Evidence for the Fucoidan/P-Selectin Axis as a Therapeutic Target in Hypoxia-induced Pulmonary Hypertension.

Rationale: Pulmonary arterial hypertension (PAH) is characterized by vascular remodeling and excessive proliferation of pulmonary artery smooth muscle cells (PASMCs). Fucoidan, a polysaccharidic ligand of the adhesion molecule P-selectin, exhibits antiproliferative properties. The effects of the fucoidan/P-selectin axis on vascular remodeling and pulmonary hypertension (PH) after hypoxia remain unexplored. Objectives: We aimed to evaluate the therapeutic potential of targeting the fucoidan/P-selectin axis in PH. Methods: Mice with PH induced by chronic hypoxia (35 d) were given either fucoidan (from Fucus vesiculosus) or anti-P-selectin antibody (Rb40.34) during Days 21-35. Right ventricular (RV) function was determined by echocardiography. Vascular morphometry was assessed by immunohistochemistry. Human and experimental PH lungs and PASMCs were used for assessment of P-selectin expression and function. Measurements and Main Results: Fucoidan attenuated chronic hypoxia-induced PH in mice, reducing pulmonary vascular remodeling and restoring RV function. In vitro, fucoidan inhibited hypoxia and growth factor-stimulated PASMC proliferation and migration. Chronic hypoxia caused an upregulation of P-selectin in the medial layer of the small pulmonary arteries. P-selectin was persistently upregulated in PASMCs of human and hypoxia-induced experimental PH. HIF-1α (hypoxia-inducible factor 1α) directly bound to the P-selectin promoter and transcriptionally activated P-selectin in hypoxia. P-selectin blockage resulted in a marked reduction of PASMC proliferation in vitro. Blockage of P-selectin by administration of anti-P-selectin Rb40.34 antibody and P-selectin-deficient mice improved vascular remodeling and restored RV function. Conclusions: Fucoidan is a potent natural adjuvant that represents a promising therapeutic approach for PH. Our data indicate a previously unrecognized role of P-selectin in the proliferative response of PASMCs associated with PH.

A Medical Student-Delivered Smoking Prevention Program, Education Against Tobacco, for Secondary Schools in Germany: Randomized Controlled Trial.

BACKGROUND: More than 8.5 million Germans suffer from chronic diseases attributable to smoking. Education Against Tobacco (EAT) is a multinational network of medical students who volunteer for school-based prevention in the classroom setting, amongst other activities. EAT has been implemented in 28 medical schools in Germany and is present in 13 additional countries around the globe. A recent quasi-experimental study showed significant short-term smoking cessation effects on 11-to-15-year-old adolescents. OBJECTIVE: The aim of this study was to provide the first randomized long-term evaluation of the optimized 2014 EAT curriculum involving a photoaging software for its effectiveness in reducing the smoking prevalence among 11-to-15-year-old pupils in German secondary schools. METHODS: A randomized controlled trial was undertaken with 1504 adolescents from 9 German secondary schools, aged 11-15 years in grades 6-8, of which 718 (47.74%) were identifiable for the prospective sample at the 12-month follow-up. The experimental study design included measurements at baseline (t1), 6 months (t2), and 12 months postintervention (t3), via questionnaire. The study groups consisted of 40 randomized classes that received the standardized EAT intervention (two medical student-led interactive modules taking 120 minutes total) and 34 control classes within the same schools (no intervention). The primary endpoint was the difference in smoking prevalence from t1 to t3 in the control group versus the difference from t1 to t3 in the intervention group. The differences in smoking behavior (smoking onset, quitting) between the two groups, as well as gender-specific effects, were studied as secondary outcomes. RESULTS: None of the effects were significant due to a high loss-to-follow-up effect (52.26%, 786/1504). From baseline to the two follow-up time points, the prevalence of smoking increased from 3.1% to 5.2% to 7.2% in the control group and from 3.0% to 5.4% to 5.8% in the intervention group (number needed to treat [NNT]=68). Notable differences were observed between the groups for the female gender (4.2% to 9.5% for control vs 4.0% to 5.2% for intervention; NNT=24 for females vs NNT=207 for males), low educational background (7.3% to 12% for control vs 6.1% to 8.7% for intervention; NNT=30), and migrational background (students who claimed that at least one parent was not born in Germany) at the 12-month follow-up. The intervention appears to prevent smoking onset (NNT=63) but does not appear to initiate quitting. CONCLUSIONS: The intervention appears to prevent smoking, especially in females and students with a low educational background.

ChatGPT: Evaluating answers on contrast media related questions and finetuning by providing the model with the ESUR guideline on contrast agents.

OBJECTIVE: This study aimed to assess the feasibility of GPT-4 for answering questions related to contrast media with and without the context of the European Society of Urogenital Radiology (ESUR) guideline on contrast agents. The overarching goal was to determine whether contextual enrichment by providing guideline information improves answers of GPT-4 for clinical decision-making in radiology. METHODS: A set of 64 questions, based on the ESUR guideline on contrast agents mirroring pertinent sections, was developed and posed to GPT-4 both directly and after providing the guideline using a plugin. Responses were graded by experienced radiologists for quality of information and accuracy in pinpointing information from the guideline as well as by radiology residents for utility, using Likert-scales. RESULTS: GPT-4's performance improved significantly with the guideline. Without the guideline, average quality rating was 3.98, which increased to 4.33 with the guideline (p = 0036). In terms of accuracy, 82.3% of answers matched the information from the guideline. Utility scores also reflected a significant improvement with the guideline, with average scores of 4.1 (without) and 4.4 (with) (p = 0.008) with a Fleiss´ Kappa of 0.44. CONCLUSION: GPT-4, when contextually enriched with a guideline, demonstrates enhanced capability in providing guideline-backed recommendations. This approach holds promise for real-time clinical decision-support, making guidelines more actionable. However, further refinements are necessary to maximize the potential of large language models (LLMs). Inherent limitations need to be addressed.

Puncture Cube Patient-Mounted Navigation System versus Freehand Method for CT-Guided Needle Placement: Study on a Neoprene Covered Elliptical Cylinder Gelatin Phantom.

PURPOSE: The study aims to show how the "Puncture Cube" (PC) (Medical Templates, Egg, Switzerland) compares to the freehand method (FHM) for CT-guided punctures. METHODS: The PC is a patient-mounted disassemblable cube consisting of an upper and lower template with multiple holes each to predefine puncture trajectory. A total of 80 punctures (FHM in-plane, FHM off-plane, PC in-plane, PC off-plane) was performed by 4 radiologists on a target 9.1 cm below surface level of a neoprene covered elliptical cylinder gelatin phantom. The PC was never disassembled. Evaluated parameters were procedure time, number of CT-scans, euclidean distance (ED) and normal distance (ND). Respective parameters of FHM and PC were compared using the Wilcoxon signed-rank test and Levene test with significance levels of 5%. RESULTS: PC achieved smaller ED and ND values after initial needle insertion without corrections for both in-plane and off-plane punctures (P > 0.05). Variance of initial NDs was off-plane significantly larger for FHM. Final ED after needle path corrections was smaller for FHM both in- and off-plane (P < 0.05). Final off-plane ND was significantly lower for FHM with no significant difference in final in-plane ND. FHM off-plane punctures were significantly faster. There was no significant difference in CT-scans between both methods. CONCLUSION: Utilizing the PC may improve initial needle positioning and safety especially off-plane. However, better final needle positioning after correction with the greater freedom of movement method may suggest need for disassembly of the cube.

pTEVAR of an aorto-esophageal fistula in esophageal cancer: Case report and review of the literature.

An aorto-esophageal fistula (AEF) is a rare and life-threatening situation, associated with aneurysms, foreign bodies, infiltrating tumors, and radiotherapy. The ideal management is unclear. Open surgery of AEF has a high mortality and morbidity. Thoracic endovascular aortic repair (TEVAR) of an AEF is an effective and safe emergency treatment for these patients. We describe a case of AEF due to esophageal cancer successfully treated the first time by total percutaneous TEVAR (pTEVAR). A 70-year-old male patient presented with massive hematemesis at the emergency department. The patient had a known history of esophageal cancer previously treated by radiochemotherapy which was completed 3 days before. Emergency upper gastrointestinal endoscopy failed to stop the bleeding. Subsequent contrast-enhanced computed tomography revealed an aorto-esophageal fistula and emergency pTEVAR was performed. The bleeding stopped directly after stent graft placement and the patient was discharged after 10 days later. He died 3 months after pTEVAR from cancer progression. pTEVAR is an effective and safe treatment option for AEF. It can be applied as a first-line treatment and offers the potential to improve survival in the emergency setting.

Photoaging smartphone app promoting poster campaign to reduce smoking prevalence in secondary schools: the Smokerface Randomized Trial: design and baseline characteristics.

INTRODUCTION: Smoking is the largest cause of preventable death globally. Most smokers smoke their first cigarette in early adolescence. We took advantage of the widespread availability of mobile phones and adolescents' interest in appearance to develop a free photoaging app which is promoted via a poster campaign in secondary schools. This study aims to evaluate its effectiveness regarding smoking prevalence and students' attitudes towards smoking. METHODS AND ANALYSIS: A randomised controlled trial is conducted with 9851 students of both genders with an average age of 12 years in grades 6 and 7 of 126 secondary schools in Germany. At present, cigarette smoking prevalence in our sample is 4.7%, with 4.6% of the students currently using e-cigarettes (1.6% use both). The prospective experimental study design includes measurements at baseline and at 6, 12 and 24 months postintervention via a questionnaire plus a random cotinine saliva sample at 24 months postintervention. The study groups consist of randomised schools receiving the Smokerface poster campaign and control schools with comparable baseline data (no intervention). The primary end point is the difference of change in smoking prevalence in the intervention group versus the difference in the control group at 24 months follow-up. Longitudinal changes in smoking-related attitudes, the number of new smokers and quitters and the change in the number of never-smokers will be compared between the two groups as secondary outcomes. ETHICS AND DISSEMINATION: Ethical approval was obtained from the ethics committee of the University of Gießen and the ministries of cultural affairs, both in Germany. Results will be disseminated at conferences, in peer-reviewed journals, on our websites and throughout the multinational Education Against Tobacco network. TRIAL REGISTRATION NUMBER: NCT02544360, Pre-results.