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BACKGROUND: Acute kidney injury (AKI) after orthotopic liver transplantation (OLT) contributes to morbidity and mortality. Donation after circulatory death (DCD) has been established to increase the pool of organs. While surgical complications are reported to be comparable in DCD and donation after brain death (DBD) OLT, there is a knowledge gap concerning adverse kidney events in these 2 groups. MATERIAL AND METHODS: In this retrospective cohort study, 154 patients received a DBD and 68 received a DCD organ (2016-2020). The primary outcome was a major adverse kidney event within 30 days (MAKE-30). The secondary outcome was dynamics of AKI and kidney replacement therapy (KRT) during the first postoperative week and on postoperative day 30. Incidence and resolution from AKI and KRT and patient survival (PS) 30 days after OLT were compared between the DCD and DBD recipients. RESULTS: MAKE-30 incidence after OLT was comparable in DCD (n=27, 40%) vs DBD (n=41, 27%) recipients (risk ratio 1.49 [95% CI 1.01, 2.21], p=0.073). AKI incidence was comparable in DCD (n=58, 94%) vs DBD (n=95, 82%) recipients (risk ratio 1.14 [95% CI: 1.03, 1.27], P=0.057). Overall, 40% (n=88) of patients required KRT, with no difference between DCD (n=27, 40%) vs DBD (n=61, 40%) recipients (risk ratio 1.00 [95% CI 0.71, 1.43], P>0.999). Resolution of AKI by day 30 was lower in DCD (n=29, 50%) than in DBD (n=66, 69%) recipients (risk ratio 0.71 [95% CI: 0.53, 0.95], P=0.032). Survival after 30 days (DCD: n=64, 94% vs DBD: n=146, 95%, risk ratio 0.99 [95% CI 0.93, 1.06], P>0.999) was also comparable. CONCLUSIONS: MAKE-30, short-term renal outcome, and survival did not significantly differ between DBD and DCD-OLT. Resolution of AKI by day 30 was lower in DCD than in DBD recipients.

The identification of phenotypes within complex diseases or syndromes is a fundamental component of precision medicine, which aims to adapt healthcare to individual patient characteristics. Postoperative delirium (POD) is a complex neuropsychiatric condition with significant heterogeneity in its clinical manifestations and underlying pathophysiology. We hypothesize that POD comprises several distinct phenotypes, which cannot be directly observed in clinical practice. Identifying these phenotypes could enhance our understanding of POD pathogenesis and facilitate the development of targeted prevention and treatment strategies. In this paper, we propose an approach that combines supervised machine learning for personalized POD risk prediction with unsupervised clustering techniques to uncover potential POD phenotypes. We first demonstrate our approach using synthetic data, where we simulate patient cohorts with predefined phenotypes based on distinct sets of informative features. We aim to mimic any clinical disease with our synthetic data generation method. By training a predictive model and applying SHAP, we show that clustering patients in the SHAP feature importance space successfully recovers the true underlying phenotypes, outperforming clustering in the raw feature space. We then present a case study using real-world data from a cohort of elderly surgical patients. The results showcase the utility of our approach in uncovering clinically relevant subtypes of complex disorders like POD, paving the way for more precise and personalized treatment strategies.

Delirium in the general intensive care unit (ICU) population is common, associated with adverse outcomes and well studied. However, knowledge on delirium in the increasing number of ICU patients with malignancy is scarce. The aim was to assess the frequency of delirium and its impact on resource utilizations and outcomes in ICU patients with malignancy. This retrospective, single-center longitudinal cohort study included all patients with malignancy admitted to ICUs of a University Hospital during one year. Delirium was diagnosed by an Intensive Care Delirium Screening Checklist (ICDSC) score ≥ 4. Of 488 ICU patients with malignancy, 176/488 (36%) developed delirium. Delirious patients were older (66 [55-72] vs. 61 [51-69] years, p = 0.001), had higher SAPS II (41 [27-68] vs. 24 [17-32], p < 0.001) and more frequently sepsis (26/176 [15%] vs. 6/312 [1.9%], p < 0.001) and/or shock (30/176 [6.1%] vs. 6/312 [1.9%], p < 0.001). In multivariate analysis, delirium was independently associated with lower discharge home (OR [95% CI] 0.37 [0.24-0.57], p < 0.001), longer ICU (HR [95% CI] 0.30 [0.23-0.37], p < 0.001) and hospital length of stay (HR [95% CI] 0.62 [0.50-0.77], p < 0.001), longer mechanical ventilation (HR [95% CI] 0.40 [0.28-0.57], p < 0.001), higher ICU nursing workload (B [95% CI] 1.92 [1.67-2.21], p < 0.001) and ICU (B [95% CI] 2.08 [1.81-2.38], p < 0.001) and total costs (B [95% CI] 1.44 [1.30-1.60], p < 0.001). However, delirium was not independently associated with in-hospital mortality (OR [95% CI] 2.26 [0.93-5.54], p = 0.074). In conclusion, delirium was a frequent complication in ICU patients with malignancy independently associated with high resource utilizations, however, it was not independently associated with in-hospital mortality.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a distinct form of precapillary pulmonary hypertension classified as group 4 by the World Symposium on Pulmonary Hypertension (WSPH) and should be excluded during an episode of acute pulmonary embolism (PE). Patients presenting to emergency departments with sudden onset of signs and symptoms of acute PE may already have a pre-existing CTEPH condition decompensated by the new PE episode. Identifying an underlying and undiagnosed CTEPH during acute PE, while challenging, is an important consideration as it will alter the patients' acute and long-term management. Differential diagnosis and evaluation require an interdisciplinary expert team. Analysis of the clinical condition, the CT angiogram, and the hemodynamic situation are important considerations; patients with CTEPH usually have significantly higher sPAP at the time of index PE, which is unusual and unattainable in the context of acute PE and a naïve right ventricle. The imaging may reveal signs of chronic disease such as right ventricle hypertrophy bronchial collaterals and atypical morphology of the thrombus. There is no standard for the management of acute on chronic CTEPH. Herein, we provide a diagnostic and management algorithm informed by several case descriptions and a review of the literature.

Delirium in the general intensive care unit (ICU) population is common, associated with adverse outcomes and well studied. However, knowledge on delirium in the increasing number of ICU patients with malignancy is scarce. The aim was to assess the frequency of delirium and its impact on resource utilizations and outcomes in ICU patients with malignancy. This retrospective, single-center longitudinal cohort study included all patients with malignancy admitted to ICUs of a University Hospital during one year. Delirium was diagnosed by an Intensive Care Delirium Screening Checklist (ICDSC) score ≥ 4. Of 488 ICU patients with malignancy, 176/488 (36%) developed delirium. Delirious patients were older (66 [55–72] vs. 61 [51–69] years, p = 0.001), had higher SAPS II (41 [27–68] vs. 24 [17–32], p < 0.001) and more frequently sepsis (26/176 [15%] vs. 6/312 [1.9%], p < 0.001) and/or shock (30/176 [6.1%] vs. 6/312 [1.9%], p < 0.001). In multivariate analysis, delirium was independently associated with lower discharge home (OR [95% CI] 0.37 [0.24–0.57], p < 0.001), longer ICU (HR [95% CI] 0.30 [0.23–0.37], p < 0.001) and hospital length of stay (HR [95% CI] 0.62 [0.50–0.77], p < 0.001), longer mechanical ventilation (HR [95% CI] 0.40 [0.28–0.57], p < 0.001), higher ICU nursing workload (B [95% CI] 1.92 [1.67–2.21], p < 0.001) and ICU (B [95% CI] 2.08 [1.81–2.38], p < 0.001) and total costs (B [95% CI] 1.44 [1.30–1.60], p < 0.001). However, delirium was not independently associated with in-hospital mortality (OR [95% CI] 2.26 [0.93–5.54], p = 0.074). In conclusion, delirium was a frequent complication in ICU patients with malignancy independently associated with high resource utilizations, however, it was not independently associated with in-hospital mortality.

BACKGROUND Severe coronavirus disease 2019 (COVID-19) frequently entails complications that bear similarities to autoimmune diseases. To date, there is little data on possible IgA-mediated autoimmune responses. Here, we aim to determine whether COVID-19 is associated with a vigorous total IgA response and if IgA antibodies are associated with complications of severe illness. Since thrombotic events are frequent in severe COVID-19 and resemble hypercoagulation of antiphospholipid syndrome (APS), our approach focused on antiphospholipid antibodies (aPL). METHODS In this retrospective cohort study clinical data and aPL from 64 patients with COVID-19 were compared from three independent tertiary hospitals (one in Liechtenstein, two in Switzerland). Samples were collected from April 9 th to May 1 st, 2020. RESULTS Clinical records of 64 patients with COVID-19 were reviewed and divided into a cohort with mild illness (mCOVID) (41%), a discovery cohort with severe illness (sdCOVID) (22%) and a confirmation cohort with severe illness (scCOVID) (38%). Total IgA, IgG and aPL were measured with clinical diagnostic kits. Severe illness was significantly associated with increased total IgA (sdCOVID, P=0.01; scCOVID, p-value<0.001), but not total IgG. Among aPL, both cohorts with severe illness significantly correlated with elevated anti-Cardiolipin IgA (sdCOVID and scCOVID, p-value<0.001), anti-Cardiolipin IgM (sdCOVID, P=0.003; scCOVID, P<0.001), and anti-Beta2 Glycoprotein-1 IgA (sdCOVID and scCOVID, P<0.001). Systemic lupus erythematosus was excluded from all patients as a potential confounder. CONCLUSIONS Higher total IgA and IgA-aPL were consistently associated with severe illness. These novel data strongly suggest that a vigorous antiviral IgA-response, possibly triggered in the bronchial mucosa, induces systemic autoimmunity.

AIMS OF THE STUDY: During the ongoing COVID-19 pandemic, the launch of a large-scale vaccination campaign and virus mutations have hinted at possible changes in transmissibility and the virulence affecting disease progression up to critical illness, and carry potential for future vaccination failure. To monitor disease development over time with respect to critically ill COVID-19 patients, we report near real-time prospective observational data from the RISC-19-ICU registry that indicate changed characteristics of critically ill patients admitted to Swiss intensive care units (ICUs) at the onset of a third pandemic wave. METHODS: 1829 of 3344 critically ill COVID-19 patients enrolled in the international RISC-19-ICU registry as of 31 May 2021 were treated in Switzerland and were included in the present study. Of these, 1690 patients were admitted to the ICU before 1 February 2021 and were compared with 139 patients admitted during the emerging third pandemic wave RESULTS: Third wave patients were a mean of 5.2 years (95% confidence interval [CI] 3.2–7.1) younger (median 66.0 years, interquartile range [IQR] 57.0–73.0 vs 62.0 years, IQR 54.5–68.0; p <0.0001) and had a higher body mass index than patients admitted in the previous pandemic period. They presented with lower SAPS II and APACHE II scores, less need for circulatory support and lower white blood cell counts at ICU admission. P/F ratio was similar, but a 14% increase in ventilatory ratio was observed over time (p = 0.03) CONCLUSION: Near real-time registry data show that the latest COVID-19 patients admitted to ICUs in Switzerland at the onset of the third wave were on average 5 years younger, had a higher body mass index, and presented with lower physiological risk scores but a trend towards more severe lung failure. These differences may primarily be related to the ongoing nationwide vaccination campaign, but the possibility that changes in virus-host interactions may be a co-factor in the age shift and ch

Sepsis is a highly heterogenous syndrome with variable causes and outcomes. As part of the SPHN/PHRT funding program, we aim to build a highly interoperable, interconnected network for data collection, exchange and analysis of patients on intensive care units in order to predict sepsis onset and mortality earlier. All five University Hospitals, Universities, the Swiss Institute of Bioinformatics and ETH Zurich are involved in this multi-disciplinary project. With two prospective clinical observational studies, we test our infrastructure setup and improve the framework gradually and generate relevant data for research.

Background Venous thromboembolism (VTE) is a recognized complication in patients with traumatic brain injury (TBI) and is associated with increased morbidity and mortality. Currently, no standard exists for optimal timing or a pharmacological agent for VTE prophylaxis (pharmacological thromboprophylaxis – PTP) in patients with TBI. PTP is often delayed out of fear of causing extension of intracranial hemorrhage (ICH). The purpose of this study was to report the frequency of VTE and ICH progression after initiation of PTP with a continuous infusion of unfractionated heparin in patients with moderate to severe TBI, and to identify risk factors associated with development of VTE. Methods In this single-center retrospective study, patients with moderate to severe TBI admitted to the ICU of a Swiss Level I Trauma Center over a three-year period were analyzed. Results In 23 (13%) of the 177 patients included in the study a VTE episode occurred during the hospital stay. ICH progression after initiation of PTP occurred in 7 (4%) patients. In a multivariable logistic regression model, only the timing of initiation of PTP was identified as an independent predictor of VTE. Conclusions In this study population, the risk of developing VTE increased with the delay of initiation of a pharmacological VTE prophylaxis, while ICH progression after initiation of PTP was a rare event.

AIMS OF THE STUDY An extracorporeal membrane oxygenation system (ECMO), as a bridge to either recovery, a ventricular assist device (VAD), or heart or lung transplantation, may be the only lifesaving option for critically ill patients suffering from refractory cardiac, respiratory or combined cardiopulmonary failure. As peripheral hospitals may not offer ECMO treatment, tertiary care centres provide specialised ECMO teams for on-site implantation and subsequent patient transfer on ECMO to the tertiary hospital. This study reports the results of the largest ECMO transportation programme in Switzerland and describes its feasibility and safety. METHODS Patients transported on ECMO by our mobile ECMO team to our tertiary centre between 1 September 2009 and 31 December, 2016 underwent retrospective analysis. Implantation was performed by our specialised ECMO team (primary transport) or by the medical staff of the referring hospital (secondary transport) with subsequent transfer to our institution. Type of ECMO, transport data, patient baseline characteristics, operative variables and postoperative outcomes including complications and mortality were collected from medical records. RESULTS Fifty-eight patients were included (three patients excluded: one repatriation, two with incomplete medical records). Thirty-five patients (60%) received veno-venous, 22 (38%) veno-arterial and one patient (2%) veno-venoarterial ECMO. Forty-nine (84%) patients underwent primary and nine (16%) secondary transport. Thirty-five (60%) patients were transferred by helicopter and 23 (40%) by ambulance, with median distances of 38.1 (13–225) km and 21 (3-71) km respectively. No clinical or technical complications occurred during transportation. During hospitalisation, three patients had ECMO-associated complications (two compartment syndrome of lower limb, one haemothorax after central ECMO upgrade). Median days on ECMO was 8 (<1–49) and median days in hospital was 17 (<1&ndash

Recognition of multifocal vasculopathy due to varicella-zoster virus (VZV) is often problematic. We describe a human immunodeficiency virus-infected patient who had progressive central nervous system disease for >3 months. Both VZV DNA and antibody were detected in cerebrospinal fluid (CSF) specimens; serial polymerase chain reaction analyses confirmed the diagnosis and guided the duration of therapy. Reduced ratios of VZV antibody in serum to that in CSF were also demonstrated.