Severe pulmonary mucorales superinfection in three influenzapatients with and without influenza-associated aspergillosis

Mucormycosisis an opportunistic fungal disease which affects immunocompromised hosts including patients with haematologic malignancies and poorly controlled diabetes mellitus. Mucorales grow invasively and are associated with high mortality even if promptly diagnosed. Viral infection like influenza can cause severe pneumonia and is associated with pulmonary aspergillosis. Here we report three separate cases of Mucorales super infection in critically-ill patients with influenza infection, one of them histologically confirmed. Two patients also had influenza-associated pulmonary aspergillosis. Two patients had fatal clinical outcome despite intensive care. The simultaneous detection of these two rare mold infections in patients with severe influenza is highly remarkable and calls for increased awareness

Impact of the matching algorithm on the treatment effect estimate: A neutral comparison study

Propensity score matching is increasingly being used in the medical literature. Choice of matching algorithms, reporting quality, and estimands are oftentimes not discussed. We evaluated the impact of propensity score matching algorithms, based on a recent clinical dataset, with three commonly used outcomes. The resulting estimands for different strengths of treatment effects were compared in a neutral comparison study and based on a thoroughly designed simulation study. Different algorithms yielded different levels of balance after matching. Along with full matching and genetic matching with replacement, good balance was achieved with nearest neighbor matching with caliper but thereby more than one fifth of the treated units were discarded. Average marginal treatment effect estimates were least biased with genetic or nearest neighbor matching, both with replacement and full matching. Double adjustment yielded conditional treatment effects that were closer to the true values, throughout. The choice of the matching algorithm had an impact on covariate balance after matching as well as treatment effect estimates. In comparison, genetic matching with replacement yielded better covariate balance than all other matching algorithms. A literature review in the British Medical Journal including its subjournals revealed frequent use of propensity score matching; however, the use of different matching algorithms before treatment effect estimation was only reported in one out of 21 studies. Propensity score matching is a methodology for causal treatment effect estimation from observational data; however, the methodological difficulties and low reporting quality in applied medical research need to be addressed

Current clinical practice in using adjunctive extracorporeal blood purification in sepsis and septic shock: results from the ESICM “EXPLORATION” survey

Background: Despite a lack of clear evidence extracorporeal blood purification (EBP) is increasingly used as an adjunctive treatment in septic shock based on its biological plausibility. However, current state of praxis and believes in both efficacy and level of evidence are very heterogeneous. Methods: The "EXPLORATION" (Current Clinical Practice in using adjunctive extracorporeal blood purification in septic shock), a web-based survey endorsed by the European Society of Intensive Care Medicine (ESICM), questioned both the current local clinical practices as well as future perspectives of EBP in sepsis and septic shock. Results: One hundred and two people participated in the survey. The majority of three quarters of participants (74.5%) use adjunctive EBP in their clinical routine with a varying frequency of description. Unselective cytokine adsorption (CA) (37.5%) and therapeutic plasma exchange (TPE) (34.1%) were by far the most commonly used modalities. While the overall theoretical rational was found to be moderate to high by the majority of the participants (74%), the effectively existing clinical evidence was acknowledged to be rather low (66%). Although CA was used most frequently in clinical practice, both the best existing clinical evidence endorsing its current use (45%) as well the highest potential to be explored in future clinical trials (51.5%) was attributed to TPE. Conclusions: Although the majority of participants use EBP techniques in their clinical practice and acknowledge a subjective good theoretical rationale behind it, the clinical evidence is assessed to be limited. While both CA and TPE are by far the most common used technique, both clinical evidence as well as future potential for further exploration in clinical trials was assessed to be the highest for TPE

Targeting the host response in sepsis: current approaches and future evidence

Sepsis, a dysregulated host response to infection characterized by organ failure, is one of the leading causes of death worldwide. Disbalances of the immune response play an important role in its pathophysiology. Patients may develop simultaneously or concomitantly states of systemic or local hyperinflammation and immunosuppression. Although a variety of effective immunomodulatory treatments are generally available, attempts to inhibit or stimulate the immune system in sepsis have failed so far to improve patients’ outcome. The underlying reason is likely multifaceted including failure to identify responders to a specific immune intervention and the complex pathophysiology of organ dysfunction that is not exclusively caused by immunopathology but also includes dysfunction of the coagulation system, parenchymal organs, and the endothelium. Increasing evidence suggests that stratification of the heterogeneous population of septic patients with consideration of their host response might led to treatments that are more effective. The purpose of this review is to provide an overview of current studies aimed at optimizing the many facets of host response and to discuss future perspectives for precision medicine approaches in sepsis

Ventilation management and outcomes in out-of-hospital cardiac arrest: a protocol for a preplanned secondary analysis of the TTM2 trial

IntroductionMechanical ventilation is a fundamental component in the management of patients post cardiac arrest. However, the ventilator settings and the gas-exchange targets used after cardiac arrest may not be optimal to minimise post-anoxic secondary brain injury. Therefore, questions remain regarding the best ventilator management in such patients.Methods and analysisThis is a preplanned analysis of the international randomised controlled trial, targeted hypothermia versus targeted normothermia after out-of-hospital cardiac arrest (OHCA)–target temperature management 2 (TTM2). The primary objective is to describe ventilatory settings and gas exchange in patients who required invasive mechanical ventilation and included in the TTM2 trial. Secondary objectives include evaluating the association of ventilator settings and gas-exchange values with 6 months mortality and neurological outcome. Adult patients after an OHCA who were included in the TTM2 trial and who received invasive mechanical ventilation will be eligible for this analysis. Data collected in the TTM2 trial that will be analysed include patients’ prehospital characteristics, clinical examination, ventilator settings and arterial blood gases recorded at hospital and intensive care unit (ICU) admission and daily during ICU stay.Ethics and disseminationThe TTM2 study has been approved by the regional ethics committee at Lund University and by all relevant ethics boards in participating countries. No further ethical committee approval is required for this secondary analysis. Data will be disseminated to the scientific community by abstracts and by original articles submitted to peer-reviewed journals.Trial registration numberNCT02908308

Oxygen targets and 6-month outcome after out of hospital cardiac arrest: a pre-planned sub-analysis of the targeted hypothermia versus targeted normothermia after Out-of-Hospital Cardiac Arrest (TTM2) trial

Background: Optimal oxygen targets in patients resuscitated after cardiac arrest are uncertain. The primary aim of this study was to describe the values of partial pressure of oxygen values (PaO2) and the episodes of hypoxemia and hyperoxemia occurring within the first 72 h of mechanical ventilation in out of hospital cardiac arrest (OHCA) patients. The secondary aim was to evaluate the association of PaO2 with patients' outcome. Methods: Preplanned secondary analysis of the targeted hypothermia versus targeted normothermia after OHCA (TTM2) trial. Arterial blood gases values were collected from randomization every 4 h for the first 32 h, and then, every 8 h until day 3. Hypoxemia was defined as PaO2 300 mmHg. Mortality and poor neurological outcome (defined according to modified Rankin scale) were collected at 6 months. Results: 1418 patients were included in the analysis. The mean age was 64 ± 14 years, and 292 patients (20.6%) were female. 24.9% of patients had at least one episode of hypoxemia, and 7.6% of patients had at least one episode of severe hyperoxemia. Both hypoxemia and hyperoxemia were independently associated with 6-month mortality, but not with poor neurological outcome. The best cutoff point associated with 6-month mortality for hypoxemia was 69 mmHg (Risk Ratio, RR = 1.009, 95% CI 0.93-1.09), and for hyperoxemia was 195 mmHg (RR = 1.006, 95% CI 0.95-1.06). The time exposure, i.e., the area under the curve (PaO2-AUC), for hyperoxemia was significantly associated with mortality (p = 0.003). Conclusions: In OHCA patients, both hypoxemia and hyperoxemia are associated with 6-months mortality, with an effect mediated by the timing exposure to high values of oxygen. Precise titration of oxygen levels should be considered in this group of patients. Trial registration: clinicaltrials.gov NCT02908308 , Registered September 20, 2016. Keywords: Cardiac arrest; Hyperoxemia; Hypoxemia; Mortality; Neurological outcom