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Abstract Background and Aim Maintenance haemodialysis patients have increased morbidity and mortality which is mainly driven by an elevated inflammation level due to the uraemic milieu. A major part of this increased inflammation level is the degree of oxidative stress which can be assessed by albumin redox state (ARS). Aim of this study was to evaluate how the ARS is affected by a haemodialysis treatment and different dialyzer properties. Methods ARS was determined before and after haemodialysis treatment by fractionating it into reduced human mercaptalbumin (HMA), reversibly oxidized human non-mercaptalbumin 1 (HNA-1), and irreversibly oxidized human non-mercaptalbumin 2 (HNA-2) by high-performance liquid chromatography. In healthy individuals, albumin circulates in the following proportions: HMA 70–80%, HNA-1 20–30% and HNA-2 2–5%. High flux (FX 100 [Fresenius Medical Care], BG 1.8 [Toray], Xevonta Hi 18 [B. Braun], CTA-2000 [Kawasumi]) and low flux FX10 [Fresenius Medical Care] dialyzers were used. Results 58 patients (59% male, median age 68 years, median time on haemodialysis 32 month) were included in the study. Before haemodialysis treatment, HMA (median 55.9%, IQR 50.1–61.2%) was substantially lower than in healthy individuals. Accordingly, oxidized albumin fractions were above the level of healthy individuals (median HNA-1 38.5%, IQR 33.3–43.2%; median HNA-2 5.8%, IQR 5.1–6.7%). Before haemodialysis treatment HMA was significantly higher in patients usually treated with high flux membranes (p

Abstract Introduction Immunosuppressive therapy is associated with an increased risk of severe courses of SARS-CoV-2 infection, with frequently delayed viral clearance. We report a case of an acute kidney transplant failure in persistent SARS-CoV-2 infection in a patient with absolute B-cell depletion after administration of rituximab for AB0-incompatible living donor kidney transplantation. Case presentation A 34-year-old unvaccinated patient is diagnosed with SARS-CoV-2 infection four months after kidney transplantation. With only mild symptoms and an estimated glomerular filtration rate (eGFR) of 44 ml/min/1.73 m2, therapy with molnupiravir was initially given. Within the next eight weeks, transplant biopsies were performed for acute graft failure. These showed acute T-cell rejection with severe acute tubular epithelial damage with only mild interstitial fibrosis and tubular atrophy (BANFF cat. 4 IB), and borderline rejection (BANFF cat. 3). A therapy with prednisolone and intravenous immunoglobulins was performed twice. With unchanged graft failure, the third biopsy also formally showed BANFF cat. 4 IB. However, fluorescence in situ hybridization detected SARS-CoV-2 viruses in large portions of the distal tubules. After nine weeks of persistent COVID-19 disease neither anti-SARS-CoV-2 IgG nor a SARS-CoV-2-specific cellular immune response could be detected, leading to the administration of sotrovimab and remdesivir. Among them, SARS-CoV-2 clearance, detection of IgG, and improvement of graft function were achieved. Conclusion Lack of viral clearance can lead to complications of SARS-CoV-2 infection with atypical manifestations. In kidney transplant patients, before initiating therapy, the differential diagnoses of “rejection” and “virus infection” should be weighed against each other in an interdisciplinary team of nephrologists, infectious diseases specialists and pathologists.

Abstract Plasmapheresis (PE) is an established form of therapeutic apheresis (TA). Purpose of this longitudinal prospective single center study was to investigate the effect of PE on albumin redox state (ARS), as infusion of commercial albumin during PE may alter albumin oxidation which has an impact on its functional properties and oxidative stress level. 43 subjects with autoimmune-mediated neurological disorders were included. 20 subjects in the experimental group received five treatments of PE. 13 subjects received five treatments of immunoadsorption and 10 subjects received no TA as controls. ARS was determined before and after TA and 12 days after the last TA by fractionating it into human mercaptalbumin (HMA), human non-mercaptalbumin 1 (HNA-1), and human non-mercaptalbumin 2 (HNA-2) by high-performance liquid chromatography. Irreversibly oxidised HNA-2 increased over the course of five PE treatments from 2.8% (IQR 1.3–3.7%) to 13.6% (IQR 10.9–15.9) (P

Patients on dialysis have dysfunctions of innate and adaptive immune system responses. The transcriptional factor IRF8 (interferon regulatory factor 8) is primarily expressed in plasmacytoid cells (pDCs) and myeloid dendritic cells (mDCs), playing a crucial role in the maturation of dendritic cells, monocytes, and macrophages, and contributing to protection against bacterial infections. The current study analyzed the expression patterns of IRF8 and assessed its association with the risk of infections in 79 dialysis patients compared to 44 healthy controls. Different subsets of leukocytes and the intracellular expression of IRF8 were measured using flow cytometry. Compared to the healthy controls, the dialysis patients showed significantly reduced numbers of pDCs and significantly increased numbers of natural killer cells and classical and intermediate monocytes. The dialysis patients exhibited decreased numbers of IRF8-positive dendritic cells (pDC p < 0.001, mDC1 p < 0.001, mDC2 p = 0.005) and increased numbers of IRF8-positive monocytes (p < 0.001). IRF8 expression in pDC, mDC, and classical monocytes was lower in the dialysis patients than in the controls. Dialysis patients who required hospitalization due to infections within one year of follow-up displayed significantly reduced IRF8 expression levels in pDCs compared to patients without such infections (p = 0.04). Our results suggest that reduced IRF8 expression in pDCs is a potential risk factor predisposing dialysis patients to serious infections.

Abstract Background Severe thromboembolic events are one of the major complications associated with COVID-19 infection, especially among critically ill patients. We analysed ROTEM measurements in COVID-19 patients with a severe disease course and in patients with severe sepsis. Methods In this study, data obtained by extended analysis of haemostasis with standard laboratory tests and thromboelastometry of 20 patients with severe course of COVID-19 were retrospectively analysed and compared with similar data from 20 patients with severe sepsis but no COVID-19. Results The thromboelastometry values obtained from 20 sepsis patients contained a maximum clot firmness above the normal range but among COVID-19 patients, hypercoagulability was much more pronounced, with significantly higher maximum clot firmness (FIBTEM: 38.4 ± 10.1 mm vs. 29.6 ± 10.8 mm; P = 0.012; EXTEM: 70.4 ± 10.4 mm vs. 60.6 ± 14.8 mm; P = 0.022). Additionally, fibrinogen levels were significantly higher among COVID-19 patients (757 ± 135 mg/dl vs. 498 ± 132 mg/dl, P

Abstract Background Peritoneal dialysis (PD)-related peritonitis is a rare but serious complication and is associated with increased morbidity and mortality rates. It is most commonly caused by Staphylococcus aureus or Staphylococcus epidermidis, but infection with Listeria monocytogenes may also occur. Recommendations for antibiotic treatment of a Listeria infection are currently based on a small number of case reports and suggest the administration of ampicillin. But unlike vancomycin or gentamicin, for ampicillin the route of application, the dosage, and the duration of treatment have not yet been established. We report a case in which PD-associated peritonitis due to Listeria infection was treated with ampicillin administered intravenously and intraperitoneally, separately and in combination. Case presentation A 72-year-old man with chronic kidney disease stage 5 dialysis (CKDG5D) secondary to hypertension and diabetes was hospitalised in April 2020 because of PD-related peritonitis caused by a Listeria infection. In accordance with the results of resistance tests, the patient was treated with intravenous ampicillin at a dosage of 6 g twice daily. After initial treatment the leukocyte count in the PD effluent had decreased substantially, but it was permanently reduced only with the addition of intraperitoneal ampicillin (4 g daily). Efficient serum concentrations of ampicillin were determined for both routes of administration, intravenous and intraperitoneal. Conclusion This is the first case report demonstrating that PD-related peritonitis due to Listeria monocytogenes infection can be treated with intraperitoneal ampicillin and monitored by the determination of peripheral serum concentrations of ampicillin.

BackgroundPostoperative sepsis is an important cause of morbidity and mortality in patients with infective endocarditis undergoing surgical therapy. Blood purification using hemoadsorption therapy shows promising results in the treatment of sepsis. In this study, the clinical effects of intraoperative hemoadsorption in high-risk patients with infective endocarditis were evaluated.MethodsEligible candidates were high-risk patients with infective endocarditis undergoing cardiac surgery between January 2014 and December 2019. Patients with intraoperative hemoadsorption (hemoadsorption) were compared to patients without hemoadsorption (control). The endpoints were the incidence of postoperative sepsis, sepsis-associated death and in-hospital mortality. Additionally, postoperative vasopressor need, systemic vascular resistance indices and Sequential Organ Failure Assessment (SOFA) scores were compared.ResultsAfter propensity score matching, 70 high-risk patients were included. Postoperative sepsis occurred in 14 patients in the hemoadsorption group and in 16 patients in the control group, p = 0.629. Four patients died due to postoperative sepsis in the hemoadsorption group, while 11 postoperative septic patients died in the control group, p = 0.041. In-hospital mortality was 34% in the hemoadsorption group versus 43% in the control group, p = 0.461. On ICU-admission and the first postoperative day, the cumulative vasopressor need was 0.17 versus 0.25 μg/kgBW/min, p = 0.123 and 0.06 versus 0.11 μg/kgBW/min, p = 0.037, and the systemic vascular resistance index was 1448 versus 941 dyn·s·cm-5, p = 0.013 and 1156 versus 858 dyn·s·cm-5, p = 0.110 in the hemoadsorption versus control group, respectively. Postoperative course of SOFA score normalized significantly (p = 0.01) faster in the hemoadsorption group.ConclusionsIn high-risk cardiac surgical patients with infective endocarditis, intraoperative hemoadsorption significantly reduced sepsis-associated mortality. Furthermore, intraoperative hemoadsorption resulted in significant faster recovery of hemodynamics and organ function. Intraoperative hemoadsorption seems to attenuate the severity of postoperative sepsis.

Vulnerable patients such as immunosuppressed or elderly patients are at high risk for a severe course of COVID-19 upon SARS-CoV-2 infection. Immunotherapy with SARS-CoV-2 specific monoclonal antibodies (mAb) or convalescent plasma represents a considerable treatment option to protect these patients from a severe or lethal course of infection. However, monoclonal antibodies are not always available or less effective against emerging SARS-CoV-2 variants. Convalescent plasma is more commonly available and may represent a good treatment alternative in low-income countries. We retrospectively evaluated outcomes in individuals treated with mAbs or convalescent plasma and compared the 30-day overall survival with a patient cohort that received supportive care due to a lack of SARS-CoV-2 specific therapies between March 2020 and April 2021. Our data demonstrate that mAb treatment is highly effective in preventing severe courses of SARS-CoV-2 infection. All patients treated with mAb survived. Treatment with convalescent plasma improved overall survival to 82% compared with 61% in patients without SARS-CoV-2 targeted therapy. Our data indicate that early convalescent plasma treatment may be an option to improve the overall survival of high-risk COVID-19 patients. This is especially true when other antiviral drugs are not available or their efficacy is significantly reduced, which may be the case with emerging SARS-CoV-2 variants.

BackgroundExtracorporeal cytokine adsorption is an option in septic shock as an additional measure to treat a pathological immune response. Purpose of this study was to investigate the effects of extracorporeal cytokine adsorption on hemodynamic parameters in patients with acute kidney injury (AKI) on continuous renal replacement therapy (CRRT) and septic shock after cardiac surgery.MethodsIn this retrospective study, a total of 98 patients were evaluated. Hemoadsorption was performed by the CytoSorb® adsorber. In all patients cytokine adsorption was applied for at least 15 hours and at least one adsorber was used per patient. To compare cumulative inotrope need in order to maintain a mean arterial pressure (MAP) of ≥ 65 mmHg, we applied vasoactive score (VAS) for each patient before and after cytokine adsorption. A paired t-test has been performed to determine statistical significance.ResultsBefore cytokine adsorption the mean VAS was 56.7 points. This was statistically significant decreased after cytokine adsorption (27.7 points, p< 0.0001). Before cytokine adsorption, the mean noradrenalin dose to reach a MAP of ≥ 65 mmHg was 0.49 μg/kg bw/min, the mean adrenalin dose was 0.12 μg/kg bw/min. After cytokine adsorption, significantly reduced catecholamine doses were necessary to maintain a MAP of ≥ 65 mmHg (0.24 μg/kg bw/min noradrenalin; p< 0.0001 and 0.07 μg/kg bw/min adrenalin; p < 0.0001). Moreover, there was a significant reduction of serum lactate levels after treatment (p< 0.0001). The mean SOFA-score for these patients with septic shock and AKI before cytokine adsorption was 16.7 points, the mean APACHE II-score was 30.2 points. The mean predicted in-hospital mortality rate based on this SOFA-score of 16.7 points was 77,0%, respectively 73,0% on APACHE II-score, while the all-cause in-hospital mortality rate of the patients in this study was 59.2%.ConclusionIn patients with septic shock and AKI undergoing cardiac surgery, extracorporeal cytokine adsorption could significantly lower the need for postoperative inotropes. Additionally, observed versus SOFA- and APACHE II-score predicted in-hospital mortality rate was decreased.