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Expression of concern for 'Highly effective photodynamic inactivation of E. coli using gold nanorods/SiO 2 core-shell nanostructures with embedded verteporfin' by Kostiantyn Turcheniuk et al. , Chem. Commun. , 2015, 51 , 16365-16368, https://doi.org/10.1039/C5CC06738C.

Expression of concern for 'Plasmonic photothermal destruction of uropathogenic E. coli with reduced graphene oxide and core/shell nanocomposites of gold nanorods/reduced graphene oxide' by Kostiantyn Turcheniuk et al. , J. Mater. Chem. B , 2015, 3 , 375-386, https://doi.org/10.1039/C4TB01760A.

Expression of concern for 'Particle-based photodynamic therapy based on indocyanine green modified plasmonic nanostructures for inactivation of a Crohn's disease-associated Escherichia coli strain' by Roxana Jijie et al. , J. Mater. Chem. B , 2016, 4 , 2598-2605, https://doi.org/10.1039/C5TB02697K.

Background: Pancreatic islet transplantation for type 1 diabetes mellitus (T1DM) is efficacious in supressing severe hypoglycaemic episodes (SHE) and restoring glycaemic regulation, which are both pivotal in increasing health-related quality of life (HRQoL). Therefore, a systematic assessment of reports detailing HRQoL outcomes is warranted to better understand the benefits of islet transplantation. To this end, we performed a systematic review of the literature to assess the impact of islet transplantation on HRQoL in individuals with T1DM, whether as a standalone procedure (ITA) or following renal transplantation (IAK)., Method: All studies providing a quantitative assessment of HRQoL following ITA or IAK were included. Selected studies had to meet the following criteria: they had to (i) involve adult recipients of islet grafts for T1DM, (ii) use either generic or disease-specific QoL assessment tools, (iii) provide a comparative analysis of QoL metrics between the pre- and post-transplantation state or between the post-transplantation state and other pre-transplant patients or the general population., Results: Seven studies that met the inclusion criteria provided data on 205 subjects. In the included studies, HRQoL was measured using both generic instruments, such as the 36-item Short Form Health Survey (SF-36) and the Health Status Questionnaire (HSQ) 2.0, and disease-specific instruments, such as the Diabetes Distress Scale (DDS), the Diabetes Quality of Life Questionnaire, and the Hypoglycaemia Fear Survey (HFS). These instruments cover physical, mental, social, or functional health dimensions. We found that pancreatic islet transplantation was associated with improvements in all HRQoL dimensions compared with the pre-transplant baseline., Conclusions: Our systematic review demonstrates that islet transplantation significantly enhances quality of life in individuals with T1DM who are experiencing SHE. To our knowledge, this is the most extensive systematic review conducted to date, evaluating the impact of islet transplantation on HRQoL., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Pain is reported in 66% of cancer patients with advanced disease. Adequate pain management is a cornerstone of comprehensive supportive cancer care., Purpose: The purpose of this study was to assess pain management in Oncology Units in Belgium., Methods: A descriptive research design was applied. A structured questionnaire developed by a writing committee was sent to 37 healthcare professionals in 2021. Twenty-four replied., Results: In most centers, pain management is organized through the pain clinic (91.7%), followed by a multidisciplinary team (83.3%) and the palliative care unit (75%). Eighty-seven percent use tools to assess the pain, mostly for in-patients. Pain guidelines are applied in 17 centers with the ESMO guidelines being the most often mentioned. Mild to moderate pain is managed with paracetamol, non-steroidal anti-inflammatory drugs, and tramadol. All centers handle severe pain with strong opioids, including buprenorphine and fentanyl. Only 62% are concerned about the side effects of strong opioids. In case of neuropathic pain, treatments with pregabalin, gabapentine, and tricyclic antidepressants are the most common, followed by opioids and interventional therapies for refractory neuropathic pain. Asking advice to the pain clinic, combination therapy and opioid rotation are used for patients with inadequate analgesia. Eighty to 90% of the centers have access to intraspinal and epidural techniques, respectively. An active teaching program on pain relief is offered in 66%, but only 33% of the centers do active research focused on pain management., Conclusions: This is the first survey on pain management in the Belgian centers. Surprisingly only one-third of the health professionals ask advice to the pain clinic in case of inadequate pain relief, meaning that we are far away from a multidisciplinary patient-centered approach. Therefore, the BSMO Supportive Care Task Force promotes the development of an interdisciplinary committee in every oncology unit., Competing Interests: Declarations. Ethics approval: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: The dual mobility cup (DMC) reduces the dislocation rates in total hip arthroplasty (THA). DMC systems include anatomical (non-modular or monoblock) (ADM) and modular dual mobility (MDM) components (Stryker Orthopaedics, Mahwah, NJ, USA). This review aims to assess differences between these two types of DMC implants concerning dislocation and revision rates, as well as patient-reported outcomes., Methods: This systematic review and meta-analysis of studies reports data from patients undergoing primary THA using MDM and/or ADM implants. Following the PRISMA guidelines, we analyzed articles from Science Direct/Scopus, PubMed, and the Cochrane Database of Systematic Reviews. We compared dislocation rates, revisions for any reason, aseptic loosening, infections, fractures, and functional outcomes between ADM and MDM components., Results: Eleven studies were considered eligible for further analysis. A total of 3369 patients (mean age = 65.4 years) underwent primary THA, including 3386 DMC implants. The mean follow-up for the MDM and ADM groups was 2.9 years and 3.9 years, respectively. The study revealed one dislocation in the MDM and none in the ADM. By proportion metanalysis, the review did not show statistical differences in all-cause revisions (p = 0.93, [CI [0.01;0.02]) or periprosthetic fractures (p = 0.18, CI [0.01;0.02])., Conclusions: MDM and ADM systems, both, represent safe DM options regarding dislocation, all-causes revisions and functional outcomes., Competing Interests: Declarations Conflict of interest VG, CK, EK, ET, AD, CHFL, PH declare that they have no conflict of interest. SL: consultant for Stryker, Smith Nephew, Heraeus, Depuy Synthes; Institutional research support from Groupe Lepine, Amplitude; Editorial Board for Journal of Bone and Joint Surgery (Am). Consent for publication Not applicable. Informed consent Not applicable. PROSPERO number CRD42024525385., (© 2024. The Author(s), under exclusive licence to Springer-Verlag France SAS, part of Springer Nature.)

Introduction: Since the early 2000's, the appeal of certain operating room specialties has decreasedamong medical school graduate students. The recent reform of the second and third cycles of medical studies in France provides an opportunity to set up teaching programs around operating room specialties. We have organised a teaching unit which is part of the final year of medical studies. The main objectives are: (1) to examine whether a boot camp can modify students' opinions and preconceived assumptions about a surgical and/or anaesthetist career (2) to determine whether these changes in perception, have an impact on students' interest in pursuing a surgical/anaesthetic career compared with the current situation., Materials and Methods: The "working in the operating theatre" boot camp (UETB) took place after the written exams of the sixth year of medical school, before students choose their future specialty for residency. This program included practical workshops, readings and time for exchanges surgeons and anaesthetists. At the beginning and at the end of the UETB, feedback forms were collected., Results: The cohort included 59 students from the Toulouse medical school, academic year 2023-2024. After attending the UETB, there was a significant qualitative improvement in interest in a surgical and intensive care-anaesthesia career. Feedback on how the UETB influenced the choice of a future specialty was very positive, with statistically significant qualitive improvement., Additionally, the students' perception of a work-life quality as a surgeon and/or anaesthetist improved significantly., Conclusion: The outcome of this study makes a strong case for integrating additional exposure to the various surgical subspecialties into the graduate medical curriculum in France. By helping to dispel misperceptions of "a surgical/anaesthetist career" early on, opportunities such as the UETB program may enable addressing the attrition rate observed among surgical and anaesthetic residency applications., (© 2024. The Author(s).)

The objective was to investigate the outcomes of concomitant venoarterial extracorporeal membrane oxygenation (ECMO) and left ventricular unloading with Impella (ECPELLA) compared with ECMO alone to treat patients affected by cardiogenic shock. Data from patients needing mechanical circulatory support from 4 international centers were analyzed. Of 438 patients included, ECMO alone and ECPELLA were adopted in 319 (72.8%) and 119 (27.2%) patients, respectively. Propensity score matching analysis identified 95 pairs. In the matched cohort, 30-day mortality rates in the ECMO and ECPELLA were 49.5% and 43.2% ( P = 0.467). The incidences of complications did not differ significantly between groups ( P = 0.877, P = 0.629, P = 1.000, respectively). After a median follow-up of 0.18 years (interquartile range 0.02-2.55), the use of ECPELLA was associated with similar mortality compared with ECMO alone (hazard ratio 0.81, 95% confidence interval 0.54-1.20, P = 0.285), with 1-year overall survival rates of 51.3% and 46.6%, for ECPELLA and ECMO alone, respectively. ECMO alone and ECPELLA are both effective strategies in patients needing mechanical circulatory support for cardiogenic shock, showing similar rates of early and mid-term survival., Competing Interests: Disclosure: The authors have no conflicts of interest to disclose., (Copyright © ASAIO 2024.)

Background: The value of simulation in emergency medicine is indisputable because it allows training and acquisition of many technical and non-technical skills (TS and NTS). In France, there are no curriculum regarding the use of simulation as a teaching tool during emergency medicine residency. The aim of this study was to design the content of a national simulation-based curriculum for emergency medicine residency programs., Methods: The Delphi method was conducted between March and June 2022. The questionnaire was divided into three sections: TS, NTS and clinical situations as starting points (SSPs). A panel of emergency physicians' experts on simulation education was established. An online survey was conducted in which they were asked to score, on a four-point Likert scale, the suitability of skills and SSPs to be taught through simulation courses during the emergency medicine residency. The questionnaire was revised between each round following comments or suggestions for additional items from the experts., Results: Sixty-six experts completed the Delphi process. The initial questionnaire included 64 TS, 37 NTS and 103 SSPs. The experts' comments led to the addition of 12 TS, 24 NTS and 6 SSPs. Consensus was obtained after three rounds. The experts selected 24 TS and 20 NTS to be taught as a priority through simulation during the emergency medicine residency, and 15 SSPs to be used in priority., Conclusion: With a Delphi method, French experts in simulation-based emergency medicine education have selected 24 technical and 20 non-technical skills to be taught as a priority with simulation-based training to emergency medicine residents., (© 2024. The Author(s).)

Purpose: Craniofacial osteotomies involving pterygomaxillary disjunction are common procedures in maxillofacial surgery. Surgeons still rely on their proprioception to determine when to stop impacting the osteotome, which is important to avoid complications such as dental damage and bleeding. Our group has developed a technique consisting in using an instrumented hammer that can provide information on the mechanical properties of the tissue located around the osteotome tip. The aim of this study is to determine whether a mallet instrumented with a force sensor can be used to predict the crossing of the osteotome through the pterygoid plates., Methods: 31 osteotomies were carried out in 16 lamb skulls. For each impact, the force signal obtained was analysed using a dedicated signal processing technique. A prediction algorithm based on an SVM classifier and a cost matrix was applied to the database., Results: We showed that the device could always detect the crossing of the osteotome, sometimes before its occurrence. The prediction accuracy of the device was 94.7%. The method seemed to be sensitive to the thickness of the plate and to crack apparition and propagation., Conclusion: These results pave the way for the development of a per-operative decision support system in maxillofacial surgery., (© 2024. The Author(s).)

This study aimed to evaluate the feasibility of preclinical training, specifically in root canal preparation, using a virtual educational system equipped with an operating microscope. Ten postgraduate general dentistry trainees and practitioners undergoing postgraduate training in endodontics participated. The telesimulation course included three steps: theory, demonstration of practical work by the teacher and lastly practical training by the participants. The digital environment including the dental microscope was presented, and the feedback was collected with a questionnaire. The majority of participants considered that the online video conference format allowed them to acquire theoretical content but also practical knowledge and skills, owing to the contribution of the operating microscope. The technical feasibility of endodontic telesimulation was demonstrated. The operating microscope has a potential role in distance education, enabling teaching to occur synchronously and collaboratively. This allows learners to interact with each other and demonstrators in real time., (© 2024 Australian Society of Endodontology Inc.)

Characterizing the binding preferences of transcription factors (TFs) in different cell types and conditions is key to understand how they orchestrate gene expression. Here, we develop TFscope, a machine learning approach that identifies sequence features explaining the binding differences observed between two ChIP-seq experiments targeting either the same TF in two conditions or two TFs with similar motifs (paralogous TFs). TFscope systematically investigates differences in the core motif, nucleotide environment and co-factor motifs, and provides the contribution of each key feature in the two experiments. TFscope was applied to > 305 ChIP-seq pairs, and several examples are discussed., (© 2024. The Author(s).)

Motivations: Gene regulatory networks (GRNs) are traditionally inferred from gene expression profiles monitoring a specific condition or treatment. In the last decade, integrative strategies have successfully emerged to guide GRN inference from gene expression with complementary prior data. However, datasets used as prior information and validation gold standards are often related and limited to a subset of genes. This lack of complete and independent evaluation calls for new criteria to robustly estimate the optimal intensity of prior data integration in the inference process., Results: We address this issue for two regression-based GRN inference models, a weighted random forest (weigthedRF) and a generalized linear model estimated under a weighted LASSO penalty with stability selection (weightedLASSO). These approaches are applied to data from the root response to nitrate induction in Arabidopsis thaliana. For each gene, we measure how the integration of transcription factor binding motifs influences model prediction. We propose a new approach, DIOgene, that uses model prediction error and a simulated null hypothesis in order to optimize data integration strength in a hypothesis-driven, gene-specific manner. This integration scheme reveals a strong diversity of optimal integration intensities between genes, and offers good performance in minimizing prediction error as well as retrieving experimental interactions. Experimental results show that DIOgene compares favorably against state-of-the-art approaches and allows to recover master regulators of nitrate induction., Availability and Implementation: The R code and notebooks demonstrating the use of the proposed approaches are available in the repository https://github.com/OceaneCsn/integrative_GRN_N_induction., (© The Author(s) 2024. Published by Oxford University Press.)

Background: Prediction of outcomes remains an unmet need in candidates for LVADs. The development of right-heart failure portends an excess in mortality rates, but imaging parameters of right ventricular systolic function have failed to demonstrate a prognostic role. By integrating pulmonary pressure, right ventriculoarterial coupling could fill this gap., Methods: The ASSIST-ICD registry was used to test right ventriculoarterial coupling as a surrogate parameter at implantation for the prediction of all-cause mortality., Results: The ratio of the tricuspid annular-plane systolic excursion over the estimated systolic pulmonary pressure (TAPSE/sPAP) was not associated with long-term survival in univariate analysis (P = 0.89), nor was the pulmonary artery pulsatility index (PAPi) (P = 0.13). Conversely, the ratio of the right atrial pressure over the pulmonary capillary wedge pressure (RAP/PCWP) was associated with all-cause mortality (P < 0.01). After taking tricuspid regurgitation severity, LVAD indication, LVAD model, age, blood urea nitrogen levels, and pulmonary vascular resistance into account, RAP/PCWP remained associated with survival (HR 1.35 [1.10 - 1.65]; P < 0.01)., Conclusion: Among pre-implant RVAC surrogates, only RAP/PCWP was associated with long-term all-cause mortality in LVAD recipients. This association was independent of established risk factors., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

We investigated the impact of mesenchymal stem cell (MSC) therapy on treating bilateral human hip osteonecrosis, analyzing 908 cases. This study assesses factors such as tissue source and cell count, comparing core decompression with various cell therapies. This research emphasizes bone repair according to pre-treatment conditions and the specificities of cell therapy in osteonecrosis repair, indicating a potential for improved bone repair strategies in hips without femoral head collapse. This study utilized a single-center retrospective analysis to investigate the efficacy of cellular approaches in the bone repair of osteonecrosis. It examined the impact on bone repair of tissue source (autologous bone marrow concentrate, allogeneic expanded, autologous expanded), cell quantity (from none in core decompression alone to millions in cell therapy), and osteonecrosis stage and volume. Excluding hips with femoral head collapse, it focused on patients who had bilateral hip osteonecrosis, both pre-operative and post-operative MRIs, and a follow-up of over five years. The analysis divided these patients into seven groups based on match control treatment variations in bilateral hip osteonecrosis, primarily investigating the outcomes between core decompression, washing effect, and different tissue sources of MSCs. Younger patients (<30 years) demonstrated significantly better repair volumes, particularly in stage II lesions, than older counterparts. Additionally, bone repair volume increased with the number of implanted MSCs up to 1,000,000, beyond which no additional benefits were observed. No significant difference was observed in repair outcomes between different sources of MSCs (BMAC, allogenic, or expanded cells). The study also highlighted that a 'washing effect' was beneficial, particularly for larger-volume osteonecrosis when combined with core decompression. Partial bone repair was the more frequent event observed, while total bone repair of osteonecrosis was rare. The volume and stage of osteonecrosis, alongside the number of injected cells, significantly affected treatment outcomes. In summary, this study provides comprehensive insights into the effectiveness and variables influencing the use of mesenchymal stem cells in treating human hip osteonecrosis. It emphasizes the potential of cell therapy while acknowledging the complexity and variability of results based on factors such as age, cell count, and disease stage.

Importance: Implementation of new cancer treatment strategies as recommended by evidence-based guidelines is often slow and suboptimal., Objective: To improve the implementation of guideline-based best practices in the Netherlands in pancreatic cancer care and assess the impact on survival., Design, Setting, and Participants: This multicenter, stepped-wedge cluster randomized trial compared enhanced implementation of best practices with usual care in consecutive patients with all stages of pancreatic cancer. It took place from May 22, 2018 through July 9, 2020. Data were analyzed from April 1, 2022, through February 1, 2023. It included all patients in the Netherlands with pathologically or clinically diagnosed pancreatic ductal adenocarcinoma. This study reports 1-year follow-up (or shorter in case of deceased patients)., Intervention: The 5 best practices included optimal use of perioperative chemotherapy, palliative chemotherapy, pancreatic enzyme replacement therapy (PERT), referral to a dietician, and use of metal stents in patients with biliary obstruction. A 6-week implementation period was completed, in a randomized order, in all 17 Dutch networks for pancreatic cancer care., Main Outcomes and Measures: The primary outcome was 1-year survival. Secondary outcomes included adherence to best practices and quality of life (European Organisation for Research and Treatment of Cancer [EORTC] global health score)., Results: Overall, 5887 patients with pancreatic cancer (median age, 72.0 [IQR, 64.0-79.0] years; 50% female) were enrolled, 2641 before and 2939 after implementation of best practices (307 during wash-in period). One-year survival was 24% vs 23% (hazard ratio, 0.98, 95% CI, 0.88-1.08). There was no difference in the use of neoadjuvant chemotherapy (11% vs 11%), adjuvant chemotherapy (48% vs 51%), and referral to a dietician (59% vs 63%), while the use of palliative chemotherapy (24% vs 30%; odds ratio [OR], 1.38; 95% CI, 1.10-1.74), PERT (34% vs 45%; OR, 1.64; 95% CI, 1.28-2.11), and metal biliary stents increased (74% vs 83%; OR, 1.78; 95% CI, 1.13-2.80). The EORTC global health score did not improve (area under the curve, 43.9 vs 42.8; median difference, -1.09, 95% CI, -3.05 to 0.94)., Conclusions and Relevance: In this randomized clinical trial, implementation of 5 best practices in pancreatic cancer care did not improve 1-year survival and quality of life. The finding that most patients received no tumor-directed treatment paired with the poor survival highlights the need for more personalized treatment options., Trial Registration: ClinicalTrials.gov Identifier: NCT03513705.

Background & Aims: Malnutrition can develop in patients with obesity suffering from acute or chronic illness or after obesity surgery, promoting sarcopenic obesity. A better understanding of this pathophysiology and the development of new therapeutics for chronic diseases, that are often complicated with malnutrition and obesity, justify the development of new animal experimental models close to the human physiology. This study aims to characterize the effects of obesity and underfeeding on Yucatan obese minipigs, assessing its validity as a preclinical model for obesity-related malnutrition., Methods: Sixteen 30-month-old Yucatan minipigs were divided into two groups for 8 weeks: a standard diet group (ST, n = 5) and an obesogenic diet group (OB, n = 11). After 8 weeks, the OB group was further divided into two sub-groups: a standard diet group (OB-ST, n = 5) and a low-calorie/low-protein diet group (OB-LC/LP, n = 6) for 8 weeks. Body composition by CT-Scan and blood parameters were monitored, and trapezius muscle biopsies were collected to analyse signaling pathways involved in protein turnover and energy metabolism., Results: At W8, OB-ST animals exhibited significantly higher body weight (+37.7%, p = 0.03), muscle mass (+24.9%, p = 0.02), and visceral fat (+192.0%, p = 0.03) compared to ST. Trapezius cross sectional area (CSA) normalized to body weight was lower in OB-ST animals (-15.02%, p = 0.017). At W16, no significant changes were observed in protein turnover markers, although REDD1 increased in OB-ST (96.4%, p = 0.02). After 8 weeks of low-caloric/low protein diet, OB-LC/LP showed decreased body weight (-9.8%, p = 0.03), muscle mass (-6.5%, p = 0.03), and visceral fat (-41.5%, p = 0.03) compared to OB-ST animals. Trapezius fiber CSA significantly decreased in OB-LC/LP (-36.1%, p < 0.0001) and normalized to body weight (-25.4%, p < 0.0001), combined to higher ubiquitinated protein content (+38.3%, p = 0.02)., Conclusion: Our data support that the Yucatan minipig model mimics nutritional and skeletal muscle phenotypes observed in obese patients, with or without protein-energy malnutrition. It also reproduces muscle atrophy observed in chronic diseases or post-obesity surgery, making it a promising preclinical model for obesity-related malnutrition., Competing Interests: Conflicts of interest No conflicts of interest, financial or otherwise, are declared by the authors., (Copyright © 2023 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background: Physiological changes associated with ageing could negatively impact the crisis resource management skills of acute care physicians. This study was designed to determine whether physician age impacts crisis resource management skills, and crisis resource management skills learning and retention using full-body manikin simulation training in acute care physicians., Methods: Acute care physicians at two Canadian universities participated in three 8-min simulated crisis (pulseless electrical activity) scenarios. An initial crisis scenario (pre-test) was followed by debriefing with a trained facilitator and a second crisis scenario (immediate post-test). Participants returned for a third crisis scenario 3-6 months later (retention post-test)., Results: For the 48 participants included in the final analysis, age negatively correlated with baseline Global Rating Scale (GRS; r=-0.30, P<0.05) and technical checklist scores (r=-0.44, P<0.01). However, only years in practice and prior simulation experience, but not age, were significant in a subsequent stepwise regression analysis. Learning from simulation-based education was shown with a mean difference in scores from pre-test to immediate post-test of 2.28 for GRS score (P<0.001) and 1.69 for technical checklist correct score (P<0.001); learning was retained for 3-6 months. Only prior simulation experience was significantly correlated with a decreased change in learning (r=-0.30, P<0.05)., Conclusions: A reduced amount of prior simulation training and increased years in practice, but not age on its own, were significant predictors of low baseline crisis resource management performance. Simulation-based education leads to crisis resource management learning that is well retained for 3-6 months, regardless of age or years in practice., (Copyright © 2023 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Background: The management of residual aortic dissection after initial type A repair with the Frozen elephant trunk technique remains mostly unexplored. This work aimed to evaluate endovascular second-stage surgery for patients with residual aortic dissection., Methods: A retrospective analysis of consecutive patients that underwent Type A aortic repair with Frozen elephant trunk, followed by a second-stage endovascular procedure was done from March 2016 to December 2021. The primary outcome was aortic-related adverse events or mortality, and secondary outcomes were aortic remodeling and perioperative complications. Remodeling was assessed by comparing the difference in ratios for true lumen/total aortic diameters on pre-operative and follow-up scans., Results: Thirty-four patients underwent second-stage surgery after Type A repair during the study period (7 thoracic endovascular aortic repair extensions, 1 STABLE/PETTICOAT, and 26 STABILISE). Median follow-up was 23 months (range 2-66 months). There were no perioperative deaths or major complications and 1 reoperation for left subclavian re-embolization. At the last follow-up, there was no aortic-related mortality. There were 5 aortic-related adverse events, including another subclavian re-embolization and a preplanned open conversion. Risk factors were connective tissue disorders (P = 0.01) and aortic aneurysms >55 mm (P = 0.03). Distal remodeling reached statistical significance in all segments (P < 0.01) and was greater for patients treated with the STABILISE technique when compared to extended thoracic endovascular aortic repair (P = 0.01)., Conclusions: Second-stage endovascular management of residual aortic dissection after initial Frozen elephant trunk repair showed excellent perioperative and good midterm outcomes and induced significant remodeling of the entire aorta in most cases, particularly with the STABILISE procedure., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background and Importance: Emergency Department (ED) workload may lead to ED crowding and increased ED length of stay (LOS). ED crowding has been shown to be associated with adverse events and increasing mortality. We hypothesised that ED-LOS is associated with mortality., Objective: To study the relationship between ED-LOS and in-hospital mortality., Design: Observational retrospective cohort study., Settings and Participants: From 1 January 2015 to 30 September 2018, all visits by patients aged 15 or older to one of the two ED at Toulouse University Hospital were screened. Patients admitted to the hospital after ED visits were included. Visits followed by ED discharge, in-ED death or transfer to ICU or another hospital were not included., Outcome Measure and Analysis: The primary outcome was 30-day in-hospital mortality. ED-LOS was defined as time from ED registration to inpatient admission. ED-LOS was categorised according to quartiles [<303 min (Q1), between 303 and 433 minutes (Q2), between 434 and 612 minutes (Q3) and >612 min (Q4)]. A multivariable logistic regression tested the association between ED-LOS and in-hospital mortality., Main Results: A total of 49 913 patients were admitted to our hospital after ED visits and included in the study. ED-LOS was not independently associated with in-hospital mortality. Compared to ED-LOS < 303 min (Q1, reference), odd-ratios (OR) [95% CI] of in-hospital mortality for Q2, Q3, and Q4 were respectively 0.872 [0.747-1.017], 0.906 [0.777-1.056], and 1.137 [0.985-1.312]. Factors associated to in-hospital mortality were: aged over 75 years (OR [95% CI] = 4.3 [3.8-4.9]), Charlson Comorbidity Index score > 1 (OR [95% CI] = 1.3 [1.1-1.5], and 2.2 [1.9-2.5] for scores 2 and ≥ 3 respectively), high acuity at triage (OR [95% CI] = 3.9 [3.5-4.4]), ED visit at Hospital 1 (OR [95% CI] = 1.6 [1.4-1.7]), and illness diagnosis compared to trauma (OR [95% CI] = 2.1 [1.7-2.6]). Night-time arrival was associated with decreased in-hospital mortality (OR [95% CI] = 0.852 [0.767-0.947])., Conclusion: In this retrospective cohort study, there was no independent association between ED-LOS before admission to general non-ICU wards and in-patient mortality., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

We present early vaccine effectiveness (VE) estimates of the 2023 seasonal COVID-19 XBB.1.5 vaccine against COVID-19 hospitalisation and admission to an intensive care unit (ICU) in previously vaccinated adults ≥ 60 years in the Netherlands. We compared vaccination status of 2,050 hospitalisations including 92 ICU admissions with age group-, sex-, region- and date-specific population vaccination coverage between 9 October and 5 December 2023. VE against hospitalisation was 70.7% (95% CI: 66.6-74.3), VE against ICU admission was 73.3% (95% CI: 42.2-87.6).

Ventricular septal defect (VSD) is a rare but severe complication of myocardial infarction (MI). Temporary mechanical circulatory support (MCS) can be used as a bridge to VSD closure, heart transplantation, or ventricular assist device. We describe the use of Impella device in this context based on a multicenter European retrospective registry (17 centers responded). Twenty-eight post-MI VSD patients were included (Impella device were 2.5 for 1 patient, CP for 20, 5.0 for 5, and unknown for 2). All patients were in cardiogenic shock with multiple organ failure (SAPS II 41 [interquantile range {IQR} = 27-53], lactate 4.0 ± 3.5 mmol/L) and catecholamine support (dobutamine 55% and norepinephrine 96%). Additional temporary MCS was used in 14 patients (50%), mainly extracorporeal life support (ECLS) (n = 9, 32%). Severe bleedings were frequent (50%). In-hospital and 1 year mortalities were 75%. Ventricular septal defect management was surgical for 36% of patients, percutaneous for 21%, and conservative for 43%. Only surgically managed patients survived (70% in-hospital survival). Type and combination of temporary MCS used were not associated with mortality (Impella alone or in combination with intra-aortic balloon pump [IABP] or ECLS, p = 0.84). Impella use in patients with post-MI VSD is feasible but larger prospective registries are necessary to further elucidate potential benefits of left ventricular unloading in this setting., Competing Interests: Disclosure: C.D. has received personal fees from Abott and Abiomed outside the submitted work. G.L. has received proctor, orator and consulting fees from Abbott SA. E.V.P. has received institutional fees from Abott, Medtronic, and Abiomed outside the submitted work. J.L. has received research funds that were paid to the institution from Shockwave Medical Inc. and from Abiomed, and payment or honoraria from AstraZeneca and Boston Scientific, outside the submitted work. J.M. has received personal fees from Abiomed outside the submitted work. P.L. has received personal fees from Abiomed outside the submitted work. N.M. has received personal fees from Edwards Lifesciences, Medtronic, Biotronik, Novartis, Sanofi Genzyme, AstraZeneca, Pfizer, Bayer, Abbott, Abiomed, and Boston Scientific outside the submitted work. The other authors have no conflicts of interest to report., (Copyright © ASAIO 2023.)

Introduction: Enhanced Rehabilitation After Surgery (ERAS) pathways significantly improve the care of patients in orthopedic surgery. However, patient knowledge and memorization of the information provided are currently poorly documented., Hypothesis: The information provided by a postoperative pharmacist could have a positive impact on patient care, in particular by improving knowledge about their prosthesis., Material and Method: This prospective feasibility study included a cohort of 80 patients operated on for a hip or knee prosthesis and who received postoperative pharmacist interviews (POPI). These POPIs informed the patient about the prosthesis, the complications, positions to avoid, as well as the postoperative follow-up. The objective was to measure the patient's knowledge before and after the POPI. Qualitative and quantitative analyses, by indication and patient pathway, were performed., Results: The patient's knowledge before POPI was 70% correct. After POPI this rate rose to 91%., Discussion: Patients' knowledge was weak and heterogeneous, especially regarding the implanted prosthesis. The POPI led to significant improvement and standardization of knowledge which should contribute to the prevention of iatrogenic harm (positions to avoid, infection prevention, compliance with analgesics and anticoagulants)., Conclusion: A POPI with a pharmacist improves overall patient management during hip or knee arthroplasty., Level of Evidence: III; non-randomized prospective feasibility study., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Purpose: Parotidectomies are rarely performed on an outpatient basis. The specific perioperative outcomes and their management remains insufficiently described to change daily practice. The objectives were to study the outcomes, the complications and the patient satisfaction rate in parotidectomy performed on an outpatient basis., Materials and Methods: We conducted a retrospective monocentric database study on 85 patients who underwent parotidectomy as a first and sole procedure from 2015 to 2020. We analyzed perioperative outcomes between outpatients and inpatients., Results: Among 28 outpatients and 57 inpatients, no significant differences in total perioperative complications (p = .66; OR = 1.25; 95 % confidence interval (CI) [0.47; 3.36]), reoperations (p = .55), readmissions (p = 1), or unplanned visits (p = .52) were shown in multivariate analysis. The conversion rate for surgical reasons was 8.6 %, and the satisfaction rate was high., Conclusion: Although outpatient parotidectomies should be as safe as for inpatients, the high rate of minor complications requires specific perioperative management, such as a systematic early postoperative visit and optimized preoperative information in order to be carried out with minimal issues., Competing Interests: Declaration of competing interest This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. It has received ethics approval and patients consent to participate an publish. Printing in color is not necessary., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Free-electron lasers provide bright, ultrashort, and monochromatic x-ray pulses, enabling novel spectroscopic measurements not only with femtosecond temporal resolution: The high fluence of their x-ray pulses can also easily enter the regime of the non-linear x-ray-matter interaction. Entering this regime necessitates a rigorous analysis and reliable prediction of the relevant non-linear processes for future experiment designs. Here, we show non-linear changes in the L 3 -edge absorption of metallic nickel thin films, measured with fluences up to 60 J/cm 2 . We present a simple but predictive rate model that quantitatively describes spectral changes based on the evolution of electronic populations within the pulse duration. Despite its simplicity, the model reaches good agreement with experimental results over more than three orders of magnitude in fluence, while providing a straightforward understanding of the interplay of physical processes driving the non-linear changes. Our findings provide important insights for the design and evaluation of future high-fluence free-electron laser experiments and contribute to the understanding of non-linear electron dynamics in x-ray absorption processes in solids at the femtosecond timescale., Competing Interests: The authors have no conflicts to disclose., (© 2023 Author(s).)

Objective: The Evaluation of Transit-Time Flow in Coronary Artery Disease Surgery (EFCAD) registry aims to assess the influence of transit-time flow measurement (TTFM) in daily practice., Methods: EFCAD is a prospective, multicenter study involving 9 centers performing TTFM during isolated coronary artery bypass grafting. Primary end point was occurrence and risk factors of major adverse cardiac events, including perioperative myocardial infarction, urgent postoperative coronary angiogram and/or revascularization, and hospital mortality. Secondary end points were rate of graft revision during surgery and factors affecting graft flow. We respected the limit values set by the experts: mean graft flow >15 mL/minute and pulsatility index ≤5., Results: Between May 2017 and March 2021, 1616 patients were registered in the EFCAD database. After review, 1414 were included for analyses. Of those, 1176 were eligible for primary end point analysis. Graft revision, mainly due to inadequate TTFM values, occurred in 2% (29 patients). The primary end point occurred in 46 (3.9%) patients, and it was related with left anterior descending artery graft flow ≤15 mL/minute (odds ratio, 3.64; P  < .001). Graft flow was related with number of grafts (3 vs 1-2, β = -1.6; 4-6 vs 1-2, β = -4.1; P  < .001; β > 0 indicates higher flow), and graft origin (aorta vs Y, β = 9.2; in situ left internal thoracic artery vs Y, β = 3.2; in situ right internal thoracic artery vs Y, β = 2.3; P  < .001)., Conclusions: Data from EFCAD study suggest that TTFM is reliable to evaluate graft flow, and acceptance of inadequate flow on left anterior descending artery anastomosis influence postoperative outcomes. In our opinion, TTFM assessment should be routinely used in coronary artery bypass procedures, even if interpretation depends on learning curves., Competing Interests: Dr Laali has received speaker honoraria from Medistim ASA. All other authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest., (© 2023 The Author(s).)

Immune checkpoint inhibitors (ICIs) have improved the management of patients with intermediate- and advanced-stage HCC, even making some of them potential candidates for liver transplantation. However, acute rejection has been observed after ICI therapy, challenging its safety in transplant settings. We summarize the key basic impact of immune checkpoints on HCC and liver transplantation. We analyze the available case reports and case series on the use of ICI therapy prior to and after liver transplantation. A three-month washout period is desirable between ICI therapy and liver transplantation to reduce the risk of acute rejection. Whenever possible, ICIs should be avoided after liver transplantation, and especially so early after a transplant. Globally, more robust prospective data in the field are required.

Aim: Histidine-containing dipeptides (HCDs) are pleiotropic homeostatic molecules with potent antioxidative and carbonyl quenching properties linked to various inflammatory, metabolic, and neurological diseases, as well as exercise performance. However, the distribution and metabolism of HCDs across tissues and species are still unclear., Methods: Using a sensitive UHPLC-MS/MS approach and an optimized quantification method, we performed a systematic and extensive profiling of HCDs in the mouse, rat, and human body (in n = 26, n = 25, and n = 19 tissues, respectively)., Results: Our data show that tissue HCD levels are uniquely produced by carnosine synthase (CARNS1), an enzyme that was preferentially expressed by fast-twitch skeletal muscle fibres and brain oligodendrocytes. Cardiac HCD levels are remarkably low compared to other excitable tissues. Carnosine is unstable in human plasma, but is preferentially transported within red blood cells in humans but not rodents. The low abundant carnosine analogue N-acetylcarnosine is the most stable plasma HCD, and is enriched in human skeletal muscles. Here, N-acetylcarnosine is continuously secreted into the circulation, which is further induced by acute exercise in a myokine-like fashion., Conclusion: Collectively, we provide a novel basis to unravel tissue-specific, paracrine, and endocrine roles of HCDs in human health and disease., (© 2023 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.)

E- and P-selectins are adhesion proteins implicated in immune cell recruitment at sites of infection, making them important drug targets for diseases involving excessive and uncontrolled inflammation. In this study, we developed an efficient strategy to synthesize bicyclic galactopyranosides through a key stereoselective equatorial C4-propiolate addition and TMSCN axial C-glycosidation. The nitrile group can then be converted to the carboxyl and different bioisosteres at a late stage in the synthesis, allowing for various derivatizations to potentially enhance biological activity. The sialyl Lewis X glycomimetic featuring this rigidified bicyclic galactopyranoside moiety prevents neutrophil adhesion to endothelial cells in vitro by binding to both E- and P-selectins. We show here that the axial carboxyl analogue blocks immune cell recruitment in vivo , demonstrating its potential as an immunomodulator.

The action of cis-regulatory elements with either activation or repression functions underpins the precise regulation of gene expression during normal development and cell differentiation. Gene activation by the combined activities of promoters and distal enhancers has been extensively studied in normal and pathological contexts. In sharp contrast, gene repression by cis-acting silencers, defined as genetic elements that negatively regulate gene transcription in a position-independent fashion, is less well understood. Here, we repurpose the STARR-seq approach as a novel high-throughput reporter strategy to quantitatively assess silencer activity in mammals. We assessed silencer activity from DNase hypersensitive I sites in a mouse T cell line. Identified silencers were associated with either repressive or active chromatin marks and enriched for binding motifs of known transcriptional repressors. CRISPR-mediated genomic deletions validated the repressive function of distinct silencers involved in the repression of non-T cell genes and genes regulated during T cell differentiation. Finally, we unravel an association of silencer activity with short tandem repeats, highlighting the role of repetitive elements in silencer activity. Our results provide a general strategy for genome-wide identification and characterization of silencer elements., (© The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Background: Small bowel obstruction (SBO) is a common hospital admission diagnosis. Identification of patients who will require a surgical resection because of a nonviable small bowel remains a challenge. Through a prospective cohort study, the authors aimed to validate risk factors and scores for intestinal resection, and to develop a practical clinical score designed to guide surgical versus conservative management., Patients and Methods: All patients admitted for an acute SBO between 2004 and 2016 in the center were included. Patients were divided in three categories depending on the management: conservative, surgical with bowel resection, and surgical without bowel resection. The outcome variable was small bowel necrosis. Logistic regression models were used to identify the best predictors., Results: Seven hundred and thirteen patients were included in this study, 492 in the development cohort and 221 in the validation cohort. Sixty-seven percent had surgery, of which 21% had small bowel resection. Thirty-three percent were treated conservatively. Eight variables were identified with a strong association with small bowel resection: age 70 years of age and above, first episode of SBO, no bowel movement for greater than or equal to 3 days, abdominal guarding, C-reactive protein greater than or equal to 50, and three abdominal computer tomography scanner signs: small bowel transition point, lack of small bowel contrast enhancement, and the presence of greater than 500 ml of intra-abdominal fluid. Sensitivity and specificity of this score were 65 and 88%, respectively, and the area under the curve was 0.84 (95% CI: 0.80-0.89)., Conclusion: The authors developed and validated a practical clinical severity score designed to tailor management of patients presenting with an SBO., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction The simulation of patient death remains controversial in simulation-based education. We investigated the effect of simulated patient death on learners' skill retention, stress levels, and emotions. Methods After ethics approval, we recruited residents at two Canadian universities. Participants were randomized to manage a simulated cardiac arrest ending with either the unexpected death (intervention group) or survival (control group) of the simulated patient (i.e., manikin). Three months later, all participants performed the same scenario but with the opposite outcome. Blinded video raters assessed participants' non-technical and technical crisis resource management (CRM) skills at both time points. Stress levels (represented by anxiety level, salivary cortisol concentration, and cognitive appraisal) and emotional valence were measured. Outcomes were analyzed using analysis of covariance (ANCOVA) or generalized estimating equations as appropriate. Results The analysis included 46 participants (intervention: n=24; control: n=22). Simulated death neither affected retention of non-technical CRM skills (mean retention Ottawa Global Rating Scale score in the death group [29.4, 95% CI: 27.0, 31.8] versus control group [29.4, 95% CI: 26.8, 32.0; p = 0.87]) nor technical CRM skills (mean retention task-specific checklist score in the manikin death group [11.8, 95% CI: 10.5, 13.0] versus the control group [12.5, 95% CI: 11.3, 13.7; p=0.69]). The simulated death had negative effects on participants' anxiety levels, cognitive appraisal, and emotions. Conclusion Simulated patient death did not affect the retention of non-technical or technical CRM skills but led to greater levels of short-term anxiety, stress, and negative emotions among learners., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Khanduja et al.)

Periprosthetic femoral bone fractures are frequent complications of Total Hip Arthroplasty (THA) and may occur during the insertion of uncemented Femoral Stems (FS), due to the nature of the press-fit fixation. Such fracture may lead to the surgical failure of the THA and require a revision surgery, which may have dramatic consequences. Therefore, an early detection of intra-operative fractures is important to avoid worsening the fracture and/or to enable a peroperative treatment. The aim of this in vitro study is to determine the sensitivity of a method based on resonance frequency analysis of the bone-stem-ancillary system for periprosthetic fractures detection. A periprosthetic fracture was artificially created close to the lesser-trochanter of 10 femoral bone mimicking phantoms. The bone-stem-ancillary resonance frequencies in the range (2-12) kHz were measured on an ancillary instrumented with piezoelectric sensors, which was fixed to the femoral stem. The measurements were repeated for different fracture lengths from 4 to 55 mm. The results show a decrease of the resonance frequencies due to the fracture occurrence and propagation. The frequency shift reached up to 170 Hz. The minimum fracture length that can be detected varies from 3 . 1 ± 1 . 7  mm to 5 . 9 ± 1 . 9  mm according to the mode and to the specimen. A significantly higher sensitivity ( p  = 0.011) was obtained for a resonance frequency around 10.6 kHz, corresponding to a mode vibrating in a plane perpendicular to the fracture. This study opens new paths toward the development of non-invasive vibration-based methods for intra-operative periprosthetic fractures detection.

Introduction: In the Emergency Departments, almost one out of two head CT scans are carried out for traumatic brain injuries among elderly victims of ground level-falls. Recently, a new predictive factor for intracranial lesions in this population has been suggested: presence and location of cutaneous impact. The aim of this study was to establish determinants of intracranial lesion among older patients admitted to EDs due to ground-level falls with traumatic brain injury using the head cutaneous impact location., Methods: A retrospective, observational and monocentric study of patients admitted to Emergency Department for ground-level falls with traumatic brain injury was carried out between 01 January 2017 and 31 July 2017. The primary outcome was identification of an acute intracranial lesion. A bootstrap procedure was employed to evaluate performance and internal validity of the final model., Results: Among the 1036 patients included, the mean age was 85.6 (SD 7.6) years and 94/1036 (9.1%, 95% CI 7.4-10.9) patients presented with an acute intracranial lesion. Multivariable analysis adjusted by bootstrap shrinkage showed that compared with temporal-parietal or occipital impact, Odds Ratio of intracranial lesions were 0.61 (95% CI 0.39-0.95, p = 0.03) in patients with frontal impact, 0.27 (95% CI 0.12-0.59, p = 0.001) in patients with facial impact and 0.21 (95% CI 0.06-0.77, p = 0.018) in patients without cutaneous impact. Subcutaneous hematoma (OR 1.97, p = 0.007), loss of consciousness (OR 4.66, p<0.001), fall-related amnesia (OR 2.58, p = 2.6), vomiting (OR 2.62, p = 0.002) and altered Glasgow Score (OR 6.79, p<0.001) were as well associated with high risk of intracranial lesion. Taking antiplatelets or anticoagulants were not associated with an increased risk of intracranial lesions. The model discrimination was adequate (C-statistic 0.79; 95% CI 0.73 - 0.85)., Conclusion: Our results establish specific determinants of intracranial lesions among elderly after ground level-falls. The cutaneous impact location may identify patients with high risk of intracranial lesion. Further researches are needed to propose a specific score based on these determinants so as to better target Head CT scan use., Competing Interests: Declaration of Competing Interest Authors assumed no relevant conflicts of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objectives: To assess whether a Quantra-guided hemostatic algorithm would reduce transfusion requirement and major bleeding compared with laboratory-guided testing in patients facing high-bleeding-risk cardiac surgery., Design: Single-center before-and-after study., Setting: University hospital., Participants: Patients facing high-bleeding-risk cardiac surgery with cardiopulmonary bypass., Interventions: Hemostatic algorithm was based on standard laboratory testing during the control period, then on the Quantra during the Quantra period. The primary endpoint was the number of red blood cell (RBC) units transfused on day 1 after surgery., Measurements and Main Results: After propensity-score matching, 66 patients were included in the Quantra group and 117 in the control group. The Quantra group received fewer RBC units on day 1 than the control group (2 [0-5] v 4 [2-6], p = 0.016, respectively). Intraoperatively, the Quantra group received fewer RBC (2 [0-3] v 3 [1-5], p = 0.005), less fresh frozen plasma (0 [0-3] v 3[2-5], p < 0.0001), and fewer platelet units (7.5 [0-10] v 8.2 [6.3-11.7], p = 0.014). The intraoperative rates of RBC, plasma, and platelet transfusion were reduced (64% v 78%, p = 0.05; 41% v 85%, p < 0.001; 55% v 82%, p = 0.001, respectively). The RBC and plasma transfusions were reduced on days 1, 2, and 7. The incidence of major bleeding on day 1 also was reduced (36% v 56%, p = 0.014). In multivariate analysis, implementation of the Quantra-guided hemostatic algorithm was associated independently with reductions in major bleeding., Conclusion: Implementation of a Quantra-based hemostatic algorithm was associated with a decrease in transfusion requirement and major bleeding after high-bleeding-risk cardiac surgery. Randomized trials are needed to confirm these results., Competing Interests: Declaration of competing interest A. G. received honoraria for lectures in symposia from Aguettant, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb/Pfizer, LFB, Sanofi, outside the submitted work., (Copyright © 2023 Elsevier Inc. All rights reserved.)

A 67-year-old patient with history of heart transplantation was referred for symptomatic severe tricuspid regurgitation. Diagnostic workup showed chordal ruptures on the septal and anterior leaflets, most likely related to endomyocardial biopsies. Given the high surgical risk, the patient was treated percutaneously, with good results persisting at 3 months. ( Level of Difficulty: Intermediate. )., Competing Interests: Dr Martin has received consultant fees and research grant from Alliance BMS-Pfizer and consultant fees from Abbott, Bayer, and Novartis outside the submitted work. Dr Karam has received consultant fees from Abbott Vascular, Edwards Lifesciences, and Medtronic outside the submitted work. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2023 The Authors.)

Introduction: The French Tele-Medical Assistance Service (TMAS) provides medical teleconsultation for any ship at sea. At the end of the consultation, the doctor decides whether the problem can be taken care of onboard or not. In this study, we determined the factors associated with the decision for disembarkation or evacuation in case of wounds. Methods: We conducted a retrospective epidemiological study between 2011 and 2019 from consultations with the French TMAS. The inclusion criterion was the presence of an acute wound. Results: One thousand six patients ( n  = 1,006) were analyzed and 586 (58%) patients were disembarked or evacuated. Factors associated with disembarkation or evacuation are wound characteristics (severity and location), the onboard staff's medical training, the availability of photography, and the ship's location. Wound severity is a risk factor for disembarkation or evacuation. The availability of photography, staff with advanced training, and being at >1 day of navigation from a harbor are protective factors against being disembarked or evacuated. Conclusion: The added value of photography and an update of medium medical training could increase the number of wounds taken care of onboard.

The ability to visualize RNA in its native subcellular environment by using single-molecule fluorescence in situ hybridization (smFISH) has reshaped our understanding of gene expression and cellular functions. A major hindrance of smFISH is the difficulty to perform systematic experiments in medium- or high-throughput formats, principally because of the high cost of generating the individual fluorescent probe sets. Here, we present high-throughput smFISH (HT-smFISH), a simple and cost-efficient method for imaging hundreds to thousands of single endogenous RNA molecules in 96-well plates. HT-smFISH uses RNA probes transcribed in vitro from a large pool of unlabeled oligonucleotides. This allows the generation of individual probes for many RNA species, replacing commercial DNA probe sets. HT-smFISH thus reduces costs per targeted RNA compared with many smFISH methods and is easily scalable and flexible in design. We provide a protocol that combines oligo pool design, probe set generation, optimized hybridization conditions and guidelines for image acquisition and analysis. The pipeline requires knowledge of standard molecular biology tools, cell culture and fluorescence microscopy. It is achievable in ~20 d. In brief, HT-smFISH is tailored for medium- to high-throughput screens that image RNAs at single-molecule sensitivity., (© 2022. Springer Nature Limited.)

Clinical islet transplantation (CIT) is an established noninvasive treatment for type I diabetes (T1D) and has demonstrated improved glycemic control, preventing the occurrence of severe hypoglycemia. However, CIT has several limitations, such as the need for multiple donors, lifelong immunosuppression, and suboptimal long-term graft function. Most of the transplanted islets are lost due to inflammation, ischemic damage, and delayed revascularization.Generation of organoids have gained increasing interest in regenerative medicine in recent years. In the context of beta-cell replacement, it offers a possibility to address limitations of CIT by allowing to produce uniform organoids from single or multiple cell types facilitating revascularization and anti-inflammatory and/or immunomodulatory protection. We have previously generated multicellular insulin-secreting organoids composed of islet cells and the human amniotic epithelial cells (hAECs). These 3D insulin-secreting structures demonstrated improved viability and function both in vitro and in vivo. Here we detail a stepwise methodology to generate insulin-secreting organoids using two different methods. In addition, quality assessment in vitro tests are also described., (© 2023. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

The effect of emergency department (ED) length of stay (EDLOS) on in-hospital mortality (IHM) remains unclear. The aim of this systematic review and meta-analysis was to determine the association between EDLOS and IHM. We searched the PubMed, Medline, Embase, Web of Science, Cochrane Controlled Register of Trials, CINAHL, PsycInfo, and Scopus databases from their inception until 14−15 January 2022. We included studies reporting the association between EDLOS and IHM. A total of 11,337 references were identified, and 52 studies (total of 1,718,518 ED patients) were included in the systematic review and 33 in the meta-analysis. A statistically significant association between EDLOS and IHM was observed for EDLOS over 24 h in patients admitted to an intensive care unit (ICU) (OR = 1.396, 95% confidence interval [CI]: 1.147 to 1.701; p < 0.001, I2 = 0%) and for low EDLOS in non-ICU-admitted patients (OR = 0.583, 95% CI: 0.453 to 0.745; p < 0.001, I2 = 0%). No associations were detected for the other cut-offs. Our findings suggest that there is an association between IHM low EDLOS and EDLOS exceeding 24 h and IHM. Long stays in the ED should not be allowed and special attention should be given to patients admitted after a short stay in the ED.