Myocarditis incidence and hospital mortality from 2007 to 2022: insights from a nationwide registry.

OBJECTIVES: To investigate the burden of disease of myocarditis in Germany and identify similarities and differences in myocarditis with or without COVID-19. METHODS: All patients hospitalized with myocarditis in Germany were included in this nationwide retrospective analysis. Data were retrieved from the Federal Statistical Office of Germany (DESTATIS) for the years from 2007 to 2022. The primary endpoint was hospital mortality. RESULTS: A total of 88,159 patients hospitalized with myocarditis were analyzed. Annual cases increased from 5100 in 2007 to 6593 in 2022 (p < 0.001 for trend) with higher incidence during winter months. Incidence per 100,000 inhabitants was 6.2 in 2007 rising to 7.8 in 2022 (p < 0.001 for trend). Hospital mortality remained constant at an average of 2.44% (p = 0.164 for trend). From 2020 to 2022, 1547/16,229 (9.53%) patients were hospitalized with both, myocarditis and COVID-19 (incidence 0.62/100,000 inhabitants and 180/100,000 hospitalizations with COVID-19). These patients differed significantly in most patient characteristics and had a higher rate of hospital mortality compared to myocarditis without COVID-19 (12.54% vs. 2.26%, respectively, p < 0.001). CONCLUSIONS: Myocarditis hospitalizations were slowly rising over the past 16 years with hospital mortality remaining unchanged. Incidence of hospitalizations with combined myocarditis and COVID-19 was low, but hospital mortality was high.

Corrigendum: Survival outcomes and mobilization during venovenous extracorporeal membrane oxygenation: a retrospective cohort study.

[This corrects the article DOI: 10.3389/fmed.2023.1271540.].

Cytokine adsorption in patients with acute-on-chronic liver failure (CYTOHEP): A single center, open-label, three-arm, randomized, controlled intervention pilot trial.

BACKGROUND: To investigate the efficacy of bilirubin reduction by hemoadsorption with CytoSorb® in patients with acute-on-chronic liver failure (ACLF) receiving continuous renal replacement therapy (CRRT). METHODS: A prospective, randomized, single-center, open-label, controlled pilot trial. Patients with ACLF, acute kidney injury, and serum bilirubin ≥5 mg/dL were assigned 1:1:1 to one of three study groups (CRRT with or without hemoadsorption, no CRRT). In the hemoadsorption group, the CytoSorb adsorber was incorporated into the CRRT system, replaced after 12, 24, and 48 h, and removed after 72 h. The primary endpoint was the serum bilirubin level after 72 h. RESULTS: CYTOHEP was terminated early due to difficulties in recruiting patients and ethical concerns. Three of 9 patients (33%) were treated in each group. Comparing the three groups, mean bilirubin levels after 72 h were lower by -8.0 mg/dL in the "CRRT with hemoadsorption" group compared to "CRRT without hemoadsorption" (95% CI, -21.3 to 5.3 mg/dL; p = 0.17). The corresponding mean difference between "CRRT without hemoadsorption" and "no CRRT" was -1.4 mg/dL (95% CI, -14.2 to 11.5 mg/dL; p = 0.78). Comparing "CRRT with hemoadsorption" and "no CRRT," it was -9.4 mg/dL (95% CI, -20.8 to 2.1 mg/dL; p = 0.0854). Only 1/9 patients (11%, "no CRRT" group) survived day 30 after study inclusion but died on day 89. IL-6, liver function parameters, and clinical scores were similar between the study groups. CONCLUSIONS: CYTOHEP failed to demonstrate that extracorporeal hemoadsorption combined with CRRT can reduce serum bilirubin in ACLF patients with acute kidney failure.

Alternative venous access sites for dual-lumen extracorporeal membrane oxygenation cannulation.

OBJECTIVES: Dual-lumen cannulas for veno-venous (VV) extracorporeal membrane oxygenation (ECMO) support are typically inserted in the right internal jugular vein (RIJV); however, some scenarios can make this venous route inaccessible. This multicentre case series aims to evaluate if single-site cannulation using an alternative venous access is safe and feasible in patients with an inaccessible RIJV. METHODS: We performed a multi-institutional retrospective analysis including high-volume ECMO centres with substantial experience in dual-lumen cannulation (DLC) (defined as >10 DLC per year). Three centres [Freiburg (Germany), Toronto (Canada) and Vienna (Austria)] agreed to share their data, including baseline characteristics, technical ECMO and cannulation data as well as complications related to ECMO cannulation and outcome. RESULTS: A total of 20 patients received alternative DLC for respiratory failure. Cannula insertion sites included the left internal jugular vein (n = 5), the right (n = 7) or left (n = 3) subclavian vein and the right (n = 4) or left (n = 1) femoral vein. The median cannula size was 26 (19-28) French. The median initial target ECMO flow was 2.9 (1.8-3.1) l/min and corresponded with used cannula size and estimated cardiac output. No procedural complications were reported during cannulation and median ECMO runtime was 15 (9-22) days. Ten patients were successfully bridged to lung transplantation (n = 5) or lung recovery (n = 5). Ten patients died during or after ECMO support. CONCLUSIONS: Alternative venous access sites for single-site dual-lumen catheters are a safe and feasible option to provide veno-venous ECMO support to patients with inaccessible RIJV.

A Solution for Distal Femoral Occlusion After Venoarterial Extracorporeal Membrane Oxygenation Decannulation: Distal Femoral Access and Thrombectomy.

For patients on venoarterial extracorporeal membrane oxygenation support where ready-to-wean criteria are met, complications during the decannulation are quite common. Management of these complications can be challenging as many of the remaining standard arterial access sites are in use or had prior closure by a closure device. In this case report of a 70-year-old patient, explantation of the arterial cannula with the help of a vascular closure device led to thrombotic occlusion of the distal femoral artery. Here, we describe a step-by-step guide outlining our approach on management of this complication. Most relevantly, a distal femoral access via the superficial femoral artery was used, and thrombus aspiration was done with the help of the AngioJet peripheral thrombectomy system.

A Mortality Prediction Score for Patients With Veno-Venous Extracorporeal Membrane Oxygenation (VV-ECMO): The PREDICT VV-ECMO Score.

Mortality prediction for patients with the severe acute respiratory distress syndrome (ARDS) supported with veno-venous extracorporeal membrane oxygenation (VV-ECMO) is challenging. Clinical variables at baseline and on day 3 after initiation of ECMO support of all patients treated from October 2010 through April 2020 were analyzed. Multivariate logistic regression analysis was used to identify score variables. Internal and external (Monza, Italy) validation was used to evaluate the predictive value of the model. Overall, 272 patients could be included for data analysis and creation of the PREDICT VV-ECMO score. The score comprises five parameters (age, lung fibrosis, immunosuppression, cumulative fluid balance, and ECMO sweep gas flow on day 3). Higher score values are associated with a higher probability of hospital death. The score showed favorable results in derivation and external validation cohorts (area under the receiver operating curve, AUC derivation cohort 0.76 [95% confidence interval, CI, 0.71-0.82] and AUC validation cohort 0.74 [95% CI, 0.67-0.82]). Four risk classes were defined: I ≤ 30, II 31-60, III 61-90, and IV ≥ 91 with a predicted mortality of 28.2%, 56.2%, 84.8%, and 96.1%, respectively. The PREDICT VV-ECMO score suggests favorable performance in predicting hospital mortality under ongoing ECMO support providing a sound basis for further evaluation in larger cohorts.

The Effect of Cytokine Adsorption on Leukocyte and Platelet Activation after Extracorporeal Cardiopulmonary Resuscitation.

BACKGROUND: Post-cardiac arrest syndrome (PCAS) is a frequent complication following successful cardiopulmonary resuscitation and correlates with poor outcome. PCAS is characterized by an excessive inflammatory response to whole-body ischemia and reperfusion. Cytokine adsorption was suggested as an adjunctive treatment option for the removal of cytokines from the patients' blood to restore the physiological equilibrium of pro- and anti-inflammatory activity and thus mitigate hemodynamic instability and end-organ complications. MATERIAL AND METHODS: To better understand the cellular effects of cytokine adsorption in patients receiving extracorporeal cardiopulmonary resuscitation (ECPR) after in- and out-of-hospital cardiac arrest, we compared the activation status of neutrophils, monocytes, and platelets as well as the formation of platelet-leukocyte complexes in intravenous whole blood samples from an exploratory subgroup (n = 24) from the randomized CYTER study. RESULT: At 48 hours after initiation of ECPR, flow cytometry analyses did neither reveal significant differences in neutrophil (CD11b, CD66b, L-selectin, and PSGL-1) and monocyte (CD11b, L-selectin, and PSGL-1) surface molecule expression nor in circulating platelet-monocyte complexes between patients receiving cytokine adsorption and those without. CONCLUSION: Data did not show a relevant effect of cytokine adsorption on neutrophil and monocyte activation during the first 48 hours after initiation of ECPR.

Survival outcomes and mobilization during venovenous extracorporeal membrane oxygenation: a retrospective cohort study.

Introduction: Venovenous extracorporeal membrane oxygenation (V-V ECMO) can be considered in critically ill patient in severe pulmonary failure. However, the mobilization of patients on V-V ECMO can be challenging due to logistic and safety concerns. This study aimed to investigate whether 30 days survival was improved in patients who were mobilized during V-V ECMO support. Methods: We conducted a retrospective cohort all-comer study that included all patients cannulated for V-V ECMO at a single center. Patients with a V-V ECMO duration below 24 h were excluded from the analysis. The patients were grouped based on the ICU mobility scale documented during V-V ECMO support. The primary endpoint was 30 days survival, and secondary endpoints included weaning from ECMO and mechanical ventilation, as well as hospital survival. Results: A total of 343 patients were included in the study, with a median age of 56 years and 32% were female. Among them, 28% had chronic lung disease. The ICU mobilization scale ≥2 during ECMO was documented in 62/343 (18%) patients. There were no significant differences in age, gender and preexisting lung disease. Duration of ICU stay (13.1 vs. 15.6 days), time on ECMO (186 vs. 190 h) and mechanical ventilation (11.2 vs. 13.6 days) were slightly shorter in patients with ICU mobility scale <2 compared to those with ≥2 (all p = 0.0001). However, patients with ICU mobilization scale ≥2 showed significantly better 30 days survival (71.0 vs. 48.0%, OR 2.6 (1.5 to 4.8), p = 0.0012) compared to those with <2. In the ≥2 mobility scale group, a significantly higher number of patients were successfully weaned from the ventilator (61.3 vs. 46.6%, OR 1.8 (1.0 to 3.2), p = 0.049). A stronger correlation was observed between more intense mobilizations, such as being in a standing position (OR 5.0 (1.7 to 14.0), p = 0.0038), and higher 30 days survival. Conclusion: The findings of this study suggest that active mobilization during V-V ECMO support is associated with improved 30 days survival and successful weaning from the respirator. Incorporating mobilization as part of the therapeutic approach during ECMO support may offer potential benefits for critically ill patients.

Clinical covariates influencing clinical outcomes in primary membranous nephropathy.

BACKGROUND: Primary membranous nephropathy (PMN) frequently causes nephrotic syndrome and declining kidney function. Disease progression is likely modulated by patient-specific and therapy-associated factors awaiting characterization. These cofactors may facilitate identification of risk groups and could result in more individualized therapy recommendations. METHODS: In this single-center retrospective observational study, we analyze the effect of patient-specific and therapy-associated covariates on proteinuria, hypoalbuminemia, and estimated glomerular filtration rate (eGFR) in 74 patients diagnosed with antibody positive PMN and nephrotic-range proteinuria (urine-protein-creatinine-ratio [UPCR] ≥ 3.5 g/g), treated at the University of Freiburg Medical Center between January 2000 - November 2022. The primary endpoint was defined as time to proteinuria / serum-albumin response (UPCR ≤ 0.5 g/g or serum-albumin ≥ 3.5 g/dl), the secondary endpoint as time to permanent eGFR decline (≥ 40% relative to baseline). RESULTS: The primary endpoint was reached after 167 days. The secondary endpoint was reached after 2413 days. Multivariate time-to-event analyses showed significantly faster proteinuria / serum-albumin response for higher serum-albumin levels (HR 2.7 [95% CI: 1.5 - 4.8]) and cyclophosphamide treatment (HR 3.6 [95% CI: 1.3 - 10.3]). eGFR decline was significantly faster in subjects with old age at baseline (HR 1.04 [95% CI: 1 - 1.1]). CONCLUSION: High serum-albumin levels, and treatment with cyclophosphamide are associated with faster proteinuria reduction and/or serum-albumin normalization. Old age constitutes a risk factor for eGFR decline in subjects with PMN.

Dual lumen cannulation and mobilization of patients with venovenous extracorporeal membrane oxygenation.

BACKGROUND: Mobilization is important in longer courses in intensive care unit (ICU), typical for patients requiring venovenous extracorporeal membrane oxygenation (V-V ECMO). For patients supported with ECMO, especially out-of-bed mobilizations improve outcome. We hypothesized that utilization of a dual lumen cannula (DLC) for V-V ECMO would facilitate out-of-bed mobilization compared to single lumen cannulas (SLC). METHODS: Retrospective single center registry study including all V-V ECMO patients cannulated between 10/2010 and 05/2021 for respiratory failure. RESULTS: The registry included 355 V-V ECMO patients (median age 55.6 years, 31.8% female, 27.3% with preexisting pulmonary disease), 289/355 (81.4%) primary cannulated with DLC, and 66/355 (18.6%) using SLC. Both groups had similar pre-ECMO characteristics. The runtime of the first ECMO cannula was significantly longer in DLC compared to SLC (169 vs. 115 h, p = 0.015). The frequency of prone positioning during V-V ECMO was similar in both groups (38.4 vs. 34.8%, p = 0.673). There was no difference in in-bed mobilization (41.2 vs. 36.4%, for DLC and SLC, respectively, p = 0.491). Patients with DLC were more often mobilized out-of-bed (25.6 vs. 12.1%, OR 2.495 [95% CI 1.150 to 5.268], for DLC and SLC, respectively, p = 0.023). Hospital survival was similar in both groups (46.4 vs. 39.4%, for DLC and SLC, respectively, p = 0.339). CONCLUSION: Patients cannulated with a dual lumen cannula for V-V ECMO support were significantly more often mobilized out-of-bed. Since mobilization is important in prolonged ICU courses typical for ECMO patients, this might be an important benefit. Other benefits of DLC were the longer runtime of the initial cannula set and fewer suction events.

Identification of Covariates Modulating B-Cell Repopulation Kinetics in Subjects Receiving Rituximab Treatment.

OBJECTIVE: B-cell depletion using the anti-CD20 monoclonal antibody rituximab is a cornerstone in the therapeutic concept of multiple autoimmune diseases. B-cell depletion is associated with a higher risk for severe infections, and the time span of B-cell repopulation differs greatly between individuals. Data on factors influencing B-cell repopulation kinetics are limited. This study aims to identify patient-specific and therapy-associated covariates that modulate B-cell repopulation. METHODS: This single-center retrospective observational study presents data of 839 subjects receiving 2,017 courses of rituximab for autoimmune diseases. Assessed covariates are patient-specific factors (sex, age, kidney function, and underlying disease) and co-immunosuppression with common agents (azathioprine, cyclosporine A, cyclophosphamide, hydroxychloroquine, methotrexate, mycophenolate mofetil, tacrolimus, and corticosteroids). The primary end point is the time to B-cell repopulation (≥5/µl). The secondary end point is the time to B-cell reconstitution (≥50/µl). Multivariate time-to-event analysis and logistic regression models were applied to estimate the influence of covariates. RESULTS: Age over 60 years (hazard ratio [HR] 0.71 for repopulation, P = 0.008), impaired kidney function (HR 0.72, P = 0.001), antineutrophil cytoplasmic antibody-associated vasculitis (HR 0.61, P < 0.001), solid organ transplantation (HR 0.4, P < 0.001), and co-immunosuppression with corticosteroids (HR 0.64, P < 0.001) or azathioprine (HR 0.49, P < 0.001) were associated with impaired B-cell repopulation and reconstitution. Effects of corticosteroids (P = 0.043) and azathioprine (P = 0.025) were dose dependent. CONCLUSION: Prolonged rituximab dosing intervals may be effective to achieve B-cell depletion and reduce risk of infection in advanced age or patients with impaired kidney function. Co-medication with corticosteroids or azathioprine prolongs B-cell recovery, which may increase therapeutic effects but also the rate of adverse events.

Extracorporeal membrane oxygenation in adults receiving haematopoietic cell transplantation: an international expert statement.

Combined advances in haematopoietic cell transplantation (HCT) and intensive care management have improved the survival of patients with haematological malignancies admitted to the intensive care unit. In cases of refractory respiratory failure or refractory cardiac failure, these advances have led to a renewed interest in advanced life support therapies, such as extracorporeal membrane oxygenation (ECMO), previously considered inappropriate for these patients due to their poor prognosis. Given the scarcity of evidence-based guidelines on the use of ECMO in patients receiving HCT and the need to provide equitable and sustainable access to ECMO, the European Society of Intensive Care Medicine, the Extracorporeal Life Support Organization, and the International ECMO Network aimed to develop an expert consensus statement on the use of ECMO in adult patients receiving HCT. A steering committee with expertise in ECMO and HCT searched the literature for relevant articles on ECMO, HCT, and immune effector cell therapy, and developed opinion statements through discussions following a Quaker-based consensus approach. An international panel of experts was convened to vote on these expert opinion statements following the Research and Development/University of California, Los Angeles Appropriateness Method. The Appraisal of Guidelines for Research and Evaluation statement was followed to prepare this Position Paper. 36 statements were drafted by the steering committee, 33 of which reached strong agreement after the first voting round. The remaining three statements were discussed by all members of the steering committee and expert panel, and rephrased before an additional round of voting. At the conclusion of the process, 33 statements received strong agreement and three weak agreement. This Position Paper could help to guide intensivists and haematologists during the difficult decision-making process regarding ECMO candidacy in adult patients receiving HCT. The statements could also serve as a basis for future research focused on ECMO selection criteria and bedside management.