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

Epidemiological studies of severe infections in COPD

It is well known that patients with COPD have an increased risk of lower respiratory tract infections, but less is known about the association with other infections. The aim of this thesis was to explore epidemiological aspects of severe infections in COPD, using public registries in Sweden. In the first study, incidence rates of tuberculosis were compared in all individuals discharged with COPD, 1987-2003, with reference individuals from the general population. COPD patients were found to have a three-fold increased incidence of active tuberculosis. In the second study, incidence rates of tuberculosis were examined in participants in a health screening programme 1974-1992 who performed a spirometry at baseline. The risk of tuberculosis was found to be inversely correlated with the level of lung function. In the third study, a discharge diagnosis of COPD was validated against the original medical files. The degree of certainty of the COPD-diagnosis varied and around 10% were considered to be misclassified. In the fourth study, we compared the incidence rates of bacteraemia in individuals discharged with a COPD diagnosis, 1990-2003, and controls. COPD patients had a 2.5-fold increased incidence of bacteraemia which was paralleled by an increased risk of hospitalisation for infectious diseases. In the fifth study, the association between invasive pneumococcal disease and an underlying pulmonary disease was assessed, comparing pneumococcal cases from Southern Sweden, 1990-2008, to controls. Several chronic pulmonary diseases increased the risk of invasive pneumococcal disease but did not influence the mortality risk. Our findings show that COPD confers susceptibility to a broad spectrum of severe infections. Increased awareness could benefit these patients, reducing morbidity and mortality

Prognostic significance of body temperature in the emergency department vs the ICU in Patients with severe sepsis or septic shock : A nationwide cohort study

Background Increased body temperature in the Emergency Department (BT-ED) and the ICU (BT-ICU) is associated with lower mortality in patients with sepsis. Here, we compared how well BTED and BT-ICU predict mortality; investigated mortality in various combinations of BT-ED and BT-ICU, and; compared degree of fever in the ED and ICU and associated quality of care. Methods 2385 adults who were admitted to an ICU within 24 hours of ED arrival with severe sepsis or septic shock were included. Results Thirty-day mortality was 23.6%. Median BT-ED and BT-ICU was 38.1 and 37.6°C. Crude mortality decreased more than 5% points per°C increase for both BT-ED and BT-ICU. Adjusted OR for mortality was 0.82/°C increase for BT-ED (0.76-0.88, p < 0.001), and 0.89 for BT-ICU (0.83-0.95, p<0.001). Patients who were at/below median temperature in both the ED and in the ICU had the highest mortality, 32%, and those with over median in the ED and at/below in the ICU had the lowest, 16%, (p<0.001). Women had 0.2°C lower median BT-ED (p = 0.03) and 0.3°C lower BT-ICU (p<0.0001) than men. Older patients had lower BT in the ICU, but not in the ED. Fever was associated with a higher rate of sepsis bundle achievement in the ED, but lower nurse workload in the ICU. Conclusions BT-ED was more useful to prognosticate mortality than BT-ICU. Despite better prognosis in patients with elevated BT, fever was associated with higher quality of care in the ED. Future studies should assess how BT-ED can be used to improve triage of infected patients, assigning higher priority to patients with low-grade/no fever and vice versa. Patients with at/ below median BT in both ED and ICU have the highest mortality and should receive special attention. Different BT according to sex and age also needs further study

Recurrent erysipelas - risk factors and clinical presentation.

Erysipelas is a common infection that often recurs, but the impact of specific risk factors for reoccurrence remains elusive. In the present study we aimed at clarifying predisposing conditions for reoccurrence

Oral fluoroquinolone use and the risk of acute liver injury: a nationwide cohort study

Antibiotics are considered to be among the most frequent causes of drug-related acute liver injury (ALI). Although many ALIs have mild and reversible clinical outcomes, there is substantial risk of severe reactions leading to acute liver failure, need for liver transplant, and death. Recent studies have raised concerns of hepatotoxic potential related to the use of fluoroquinolones.MethodsThis study examined the risk of ALI associated with oral fluoroquinolone treatment compared with amoxicillin (419 930 courses, propensity score matched 1:1). The information on drug use was collected from a national, registry-based cohort derived from all Swedish adults aged 40–85 years.ResultsDuring a follow-up period of 60 days, users of oral fluoroquinolones had a >2-fold risk of ALI compared to users of amoxicillin (hazard ratio, 2.32 [95% confidence interval {CI}, 1.01–5.35). The adjusted absolute risk difference for use of fluoroquinolones as compared to amoxicillin was 4.94 (95% CI, .04–16.3) per 1 million episodes.ConclusionsIn this propensity score–matched study, fluoroquinolone treatment was associated with an increased risk of ALI in the first 2 months after starting treatment