Purified granulocytes in extracorporeal cell therapy: A multifaceted approach to combat sepsis-induced immunoparalysis.

BACKGROUND: Immune cell dysfunction plays a central role in sepsis-induced immunoparalysis. Targeted treatment using healthy donor immune cell transfusions, particularly granulocyte concentrates (GC) potentially induces tissue damage. Initial trials using GC in an extracorporeal immune cell perfusion system provided evidence for beneficial effects with fewer side effects, by separating patient and donor immune cell compartments. A multicenter clinical trial is exploring feasibility and effects of a 6-h treatment (NCT06143137). This ex vivo study examines technical feasibility and cellular effects of an extended treatment interval up to 24 h. METHODS: Standard GC were purified to increase the potential storage time and subsequently implemented in the extracorporeal immune cell perfusion system. Parameters assessed included cell viability, phagocytosis activity, oxidative burst, cytokine release, and metabolic parameters of purified. GC during an extended circulation time of up to 24 h. RESULTS: After storage of 72 h granulocytes were viable throughout the study period and exhibited preserved functionality and metabolic activity. The findings highlight a time-dependent nature of cytokine release by neutrophils in the extracorporeal circuit, as cytokine secretion patterns showed IL-8 peaking within 6 h, while MCP-1, IL-6, IL-1ß, and TNF-α increased after 24 h of circulation. CONCLUSION: Purified GC remain functional after 72 h of storage and additional 24 h in the circulating treatment model. Cytokine secretion patterns revealed a significant increase, especially between 10 and 24 h of treatment. Extending treatment time holds promise for enhancing immune response against sepsis-induced immunoparalysis. These findings provide valuable insights for optimizing immune-targeted therapeutic interventions.

Increased impairment of cerebral autoregulation in COVID-19 associated pulmonary failure requiring extracorporeal membrane oxygenation.

Introduction: Cerebrovascular complications are feared but also commonly reported in patients with COVID-19 requiring extracorporeal membrane oxygenation (ECMO) support therapy. Besides other reasons, a connection between impaired cerebral autoregulation and SARS-CoV-2 infection as a mechanism for an increase in cerebrovascular complications has been hypothesized. Methods: In an observational single-center study, we investigated a cohort of 48 patients requiring veno-venous ECMO support therapy with (n = 31) and without SARS-CoV-2 infection (n = 17). Cerebral autoregulation was assessed with the cerebral oximetry-derived autoregulation index (ORx) based on a moving correlation between arterial pressure and cerebral oximetry. Results: Patients with ECMO support therapy and SARS-CoV-2 experienced more time with impaired cerebral autoregulation than without SARS-CoV-2 [17 ± 9 vs. 13 ± 9% (p = 0.027)]. Patients with SARS-CoV-2 suffering from cerebrovascular complications had more time with impaired autoregulation than non SARS-CoV-2 patients with these complications (19 ± 9 vs. 10 ± 4%, p = 0.032). Conclusion: Our results suggest a connection between SARS-CoV-2 and impaired cerebral autoregulation as well as cerebrovascular complications in SARS-CoV-2 patients.

Prevalence and prognostic relevance of invasive fungal disease during veno-arterial ECMO: A retrospective single-center study.

PURPOSE: To assess the prevalence and relevance of invasive fungal disease (IFD) during veno-arterial (V-A) extracorporeal membrane oxygenation (ECMO). METHODS: Retrospective analysis from January 2013 to November 2023 of adult V-A ECMO cases at a German University Hospital. Parameters relating to IFD, demographics, length of stay (LoS), days on ECMO and mechanical ventilation, prognostic scores and survival were assessed. Multivariable logistic regression analyses with IFD and death as dependent variables were performed. Outcome was assessed after propensity score matching IFD-patients to non-IFD-controls. RESULTS: 421 patients received V-A ECMO. 392 patients with full electronic datasets were included. The prevalence of IFD, invasive candidiasis and probable invasive pulmonary aspergillosis was 4.6%, 3.8% and 1.0%. Severity of acute disease, pre-existing moderate-to-severe renal disease and continuous kidney replacement therapy were predictive of IFD. In-hospital mortality (94% (17/18) compared to 67% (252/374) in non-IFD patients (p = 0.0156)) was predicted by female sex, SOFA score at admission, SAVE score and IFD (for IFD: OR: 8.31; CI: 1.60-153.18; p: 0.044). There was no difference in outcome after matching IFD-cases to non-IFD-controls. CONCLUSIONS: IFD are detected in about one in 20 patients on V-A ECMO, indicating mortality >90%. However, IFD do not contribute to prognosis in this population.

Analysis of Patients with Severe ARDS on VV ECMO Treated with Inhaled NO: A Retrospective Observational Study.

(1) Background: This retrospective study focused on severe acute respiratory distress syndrome (ARDS) patients treated with veno-venous (VV) extracorporeal membrane oxygenation (ECMO) and who inhaled nitric oxide (NO) for pulmonary arterial hypertension (PAH) and/or right ventricular failure (RV failure). (2) Methods: Out of 662 ECMO-supported patients, 366 received VV ECMO, including 48 who inhaled NO. We examined the NO's indications, dosing, duration, and the ability to lower PAH. We compared patients with and without inhaled NO in terms of mechanical ventilation duration, ECMO weaning, organ dysfunction, in-hospital mortality, and survival. (3) Results: Patients received 14.5 ± 5.5 ppm NO for 3 days with only one-third experiencing decreased pulmonary arterial pressure. They spent more time on VV ECMO, had a higher ECMO weaning failure frequency, and elevated severity scores (SAPS II and TIPS). A Kaplan-Meier analysis revealed reduced survival in the NO group. Multiple variable logistic regression indicated a twofold increased risk of death for ARDS patients on VV ECMO with NO. We observed no increase in continuous renal replacement therapy. (4) Conclusions: This study suggests that persistent PAH and/or RV failure is associated with poorer outcomes in severe ARDS patients on VV-ECMO, with an inhaled NO responder rate of only 30%, and it does not impact acute kidney failure rates.

Understanding the biases to sepsis surveillance and quality assurance caused by inaccurate coding in administrative health data.

PURPOSE: Timely and accurate data on the epidemiology of sepsis are essential to inform policy decisions and research priorities. We aimed to investigate the validity of inpatient administrative health data (IAHD) for surveillance and quality assurance of sepsis care. METHODS: We conducted a retrospective validation study in a disproportional stratified random sample of 10,334 inpatient cases of age ≥ 15 years treated in 2015-2017 in ten German hospitals. The accuracy of coding of sepsis and risk factors for mortality in IAHD was assessed compared to reference standard diagnoses obtained by a chart review. Hospital-level risk-adjusted mortality of sepsis as calculated from IAHD information was compared to mortality calculated from chart review information. RESULTS: ICD-coding of sepsis in IAHD showed high positive predictive value (76.9-85.7% depending on sepsis definition), but low sensitivity (26.8-38%), which led to an underestimation of sepsis incidence (1.4% vs. 3.3% for severe sepsis-1). Not naming sepsis in the chart was strongly associated with under-coding of sepsis. The frequency of correctly naming sepsis and ICD-coding of sepsis varied strongly between hospitals (range of sensitivity of naming: 29-71.7%, of ICD-diagnosis: 10.7-58.5%). Risk-adjusted mortality of sepsis per hospital calculated from coding in IAHD showed no substantial correlation to reference standard risk-adjusted mortality (r = 0.09). CONCLUSION: Due to the under-coding of sepsis in IAHD, previous epidemiological studies underestimated the burden of sepsis in Germany. There is a large variability between hospitals in accuracy of diagnosing and coding of sepsis. Therefore, IAHD alone is not suited to assess quality of sepsis care.

9-Month observational Dia-Vacc study of vaccine type influence on SARS-CoV-2 immunity in dialysis and kidney transplant patients.

BACKGROUND: SARS-CoV-2mRNA vaccination related seroconversion rates are reduced in dialysis and kidney transplant patients. METHODS: We evaluated nine months follow up data in our observational Dia-Vacc study exploring specific cellular (interferon-γ release assay) or/and humoral immune responses after 2x SARS-CoV-2mRNA vaccination in 880 participants including healthy medical personnel (125-MP), dialysis patients (595-DP), kidney transplant recipients (111-KTR), and apheresis patients (49-AP) with positive seroconversion (de novo IgA or IgG antibody positivity by ELISA) after eight weeks. FINDINGS: Nine months after first vaccination, receptor binding domain (RBD) antibodies were still positive in 90 % of MP, 86 % of AP, but only 55 %/48 % of DP/KTR, respectively. Seroconversion remained positive in 100 % of AP and 99·2 % of MP, but 86 %/81 % of DP/KTR, respectively. Compared to MP, DP but not KTR or AP were at risk for a strong RBD decline, while KTR kept lowest RBD values over time. By multivariate analysis, BNT162b2mRNA versus 1273-mRNA vaccine type was an independent risk factor for a strong decline of RBD antibodies. Within the DP group, only time on dialysis was another (inverse) risk factor for the DP group. Compared to humoral immunity, T-cell immunity decline was less prominent. INTERPRETATION: While seroconverted KTR reach lowest RBD values over time, DP are at specific risk for a strong decline of RBD antibodies after successful SARS-CoV-2mRNA vaccination, which also depends on the vaccine type being used. Therefore, booster vaccinations for DP should be considered earlier compared to normal population.

Functional intervention following cardiac surgery to prevent postoperative delirium in older patients (FEEL WELL study).

BACKGROUND: Postoperative delirium is a common complication in patients after cardiac surgery, especially in older patients, and can manifest as a disturbance of attention and consciousness. It can lead to increased postoperative morbidity, prolonged need for care, and mortality. The presented study investigates whether the occurrence of postoperative delirium after cardiac surgery can be prevented by a multisensory stimulation. It was conducted as a prospective, randomized, controlled, non-pharmacological intervention study in the years 2021 and 2022 at the University Hospital Bonn in Germany. A total of 186 patients over 65 years with elective cardiac surgery were enrolled. Patients were randomized either to the intervention or control group. In both groups, postoperative delirium was assessed with the 3-min diagnostic interview for confusion assessment method on the first 5 days after surgery and pain was assessed using the Numeric Rating Scale. Multisensory stimulation was performed 20 min a day for the first three postoperative days in the intervention group. RESULTS: The incidence of postoperative delirium was 22.6% in the intervention group and 49.5% in the control group (p < 0.001). Duration of postoperative delirium was significantly shorter in the intervention group (p < 0.001). Stay in the intensive care unit was significantly longer in the control group (p = 0.006). In the regression model non-intervention, high pain scores, advanced age, and prolonged mechanical ventilation were associated with postoperative delirium (p = 0.007; p = 0.032; p = 0.006; p = 0.006, respectively). CONCLUSIONS: Results of the study imply that a multisensory stimulation done on the first 3 days after planned cardiac surgery can reduce the incidence and duration of postoperative delirium in older patients. Influence of the treatment on the incidence of delirium in other patient groups, the length of stay in the intensive care unit, and patients´ postoperative pain should be confirmed in further clinical studies. TRIAL REGISTRATION: DRKS, DRKS00026909. Registered 28 October 2021, Retrospectively registered, https://drks.de/search/de/trial/DRKS00026909 .

Lung Ultrasound in Predicting Outcomes in Patients with COVID-19 Treated with Extracorporeal Membrane Oxygenation.

Pulmonary involvement due to SARS-CoV-2 infection can lead to acute respiratory distress syndrome in patients with COVID-19. Consequently, pulmonary imaging is crucial for management of COVID-19. This study aimed to evaluate the prognostic value of lung ultrasound (LUS) with a handheld ultrasound device (HHUD) in patients with COVID-19 treated with extracorporeal membrane oxygenation (ECMO). Therefore, patients underwent LUS with a HHUD every two days until they were either discharged from the intensive care unit or died. The study was conducted at the University Hospital of Bonn's anesthesiological intensive care ward from December 2020 to August 2021. A total of 33 patients (median [IQR]: 56.0 [53-60.5] years) were included. A high LUS score was associated with a decreased P/F ratio (repeated measures correlation [rmcorr]: -0.26; 95% CI: -0.34, -0.15; p < 0.001), increased extravascular lung water, defined as fluid accumulation in the pulmonary interstitium and alveoli (rmcorr: 0.11; 95% CI: 0.01, 0.20; p = 0.030), deteriorated electrolyte status (base excess: rmcorr: 0.14; 95% CI: 0.05, 0.24; p = 0.004; pH: rmcorr: 0.12; 95% CI: 0.03, 0.21; p = 0.001), and decreased pulmonary compliance (rmcorr: -0.10; 95% CI: -0.20, -0.01; p = 0.034). The maximum LUS score was lower in survivors (median difference [md]: -0.35; 95% CI: -0.55, -0.06; p = 0.006). A cutoff value for non-survival was calculated at a LUS score of 2.63. At the time of maximum LUS score, P/F ratio (md: 1.97; 95% CI: 1.12, 2.76; p < 0.001) and pulmonary compliance (md: 18.67; 95% CI: 3.33, 37.15; p = 0.018) were higher in surviving patients. In conclusion, LUS with a HHUD enables continuous evaluation of cardiopulmonary function in COVID-19 patients receiving ECMO support therapy and provides prognostic value in determining the patients' likelihood of survival.

Exploring Albumin Functionality Assays: A Pilot Study on Sepsis Evaluation in Intensive Care Medicine.

Human serum albumin (HSA) as the most abundant plasma protein carries multifunctional properties. A major determinant of the efficacy of albumin relies on its potent binding capacity for toxins and pharmaceutical agents. Albumin binding is impaired in pathological conditions, affecting its function as a molecular scavenger. Limited knowledge is available on the functional properties of albumin in critically ill patients with sepsis or septic shock. A prospective, non-interventional clinical trial assessed blood samples from 26 intensive care patients. Albumin-binding capacity (ABiC) was determined by quantifying the unbound fraction of the fluorescent marker, dansyl sarcosine. Electron paramagnetic resonance fatty acid spin-probe evaluated albumin's binding and detoxification efficiencies. Binding efficiency (BE) reflects the strength and amount of bound fatty acids, and detoxification efficiency (DTE) indicates the molecular flexibility of patient albumin. ABiC, BE, and DTE effectively differentiated control patients from those with sepsis or septic shock (AUROC > 0.8). The diagnostic performance of BE showed similarities to procalcitonin. Albumin functionality correlates with parameters for inflammation, hepatic, or renal insufficiency. Albumin-binding function was significantly reduced in critically ill patients with sepsis or septic shock. These findings may help develop patient-specific algorithms for new diagnostic and therapeutic approaches.

COVID-19 Is an Independent Risk Factor for Detrimental Invasive Fungal Disease in Patients on Veno-Venous Extracorporeal Membrane Oxygenation: A Retrospective Study.

Invasive fungal disease (IFD) is associated with the mortality of patients on extracorporeal membrane oxygenation (ECMO). Several risk factors for IFD have been identified in patients with or without ECMO. Here, we assessed the relevance of coronavirus disease (COVID-19) for the occurrence of IFD in patients on veno-venous (V-V) ECMO for respiratory failure. In a retrospective analysis of all ECMO cases between January 2013 and December 2022 (2020-2022 for COVID-19 patients), active COVID-19 and the type, timing and duration of IFD were investigated. Demographics, hospital, ICU length of stay (LoS), duration of ECMO, days on invasive mechanical ventilation, prognostic scores (Respiratory ECMO Survival Prediction (RESP) score, Charlson Comorbidity Index (CCI), Therapeutic Intervention Scoring System (TISS)-10, Sequential Organ Failure Assessment (SOFA) score and Simplified Acute Physiology Score (SAPS)-II) and length of survival were assessed. The association of COVID-19 with IFD was investigated using propensity score matching and uni- and multivariable logistic regression analyses. We identified 814 patients supported with ECMO, and 452 patients were included in further analyses. The incidence of IFD was 4.8% and 11.0% in patients without and with COVID-19, respectively. COVID-19 status represented an independent risk factor for IFD (OR 4.30; CI 1.72-10.85; p: 0.002; multivariable regression analysis). In patients with COVID-19, 84.6% of IFD was candidemia and 15.4% represented invasive aspergillosis (IA). All of these patients died. In patients on V-V ECMO, we report that COVID-19 is an independent risk factor for IFD, which is associated with a detrimental prognosis. Further studies are needed to investigate strategies of antifungal therapy or prophylaxis in these patients.

Cardiovascular Magnetic Resonance in Survivors of Critical Illness: Cardiac Abnormalities Are Associated With Acute Kidney Injury.

Background The objective of this study was to investigate cardiac abnormalities in intensive care unit (ICU) survivors of critical illness and to determine whether temporary acute kidney injury (AKI) is associated with more pronounced findings on cardiovascular magnetic resonance. Methods and Results There were 2175 patients treated in the ICU (from 2015 until 2021) due to critical illness who were screened for study eligibility. Post-ICU patients without known cardiac disease were prospectively recruited from March 2021 to May 2022. Participants underwent cardiovascular magnetic resonance including assessment of cardiac function, myocardial edema, late gadolinium enhancement, and mapping including extracellular volume fraction. Student t test, Mann-Whitney U test, and χ2 tests were used. There were 48 ICU survivors (46±15 years of age, 28 men, 29 with AKI and continuous kidney replacement therapy, and 19 without AKI) and 20 healthy controls who were included. ICU survivors had elevated markers of myocardial fibrosis (T1: 995±31 ms versus 957±21 ms, P<0.001; extracellular volume fraction: 24.9±2.5% versus 22.8±1.2%, P<0.001; late gadolinium enhancement: 1% [0%-3%] versus 0% [0%-0%], P<0.001), more frequent focal late gadolinium enhancement lesions (21% versus 0%, P=0.03), and an impaired left ventricular function (eg, ejection fraction: 57±6% versus 60±5%, P=0.03; systolic longitudinal strain: 20.3±3.7% versus 23.1±3.5%, P=0.004) compared with healthy controls. ICU survivors with AKI had higher myocardial T1 (1002±33 ms versus 983±21 ms; P=0.046) and extracellular volume fraction values (25.6±2.6% versus 23.9±1.9%; P=0.02) compared with participants without AKI. Conclusions ICU survivors of critical illness without previously diagnosed cardiac disease had distinct abnormalities on cardiovascular magnetic resonance including signs of myocardial fibrosis and systolic dysfunction. Findings were more abnormal in participants who experienced AKI with necessity of continuous kidney replacement therapy during their ICU stay. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT05034588.

Monitoring of Cerebral Oxygen Saturation in Interhospital Transport of Patients Receiving Extracorporeal Membrane Oxygenation.

Extracorporeal membrane oxygenation (ECMO) in acute respiratory distress syndrome (ARDS) is used to achieve oxygenation and protect lung ventilation. Near infrared spectroscopy (NIRS) measures cerebral regional tissue oxygenation (rSO 2 ) and may contribute to patient safety during interhospital transport under ECMO support. We evaluated 16 adult ARDS patients undergoing interhospital ECMO transport by measuring cerebral rSO 2 before and after initiation of ECMO support and continuously during transport. To compare peripheral oxygen saturation (SpO 2 ) measurement with rSO 2 , both parameters were analyzed. NIRS monitoring for initiation of ECMO and interhospital transport under ECMO support was feasible, and there was no significant difference in the percentage of achievable valid measurements over time between cerebral rSO 2 (88.4% [95% confidence interval {CI}, 81.3-95.0%]) and standard SpO 2 monitoring 91.7% (95% CI, 86.1-94.2%), p = 0.68. No change in cerebral rSO 2 was observed before 77% (73.5-81%) (median [interquartile range {IQR}]) and after initiation of ECMO support 78% (75-81%), p = 0.2. NIRS for cerebral rSO 2 measurement is feasible during ECMO initiation and interhospital transport. Achievement of valid measurements of cerebral rSO 2 was not superior to SpO 2 . In distinct patients ( e.g. , shock), measurement of cerebral rSO 2 may contribute to improvement of patient safety during interhospital ECMO transport.

Be Patient: Prolonged Extracorporeal Membrane Oxygenation Support Including Full System Switch With Favorable Outcome.

Despite tremendous advances in treatment, acute respiratory distress syndrome (ARDS) remains a disease with high mortality (42-48%). Veno-venous extracorporeal membrane oxygenation (VV-ECMO) is often used as a last treatment option, which poses complex problems for the treatment team, especially with prolonged ECMO support. We report an interesting case of a 40-year-old female patient who developed influenza pneumonia leading to ARDS and subsequently requiring ECMO. Due to severe clotting complications, a prolonged ECMO run time with numerous filter changes was required. After a total of 56 days of ECMO therapy, the patient was successfully weaned. Fortunately, further in the course of treatment, complete recovery with restitutio ad integrum was achieved. A distinguishing feature of this case report is the description of a complete ECMO system change and the concurrent use of two ECMO systems for the same patient. Additionally, we provide data on the patient's current health-related quality of life as measured using the World Health Organization Disability Assessment Schedule 2.0.

Outcomes of patients with acute respiratory failure on veno-venous extracorporeal membrane oxygenation requiring additional circulatory support by veno-venoarterial extracorporeal membrane oxygenation.

Objective: Veno-venous (V-V) extracorporeal membrane oxygenation (ECMO) is increasingly used to support patients with severe acute respiratory distress syndrome (ARDS). In case of additional cardio-circulatory failure, some experienced centers upgrade the V-V ECMO with an additional arterial return cannula (termed V-VA ECMO). Here we analyzed short- and long-term outcome together with potential predictors of mortality. Design: Multicenter, retrospective analysis between January 2008 and September 2021. Setting: Three tertiary care ECMO centers in Germany (Hannover, Bonn) and Switzerland (Zurich). Patients: Seventy-three V-V ECMO patients with ARDS and additional acute cardio-circulatory deterioration required an upgrade to V-VA ECMO were included in this study. Measurements and main results: Fifty-three patients required an upgrade from V-V to V-VA and 20 patients were directly triple cannulated. Median (Interquartile Range) age was 49 (28-57) years and SOFA score was 14 (12-17) at V-VA ECMO upgrade. Vasoactive-inotropic score decreased from 53 (12-123) at V-VA ECMO upgrade to 9 (3-37) after 24 h of V-VA ECMO support. Weaning from V-VA and V-V ECMO was successful in 47 (64%) and 40 (55%) patients, respectively. Duration of ECMO support was 12 (6-22) days and ICU length of stay was 32 (16-46) days. Overall ICU mortality was 48% and hospital mortality 51%. Two additional patients died after hospital discharge while the remaining patients survived up to two years (with six patients being lost to follow-up). The vast majority of patients was free from higher degree persistent organ dysfunction at follow-up. A SOFA score > 14 and higher lactate concentrations at the day of V-VA upgrade were independent predictors of mortality in the multivariate regression analysis. Conclusion: In this analysis, the use of V-VA ECMO in patients with ARDS and concomitant cardiocirculatory failure was associated with a hospital survival of about 50%, and most of these patients survived up to 2 years. A SOFA score > 14 and elevated lactate levels at the day of V-VA upgrade predict unfavorable outcome.

Thromboprophylaxis with argatroban in critically ill patients with sepsis: a review.

During sepsis, an initial prothrombotic shift takes place, in which coagulatory acute-phase proteins are increased, while anticoagulatory factors and platelet count decrease. Further on, the fibrinolytic system becomes impaired, which contributes to disease severity. At a later stage in sepsis, coagulation factors may become depleted, and sepsis patients may shift into a hypo-coagulable state with an increased bleeding risk. During the pro-coagulatory shift, critically ill patients have an increased thrombosis risk that ranges from developing micro-thromboses that impair organ function to life-threatening thromboembolic events. Here, thrombin plays a key role in coagulation as well as in inflammation. For thromboprophylaxis, low molecular weight heparins (LMWH) and unfractionated heparins (UFHs) are recommended. Nevertheless, there are conditions such as heparin resistance or heparin-induced thrombocytopenia (HIT), wherein heparin becomes ineffective or even puts the patient at an increased prothrombotic risk. In these cases, argatroban, a direct thrombin inhibitor (DTI), might be a potential alternative anticoagulatory strategy. Yet, caution is advised with regard to dosing of argatroban especially in sepsis. Therefore, the starting dose of argatroban is recommended to be low and should be titrated to the targeted anticoagulation level and be closely monitored in the further course of treatment. The authors of this review recommend using DTIs such as argatroban as an alternative anticoagulant in critically ill patients suffering from sepsis or COVID-19 with suspected or confirmed HIT, HIT-like conditions, impaired fibrinolysis, in patients on extracorporeal circuits and patients with heparin resistance, when closely monitored.

Risk of strong antibody decline in dialysis and transplant patients after SARS-CoV-2mRNA vaccination: Six months data from the observational Dia-Vacc study.

Background: Vulnerable dialysis and kidney transplant patients show impaired seroconversion rates compared to medical personnel eight weeks after SARS-CoV-2mRNA vaccination. Methods: We evaluated six months follow up data in our observational Dia-Vacc study exploring specific cellular (interferon-γ release assay) or/and humoral immune responses after 2x SARS-CoV-2mRNA vaccination in 1205 participants including medical personnel (125 MP), dialysis patients (970 DP) and kidney transplant recipients (110 KTR) with seroconversion (de novo IgA or IgG antibody positivity by ELISA) after eight weeks. Findings: Six months after vaccination, seroconversion remained positive in 98% of MP, but 91%/87% of DP/KTR (p = 0·005), respectively. Receptor binding domain-IgG (RBD-IgG) antibodies were positive in 98% of MP, but only 68%/57% of DP/KTR (p < 0·001), respectively. Compared to MP, DP and KTR were at risk for a strong IgG or RBD-IgG decline (p < 0·001). Within the DP but not KTR group male gender, peritoneal dialysis, short time on dialysis, BNT162b2mRNA vaccine, immunosuppressive drug use and diabetes mellitus were independent risk factors for a strong decline of IgG or RBD antibodies. The percentage of cellular immunity decline was similar in all groups. Interpretation: Both vulnerable DP and KTR groups are at risk for a strong decline for IgG and RBD antibodies. In KTR, antibody titres peak at a markedly lower level and accelerated antibody decline is mixed with a delayed/increasing IgG, RBD-IgG, or cellular immune response in a 16% fraction of patients. In both populations, immune monitoring should be used for early timing of additional booster vaccinations. Funding: This study was funded by the Else Kröner Fresenius Stiftung, Bad Homburg v. d. H., grant number Fördervertrag EKFS 2021_EKSE.27.

Impact of Invasive Fungal Diseases on Survival under Veno-Venous Extracorporeal Membrane Oxygenation for ARDS.

OBJECTIVE: To assess the incidence and significance of invasive fungal diseases (IFD) during veno-venous (VV) ECMO support for acute respiratory distress syndrome (ARDS). METHODS: Retrospective analysis from January 2013 to April 2021 of all ECMO cases for ARDS at a German University Hospital. In patients with IFD (IFD patients), type of IFD, time of IFD, choice of antifungal agent, duration, and success of therapy were investigated. For comparison, patients without IFD (non-IFD patients) were selected by propensity score matching using treatment-independent variables (age, gender, height, weight, and the Sequential Organ Failure Assessment (SOFA) score at ICU admission). Demographics, hospital and ICU length of stay, duration of ECMO therapy, days on mechanical ventilation, prognostic scores (Charlson Comorbidity Index (CCI), Therapeutic Intervention Scoring System (TISS), and length of survival were assessed. RESULTS: A total of 646 patients received ECMO, 368 patients received VV ECMO. The incidence of IFD on VV ECMO was 5.98%, with 5.43% for Candida bloodstream infections (CBSI) and 0.54% for invasive aspergillosis (IA). In IFD patients, in-hospital mortality was 81.8% versus 40.9% in non-IFD patients. The hazard ratio for death was 2.5 (CI 1.1-5.4; p: 0.023) with IFD. CONCLUSIONS: In patients on VV ECMO for ARDS, about one in 17 contracts an IFD, with a detrimental impact on prognosis. Further studies are needed to address challenges in the diagnosis and treatment of IFD in this population.

Veno-venous extracorporeal membrane oxygenation (vv-ECMO) for severe respiratory failure in adult cancer patients: a retrospective multicenter analysis.

PURPOSE: The question of whether cancer patients with severe respiratory failure benefit from veno-venous extracorporeal membrane oxygenation (vv-ECMO) remains unanswered. We, therefore, analyzed clinical characteristics and outcomes of a large cohort of cancer patients treated with vv-ECMO with the aim to identify prognostic factors. METHODS: 297 cancer patients from 19 German and Austrian hospitals who underwent vv-ECMO between 2009 and 2019 were retrospectively analyzed. A multivariable cox proportional hazards analysis for overall survival was performed. In addition, a propensity score-matched analysis and a latent class analysis were conducted. RESULTS: Patients had a median age of 56 (IQR 44-65) years and 214 (72%) were males. 159 (54%) had a solid tumor and 138 (47%) a hematologic malignancy. The 60-day overall survival rate was 26.8% (95% CI 22.1-32.4%). Low platelet count (HR 0.997, 95% CI 0.996-0.999; p = 0.0001 per 1000 platelets/µl), elevated lactate levels (HR 1.048, 95% CI 1.012-1.084; p = 0.0077), and disease status (progressive disease [HR 1.871, 95% CI 1.081-3.238; p = 0.0253], newly diagnosed [HR 1.571, 95% CI 1.044-2.364; p = 0.0304]) were independent adverse prognostic factors for overall survival. A propensity score-matched analysis with patients who did not receive ECMO treatment showed no significant survival advantage for treatment with ECMO. CONCLUSION: The overall survival of cancer patients who require vv-ECMO is poor. This study shows that the value of vv-ECMO in cancer patients with respiratory failure is still unclear and further research is needed. The risk factors identified in the present analysis may help to better select patients who may benefit from vv-ECMO.

Intracranial Hemorrhages on Extracorporeal Membrane Oxygenation: Differences Between COVID-19 and Other Viral Acute Respiratory Distress Syndrome.

OBJECTIVES: Extracorporeal membrane oxygenation (ECMO) is a potentially lifesaving procedure in acute respiratory distress syndrome (ARDS) due to COVID-19. Previous studies have shown a high prevalence of clinically silent cerebral microbleeds in patients with COVID-19. Based on this fact, together with the hemotrauma and the requirement of therapeutic anticoagulation on ECMO support, we hypothesized an increased risk of intracranial hemorrhages (ICHs). We analyzed ICH occurrence rate, circumstances and clinical outcome in patients that received ECMO support due to COVID-19-induced ARDS in comparison to viral non-COVID-19-induced ARDS intracerebral hemorrhage. DESIGN: Multicenter, retrospective analysis between January 2010 and May 2021. SETTING: Three tertiary care ECMO centers in Germany and Switzerland. PATIENTS: Two-hundred ten ARDS patients on ECMO support (COVID-19, n = 142 vs viral non-COVID, n = 68). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Evaluation of ICH occurrence rate, parameters of coagulation and anticoagulation strategies, inflammation, and ICU survival. COVID-19 and non-COVID-19 ARDS patients showed comparable disease severity regarding Sequential Organ Failure Assessment score, while the oxygenation index before ECMO cannulation was higher in the COVID group (82 vs 65 mm Hg). Overall, ICH of any severity occurred in 29 of 142 COVID-19 patients (20%) versus four of 68 patients in the control ECMO group (6%). Fifteen of those 29 ICH events in the COVID-19 group were classified as major (52%) including nine fatal cases (9/29, 31%). In the control group, there was only one major ICH event (1/4, 25%). The adjusted subhazard ratio for the occurrence of an ICH in the COVID-19 group was 5.82 (97.5% CI, 1.9-17.8; p = 0.002). The overall ICU mortality in the presence of ICH of any severity was 88%. CONCLUSIONS: This retrospective multicenter analysis showed a six-fold increased adjusted risk for ICH and a 3.5-fold increased incidence of ICH in COVID-19 patients on ECMO. Prospective studies are needed to confirm this observation and to determine whether the bleeding risk can be reduced by adjusting anticoagulation strategies.