Congenital Diaphragmatic Hernia: 10-Year Evaluation of Survival, Extracorporeal Membrane Oxygenation, and Foetoscopic Endotracheal Occlusion in Four High-Volume Centres

Background: Congenital diaphragmatic hernia (CDH) is a severe congenital anomaly with significant mortality. Objectives: The aim of this study was to determine if there were trends in survival over the last decade and to compare patient populations, treatment options, and survival rates between 4 high-volume centres, and hence determine which factors were associated with survival. Methods: In 4 high-volume CDH centres from the CDH EURO Consortium, data from all CDH patients born between 2004 and 2013 were analysed. The predictive value of variables known at birth and the influence of centre-specific treatments (extracorporeal membrane oxygenation, ECMO, and foetoscopic endotracheal occlusion, FETO) on survival were evaluated in multivariable logistic regression analyses. Results: Nine hundred and seventy-five patients were included in the analysis, of whom 274 (28.1%) died. ECMO was performed in 259 patients, of whom 81 (31.3%) died. One hundred and forty-five patients (14.9%) underwent FETO, and from those 76 patients (52.4%) survived. Survival differed significantly between years (p = 0.006) and between the 4 centres (p < 0.001). In the multivariable logistic regression analysis, lung-to-head ratio, gestational age at birth, ECMO, centre of birth, and year of birth were significantly associated with survival, whereas FETO was not. Conclusions: The patient populations were different between centres, which influenced outcomes. There was a significant variability in survival over time and between centres, which should be taken into consideration in the planning of future trials

Rancang Bangun Alat Pereduksi Particulate Matter (PM) Gas Buang Mesin Diesel Dengan Metode Cyclone

Gas buang dari hasil proses pembakaran berpengaruh terhadap pencemaran udara dan lingkungan khususnya motor diesel. Proses pembakaran bahan bakar pada motor bakar menghasilkan gas buang yang mengandung unsur Nitrogen Oksida (NOx), Sulfur Oksida (SOx), Particulate Matter (PM), Karbon Monoksida (CO), dan Hidrokarbon (HC) yang bersifat mencemari udara. Agar motor diesel yang digunakan tidak mengakibatkan pencemaran udara berlebih, perlu dilakukan suatu penelitian menurunkan emisi gas buang motor diesel dengan pemilihan teknologi dan metode yang tepat. Penelitian cylone separator ini berdasarkan prinsip kerja separator yang memanfaatkan gaya sentrifugal dan perbedaan massa jenis. Karena massa jenis PM lebih besar dari pada massa jenis gas buang, PM akan terpisah dari gas buang karena gaya sentrifugal dan adanya perbedaan massa jenis. Pada tahap awal penelitian ini yaitu dibuat desain dan kemudian dilakukan CFD analisis untuk dicari yang paling efisien dari segi kecepatan dan jenis aliran. Pada hasil analisa CFD disimpulkan bahwa metode Perry lebih efisien dibanding 3 metode yang lain. Setelah didapat desain yang efisien maka dilanjutkan dengan pembuatan prototipe, untuk selanjutnya dilakukan uji ekperimen. Berdasar uji eksperimen, cyclone separator dapar mereduksi PM gas Buang motor diesel pada beban 2000 watt sebesar 8,71%. Sedangkan pada beban 2500 watt, cylone separator dapat mereduksi PM sebesar 34,49%

Neurodevelopmental Outcome in High-Risk Congenital Diaphragmatic Hernia Patients: An Appeal for International Standardization

BACKGROUND: Since mortality in congenital diaphragmatic hernia (CDH) is decreasing, morbidity such as neurodevelopmental outcome is becoming increasingly important. OBJECTIVES: We evaluated neurodevelopmental outcome in high-risk CDH patients treated according to the CDH EURO Consortium standardized treatment protocol. METHODS: This observational, prospective cohort study was conducted in two European centers. Neurodevelopment of 88 patients (Rotterdam n = 49; Rome n = 39) was assessed at 12 and 24 months with the Bayley Scales of Infant Development (BSID)-II-NL (Rotterdam) or BSID-III (Rome). Data of the centers were analyzed separately. RESULTS: Cognition was normal in 77.8% of children from Rotterdam and in 94.8% from Rome at 12 months, and in 70.7 and 97.4%, respectively, at 24 months. Motor function was normal in 64.3% from Rotterdam and in 81.6% from Rome at 12 months and in 45.7 and 89.8%, respectively, at 24 months. Longer length of hospital stay (LoS) was associated with worse cognitive outcome and motor function; LoS, low socioeconomic status, and ethnicity were associated with lower cognition. CONCLUSIONS: At 2 years, most CDH patients have normal cognition, but are at risk for motor function delay. Due to differences in outcomes between centers, careful interpretation is needed before conclusions can be drawn for other centers. Future multicenter collaboration should not only focus on standardization of postnatal care, but also on international standardization of follow-up to identify risk factors and thereby reduce morbidity

Single-layer vs double-layer uterine closure during cesarean delivery:3-year follow-up of a randomized controlled trial (2Close study)

Background: The rising rate of cesarean deliveries has led to an increased incidence of long long-term complications, including niche formation in the uterine scar. Niche development is associated with various gynecologic complaints and complications in subsequent pregnancies, such as uterine rupture and placenta accreta spectrum disorders. Although uterine closure technique is considered a potential risk factor for niche development, consensus on the optimal technique remains elusive. Objective: We aimed to evaluate the effect of single-layer vs double-layer closure of the uterine incision on live birth rate at a 3-year follow-up with secondary objectives focusing on gynecologic, fertility, and obstetrical outcomes at the same follow-up. Study Design: A multicenter, double-blind, randomized controlled trial was performed at 32 hospitals in the Netherlands. Women ≥18 years old undergoing a first cesarean delivery were randomly assigned (1:1) to receive either single-layer or double-layer closure of the uterine incision. The primary outcome of the long-term follow-up was the live birth rate; with secondary outcomes, including pregnancy rate, the need for fertility treatment, mode of delivery, and obstetrical and gynecologic complications. This trial is registered on the International Clinical Trials Registry Platform www.who.int (NTR5480; trial finished). Results: Between 2016 and 2018, the 2Close study randomly assigned 2292 women, with 830 of 1144 and 818 of 1148 responding to the 3-year questionnaire in the single-layer and double-layer closure. No differences were observed in live birth rates; also there were no differences in pregnancy rate, need for fertility treatments, mode of delivery, or uterine ruptures in subsequent pregnancies. High rates of gynecologic symptoms, including spotting (30%–32%), dysmenorrhea (47%–49%), and sexual dysfunction (Female Sexual Function Index score, 23) are reported in both groups. Conclusion: The study did not demonstrate the superiority of double-layer closure over single-layer closure in terms of reproductive outcomes after a first cesarean delivery. This challenges the current recommendation favoring double-layer closure, and we propose that surgeons can choose their preferred technique. Furthermore, the high risk of gynecologic symptoms after a cesarean delivery should be discussed with patients.</p

A Transcriptomic Signature of the Hypothalamic Response to Fasting and BDNF Deficiency in Prader-Willi Syndrome.

Transcriptional analysis of brain tissue from people with molecularly defined causes of obesity may highlight disease mechanisms and therapeutic targets. We performed RNA sequencing of hypothalamus from individuals with Prader-Willi syndrome (PWS), a genetic obesity syndrome characterized by severe hyperphagia. We found that upregulated genes overlap with the transcriptome of mouse Agrp neurons that signal hunger, while downregulated genes overlap with the expression profile of Pomc neurons activated by feeding. Downregulated genes are expressed mainly in neuronal cells and contribute to neurogenesis, neurotransmitter release, and synaptic plasticity, while upregulated, predominantly microglial genes are involved in inflammatory responses. This transcriptional signature may be mediated by reduced brain-derived neurotrophic factor expression. Additionally, we implicate disruption of alternative splicing as a potential molecular mechanism underlying neuronal dysfunction in PWS. Transcriptomic analysis of the human hypothalamus may identify neural mechanisms involved in energy homeostasis and potential therapeutic targets for weight loss

Induction of broad multifunctional CD8+ and CD4+ T cells by hepatitis B virus antigen-based synthetic long peptides ex vivo

Introduction: Therapeutic vaccination based on synthetic long peptides (SLP®) containing both CD4+ and CD8+ T cell epitopes is a promising treatment strategy for chronic hepatitis B infection (cHBV). Methods: We designed SLPs for three HBV proteins, HBcAg and the non-secreted proteins polymerase and X, and investigated their ability to induce T cell responses ex vivo. A set of 17 SLPs was constructed based on viral protein conservation, functionality, predicted and validated binders for prevalent human leukocyte antigen (HLA) supertypes, validated HLA I epitopes, and chemical producibility. Results: All 17 SLPs were capable of inducing interferon gamma (IFNɣ) production in samples from four or more donors that had resolved an HBV infection in the past (resolver). Further analysis of the best performing SLPs demonstrated activation of both CD8+ and CD4+ multi-functional T cells in one or more resolver and patient sample(s). When investigating which SLP could activate HBV-specific T cells, the responses could be traced back to different peptides for each patient or resolver. Discussion: This indicates that a large population of subjects with different HLA types can be covered by selecting a suitable mix of SLPs for therapeutic vaccine design. In conclusion, we designed a set of SLPs capable of inducing multifunctional CD8+ and CD4+ T cells ex vivo that create important components for a novel therapeutic vaccine to cure cHBV.</p

The CLEAR (Considering Leading Experts’ Antithrombotic Regimes around peripheral angioplasty) survey:an international perspective on antiplatelet and anticoagulant practice for peripheral arterial endovascular intervention

BACKGROUND: Antiplatelet and anticoagulant therapy are commonly used before, during and after peripheral arterial endovascular intervention. This survey aimed to establish antiplatelet and anticoagulant choice for peripheral arterial endovascular intervention in contemporary clinical practice. METHODS: Pilot-tested questionnaire distributed via collaborative research networks. RESULTS: One hundred and sixty-two complete responses were collected from responders in 22 countries, predominantly the UK (48%) and the rest of the European Union (44%). Antiplatelet monotherapy was the most common choice pre-procedurally (62%). In the UK, there was no difference between dual and single antiplatelet therapy use post procedure (50% vs. 37% p = 0.107). However, a significant majority of EU respondents used dual therapy (68% vs. 20% p < 0.001). There was variation in choice of antiplatelet therapy by the device used and the anatomical location of the intervention artery. The majority (82%) of respondents believed there was insufficient evidence to guide antithrombotic therapy after peripheral endovascular intervention and most (92%) would support a randomised trial. CONCLUSIONS: There is widespread variation in the use of antiplatelet therapy, especially post peripheral arterial endovascular intervention. Clinicians would support the development of a randomised trial comparing dual antiplatelet therapy with monotherapy

The CLEAR (considering leading experts' antithrombotic regimes around peripheral angioplasty) survey: an international perspective on antiplatelet and anticoagulant practice for peripheral arterial endovascular intervention.

Background Antiplatelet and anticoagulant therapy are commonly used before, during and after peripheral arterial endovascular intervention. This survey aimed to establish antiplatelet and anticoagulant choice for peripheral arterial endovascular intervention in contemporary clinical practice. Methods Pilot-tested questionnaire distributed via collaborative research networks. Results One hundred and sixty-two complete responses were collected from responders in 22 countries, predominantly the UK (48%) and the rest of the European Union (44%). Antiplatelet monotherapy was the most common choice pre-procedurally (62%). In the UK, there was no difference between dual and single antiplatelet therapy use post procedure (50% vs. 37% p = 0.107). However, a significant majority of EU respondents used dual therapy (68% vs. 20% p < 0.001). There was variation in choice of antiplatelet therapy by the device used and the anatomical location of the intervention artery. The majority (82%) of respondents believed there was insufficient evidence to guide antithrombotic therapy after peripheral endovascular intervention and most (92%) would support a randomised trial. Conclusions There is widespread variation in the use of antiplatelet therapy, especially post peripheral arterial endovascular intervention. Clinicians would support the development of a randomised trial comparing dual antiplatelet therapy with monotherapy