The Fcγ Receptor IIA-R/R131 Genotype Is Associated with Severe Sepsis in Community-Acquired Pneumonia ▿

Community-acquired pneumonia (CAP) can be caused by a variety of microorganisms but is most frequently associated with Streptococcus pneumoniae and gram-negative bacteria like Haemophilus influenzae. Encapsulated bacteria are able to escape phagocytosis, unless they are bound by immunoglobulin G2 subclass antibodies. These antibodies interact with Fcγ receptor IIa (Fcγ-RIIa), thereby facilitating opsonophagocytosis of the encapsulated bacteria. We studied the relationship between the Fcγ-RIIa-R/H131 polymorphism and the clinical course of CAP and pathogen-specific susceptibility. Regarding methodology, the Fcγ-RIIa genotype R/H131 was determined in 200 patients with CAP and in 313 healthy controls and was correlated with the clinical course, laboratory parameters, and causative microorganism. The Fcγ-RIIa-R/R131 genotype was found more frequently in patients with severe sepsis (odds ratio [OR], 2.55; 95% confidence interval [CI], 1.30 to 5.00; P < 0.01). The majority of patients in this group suffered from invasive pneumococcal disease. The duration of hospital stay was longer for patients with the Fcγ-RIIa-R/R131 genotype. Fcγ-RIIa genotypes were not associated with an increased risk of CAP in general; however, the Fcγ-RIIa-R/R131 genotype was found more frequently in patients with CAP caused by H. influenzae than in controls (OR, 3.03; CI, 1.04 to 9.09; P < 0.05). In conclusion, the Fcγ-RIIa-R/R131 genotype is associated with severity of CAP and is more frequent in CAP caused by H. influenzae

A Microfluidics-Based Screening Tool to Assess the Impact of Blood Plasma Factors on Microvascular Integrity

This study provides a method to assess the impact of circulating plasma factors on microvascular integrity by using a recently developed microvessel-on-a-chip platform featuring the human endothelium that is partly surrounded by the extracellular matrix. The system is high-throughput, which allows parallel analysis of organ-level microvessel pathophysiology, including vascular leakage. Ethylenediaminetetraacetic acid plasma samples are mixed with inhibitors for recalcification of the plasma samples to avoid activation of the coagulation- or complement system. Moreover, the assay is validated by spiking vascular endothelial growth factor, histamine, or tumor necrosis factor alpha to recalcified plasma and confirms their modulation of microvessel barrier function at physiologically relevant concentrations. Finally, this study shows that perfusing the microvessels with recalcified plasma samples of coronavirus disease-2019 patients, with a confirmed proinflammatory profile, results in markedly increased leakage of the microvessels. The assay provides opportunities for diagnostic screening of inflammatory or endothelial disrupting plasma factors associated with endothelial dysfunction

Cost-effectiveness in extracorporeal life support in critically ill adults in the Netherlands

Contains fulltext : 190109.pdf (publisher's version ) (Open Access

Cost-effectiveness in extracorporeal life support in critically ill adults in the Netherlands

BACKGROUND: Extracorporeal life support (ECLS) is used to support the cardiorespiratory function in case of severe cardiac and/or respiratory failure in critically ill patients. According to the ELSO guidelines ECLS should be considered when estimated mortality risk approximates 80%. ECLS seems an efficient therapy in terms of survival benefit, but no undisputed evidence is delivered yet. The aim of the study is to assess the health-related quality of life after ECLS treatment and its cost effectiveness. METHODS: We will perform a prospective observational cohort study. All adult patients who receive ECLS in the participating centers will be included. Exclusion criteria are patients in whom the ECLS is only used to bridge a procedure (like a high risk percutaneous coronary intervention or surgery) or the absence of informed consent. Data collection includes patient characteristics and data specific for ECLS treatment. Severity of illness and mortality risk is measured as precisely as possible using measurements for the appropriate age group and organ failure. For analyses on survival patients will act as their own control as we compare the actual survival with the estimated mortality on initiation of ECLS if conservative treatment would have been continued. Survivors are asked to complete validated questionnaires on health related quality of life (EQ5D-5 L) and on medical consumption and productivity losses (iMTA/iPCQ) at 6 and 12 months. Also the health related quality of life 1 month prior to ECLS initiation will be obtained by a questionnaire, if needed provided by relatives. With an estimated overall survival of 62% 210 patients need to be recruited to make a statement on cost effectiveness for all ECLS indications. DISCUSSION: If our hypothesis that ECLS treatment is cost-effective is confirmed by this prospective study this could lead to an even broader use of ECLS treatment. TRIAL REGISTRATION: The trial is registered at ( NCT02837419 ) registration date July 19, 2016 and with the Dutch trial register, http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=6599

Between-centre differences in care for in-hospital cardiac arrest

Background: Survival after in-hospital cardiac arrest is poor, but current literature shows substantial heterogeneity in reported survival rates. This study aims to evaluate care for patients suffering in-hospital cardiac arrest (IHCA) in the Netherlands by assessing between-hospital heterogeneity in outcomes and to explain this heterogeneity stemming from differences in case-mix or differences in quality of care. Methods: A prospective multicentre study was conducted comprising 14 centres. All IHCA patients were included. The adjusted variation in structure and process indicators of quality of care and outcomes (in-hospital mortality and cerebral performance category [CPC] scale) was assessed with mixed effects regression with centre as random intercept. Variation was quantified using the median odds ratio (MOR), representing the expected odds ratio for poor outcome between two randomly picked centres. Results: After excluding centres with less than 10 inclusions (2 centres), 701 patients were included of whom, 218 (32%) survived to hospital discharge. The unadjusted and case-mix adjusted MOR for mortality was 1.19 and 1.05, respectively. The unadjusted and adjusted MOR for CPC score was 1.24 and 1.19, respectively. In hospitals where personnel received cardiopulmonary resuscitation (CPR) training twice per year, 183 (64.7%) versus 290 (71.4%) patients died or were in a vegetative state, and 59 (20.8%) versus 68 (16.7%) patients showed full recovery (p &lt; 0.001). Conclusion: In the Netherlands, survival after IHCA is relatively high and between-centre differences in outcomes are small. The existing differences in survival are mainly attributable to differences in case-mix. Variation in neurological outcome is less attributable to case-mix