Cell shape characteristics of human skeletal muscle cells as a predictor of myogenic competency: A new paradigm towards precision cell therapy

Skeletal muscle-derived cells (SMDC) hold tremendous potential for replenishing dysfunctional muscle lost due to disease or trauma. Current therapeutic usage of SMDC relies on harvesting autologous cells from muscle biopsies that are subsequently expanded in vitro before re-implantation into the patient. Heterogeneity can arise from multiple factors including quality of the starting biopsy, age and comorbidity affecting the processed SMDC. Quality attributes intended for clinical use often focus on minimum levels of myogenic cell marker expression. Such approaches do not evaluate the likelihood of SMDC to differentiate and form myofibres when implanted in vivo, which ultimately determines the likelihood of muscle regeneration. Predicting the therapeutic potency of SMDC in vitro prior to implantation is key to developing successful therapeutics in regenerative medicine and reducing implementation costs. Here, we report on the development of a novel SMDC profiling tool to examine populations of cells in vitro derived from different donors. We developed an image-based pipeline to quantify morphological features and extracted cell shape descriptors. We investigated whether these could predict heterogeneity in the formation of myotubes and correlate with the myogenic fusion index. Several of the early cell shape characteristics were found to negatively correlate with the fusion index. These included total area occupied by cells, area shape, bounding box area, compactness, equivalent diameter, minimum ferret diameter, minor axis length and perimeter of SMDC at 24 h after initiating culture. The information extracted with our approach indicates live cell imaging can detect a range of cell phenotypes based on cell-shape alone and preserving cell integrity could be used to predict propensity to form myotubes in vitro and functional tissue in vivo

La mesure de la distensibilité pylorique est prédictive de la réponse symptomatique aux injections intra-pyloriques de toxine botulique

De récentes études ont rapport que la distensibilité pylorique pouvait être altérée chez 30 à 50% des patients atteints de gastroparésie et qu’il existait une corrélation avec le ralentissement de la vidange gastrique et la sévérité des symptômes. L’objectif de cette étude était d’évaluer si la mesure de la distensibilité pylorique pouvait être prédictive de la réponse symptomatique aux injections intra-pyloriques de toxine botulique. Méthode La distensibilité pylorique était mesurée en utilisant le système EndoFLIPâ avant injections intra-pyloriques de toxine botulique. La distensibilité pylorique altérée était définie comme inférieure à 10 mm2/mmHg. Le score Total symptomatic score (TSS), les symptômes dyspeptiques, le score Gastrointestinal Quality of Life Index (GIQLI) et la vidange gastrique étaient étudiés prospectivement avant et après la réalisation des injections de toxine botulique. Résultats : Dix-neuf sur 35 patients avaient une distensibilité pylorique altérée. Chez ces patients, le score TSS était diminué à 3 mois de 13,5 à 10,5 (p<0,01), tandis qu’il restait inchangé chez les patients avec distensibilité pylorique normale (p=0,7). La plénitude gastrique (de 3,5 à 2,5 ; p=0,03) et les ballonnements (de 3,0 à 2,0 ; p=0,01) étaient les seuls symptômes améliorés chez les patients avec distensibilité pylorique altérée, alors qu’aucun symptôme dyspeptique n’était amélioré chez les patients avec distensibilité pylorique normale. Le score GIQLI était augmenté de 59,5 à 76,5 chez les patients avec distensibilité pylorique altérée (p=0,02) tandis qu’il n’y avait aucune différence chez les patients avec distensibilité pylorique normale (p=0,43). Chez les patients avec distensibilité pylorique altérée, le temps de demividange gastrique était de 223 min avant versus 19

Evaluation des compétences sphinctériennes du système gastro-intestinal par systéme EndoFLIP

The EndoFLIP system allows the obtention of geometrical data at different levels in the digestive system, in particularly in sphincters. Most studies assessed its relevance in the esophageal area, but only a few studies evaluated its interest regarding both pyloric and canal anal evaluation. The first step of this work was to assess the mechanistic interest of the pyloric and anal EndoFLIP. We found that 56.5% of patients with diabetic gastroparesis exhibited altered pyloric distensibility, in a similar range as the one found in idiopathic gastroparesis (51.5%). However, we did not find any correlation between diabetes characteristics and pyloric parameters in patients with diabetic gastroparesis. In patients with dyspeptic symptoms developed after oeso-gastric surgery, we found an altered pyloric distensibility in 61.1% of patients with prior anti reflux surgery, 75.0% of patients with prior esophagectomy and 18.7% of patients with sleeve-gastrectomy. Lastly, we found a weak correlation between fecal incontinence subtypes and anal sphincter distensibility. The 2nd step of this work was to assess the interest of the EndoFLIP used to evaluate treatment efficacy. We found that pyloric distensibility was predictive of the efficacy of intrapyloric botulinum toxin injections in patients with refractory gastroparesis. The 3rd step of this work was to improve the method of the EndoFLIP. We found that there was an impact of general anesthesia and anesthetics on the pyloric EndoFLIP measurements.Le système EndoFLIP permet l’obtention de données géométriques à différent niveaux du système digestif, notamment les sphincters. La plupart des études ont évalué son utilité au niveau de l’œsophage, mais peu d’études se sont intéressées à son intérêt au niveau du sphincter pylorique et du canal anal. Le premier axe de ce travail avait pour but d’évaluer l’intérêt mécanistique de l’EndoFLIP du pylore et du canal anal. Nous avons pu montrer que 56,5% des patients atteints de gastroparésie diabétique présentaient une distensibilité pylorique altérée, avec un taux similaire retrouvé chez les patients atteints de gastroparésie idiopathique (51,5%). En revanche, il n’existait pas de corrélation entre les caractéristiques du diabète et les différents paramètres du pylore chez les patients atteints de gastroparésie diabétique. Chez les patients avec symptômes dyspeptiques apparus après chirurgie oeso-gastrique, la distensibilité pylorique était altérée chez 61,1% des patients du groupe chirurgie anti-reflux, 75,0% du groupe oesophagectomie et 18,7% du groupe sleeve-gastrectomie. Nous avons pu montrer qu’il existait une faible relation entre le type d’incontinence fécale et la distensibilité du canal anal. Le 2ème axe de notre travail portait sur l’intérêt de l’EndoFLIP pour évaluer l’efficacité d’un traitement. La mesure de la distensibilité pylorique était ainsi prédictive de la réponse symptomatique aux injections intra-pyloriques de toxine botulique chez les patients atteints de gastroparésie réfractaire. Le 3ème axe de notre travail portait sur l’amélioration de la technique d’EndoFLIP. Nous avons pu mettre en évidence qu’il existait un impact de l’anesthésie générale et des anesthésiants sur les résultats de l’EndoFLIP du pylore

Evaluation des compétences sphinctériennes du système gastro-intestinal par systéme EndoFLIP

The EndoFLIP system allows the obtention of geometrical data at different levels in the digestive system, in particularly in sphincters. Most studies assessed its relevance in the esophageal area, but only a few studies evaluated its interest regarding both pyloric and canal anal evaluation. The first step of this work was to assess the mechanistic interest of the pyloric and anal EndoFLIP. We found that 56.5% of patients with diabetic gastroparesis exhibited altered pyloric distensibility, in a similar range as the one found in idiopathic gastroparesis (51.5%). However, we did not find any correlation between diabetes characteristics and pyloric parameters in patients with diabetic gastroparesis. In patients with dyspeptic symptoms developed after oeso-gastric surgery, we found an altered pyloric distensibility in 61.1% of patients with prior anti reflux surgery, 75.0% of patients with prior esophagectomy and 18.7% of patients with sleeve-gastrectomy. Lastly, we found a weak correlation between fecal incontinence subtypes and anal sphincter distensibility. The 2nd step of this work was to assess the interest of the EndoFLIP used to evaluate treatment efficacy. We found that pyloric distensibility was predictive of the efficacy of intrapyloric botulinum toxin injections in patients with refractory gastroparesis. The 3rd step of this work was to improve the method of the EndoFLIP. We found that there was an impact of general anesthesia and anesthetics on the pyloric EndoFLIP measurements.Le système EndoFLIP permet l’obtention de données géométriques à différent niveaux du système digestif, notamment les sphincters. La plupart des études ont évalué son utilité au niveau de l’œsophage, mais peu d’études se sont intéressées à son intérêt au niveau du sphincter pylorique et du canal anal. Le premier axe de ce travail avait pour but d’évaluer l’intérêt mécanistique de l’EndoFLIP du pylore et du canal anal. Nous avons pu montrer que 56,5% des patients atteints de gastroparésie diabétique présentaient une distensibilité pylorique altérée, avec un taux similaire retrouvé chez les patients atteints de gastroparésie idiopathique (51,5%). En revanche, il n’existait pas de corrélation entre les caractéristiques du diabète et les différents paramètres du pylore chez les patients atteints de gastroparésie diabétique. Chez les patients avec symptômes dyspeptiques apparus après chirurgie oeso-gastrique, la distensibilité pylorique était altérée chez 61,1% des patients du groupe chirurgie anti-reflux, 75,0% du groupe oesophagectomie et 18,7% du groupe sleeve-gastrectomie. Nous avons pu montrer qu’il existait une faible relation entre le type d’incontinence fécale et la distensibilité du canal anal. Le 2ème axe de notre travail portait sur l’intérêt de l’EndoFLIP pour évaluer l’efficacité d’un traitement. La mesure de la distensibilité pylorique était ainsi prédictive de la réponse symptomatique aux injections intra-pyloriques de toxine botulique chez les patients atteints de gastroparésie réfractaire. Le 3ème axe de notre travail portait sur l’amélioration de la technique d’EndoFLIP. Nous avons pu mettre en évidence qu’il existait un impact de l’anesthésie générale et des anesthésiants sur les résultats de l’EndoFLIP du pylore

Impact of anesthesia drugs on digestive motility measurements in humans: A systematic review

International audienceAbstract Background and Purpose Measurement of gastro‐intestinal motility is increasingly performed under general anesthesia during endoscopic or surgical procedures. The aim of the present study was to review the impact of different anesthetic agents on digestive motility measurements in humans. Methods This systematic review was performed using the Medline‐Pubmed and Web of Science databases. All articles published until October 2023 were screened by identification of key words. Studies were reviewed if patients had an assessment of digestive motility using conventional perfused manometry, high‐resolution manometry, electronic barostat or functional lumen impedance planimetry with the use of inhaled or intravenous anesthetic anesthetic agents (propofol, ketamine, halogens, nitrous oxide, opioids, and neuromuscular blockades). Results Four hundred and eighty‐eight unique citations were identified, of which 42 studies met the inclusion criteria and were included in the present review. The impact of anesthetics was mostly studied in patients who underwent esophageal manometry. There was a heterogeneity in both the dose and timing of administration of anesthetics among the studies. Remifentanil analgesia was the most studied anesthetic drug in the literature, showing a decrease in both distal latency and lower esophageal sphincter pressure after its administration, but the impact on Chicago classification was not studied. Inhaled anesthetics administration elicited a decrease in lower esophageal sphincter pressure, but contradictory findings were shown on esophageal motility following propofol or neuromuscular blocking agents administration. Conclusion Studies of the impact of anesthetics on digestive motility remain scarce in the literature, although some agents have been reported to profoundly affect gastro‐intestinal motility

Life-threatening acute airway obstruction induced by unsuspected achalasia

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Sleep Quality and Insomnia Are Associated With Quality of Life in Functional Dyspepsia

International audienceBackground Sleep disturbances are common in patients with functional dyspepsia. Our aim was to assess the relationship between subjective sleep and quality of life and to identify factors associated with impaired sleep in functional dyspepsia. Methods One thousand two hundred and twenty patients referred for functional gastrointestinal disorders at a single tertiary care center between end 2017 and June 2019 were studied using a self-administered questionnaire. 355 patients with Rome IV-based functional dyspepsia were identified. Sleep was assessed using both the Pittsburgh Sleep Quality Index (PSQI) and the Insomnia Severity Index (ISI). The severity of dyspeptic symptoms was assessed using the Total Symptom Score (TSS). Quality of life was assessed by the GastroIntestinal Quality of Life Index (GIQLI). Anxiety and depression levels were evaluated using the Hospital Anxiety and Depression (HAD) scale. Key Results Among the 355 patients with functional dyspepsia, 66 (18.6%) patients displayed normal sleep quality whereas 289 (81.4%) patients had altered sleep quality. Functional dyspepsia patients with sleep disturbances were older (48.1 ± 15.4 vs. 41.4 ± 16.0, p = 0.0009), had decreased quality of life (GIQLI: 75.3 ± 18.5 vs. 92.1 ± 15.4, p &lt; 0.0001), greater severity of their symptoms (TSS: 18.9 ± 3.6 vs. 17.2 ± 3.9, p = 0.0007), and higher anxiety and depression scores (HADS: 17.7 ± 7.2 vs. 11.9 ± 5.1, p &lt; 0.0001). A correlation was found between sleep quality and quality of life [ r = −0.43 (95% CI: −0.51 to −0.34), p &lt; 0.0001]. Independent factors predicting poor sleep quality were age [OR 1.03 (95% CI = 1.01–1.05), p = 0.006], depression level [OR 1.27 (95% CI = 1.16–1.39); p &lt; 0.0001], and the severity of dyspeptic symptoms [OR 1.13 (95% CI = 1.04–1.22); p = 0.004]. Conclusion and Inferences A high prevalence of sleep disturbances was found in patients suffering from functional dyspepsia, with 81% of them having altered sleep quality and 61% having insomnia based on subjective assessment. Altered sleep quality and insomnia were associated with altered quality of life, higher severity of symptoms, and higher anxiety and depression scores in this disorder