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.

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.

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.

Venous and Arterial Thromboembolism in Lung Cancer Patients: A Retrospective Analysis.

Background: Patients with lung cancer face an increased incidence of venous (VTE) and arterial (ATE) thromboembolism. Risk factors for thrombosis remain unclear, particularly the impact of the use of immune checkpoint inhibitors (ICIs). We sought to compare the incidence of VTE and ATE in lung cancer patients receiving platinum-based therapy versus those receiving ICIs alone or in combination with chemotherapy and to validate the Khorana risk score for predicting VTE in the era of ICIs. Methods: A retrospective single-institution data analysis of 173 patients diagnosed with locally advanced or metastatic lung cancer at the Jena University hospital between 2015 and 2021. Results: The study revealed a high incidence of VTE (17.9%) and ATE (5.8%). The VTE risk was higher in patients diagnosed with adenocarcinoma (OR 0.29, 95% CI 0.09-0.93) than in patients with other histological types. A prior venous event was associated with an increased risk of recurrent VTE (OR 4.46, 95% CI 1.20-16.63). The incidence of thrombosis under first-line platinum-based chemotherapy did not differ from the incidence under ICIs (p = 0.19). There were no differences in the subgroup of patients who received ICIs alone or combined immunochemotherapy (p = 0.43). The Khorana score failed to predict the risk of VTE correctly. Conclusions: We did not find evidence supporting the theory that ICI therapy (alone or combined) increases the risk of thrombotic events. Adenocarcinoma and a prior history of VTE were strongly associated with an increased risk of VTE. Other scores for thrombotic risk assessment in lung cancer patients should be tested in prospective studies.

Who Still Gets Ligated? Reasons for Persistence of Surgical Ligation of the Patent Ductus Arteriosus Following Availability of Transcatheter Device Occlusion for Premature Neonates.

(1) Background: To identify reasons for the persistence of surgical ligation of the patent ductus arteriosus (PDA) in premature infants after the 2019 Food and Drug Administration (FDA) approval of transcatheter device closure; (2) Methods: We performed a 10-year (2014-2023) single-institution retrospective study of premature infants (<37 weeks) and compared clinical characteristics and neonatal morbidities between neonates that underwent surgical ligation before (epoch 1) and after (epoch 2) FDA approval of transcatheter closure; (3) Results: We identified 120 premature infants that underwent surgical ligation (n = 94 before, n = 26 after FDA approval). Unfavorable PDA morphology, active infection, and recent abdominal pathology were the most common reasons for surgical ligation over device occlusion in epoch 2. There were no differences in demographics, age at closure, or outcomes between infants who received surgical ligation in the two epochs; (4) Conclusions: Despite increasing trends for transcatheter PDA closure in premature infants, surgical ligation persists due to unfavorable ductal morphology, active infection, or abdominal pathology.

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.

Diastolic exercise stress testing in heart failure with preserved ejection fraction: The DEST-HF study.

AIMS: Pulmonary capillary wedge pressure (PAWP) ≥25 mmHg during bicycle ergometry is recommended to uncover occult heart failure with preserved ejection fraction. We hypothesized that PAWP increase would differ in available diastolic stress tests and that the margin of PAWP ≥25 mmHg would only be reliably achieved through ergometry. METHODS AND RESULTS: We conducted a prospective, single-arm study in patients with an intermediate risk for heart failure with preserved ejection fraction according to the ESC HFA-PEFF score. A total of 19 patients underwent four stress test modalities in randomized order: leg raise, fluid challenge, handgrip, and bicycle ergometry. The primary outcome was the difference (Δ) between resting and exercise PAWP in each modality. Secondary outcomes were differences (Δ) in mean pulmonary artery pressure (mPAP), cardiac output (CO), as well as the ratios between mPAP and PAWP to CO. Compared to resting values, passive leg raise (Δ7.7 ± 8.0 mmHg, p = 0.030), fluid challenge (Δ9.2 ± 6.4 mmHg, p = 0.003), dynamic handgrip (Δ9.6 ± 7.5 mmHg, p = 0.002), and bicycle ergometry (Δ22.3 ± 5.0 mmHg, p < 0.001) uncovered increased PAWP during exercise. Amongst these, bicycle ergometry also demonstrated the highest ΔmPAP (27.2 ± 7.1 mmHg, p < 0.001), ΔCO (3.3 ± 2.6 L/min, p < 0.001), ΔmPAP/CO ratio (2.3 ± 2.0 mmHg/L/min, p < 0.001), and ΔPAWP/CO ratio (2.2 ± 1.4 mmHg/L/min, p < 0.001) compared to other modalities. PAWP ≥25 mmHg was only reliably achieved in bicycle ergometry (31.1 ± 3.9 mmHg). In all other modalities only 10.5% of patients achieved PAWP ≥25 mmHg (handgrip 18.4 ± 6.6 mmHg, fluid 18.1 ± 5.6 mmHg, leg raise 16.5 ± 7.0 mmHg). CONCLUSIONS: We demonstrate that bicycle ergometry exhibits a distinct haemodynamic response with higher increase of PAWP compared to other modalities. This finding needs to be considered for valid detection of exercise PAWP ≥25 mmHg when non-bicycle tests remain inconclusive.

[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.

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.

The DZHK research platform: maximisation of scientific value by enabling access to health data and biological samples collected in cardiovascular clinical studies.

The German Centre for Cardiovascular Research (DZHK) is one of the German Centres for Health Research and aims to conduct early and guideline-relevant studies to develop new therapies and diagnostics that impact the lives of people with cardiovascular disease. Therefore, DZHK members designed a collaboratively organised and integrated research platform connecting all sites and partners. The overarching objectives of the research platform are the standardisation of prospective data and biological sample collections among all studies and the development of a sustainable centrally standardised storage in compliance with general legal regulations and the FAIR principles. The main elements of the DZHK infrastructure are web-based and central units for data management, LIMS, IDMS, and transfer office, embedded in a framework consisting of the DZHK Use and Access Policy, and the Ethics and Data Protection Concept. This framework is characterised by a modular design allowing a high standardisation across all studies. For studies that require even tighter criteria additional quality levels are defined. In addition, the Public Open Data strategy is an important focus of DZHK. The DZHK operates as one legal entity holding all rights of data and biological sample usage, according to the DZHK Use and Access Policy. All DZHK studies collect a basic set of data and biosamples, accompanied by specific clinical and imaging data and biobanking. The DZHK infrastructure was constructed by scientists with the focus on the needs of scientists conducting clinical studies. Through this, the DZHK enables the interdisciplinary and multiple use of data and biological samples by scientists inside and outside the DZHK. So far, 27 DZHK studies recruited well over 11,200 participants suffering from major cardiovascular disorders such as myocardial infarction or heart failure. Currently, data and samples of five DZHK studies of the DZHK Heart Bank can be applied for.

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.

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.

Cochlear Implantation in Obliterated Cochlea: A Retrospective Analysis and Comparison between the IES Stiff Custom-Made Device and the Split-Array and Regular Electrodes.

Anatomical malformations, obliterations of the cochlea, or re-implantations pose particular challenges in cochlear implantation. Treatment methods rely on radiological and intraoperative findings and include incomplete insertion, the implantation of a double array, and radical cochleostomy. In addition, a stiff electrode array, e.g., the IE stiff (IES) custom-made device (CMD, MED-EL), was prescribed individually for those special cases and pre-inserted prior to facilitate cochlear implantation in challenging cases. Data on outcomes after implantation in obliterated cochleae are usually based on individual case reports since standardised procedures are lacking. A retrospective analysis was conducted to analyse our cases on obliterated cochleae treated with MED-EL devices in order to allow the different cases to be compared. Impedances and speech perception data of patients treated with the IES CMD and the double array were retrospectively compared to patients treated with a STANDARD or FLEX electrode array (the REGULAR group). Patients with a Split-Array CMD had a poor speech perception when compared to patients treated with the IES CMD device. Thus, the IES CMD can successfully be used in patients with obliterated cochleae who would otherwise be non-users, candidates for a Split-Array CMD, or candidates for partial insertion with insufficient cochlear coverage.

Dietary Supplementation Before, During and After Pregnancy: Results of the Cluster-Randomized GeliS Study.

Introduction The nutritional status of women before, during, and after pregnancy plays an important role in the health of mother and child. In addition to a balanced mixed diet, the increased need for folic acid and iodine should be met and ensured with supplements. The aim of this study was to assess dietary supplementation in the context of pregnancy and to investigate the effect of targeted counselling on supplementation behavior during and after pregnancy. Methods In the context of the "Gesund leben in der Schwangerschaft" (GeliS; "Healthy living in pregnancy") trial, women in the intervention group (IG) received four structured lifestyle counselling sessions during pregnancy as well as postpartum, during which they were informed about appropriate dietary supplementation. The women in the control group (CG) received routine prenatal care. The intake of dietary supplements was recorded at different points using a questionnaire. Results In total, 2099 women were included in the analysis. Prior to conception, 31.3% of the women in the IG and 31.4% of the women in the CG took folic acid supplements. Prenatally, about half of the women took folic acid (IG: 54.1%; CG: 52.0%) and iodine (IG: 50.2%; CG: 48.2%). Statistically significant differences between the groups with regard to supplementation behavior could not be observed, neither prior to inclusion in the study nor during the intervention. During pregnancy, 23.0% of all women took docosahexaenoic acid (DHA) supplements and 21.8% iron supplements. 49.4% of the women additionally took vitamin D supplements. A higher educational level (p < 0.001), advanced age (p < 0.001), primiparity (p < 0.001), and a vegetarian diet (p = 0.037) were all associated with a higher level of dietary supplementation. Conclusion The GeliS lifestyle counselling did not significantly improve the supplementation behavior of women during and after pregnancy. Women should be informed about adequate dietary supplementation early on within the scope of gynecological prenatal care.

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.