravenous methylprednisolone (IVMP) 500 mg (124 patients) or a placebo (118) daily for 5 days. Patients were diagnosed by standard clinical criteria and entered the trial within 15 days of onset of neurological symptoms. All patients were too weak to run. Some patients received plasma exchange depending on the practice of their centre. Disability was graded on a scale from 0 (healthy) to 6 (dead) at intervals for 48 weeks. There was no significant difference in any outcome variable between patients treated with IVMP and those given placebo. The most important outcome was the difference between the groups in disability grade 4 weeks after randomisation, which was only a 0.06 grade (95% Cl -0.23 to 0.36) greater improvement in the IVMP than the placebo group. The 39 patients in the IVMP group who required ventilation did so for a median of 18 days, 9 days fewer than the 44 patients who had a placebo and required ventilation (95% Cl -9.6 to 27.6). Median time to walk unaided was 38 days in the IVMP patients and 50 days in the placebo patients (difference 12 days, (95% Cl -21.3 to 45.3). A short course of high-dose IVMP given early in GBS is ineffective.

Of 40 patients with thrombotic thrombocytopenic purpura, 17 were treated with plasma exchange, 15 with exchange transfusions, and 6 with both types of therapy. One patient died before being treated and another patient was seen but not treated. Plasma exchange was performed daily for a mean of seven exchanges per patient. The replacement fluid during plasma exchange was fresh frozen plasma in all cases. The complete response rates for each type of treatment were as follows: 88% for plasma exchange (15 patients), 47% for exchange transfusions (7 patients), and 67% for exchange transfusions and plasma exchange (4 patients). Clinical and laboratory factors were examined for any statistically significant association with therapy response. Treatment with plasma exchange was statistically the initial factor most strongly associated with prognosis. Paresis, paresthesias, seizures, mental status change, and coma showed no association with response to treatment. Some of the laboratory factors that did not show significant association with treatment response were the initial creatinine, hemoglobin, platelet count, lactate dehydrogenase, and total bilirubin. This study supports the hypothesis that plasma exchange has significantly improved the prognosis of patients with thrombotic thrombocytopenic purpura. These patients should be treated aggressively regardless of the severity of their symptoms.