Treatment of sleep apnoea early after myocardial infarction with adaptive servo-ventilation - a proof-of-concept randomised controlled trial.

INTRODUCTION: Sleep-disordered breathing has been associated with less myocardial salvage and smaller infarct size reduction after acute myocardial infarction (AMI). The Treatment of sleep apnoea Early After Myocardial infarction with Adaptive Servo-Ventilation (TEAM-ASV I) trial investigated the effects of adding adaptive servo-ventilation (ASV) for sleep-disordered breathing (SDB) to standard therapy on myocardial salvage index (MSI) and change in infarct size within 12 weeks after AMI. METHODS: In this multicentre, randomised, open-label trial, patients with AMI and successful percutaneous coronary intervention within 24 h after symptom onset plus SDB (apnoea-hypopnoea index ≥15/h) were randomised to standard medical therapy alone (control) or plus ASV (starting 3.6±1.4 days post-AMI). The primary outcome was MSI at 12 weeks post-AMI. Cardiac magnetic resonance (CMR) imaging was performed at ≤5 days and 12 weeks after AMI. RESULTS: Seventy-six individuals were enrolled from February 2014 to August 2020; 39 had complete CMR data for analysis of the primary endpoint. MSI was significantly higher in the ASV versus control group (difference 14.6% of left ventricular mass [LVM]; 95% confidence interval 0.14-29.1; p=0.048). At 12 weeks, absolute [interquartile range] (6.6 [4.8-8.5] versus 2.8 [0.9-4.8] %LVM; p=0.003) and relative (44 [30-57] versus 21 [6-35] % of baseline; p=0.013) reductions in infarct size were greater in the ASV versus control group. No serious treatment-related adverse events occurred. CONCLUSIONS: Early treatment of SDB with ASV improved the MSI and decreased the infarct size at 12 weeks after AMI. Larger randomised trials are required to confirm these findings.

Prevalence and Risk Factors for Weaning Failure From Venovenous Extracorporeal Membrane Oxygenation in Patients With Severe Acute Respiratory Insufficiency.

OBJECTIVE: Analysis of the prevalence and risk factors for weaning failure from venovenous extracorporeal membrane oxygenation (VV-ECMO) in patients with severe acute respiratory insufficiency. DESIGN: Single-center retrospective observational study. SETTING: Sixteen beds medical ICU at the University Hospital Regensburg. PATIENTS: Two hundred twenty-seven patients with severe acute respiratory insufficiency requiring VV-ECMO support between October 2011 and December 2017. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients meeting our ECMO weaning criteria (Sp o2 ≥ 90% with F io2 ≤ 0.4 or Pa o2 /F io2 > 150 mm Hg, pH = 7.35-7.45, positive end-expiratory pressure ≤ 10 cm H 2 O, driving pressure < 15 cm H 2 O, respiratory rate < 30/min, tidal volume > 5 mL/kg, ECMO bloodflow ≈ 1. 5 L/min, sweep gas flow ≈ 1 L/min, heart rate < 120/min, systolic blood pressure 90-160 mm Hg, norepinephrine < 0.2 µg/[kg*min]) underwent an ECMO weaning trial (EWT) with pausing sweep gas flow. Arterial blood gas analysis, respiratory and ventilator parameters were recorded prior, during, and after EWTs. Baseline data, including demographics, vitals, respiratory, ventilator, and laboratory parameters were recorded at the time of cannulation. One hundred seventy-nine of 227 (79%) patients were successfully decannulated. Ten patients (4%) underwent prolonged weaning of at least three failed EWTs before successful decannulation. The respiratory rate (19/min vs 16/min, p = 0.002) and Pa co2 (44 mm Hg vs 40 mm Hg, p = 0.003) were higher before failed than successful EWTs. Both parameters were risk factors for ECMO weaning failure (Pa co2 : odds ratio [OR] 1.05; 95% CI, 1.001-1.10; p = 0.045; respiratory rate: OR 1.10; 95% CI, 1.04-1.15; p < 0.001) in multivariable analysis. The rapid shallow breathing index [42 (1/L*min), vs 35 (1/L*min), p = 0.052) was higher before failed than successful EWTs. The decline of Sa o2 and Pa o2 /F io2 during EWTs was higher in failed than successful trials. CONCLUSIONS: Seventy-nine percent of patients were successfully decannulated with only 4% needing prolonged ECMO weaning. Before EWT only parameters of impaired ventilation (insufficient decarboxylation, higher respiratory rate) but not of oxygenation were predictive for weaning failure, whereas during EWT-impaired oxygenation was associated with weaning failure.

Short report: impact of selective reporting of antibiotic susceptibility testing on antibiotic use in patients with bloodstream infection with Enterococcus faecalis.

INTRODUCTION: Bloodstream infections with Enterococcus faecalis are associated with relevant morbidity and mortality. Targeted antimicrobial therapy is essential. The choice of an adequate treatment may be challenging when susceptibility testing offers different options. Selective reporting of antibiotic susceptibility test results might lead to a more tailored antibiotic therapy and could therefore be an important antimicrobial stewardship program intervention. The aim of this study was to analyse whether the introduction of selective reporting of antibiotic test results leads to a more targeted antibiotic therapy in patients with bloodstream infection with Enterococcus faecalis. METHODS: This study was performed as a retrospective cohort study at the University Hospital Regensburg, Germany. All patients with blood cultures positive for Enterococcus faecalis between March 2003 and March 2022 were analysed. In February 2014 selective reporting of antibiotic susceptibility test results omitting sensitivity results for agents not recommended was introduced. RESULTS: 263 patients with blood cultures positive for Enterococcus faecalis were included. After introduction of selective reporting of antibiotic tests (AI) significantly more patients received ampicillin than before introduction of selective reporting (BI) (9.6% BI vs. 34.6% AI, p < 0.001). CONCLUSION: Selective reporting of antibiotic susceptibility test results led to a significantly higher use of ampicillin.

Intracranial hemorrhage in a large cohort of patients supported with veno-venous ECMO. A retrospective single-center analysis.

BACKGROUND: Intracranial bleeding (ICB) is a serious complication during veno-venous extracorporeal membrane oxygenation (V-V ECMO), with potentially fatal consequences. PURPOSE: This study aimed to evaluate the incidence, time of detection of ICB among patients treated with V-V ECMO and potential risk factors for developing ICB during V-V ECMO. METHODS: Five hundred fifty six patients were included in this retrospective single center analysis. RESULTS: Median time on V-V ECMO was 9 (IQR 6-15) days. Intracranial bleeding during V-V ECMO was detected in 10.9% of all patients (61 patients with ICB). Only 17 patients with ICB presented obvious clinical symptoms. Intracranial bleeding was detected on cerebral imaging in median after 5 days (IQR 1-14) after starting V-V ECMO. Overall survival to hospital discharge was 63.7% (ICB: 29.5%). Risk factors of ICB before starting V-V ECMO in univariable analysis were platelets <100/nl (OR: 3.82), creatinine >1.5mg/dl (OR: 1.98), norepinephrine >2.5mg/h (OR: 2.5), ASAT >80U/L (OR: 1.86), blood-urea >100mg/dl (OR: 1.81) and LDH >550u/L (OR: 2.07). Factors associated with cannulation were rapid decrease in paCO2 >35mmHg (OR: 2.56) and rapid decrease in norepinephrine >1mg/h (OR: 2.53). Multivariable analysis revealed low platelets, high paCO2 before ECMO, and rapid drop in paCO2 after V-V ECMO initiation as significant risk factors for ICB. CONCLUSION: The results emphasize that ICB is a frequent complication during V-V ECMO. Many bleedings were incidental findings, therefore screening for ICB is advisable. The univariate risk factors reflect the underlying disease severity, coagulation disorders and peri-cannulation factors, and may help to identify patients at risk.

Comparison of transbronchial biopsy techniques using needle and forceps biopsies in lung cancer for molecular diagnostics: a prospective, randomized crossover trial.

Background: In lung cancer, molecular testing and next-generation sequencing (NGS) are needed to identify therapeutic targets and are increasingly being used in earlier stages of the disease. Despite its longstanding use, it remains unclear whether transbronchial needle aspiration (TBNA) of peripheral lung lesions provides as adequate material for genetic testing as transbronchial forceps biopsies (TBFBs). In this study, we aim to analyze the use of TBNA using median viable cell area (MVCA) as a surrogate parameter to analyze sample quality. Methods: This prospective single-center study analyzed biopsy specimens or aspirates of patients who underwent bronchoscopy with transbronchial biopsy. Patients underwent bronchoscopy with TBFB and TBNA for suspected lung cancer in peripheral lung lesions. Patients were randomized 1:1 to receive either TBFB or TBNA as the first biopsy technique and then switched to the other. After routine workup, sample slides were digitally scanned, and MVCA was calculated by a pathologist blinded to the biopsy technique used. The primary endpoint was MVCA of TBNA versus TBFB. Secondary endpoints were complications categorized as bleeding, pneumothorax, and other. Results: Between August 2021 and April 2022, 15 patients were included in the per-protocol analysis. Six patients were included in cohort 1 and nine patients in cohort 2. A malignant diagnosis was confirmed in 11/15 (73.3%) cases, of which nine were primary lung malignancies. Overall, MVCA in samples obtained by TBFB was significantly larger than TBNA samples {TBFB-MVCA 9.80 mm2 [interquartile range (IQR), 2.70-10.39 mm2] vs. TBNA-MVCA 2.70 mm2 (IQR, 0.14-8.21 mm2), P=0.008}. Despite this difference, molecular testing was feasible in both TBNA and TBFB samples. No major complications were observed. Conclusions: Despite a significantly smaller MVCA provided by TBNA, samples were still considered feasible for NGS, indicating that TBNA represents an alternative method to obtain sufficient tumor tissue in peripheral nodules as part of the diagnosis of suspected lung cancer.

Impact of Selective Reporting of Antibiotic Susceptibility Test Results on Antibiotic Use in Patients with Bloodstream Infection with Streptococcus pneumoniae.

Introduction: Invasive pneumococcal disease is a major cause of morbidity and mortality in infectious diseases. Selective reporting of antibiotic susceptibility test results might lead to a tailored antibiotic therapy and could therefore be an important antibiotic stewardship program intervention. The aim of this study was to analyse whether a switch to selective reporting of antibiotic test results leads to a more focused antibiotic therapy in patients with a bloodstream infection with Streptococcus pneumoniae. Methods: This study was performed as a retrospective cohort study at the University Hospital Regensburg, Germany. All blood cultures positive for Streptococcus pneumoniae between 2006 and 2021 were analysed. In 2014, a switch to selective reporting of antibiotic susceptibility test results omitting sensitivity results for agents not recommended was introduced. Results: Twenty-four hours after final antibiotic susceptibility test results were available, 20.9% before (BI) versus 15.4% after implementation (AI) of selective reporting of antibiotic test results received a narrow-spectrum penicillin, while only 2.3% BI versus 5.8% AI received a narrow-spectrum penicillin from the beginning. Conclusion: Selective reporting of antibiotic susceptibility test results without further antimicrobial stewardship interventions did not lead to a higher use of a narrow-spectrum penicillin in this study.

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.

Prognostic factors for favorable outcomes after veno-venous extracorporeal membrane oxygenation in critical care patients with COVID-19.

BACKGROUND: Patients with COVID-19 and severe acute respiratory failure may require veno-venous extracorporeal membrane oxygenation (VV ECMO). Yet, this procedure is resource-intensive and high mortality rates have been reported. Thus, predictors for identifying patients who will benefit from VV ECMO would be helpful. METHODS: This retrospective study included 129 patients with COVID-19 and severe acute respiratory failure, who had received VV ECMO at the University Medical Center Regensburg, Germany, between 1 March 2020 and 31 December 2021. Patient-specific factors and relevant intensive-care parameters at the time of the decision to start VV ECMO were investigated regarding their value as predictors of patient survival. In addition, the intensive-care course of the first 10 days of VV ECMO was compared between survivors and patients who had died in the intensive care unit. RESULTS: The most important parameters for predicting outcome were patient age and platelet count, which differed significantly between survivors and non-survivors (age: 52.6±8.1 vs. 57.4±10.1 years, p<0.001; platelet count before VV ECMO: 321.3±132.2 vs. 262.0±121.0 /nL, p = 0.006; average on day 10: 199.2±88.0 vs. 147.1±57.9 /nL, p = 0.002). A linear regression model derived from parameters collected before the start of VV ECMO only included age and platelet count. Patients were divided into two groups by using receiver operating characteristics (ROC) analysis: group 1: 78% of patients, mortality 26%; group 2: 22% of patients, mortality 75%. A second linear regression model included average blood pH, minimum paO2, and average pump flow on day 10 of VV ECMO in addition to age and platelet count. The ROC curve resulted in two cut-off values and thus in three groups: group 1: 25% of patients, mortality 93%; group 2: 45% of patients, mortality 31%; group 3: 30% of patients, mortality 0%.

Treatment of Refractory Cardiac Arrest by Controlled Reperfusion of the Whole Body: A Multicenter, Prospective Observational Study.

Background: Survival following cardiac arrest (CA) remains poor after conventional cardiopulmonary resuscitation (CCPR) (6-26%), and the outcomes after extracorporeal cardiopulmonary resuscitation (ECPR) are often inconsistent. Poor survival is a consequence of CA, low-flow states during CCPR, multi-organ injury, insufficient monitoring, and delayed treatment of the causative condition. We developed a new strategy to address these issues. Methods: This all-comers, multicenter, prospective observational study (69 patients with in- and out-of-hospital CA (IHCA and OHCA) after prolonged refractory CCPR) focused on extracorporeal cardiopulmonary support, comprehensive monitoring, multi-organ repair, and the potential for out-of-hospital cannulation and treatment. Result: The overall survival rate at hospital discharge was 42.0%, and a favorable neurological outcome (CPC 1+2) at 90 days was achieved for 79.3% of survivors (CPC 1+2 survival 33%). IHCA survival was very favorable (51.7%), as was CPC 1+2 survival at 90 days (41%). Survival of OHCA patients was 35% and CPC 1+2 survival at 90 days was 28%. The subgroup of OHCA patients with pre-hospital cannulation showed a superior survival rate of 57.1%. Conclusions: This new strategy focusing on repairing damage to multiple organs appears to improve outcomes after CA, and these findings should provide a sound basis for further research in this area.

ß2-Adrenergic Receptor Expression and Intracellular Signaling in B Cells Are Highly Dynamic during Collagen-Induced Arthritis.

The sympathetic nervous system (SNS) has either a pro-inflammatory or anti-inflammatory effect, depending on the stage of arthritis. In the past, treatment of arthritic B cells with a ß2-adrenergic receptor (ß2-ADR) agonist has been shown to attenuate arthritis. In this study, the expression and signaling of ß2-ADR in B cells during collagen-induced arthritis (CIA) were investigated to provide an explanation of why only B cells from arthritic mice are able to improve CIA. Splenic B cells were isolated via magnetic-activated cell sorting (MACS). Adrenergic receptors on B cells and intracellular ß2-ADR downstream molecules (G protein-coupled receptor kinase 2 (GRK-2), ß-Arrestin 2, p38 MAPK, extracellular signal-regulated kinase 1/2 (ERK1/2) and cAMP response element-binding protein (CREB)) were analyzed at different time points in naïve and arthritic B cells with and without stimulation of ß2-ADR agonist terbutaline by flow cytometry. ß2-ADR-expressing B cells increase during CIA without a change in receptor density. Moreover, we observed a profound downregulation of GRK-2 shortly after induction of arthritis and an increase in ß-Arrestin 2 only at late stage of arthritis. The second messengers studied (p38, ERK1/2 and CREB) followed a biphasic course, characterized by a reduction at onset and an increase in established arthritis. Stimulation of CIA B cells with the ß-ADR agonist terbutaline increased pp38 MAPK independent of the timepoint, while pERK1/2 and pCREB were enhanced only in the late phase of arthritis. The phosphorylation of p38 MAPK, ERK1/2 and CREB in the late phase of arthritis was associated with increased IL-10 produced by B10 cells. The change of ß2-ADR expression and signaling during sustained inflammation might be an integral part of the switch from pro- to anti-inflammatory action of sympathetic mechanisms in late arthritis.

Arterial and venous vascular complications in patients requiring peripheral venoarterial extracorporeal membrane oxygenation.

Introduction: The aim of this study was to investigate the prevalence of arterial and venous complications in patients requiring peripheral venoarterial extracorporeal membrane oxygenation (VA ECMO) and its risk factors at the time of cannulation and during extracorporeal membrane oxygenation (ECMO) support and to assess vascular complications in association with decannulation. Material and methods: Between January 2010 to January 2020, out of 1,030 eligible patients requiring VA-ECMO, 427 with analyzable vascular screening were included. Duplex sonography and/or CT scan after decannulation were used to screen for thrombosis and pulmonary embolism as well as arterial complications. Near-infrared spectrometry (NIRS) was established at the time of cannulation and was continuously monitored during the ECMO therapy. Results: The prevalence of venous complications was 27%. Thrombosis and pulmonary embolism were observed in 21 and 7% of patients, respectively. Pulmonary embolism was more frequently diagnosed in patients with thrombosis (22 vs. 3%, p < 0.001). In multivariate analysis, cannulation in the jugular vein was determined as a risk factor for venous thrombosis in contrast to the extent of anticoagulation. The prevalence of arterial complications was 37%, mainly ischemia followed by bleeding, dissection, and compartment syndrome. Vascular surgery was necessary for 19% of the patients, of whome 1% required major amputations. A distal perfusion cannula (DPC) was implanted at cannulation in 24% of patients and secondarily in 16% of patients after cannulation as required during ECMO support. In the multivariate analysis, risk factors for leg ischemia at the time of cannulation were elevated D-dimers, lower NIRS on the cannulated leg, and lack of a DPC. The best discriminative parameter was the difference in NIRS between the non-cannulated leg and the cannulated leg. In contrast, during ECMO support, only the lack of a DPC was associated with leg ischemia. A similar rate of complications associated with decannulation, mainly arterial thrombosis, ischemia, or bleeding, was seen with percutaneous and surgical approaches (18 vs. 17%, p = 0.295). Conclusion: Patients requiring VA ECMO should be routinely screened for vascular complications. The decision to insert a DPC should be evaluated individually. However, NIRS monitoring of the cannulated leg and the non-cannulated leg is essential to identify the legs at risk for critical ischemia. As complications associated with decannulation were equally distributed between percutaneous and surgical approaches, the applied method may be chosen according to local experience.

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 (rSO2) 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). rSO2 = 15% (11/97) prior to cannulation was only found in non-survivors. Among survivors, initial rSO2 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, rSO2 = 15% immediately prior to cannulation for ECPR did not result in any survivors, thus might be a marker for futile cannulation in ECPR. Higher rSO2 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.