Author Correction: Beta Trace Protein does not outperform Creatinine and Cystatin C in estimating Glomerular Filtration Rate in Older Adults.

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Beta Trace Protein does not outperform Creatinine and Cystatin C in estimating Glomerular Filtration Rate in Older Adults.

Despite intense research the optimal endogenous biomarker for glomerular filtration rate (GFR) estimation has not been identified yet. We analyzed if ß-trace protein (BTP) improved GFR estimation in elderly. 566 participants aged 70+ from the population-based Berlin Initiative Study were included in a cross-sectional validation study. BTP, standardized creatinine and cystatin C were measured in participants with iohexol clearance measurement as gold standard method for measured GFR (mGFR). In a double logarithmic linear model prediction of mGFR by BTP was assessed. Analyses with BTP only and combined with creatinine and cystatin C were performed. Additionally, performance of GFR estimating equations was compared to mGFR. We found that the combination of all three biomarkers showed the best prediction of mGFR (r2 = 0.83), whereat the combination of creatinine and cystatin C provided only minimally diverging results (r2 = 0.82). Single usage of BTP showed worst prediction (r2 = 0.67) within models with only one biomarker. Subgroup analyses (arterial hypertension, diabetes, body mass index ≤23 and >30) demonstrated a slight additional benefit of including BTP into the prediction model for diabetic, hypertensive and lean patients. Among BTP-containing GFR equations the Inker BTP-based equation showed superior performance. Especially the use of cystatin C renders the addition of BTP unnecessary.

Effects of Volatile Anesthetics on Mortality and Postoperative Pulmonary and Other Complications in Patients Undergoing Surgery: A Systematic Review and Meta-analysis.

BACKGROUND: It is not known whether modern volatile anesthetics are associated with less mortality and postoperative pulmonary or other complications in patients undergoing general anesthesia for surgery. METHODS: A systematic literature review was conducted for randomized controlled trials fulfilling following criteria: (1) population: adult patients undergoing general anesthesia for surgery; (2) intervention: patients receiving sevoflurane, desflurane, or isoflurane; (3) comparison: volatile anesthetics versus total IV anesthesia or volatile anesthetics; (4) reporting on: (a) mortality (primary outcome) and (b) postoperative pulmonary or other complications; (5) study design: randomized controlled trials. The authors pooled treatment effects following Peto odds ratio (OR) meta-analysis and network meta-analysis methods. RESULTS: Sixty-eight randomized controlled trials with 7,104 patients were retained for analysis. In cardiac surgery, volatile anesthetics were associated with reduced mortality (OR = 0.55; 95% CI, 0.35 to 0.85; P = 0.007), less pulmonary (OR = 0.71; 95% CI, 0.52 to 0.98; P = 0.038), and other complications (OR = 0.74; 95% CI, 0.58 to 0.95; P = 0.020). In noncardiac surgery, volatile anesthetics were not associated with reduced mortality (OR = 1.31; 95% CI, 0.83 to 2.05, P = 0.242) or lower incidences of pulmonary (OR = 0.67; 95% CI, 0.42 to 1.05; P = 0.081) and other complications (OR = 0.70; 95% CI, 0.46 to 1.05; P = 0.092). CONCLUSIONS: In cardiac, but not in noncardiac, surgery, when compared to total IV anesthesia, general anesthesia with volatile anesthetics was associated with major benefits in outcome, including reduced mortality, as well as lower incidence of pulmonary and other complications. Further studies are warranted to address the impact of volatile anesthetics on outcome in noncardiac surgery.

Atopic dermatitis is associated with an increased risk for rheumatoid arthritis and inflammatory bowel disease, and a decreased risk for type 1 diabetes.

BACKGROUND: Atopic dermatitis (AD) is characterized by epidermal barrier failure and immune-mediated inflammation. Evidence on AD as a potential risk factor for inflammatory comorbidities is scarce. OBJECTIVES: We sought to test the hypothesis that prevalent AD is a risk factor for incident rheumatoid arthritis (RA) and inflammatory bowel disease (IBD; Crohn disease [CD], ulcerative colitis [UC]) and is inversely related to type 1 diabetes (T1D) and to investigate established RA, IBD, and T1D susceptibility loci in AD. METHODS: This cohort study used data from German National Health Insurance beneficiaries aged 40 years or younger (n = 655,815) from 2005 through 2011. Prevalent AD in the period 2005 to 2006 was defined as primary exposure, and incident RA, IBD, and T1D in the period 2007 to 2011 were defined as primary outcomes. Risk ratios were calculated with generalized linear models. Established RA, IBD, and T1D loci were explored in high-density genotyping data from 2,425 cases with AD and 5,449 controls. RESULTS: Patients with AD (n = 49,847) were at increased risk for incident RA (risk ratio [RR], 1.72; 95% CI, 1.25-2.37) and/or IBD (CD: RR, 1.34; 95% CI, 1.11-1.61; UC: RR, 1.25; 95% CI, 1.03-1.53). After adjusting for health care utilization, there was a nominally significant inverse effect on T1D risk (RR, 0.72; 95% CI, 0.53-0.998). There was no disproportionate occurrence of known RA, CD, UC, or T1D risk alleles in AD. CONCLUSIONS: AD is a risk factor for the development of RA and IBD. This excess comorbidity cannot be attributed to major known IBD and RA genetic risk factors.

Allergy immunotherapy for allergic rhinitis effectively prevents asthma: Results from a large retrospective cohort study.

BACKGROUND: Allergic rhinitis (AR) is a main risk factor for the development of asthma. Two randomized open-label trials indicated that allergy immunotherapy (AIT) prevents the onset of asthma in patients with AR. However, these trials have methodological limitations, and it is unclear to what extent this experimental efficacy translates into clinical effectiveness. OBJECTIVES: We sought to investigate the effectiveness of AIT to prevent asthma in patients with AR. METHODS: Using routine health care data from German National Health Insurance beneficiaries, we identified a consecutive cohort of 118,754 patients with AR but without asthma who had not received AIT in 2005. These patients were stratified into one group starting AIT in 2006 and one group receiving no AIT in 2006. Both groups were observed regarding the risk of incident asthma in 2007 to 2012. Risk ratios (RRs) were calculated with generalized linear models by using a Poisson link function with robust error variance and adjustment for age, sex, health care use because of AR, and use of antihistamines. RESULTS: In a total of 2431 (2.0%) patients, AIT was started in 2006. Asthma was newly diagnosed from 2007-2012 in 1646 (1.4%) patients. The risk of incident asthma was significantly lower in patients exposed to AIT (RR, 0.60; 95% CI, 0.42-0.84) compared with patients receiving no AIT in 2006. Sensitivity analyses suggested significant preventive effects of subcutaneous immunotherapy (RR, 0.54; 95% CI, 0.38-0.84) and AIT including native (nonallergoid) allergens (RR, 0.22; 95% CI, 0.02-0.68). AIT for 3 or more years tended to have stronger preventive effects than AIT for less than 3 years. CONCLUSION: AIT effectively prevents asthma in patients with AR in a real-world setting. Confounding by indication cannot be excluded but would lead to an underestimation of the true preventive effects of AIT.

Behavioral traits and airport type affect mammal incidents with U.S. civil aircraft.

Wildlife incidents with aircraft cost the United States (U.S.) civil aviation industry >US$1.4 billion in estimated damages and loss of revenue from 1990 to 2009. Although terrestrial mammals represented only 2.3 % of wildlife incidents, damage to aircraft occurred in 59 % of mammal incidents. We examined mammal incidents (excluding bats) at all airports in the Federal Aviation Administration (FAA) National Wildlife Strike Database from 1990 to 2010 to characterize these incidents by airport type: Part-139 certified (certificated) and general aviation (GA). We also calculated relative hazard scores for species most frequently involved in incidents. We found certificated airports had more than twice as many incidents as GA airports. Incidents were most frequent in October (n = 215 of 1,764 total) at certificated airports and November (n = 111 of 741 total) at GA airports. Most (63.2 %) incidents at all airports (n = 1,523) occurred at night but the greatest incident rate occurred at dusk (177.3 incidents/hr). More incidents with damage (n = 1,594) occurred at GA airports (38.6 %) than certificated airports (19.0 %). Artiodactyla (even-toed ungulates) incidents incurred greatest (92.4 %) damage costs (n = 326; US$51.8 million) overall and mule deer (Odocoileus hemionus) was the most hazardous species. Overall, relative hazard score increased with increasing log body mass. Frequency of incidents was influenced by species relative seasonal abundance and behavior. We recommend airport wildlife officials evaluate the risks mammal species pose to aircraft based on the hazard information we provide and consider prioritizing management strategies that emphasize reducing their occurrence on airport property.

Early Life Eczema, Food Introduction, and Risk of Food Allergy in Children.

The effect of food introduction timing on the development of food allergy remains controversial. We sought to examine whether the presence of childhood eczema changes the relationship between timing of food introduction and food allergy. The analysis includes 960 children recruited as part of a family-based food allergy cohort. Food allergy was determined by objective symptoms developing within 2 hours of ingestion, corroborated by skin prick testing/specific IgE. Physician diagnosis of eczema and timing of formula and solid food introduction were obtained by standardized interview. Cox Regression analysis provided hazard ratios for the development of food allergy for the same subgroups. Logistic regression models estimated the association of eczema and formula/food introduction with the risk of food allergy, individually and jointly. Of the 960 children, 411 (42.8%) were allergic to 1 or more foods and 391 (40.7%) had eczema. Children with eczema had a 8.4-fold higher risk of food allergy (OR, 95% CI: 8.4, 5.9-12.1). Among all children, later (>6 months) formula and rice/wheat cereal introduction lowered the risk of food allergy. In joint analysis, children without eczema who had later formula (OR, 95% CI: 0.5, 0.3-0.9) and later (>1 year) solid food (OR, 95% CI: 0.5, 0.3-0.95) introduction had a lower risk of food allergy. Among children with eczema, timing of food or formula introduction did not modify the risk of developing food allergy. Later food introduction was protective for food allergy in children without eczema but did not alter the risk of developing food allergy in children with eczema.

Physiological and psychological stress reactivity in chronic tinnitus.

Several models of tinnitus maintenance emphasize the importance of cognitive, emotional and psychophysiological processes. These factors contribute to distress in patients with decompensated tinnitus symptoms. We investigated whether tinnitus patients show increased physiological levels of arousal, more intense stress reactivity patterns and exaggerated psychological strain compared to healthy controls. Seventy tinnitus patients and 55 healthy controls underwent various stress tests. Muscular reactivity and peripheral arousal as well as strain ratings were assessed. Tinnitus patients reported significantly more strain during stress tests compared to healthy controls. Few physiological reactivity patterns differed significantly between the two groups. The physiological data thus only partly supported a hyperreactivity hypothesis. Strain reports and physiological data were only marginally correlated. Tinnitus patients show maladaptive appraisal processes during stress exposure, yet physiological reactivity is only slightly affected. Treatment programs for patients with decompensated tinnitus symptoms should account for appraisal processes and coping mechanisms in stressful situations.

The rat leukocyte-type 12-lipoxygenase exhibits an intrinsic hepoxilin A3 synthase activity.

Hepoxilins are biologically relevant eicosanoids formed via the 12-lipoxygenase pathway of the arachidonic acid cascade. Although these eicosanoids exhibit a myriad of biological activities, their biosynthetic mechanism has not been investigated in detail. We examined the arachidonic acid metabolism of RINm5F rat insulinoma cells and found that they constitutively express a leukocyte-type 12S-lipoxygenase. Moreover, we observed that RINm5F cells exhibit an active hepoxilin A(3) synthase that converts exogenous 12S-HpETE (12S-5Z,8-Z,10E,14Z-12-hydro(pero)xy-eicosa-5,8,10,14-tetraenoic acid) or arachidonic acid predominantly to hepoxilin A(3). 12S-lipoxygenase and hepoxilin A(3) synthase activities were co-localized in the cytosol; immunoprecipitation with an anti-12S-lipoxygenase antibody co-precipitated the two catalytic activities. These data suggested that hepoxilin A(3) synthase activity may be considered an intrinsic catalytic property of the leukocyte-type 12S-lipoxygenase. To test this hypothesis we cloned the leukocyte-type 12S-LOX from RINm5F cells, expressed it in Pichia pastoris, and found that the recombinant enzyme exhibited both 12S-lipoxygenase and hepoxilin A(3) synthase activities. The recombinant human platelet-type 12S-lipoxygenase and the porcine leukocyte-type 12S-lipoxygenase also exhibited hepoxilin A(3) synthase activity. In contrast, the native rabbit reticulocyte-type 15S-lipoxygenase did not convert 12S-HpETE to hepoxilin isomers. These data suggest that the positional specificity of lipoxygenases may be crucial for this catalytic function. This hypothesis was confirmed by site-directed mutagenesis studies that altered the positional specificity of the rat leukocyte-type 12S- and the rabbit reticulocyte-type 15-lipoxygenase. In summary, it may be concluded that naturally occurring 12S-lipoxygenases exhibit an intrinsic hepoxilin A(3) synthase activity that is minimal in lipoxygenase isoforms with different positional specificity.