Refractory circulatory failure in COVID-19 patients treated with veno-arterial ECMO a retrospective single-center experience

Objective In this retrospective case series, survival rates in different indications for veno-arterial extracorporeal membrane oxygenation (VA-ECMO) and differential diagnoses of COVID-19 associated refractory circulatory failure are investigated. Methods Retrospective analysis of 28 consecutive COVID-19 patients requiring VA-ECMO. All VA-ECMO’s were cannulated peripherally, using a femoro-femoral cannulation. Results At VA-ECMO initiation, median age was 57 years (IQR: 51–62), SOFA score 16 (IQR: 13–17) and norepinephrine dosing 0.53μg/kg/min (IQR: 0.35–0.87). Virus-variants were: 61% wild-type, 14% Alpha, 18% Delta and 7% Omicron. Indications for VA-ECMO support were pulmonary embolism (PE) (n = 5, survival 80%), right heart failure due to secondary pulmonary hypertension (n = 5, survival 20%), cardiac arrest (n = 4, survival 25%), acute heart failure (AHF) (n = 10, survival 40%) and refractory vasoplegia (n = 4, survival 0%). Among the patients with AHF, 4 patients suffered from COVID-19 associated heart failure (CovHF) (survival 100%) and 6 patients from sepsis associated heart failure (SHF) (survival 0%). Main Complications were acute kidney injury (AKI) 93%, renal replacement therapy was needed in 79%, intracranial hemorrhage occurred in 18%. Overall survival to hospital discharge was 39%. Conclusion Survival on VA-ECMO in COVID-19 depends on VA-ECMO indication, which should be considered in further studies and clinical decision making. A subgroup of patients suffers from acute heart failure due to inflammation, which has to be differentiated into septic or COVID-19 associated. Novel biomarkers are required to ensure reliable differentiation between these entities; a candidate might be soluble interleukin 2 receptor

Full-Length L1CAM and Not Its Δ2Δ27 Splice Variant Promotes Metastasis through Induction of Gelatinase Expression

Tumour-specific splicing is known to contribute to cancer progression. In the case of the L1 cell adhesion molecule (L1CAM), which is expressed in many human tumours and often linked to bad prognosis, alternative splicing results in a full-length form (FL-L1CAM) and a splice variant lacking exons 2 and 27 (SV-L1CAM). It has not been elucidated so far whether SV-L1CAM, classically considered as tumour-associated, or whether FL-L1CAM is the metastasis-promoting isoform. Here, we show that both variants were expressed in human ovarian carcinoma and that exposure of tumour cells to pro-metastatic factors led to an exclusive increase of FL-L1CAM expression. Selective overexpression of one isoform in different tumour cells revealed that only FL-L1CAM promoted experimental lung and/or liver metastasis in mice. In addition, metastasis formation upon up-regulation of FL-L1CAM correlated with increased invasive potential and elevated Matrix metalloproteinase (MMP)-2 and -9 expression and activity in vitro as well as enhanced gelatinolytic activity in vivo. In conclusion, we identified FL-L1CAM as the metastasis-promoting isoform, thereby exemplifying that high expression of a so-called tumour-associated variant, here SV-L1CAM, is not per se equivalent to a decisive role of this isoform in tumour progression

Comparative analysis of different transection techniques in minor and major hepatic resections

Die Leberchirurgie gehört bis heute zu den anspruchsvollsten Feldern der Chirurgie. Der Wahl der optimalen Operationstechnik kommt hierbei eine besondere Bedeutung für das Outcome des Patienten zu. Ziel dieser unizentrisch angelegten Analyse war es daher auf Basis einer möglichst großen Datenbasis Hinweise für die optimale Resektionstechnik bieten zu können. Dazu wurden in den Jahren 2007 bis 2012 insgesamt 562 Fälle prospektiv erfasst und analysiert. Hierbei zeigte sich ein statistisch signifikanter Vorteil von Minor-Leberresektionen von < 3 Segmenten gegenüber ausgedehnteren Leberresektionen. So lag die Gesamtmorbidität bei den Major-Resektionen bei 49,5 % gegenüber 25,7 % bei den Minor-Resektionen. Die Mortalität war ebenfalls in der Gruppe der Major-Resektionen höher, jedoch ohne statistisch signifikanten Effekt. Auch hinsichtlich Dauer des Intensivaufenthaltes und Transfusionsbedarf waren die Minor-Resektionen überlegen. Sowohl in der Subgruppe der Minor-, wie auch bei den Major-Leberresektionen zeigte sich jedoch kein statistisch signifikanter Vorteil für eine der angewandten Leberresektions-Techniken. Dennoch kann man feststellen, dass Minor-Leberresektionen ohne Mortalität und mit nur geringer Morbidität mit Elektrokauterisation durchgeführt werden können. Die Waterjet-Technik kann für Major- und Minor-Leberresektionen als zuverlässige Methode empfohlen werden. In unserer Kosten-Effektivitäts-Analyse konnten wir zeigen, dass die Stapler-Methode ökonomisch unterlegen ist. Wenn nach sorgfältiger Abwägung die zusätzlichen Kosten angemessen erscheinen, kann eine Stapler-Leberresektion dennoch empfehlenswert sein. Abschließend bleibt jedoch festzuhalten, dass die optimale Resektionstechnik stark vom Operateur und dessen Präferenzen, sowie seiner persönlichen Expertise mit dieser Methode abhängig ist.  In liver surgery different transection techniques are available without clear evidence regarding indication and advantage for each technique. The aim of this study was to identify the most superior liver transection technique between the different techniques (stapler, water-jet and electrocautery). Comparative analyses were performed for minor and major hepatectomies. Methods: In a single-center study, all liver resections performed between July 2007 and July 2012 were prospectively recorded and analysed. Results: 366 liver resections were included according to predefined eligibility criteria. No clear benefit for one particular technique in minor or major hepatectomy could be shown. Costeffectiveness analysis revealed disadvantages for stapler-hepatectomies. However, minor hepatectomies were performed with significantly lower morbidity (p < 0.001), lower operating time (p < 0.001), fewer need of transfusion (p < 0.0001) and shorter ICU stay (p < 0.001) than major hepatectomies. Conclusions: If possible, minor hepatectomies should be chosen. Competing techniques, selected according to surgeon’s preference, revealed no significant differences in primary outcome measures

Comparative analysis of different transection techniques in minor and major hepatic resections

Die Leberchirurgie gehört bis heute zu den anspruchsvollsten Feldern der Chirurgie. Der Wahl der optimalen Operationstechnik kommt hierbei eine besondere Bedeutung für das Outcome des Patienten zu. Ziel dieser unizentrisch angelegten Analyse war es daher auf Basis einer möglichst großen Datenbasis Hinweise für die optimale Resektionstechnik bieten zu können. Dazu wurden in den Jahren 2007 bis 2012 insgesamt 562 Fälle prospektiv erfasst und analysiert. Hierbei zeigte sich ein statistisch signifikanter Vorteil von Minor-Leberresektionen von < 3 Segmenten gegenüber ausgedehnteren Leberresektionen. So lag die Gesamtmorbidität bei den Major-Resektionen bei 49,5 % gegenüber 25,7 % bei den Minor-Resektionen. Die Mortalität war ebenfalls in der Gruppe der Major-Resektionen höher, jedoch ohne statistisch signifikanten Effekt. Auch hinsichtlich Dauer des Intensivaufenthaltes und Transfusionsbedarf waren die Minor-Resektionen überlegen. Sowohl in der Subgruppe der Minor-, wie auch bei den Major-Leberresektionen zeigte sich jedoch kein statistisch signifikanter Vorteil für eine der angewandten Leberresektions-Techniken. Dennoch kann man feststellen, dass Minor-Leberresektionen ohne Mortalität und mit nur geringer Morbidität mit Elektrokauterisation durchgeführt werden können. Die Waterjet-Technik kann für Major- und Minor-Leberresektionen als zuverlässige Methode empfohlen werden. In unserer Kosten-Effektivitäts-Analyse konnten wir zeigen, dass die Stapler-Methode ökonomisch unterlegen ist. Wenn nach sorgfältiger Abwägung die zusätzlichen Kosten angemessen erscheinen, kann eine Stapler-Leberresektion dennoch empfehlenswert sein. Abschließend bleibt jedoch festzuhalten, dass die optimale Resektionstechnik stark vom Operateur und dessen Präferenzen, sowie seiner persönlichen Expertise mit dieser Methode abhängig ist.  In liver surgery different transection techniques are available without clear evidence regarding indication and advantage for each technique. The aim of this study was to identify the most superior liver transection technique between the different techniques (stapler, water-jet and electrocautery). Comparative analyses were performed for minor and major hepatectomies. Methods: In a single-center study, all liver resections performed between July 2007 and July 2012 were prospectively recorded and analysed. Results: 366 liver resections were included according to predefined eligibility criteria. No clear benefit for one particular technique in minor or major hepatectomy could be shown. Costeffectiveness analysis revealed disadvantages for stapler-hepatectomies. However, minor hepatectomies were performed with significantly lower morbidity (p < 0.001), lower operating time (p < 0.001), fewer need of transfusion (p < 0.0001) and shorter ICU stay (p < 0.001) than major hepatectomies. Conclusions: If possible, minor hepatectomies should be chosen. Competing techniques, selected according to surgeon’s preference, revealed no significant differences in primary outcome measures

Does cerebral near‐infrared spectroscopy (NIRS) help to predict futile cannulation in extracorporeal cardiopulmonary resuscitation (ECPR)?

Aim of the study: Extracorporeal cardiopulmonary resuscitation (ECPR) is an evolving technique to improve cardiopulmonary resuscitation (CPR) outcomes. Identifying a readily available tool helpful for predicting patient's outcome is warranted. The aim of the study was to evaluate the capability of cranial near-infrared spectroscopy (cNIRS) to identify non-survivors or patients with unfavorable neurologic outcome prior to cannulation for ECPR to avoid futile cannulations. Methods: Retrospective analysis (2015-2021) of 97 patients requiring ECPR due to cardiac arrest with prior cNIRS measurement, which was performed immediately after ECPR team arrived on scene. Lowest possible regional cerebral oxygen saturation (rSO(2)) is 15%. Results: Mortality was 72.1% (70/97). Survivors showed in 88.9% (24/27) good neurological outcome (Cerebral Performance Category (CPC) 1 + 2). rSO(2) = 15% (11/97) prior to cannulation was only found in non-survivors. Among survivors, initial rSO(2) was not associated with neurological outcome. Non-shockable initial rhythm was associated with higher mortality (44/50). In survivors, time to ECPR was shorter (p = 0.006), and initial lactate was significantly lower, whereas initial pH and hemoglobin levels were higher (p = 0.001). Survivors and those with favorable neurological outcome showed lower maximal NSE levels in the first 72 hours (p < 0.001; p = 0.041). Conclusion: In our patient cohort, rSO(2) = 15% immediately prior to cannulation for ECPR did not result in any survivors, thus might be a marker for futile cannulation in ECPR. Higher rSO(2) values were not associated with favorable neurologic outcome. Lower initial lactate and lower maximal NSE within the first 72 h after arrest were associated with favorable outcome

Secondary hemophagocytic lymphohistiocytosis and severe liver injury induced by hepatic SARS-CoV-2 infection unmasking Wilson’s disease: Balancing immunosuppression

A 21-year-old woman was hospitalized due to coronavirus disease 2019 (COVID-19)-associated respiratory and hepatic impairment concomitant with severe hemolytic anemia. Upon diagnosis of secondary hemophagocytic lymphohistiocytosis, immunosuppression with anakinra and steroids was started, leading to a hepatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and viremia. Subsequent liver biopsy revealed virus particles in hepatocytes by electron microscopy and SARS-CoV-2 virus could be isolated and cultured. Immunosuppression was stopped and convalescent donor plasma given. In the differential diagnosis, an acute crisis of Wilson’s disease was raised by laboratory and genetic testing. This case highlights the complexity of balancing immunosuppression to control hyperinflammation versus systemic SARS-CoV-2 dissemination

ECMO in COVID-19—prolonged therapy needed? A retrospective analysis of outcome and prognostic factors

Background: The role of venovenous extracorporeal membrane oxygenation (VV ECMO) in patients with COVID-19-induced acute respiratory distress syndrome (ARDS) still remains unclear. Our aim was to investigate the clinical course and outcome of those patients and to identify factors associated with the need for prolonged ECMO therapy. Methods: A retrospective single-center study on patients with VV ECMO for COVID-19-associated ARDS was performed. Baseline characteristics, ventilatory and ECMO parameters, and laboratory and virological results were evaluated over time. Six months follow-up was assessed. Results: Eleven of 16 patients (68.8%) survived to 6 months follow-up with four patients requiring short-term (<28 days) and seven requiring prolonged (⩾28 days) ECMO support. Lung compliance before ECMO was higher in the prolonged than in the short-term group (28.1 (28.8–32.1) ml/cmH2O vs 18.7 (17.7–25.0) ml/cmH2O, p = 0.030). Mechanical ventilation before ECMO was longer (19 (16–23) days vs 5 (5–9) days, p = 0.002) and SOFA score was higher (12.0 (10.5–17.0) vs 10.0 (9.0–10.0), p = 0.002) in non-survivors compared to survivors. Low viral load during the first days on ECMO tended to indicate worse outcomes. Seroconversion against SARS-CoV-2 occurred in all patients, but did not affect outcome. Conclusions: VV ECMO support for COVID-19-induced ARDS is justified if initiated early and at an experienced ECMO center. Prolonged ECMO therapy might be required in those patients. Although no relevant predictive factors for the duration of ECMO support were found, the decision to stop therapy should not be made dependent of the length of ECMO treatment

Metabolic imbalance of T cells in COVID-19 is hallmarked by basigin and mitigated by dexamethasone

Metabolic pathways regulate immune responses and disrupted metabolism leads to immune dysfunction and disease. Coronavirus disease 2019 (COVID-19) is driven by imbalanced immune responses, yet the role of immunometabolism in COVID-19 pathogenesis remains unclear. By investigating 87 patients with confirmed SARS-CoV-2 infection, 6 critically ill non–COVID-19 patients, and 47 uninfected controls, we found an immunometabolic dysregulation in patients with progressed COVID-19. Specifically, T cells, monocytes, and granulocytes exhibited increased mitochondrial mass, yet only T cells accumulated intracellular reactive oxygen species (ROS), were metabolically quiescent, and showed a disrupted mitochondrial architecture. During recovery, T cell ROS decreased to match the uninfected controls. Transcriptionally, T cells from severe/critical COVID-19 patients showed an induction of ROS-responsive genes as well as genes related to mitochondrial function and the basigin network. Basigin (CD147) ligands cyclophilin A and the SARS-CoV-2 spike protein triggered ROS production in T cells in vitro. In line with this, only PCR-positive patients showed increased ROS levels. Dexamethasone treatment resulted in a downregulation of ROS in vitro and T cells from dexamethasone-treated patients exhibited low ROS and basigin levels. This was reflected by changes in the transcriptional landscape. Our findings provide evidence of an immunometabolic dysregulation in COVID-19 that can be mitigated by dexamethasone treatment