Early in-hospital course of critically ill nontrauma patients in a resuscitation room of a German emergency department (OBSERvE2 study).

BACKGROUND: Management of critically ill nontrauma (CINT) patients in the resuscitation room of the emergency department (ED) is very challenging. Detailed data describing the patient characteristics and management of this population are lacking. This observational study describes the epidemiology, management and outcome in CINT ED patients in the resuscitation room. METHODS: This prospective, single center observational study included all adult patients who were consecutively admitted to the ED resuscitation room during 2 periods of 1 year (September 2014-August 2015 vs. September 2017- August 2018). Patient characteristics, out-of-hospital/in-hospital treatment, admission-related conditions, time intervals for diagnostics and interventions and outcome were recorded using a self-developed questionnaire. RESULTS: A total of 34,303 patients in the first and 35,039 patients in the second study period were admitted to the ED, of whom 532 and 457 patients, respectively, were admitted to the nontrauma resuscitation room due to acute life-threatening conditions. The patient characteristics did not differ significantly between the study periods (male: 58% vs. 59%, age: 68 ± 17 years vs. 65 ± 17 years). Time intervals for diagnostic and therapeutic interventions were similar. The CINT patients during the second study period were treated faster compared to the first study period (end of ED management: 53 ± 33 min vs. 41 ± 24 min, p < 0.0001). The 30-day all-cause mortality was comparable (34.0% vs. 36.3%). CONCLUSION: Observation of critically ill patient management in the ED resuscitation room showed reliable results between both study periods. Structured ED management guidelines for CINT patients may provide comparable results at one institution.

Pre-activated antiviral innate immunity in the upper airways controls early SARS-CoV-2 infection in children.

Children have reduced severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection rates and a substantially lower risk for developing severe coronavirus disease 2019 compared with adults. However, the molecular mechanisms underlying protection in younger age groups remain unknown. Here we characterize the single-cell transcriptional landscape in the upper airways of SARS-CoV-2-negative (n = 18) and age-matched SARS-CoV-2-positive (n = 24) children and corresponding samples from adults (n = 44), covering an age range of 4 weeks to 77 years. Children displayed higher basal expression of relevant pattern recognition receptors such as MDA5 (IFIH1) and RIG-I (DDX58) in upper airway epithelial cells, macrophages and dendritic cells, resulting in stronger innate antiviral responses upon SARS-CoV-2 infection than in adults. We further detected distinct immune cell subpopulations including KLRC1 (NKG2A)+ cytotoxic T cells and a CD8+ T cell population with a memory phenotype occurring predominantly in children. Our study provides evidence that the airway immune cells of children are primed for virus sensing, resulting in a stronger early innate antiviral response to SARS-CoV-2 infection than in adults.

[Interhospital transport of patients with ARDS]. / Interhospitaltransport von Patienten mit ARDS.

In patients with severely compromised gas exchange, interhospital transportation is frequently necessary due to the need to provide access to specialized care. Risks are inherent during transport, so the anticipated benefits of transportation must be weighed against the possible negative outcome during the transport. The use of specialized teams during transportation can help to reduce adverse events. Diligent planning of the transportation, monitoring and medical staff during transport can decrease adverse events and reduce risks. This article defines the group of patients that may benefit from referral. This article discusses the risks associated with the transportation of patients with severely impaired gas exchange and the risks related to different means of transportation. The decisions required before transportation are described as well as the practical approach starting at the transferring hospital until arrival at the admitting hospital.

[Prone positioning of patients during venovenous extracorporeal membrane oxygenation is safe and feasible]. / Bauchlagerung von Patienten an der venovenösen ECMO ist möglich und sicher.

BACKGROUND: Prone positioning of patients with acute respiratory distress syndrome (ARDS) has been shown to significantly improve survival rates. Prone positioning reduces collapse of dorsal lung segments with subsequent reduction of alveolar overdistension of ventral lung segments, optimizes lung recruitment and enhances drainage. Patients with ARDS treated by extracorporeal membrane oxygenation (ECMO) can also benefit from prone positioning; however, the procedure is associated with a possible higher risk of serious adverse events. OBJECTIVE: The aim of this study was to evaluate the safety and feasibility of prone positioning for patients with severe ARDS during ECMO therapy. MATERIAL AND METHODS: This study involved a retrospective analysis of all patients placed in a prone position while being treated by venovenous ECMO (vvECMO) for severe hypoxemia in ARDS as bridge to recovery in the interdisciplinary intensive care unit at the University Hospital Leipzig between January 2009 and August 2013. Baseline data, hospital mortality and serious adverse events were documented. Serious adverse events were defined as dislocation or obstruction of endotracheal tube or tracheal cannula, ECMO cannulas and cardiac arrest. Prone positioning was carried out by at least one doctor and three nurses according to a standardized protocol. Results are given as the median (1st and 3rd quartiles). RESULTS: A total of 26 patients were treated with vvECMO as bridge to recovery due to severe ARDS. Causes for ARDS were pneumonia (n = 20) and aspiration (n = 2) and four patients had different rare causes of ARDS. The median time on ECMO was 8 days (6;11) and during this period 134 turning events were documented. Patients were proned for a median of 5 (3;7) periods with a median duration of 12 h (8;12). No serious adverse events were recorded. The hospital mortality was 42% and mortality during the ECMO procedure was 35%. CONCLUSION: Prone positioning significantly reduces the mortality of patients with severe ARDS. In this series of 26 patients with severe ARDS during ECMO therapy no serious adverse events were found during the use of prone positioning.

Colonization of liver transplant recipients with KPC-producing Klebsiella pneumoniae is associated with high infection rates and excess mortality: a case-control analysis.

PURPOSE: From mid-2010 to early 2013 there was a large single-center (Leipzig University Hospital, Germany) outbreak of Klebsiella pneumoniae carbapenemase (KPC) type 2 producing K. pneumoniae (KPC-2-KP) involving a total of 103 patients. The aim of this study was to compare KPC-positive liver transplant recipients (LTR) and KPC-negative controls to determine both the relative risk of infection following colonization with KPC-2-KP and the case fatality rate associated with KPC-2-KP. METHODS: The study cohort of this retrospective observational study comprised nine patients who had undergone orthotopic liver transplantation (LTx) (median age of 52 years, range 28-73 years) with confirmed evidence of colonization with KPC-2-KP. The data from these nine LTR were matched to 18 LTR (1:2) in whom carbapenem-resistant pathogens were not present and compared for clinical outcomes. RESULTS: Of these nine cases, eight (89 %) progressed to infection due to KPC-2-KP, and five (56 %) were confirmed to have bloodstream infection with KPC-2-KP. Matched-pair analysis of KPC-positive LTR and KPC-negative controls revealed a substantially increased relative risk of 7.0 (95 % confidence interval 1.8-27.1) for fatal infection with KPC-2-producing K. pneumoniae after transplantation with a mortality rate of 78 % (vs. 11 %, p = 0.001). CONCLUSIONS: Colonization with KPC-2-KP in LTR leads to high infection rates and excess mortality. Therefore, frequent screening for carbapenem-resistant bacteria in patients on LTx waiting lists appears to be mandatory in an outbreak setting. Patients with evidence of persistent colonization with KPC-producing pathogens should be evaluated with extreme caution for LTx.

[Hepatorenal syndrome]. / Hepatorenales Syndrom.

Hepatorenal syndrome (HRS) is a unique form of acute renal failure occurring in patients with advanced cirrhosis or acute liver failure. In patients with ascites the incidence of HRS is 8 % and in end-stage liver disease 75 % of patients suffer from HRS. Vasodilation of splanchnic arteries with subsequent decrease of effective blood volume, arterial pressure and renal vasoconstriction is hypothesized to be the central pathophysiological mechanism leading to acute renal failure. Moreover, cardiac output might be decreased in advanced cirrhosis. There are two types of HRS: while HRS type 1 is characterized by a rapid progression to acute renal failure often triggered by a precipitating event, e. g. bacterial peritonitis, which can rapidly develop into multiorgan failure, HRS type 2 shows a more steadily or slowly progressive course to renal failure with increasing ascites. Type 1 HRS has the worst prognosis. Treatment options include pharmacological treatment with vasoconstrictors and albumin and placement of transjugular intrahepatic portosystemic shunts (TIPS) but can only partially improve the survival rate. Liver transplantation is the ultimate and only definitive treatment of patients with HRS.

Worsening of long-term myocardial function after successful pharmacological pretreatment with cyclosporine.

Pretreatment with cyclosporine (CsA) decreases infarct size 24h after myocardial ischemia/reperfusion (I/R). The goal of this study was to determine effects of CsA pretreatment on long-term cardiac function after I/R-injury. Rats were randomly assigned to group-1: vehicle-only, group-2: CsA-5mg/kg/day, and group-3: CsA-12.5mg/kg/day given orally for three days prior to I/R-injury (30 min of left anterior descending coronary artery occlusion). Post-I/R survival and cardiac function were evaluated 14 days after I/R-injury by echocardiography and invasive hemodynamic measurements. Rats with I/R-injury showed increased left ventricular pressure (LVEDP) compared to rats without I/R-injury (p<0.005). Although CsA initially decreased infarct size, no differences of LVEDP were seen 14 days after I/R-injury (vehicle: 21.2+/-8.9 mmHg, CsA-5mg/kg/day: 21.5+/-0.7 mmHg, CsA-12.5mg/kg/day: 20.5+/-9.4 mmHg). Ejection fraction and fractional shortening were decreased compared to baseline, but showed no differences between groups. On day 14, a dose-dependent increase in left ventricular end diastolic diameter was seen (p<0.001). CsA pretreatment was associated with a dose-dependent decrease in post-I/R-survival (vehicle: 56%, CsA-5mg/kg/day: 32%, CsA-12.5mg/kg/day: 16%; p=0.017). CsA pretreatment did not improve long-term cardiac function despite decreased infarct size 24h after I/R-injury, but increased post-I/R mortality significantly. Poor cardiac function after CsA pretreatment might be caused by left ventricular dilation.

1H-NMR metabolic profiling of human neonatal urine.

OBJECT: The measurement of different urine components and their changes over time may provide comprehensive and early information about perinatal metabolic processes and physiological changes. We hypothesized that (1) H-NMR-spectroscopy generating a complex spectral profile without pre-selection of urinary metabolites could identify metabolites determining the neonatal physiological status and discriminating between different metabolic states. MATERIALS AND METHODS: We studied spot urine of three groups of neonates (healthy term-born, term-born with non-specific bacterial infections, and preterm neonates) for the first 6 days of life using (1) H-NMR-spectroscopy. In the group of healthy neonates metabolites changing were identified and their excretion patterns compared between groups. RESULTS: Six metabolites indicating physiological changes were identified: N-methylnicotinamide (NAD (+)-pathway), formate, hippurate, betaine (kidney development), taurine (neuronal development), and bile acids (hepatic clearance). While the dynamic changes over the first 6 days were the same for all metabolites in both groups of term-born neonates, the excretion of N-methylnicotinamide and taurine was significantly higher in preterm neonates compared to healthy term neonates and neonates with bacterial infections from the third day after birth (P < 0.05). CONCLUSION: Urine analysis using (1) H-NMR-spectroscopy could identify markers for perinatal metabolic changes. Further studies have to clarify if the proposed physiological interpretation will correlate with long-term physiological development.