Université Victor Segalen Bordeaux 2

Background Esophageal cancer posed significant global health challenges, particularly due to poor survival rates, especially in advanced stages. Primary endoscopic resection had emerged as an alternative treatment for early esophageal cancer, aiming to preserve organ function and reduce surgical morbidity. Methods This retrospective multicenter cohort study included 334 patients with early esophageal cancer (T1a-b, N0) from 30 French-speaking European centers between 2000 and 2010. Patients underwent either primary endoscopic resection followed by esophagectomy (E group, n = 36) or esophagectomy alone (S group, n = 298). Cox proportional hazards models adjusted for TNM stage and propensity score weighting were used to assess the impact of primary endoscopic resection on recurrence-free survival (RFS), overall survival (OS), and postoperative complications. Results Primary endoscopic resection did not significantly influence RFS (adjusted HR 0.92, 95% CI 0.31 to 2.68, p = 0.88) or OS (adjusted HR 1.06, 95% CI 0.35 to 3.13, p = 0.92) compared to esophagectomy alone. Initial higher thromboembolic complications in the endoscopic resection group were not significant after adjustment (adjusted OR 4.73, 95% CI 0.34 to 64.27, p = 0.24). Conclusions Primary endoscopic resection followed by esophagectomy for early esophageal cancer did not alter oncological outcomes or overall survival in this retrospective cohort. These findings supported the role of primary endoscopic resection as a safe initial treatment strategy, warranting validation in larger prospective studies. Registration: Our study was registered retrospectively on the Clinicaltrials.com website under the identifier NCT 01927016. We acknowledge the importance of prospective registration and regret that this was not done before the commencement of the study

We analyse a system of nonlinear stochastic partial differential equations (SPDEs) of mixed elliptic-parabolic type that models the propagation of electric signals and their effect on the deformation of cardiac tissue. The system governs the dynamics of ionic quantities, intra and extra-cellular potentials, and linearised elasticity equations. We introduce a framework called the active strain decomposition, which factors the material gradient of deformation into an active (electrophysiology-dependent) part and an elastic (passive) part, to capture the coupling between muscle contraction, biochemical reactions, and electric activity. Under the assumption of linearised elastic behaviour and a truncation of the nonlinear diffusivities, we propose a stochastic electromechanical bidomain model, and establish the existence of weak solutions for this model. To prove existence through the convergence of approximate solutions, we employ a stochastic compactness method in tandem with an auxiliary non-degenerate system and the Faedo–Galerkin method. We utilise a stochastic adaptation of de Rham’s theorem to deduce the weak convergence of the pressure approximations.

Background According to current international guidelines, stage cT2N0M0 gastric adenocarcinoma warrants preoperative chemotherapy followed by surgery. However, upfront surgery is often preferred in clinical practice, depending on patient clinical status and local treatment preferences. Objective The aim of the present study was to assess the impact of neoadjuvant chemotherapy in overall survival (OS) and disease-free survival (DFS) of cT2N0M0 patients. Methods A retrospective analysis was performed among 32 centers, including gastric adenocarcinoma patients operated between January 2007 and December 2017. Patients with cT2N0M0 stage were divided into upfront surgery (S) and neoadjuvant chemotherapy followed by surgery (CS) groups. Inverse probability of treatment weighting (IPTW) was used to compensate for baseline differences between the groups. Results Among the 202 patients diagnosed with cT2N0M0 stage, 68 (33.7%) were in the CS group and 134 (66.3%) were in the S group. CS patients were younger (mean age 62.7 ± 12.8 vs. 69.8 ± 12.1 years for S patients; p < 0.001) and had a better health status (World Health Organization performance status = 0 in 60.3% of CS patients vs. 34.5% of S patients; p = 0.006). During follow-up, recurrence occurred in 27.2% and 19.6% of CS and S patients, respectively, after IPTW ( p = 0.32). Five-year OS was similar between CS and S patients (78.9% vs. 68.3%; p = 0.42), as was 5-year DFS (70.4% vs. 68.5%; p = 0.96). Neoadjuvant chemotherapy was associated with neither OS nor DFS in multivariable analysis after IPTW. Conclusions Patients with cT2N0M0 gastric adenocarcinoma did not present a survival or recurrence benefit if treated with perioperative chemotherapy followed by surgery as opposed to surgery alone.

In the intensive care unit (ICU), many patients with acquired brain injury (ABI) benefit from tracheostomy. Tracheostomy weaning protocols typically include cuff deflation and tube capping. However, the roles and importance of these steps are debated. The rationale behind tube capping is to recreate airflow through the upper airway that promotes laryngeal reafferentiation, natural heating, air filtration, humidification through the nose, swallowing, and improved subglottic pressure. However, tube capping can increase the respiratory workload by reducing the tracheal lumen diameter because it forces the airflow around the cannula. Therefore, this may be considered risky or too demanding. Cuff deflation without tube capping is sometimes suggested instead of cuff deflation with tube capping, but it has not been proven that this sufficiently recreates the upper airway airflow necessary for tracheostomy weaning. The objective of this study was to describe and compare the upper airway airflow, swallowing, and signs of increased respiratory workload under the following conditions: cuff deflation alone and cuff deflation with a speaking valve. To our knowledge, this comparison is novel.

Significance: Oxidative folding within the endoplasmic reticulum (ER) introduces disulfide bonds into nascent polypeptides, ensuring proteins' stability and proper functioning. Consequently, this process is critical for maintaining proteome integrity and overall health. The productive folding of thousands of secretory proteins requires stringent quality control measures, such as the unfolded protein response (UPR) and ER-Associated Degradation (ERAD), which contribute significantly to maintaining ER homeostasis. ER-localized protein disulfide isomerases (PDIs) play an essential role in each of these processes, thereby contributing to various aspects of ER homeostasis, including maintaining redox balance, proper protein folding, and signaling from the ER to the nucleus. Recent Advances: Over the years, there have been increasing reports of the (re)localization of PDI family members and other ER-localized proteins to various compartments. A prime example is the anterior gradient (AGR) family of PDI proteins, which have been reported to relocate to the cytosol or the extracellular environment, acquiring gain of functions that intersect with various cellular signaling pathways. Critical Issues: Here, we summarize the functions of PDIs and their gain or loss of functions in non-ER locations. We will focus on the activity, localization, and function of the AGR proteins: AGR1, AGR2, and AGR3. Future Directions: Targeting PDIs in general and AGRs in particular is a promising strategy in different human diseases. Thus, there is a need for innovative strategies and tools aimed at targeting PDIs; those strategies should integrate the specific localization and newly acquired functions of these PDIs rather than solely focusing on their canonical roles.

Neurological patients frequently have disorders of consciousness, swallowing disorders, or neurological states that are incompatible with extubation. Therefore, they frequently require tracheostomies during their stay in an intensive care unit. After the acute phase, tracheostomy weaning and decannulation are generally expected to promote rehabilitation. However, few reliable predictive factors (PFs) for decannulation have been identified in this patient population. We sought to identify PFs that may be used during tracheostomy weaning and decannulation in patients with brain injuries. We conducted a systematic review of the literature regarding potential PFs for decannulation; searches were performed on 16 March 2021 and 1 June 2022. The following databases were searched: MEDLINE, EMBASE, CINAHL, Scopus, Web of Science, PEDro, OPENGREY, OPENSIGLE, Science Direct, CLINICAL TRIALS and CENTRAL. We searched for all article types, except systematic reviews, meta-analyses, abstracts, and position articles. Retrieved articles were published in English or French, with no date restriction. In total, 1433 articles were identified; 26 of these were eligible for inclusion in the review. PFs for successful decannulation in patients with acquired brain injuries (ABIs) included high neurological status, traumatic brain injuries rather than stroke or anoxic brain lesions, younger age, effective swallowing, an effective cough, and the absence of pulmonary infections. Secondary PFs included early tracheostomy, supratentorial lesions, the absence of critical illness polyneuropathy/myopathy, and the absence of tracheal lesions. To our knowledge, this is the first systematic review to identify PFs for decannulation in patients with ABIs. These PFs may be used by clinicians during tracheostomy weaning.

Concurrently to the recent development of percutaneous tracheostomy techniques in the intensive care unit (ICU), the amount of tracheostomized brain-injured patients has increased. Despites its advantages, tracheostomy may represent an obstacle to their orientation towards conventional hospitalization or rehabilitation services. To date, there is no recommendation for tracheostomy weaning outside of the ICU. We created a pluridisciplinary tracheostomy weaning protocol relying on standardized criteria but adapted to each patient’s characteristics and that does not require instrumental assessment. It was tested in a prospective, single-centre, non-randomized cohort study. Inclusion criteria were age > 18 years, hospitalized for an acquired brain injury (ABI), tracheostomized during an ICU stay, and weaned from mechanical ventilation. The exclusion criterion was severe malnutrition. Decannulation failure was defined as recannulation within 96 h after decannulation. Thirty tracheostomized ABI patients from our neurosurgery department were successively and exhaustively included after ICU discharge. Twenty-six patients were decannulated (decannulation rate, 90%). None of them were recannulated (success rate, 100%). Two patients never reached the decannulation stage. Two patients died during the procedure. Mean tracheostomy weaning duration (inclusion to decannulation) was 7.6 (standard deviation [SD]: 4.6) days and mean total tracheostomy time (insertion to decannulation) was 42.5 (SD: 24.8) days. Our results demonstrate that our protocol might be able to determine without instrumental assessment which patient can be successfully decannulated. Therefore, it may be used safely outside ICU or a specialized unit. Moreover, our tracheostomy weaning duration is very short as compared to the current literature.

Two central questions in COVID-19 treatment which should be considered are: "How does the imbalance of the complement system affect the therapeutic approaches?" and "Do we consider complement inhibitors in therapeutic protocols?". The complement system is a double-edged sword since it may either promote immune responses against COVID-19 or contribute to destructive inflammation in the host. Therefore, it is crucial to regulate this system with complement inhibitors. In this manuscript, we discuss the molecular mechanisms of complement and complement inhibitors in COVID-19 patients. We searched the terms "COVID-19", "Complement", "Complement inhibitor", "SARS-CoV-2", and all complement fragments and inhibitors from 2000 to 2022 in PubMed and google scholar and checked the pathways in "KEGG pathway database". Complement is not well-appreciated in the treatment protocols despite its multiple roles in the disease, and most of the preventive anti-inflammatory therapeutic approaches did not include a complement inhibitor in COVID-19 therapeutic protocols. In this review article, we discussed the most recent studies regarding complement components mediated interventions and the mechanism of these interventions in COVID-19 patients. Since the control of the complement system overactivation is associated with a better prognosis in the initial stages of COVID-19, heparin, anti-thrombin, C1-inhibitor, montelukast, and hydralazine can be effective in the initial stages of this viral infection. Recombinant complement activation (RCA) proteins are more effective in regulating complement compared to terminal pathway therapeutic approaches such as the C3a and C5a inhibitors.

Simple Summary Despite considerable advances in esogastric cancer surgeries, postoperative malnutrition remains a significant yet overlooked challenge. It triggers weight loss, muscle mass reduction, and essential nutrient deficiencies, detrimentally impacting patients’ quality of life and prognosis. Our study reveals that micronutrient deficiencies are just as prevalent in patients post-esophagectomy as after partial or total gastrectomy. These findings underscore the need for proactive measures, including prevention, early detection, and prompt management. Abstract Primary surgical indications for the esophagus and stomach mainly involve cancer surgeries. In recent years, significant progress has been made in the field of esogastric surgery, driven by advancements in surgical techniques and improvements in perioperative care. The rate of resectability has increased, and surgical strategies have evolved to encompass a broader patient population. However, despite a reduction in postoperative mortality and morbidity, malnutrition remains a significant challenge after surgery, leading to weight loss, muscle mass reduction, and deficiencies in essential nutrients due to digestive complications. Malnutrition worsens quality of life and increases the risk of tumor recurrence, significantly affecting prognosis. Nevertheless, the nutritional consequences following surgery are frequently overlooked, mainly due to a lack of awareness regarding their long-term effects on patients who have undergone digestive surgery, extending beyond six months. Micronutrient deficiencies are frequently observed following both partial and total gastrectomy, as anticipated. Surprisingly, these deficiencies appear to be similarly prevalent in patients who have undergone esophagectomy with iron, vitamins A, B1, B12, D, and E deficiencies commonly observed in up to 78.3% of the patients. Recognizing the distinct consequences associated with each type of intervention underscores the importance of implementing preventive measures, early detection, and prompt management.

Introduction In-bed leg cycling with critically ill patients is a promising intervention aimed at minimising immobility, thus improving physical function following intensive care unit (ICU) discharge. We previously completed a pilot randomised controlled trial (RCT) which supported the feasibility of a large RCT. In this report, we describe the protocol for an international, multicentre RCT to determine the effectiveness of early in-bed cycling versus routine physiotherapy (PT) in critically ill, mechanically ventilated adults. Methods and analysis We report a parallel group RCT of 360 patients in 17 medical-surgical ICUs and three countries. We include adults (≥18 years old), who could ambulate independently before their critical illness (with or without a gait aid), ≤4 days of invasive mechanical ventilation and ≤7 days ICU length of stay, and an expected additional 2-day ICU stay, and who do not fulfil any of the exclusion criteria. After obtaining informed consent, patients are randomised using a web-based, centralised system to either 30 min of in-bed cycling in addition to routine PT, 5 days per week, up to 28 days maximum, or routine PT alone. The primary outcome is the Physical Function ICU Test-scored (PFIT-s) at 3 days post-ICU discharge measured by assessors blinded to treatment allocation. Participants, ICU clinicians and research coordinators are not blinded to group assignment. Our sample size estimate was based on the identification of a 1-point mean difference in PFIT-s between groups. Ethics and dissemination C ritical Care C yc ling to improve L ower E xtremity (CYCLE) is approved by the Research Ethics Boards of all participating centres and Clinical Trials Ontario (Project 1345). We will disseminate trial results through publications and conference presentations. Trial registration number NCT03471247 (Full RCT); NCT02377830 (CYCLE Vanguard 46 patient internal pilot).

Introduction With the end of the Millennium Agenda, the United Nations Member States adopted the Sustainable Development Agenda in 2015. This new agenda identifies 17 Sustainable Development Goals (SDGs) and 169 targets for 2030, including Water, Sanitation and Hygiene (WASH). Objective To study the evolution of household access to WASH services over the last two decades in Benin and make projections for 2030. Methods In this study, secondary analyses were performed using the datasets of the Demographic and Health Surveys in Benin from 2001 to 2017–2018. The statistical unit was the household. The achievement of the WASH SDGs targets was monitored through the proportion of households using individual basic WASH services, the proportion of households using surface water for drinking, and the proportion of households practising open defecation. The study generated Annual Percentage Changes (APCs) for outcome variables. Based on the APCs between 2001 and 2017–2018, projections were made for 2030. Results From 2001 to 2017–2018, household access to individual basic WASH services increased from 50.54% to 63.98% (APC = +1.44%), 5.39% to 13.29% (APC = +5.62%), and 2.12% to 10.11% (APC = +9.92%), respectively. At the same time, the prevalence of surface water consumption and open defecation among households decreased from 10.54% to 5.84% (APC = -3.52%) and 67.03% to 53.91% (APC = -1.31%), respectively. If the trend observed between 2001 and 2017–2018 remains unchanged, the national coverage of households with basic individual WASH services would be 76.50%, 26.33% and 10.51%, respectively, by 2030. The prevalence of surface water consumption and open defecation among households would be 3.73% and 45.71%, respectively, by 2030. Conclusion Benin achieved significant progress in household coverage of adequate WASH services over the last two decades. However, progress appears insufficient to achieve universal coverage of households with basic WASH services, and eliminate surface water consumption and open defecation by 2030. There is a need to strengthen research into the drivers of household access to adequate WASH services.

Less than one-quarter of oral health trials are registered in a public registry. However, no study has assessed the extent of study publication and selective outcome reporting bias in the field of oral health. We identified oral health trials registered between 2006 and 2016 in ClinicalTrials.gov. We assessed whether results of early discontinued trials, trials having an unknown status, and completed trials had been published and, among published trials, whether outcomes differed between the registered record and the corresponding publication. We included 1,399 trials, of which 81 (5.8%) were discontinued, 247 (17.7%) had an unknown status, and 1,071 (76.6%) were completed. The registration was prospective for 719 (51.9%) trials. Over half the registered trials were unpublished (n = 793, 56.7%). To explore the association between trials publication and characteristics of trials, we performed a multivariate logistic regression analysis. Trials conducted in the United States (P = 0.003) or Brazil (P < 0.001) were associated with increased odds of publication, whereas trials registered prospectively (P = 0.001) and industry-sponsored trials (P = 0.02) were associated with decreased odds. Among the 479 published trials with completed status, the primary outcomes of 215 (44.9%) articles differed from that registered. Major discrepancies consisted of the introduction of a new primary outcome in the published article (196 [91.2%]) and the transformation of a registered secondary outcome into a primary outcome (112 [52.1%]). In the remaining 264 (55.1%) trials, primary outcomes did not differ from that registered, but 141 (53.4%) had been registered retrospectively. Our study highlights the high rate of nonpublication and selective outcome reporting in the field of oral health. These results could alert sponsors, funders, authors of systematic reviews, and the oral health research community at large to combat the nondisclosure of trial results.

In this paper, we investigate the qualitative behavior of a class of fractional SEIR epidemic models with a more general incidence rate function and time delay to incorporate latent infected individuals. We first prove positivity and boundedness of solutions of the system. The basic reproduction number R0${\mathcal{R}}_0$ of the model is computed using the method of next generation matrix, and we prove that if R0<1${\mathcal{R}}_0<1$, the healthy equilibrium is locally asymptotically stable, and when R0>1${\mathcal{R}}_0>1$, the system admits a unique endemic equilibrium which is locally asymptotically stable. Moreover, using a suitable Lyapunov function and some results about the theory of stability of differential equations of delayed fractional‐order type, we give a complete study of global stability for both healthy and endemic steady states. The model is used to describe the COVID‐19 outbreak in Algeria at its beginning in February 2020. A numerical scheme, based on Adams–Bashforth–Moulton method, is used to run the numerical simulations and shows that the number of new infected individuals will peak around late July 2020. Further, numerical simulations show that around 90% of the population in Algeria will be infected. Compared with the WHO data, our results are much more close to real data. Our model with fractional derivative and delay can then better fit the data of Algeria at the beginning of infection and before the lock and isolation measures. The model we propose is a generalization of several SEIR other models with fractional derivative and delay in literature.

Simple Summary Gastric adenocarcinoma remains associated with a poor prognosis despite recent therapeutical advances. As diagnosis is frequently made at an advanced stage, long-term outcome is dismal. Individualized identification of factors associated with poor prognosis allows more precise survival prediction and, in some cases, to propose targeted treatment through individualized precision medicine. This review aims to highlight the prognosis determinants of these tumors and potential therapeutical impact from the available literature. Abstract Gastric adenocarcinoma remains associated with a poor long-term survival, despite recent therapeutical advances. In most parts of the world where systematic screening programs do not exist, diagnosis is often made at advanced stages, affecting long-term prognosis. In recent years, there is increasing evidence that a large bundle of factors, ranging from the tumor microenvironment to patient ethnicity and variations in therapeutic strategy, play an important role in patient outcome. A more thorough understanding of these multi-faceted parameters is needed in order to provide a better assessment of long-term prognosis in these patients, which probably also require the refinement of current staging systems. This study aims to review existing knowledge on the clinical, biomolecular and treatment-related parameters that have some prognostic value in patients with gastric adenocarcinoma.