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ABSTRACT Aims Methods Conclusion Pilot studies indicate that immunoadsorption with subsequent IgG substitution (IA/IgG) induces beneficial effects in patients with dilated cardiomyopathy (DCM) and heart failure. This placebo‐controlled study investigates whether IA/IgG treatment enhances left ventricular (LV) systolic function as compared to a control group receiving pseudo‐treatment.This multicentre, randomized, double‐blind, parallel‐group trial aims to include 200 patients with heart failure due to DCM (LV ejection fraction [LVEF] <40%) on optimized guideline‐directed heart failure medication. Participants are randomly assigned in a 1:1 ratio to IA/IgG using protein‐A columns, or to pseudo‐immunoadsorption followed by an intravenous infusion without IgG. Follow‐up visits take place by telephone after 1 and 3 months and at the study centres after 6, 12 and 24 months. The primary efficacy endpoint is the change in LVEF from baseline to 6 months determined by contrast echocardiography, analysed at a core lab. In addition, LV end‐diastolic and end‐systolic volumes will be analysed as secondary endpoints over the entire study period to assess whether IA/IgG affects LV remodelling. As main secondary outcome, a composite of all‐cause death, cardiac resuscitation, hospitalization for heart failure, and need for cardiac surgery to improve myocardial pump function will be evaluated after 24 months. In addition, exploratory outcomes as well as safety endpoints related to the treatment will be assessed throughout the whole study period.IASO‐DCM is a randomized study which will provide comprehensive insights into the effects of immunoadsorption with subsequent IgG substitution in patients with DCM. [ABSTRACT FROM AUTHOR]

Background: Therapeutic apheresis (TA) is already used to treat various diseases in the field of nephrology. The aim of this study was to evaluate the frequency and types of complications that occur during TA in children with kidney disease. Methods: Records of children (≤ 18 years) who underwent TA between 2007 and 2022 were retrospectively reviewed. Children with missing data and those with a diagnosis of nonnephrological disease were excluded. Results: A total of 1214 TA sessions, including 1147 therapeutic plasma exchange (TPE) sessions and 67 immunoadsorption (IA) sessions, were performed on the 108 patients enrolled in the study. Forty-seven percent of the patients were male, and the mean age was 12.22 ± 4.47 years. Posttransplant antibody-mediated rejection (64.8%) and hemolytic uremic syndrome (14.8%) were the most common diagnoses indicating TA. Overall, 17 different complications occurred in 58 sessions (4.8%), and 53 sessions (4.6%) were not completed because of these complications. The distribution of complications among the patients was as follows: 41.4% had technical complications, 25.9% had allergic complications, and 32.7% had others. The most common technical complication was insufficient flow (37.5%). The incidence of complications was greater in patients aged 3–6 years than in patients in the other age groups (p = 0.031). The primary disease, type of vascular access, and rate of fresh frozen plasma/albumin use were similar between patients with and without complications (p values of 0.359 and 0.125 and 0.118, respectively). Conclusions: Our study showed that complications occurred in only 4.8% of TA sessions. The most common complication was technical problems. [ABSTRACT FROM AUTHOR]

Background and purpose: The predictive value of serum neurofilament light chain (sNfL) and serum glial fibrillary acidic protein (sGFAP) for apheresis outcome in steroid‐refractory multiple sclerosis (MS) relapse has not yet been evaluated. Methods: We used pre‐ and postapheresis serum samples from 38 participants of the IAPEMS trial (clinicaltrials.gov: NCT02671682), which investigated the use of immunoadsorption versus plasma exchange for the treatment of steroid‐refractory MS attacks. Response to apheresis was classified based on improvement on (i) the Expanded Disability Status Scale (EDSS), (ii) the affected functional system scores (FSS) of the EDSS, or (iii) the visual acuity for patients with optic neuritis, 4 weeks postapheresis. sNFL and sGFAP were measured by single molecule arrays. Results: Preprocedural sGFAP levels could discriminate between responders and nonresponders, determined by FSS improvement (p = 0.017). In multivariate logistic regression analysis, younger age (odds ratio [OR] = 0.781, 95% confidence interval [CI] = 0.635–0.962, p = 0.020) and lower sGFAP levels (OR = 0.948, 95% CI = 0.903–0.995, p = 0.031) could predict response to apheresis in the overall cohort. We could observe a trend towards a favourable apheresis outcome with higher sNfL levels (OR = 1.413, 95% CI = 0.965–2.069, p = 0.076). Analysis of the sNfL‐to‐sGFAP ratio showed an OR of 1.924 (95% CI = 1.073–3.451, p = 0.028) for predicting apheresis response. The ratio showed a better predictive value than the individual parameters. Neither biomarker was affected by the number of steroid cycles preapheresis. Conclusions: Lower sGFAP levels, a higher sNfL‐to‐sGFAP ratio, and younger age are associated with a favourable apheresis outcome. [ABSTRACT FROM AUTHOR]

Background and Objectives: Initial therapeutic efforts to treat severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) included the use of plasma from convalescent donors containing anti‐SARS‐CoV‐2 antibodies. High‐neutralizing antibody titres are required for therapeutic efficacy. This study aims to show that immunoadsorption followed by tangential flow filtration can be used to obtain antibody concentrates with high‐neutralizing capacities. Materials and Methods: Eligible donors (n = 10, five males and three females) underwent immunoadsorption using adsorber columns specific for human antibodies. Glycine‐washed out eluates of 1.5 L volume were further concentrated by tangential flow filtration using 30 kDa ultrafiltration membranes. The same membranes were applied for diafiltrations to exchange residual glycine for 0.9% normal saline. Results: Antibody concentrates were obtained within 8 h from the start of donation and had 4.58 ± 1.95, 3.28 ± 1.28 and 2.02 ± 0.92 times higher total IgG, IgA and IgM concentrations, 3.29 ± 1.62 and 3.74 ± 0.6 times higher SARS‐CoV‐2 N and S antibody concentrations and 3.85 ± 1.71 times higher SARS‐CoV‐2 S‐specific IgG concentrations compared to the donors' peripheral blood. The specific SARS‐CoV‐2 virus neutralization capacities increased in all but one concentrate. All antibody concentrates (50–70 mL final volume) passed microbiological tests, were free of hazardous glycine levels and could be stored at −80°C and 4°C for 1 year with 20 ± 3% antibody loss. Conclusion: Immunoadsorption followed by tangential flow filtration is a feasible procedure to collect IgG, IgA and IgM as well as SARS‐CoV‐2 N‐ and S‐specific antibody concentrates of low volume, free of albumin and coagulation factors. Whether these concentrates can be used as passive immunisation in infected patients remains to be elucidated. [ABSTRACT FROM AUTHOR]

Abstract Purpose Glial fibrillary acidic protein astrocytopathy (GFAP-A) pathogenesis remains uncertain, with potential viral involvement. More clinical cases are needed to deepen our understanding of this disease, along with the exploration of more effective treatment options to provide clinicians with additional choices. Methods We report a severe case of GFAP-A secondary to EBV infection, characterized predominantly by central respiratory failure. Additionally, we conducted a literature review summarizing the characteristics of GFAP-IgG-positive patients associated with EBV infection. Results Among the 13 patients identified, fever (92.3%) and headache (84.6%) were the most common initial symptoms, while urinary dysfunction was universally present in all patients. Over half of the patients with altered consciousness required endotracheal intubation (7/11, 63.6%), with only one individual experiencing complete resolution without any residual sequela. Only two patients (16.7%) displayed the classic feature of periventricular enhancement on neuroimaging, whereas T2-FLAIR hyperintensities were more prevalent. All patients tested positive for GFAP-IgG in CSF, and 91.7% (11/12) had detectable serum GFAP-IgG antibodies. Three patients (23.1%) achieved full recovery solely through antiviral therapy. In patients receiving various immunotherapies, 60% (6/10) still had residual sequelae. Conclusion EBV infection may contribute to the pathogenesis of GFAP-A. GFAP antibody testing is recommended for diagnostic evaluation in cases of central nervous system viral infections presenting with respiratory insufficiency. For severe GFAP-A patients, Protein A immunoadsorption (Protein A IA).

The treatment of primary Sjögren’s syndrome (pSS) coexisting with neuromyelitis optica spectrum disorder (NMOSD) using protein-A immunoadsorption combined with immunosuppressive therapy has rarely been reported. Herein, we present the case of a 35-year-old female diagnosed with pSS concomitant with NMOSD (pSS-NMOSD) who demonstrated a positive response to protein-A immunoadsorption after failing to respond to therapy comprising high-dose intravenous methylprednisolone (IVMP) and intravenous immunoglobulin (IVIG). Within one week of receiving three sessions of immunoadsorption combined with immunosuppressive treatment, the patient’s clinical symptoms (blurred vision, paraparesis, and dysfunctional proprioception) significantly improved. Additionally, a rapid decrease in the circulating levels of Aquaporin-4 immunoglobulin G antibodies (AQP4-IgG), immunoglobulin (Ig) A, IgG, IgM, erythrocyte sedimentation rate (ESR), and rheumatoid factor (RF) were observed. Magnetic resonance imaging (MRI) further revealed a significant reduction in the lesions associated with longitudinal extensive transverse myelitis. During the follow-up period, prednisolone was gradually tapered to a maintenance dose of 5-10 mg/day, whereas mycophenolate mofetil (MMF) was maintained at 1.0-1.5 g/day. The patient’s condition has remained stable for four years, with no signs of recurrence or progression observed on imaging examination. Therefore, this case suggests that protein A immunoadsorption may represent a potentially effective therapeutic option for patients with pSSNMOSD who are refractory to conventional treatments. [ABSTRACT FROM AUTHOR]

Introduction: This study aims to evaluate the predictive value of color Doppler ultrasound for the diagnosis of aberrant right subclavian artery (ARSA) with a co-occurring non-recurrent right laryngeal nerve (NRLN). Material and methods: In the present study, 58 patients with ARSA (ARSA group) and 1,280 patients without ARSA (controls) were diagnosed by ultrasonography. In addition, 32 patients with ARSA (ARSA operation group) and controls underwent thyroidectomy with surgical exploration with or without NRLN. Then, the incidence of NRLN was analyzed. The right common carotid artery (RCCA) and right subclavian artery (RSA) trends were observed by ultrasound, and classified into two types: RCCA and RSA originating from the innominate artery (IA) (type I), and IA could not be detected (type II). Results: A total of 32 cases of NRLN were found in the ARSA operation group, but no case was found in controls, and the difference was statistically significant (p = 0.0006). The difference in the constituent ratio of type I and type II was statistically significant between the ARSA group and controls (p = 0.0002). That is, the IA could not be detected in the ARSA group, which was accompanied by the RCCA that originated from the aortic arch, while the IA was detected in most patients in the control group at the level of the sternoclavicular joints. Conclusions: Aberrant right subclavian artery can be rapidly detected by ultrasonography. Aberrant right subclavian artery occurs when the RCCA originates from the aortic arch during detection. Patients with ARSA sometimes have co-occurring NRLN. Hence, vigilance in protecting the NRLN is needed during an operation. [ABSTRACT FROM AUTHOR]

The usage of cardiopulmonary bypass (CPB) in cardiothoracic surgery contributes to the activation of the inflammatory response. In certain cases, the systemic inflammatory response may be immoderate, leading to organ dysfunction, such as acute renal failure or multiorgan dysfunction. This study aimed to examine the effect of haemoadsorption (HA) therapy on inflammatory markers and renal damage indices during cardiopulmonary bypass and in the early postoperative period. We conducted a retrospective analysis of prospectively collected data in a single tertiary care center on patients operated between January 2021 and May 2022. The levels of inflammatory markers and renal parameters in blood samples (Interleukin (IL) 6, C-reactive protein (CRP), white blood cells, lactate, procalcitonin (PCT), and NT-proBNP, urea, creatinine, glomerular filtration rate (GFR), mechanical ventilation days and intensive care unit (ICU) days) were compared between the three groups. Data from the Jafron HA 330 (n = 20) and CytoSorb300 (n = 20) groups were compared with those from the control group (n = 20). All patients underwent cardiopulmonary bypass for more than 120 min. Baseline patient characteristics were similar in all three groups. Acute kidney injury (AKI) was diagnosed in 17 patients (28.3%); seven patients were in the Jafron HA 330, two in the CytoSorb300, and eight in the control group. We found that IL1a, IL 6, IL8, Lactate dehydrogenase, PCT, NT-proBNP, CRP, Leukocyte, and TNFa had no significant or clinical difference between the CytoSorb 300 and Jafron HA 330 adsorber groups. Our results indicate that haemoadsorption therapy does not significantly reduce the risk of AKI after prolonged CPB, but decreases the need for renal replacement therapy. [ABSTRACT FROM AUTHOR]

Idiopathic inflammatory myopathy (IIM) summarizes rare, systemic autoimmune conditions primarily characterized by inflammatory damage to the skeletal muscle. Although primary damage occurs to the muscle, these IIM-related conditions involve other organs, including the skin, lungs, upper gastrointestinal tract, joints, and heart. While many patients have an adequate response to immunosuppressive treatment, some patients develop rapidly progressive and treatment-resistant life-threatening courses. Treatment-resistant IIM is challenging for the treating physician and requires interdisciplinary and individualized treatment approaches. Extracorporeal therapy is one option for rescue therapy, with immunoadsorption (IA) having proven more effective than plasma exchange regarding the removal of circulating antibodies. Despite its efficacy and desirable safety profile, the clinical value of IA use in IIM is understudied with no controlled trials reported. Here, we present a review of the current knowledge regarding the management of treatment-resistant IIM and the cases of three patients with treatment-resistant IIM (two with dermatomyositis and one with immune-mediated necrotizing myopathy) who have successfully been treated with IA. All patients responded well to the therapy and experienced no IA-related complications. Taken together, we found IA to be a safe and effective treatment option in treatment-resistant IIM. [ABSTRACT FROM AUTHOR]

Background: Extracorporeal blood purification has been widely used in intensive care medicine, nephrology, toxicology, and other fields. During the last decade, with the emergence of new adsorptive blood purification devices, hemoadsorption has been increasingly applied during CPB in cardiac surgery, for patients at different inflammatory risks, or for postoperative complications. Clinical evidence so far has not provided definite answers concerning this adjunctive treatment. The current systematic review aimed to critically assess the role of perioperative hemoadsorption in cardiac surgery, by summarizing the current knowledge in this clinical setting. Methods: A literature search of PubMed, Cochrane library, and the database provided by CytoSorbents was conducted on June 1st, 2023. The search terms were chosen by applying neutral search keywords to perform a non-biased systematic search, including language variations of terms "cardiac surgery" and "hemoadsorption". The screening and selection process followed scientific principles (PRISMA statement). Abstracts were considered for inclusion if they were written in English and published within the last ten years. Publications were eligible for assessment if reporting on original data from any type of study (excluding case reports) in which a hemoadsorption device was investigated during or after cardiac surgery. Results were summarized according to sub-fields and presented in a tabular view. Results: The search resulted in 29 publications with a total of 1,057 patients who were treated with hemoadsorption and 988 control patients. Articles were grouped and descriptively analyzed due to the remarkable variability in study designs, however, all reported exclusively on CytoSorb® therapy. A total of 62% (18/29) of the included articles reported on safety and no unanticipated adverse events have been observed. The most frequently reported clinical outcome associated with hemoadsorption was reduced vasopressor demand resulting in better hemodynamic stability. Conclusions: The role of hemoadsorption in cardiac surgery seems to be justified in selected high-risk cases in infective endocarditis, aortic surgery, heart transplantation, and emergency surgery in patients under antithrombotic therapy, as well as in those who develop a dysregulated inflammatory response, vasoplegia, or septic shock postoperatively. Future large randomized controlled trials are needed to better define proper patient selection, dosing, and timing of the therapy. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to investigate the factors affecting extraocular muscle enlargement in thyroid eye disease (TED). Study design: Retrospective study. Methods: The thyroid-stimulating hormone (TSH) receptor antibody (TRAb), thyroid-stimulating antibody (TSAb), antithyroid peroxidase antibody (ATPO), and antithyroglobulin antibody (ATG) levels in patients diagnosed with TED who underwent orbital magnetic resonance imaging were assessed. The control group comprised the contralateral eye of patients who underwent orbital magnetic resonance imaging (MRI) for unilateral eyelid tumors or orbital disease. The thickness of the bilateral rectus muscles and superior oblique muscles was measured on orbital MRI. Muscle enlargement was classified as unilateral/bilateral and symmetric/asymmetric. The effects of age, sex, smoking history, TSH, thyroid hormone, and thyroid autoantibodies on the muscle thickness and number of enlarged muscles were assessed by use of simple and multiple regression analyses. Results: The TED and control groups comprised 41 and 44 cases, respectively. The positivity rate of TSAb in patients with TED was 92.7% higher than that of the other autoantibodies. Muscle enlargement was observed in 29 of the 41 cases (70.7%). Older age and higher TSAb levels were identified as significant factors affecting the total muscle thickness and number of enlarged muscles. Bilateral muscle enlargement and asymmetrical muscle enlargement were observed in 17 (58.6%) and 23 (79.3%) of the 29 cases, respectively. The TSAb levels and age had no significant effect on the type of muscle enlargement. Conclusions: TSAb showed significant associations with extraocular muscle enlargement. Measurement of TSAb, rather than of TRAb, may be more useful for diagnosing extraocular muscle enlargement in patients with TED. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the safety and efficacy of the Gekko coil system in treating intracranial aneurysms (IAs) in clinical practice. A prospective multicenter randomized open-label parallel positive control noninferiority trial was conducted by 11 centers in China. Patients with a target IA were randomized 1:1 to coiling with either Gekko or Axium coils. The primary outcome was successful aneurysm occlusion at 6 months postoperative follow-up, whereas the secondary outcomes included the successful occlusion aneurysm rate in the immediate postoperative period, recanalization rate at the 6 months follow-up, and technical success and security. Between May 2018 and September 2020, 256 patients were enrolled and randomized. Per-protocol analysis showed that the successful aneurysm occlusion rate at 6 months was 96.08% for the Gekko coil group compared with 96.12% in the Axium coil group, with a difference of –0.04% (P = 0.877). The successful immediate aneurysm occlusion rates were 86.00% and 77.45% in the Gekko coil group and the Axium coil group, respectively, showing no significant difference between the 2 groups (P = 0.116), whereas the recanalization rates during the 6 months follow-up were 2.02% and 1.96% in the Gekko and Axium coil groups, respectively, which was not statistically significant (P = 1.000). This trial showed that the Gekko coil system was noninferior to the Axium coil system in terms of efficacy and safety for IA embolization. In clinical practice, the Gekko coil system can be considered safe and effective for treating patients with IA. [ABSTRACT FROM AUTHOR]

Background Pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are potentially life-threatening autoimmune blistering diseases. Treatment is based on long-term immunosuppression with high doses of glucocorticosteroids in combination with potentially corticosteroid-sparing agents and/or rituximab. Immunoadsorption (IA) has emerged as a fast-acting adjuvant treatment option. Objectives To assess the clinical efficacy of IA in addition to best medical treatment (BMT). Methods We conducted a multicentre (26 centres from Germany and Austria) randomized controlled trial in 72 patients with newly diagnosed, relapsed or chronic active PV or PF (34 female patients and 38 male patients, aged 42–72   years) comparing BMT (prednisolone 1.0   mg kg−1 per day plus azathioprine or mycophenolate) with adjuvant IA (BMT + IA). Central 1 : 1 randomization was done at the coordinating centre for clinical trials (KKS Marburg). The primary endpoint was analysed using Kaplan–Meier and Cox regression methods. Results The study was ended prematurely owing to safety concerns after random allocation of 72 patients to BMT + IA (n = 34) or BMT (n = 38). The primary endpoint, time to complete remission on therapy, was not significantly different for the two groups [hazard ratio (HR) 1.35, 95% confidence interval (CI) 0.68–2.69; P = 0.39]. The cumulative dose of prednisolone was significantly lower in the BMT + IA group compared with BMT alone (difference −1214, 95% CI −2225 to −70; P = 0.03). In a post hoc analysis, patients with more extensive PV/PF showed a tendency towards a shorter time to remission in the BMT + IA group compared with the BMT group (HR 1.87, P = 0.17 in patients with baseline Pemphigus Disease Area Index ≥ 15). While more adverse events were observed in patients in the BMT group (29 vs. 25), severe adverse events were more frequent in patients in the BMT + IA group (17 events in 10 patients vs. 11 events in 8 patients). Conclusions In this study, adjuvant IA did not demonstrate a shorter time to clinical remission, but a corticosteroid-sparing effect was observed. In patients with extensive PV/PF, post hoc analysis suggests that adjuvant IA may lead to earlier remission, but potential adverse events must be carefully weighed against the expected benefits. [ABSTRACT FROM AUTHOR]

Objective: Plasma exchange (PE) and immunoadsorption (IA) are recognized as effective ways to treat attacks in AQP4 antibody‐positive NMOSD, but high‐quality evidence was lacking. To evaluate the efficacy and safety of PE/IA plus intravenous methylprednisolone (IVMP) in NMOSD attacks using propensity scores to match IVMP as control. Methods: Patients were from a prospective observational cohort study. Stratification and interval propensity score matching (PSM) were used to reduce selection bias by matching baseline characteristics (gender, age, time to IVMP, EDSS at attack) between PE/IA + IVMP and IVMP group (in a ratio of 1:2). The primary endpoint of efficacy was EDSS change at 6 months. Adverse events and changes in laboratory tests were recorded. Results: Four hundred and eleven attacks of 336 patients were screened for PSM, and 90 attacks (30 PE/IA + IVMP and 60 IVMP) were included in the analysis. There were significant differences in EDSS [6.25 vs. 6.75; IQR (4.50–8.38 vs. 5.00–8.00), p = 0.671] and visual acuity [median logMAR = 0.35 vs. 1.00; IQR (0.30–0.84 vs. 0.95–1.96), p = 0.002] change between two groups at 6 months. PE/IA + IVMP treatment demonstrated predictive capacity for good recovery as indicated by an area under the curve (AUC) of 0.726. Fibrinogen reduction was found during PE/IA + IVMP treatment [n = 15 (50.00%)], but no severe adverse events led to apheresis treatment discontinuation. Discussion: After PSM analysis, IVMP+PE/IA in acute attack of NMOSD achieved better and continuous improvement in neurological function within 6 months compared with IVMP alone. PE/IA treatment showed a good safety profile. [ABSTRACT FROM AUTHOR]

Abstract Background Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a severely debilitating condition which markedly restricts activity and function of affected people. Since the beginning of the COVID-19 pandemic ME/CFS related to post-acute COVID-19 syndrome (PACS) can be diagnosed in a subset of patients presenting with persistent fatigue 6 months after a mostly mild SARS-CoV-2 infection by fulfillment of the Canadian Consensus Criteria (CCC 2003). Induction of autoimmunity after viral infection is a mechanism under intensive investigation. In patients with ME/CFS, autoantibodies against thyreoperoxidase (TPO), beta-adrenergic receptors (ß2AR), and muscarinic acetylcholine receptors (MAR) are frequently found, and there is evidence for effectiveness of immunomodulation with B cell depleting therapy, cyclophosphamide, or intravenous immunoglobulins (IVIG). Preliminary studies on the treatment of ME/CFS patients with immunoadsorption (IA), an apheresis that removes antibodies from plasma, suggest clinical improvement. However, evidence from placebo-controlled trials is currently missing. Methods In this double-blinded, randomized, sham-controlled, exploratory trial the therapeutic effect of five cycles of IA every other day in patients with ME/CFS, including patients with post-acute COVID-19 chronic fatigue syndrome (PACS-CFS), will be evaluated using the validated Chalder Fatigue Scale, a patient-reported outcome measurement. A total of 66 patients will be randomized at a 2:1 ratio: 44 patients will receive IA (active treatment group) and 22 patients will receive a sham apheresis (control group). Moreover, safety, tolerability, and the effect of IA on patient-reported outcome parameters, biomarker-related objectives, cognitive outcome measurements, and physical parameters will be assessed. Patients will be hospitalized at the clinical site from day 1 to day 10 to receive five IA treatments and medical visits. Four follow-up visits (including two visits at site and two visits via telephone call) at month 1 (day 30), 2 (day 60), 4 (day 120), and 6 (day 180; EOS, end of study visit) will take place. Discussion Although ME/CFS including PACS-CFS causes an immense individual, social, and economic burden, we lack efficient therapeutic options. The present study aims to investigate the efficacy of immunoadsorption and to contribute to the etiological understanding and establishment of diagnostic tools for ME/CFS. Trial registration Registration Number: NCT05710770 . Registered on 02 February 2023.

Objectives: The use of hemoadsorption (HA) has become popular in the treatment of vasoplegic states associated with massive cytokine release, including septic shock. However, this approach does not seem to be based on robust evidence, and it does not follow international guidelines. To understand the pathophysiological rationale and timing of HA, we conducted a large animal septic shock experiment. Design: Prospective randomized large-animal peritoneal septic shock experiment. Setting: Laboratory investigation. Subjects: Twenty-six anesthetized, mechanically ventilated, and instrumented pigs randomly assigned into (1) sham-operated group with HA (SHAM, n = 5); (2) sepsis animals without HA (SEPSIS, n = 5); (3) sepsis group with HA at norepinephrine initiation (EARLY, n = 8); and (4) sepsis group with HA initiated at norepinephrine rate reaching 0.5 μg/kg/min (LATE, n = 8). Interventions: Peritoneal sepsis was induced by cultivated autologous feces inoculation. A CytoSorb cartridge (200 g) with a blood flow rate of 200 mL/min and heparin anticoagulation was used to perform HA. The animals received sedation and intensive organ support up to 48 h or until they experienced cardiovascular collapse. Measurements and main results: Systemic hemodynamics, multiple-organ functions, and immune-inflammatory response were measured at predefined periods. The HA treatment was not associated with any measurable benefit in terms of systemic hemodynamics and organ support. The systemic inflammatory markers were unaffected by any of the treatment timings. In contrast, the HA resulted in higher vasopressor load and decreased 36-h survival (5 animals in SHAM (100%), 4 (80%) in SEPSIS, 4 (57%) in EARLY, and 2 (25%) in LATE; p = 0.041). The HA exposure in healthy animals was associated with hemodynamic deterioration, systemic inflammatory response, and cytopenia. Conclusions: In this large-animal-controlled fulminant sepsis study, the HA was unable to counteract the disease progression in the early or advanced septic shock phase. However, findings from the HA-exposed sham animals suggest potential safety concerns. Keypoints: Question: To understand hemoadsorption using CytoSorb device pathophysiological rationale and timing on disease progression in septic subjects. Findings: In this large-animal-controlled fulminant sepsis study, the CytoSorb hemoadsorption did not counteract the disease progression in the early or advanced septic shock phase. However, findings from the hemoadsorption-exposed sham animals suggest potential safety concerns. Meaning: Considering the limited evidence, the clinical use of CytoSorb for hemoadsorption in septic patients should be limited to well-designed interventional studies. [ABSTRACT FROM AUTHOR]

Background: Overall survival (OS) varies significantly among individuals with heterogeneous retroperitoneal liposarcoma (RPLS), even among those with the same clinical stage. Improved staging of RPLS is a critical unmet need, given the disappointing results of external validations of the 8th American Joint Committee on Cancer (AJCC) TNM staging system. Methods: The cohort study included 220 consecutive patients who underwent surgical resection for primary RPLS at the largest sarcoma centre of Fudan University in China from September 2009 to August 2021, combined with 277 adult patients with RPLS in the SEER database from 1975 to 2020. Data analysis was performed from December 2021 to December 2022. Patients were retrospectively restaged according to the 8th and 7th editions of the TNM staging system as well as the new TNM (nTNM) staging system. The primary endpoint was overall survival (OS). Comparative analysis of postoperative survival was performed using the Kaplan-Meier method, and differences between subgroups were tested using the log-rank test. The OS prediction nomogram was generated based on baseline variables and tumour characteristics. Harrell's consistency index (C-index), area under the curve (AUC) of receiver operating characteristic curves (ROC), and calibration curves were used to evaluate the performance of the nomogram. Results: A total of 497 patients were enrolled in the study, including 282 (56.7%) male patients. The median follow-up was 51 months (interquartile range, IQR, 23-83), and the OS rates at 1, 3, and 5 years were 87.9%, 75.3%, and 64.9%, respectively. According to the staging distribution of the AJCC 7th edition, 6 patients were stage IA (1.2%), 189 patients were stage IB (38%), 12 patients were stage IIA (2.4%), 150 patients were stage IIB (30.1%), 131 patients were stage III (26.3%), and 9 patients were stage IV (1.8%). With the 8th edition staging, this distribution changed: 6 patients (1.2%) were stage IA, 189 patients (38%) were stage IB, 12 patients (2.4%) were stage II, 24 patients (4.8%) were stage IIIA, 257 patients (51.7%) were stage IIIB, and 9 patients (1.8%) were stage IV. 182 patients (36.6%) were reclassified according to the nTNM staging system with the new T stage classification. The C-index and log-rank score improved after implementation of nTNM implementation. The nTNM system was associated with improved identification of high-risk patients compared with the AJCC 7th and 8th TNM. The FNCLCC stage proved to be highly prognostic with significant intergroup differences in OS. The calibration curve shows a high degree of agreement between the actual OS rate and the nomogram estimated OS rate. Conclusion: Compared with 8th AJCC TNM, 7th AJCC TNM staging system showed a more homogeneous staging distribution and a slight improvement in the prognostic accuracy of RPLS. The revised T-stage and nTNM systems showed better risk stratification performance. The FNCLCC stage was found to have high prognostic value, further emphasising histological grade is the least negligible prognostic factor in predicting patient survival. The constructed nomogram model enables individualized prognostic analysis and helps to develop riskadapted therapy for RPLS patients. [ABSTRACT FROM AUTHOR]

The benefit of associating anti-CD38 monoclonal antibodies to proteasome inhibitor (PI)/immunomodulatory agent (IA) and dexamethasone in the treatment of patients with relapsed or refractory multiple myeloma (MM) remains unclear. PubMed, Embase, and Cochrane Library databases were searched for randomized controlled trials that investigated the addition of anti-CD38 monoclonal antibodies to a therapy composed of PI/IA and dexamethasone versus PI/IA and dexamethasone alone for treating relapsed or refractory MM. Hazard ratios (HRs) or risk ratios (RRs) were computed for binary endpoints, with 95% confidence intervals (CIs). Six studies comprising 2191 patients were included. Anti-CD38 monoclonal antibody significantly improved progression-free survival (HR 0.52; 95% CI 0.43–0.61; p < 0.001) and overall survival (HR 0.72; 95% CI 0.63–0.83; p < 0.001). There was a significant increase in hematological adverse events, such as neutropenia (RR 1.41; 95% CI 1.26–1.58; p < 0.01) and thrombocytopenia (RR 1.14; 95% CI 1.02–1.27; p = 0.02), in the group treated with anti-CD38 monoclonal antibody. Also, there was a significant increase in non-hematological adverse events, such as dyspnea (RR 1.72; 95% CI 1.38–2.13; p < 0.01) and pneumonia (RR 1.34; 95% CI 1.13–1.59; p < 0.01), in the group treated with anti-CD38 monoclonal antibody. In conclusion, the incorporation of an anti-CD38 monoclonal antibody demonstrated a promising prospect for reshaping the established MM treatment paradigms. [ABSTRACT FROM AUTHOR]

Background: Anti-human leukocyte antigen (HLA)-antibody production represents a major barrier to heart transplantation, limiting recipient compatibility with potential donors and increasing the risk of complications with poor waiting-list outcomes. Currently there is no consensus to when desensitization should take place, and through what mechanism, meaning that sensitized patients must wait for a compatible donor for many months, if not years. We aimed to determine if intraoperative immunoadsorption could provide a potential desensitization methodology. Methods: Anti-HLA antibody-containing whole blood was added to a Cardiopulmonary bypass (CPB) circuit set up to mimic a 20 kg patient undergoing heart transplantation. Plasma was separated and diverted to a standalone, secondary immunoadsorption system, with antibody-depleted plasma returned to the CPB circuit. Samples for anti-HLA antibody definition were taken at baseline, when combined with the CPB prime (on bypass), and then every 20 min for the duration of treatment (total 180 min). Results: A reduction in individual allele median fluorescence intensity (MFI) to below clinically relevant levels (<1000 MFI), and in the majority of cases below the lower positive detection limit (<500 MFI), even in alleles with a baseline MFI >4000 was demonstrated. Reduction occurred in all cases within 120 min, demonstrating efficacy in a time period usual for heart transplantation. Flowcytometric crossmatching of suitable pseudo-donor lymphocytes demonstrated a change from T cell and B cell positive channel shifts to negative, demonstrating a reduction in binding capacity. Conclusions: Intraoperative immunoadsorption in an ex vivo setting demonstrates clinically relevant reductions in anti-HLA antibodies within the normal timeframe for heart transplantation. This method represents a potential desensitization technique that could enable sensitized children to accept a donor organ earlier, even in the presence of donor-specific anti-HLA antibodies. [ABSTRACT FROM AUTHOR]

Aims: The aim of this trial was to compare the clinical effects of intraoperative haemoadsorption versus standard care in patients undergoing orthotopic heart transplantation (OHT). Methods and results: In a randomized, controlled trial, OHT recipients were randomized to receive intraoperative haemoadsorption or standard care. Outcomes were vasoactive‐inotropic score (VIS), frequency of vasoplegic syndrome (VS) in the first 24 h; post‐operative change in procalcitonin (PCT) and C‐reactive protein (CRP) levels; intraoperative change in mycophenolic acid (MPA) concentration; frequency of post‐operative organ dysfunction, major complications, adverse immunological events and length of in‐hospital stay and 1‐year survival. Sixty patients were randomized (haemoadsorption group N = 30, control group N = 25 plus 5 exclusions). Patients in the haemoadsorption group had a lower median VIS and rate of VS (VIS: 27.2 [14.6–47.7] vs. 41.9 [22.4–63.2], P = 0.046, and VS: 20.0% vs. 48.0%, P = 0.028, respectively), a 6.4‐fold decrease in the odds of early VS (OR: 0.156, CI: 0.029–0.830, P = 0.029), lower PCT levels, shorter median mechanical ventilation (MV: 25 [19–68.8] hours vs. 65 [23–287] hours, P = 0.025, respectively) and intensive care unit stay (ICU stay: 8.5 [8.0–10.3] days vs. 12 [8.5–18.0] days, P = 0.022, respectively) than patients in the control group. Patients in the haemoadsorption versus control group experienced lower rates of acute kidney injury (AKI: 36.7% vs. 76.0%, P = 0.004, respectively), renal replacement therapy (RRT: 0% vs. 16.0%, P = 0.037, respectively) and lower median per cent change in bilirubin level (PCB: 2.5 [−24.6 to 71.1] % vs. 72.1 [11.2–191.4] %, P = 0.009, respectively) during the post‐operative period. MPA concentrations measured at pre‐defined time points were comparable in the haemoadsorption compared to control groups (MPA pre‐cardiopulmonary bypass: 2.4 [1.15–3.60] μg/mL vs. 1.6 [1.20–3.20] μg/mL, P = 0.780, and MPA 120 min after cardiopulmonary bypass start: 1.1 [0.58–2.32] μg/mL vs. 0.9 [0.45–2.10] μg/mL, P = 0.786). The rates of cardiac allograft rejection, 30‐day mortality and 1‐year survival were similar between the groups. Conclusions: Intraoperative haemoadsorption was associated with better haemodynamic stability, mitigated PCT response, lower rates of post‐operative AKI and RRT, more stable hepatic bilirubin excretion, and shorter durations of MV and ICU stay. Intraoperative haemoadsorption did not show any relevant adsorption effect on MPA. There was no increase in the frequency of early cardiac allograft rejection related to intraoperative haemoadsorption use. [ABSTRACT FROM AUTHOR]

ABO-incompatible (ABOi) living kidney transplantation (KTx) is an established procedure to address the demand for kidney transplants with outcomes comparable to ABOcompatible KTx. Desensitization involves the use of immunoadsorption (IA) to eliminate preformed antibodies against the allograft. This monocentric retrospective study compares single-use antigen-selective Glycosorb® ABO columns to reusable nonantigen-specific Immunosorba® immunoglobulin adsorption columns regarding postoperative infectious complications and outcome. It includes all 138 ABOi KTx performed at Freiburg Transplant Center from 2004–2020. We compare 81 patients desensitized using antigen-specific columns (sIA) to 57 patients who received IA using non-antigen-specific columns (nsIA). We describe distribution of infections, mortality and allograft survival in both groups and use Cox proportional hazards regression to test for the association of IA type with severe infections. Desensitization with nsIA tripled the risk of severe postoperative infections (adjusted HR 3.08, 95% CI: 1.3–8.1) compared to sIA. nsIA was associated with significantly more recurring (21.4% vs. 6.2%) and severe infections (28.6% vs. 8.6%), mostly in the form of urosepsis. A significantly higher proportion of patients with sIA suffered from allograft rejection (29.6% vs. 14.0%). However, allograft survival was comparable. nsIA is associated with a two-fold risk of developing a severe postoperative infection after ABOi KTx. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the safety and efficacy of the delipid extracorporeal lipoprotein filter from plasma (DELP) system, a new low-density lipoprotein cholesterol (LDL-C) adsorption system, in acute ischemic stroke (AIS) patients. Patients and methods: In the present study, a total of 180 AIS patients were enrolled during March 2019 to February 2021. They were divided into DELP group (n1 = 90) and the control group (n2 = 90). The treatment protocol and vascular access of DELP treatment was established and evaluated. For the DELP group, clinical data and laboratory results including plasma lipid and safety parameters before and after the apheresis were collected and analyzed. For all participants, neurological scores were assessed and recorded. Results: For the DELP group, 90 patients including 70 males and 20 females were included. The mean LDL-C was significantly decreased from 3.15 ± 0.80 mmol/L to 2.18 ± 0.63 mmol/L (30.79%, p < 0.001) during a single DELP treatment, and decreased from 3.42 ± 0.87 mmol/L to 1.87 ± 0.48 mmol/L (45.32%, p < 0.001) after two DELP treatments. No clinically relevant changes were observed in hematologic safety parameters and blood pressure levels except for hematocrit and total protein throughout the whole period of DELP treatment. The DELP group showed improvement relative to the control group in National Institute of Health stroke scale scores (NIHSS) on the 14th and 90th day after stroke. Moreover, the DELP group had a significantly higher ratio of mRS 0 to 1 on the 90th day after stroke. Conclusion: The new LDL-C adsorption system, the DELP system, may provide a new option for intensive lipid lowering therapy in AIS patients in view of its safety, efficacy, and operation feasibility. [ABSTRACT FROM AUTHOR]

Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a severely debilitating condition which markedly restricts activity and function of affected people. Since the beginning of the COVID-19 pandemic ME/CFS related to post-acute COVID-19 syndrome (PACS) can be diagnosed in a subset of patients presenting with persistent fatigue 6 months after a mostly mild SARS-CoV-2 infection by fulfillment of the Canadian Consensus Criteria (CCC 2003). Induction of autoimmunity after viral infection is a mechanism under intensive investigation. In patients with ME/CFS, autoantibodies against thyreoperoxidase (TPO), beta-adrenergic receptors (ß2AR), and muscarinic acetylcholine receptors (MAR) are frequently found, and there is evidence for effectiveness of immunomodulation with B cell depleting therapy, cyclophosphamide, or intravenous immunoglobulins (IVIG). Preliminary studies on the treatment of ME/CFS patients with immunoadsorption (IA), an apheresis that removes antibodies from plasma, suggest clinical improvement. However, evidence from placebo-controlled trials is currently missing. Methods: In this double-blinded, randomized, sham-controlled, exploratory trial the therapeutic effect of five cycles of IA every other day in patients with ME/CFS, including patients with post-acute COVID-19 chronic fatigue syndrome (PACS-CFS), will be evaluated using the validated Chalder Fatigue Scale, a patient-reported outcome measurement. A total of 66 patients will be randomized at a 2:1 ratio: 44 patients will receive IA (active treatment group) and 22 patients will receive a sham apheresis (control group). Moreover, safety, tolerability, and the effect of IA on patient-reported outcome parameters, biomarker-related objectives, cognitive outcome measurements, and physical parameters will be assessed. Patients will be hospitalized at the clinical site from day 1 to day 10 to receive five IA treatments and medical visits. Four follow-up visits (including two visits at site and two visits via telephone call) at month 1 (day 30), 2 (day 60), 4 (day 120), and 6 (day 180; EOS, end of study visit) will take place. Discussion: Although ME/CFS including PACS-CFS causes an immense individual, social, and economic burden, we lack efficient therapeutic options. The present study aims to investigate the efficacy of immunoadsorption and to contribute to the etiological understanding and establishment of diagnostic tools for ME/CFS. Trial registration: Registration Number: NCT05710770. Registered on 02 February 2023. [ABSTRACT FROM AUTHOR]

Membranous nephropathy constitutes approximately 20% of adult nephrotic syndrome cases. In approximately 80% of cases, membranous nephropathy is primary, mediated by IgG autoantibodies primarily targeting podocyte antigens (PLA2R, THSD7A, etc.). The treatment involves a combination of corticosteroids and cyclophosphamide or anti-CD20-based therapies, e.g., rituximab. In the event of significant proteinuria and in order to avoid the urinary elimination of rituximab, therapeutic apheresis, in particular semi-specific immunoadsorption, may be an option allowing for a reduction in proteinuria and autoantibodies before initiating treatment with rituximab. We present the preliminary experience of three patients treated with semi-specific immunoadsorption for primary membranous nephropathy between January 2021 and March 2023. Two patients were anti-PLA2R-autoantibody-positive and one was seronegative. The average age was 59 ± 17 years. Semi-specific immunoadsorption did not reduce albuminuria, but it, nevertheless, led to an increase in serum albumin, contributing to the regression of edema. It effectively eliminated anti-PLA2R autoantibodies in the two anti-PLA2R-positive patients. Consequently, apheresis may not induce a rapid reduction in proteinuria, but could contribute to a more accelerated remission when combined with the anti-CD20 treatment. [ABSTRACT FROM AUTHOR]

Open in new tab Download slide OBJECTIVES Multi-organ failure is one of the leading causes of mortality after cardiac surgery for infective endocarditis (IE). Although the randomized evidence does not support the use of haemoadsorption during cardiac surgery for IE, observational studies suggest a beneficial effect in selected patient groups. Staphylococcus aureus is the most common pathogen, and its presence is an independent mortality predictor. We aimed to analyse the effect of haemoadsorption in patients with IE caused by S. aureus. METHODS This is a post hoc analysis of the REMOVE trial that randomized 288 patients with IE who underwent cardiac surgery with haemoadsorption using CytoSorb® or control. The primary outcome was ΔSequential Organ Failure Assessment (SOFA), defined as the difference between the mean total postoperative and baseline SOFA score within 24 h of surgery. RESULTS Among the total of 282 patients included in the modified intention-to-treat analysis of the REMOVE trial, 73 (25.9%) had S. aureus IE (38 patients in the haemoadsorption group and 35 patients in the control group). The overall ΔSOFA did not differ between the intervention groups in patients with S. aureus IE (mead difference = −0.4, 95% confidence interval −2.3 to 1.4, P  = 0.66) and neither did 30-day mortality (hazard ratios = 1.32, 95% confidence interval 0.53–3.28, P  = 0.55). No differences were observed with regard to any of the other secondary outcomes. CONCLUSIONS Based on a post hoc analysis from REMOVE trial, the intraoperative use of haemoadsorption in patients with S. aureus IE was not associated with reduction of postoperative organ dysfunction, 30-day mortality or other major clinical end points. [ABSTRACT FROM AUTHOR]

Immunoadsorption (IA) has proven to be clinically effective in the treatment of steroid-refractory multiple sclerosis (MS) relapses, but its mechanism of action remains unclear. We used miniaturized adsorber devices with a tryptophan-immobilized polyvinyl alcohol (PVA) gel sorbent to mimic the IA treatment of patients with MS in vitro. The plasma was screened before and after adsorption with regard to disease-specific mediators, and the effect of the IA treatment on the migration of neutrophils and the integrity of the endothelial cell barrier was tested in cell-based models. The in vitro IA treatment with miniaturized adsorbers resulted in reduced plasma levels of cytokines and chemokines. We also found a reduced migration of neutrophils towards patient plasma treated with the adsorbers. Furthermore, the IA-treated plasma had a positive effect on the endothelial cell barrier's integrity in the cell culture model. Our findings suggest that IA results in a reduced infiltration of cells into the central nervous system by reducing leukocyte transmigration and preventing blood–brain barrier breakdown. This novel approach of performing in vitro blood purification therapies on actual patient samples with miniaturized adsorbers and testing their effects in cell-based assays that investigate specific hypotheses of the pathophysiology provides a promising platform for elucidating the mechanisms of action of those therapies in various diseases. [ABSTRACT FROM AUTHOR]

Background: Left ventricular assist device (LVAD) candidates are at increased risk of immune dysregulation and infectious complications. To attenuate the elevated proinflammatory cytokine levels and associated adverse clinical outcomes, it has been postulated that extracorporeal blood purification could improve the overall survival rate and morbidity of patients undergoing LVAD implantation. Methods: We retrospectively reviewed prospectively collected data of 15 patients who underwent LVAD implantation at our center between January 2021 and March 2022. Of these, 15 (100%) who received HeartMate 3™ (St. Jude Medical, Abbott, MN, USA) device were eligible. Intraoperatively, patients were single randomized 1:1:1 to three groups: group 1, patients who received Cytosorb therapy (n = 5; installed in the CPB circuit); group 2, patients who received Jafron HA330 (n = 5; installed in the CPB circuit); and control group 3, patients who did not receive filter (n = 5; usual care, neither Cytosorb nor Jafron during CPB). Baseline patient characteristics and intraoperative data were compared between the groups. Blood sample analyses were performed to assess the levels of inflammatory markers (IL-1, 6, 8; CRP, Leukocyte, Lactate, PCT, NT-proBNP, TNF-α) in both preoperative and postoperative data. Results: Baseline patient characteristics were similar in all three groups. We found that IL1α; IL 6; IL8; Lactatedehydrogenase, PCT, pro-BNP, CRP; Leukocyte, and TNFα levels significantly increased with LVAD implantation and that neither Cytosorb nor Jafron influenced this response. In-hospital mortality and overall survival during follow-up were similar among the groups. Conclusion: Our preliminary results showed that hemoadsorption therapy using Cytosorb or Jafron hemoadsorption (HA) 330 may not be clinically beneficial for patients with advanced heart failure undergoing LVAD implantation. Large prospective studies are needed to evaluate the potential role of HA therapy in improving outcomes in patients undergoing LVAD implantation. [ABSTRACT FROM AUTHOR]

A three-year-old, intact female mix-breed dog, weighing 30 kg, was presented due to vomitus and diarrhea. At presentation, the patient had a slightly reduced general condition and moderately enlarged mandibular and popliteal lymph nodes. The initial blood work showed severe azotemia and hypoalbuminemia. In the urinalysis, marked proteinuria with a urine protein/creatinine ratio (UPC) of 4.69 was found. Further workup showed a high leishmania antibody titer. The dog was diagnosed with leishmaniosis and glomerulonephritis. Initial treatment consisted of intravenous fluid therapy, allopurinol, miltefosine, amlodipine, clopidogrel, and a diet with a low purine content. Creatinine temporarily decreased but increased again after three days. For further supportive treatment, intermittent hemodialysis in combination with hemoperfusion with the cytosorb® adsorber was performed. A total blood volume of 17.7 L was processed within three hours. Thereafter, immunoadsorption (IA) was performed with the COM.TEC® and ADAsorb® platforms and a LIGASORB® adsorber to eliminate circulating immunocomplexes. Treatment time for IA was two hours with a blood flow of 50 mL/min. A total plasma volume of 2.4 L was processed. Over the following days, creatinine declined, and the patient improved significantly. UPC decreased to 1.74 on day 17 after IA. The patient was discharged after two and a half weeks. Two years after the initial event, the patient is still in excellent condition, with creatinine, UPC, and albumin levels in the reference range. Therefore, IA might be an additional therapeutic option for dogs with leishmaniosis-induced glomerulonephritis and subsequent severe azotemia to improve immunocomplex-mediated glomerulonephritis. [ABSTRACT FROM AUTHOR]

Open in new tab Download slide OBJECTIVES The timing of preoperative imaging in patients with lung cancer is a debated topic, as there are limited data on cancer progression during the interval between clinical staging by imaging and pathological staging after resection. We quantified disease progression during this interval in patients with early stage non-small-cell lung cancer (NSCLC) to better understand if its length impacts upstaging. METHODS We retrospectively reviewed our institutional database to identify patients who underwent surgery for clinically staged T1N0M0 NSCLC from January 2015 through September 2022. Tumour upstaging between chest computed tomography (CT) and surgery were analysed as a function of time (<30, 30–59, ≥60 days) for different nodule subtypes. We analysed data across 3 timeframes using Pearson's chi-squared and analysis of variance tests. RESULTS During the study period, 622 patients underwent surgery for clinically staged T1N0M0 NSCLC. CT-to-surgery interval was <30 days in 228 (36.7%), 30–59 days in 242 (38.9%) and ≥60 days in 152 (24.4%) with no differences in patient or nodule characteristics observed between these groups. T-stage increased in 346 patients (55.6%) between CT imaging and surgery. Among these patients, 126 (36.4%) had ground-glass nodules, 147 (42.5%) had part-solid nodules and 73 (21.1%) had solid nodules. CT-to-surgery interval length was not associated with upstaging of any nodule subtype (full-cohort, P  = 0.903; ground-glass, P  = 0.880; part-solid, P  = 0.858; solid, P  = 0.959). CONCLUSIONS This single-centre experience suggests no significant association between tumour upstaging and time from imaging to lung resection in patients with clinical stage IA NSCLC. Further studies are needed to better understand the risk factors for upstaging. [ABSTRACT FROM AUTHOR]

Introduction: We investigated the clinical efficacy and safety of blood purification technology in patients with polymyositis/dermatomyositis. Methods: In a study of 22 patients, 10 cases received blood purification treatment (5 cases received plasma exchange, 5 cases received plasma HA280 immunoadsorption), and 12 cases served as the control group. A 3‐month follow‐up was conducted to compare the clinical manifestations and laboratory examination. Results: Symptoms and signs of patients in treatment group were significantly improved, and the hormone usage was lower than the control group. For patients with normal creatine kinase level and ferritin level below three times the upper limit of normal, there was a positive correlation between their N/L values and MDAAT scores. Conclusion: The results of this study suggest that blood purification therapy, including plasma HA280 immunoadsorption and plasma exchange, is an effective and safe treatment for patients with polymyositis/dermatomyositis, offering assistance in reducing hormone usage in the long‐term. [ABSTRACT FROM AUTHOR]

Psoriatic arthritis (PsA) and rheumatoid arthritis (RA) are two distinct inflammatory joint diseases that can coexist in some patients. This case report discusses the treatment of a 71-year-old woman with PsA and RA using a combination of immunoadsorption therapy and antirheumatic drugs. The patient experienced relief from joint discomfort and a reduction in skin rash after multiple treatment cycles. The article emphasizes the importance of tailored treatment for PsA and the potential effectiveness of immunoadsorption therapy in managing severe psoriasis. However, further research is needed to fully understand the long-term safety and impact of certain medications in treating PsA. [Extracted from the article]

This document is a summary of two articles featured in Transplant Trial Watch. The first article discusses a randomized controlled trial that investigated the use of intraoperative haemoadsorption in orthotopic heart transplant patients. The study found statistically significant differences in various outcomes, including a lower vasoactive-inotropic score and shorter ICU stay for patients receiving hemoadsorption. The second article is a systematic review on the psychological impact of living kidney donation. The review found that while quantitative studies showed stable or improved quality of life for donors, qualitative studies revealed a more complex picture with some donors experiencing post-operative fatigue, anxiety, and depression. The review highlights the importance of regular follow-up and psychological assessment for donors. [Extracted from the article]

Background: The prognostic significance of adjuvant chemotherapy (ACT) for patients with stage IA micropapillary non-predominant (MPNP) lung adenocarcinoma (LUAD) remains unknown. This study aimed to investigate the effects of postoperative ACT in patients with stage IA MPNP-LUAD. Methods: A total of 149 patients with pathological stage IA MPNP-LUAD who underwent surgery at our center were retrospectively analyzed. Propensity score matching (PSM) analysis was conducted to reduce potential selection bias. Kaplan–Meier analyses were used to assess the impact of ACT on recurrence-free survival (RFS), overall survival (OS), and disease-specific survival (DSS). Subgroup analyses were performed for the survival outcomes based on the percentage of micropapillary components. Cox proportional hazards regression analyses were applied to identify risk factors associated with survival. Results: The receipt or non-receipt of postoperative ACT had no significant effect on RFS, OS, and DSS among all enrolled patients with stage IA MPNP-LUAD (P > 0.05). For patients with a micropapillary component > 5%, the 5-year rates of RFS, OS, and DSS were significantly higher in the ACT group compared to the observation group, both before and after PSM (P < 0.05). However, the differences between the two groups were not significant for patients with a micropapillary component ≤ 5% (P > 0.05). The resection range (HR = 0.071; 95% CI: 0.020–0.251; P < 0.001), tumor size (HR = 2.929; 95% CI: 1.171–7.330; P = 0.022), and ACT (HR = 0.122; 95% CI: 0.037–0.403; P = 0.001) were identified as independent prognostic factors for RFS through Cox regression analysis. Conclusion: Patients with stage IA MPNP-LUAD who have a micropapillary component greater than 5% might benefit from postoperative ACT, while those with a micropapillary component ≤ 5% did not appear to derive the same benefit from postoperative ACT. [ABSTRACT FROM AUTHOR]

In large-scale intensive farms, dairy goats often undergo frequent estrus synchronization (ES) treatment, which may result in a decline in reproductive performance; however, the underlying mechanism remains unclear. The present study aimed to investigate the effect of pregnant mare serum gonadotropin (PMSG) and progesterone (P4)-mediated ES treatment on fertility in dairy goats, while also identifying key metabolic and endocrine mechanisms that influence reproductive performance in does subjected to repeated ES treatment. Forty-eight Saanen does were randomly assigned to two groups (24 goats each) that received ES treatments either thrice fortnightly (3-PMSG) or once (1-PMSG) simultaneously with the third ES treatment of the 3-PMSG group during the breeding season. ES treatment was performed via the intravaginal insertion of a controlled internal drug release (CIDR) device impregnated with 300mg P4, followed by 300IU PMSG injections 48h before CIDR withdrawal. Blood was collected to detect the level of hormones and blood biochemical indices. Additionally, estrus rate, fecundity rate, body weight, size, and lactation performance were measured. The results showed that repeated ES treatment markedly decreased the estrus rate and fecundity rate of goats. Among the does in all groups, there was no substantial difference in follicle stimulating hormone, luteinising hormone, gonadotropin-releasing hormone, melatonin, growth hormone, PMSG, total cholesterol, total protein, and glucose levels, as well as the body weight, body size, and lactation performance. Repeated ES treatment elevated estrogen (E2) levels 36, 48, and 72h post-CIDR removal; increased P4 upon CIDR insertion; and raised PMSG antibody levels 24, 48, and 72h post-CIDR removal. The results suggest that elevated anti-PMSG levels are the primary reason for the decline in ES efficiency, and that high E2 and P4 levels at some time points also impair reproductive performance. These findings provide novel insights into the metabolic effects of repeated PMSG stimulation in goats, guiding future reproductive hormone use in breeding practices. [ABSTRACT FROM AUTHOR]

Objective: Combined fractures of the lateral condyle of the humerus and the ipsilateral ulnar olecranon are rarely seen in children. Therefore, the mechanism and suitable treatments remain debatable. This study describes the possible mechanism of combined humeral lateral condyle and ipsilateral ulnar olecranon fractures and presents the treatment results. Methods: Children diagnosed with combined fractures of the humeral lateral condyle and ipsilateralulnar olecranon from July 2010 to July 2020 were retrospectively analyzed. Humeral lateral condyle fractures were treated with open reduction and internal fixation with bioabsorbable pins. Ulnar olecranon fractures were treated with closed reduction and percutaneous pinning with K‐wires for Mayo type IA fractures and with tension‐band wiring or a locking plate for Mayo type IIA fractures. The postoperative function and appearance of the elbow were evaluated using the Flynn criteria and Mayo Elbow Performance Score (MEPS) at follow‐up. Results: The cohort comprised 19 patients aged from 4 to 11 years. Bony compression and avulsion by attached muscles and ligaments may be the leading factors causing the combined injuries, as the children fell with an outstretched and supinated elbow. The average follow‐up time was 33 months. High MEPS of >90 indicated that good to excellent results were obtained without complications. Conclusions: This study proposed a reasonable hypothesis for the mechanism of combined humeral lateral condyle and ipsilateral ulnar olecranon fractures in children. Satisfactory outcomes were achieved with bioabsorbable pins for lateral condyle fractures and closed reduction and percutaneous pinning with K‐wires, tension‐band wiring, or locking plate for olecranon fractures. [ABSTRACT FROM AUTHOR]

Simple Summary: Acquired myasthenia gravis is an immune-mediated neuromuscular disease caused by autoantibodies directed against the neuromuscular junction, which leads to skeletal muscle weakness. The acute fulminant form is defined as rapidly progressive generalized weakness and can lead to a life-threatening condition caused by the paralysis of respiratory muscles. Traditional management consists of acetylcholinesterase inhibitors and nutritional management. This case report shows a new therapeutic option for this acute life-threatening condition. The dog was mechanically ventilated for respiratory failure due to acquired myasthenia gravis and immunoadsorption, an extracorporeal blood purification technique, was performed. During immunoadsorption, blood is purified in an extracorporeal circuit using an adsorber that binds circulating autoantibodies. After immunoadsorption, the dog was successfully weaned from mechanical ventilation and further treated with medical management. A one-year-old, female intact Samoyed, 12.5 kg, was presented with coughing for 2 weeks, progressive appendicular and axial muscle weakness, megaesophagus and labored breathing for 5 days. There was no improvement with standard treatment. Acquired myasthenia gravis was suspected and the dog was referred with increasing dyspnea. At presentation, the dog showed a severely reduced general condition, was non-ambulatory and showed abdominal and severely labored breathing. A marked hypercapnia (PvCO2 = 90.1 mmHg) was present in venous blood gas analysis. The serum anti-acetylcholine receptor antibody test was consistent with acquired myasthenia gravis (2.1 nmol/L). The dog was anesthetized with propofol and mechanically ventilated with a Hamilton C1 ventilator. Immunoadsorption was performed with the COM.TEC® and ADAsorb® platforms and a LIGASORB® adsorber to eliminate anti-acetylcholine receptor antibodies. Local anticoagulation was performed with citrate. Treatment time for immunoadsorption was 1.5 h with a blood flow of 50 mL/min. A total plasma volume of 1.2 L was processed. Further medical treatment included intravenous fluid therapy, maropitant, esomeprazole, antibiotic therapy for aspiration pneumonia and neostigmine 0.04 mg/kg intramuscularly every 6 h for treatment of acquired myasthenia gravis. Mechanical ventilation was stopped after 12 h. A percutaneous gastric feeding tube was inserted under endoscopic control on day 2 for further medical treatment and nutrition. A second treatment with immunoadsorption was performed on day 3. Again, a total plasma volume of 1.2 L was processed. Immediately after this procedure, the dog regained muscle strength and was able to stand and to walk. After 6 days, the dog was discharged from the hospital. This is the first report of immunoadsorption for emergency management of a dog with acute-fulminant acquired myasthenia gravis. Immunoadsorption may be an additional option for emergency treatment in dogs with severe signs of acquired myasthenia gravis. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to compare the outcomes of patients with ground-grass opacity (GGO)-dominant non-small cell lung cancer (NSCLC) who were treated with carbon ion radiotherapy (CIRT) versus segmentectomy. Methods: A retrospective review of medical records was conducted. The study included 123 cases of clinical stage 0/IA peripheral NSCLC treated with single-fraction CIRT from 2003 to 2012, 14 of which were determined to be GGO-dominant and were assigned to CIRT group. As a control, 48 consecutive patients who underwent segmentectomy for peripheral GGO-dominant clinical stage IA NSCLC were assigned to segmentectomy group. Results: The patients in CIRT group, compared with segmentectomy group, were significantly older (75 ± 7.2 vs. 65 ± 8.2 years, P = 0.000660), more likely to be male (13/14 vs. 22/48, P = 0.00179), and had a lower forced vital capacity (91 ± 19% vs. 110 ± 13%, P = 0.0173). There was a significant difference in the 5-years overall survival rate (86% vs. 96%, P = 0.000860), but not in the 5-years disease-specific survival rate (93% vs. 98%, P = 0.368). Discussion: Compared with segmentectomy, CIRT may be an alternative option for patients with early GGO-dominant NSCLC who are poor candidates for, or who refuse, surgery. [ABSTRACT FROM AUTHOR]

Consideration for oversizing the proximal stent graft is suggested in endovascular aortic repair. However, a special recommendation for the proximal oversizing ratio (OSR) in patients with ruptured abdominal aortic aneurysm (rAAA) is ambiguous. This study aims to evaluate the effect of different degrees of the proximal oversizing ratio (OSR) on risk of type IA endoleak (TIAEL) in hemodynamically stable and unstable patients with rAAA undergoing emergency endovascular aortic repair (EVAR). Our study included 134 rAAA patients undergoing emergent EVAR, and we did not observe a significant association between hemodynamic instability and risk of T1AEL (HR 3.89, 95%CI 0.40–37.75, p = 0.24). All three T1AELs in the hemodynamically unstable subgroup were observed in patients with OSR ≤ 30%, but no significant difference was found regarding T1AEL between patients with OSR > 30% and OSR ≤ 30% (0.00% vs. 11.11%, p = 0.19). As for hemodynamically stable patients, OSR > 20% was associated with a significantly decreased risk of T1AEL (HR 0.03, 95%CI 0.01–0.53, p = 0.016). In conclusion, a proximal OSR > 20% is associated with a decreased risk of T1AEL in hemodynamically stable patients, while an OSR > 30% did not add an additional advantage of lowering the risk of T1AEL in hemodynamically unstable patients. [ABSTRACT FROM AUTHOR]

A dysregulated host response is a common feature in critically ill patients due to both infectious and non-infectious origins that can lead to life-threatening organ dysfunction, which is still the primary cause of death in intensive care units worldwide. In its course, pathologic, unregulated levels of inflammatory mediators are often released into the circulation, a phenomenon also referred to as a "cytokine storm". To date, there are no approved therapies to modulate the excessive immune response and limit hyperinflammation with the goal of preventing related organ failure and death. In this context, extracorporeal blood purification therapies aiming at the alteration of the host inflammatory response through broad-spectrum, non-selective removal of inflammatory mediators have come into focus. A novel hemoadsorption device (CytoSorb®, CytoSorbents Inc., Princeton, NJ, USA) has shown promising results in patients with hyperinflammation from various origins. Although a significant body of literature exists, there is ongoing research to address many important remaining questions, including the optimal selection of patient groups who might benefit the most, optimal timing for therapy initiation, optimal schedule for adsorber exchanges and therapy duration, as well as an investigation into the potential removal of concomitant antibiotics and other medications. In this review, we discuss the existing evidence and provide a consensus-based best practice guidance for CytoSorb® hemoadsorption therapy in patients with vasoplegic shock. [ABSTRACT FROM AUTHOR]

Severe renal impairment is a common complication of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and is associated with poor prognosis and shorter survival. It is urgent to find effective treatments to improve the prognosis of AAV patients. This study was designed to assess the efficacy and safety of protein A immunoadsorption (PAIA) and therapeutic plasma exchange (TPE) for AAV with severe renal involvement. A total of 48 AAV patients with renal involvement admitted to the Second Xiangya Hospital from January 2018 to February 2021 were selected. Clinical data, myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA), remission at 6 months, and outcomes were evaluated. The primary outcomes of interest were death and renal survival as defined by the occurrence of end-stage renal disease (ESRD). PAIA was effective in the removal of MPO-ANCA and IgG, and showed superior over TPE in the clearance of MPO-ANCA within 1 month after treatment. After a median follow-up of 14.5 months, PAIA therapy showed an advantage in reducing mortality over TPE. There was no difference in the development of ESRD between the two groups. Multivariate Cox regression analysis indicated that higher serum creatinine (SCr) and lower haemoglobin level were independent risks of ESRD. Age > 60, lower serum albumin (ALB), and failure to achieve remission at 6 months were independent risks of death. PAIA treatment reduces MPO-ANCA and IgG as well as mortality in AAV patients, and may be beneficial for severe AAV in clinical practice. Higher SCr, lower serum ALB or haemoglobin levels, age > 60, and failure to achieve remission at 6 months independently predict the ESRD or death of AAV patients with severe renal involvement. Compared with therapeutic plasma exchange, protein A immunoadsorption treatment eliminates myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA) and IgG better and reduces mortality in ANCA-associated vasculitis (AAV) patients with severe renal involvement. Higher serum creatinine, lower serum albumin or haemoglobin levels, age > 60, and failure to achieve remission at 6 months independently predict the end-stage renal disease (ESRD) or death of AAV patients with severe renal involvement. [ABSTRACT FROM AUTHOR]

Objective: In recent years, more and more cases of intracranial aneurysms (lAs) have been found in elderly patients, and neurosurgical interventions have increased, but there is still no consensus on the best treatment strategy for elderly patients. In elderly patients, endovascular coiling (EC) is more popular than surgical clipping (SC) due to its advantages of less trauma and faster recovery. However, SC has made great progress in recent years, significantly improving the prognosis of elderly patients. Therefore, it is necessary to further explore the effects of different treatment modalities on clinical prognosis, hospital stay, and hospital cost of elderly IA patients, and select the most appropriate treatment modalities. Methods: The authors retrospectively analyzed 767 patients with intracranial aneurysms admitted to the facility between August 2017 and December 2022. Prognostic risk factors and multivariate logistic regression were analyzed for elderly patients treated with EC or SC. The area under the receiver operating characteristic (ROC) curve was used to calculate the predictive power of each independent predictor between the treatment groups. Results: Our study included 767 patients with aneurysms, of whom 348 (45.4%) were elderly, 176 (22.9%) underwent endovascular coiling, and 172 (22.4%) underwent microsurgical clipping. A comparison of elderly patients treated with EC and SC showed a higher prevalence of hypertension in the EC group (P= 0.011) and a higher Hunt-Hess score on admission in the SC group (P = 0.010). Patients in the EC group had shorter hospital stays but higher costs (P = 0.000 and P = 0.000, respectively). Patients treated with SC had a higher incidence of postoperative cerebral infarction and poor prognosis (P = 0.002 and P = 0.008, respectively). Through multi-factor logistic analysis, it was found that age (OR 1.209, 95% CI 1.047-1.397, P = 0.010), length of stay (LOS) (OR 1.160, 95 Cl% 1.041-1.289, P = 0.007), and complications (OR 31.873, 95 Cl% 11.677-320.701, P = 0.000) was an independent risk factor for poor prognosis in elderly patients with EC. In elderly patients treated with SC, age (OR 1.105, 95% CI 1.010-1.209, P = 0.029) was an independent risk factor for poor prognosis. Conclusion: EC and SC interventions in elderly adults carry higher risks compared to non-older adults, and people should consider these risks and costs when making a decision between intervention and conservative treatment. In elderly patients who received EC or SC treatments, EC showed an advantage in improving outcomes in elderly patients although it increased the economic cost of the patient's hospitalization. [ABSTRACT FROM AUTHOR]

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ABO-incompatible (ABOi) living kidney transplantation (KTx) is an established procedure to address the demand for kidney transplants with outcomes comparable to ABO-compatible KTx. Desensitization involves the use of immunoadsorption (IA) to eliminate preformed antibodies against the allograft. This monocentric retrospective study compares single-use antigen-selective Glycosorb® ABO columns to reusable non-antigen-specific Immunosorba® immunoglobulin adsorption columns regarding postoperative infectious complications and outcome. It includes all 138 ABOi KTx performed at Freiburg Transplant Center from 2004–2020. We compare 81 patients desensitized using antigen-specific columns (sIA) to 57 patients who received IA using non-antigen-specific columns (nsIA). We describe distribution of infections, mortality and allograft survival in both groups and use Cox proportional hazards regression to test for the association of IA type with severe infections. Desensitization with nsIA tripled the risk of severe postoperative infections (adjusted HR 3.08, 95% CI: 1.3–8.1) compared to sIA. nsIA was associated with significantly more recurring (21.4% vs. 6.2%) and severe infections (28.6% vs. 8.6%), mostly in the form of urosepsis. A significantly higher proportion of patients with sIA suffered from allograft rejection (29.6% vs. 14.0%). However, allograft survival was comparable. nsIA is associated with a two-fold risk of developing a severe postoperative infection after ABOi KTx.

Background: During active surveillance (AS), serum thyrotropin (TSH) levels may affect papillary thyroid microcarcinoma (PTMC) progression. We investigated AS outcomes according to whether levothyroxine (LT4) treatment was administered. Patients and Methods: From 2005 to 2019, 2896 patients with low-risk PTMC underwent AS. Of these, 2509 patients were included: 2187 patients did not receive LT4 at diagnosis (group I), 1935 patients did not receive LT4 during AS (group IA), and 252 patients started LT4 during AS (group IB). The remaining 322 patients were administered LT4 before or at diagnosis (group II). The tumor volume doubling rate (TVDR) and tumor size based on ultrasound examination results and time-weighted detailed TSH scores were calculated. Disease progression was defined as tumor enlargement ≥3 mm and/or the appearance of novel lymph node metastasis. Results: At diagnosis, group II had more high-risk features, such as younger age and larger tumors, than group I. However, group II had a lower disease progression rate (2.9% at 10 years) than group I (6.1%) (p = 0.091). The disease progression rate of group IB (13.8% at 10 years) was significantly higher than that of groups IA (5.0%) and II (2.9%) (p < 0.01). The TVDR of group IB before LT4 administration was significantly higher than that of groups IA and II (0.095 per year, −0.0085 per year, and −0.057 per year, respectively; p < 0.01), suggesting that patients with progression signs during AS were selectively prescribed LT4. The time-weighted detailed TSH score of group IB significantly decreased after LT4 administration compared with those before administration (3.35 and 3.05, respectively; p < 0.01). The TVDR also decreased from 0.13 per year to 0.036 per year (p = 0.08). The proportions of patients with rapid or moderate growth decreased significantly after LT4 (from 26.8% to 12.5%, p < 0.01). A multivariable analysis revealed group IB status was independently associated with disease progression (odds ratio [OR] = 3.42 [CI 2.15–5.44], p < 0.01), whereas age ≥40 years and <60 years and age ≥60 years were independently negatively associated with this outcome (OR = 0.23 [CI 0.14–0.38, p < 0.01 and OR = 0.16 [CI 0.10–0.27], p < 0.01). Conclusion: LT4 treatment may be associated with decreased tumor growth during AS of PTMC, but further confirmatory research is needed. [ABSTRACT FROM AUTHOR]

There is increasing evidence for an autoimmune aetiology in post-infectious Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). SARS-CoV-2 has now become the main trigger for ME/CFS. We have already conducted two small proof-of-concept studies on IgG depletion by immunoadsorption (IA) in post-infectious ME/CFS, which showed efficacy in most patients. This observational study aims to evaluate the efficacy of IA in patients with post-COVID-19 ME/CFS. The primary objective was to assess the improvement in functional ability. Due to the urgency of finding therapies for post-COVID-Syndrome (PCS), we report here the interim results of the first ten patients, with seven responders defined by an increase of between 10 and 35 points in the Short-Form 36 Physical Function (SF36-PF) at week four after IA. The results of this observational study will provide the basis for patient selection for a randomised controlled trial (RCT), including sham apheresis, and for an RCT combining IA with B-cell depletion therapy. Trial registration number: NCT05629988. [ABSTRACT FROM AUTHOR]

Background: Gene therapies based on adeno‐associated viruses (AAV) are a therapeutic option to successfully treat monogenetic diseases. However, the influence of pre‐existing immunity to AAV can compromise the application of AAV gene therapy, most notably by the presence of neutralizing antibodies (NAb) to AAV. Methods: In the following study, we investigated to what extent the treatment by immunoadsorption (IA) would reduce the levels of human anti‐AAV antibodies to AAV2 and AAV5. To that end, we screened blood sera from 40 patients receiving IA treatment because of underlying autoimmune disease or transplant rejection, with detectable AAV‐antibodies in 23 patients (22 by NAb detection, and 1 additionally by anti‐AAV5 ELISA analysis). Results: Our results show that IA efficiently depleted anti‐AAV2 NAb with a mean reduction of 3.92 ± 1.09 log2 titer steps (93.4%) after three to five single IA treatments, 45% of seropositive subjects had an anti‐AAV2 titer below the threshold titer of 1:5 after the IA treatment series. Anti‐AAV5 NAb were reduced to below the threshold titer of 1:5 in all but one of five seropositive subjects. Analysis of total anti‐AAV5 antibodies by ELISA demonstrated an anti‐AAV5 antibody reduction over the IA treatment series of 2.67 ± 1.16 log2 titer steps (84.3%). Conclusion: In summary, IA may represent a safe strategy to precondition patients with pre‐existing anti‐AAV antibodies to make this population eligible for an effective AAV‐based gene therapy. [ABSTRACT FROM AUTHOR]

Introduction: Liver transplant is a life‐saving treatment, but due to the limited availability of suitable liver donors, ABO‐incompatible liver transplants (ABOi‐LT) are conducted to increase the availability of liver donors. Perioperative desensitization for ABOi‐LT is an established strategy to circumvent the risk of graft rejection. A single prolonged session can be performed to achieve the desired titers to avoid using multiple immunoadsorption (IA) columns or off‐label reuse of single‐use columns. This study retrospectively assessed the effectiveness of a single prolonged plasmapheresis session using IA as a desensitization strategy in live donor liver transplant (LDLT). Materials and methods: This retrospective observational study conducted at a center for liver diseases in North India on six ABOi‐LDLT patients who underwent single prolonged IA sessions in the perioperative period from January 2018 to June 2021. Results: Median baseline titer in patients was 320 (64, 1024). The median plasma volume adsorbed was 7.5 volumes (4, 8) per procedure, with a mean procedure time of 600 min (310‐753). The reduction in titer ranged from 4 log to 7 log reduction per procedure. Two patients developed transient hypotension during the procedure, which was managed successfully. The median duration of pre‐transplant hospital stay was 1.5 days (1, 3). Conclusion: Desensitization therapy helps overcome the ABO barrier and decreases the waiting period before a transplant when ABO identical donors are unavailable. A single prolonged IA session reduces the cost of additional IA columns and hospital stay, thus making it a cost‐effective approach to desensitization. [ABSTRACT FROM AUTHOR]

Objective: Management of emergency care Background: Patients with COVID-19 undergoing emergency or complex surgical procedures are at increased risk of developing perioperative complications. CytoSorb is a blood purification therapy used to remove circulating cytokines in conditions of hyperinflammation. This report is of a patient with COVID-19 requiring redo replacement of the aortic valve and aorta due to aortic aneurysm of the ascending aorta (Bentall procedure) associated with Marfan syndrome. The patient was successfully treated with extracorporeal cytokine hemoadsorption. Case Report: A 34-year-old man with Marfan syndrome, who had undergone a Bentall procedure in 2018, was admitted with symptoms of worsening dyspnea, tachycardia, fever, and confirmed COVID-19. Further diagnostic workup revealed dehiscence of the aortic root as well as moderate aortic regurgitation, in the context of a hyperinflammatory state. Anti-infective treatment was initiated. Given the severity of symptoms, COVID-19, echocardiography findings, and risk of aortic rupture, urgent Bentall surgery was performed. Additionally, a CytoSorb hemoadsorber was integrated into the cardiopulmonary bypass circuit to attenuate the anticipated systemic hyperinflammation. Intraoperatively, several blood products were administered due to excessive bleeding from the friable tissues and the pre-existing anemia and thrombocytopenia. Treatment was associated with marked improvements in vital parameters and inflammatory markers, and weaning from the ventilator and inotropes was possible after 48 hours. The remaining time in hospital was uneventful. Conclusions: This report supports the findings from recent studies and reports that extracorporeal cytokine hemoadsorption has a role to play in reducing the systemic effects of cytokine storm associated with complex surgery involving cardiopulmonary bypass alongside severe infections, including COVID-19. [ABSTRACT FROM AUTHOR]

Whether immunoadsorption (IADS) as part of desensitization protocols could facilitate deceased donor kidney transplantation (KT) in highly sensitized (HS) patients remains to be proven. We retrospectively analyzed our IADS based desensitization protocol for deceased donor KTs between 2013 and 2018. Fifteen HS patients (age 52 years [40-56]) were included.Waiting time before IADSwas 6years [5-10] and the interval between IADS initiation and KT was 5months [1-12] for the 14 transplanted patients. Nine patients had prior KT. Calculated panel reactive antibody decreased significantly during the protocol (99.3% [92.5-99.9] vs. 79.4% [56.7-81.9]; p = 0.004). Death-censored graft survival was 85.7% at 1 and 2 years post-transplantation. One-year median plasma creatinine level was 135 µmol/L [111-202]. Six developed active antibody mediated rejection (ABMR) at 1 year, with a median delay of 13 days [11-26]. Eight patients developed severe infections, including two fatal outcomes. Finally, compared to 93% of patients who received desensitization receiving a KT, only 43% of a control with similar characteristics underwent transplantation. However, no difference was found in overall probability of being alive with a functioning graft at the end of follow-up. The results indicate that our IADS-based desensitization strategy was not effective due to a high rate of ABMR and severe infectious complications which pose a challenge to its universalization. [ABSTRACT FROM AUTHOR]