Elevated plasma levels of heparin-binding protein in intensive care unit patients with severe sepsis and septic shock

Introduction: Rapid detection of, and optimized treatment for, severe sepsis and septic shock is crucial for successful outcome. Heparin-binding protein (HBP), a potent inducer of increased vascular permeability, is a potentially useful biomarker for predicting outcome in patients with severe infections. Our aim was to study the systemic release and dynamics of HBP in the plasma of patients with severe sepsis and septic shock in the ICU. Methods: A prospective study was conducted of two patient cohorts treated in the ICU at Karolinska University Hospital Huddinge in Sweden. A total of 179 patients was included, of whom 151 had sepsis (126 with septic shock and 25 patients with severe sepsis) and 28 a non-septic critical condition. Blood samples were collected at five time points during six days after admission. Results: HBP levels were significantly higher in the sepsis group as compared to the control group. At admission to the ICU, a plasma HBP concentration of >= 15 ng/mL and/or a HBP (ng/mL)/white blood cell count (10(9)/L) ratio of >2 was found in 87.2% and 50.0% of critically ill patients with sepsis and non-septic illness, respectively. A lactate level of >2.5 mmol/L was detected in 64.9% and 56.0% of the same patient groups. Both in the sepsis group (n = 151) and in the whole group (n = 179), plasma HBP concentrations at admission and in the last measured sample within the 144 hour study period were significantly higher among 28-day non-survivors as compared to survivors and in the sepsis group, an elevated HBP-level at baseline was associated with an increased case-fatality rate at 28 days. Conclusions: Plasma HBP levels were significantly higher in patients with severe sepsis or septic shock compared to patients with a non-septic illness in the ICU. HBP was associated with severity of disease and an elevated HBP at admission was associated with an increased risk of death. HBP that rises over time may identify patients with a deteriorating prognosis. Thus, repeated HBP measurement in the ICU may help monitor treatment and predict outcome in patients with severe infections

COPD and the Risk of Tuberculosis - A Population-Based Cohort Study

BACKGROUND: Both chronic obstructive pulmonary disease (COPD) and tuberculosis (TB) primarily affect the lungs and are major causes of morbidity and mortality worldwide. COPD and TB have common risk factors such as smoking, low socioeconomic status and dysregulation of host defence functions. COPD is a prevalent co-morbid condition, especially in elderly with TB but in contrast to other diseases known to increase the risk of TB, relatively little is known about the specific relationship and impact from COPD on TB-incidence and mortality. METHODS AND FINDINGS: All individuals > or = 40 years of age, discharged with a diagnosis of COPD from Swedish hospitals 1987-2003 were identified in the Swedish Inpatient Register (n = 115,867). Records were linked to the Swedish Tuberculosis Register 1989-2007 and the relative risk of active TB in patients with COPD compared to control subjects randomly selected from the general population (matched for sex, year of birth and county of residence) was estimated using Cox regression. The analyses were stratified by year of birth, sex and county of residence and adjusted for immigration status, socioeconomic status (SES) and inpatient co-morbidities previously known to increase the risk of TB. COPD patients had a three-fold increased hazard ratio (HR) of developing active TB (HR 3.0 (95% confidence interval 2.4 to 4.0)) that was mainly dependent on an increased risk of pulmonary TB. In addition, logistic regression estimates showed that COPD patients who developed active TB had a two-fold increased risk of death from all causes within first year after the TB diagnosis compared to the general population control subjects with TB (OR 2.2, 95% confidence interval 1.2 to 4.1). CONCLUSIONS: This population-based study comprised of a large number of COPD patients shows that these patients have an increased risk of developing active TB compared to the general population. The results raise concerns that the increasing global burden of COPD will increase the incidence of active TB. The underlying contributory factors need to be disentangled in further studies

The troika host-pathogen-extrinsic factors in tuberculosis: modulating inflammation and clinical outcomes

The Troika Host-Pathogen-Extrinsic Factors in Tuberculosis: Modulating Inflammation and Clinical OutcomesThe already enormous burden caused by tuberculosis (TB) will be further aggravated by the association of this disease with modern epidemics, as human immunodeficiency virus and diabetes. Furthermore, the increasingly aging population and the wider use of suppressive immune therapies hold the potential to enhance the incidence of TB. New preventive and therapeutic strategies based on recent advances on our understanding of TB are thus needed. In particular, understanding the intricate network of events modulating inflammation in TB will help to build more effective vaccines and host-directed therapies to stop TB. This review integrates the impact of host, pathogen, and extrinsic factors on inflammation and the almost scientifically unexplored complexity emerging from the interactions between these three factors. We highlight the exciting data showing a contribution of this troika for the clinical outcome of TB and the need of incorporating it when developing novel strategies to rewire the immune response in TB.HN-B acknowledges the receipt of research scholarships from Bolsa D. Manuel de Mello and the Portuguese Society for Pneumology. NO acknowledges FCT IF/00474/2014. SG is funded by the European Research Council (grant number 309540-EVODRTB); the Swiss National Science Foundation (grant number 310030_166687) SystemsX.ch. IC lab is financed by Ministerio de Economía y Competitividad (Spanish Government) research grant SAF2013-43521-R, SAF2016- 77346-R, and PROMETEO/2016/122 from Generalitat Valenciana and the European Research Council (ERC) (638553-TB-ACCELERATE). The MS lab is financed by FEDER—Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020—Operacional Programme for Competitiveness and Internationalisation (POCI), Portugal 2020, and by Portuguese funds through FCT in the framework of the project “Institute for Research and Innovation in Health Sciences” (POCI-01-0145-FEDER-007274). MS is an FCT Principal Investigator. Some graphical elements in the figures were designed by kjpargeter/Freepik. The funding agencies had no role in the design of the manuscriptinfo:eu-repo/semantics/publishedVersio

Den perfekta stormen. Kan EU-arbetsrätten sänka Sjöräddningssällskapet?

Frivilligarbete har efter ett par avgöranden i EU-domstolen kommit under särskild belysning också av Parlamentet. Rättspraxis har skjutit frivilligarbete allt närmare definitionerna av anställning och förvärvsarbete, i vart fall avseende vissa bestämmelser. Artikeln konstaterar att frivilligarbete är ett betydande del av det svenska civilsamhället - exempelvis organiseras i princip all sjöräddning med frivilliga medarbetare - och författaren problematiserar kring hur en "professionalisering" eller ökad reglering av frivilligarbete skulle skapa osäkerhet kring väsentliga delar av samhällslivet på ett sätt som skulle tjäna få övergripande syften