Maternal Vascular Malperfusion and Anatomic Cord Abnormalities Are Prevalent in Pregnancies With Fetal Congenital Heart Disease.

OBJECTIVE: Impairments in the maternal-fetal environment are associated with adverse postnatal outcomes among infants with congenital heart disease. Therefore, we sought to investigate placental anomalies as they related to various forms of fetal congenital heart disease (FCHD). METHODS: We reviewed the placental pathology in singleton pregnancies with and without FCHD. FCHD was divided into separate categories (transposition physiology, obstructive left, obstructive right, biventricular without obstruction, and others). Exclusion criteria included other prenatally known structural malformations and/or aneuploidy. The significance threshold was set at p < 0.05 or False Discovery rate q < 0.05 when multiple tests were performed. RESULTS: The cohort included 215 FCHD and 122 non-FCHD placentas. FCHD placentas showed increased rates of maternal vascular malperfusion (24% vs. 5%, q < 0.001) and cord anomalies (27% vs. 1%, q < 0.001). Placentas with fetal TGA demonstrated a lower rate of hypoplasia when compared with other FCHD types (1/39 vs. 51/176, Fisher's exact p = 0.015). CONCLUSION: Placental maternal vascular malperfusion is increased in FCHD. The prevalence of vascular malperfusion did not differ by FCHD type, indicating that CHD type does not predict the likelihood of placental vascular dysfunction. Further investigation of the placental-fetal heart axis in FCHD is warranted given the importance of placental health.

Navigating the Future of Organisational Health Services Research in Germany and beyond: a Position Paper. / Die Zukunft der organisationsbezogenen Versorgungsforschung in Deutschland und darüber hinaus ­ ein Positionspapier.

BACKGROUND: Recent analyses have shown that in health services research in Germany, healthcare organisations are often considered primarily as a study setting, without fully taking their complex organisational nature into account, neither theoretically nor methodologically. Therefore, an initiative was launched to analyse the state of Organisational Health Services Research (OHSR) in Germany and to develop a strategic framework and road map to guide future efforts in the field. This paper summarizes positions that have been jointly developed by consulting experts from the interdisciplinary and international scientific community. METHODS: In July 2023, a scoping workshop over the course of three days was held with 32 (inter)national experts from different research fields centred around OHSR topics using interactive workshop methods. Participants discussed their perspectives on OHSR, analysed current challenges in OHSR in Germany and developed key positions for the field's development. RESULTS: The seven agreed-upon key positions addressed conceptual and strategic aspects. There was consensus that the field required the development of a research agenda that can guide future efforts. On a conceptual level, the need to address challenges in terms of interdisciplinarity, terminology, organisation(s) as research subjects, international comparative research and utilisation of organisational theory was recognized. On a strategic level, requirements with regard to teaching, promotion of interdisciplinary and international collaboration, suitable funding opportunities and participatory research were identified. CONCLUSIONS: This position paper seeks to serve as a framework to support further development of OHSR in Germany and as a guide for researchers and funding organisations on how to move OHSR forward. Some of the challenges discussed for German OHSR are equally present in other countries. Thus, this position paper can be used to initiate fruitful discussions in other countries.

Endoluminal Vacuum Therapy Using a New "Fistula Sponge" in Treating Defects of the Upper Gastrointestinal Tract-A Comparative, Retrospective Cohort Study.

Background and Objectives: Anastomotic insufficiencies (AI) and perforations of the upper gastrointestinal tract (uGIT) result in high morbidity and mortality. Endoscopic stent placement and endoluminal vacuum therapy (EVT) have been established as surgical revision treatment options. The Eso-Sponge® is the only licensed EVT system with limitations in treating small defects (<10 mm). Therefore, a fistula sponge (FS) was developed for the treatment of such defects as a new therapeutic approach. The aim of this study was to evaluate both EVT options' indications, success rates, and complications in a retrospective, comparative approach. Materials and Methods: Between 01/2018 and 01/2021, the clinical data of patients undergoing FS-EVT or conventional EVT (cEVT; Eso-Sponge®, Braun Melsungen, Melsungen, Germany) due to AI/perforation of the uGIT were recorded. Indication, diameter of leakage, therapeutic success, and complications during the procedure were assessed. FSs were prepared using a nasogastric tube and a porous drainage film (Suprasorb® CNP, Lohmann & Rauscher, Rengsdorf, Germany) sutured to the distal tip. Results: A total of 72 patients were included (20 FS-EVT; 52 cEVT). FS-EVT was performed in 60% suffering from AI (cEVT = 68%) and 40% from perforation (cEVT = 32%; p > 0.05). FS-EVT's duration was significantly shorter than cEVT (7.6 ± 12.0 d vs. 15.1 ± 14.3 d; p = 0.014). The mean diameter of the defect was 9 mm in the FS-EVT group compared to 24 mm in cEVT (p < 0.001). Therapeutic success was achieved in 90% (FS-EVT) and 91% (cEVT; p > 0.05). Conclusions: EVT comprises an efficient treatment option for transmural defects of the uGIT. In daily clinical practice, fistulas < 10 mm with large abscess formations poses a special challenge since intraluminal cEVT usually is ineffective. In these cases, the concept of extraluminal FS placement is safe and effective.

Pentastatin, a matrikine of the collagen IVα5, is a novel endogenous mediator of pulmonary endothelial dysfunction.

Deposition of basement membrane components, such as collagen IVα5, is associated with altered endothelial cell function in pulmonary hypertension. Collagen IVα5 harbors a functionally active fragment within its C-terminal noncollageneous (NC1) domain, called pentastatin, whose role in pulmonary endothelial cell behavior remains unknown. Here, we demonstrate that pentastatin serves as a mediator of pulmonary endothelial cell dysfunction, contributing to pulmonary hypertension. In vitro, treatment with pentastatin induced transcription of immediate early genes and proinflammatory cytokines and led to a functional loss of endothelial barrier integrity in pulmonary arterial endothelial cells. Mechanistically, pentastatin leads to ß1-integrin subunit clustering and Rho/ROCK activation. Blockage of the ß1-integrin subunit or the Rho/ROCK pathway partially attenuated the pentastatin-induced endothelial barrier disruption. Although pentastatin reduced the viability of endothelial cells, smooth muscle cell proliferation was induced. These effects on the pulmonary vascular cells were recapitulated ex vivo in the isolated-perfused lung model, where treatment with pentastatin-induced swelling of the endothelium accompanied by occasional endothelial cell apoptosis. This was reflected by increased vascular permeability and elevated pulmonary arterial pressure induced by pentastatin. This study identifies pentastatin as a mediator of endothelial cell dysfunction, which thus might contribute to the pathogenesis of pulmonary vascular disorders such as pulmonary hypertension.NEW & NOTEWORTHY This study is the first to show that pentastatin, the matrikine of the basement membrane (BM) collagen IVα5 polypeptide, triggers rapid pulmonary arterial endothelial cell barrier disruption, activation, and apoptosis in vitro and ex vivo. Mechanistically, pentastatin partially acts through binding to the ß1-integrin subunit and the Rho/ROCK pathway. These findings are the first to link pentastatin to pulmonary endothelial dysfunction and, thus, suggest a major role for BM-matrikines in pulmonary vascular diseases such as pulmonary hypertension.

Development and validation of a screening questionnaire for early identification of pregnant women at risk for excessive gestational weight gain.

BACKGROUND: Excessive weight gain during pregnancy is associated with adverse health outcomes for mother and child. Intervention strategies to prevent excessive gestational weight gain (GWG) should consider women's individual risk profile, however, no tool exists for identifying women at risk at an early stage. The aim of the present study was to develop and validate a screening questionnaire based on early risk factors for excessive GWG. METHODS: The cohort from the German "Gesund leben in der Schwangerschaft"/ "healthy living in pregnancy" (GeliS) trial was used to derive a risk score predicting excessive GWG. Sociodemographics, anthropometrics, smoking behaviour and mental health status were collected before week 12th of gestation. GWG was calculated using the last and the first weight measured during routine antenatal care. The data were randomly split into development and validation datasets with an 80:20 ratio. Using the development dataset, a multivariate logistic regression model with stepwise backward elimination was performed to identify salient risk factors associated with excessive GWG. The ß coefficients of the variables were translated into a score. The risk score was validated by an internal cross-validation and externally with data from the FeLIPO study (GeliS pilot study). The area under the receiver operating characteristic curve (AUC ROC) was used to estimate the predictive power of the score. RESULTS: 1790 women were included in the analysis, of whom 45.6% showed excessive GWG. High pre-pregnancy body mass index, intermediate educational level, being born in a foreign country, primiparity, smoking, and signs of depressive disorder were associated with the risk of excessive GWG and included in the screening questionnaire. The developed score varied from 0-15 and divided the women´s risk for excessive GWG into low (0-5), moderate (6-10) and high (11-15). The cross-validation and the external validation yielded a moderate predictive power with an AUC of 0.709 and 0.738, respectively. CONCLUSIONS: Our screening questionnaire is a simple and valid tool to identify pregnant women at risk for excessive GWG at an early stage. It could be used in routine care to provide targeted primary prevention measures to women at particular risk to gain excessive gestational weight. TRIAL REGISTRATION: NCT01958307, ClinicalTrials.gov, retrospectively registered 9 October 2013.

Exercise oscillatory ventilation in patients with advanced heart failure with and without left ventricular assist device.

BACKGROUND: Exercise oscillatory ventilation (EOV), indicating pathological fluctuations on pulmonary arterial pressure, is associated with mortality in patients with heart failure (HF). Whether left ventricular assist device (LVAD)-induced ventricular unloading can reverse EOV and may prevent short-term rehospitalization has not been investigated. METHODS: We performed a retrospective single-center in- and outpatient analysis of patients with (n = 20, LVAD) and without (n = 27, HF) circulatory support and reduced ejection fraction (EF, 22.8 ± 7.9%). The association of cardiopulmonary exercise testing (CPET) variables and 3 months-rehospitalization (3MR) as a primary outcome was analyzed. Furthermore, CPET variables were compared regarding the presence of EOV (+/-). RESULTS: Lower VO2peak (11.6 ± 4.9 ml/kg/min vs. 14.4 ± 4.3 ml/kg/min, p = 0.039), lower increase of PETCO2 (CI = 0.049-1.127; p = 0.068), and higher VE/VCO2 (43.8 ± 9.5 vs. 38.3 ± 10.6; p = 0.069) were associated with 3MR. Flattening of O2 pulse (CI = 0.139-2.379; p = 0.487) had no impact on 3MR. EOV was present in 59.5% (n = 28/47) of patients, without a significant difference between LVAD and HF patients (p = 0.959). Patients with HF/EOV+ demonstrated significantly lower VO2peak compared with HF/EOV- (p = 0.039). LVAD/EOV+ displayed significantly lower EF (p = 0.004) and fewer aortic valve opening than LVAD/EOV- (p = 0.027). CONCLUSIONS: Lower VO2peak , but not EOV, was associated with 3MR. EOV occurred at a similar rate in LVAD and HF patients, which may illustrate insufficient unloading during exercise in chronic LVAD therapy and may contribute to the limited exercise capacity following LVAD implantation. Simultaneous CPET and right heart catheterization studies are needed to elucidate whether EOV may serve as a non-invasive predictor of insufficient LV unloading necessitating LVAD reprograming.

Impairment of the NKT-STAT1-CXCL9 Axis Contributes to Vessel Fibrosis in Pulmonary Hypertension Caused by Lung Fibrosis.

Rationale: Pulmonary hypertension (PH) is a common, severe comorbidity in interstitial lung diseases such as pulmonary fibrosis (PF), and it has limited treatment options. Excessive vascular fibrosis and inflammation are often present in PH, but the underlying mechanisms are still not well understood. Objectives: To identify a novel functional link between natural killer T (NKT) cell activation and vascular fibrosis in PF-PH. Methods: Multicolor flow cytometry, secretome, and immunohistological analyses were complemented by pharmacological NKT cell activation in vivo, in vitro, and ex vivo. Measurements and Main Results: In pulmonary vessels of patients with PF-PH, increased collagen deposition was linked to a local NKT cell deficiency and decreased IL-15 concentrations. In a mouse model of PH caused by lung fibrosis, pharmacological NKT cell activation using a synthetic α-galactosylceramide analog (KRN7000) restored local NKT cell numbers and ameliorated vascular remodeling and right ventricular systolic pressure. Supplementation with activated NKT cells reduced collagen deposition in isolated human pulmonary arterial smooth muscle cells (hPASMCs) and in ex vivo precision-cut lung slices of patients with end-stage PF-PH. Coculture with activated NKT cells induced STAT1 signaling in hPASMCs. Secretome analysis of peripheral blood mononuclear cells identified CXCL9 and CXCL10 as indicators of NKT cell activation. Pharmacologically, CXCL9, but not CXCL10, potently inhibited collagen deposition in hPASMCs via the chemokine receptor CXCR3. Conclusions: Our results indicate that the absence of NKT cells impairs the STAT1-CXCL9-CXCR3 axis in PF-PH and that restoration of this axis by NKT cell activation may unravel a novel therapeutic strategy to target vascular fibrosis in interstitial lung disease.

[Measures and Recommendations for Ensuring Adequate Inpatient Care Capacities for Pandemic Management within a Region: Results of a Hybrid Delphi Method]. / Maßnahmen und Empfehlungen für die Sicherstellung adäquater stationärer Versorgungskapazitäten für das Pandemiemanagement innerhalb einer Region ­ Ergebnisse eines hybriden Delphi-Verfahrens.

INTRODUCTION: Since the beginning of the pandemic in spring 2020, inpatient healthcare has been under enormous burden, which is reflected especially in overworked staff, imprecise bed planning and/or data transfer. According to the recommendation of the Science Council, university clinics should play a controlling role in regional healthcare and act in conjunction with surrounding hospitals and practices. METHODS: In September 2021, 31 representatives from 18 university hospitals were invited to a hybrid Delphi study with a total of 4 survey rounds to discuss criteria for effective inpatient care in a pandemic situation, which were extracted from previous expert interviews. Criteria that were classified as very important/relevant by≥75% of the participants in the first round of the survey (consensus definition) were then further summarized in 4 different small groups. In a third Delphi round, all participants came together again to discuss the results of the small group discussions. Subsequently, these were prioritized as Optional ("can"), Desirable ("should") or Necessary ("must") recommendations. RESULTS: Of the invited clinical experts, 21 (67.7%) participated in at least one Delphi round. In an online survey (1st Delphi round), 233 criteria were agreed upon and reduced to 84 criteria for future pandemic management in four thematic small group discussions (2nd Delphi round) and divided into the small groups as follows: "Crisis Management and Crisis Plans" (n=20), "Human Resources Management and Internal Communication" (n=16), "Regional Integration and External Communication" (n=24) and "Capacity Management and Case & Care" (n=24). In the following group discussion (3rd Delphi round), the criteria were further modified and agreed upon by the experts, so that in the end result, there were 23 essential requirements and recommendations for effective inpatient care in a pandemic situation. CONCLUSION: The results draw attention to key demands of clinical representatives, for example, comprehensive digitization, standardization of processes and better (supra) regional networking in order to be able to guarantee needs-based care even under pandemic conditions. The present consensus recommendations can serve as guidelines for future pandemic management in the inpatient care sector.

One Website to Gather them All: Usability Testing of the New German SKin Cancer INFOrmation (SKINFO) Website-A Mixed-methods Approach.

Skin cancer patients increasingly search the internet to acquire disease-related information. However, information on the internet may be misleading. Recently, SKINFO has been launched, a website exclusively created for German-speaking skin cancer patients providing information as well as additional resources of verified quality. Here, we describe the results of the first usability test of SKINFO using a mixed-methods approach. Ten adult patients with skin cancer were recruited for usability testing in the skin cancer units of the University Hospitals of Erlangen and Dresden, Germany. Testing consisted of three different scenarios where patients were asked to find specific information on the SKINFO website guided by the think-aloud method. Descriptive analysis and content analyses were performed. All patients would recommend SKINFO and appreciated its content, design, and structure. Think-aloud analysis identified the topics layout, navigation, and content and structure which would benefit from refinement. Major criticism included the navigation through the website, and the desire for more specific information addressing patients' relatives and the latest, up-to-date information. Overall, usability testing showed that the unique web-based information platform has the potential to support patients coping with skin cancer and thus strengthen informed decision-making.

A novel TTR mutation (p.Ala65Val) underlying late-onset hereditary transthyretin (ATTRv) amyloidosis with mixed cardiac and neuropathic phenotype: a case report.

BACKGROUND: Hereditary transthyretin (ATTRv) amyloidosis is a rare, genetically heterogeneous and phenotypically variable systemic disease characterized by deposition of misfolded transthyretin fibrils in various tissues. ATTRv cardiomyopathy and progressive axonal polyneuropathy are the most common manifestations, leading to severe disability and ultimately death within approximately ten years. As disease-modifying treatment options evolve, timely diagnosis and treatment initiation are crucial to prevent rapid disease progression. CASE PRESENTATION: Here, we report on a 73-year old patient initially diagnosed with cardiac wild-type ATTR (ATTRwt) amyloidosis by endomyocardial biopsy. Molecular genetic analysis revealed a novel TTR sequence variant (p.Ala65Val) that is highly likely to be amyloidogenic in light of previously reported TTR mutations and the patient's clinical presentation and family history. CONCLUSIONS: Our findings expand the spectrum of known pathogenic TTR mutations and underline the importance of a thorough diagnostic workup in amyloidosis patients including careful genetic testing to avoid misdiagnosis and missing of treatment opportunities and to enable cascade testing and tracking of carriers.

Are pre- and early pregnancy lifestyle factors associated with the risk of preterm birth? A secondary cohort analysis of the cluster-randomised GeliS trial.

BACKGROUND: Maternal lifestyle is discussed as a modifiable determinant in the prevention of preterm birth. However, previous research on associations between individual lifestyle factors and preterm birth risk is inconclusive. In this secondary analysis, we investigated the associations between several modifiable antenatal lifestyle factors and the odds of preterm birth. METHODS: This secondary cohort analysis used data from the cluster-randomised controlled "healthy living in pregnancy" (GeliS) trial. Data were collected from early pregnancy to birth with maternity records, validated questionnaires and birth protocols. Women with complete datasets for all covariates were eligible for analysis. Multivariate logistic regression models, adjusted for recognised risk factors, were fitted to determine whether dietary quality, assessed with a healthy eating index (HEI), physical activity (PA) levels and antenatal anxiety/distress influenced the odds of preterm birth. Moreover, the combined association between pre-pregnancy body mass index (BMI) and HEI on the odds of preterm birth was explored. The independent associations of individual dietary components and types of PA on prematurity were assessed by adjusted logistic regression models. RESULTS: Overall, 1738 women were included in the analysis. A low HEI significantly increased the odds of preterm birth (OR 1.54 (CI 1.04 - 2.30), p = 0.033), while no associations with either low PA levels or antenatal anxiety/distress were observed. BMI significantly interacted with HEI on the association with prematurity (p = 0.036). Energy % from protein and the intake of average portions of vegetables and cereals were significantly negatively associated with the odds of preterm birth. There was no significant evidence of an association between different types of PA and prematurity. CONCLUSIONS: This cohort analysis revealed that low dietary quality in early pregnancy may increase the chance of giving birth prematurely, while healthier dietary choices may help to prevent preterm birth. More research on pre- and early pregnancy modifiable lifestyle factors is warranted. TRIAL REGISTRATION: This trial is registered with the Clinical Trial Registry ClinicalTrials.gov ( NCT01958307 ). Registration date 09 October 2013, retrospectively registered.

[Process for the Implementation of Evidence-Based Parenteral Nutrition in German Perinatal Centres - Outcomes of a Multidisciplinary Network]. / Prozess zur Implementierung Evidenzbasierter Parenteraler Ernährung in Deutschen Perinatalzentren ­ Ergebnisse eines Multidisziplinären Netzwerks.

INTRODUCTION: Parenteral nutrition, usually indicated for preterm infants with a birthweight<1500 g and sick newborns, enables the supply with critical nutrients. As a high degree of therapy safety is required, a European guideline provides recommendations for safe therapy procedures. The present project aimed to evaluate the implementation of the European guideline in German perinatal centers and to identify possible barriers that impede its implementation. A further goal was to develop solution approaches to overcome possible barriers. METHODS AND RESULTS: A multidisciplinary cooperation conducted an online survey questioning the current implementation procedures of the European guideline among pediatricians and hospital pharmacists. Results show barriers in the provisioning process of parenteral nutrition that hinder a guideline-compliant implementation in practice. Based on results of this survey, an expert network developed an interactive toolkit with simplified guideline recommendations, guideline-compliant advice for practice, best-practice examples, forms, and handouts. It seeks to encourage critical reflection of routine processes and provides concrete solutions to overcome barriers in practice. CONCLUSION: The current procedures related to parenteral nutrition deviate from guideline recommendations. The developed toolkit provides practice-oriented support aiming to enhance the guideline-compliant implementation of parenteral nutrition in perinatal centers.

Associations between lifestyle interventions during pregnancy and childhood weight and growth: a systematic review and meta-analysis.

BACKGROUND: Maternal health and lifestyle during pregnancy may be critical for the onset and progression of childhood obesity. Prenatal lifestyle interventions have been shown to positively affect maternal behaviors, gestational weight gain, and anthropometric outcomes in infants at birth. The influence of such interventions on child weight or growth beyond birth is unknown. We therefore examined the association between lifestyle interventions during pregnancy and anthropometric outcomes during childhood. METHODS: A systematic literature search was conducted in three electronic databases, two clinical trial registers and further sources, without language or publication status restrictions. Additionally, 110 study authors were contacted to obtain unpublished data. Randomized controlled trials comparing any antenatal lifestyle or behavioral intervention to standard prenatal care, in women of any body mass index (BMI), with offspring anthropometric data at 1 month of age or older, were considered. Two reviewers independently extracted data and assessed the risk of bias using the Cochrane Collaboration's updated tool. Data on weight, length, and BMI, and corresponding z-scores, were stratified into six age ranges and weighted mean differences (WMD) with 95% confidence intervals (CI) were calculated in univariate and multivariate random-effects meta-analytical models. RESULTS: Twenty trials comprising 11,385 women were included in this systematic review, of which 19 were combined in meta-analyses. Overall, lifestyle interventions during pregnancy were not associated with differences in weight, length, BMI, or corresponding z-scores, in children aged 1 month to 7 years (e.g. weight in 5 to 6 month old children, WMD: 0.02 kg; 95% CI: - 0.05 to 0.10 kg, I2 = 38%; 13 studies, 6667 participants). Findings remained consistent when studies were stratified by maternal baseline BMI or other risk factors, and intervention content and duration. Based on the GRADE criteria, the strength of the body of evidence was considered moderate. CONCLUSION: Prenatal lifestyle interventions were not shown to influence childhood weight or growth. Nevertheless, women should be encouraged to pursue a healthy lifestyle during pregnancy. Further efforts to establish early prevention strategies for childhood obesity are urgently needed. Thus, large, high-quality studies with pre-planned, long-term follow-ups are warranted. TRIAL REGISTRATION: PROSPERO CRD42018118678 .

Galectin-3 reflects the echocardiographic quantification of right ventricular failure.

Objectives. Galectin-3 (gal-3) is a mediator of extracellular matrix metabolism and reflects an ongoing cardiac fibrotic process. The aim of this study was to determine the potential use of gal-3 in evaluating the structural and functional parameters of the right ventricle as determined by echocardiography. Design. Ninety-one patients undergoing routine echocardiography were prospectively enrolled in this monocentric study. Serum samples for gal-3 and aminoterminal pro-brain natriuretic peptide (NT-proBNP) were collected within 24 h of echocardiographic examination. Patients were arbitrarily divided into subgroups based on right ventricular function as measured by tricuspid annular plane systolic excursion (TAPSE) and these included TAPSE >24 mm (n = 23); TAPSE 18-24 mm (n = 55); TAPSE ≤17 mm (n = 13); permitting the detailed statistical analysis of derived data. Results. Serum levels of gal-3 in all patients correlated with age (r = 0.36. p < .001), creatinine (r = 0.60, p < .001), NT-proBNP (r = 0.53, p < .001), RA area (r = 0.38, p < .001) and TAPSE (r = -0.3. p < .01). The distribution of echocardiographic indices according to TAPSE subgroups revealed an association between gal-3 and its ability to identify patients with right ventricular failure (RVF) as diagnosed by a TAPSE ≤17 mm (r = 0.04, p < .001). The multivariable logistic regression model with adjusted odds ratio showed the ability of gal-3 to identify RVF when adjusted to age and gender (adjusted odds ratio 3.60, 95% CI 1.055-12.282, p < .05). Conclusion. Gal-3 correlated with echocardiographic indices of RVF and could effectively diagnose these patients. The supplementary use of NT-proBNP strengthened the diagnostic capability of each biomarker. Trial Registration: The 'Cardiovascular Imaging and Biomarker Analyses' (CIBER Study), clinicaltrials.gov identifier: NCT03074253. Registered 3/8/2017. https://www.clinicaltrials.gov/ct2/show/NCT03074253.

[Multi-Resistant Bacteria in Patients in Hospitals and Medical Practices as well as in Residents of Nursing Homes in Saxony - Results of a Prevalence Study 2017/2018]. / Multiresistente Bakterien bei Patienten in Krankenhäusern und Arztpraxen sowie bei Bewohnern von Altenpflegeheimen in Sachsen ­ Ergebnisse einer Prävalenzstudie 2017/2018.

OBJECTIVE: The aim of this study was to determine the prevalence of methicillin-resistant Staphylococcus aureus (MRSA), multi-resistant gram-negative bacteria (MRGN) and vancomycin-resistant enterococci (VRE) in three study groups (hospital patients, residents in nursing homes for the elderly and patients in GP practices) and additionally, risk factors for carriage of multidrug-resistant organisms (MDRO). METHODS: Screening for MDRO was performed as a point prevalence study by obtaining nasal, pharyngeal and rectal swabs or stool samples from voluntary participants in 25 hospitals, 14 nursing homes for the elderly as well as 33 medical practices in 12 of 13 districts of Saxony. Suspicious isolates were further examined phenotypically and partially by molecular methods. The participants completed a questionnaire on possible risk factors for MDRO colonisation; the data were statistically evaluated by correlation analyses. RESULTS: In total, 1,718 persons, 629 from hospitals, 498 from nursing homes and 591 from medical practices, were examined. MDRO was detected in 8.4% of all participants; 1.3% persons tested positive for MRSA, 5.2% for 3MRGN, 0.1% for 4MRGN and 2.3% for VRE. Nine persons were colonized with more than one MDRO. The following independent risk factors could be significantly associated with the detection of MDRO: presence of a degree of care (MDRO), male sex (MDRO/VRE), current antibiosis (MDRO/VRE), antibiosis within the last 6 months (MDRO/MRSA/MRGN/VRE), current tumour disease (MDRO/3MRGN), peripheral artery disease (PAD) (MRSA) as well as urinary incontinence (3MRGN). CONCLUSIONS: To our knowledge, this study represents the first survey of prevalence of different multiresistant pathogen groups in 3 study groups including outpatients in Germany. 3MRGN were the pathogens most frequently detected and were also found in patients of younger age groups. VRE were found almost exclusively in specific clinics. In addition to current and past antibiotic therapy, in particular the presence of PAD for MRSA detection, urinary incontinence for 3MRGN detection and a current tumour disease for MDRO and 3MRGN detection were determined as independent risk factors.

Basement Membrane Remodeling Controls Endothelial Function in Idiopathic Pulmonary Arterial Hypertension.

The extracellular matrix (ECM) increasingly emerges as an active driver in several diseases, including idiopathic pulmonary arterial hypertension (IPAH). The basement membrane (BM) is a specialized class of ECM proteins. In pulmonary arteries, the BM is in close contact and direct proximity to vascular cells, including endothelial cells. So far, the role of the BM has remained underinvestigated in IPAH. Here, we aimed to shed light on the involvement of the BM in IPAH, by addressing its structure, composition, and function. On an ultrastructural level, we observed a marked increase in BM thickness in IPAH pulmonary vessels. BM composition was distinct in small and large vessels and altered in IPAH. Proteoglycans were mostly responsible for distinction between smaller and larger vessels, whereas BM collagens and laminins were more abundantly expressed in IPAH. Type IV collagen and laminin both strengthened endothelial barrier integrity. However, only type IV collagen concentration dependently increased cell adhesion of both donor and IPAH-derived pulmonary arterial endothelial cells (PAECs) and induced nuclear translocation of mechanosensitive transcriptional coactivator of the hippo pathway YAP (Yes-activated protein). On the other hand, laminin caused cytoplasmic retention of YAP in IPAH PAECs. Accordingly, silencing of COL4A5 and LAMC1, respectively, differentially affected tight junction formation and barrier integrity in both donor and IPAH PAECs. Collectively, our results highlight the importance of a well-maintained BM homeostasis. By linking changes in BM structure and composition to altered endothelial cell function, we here suggest an active involvement of the BM in IPAH pathogenesis.

Evaluation of antenatal risk factors for postpartum depression: a secondary cohort analysis of the cluster-randomised GeliS trial.

BACKGROUND: Maternal weight variables are important predictors of postpartum depression (PPD). While preliminary evidence points to an association between pre-pregnancy obesity and PPD, the role of excessive gestational weight gain (GWG) on PPD is less studied. In this secondary cohort analysis of the German 'healthy living in pregnancy' (GeliS) trial, we aimed to investigate associations between weight-related variables and PPD and to assess the influence of GWG on the risk for PPD. METHODS: We included women with normal weight, overweight, and obesity (BMI 18.5-40.0 kg/m2). Symptoms of PPD were assessed 6-8 weeks postpartum using the Edinburgh Postnatal Depression Scale. Pre-pregnancy BMI was self-reported. During the course of pregnancy, weight was measured at gynaecological practices within regular check-ups. GWG was defined as the difference between the last measured weight before delivery and the first measured weight at the time of recruitment (≤ 12th week of gestation). Excessive GWG was classified according to the Institute of Medicine. Multiple logistic regression analyses were used to estimate the odds of PPD in relation to pre-pregnancy BMI, GWG, and excessive GWG adjusting for important confounders. RESULTS: Of the total 1583 participants, 45.6% (n = 722) showed excessive GWG and 7.9% (n = 138) experienced PPD. Pre-pregnancy BMI (per 5-unit increase; OR = 1.23, 95% CI 1.08-1.41, p = 0.002) and pre-pregnancy overweight or obesity were significantly positively associated with the odds of developing PPD, particularly among women with an antenatal history of anxiety or depressive symptoms (overweight: OR = 1.93, 95% CI = 1.15-3.22, p = 0.01; obesity: OR = 2.11, 95% CI = 1.13-3.96, p = 0.02). Sociodemographic or lifestyle factors did not additively influence the odds of having PPD. In fully adjusted models, there was no significant evidence that GWG or the occurrence of excessive GWG increased the odds of experiencing PPD (excessive vs. non-excessive: OR = 3.48, 95% CI 0.35-34.94; GWG per 1 kg increase: OR = 1.16, 95% CI 0.94-1.44). CONCLUSION: Pre-pregnancy overweight or obesity is associated with PPD independent of concurrent risk factors. History of anxiety or depressive symptoms suggests a stress-induced link between pre-pregnancy weight and PPD. TRIAL REGISTRATION: NCT01958307 , ClinicalTrials.gov, retrospectively registered on 9 October 2013.

My niche: individual spatial niche specialization affects within- and between-species interactions.

Intraspecific trait variation is an important determinant of fundamental ecological interactions. Many of these interactions are mediated by behaviour. Therefore, interindividual differences in behaviour should contribute to individual niche specialization. Comparable with variation in morphological traits, behavioural differentiation between individuals should limit similarity among competitors and thus act as a mechanism maintaining within-species variation in ecological niches and facilitating species coexistence. Here, we aimed to test whether interindividual differences in boldness covary with spatial interactions within and between two ecologically similar, co-occurring rodent species (Myodes glareolus, Apodemus agrarius). In five subpopulations in northeast Germany, we quantified individual differences in boldness via repeated standardized tests and spatial interaction patterns via capture-mark-recapture (n = 126) and automated VHF telemetry (n = 36). We found that boldness varied with space use in both species. Individuals of the same population occupied different spatial niches, which resulted in non-random patterns of within- and between-species spatial interactions. Behavioural types mainly differed in the relative importance of intra- versus interspecific competition. Within-species variation along this competition gradient could contribute to maintaining individual niche specialization. Moreover, behavioural differentiation between individuals limits similarity among competitors, which might facilitate the coexistence of functionally equivalent species and, thus, affect community dynamics and local biodiversity.

Long non-coding RNAs influence the transcriptome in pulmonary arterial hypertension: the role of PAXIP1-AS1.

In idiopathic pulmonary arterial hypertension (IPAH), global transcriptional changes induce a smooth muscle cell phenotype characterised by excessive proliferation, migration, and apoptosis resistance. Long non-coding RNAs (lncRNAs) are key regulators of cellular function. Using a compartment-specific transcriptional profiling approach, we sought to investigate the link between transcriptional reprogramming by lncRNAs and the maladaptive smooth muscle cell phenotype in IPAH. Transcriptional profiling of small remodelled arteries from 18 IPAH patients and 17 controls revealed global perturbations in metabolic, neuronal, proliferative, and immunological processes. We demonstrated an IPAH-specific lncRNA expression profile and identified the lncRNA PAXIP1-AS1 as highly abundant. Comparative transcriptomic analysis and functional assays revealed an intrinsic role for PAXIP1-AS1 in orchestrating the hyperproliferative and migratory actions of IPAH smooth muscle cells. Further, we showed that PAXIP1-AS1 mechanistically interferes with the focal adhesion axis via regulation of expression and phosphorylation of its downstream target paxillin. Overall, we show that changes in the lncRNA transcriptome contribute to the disease-specific transcriptional landscape in IPAH. Our results suggest that lncRNAs, such as PAXIP1-AS1, can modulate smooth muscle cell function by affecting multiple IPAH-specific transcriptional programmes. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Effects of a lifestyle intervention during pregnancy to prevent excessive gestational weight gain in routine care - the cluster-randomised GeliS trial.

BACKGROUND: Excessive gestational weight gain (GWG) leads to obstetric complications, maternal postpartum weight retention and an increased risk of offspring obesity. The GeliS study examines the effect of a lifestyle intervention during pregnancy on the proportion of women with excessive GWG and pregnancy and obstetric complications, as well as the long-term risk of maternal and infant obesity. METHODS: The GeliS study is a cluster-randomised multicentre controlled trial including 2286 women with a pre-pregnancy BMI between 18.5 and 40.0 kg/m2 recruited from gynaecological and midwifery practices prior to the end of the 12th week of gestation in five Bavarian regions. In the intervention regions, four lifestyle counselling sessions covering a balanced healthy diet, regular physical activity and self-monitoring of weight gain were performed by trained healthcare providers alongside routine pre- and postnatal practice visits. In the control regions, leaflets with general recommendations for a healthy lifestyle during pregnancy were provided. RESULTS: The intervention did not result in a significant reduction of women showing excessive GWG (adjusted OR 0.95, 95% CI 0.66-1.38, p = 0.789), with 45.1% and 45.7% of women in the intervention and control groups, respectively, gaining weight above the Institute of Medicine recommendations. Gestational diabetes mellitus was diagnosed in 10.8% and 11.1% of women in the intervention and control groups, respectively (p = 0.622). Mean birth weight and length were slightly lower in the intervention group (3313 ± 536 g vs. 3363 ± 498 g, p = 0.020; 51.1 ± 2.7 cm vs. 51.6 ± 2.5 cm, p = 0.001). CONCLUSION: In the setting of routine prenatal care, lifestyle advice given by trained healthcare providers was not successful in limiting GWG and pregnancy complications. Nevertheless, the potential long-term effects of the intervention remain to be assessed. TRIAL REGISTRATION: NCT01958307 , ClinicalTrials.gov, retrospectively registered October 9, 2013.