Informing pandemic management in Germany with trustworthy living evidence syntheses and guideline development: lessons learned from the COVID-19 evidence ecosystem.

Objectives: We present the 'COVID-19 evidence ecosystem' (CEOsys) as a German network to inform pandemic management and to support clinical and public health decision-making. We discuss challenges faced when organizing the ecosystem and derive lessons learned for similar networks acting during pandemics or health-related crises.

Study Design And Setting: Bringing together 18 university hospitals and additional institutions, CEOsys key activities included research prioritization, conducting living systematic reviews (LSRs), supporting evidence-based (living) guidelines, knowledge translation (KT), detecting research gaps, and deriving recommendations, backed by technical infrastructure and capacity building.

Does Timepoint of Surgical Procedure Affect the Outcome in Simultaneous Pancreas-Kidney Transplantation? A Retrospective Single-Center Analysis over 20 Years.

: Sleep deprivation and disturbances in circadian rhythms may hinder surgical performance and decision-making capabilities. Solid organ transplantations, which are technically demanding and often begin at uncertain times, frequently during nighttime hours, are particularly susceptible to these effects. This study aimed to assess how transplant operations conducted during daytime versus nighttime influence both patient and graft outcomes and function.

Trimethylamine N-oxide (TMAO) in patients with subarachnoid hemorrhage: a prospective observational study.

Background: It is suspected that microbiome-derived trimethylamine N-oxide (TMAO) may enhance platelet responsiveness and accordingly be thrombophilic. The purpose of this prospective observational study is to evaluate TMAO in patients with subarachnoid hemorrhage (SAH) and compare it with a control group. A secondary aim was to investigate TMAO in the cerebrospinal fluid (CSF) from SAH patients.

The Role of Innate Immune Cells in the Prediction of Early Renal Allograft Injury Following Kidney Transplantation.

Background: Despite recent advances and refinements in perioperative management of kidney transplantation (KT), early renal graft injury (eRGI) remains a critical problem with serious impairment of graft function as well as short- and long-term outcome. Serial monitoring of peripheral blood innate immune cells might be a useful tool in predicting post-transplant eRGI and graft outcome after KT. Methods: In this prospective study, medical data of 50 consecutive patients undergoing KT at the University Hospital of Leipzig were analyzed starting at the day of KT until day 10 after the transplantation.

Predictive Value of HAS-BLED Score Regarding Bleeding Events and Graft Survival following Renal Transplantation.

Objective: Due to the high prevalence and incidence of cardio- and cerebrovascular diseases among dialysis-dependent patients with end-stage renal disease (ERSD) scheduled for kidney transplantation (KT), the use of antiplatelet therapy (APT) and/or anticoagulant drugs in this patient population is common. However, these patients share a high risk of complications, either due to thromboembolic or bleeding events, which makes adequate peri- and post-transplant anticoagulation management challenging. Predictive clinical models, such as the HAS-BLED score developed for predicting major bleeding events in patients under anticoagulation therapy, could be helpful tools for the optimization of antithrombotic management and could reduce peri- and postoperative morbidity and mortality.

Early spontaneous breathing for acute respiratory distress syndrome in individuals with COVID-19.

Background: Acute respiratory distress syndrome (ARDS) represents the most severe course of COVID-19 (caused by the SARS-CoV-2 virus), usually resulting in a prolonged stay in an intensive care unit (ICU) and high mortality rates. Despite the fact that most affected individuals need invasive mechanical ventilation (IMV), evidence on specific ventilation strategies for ARDS caused by COVID-19 is scarce. Spontaneous breathing during IMV is part of a therapeutic concept comprising light levels of sedation and the avoidance of neuromuscular blocking agents (NMBA).

Analysis of Volatile Anesthetic-Induced Organ Protection in Simultaneous Pancreas-Kidney Transplantation.

Background: Despite recent advances in surgical procedures and immunosuppressive regimes, early pancreatic graft dysfunction, mainly specified as ischemia-reperfusion injury (IRI)-Remains a common cause of pancreas graft failure with potentially worse outcomes in simultaneous pancreas-kidney transplantation (SPKT). Anesthetic conditioning is a widely described strategy to attenuate IRI and facilitate graft protection. Here, we investigate the effects of different volatile anesthetics (VAs) on early IRI-associated posttransplant clinical outcomes as well as graft function and outcome in SPKT recipients.

Janus kinase inhibitors for the treatment of COVID-19.

Background: With potential antiviral and anti-inflammatory properties, Janus kinase (JAK) inhibitors represent a potential treatment for symptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. They may modulate the exuberant immune response to SARS-CoV-2 infection. Furthermore, a direct antiviral effect has been described.

Correlation of Different Serum Biomarkers with Prediction of Early Pancreatic Graft Dysfunction Following Simultaneous Pancreas and Kidney Transplantation.

Background: Despite recent advances and refinements in perioperative management of simultaneous pancreas−kidney transplantation (SPKT) early pancreatic graft dysfunction (ePGD) remains a critical problem with serious impairment of early and long-term graft function and outcome. Hence, we evaluated a panel of classical blood serum markers for their value in predicting early graft dysfunction in patients undergoing SPKT. Methods: From a prospectively collected database medical data of 105 patients undergoing SPKT between 1998 and 2018 at our center were retrospectively analyzed.

Influence of Intraoperative Hemodynamic Parameters on Outcome in Simultaneous Pancreas-Kidney Transplant Recipients.

Objectives: Adequate organ perfusion, as well as appropriate blood pressure levels at the time of unclamping, is crucial for early and long-term graft function and outcome in simultaneous pancreas−kidney transplantation (SPKT). However, the optimal intraoperative mean arterial pressure (MAP) level has not well been defined. Methods: From a prospectively collected database, the medical data of 105 patients undergoing SPKT at our center were retrospectively analyzed.

ECMO use in Germany: An analysis of 29,929 ECMO runs.

Background: Extracorporeal Membrane Oxygenation (ECMO) use is increasing despite limited evidence. The aim of this study was to demonstrate heterogeneity of ECMO use and its association with hospital size and annual frequency in Germany.

Methods: This is a database analysis of all ECMO cases in Germany from 2010 to 2016 using the German Diagnosis Related Groups (DRG) coding system for ECMO.

Extracorporeal Membrane Oxygenation and Perfluorocarbon in a Therapy Refractory Case of Acute Respiratory Distress Syndrome.

Perfluorocarbons are oxygen-carrying, dense liquids initially intended for the use in partial or total liquid ventilation of patients with severe acute respiratory distress syndrome but which did not show beneficial effects in clinical studies. However, perfluorocarbons may be used for lung lavage in severe alveolar proteinosis. In acute respiratory distress syndrome, oxygenation may be so severely compromised that the use of nonoxygenated perfluorocarbons may not be possible.

A Nationwide Cross-Sectional Online Survey on the Treatment of COVID-19-ARDS: High Variance in Standard of Care in German ICUs.

Introduction: Coronavirus disease (COVID-19) has recently dominated scientific literature. Incomplete understanding and a lack of data concerning the pathophysiology, epidemiology, and optimal treatment of the disease has resulted in conflicting recommendations. Adherence to existing guidelines and actual treatment strategies have thus far not been studied systematically.

Targeted Minimal Staff-to-Patient Ratios Are Unachievable - A Nationwide Survey in German ICUs During the COVID-19 Pandemic.

Introduction Adequate staffing in the intensive care units (ICUs) is the most important factor to provide optimal care and ensure favorable outcomes in critically ill patients. Recently, the need for ICU beds has reached unprecedented levels and the management and treatment of critically ill patients has been in focus. The aim of the study was to assess the targeted and actual nurse-to-patient (NPR) and physician-to-patient ratios (PPR) regarding patients with and without COVID-19.

Key summary of German national treatment guidance for hospitalized COVID-19 patients : Key pharmacologic recommendations from a national German living guideline using an Evidence to Decision Framework (last updated 17.05.2021).

Purpose: This executive summary of a national living guideline aims to provide rapid evidence based recommendations on the role of drug interventions in the treatment of hospitalized patients with COVID-19.

Methods: The guideline makes use of a systematic assessment and decision process using an evidence to decision framework (GRADE) as recommended standard WHO (2021). Recommendations are consented by an interdisciplinary panel.

Infection control, prophylactic antibiotics, and testing for SARS-CoV-2 and PPE on German intensive care units: results from a national mixed methods survey.

Recommendations on hygiene measures, personal protective equipment (PPE), isolation, and antibiotic prophylaxis were developed during the coronavirus 2019 disease (COVID-19) pandemic and have been revised several times to date. Some of the underlying literature indicates a large evidence gap. We suspect that this leads to a large variance of measures on German intensive care units (ICU).

Hypertension delays viral clearance and exacerbates airway hyperinflammation in patients with COVID-19.

In coronavirus disease 2019 (COVID-19), hypertension and cardiovascular diseases are major risk factors for critical disease progression. However, the underlying causes and the effects of the main anti-hypertensive therapies-angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs)-remain unclear. Combining clinical data (n = 144) and single-cell sequencing data of airway samples (n = 48) with in vitro experiments, we observed a distinct inflammatory predisposition of immune cells in patients with hypertension that correlated with critical COVID-19 progression.

COVID-19 severity correlates with airway epithelium-immune cell interactions identified by single-cell analysis.

To investigate the immune response and mechanisms associated with severe coronavirus disease 2019 (COVID-19), we performed single-cell RNA sequencing on nasopharyngeal and bronchial samples from 19 clinically well-characterized patients with moderate or critical disease and from five healthy controls. We identified airway epithelial cell types and states vulnerable to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In patients with COVID-19, epithelial cells showed an average three-fold increase in expression of the SARS-CoV-2 entry receptor ACE2, which correlated with interferon signals by immune cells.

Clinical Guideline for Treating Acute Respiratory Insufficiency with Invasive Ventilation and Extracorporeal Membrane Oxygenation: Evidence-Based Recommendations for Choosing Modes and Setting Parameters of Mechanical Ventilation.

For patients with acute respiratory insufficiency, mechanical ("invasive") ventilation is a fundamental therapeutic measure to ensure sufficient gas exchange. Despite decades of strong research efforts, central questions on mechanical ventilation therapy are still answered incompletely. Therefore, many different ventilation modes and settings have been used in daily clinical practice without scientifically sound bases.

Mechanical Ventilation and Extracorporeal Membrane Oxygena tion in Acute Respiratory Insufficiency.

Background: Mechanical ventilation is life-saving for patients with acute respiratory insufficiency. In a German prevalence study, 13.6% of patients in intensive care units received mechanical ventilation for more than 12 hours; 20% of these patients received mechanical ventilation as treatment for acute respiratory distress syndrome (ARDS).

Hydroxyethyl starch for volume expansion after subarachnoid haemorrhage and renal function: Results of a retrospective analysis.

Background: Hydroxyethyl starch (HES) was part of "triple-H" therapy for prophylaxis and therapy of vasospasm in patients with subarachnoid haemorrhage (SAH). The European Medicines Agency restricted the use of HES in 2013 due to an increase of renal failure in critically ill patients receiving HES compared to crystalloid fluids. The occurrence of renal insufficiency in patients with SAH due to HES is still uncertain.

The effects of hemoglobin glutamer-200 and iNO on pulmonary vascular tone and arterial oxygenation in an experimental acute respiratory distress syndrome.

Introduction: Hemoglobin-based oxygen carriers (HBOC) have been developed as an alternative to blood transfusions. Their nitric-oxide-scavenging properties HBOC also induce vasoconstriction. In acute lung injury, an excess of nitric oxide results in a general vasodilation, reducing oxygenation by impairing the hypoxic pulmonary vasoconstriction.

Two-Year Follow-Up After Percutaneous Dilatational Tracheostomy in a Surgical ICU.

Background: The modalities of tracheostomy for critically ill patients are still controversially discussed. Although the use of percutaneous dilatational tracheostomy (PDT) is generally accepted to be a safe procedure, it is still not considered to be suitable for patients requiring a permanent tracheostomy.

Methods: This was an observational cohort study investigating long-term outcome parameters of PDT.