Role of ATP-sensitive potassium channels on hypoxic pulmonary vasoconstriction in endotoxemia

Background: ATP-regulated potassium channels (KATP) regulate pulmonary vascular tone and are involved in hypoxic pulmonary vasoconstriction (HPV). In patients with inflammation like sepsis or ARDS, HPV is impaired, resulting in a ventilation-perfusion mismatch and hypoxia. Since increase of vascular KATP channel Kir6.1 has been reported in animal models of endotoxemia, we studied the expression and physiological effects of Kir6.1 in murine endotoxemic lungs. We hypothesized that inhibition of overexpressed Kir6.1 increases HPV in endotoxemia. Methods: Mice (C57BL/6; n = 55) with (n = 27) and without (n = 28) endotoxemia (35 mg/kg LPS i.p. for 18 h) were analyzed for Kir6.1 gene as well as protein expression and HPV was examined in isolated perfused mouse lungs with and without selective inhibition of Kir6.1 with PNU-37883A. Pulmonary artery pressure (PAP) and pressure-flow curves during normoxic (FiO2 0.21) and hypoxic (FiO2 0.01) ventilation were obtained. HPV was quantified as the increase in perfusion pressure in response to hypoxic ventilation in mmHg of baseline perfusion pressure (ΔPAP) in the presence and absence of PNU-37883A. Results: Endotoxemia increases pulmonary Kir6.1 gene (+ 2.8 ± 0.3-fold) and protein expression (+ 2.1 ± 0.3-fold). Hypoxia increases HPV in lungs of control animals, while endotoxemia decreases HPV (∆PAP control: 9.2 ± 0.9 mmHg vs. LPS: 3.0 ± 0.7 mmHg, p < 0.05, means ± SEM). Inhibition of Kir6.1 with 1 μM PNU-37883A increases HPV in endotoxemia, while not increasing HPV in controls (∆PAP PNU control: 9.3 ± 0.7 mmHg vs. PNU LPS: 8.3 ± 0.9 mmHg, p < 0.05, means ± SEM). Conclusion: Endotoxemia increases pulmonary Kir6.1 gene and protein expression. Inhibition of Kir6.1 augments HPV in murine endotoxemic lungs

Prevalence and correlates of frailty among older adults: findings from the German health interview and examination survey

Background: Despite having the third highest proportion of people aged 60 years and older in the world, Germany has been recently reported as having the lowest prevalence of frailty of 15 European countries. The objective of the study is to describe the prevalence of frailty in a large nationwide population-based sample and examine associations with sociodemographic, social support and health characteristics. Methods: We performed a cross-sectional analysis of the first wave of the German Health Interview and Examination Survey for Adults (DEGS1) conducted 2008–2011. Participants were 1843 community-dwelling people aged 65–79 years. Frailty and pre-frailty were defined, according to modified Fried criteria, as 3 and more or 1–2 respectively, of the following: exhaustion, low weight, low physical activity, low walking speed and low grip strength. The Oslo-3 item Social Support Scale (OSS-3) was used. Patient Health Questionnaire (PHQ-9) measured depressive symptoms and the Digit Symbol Substitution Test (DSST) measured cognition. Associations between participants’ characteristics and frailty status were examined using unadjusted and adjusted multinomial logistic regression models estimating relative risk ratios (RRR) of frailty and pre-frailty. Results: The prevalence of frailty among women was 2.8% (CI 1.8-4.3) and pre-frailty 40.4% (CI 36.3-44.7) and among men was 2.3% (CI 1.3-4.1) and 36.9% (CI 32.7-41.3) respectively. Independent determinants of frailty, from unadjusted models, included older age, low socioeconomic status, poor social support, lower cognitive function and a history of falls. In adjusted models current depressive symptoms (RRR 12.86, CI 4.47-37.03), polypharmacy (RRR 7.78, CI 2.92-20.72) and poor hearing (RRR 5.38, CI 2.17-13.35) were statistically significantly associated with frailty. Conclusions: Frailty prevalence is relatively low among community-dwelling older adults in Germany. Modifiable characteristics like low physical activity provide relevant targets for individual and population-level frailty detection and intervention strategies

who is missed and why?

Background Public health monitoring depends on valid health and disability estimates in the population 65+ years. This is hampered by high non- participation rates in this age group. There is limited insight into size and direction of potential baseline selection bias. Methods We analyzed baseline non-participation in a register-based random sample of 1481 inner-city residents 65+ years, invited to a health examination survey according to demographics available for the entire sample, self-report information as available and reasons for non-participation. One year after recruitment, non- responders were revisited to assess their reasons. Results Five groups defined by participation status were differentiated: participants (N = 299), persons who had died or moved (N = 173), those who declined participation, but answered a short questionnaire (N = 384), those who declined participation and the short questionnaire (N = 324), and non-responders (N = 301). The results confirm substantial baseline selection bias with significant underrepresentation of persons 85+ years, persons in residential care or from disadvantaged neighborhoods, with lower education, foreign citizenship, or lower health-related quality of life. Finally, reasons for non-participation could be identified for 78 % of all non-participants, including 183 non- responders. Conclusion A diversity in health problems and barriers to participation exists among non-participants. Innovative study designs are needed for public health monitoring in aging populations

Are depressive symptoms associated with quality of care in diabetes? Findings from a nationwide populationbased study

Introduction We investigated whether the presence of depressive symptoms among adults with diagnosed diabetes is associated with adverse quality of diabetes care. Research design and methods The study population was drawn from the German national health survey ‘German Health Update’ 2014/2015-European Health Interview Survey and included 1712 participants aged ≥18 years with self-reported diabetes during the past 12 months. Depressive symptoms in the past 2weeks were assessed by the eight-item depression module of the Patient Health Questionnaire (PHQ-8), with PHQ-8 sum score values ≥10 indicating current depressive symptoms. We selected 12 care indicators in diabetes based on selfreported information on care processes and outcomes. Associations of depressive symptoms with those indicators were examined in multivariable logistic regression models with stepwise adjustments. Results Overall, 15.6% of adults with diagnosed diabetes reported depressive symptoms, which were higher in women than in men (18.7% vs 12.9%). Adjusted for age, sex, education, social support, health-related behaviors, and diabetes duration, adults with depressive symptoms were more likely to report acute hypoglycemia (OR 1.81, 95%CI 1.13 to 2.88) or hyperglycemia (OR 2.10, 95% CI 1.30 to 3.37) in the past 12 months, long-term diabetes complications (OR 2.30, 95% CI 1.55 to 3.39) as well as currently having a diet plan (OR 2.14, 95%CI 1.39 to 3.29) than adults without depressive symptoms. Significant associations between depressive symptoms and other care indicators were not observed. Conclusions The present population-based study of adults with diagnosed diabetes indicates an association between depressive symptoms and adverse diabetesspecific care with respect to outcome but largely not to process indicators. Our findings underline the need for intensified care for persons with diabetes and depressive symptoms. Future research needs to identify underlying mechanisms with a focus on the inter-relationship between diabetes, depression and diabetes-related distress.Peer Reviewe

Modifiable cardiovascular risk factors in adults aged 40–79 years in Germany with and without prior coronary heart disease or stroke

Background Control of modifiable cardiovascular disease (CVD) risk factors has substantially reduced CVD mortality, but risk factor levels in populations may change and need continuous monitoring. This study aims to provide current estimates of the prevalence of these risk factors in Germany according to sex and history of coronary heart disease (CHD) or stroke. Methods The analyses were based on data from the German Health Interview and Examination Survey for Adults (DEGS1; age 40–79 years, n = 5101), which is a cross-sectional population-based examination survey. CVD risk factors were defined according to recommendations in the European Guidelines on Cardiovascular Disease Prevention in Clinical Practice 2012. Results The mean age was 57 years and 52 % were female; 493 participants had prior CHD and 163 participants a prior stroke. The overall prevalence of behavioural risk factors ranged from 17.9 % for high risk alcohol consumption to 90 % for low vegetable intake. Blood pressure ≥ 140/90 mmHg was found in 21 % and 69 % had total cholesterol ≥ 5.0 mmol/l. Only 16 % met the targets for five behavioural factors combined (smoking, physical activity, fruit intake, alcohol intake and obesity), 13 % of those with and 16 % of those without CHD or stroke. The prevalences of most behavioural risk factors were higher among men compared to women. Conclusions There is a high prevention potential from modifiable cardiovascular risk factors in the general population aged 40–79 years in Germany and among those with prior CHD or stroke. Risk factors are often co-occurring, are interrelated and require combined educational, behavioral, medical and policy approaches

Outcomes and risk score for distal pancreatectomy with celiac axis resection (DP-CAR) : an international multicenter analysis

Background: Distal pancreatectomy with celiac axis resection (DP-CAR) is a treatment option for selected patients with pancreatic cancer involving the celiac axis. A recent multicenter European study reported a 90-day mortality rate of 16%, highlighting the importance of patient selection. The authors constructed a risk score to predict 90-day mortality and assessed oncologic outcomes. Methods: This multicenter retrospective cohort study investigated patients undergoing DP-CAR at 20 European centers from 12 countries (model design 2000-2016) and three very-high-volume international centers in the United States and Japan (model validation 2004-2017). The area under receiver operator curve (AUC) and calibration plots were used for validation of the 90-day mortality risk model. Secondary outcomes included resection margin status, adjuvant therapy, and survival. Results: For 191 DP-CAR patients, the 90-day mortality rate was 5.5% (95 confidence interval [CI], 2.2-11%) at 5 high-volume (1 DP-CAR/year) and 18% (95 CI, 9-30%) at 18 low-volume DP-CAR centers (P=0.015). A risk score with age, sex, body mass index (BMI), American Society of Anesthesiologists (ASA) score, multivisceral resection, open versus minimally invasive surgery, and low- versus high-volume center performed well in both the design and validation cohorts (AUC, 0.79 vs 0.74; P=0.642). For 174 patients with pancreatic ductal adenocarcinoma, the R0 resection rate was 60%, neoadjuvant and adjuvant therapies were applied for respectively 69% and 67% of the patients, and the median overall survival period was 19months (95 CI, 15-25months). Conclusions: When performed for selected patients at high-volume centers, DP-CAR is associated with acceptable 90-day mortality and overall survival. The authors propose a 90-day mortality risk score to improve patient selection and outcomes, with DP-CAR volume as the dominant predictor

Oxonium Ion-Guided Optimization of Ion Mobility-Assisted Glycoproteomics on the timsTOF Pro

Spatial separation of ions in the gas phase, providing information about their size as collisional cross-sections, can readily be achieved through ion mobility. The timsTOF Pro (Bruker Daltonics) series combines a trapped ion mobility device with a quadrupole, collision cell, and a time-of-flight analyzer to enable the analysis of ions at great speed. Here, we show that the timsTOF Pro is capable of physically separating N-glycopeptides from nonmodified peptides and producing high-quality fragmentation spectra, both beneficial for glycoproteomics analyses of complex samples. The glycan moieties enlarge the size of glycopeptides compared with nonmodified peptides, yielding a clear cluster in the mobilogram that, next to increased dynamic range from the physical separation of glycopeptides and nonmodified peptides, can be used to make an effective selection filter for directing the mass spectrometer to analytes of interest. We designed an approach where we (1) focused on a region of interest in the ion mobilogram and (2) applied stepped collision energies to obtain informative glycopeptide tandem mass spectra on the timsTOF Pro:glyco-polygon–stepped collision energy-parallel accumulation serial fragmentation. This method was applied to selected glycoproteins, human plasma– and neutrophil-derived glycopeptides. We show that the achieved physical separation in the region of interest allows for improved extraction of information from the samples, even at shorter liquid chromatography gradients of 15 min. We validated our approach on human neutrophil and plasma samples of known makeup, in which we captured the anticipated glycan heterogeneity (paucimannose, phosphomannose, high mannose, hybrid and complex glycans) from plasma and neutrophil samples at the expected abundances. As the method is compatible with off-the-shelve data acquisition routines and data analysis software, it can readily be applied by any laboratory with a timsTOF Pro and is reproducible as demonstrated by a comparison between two laboratories