Identification and Management of Pelvic Fractures in Prehospital and Emergency Department Settings.

INTRODUCTION: This study aims to describe the characteristics of patients with a pelvic fracture treated at a level 1 trauma center, the proportion of prehospital undertriage and the use of pelvic circumferential compression device (PCCD). METHODS: This is a retrospective cohort study. Prehospital and inhospital medical records of adults (≥16 y old) with a pelvic fracture who were treated at Hopital de l'Enfant-Jesus-CHU de Québec (Quebec City, Canada), a university-affiliated level 1 trauma center, between September 01, 2017 and September 01, 2021 were reviewed. Isolated hip or pubic ramus fracture were excluded. Data are presented using proportions and means with standard deviations. RESULTS: A total of 228 patients were included (males: 62.3%; mean age: 54.6 [standard deviation 21.1]). Motor vehicle collision (47.4%) was the main mechanism of injury followed by high-level fall (21.5%). Approximately a third (34.2%) needed at least one blood transfusion. Compared to those admitted directly, transferred patients were more likely to be male (73.0% versus 51.3%, P < 0.001) and to have a surgical procedure performed at the trauma center (71.3% versus 46.9%, P < 0.001). The proportion of prehospital undertriage was 22.6%. Overall, 17.1% had an open-book fracture and would have potentially benefited from a prehospital PCCD. Forty-six transferred patients had a PCCD applied at the referral hospital of which 26.1% needed adjustment. CONCLUSIONS: Pelvic fractures are challenging to identify in the prehospital environment and are associated with a high undertriage of 22.6%. Reducing undertriage and optimizing the use of PCCD are key opportunities to improve care of patients with a pelvic fracture.

Evaluation of physicians' current practices and awareness regarding the treatment of acute uncomplicated diverticulitis: results of a provincial survey.

OBJECTIVE: International guidelines now recommend nonantibiotic treatment of uncomplicated diverticulitis. We assessed physicians' current management strategies for uncomplicated diverticulitis, their awareness of the updated recommendations, and barriers to practice change. METHODS: A 21-question web-based survey conducted between 09/2022 and 11/2022 was sent to participants through their respective Quebec provincial associations or working groups. Participants included general surgeons, emergency physicians, gastroenterologists and general practitioners. Physicians who did not treat diverticulitis were excluded. The main outcomes were awareness of guideline recommendations on uncomplicated diverticulitis treatment, the use of nonantibiotic management for uncomplicated diverticulitis and identification of perceived barriers to practice change. RESULTS: The participation rate was 15.9%. The 465 participants consisted primarily of general practitioners (41.7%), general surgeons (29.2%) and emergency physicians (17.8%). Eighty-two percent had heard of the nonantibiotic treatment strategy for uncomplicated diverticulitis; 7.5% were "uncomfortable" and 44.6% "somewhat uncomfortable" with this practice. A third (31.8%) of all physicians had no knowledge of the updated guidelines on uncomplicated diverticulitis treatment. Most reported "never" (41.6%) or "rarely" (25.1%) omitting antibiotics for uncomplicated diverticulitis. When informed about nonantibiotic treatment, 28.7% and 51.4% of all physicians, respectively, indicated that this "will" change or "may" change their practice. Common perceived barriers to nonantibiotic treatment were concerns about treatment failure (69.6%), unawareness of updated recommendations (67.0%), difficulty in ensuring proper follow-up (59.0%) and workplace culture (54.9%). CONCLUSION: Physicians' awareness of practice guidelines recommending nonantibiotic treatment for uncomplicated diverticulitis and their application are suboptimal. Knowledge transfer activities, educational interventions and optimization of local protocols are needed to ensure the rational use of antibiotics.

RéSUMé: OBJECTIF: Les lignes directrices internationales recommandent désormais un traitement non antibiotique de la diverticulite non compliquée. Nous avons évalué les stratégies de traitement actuelles des médecins pour la diverticulite non compliquée, leur connaissance des recommandations mises à jour et les obstacles au changement de pratique. MéTHODES: Un sondage en ligne de 21 questions mené entre le 09/2022 et le 11/2022 a été envoyé aux participants par l'intermédiaire de leurs associations ou groupes de travail provinciaux respectifs au Québec. Les participants comprenaient des chirurgiens généraux, des urgentologues, des gastroentérologues et des médecins de famille. Les médecins qui ne traitaient pas de diverticulite ont été exclus. Les principales issues étaient la connaissance des recommandations des lignes directrices sur le traitement de la diverticulite non compliquée, l'utilisation du traitement non antibiotique pour la diverticulite non compliquée et l'identification des obstacles perçus au changement de pratique. RéSULTATS: Le taux de participation était de 15,9 %. Les 465 participants étaient principalement des médecins de famille (41,7 %), des chirurgiens généraux (29,2 %) et des urgentologues (17,8 %). Quatre-vingt-deux pour cent avaient entendu parler de la stratégie de traitement non antibiotique pour la diverticulite non compliquée; 7,5% étaient "inconfortables" et 44,6% "quelque peu inconfortables" avec cette pratique. Un tiers (31,8 %) des médecins ne connaissaient pas les lignes directrices mises à jour sur le traitement de la diverticulite non compliquée. La plupart ont rapporté "jamais" (41,6%) ou "rarement" (25,1%) omettre les antibiotiques pour la diverticulite non compliquée. Lorsqu'ils ont été informés du traitement non antibiotique, 28,7 % et 51,4 % de tous les médecins ont indiqué que cela «changera¼ ou «pourrait changer¼ leur pratique. Les fréquents obstacles au traitement non antibiotique étaient les préoccupations concernant l'échec du traitement (69,6 %), l'ignorance des recommandations mises à jour (67,0 %), la difficulté d'assurer un suivi approprié (59,0 %) et la culture en milieu de travail (54,9 %). CONCLUSIONS: La connaissance des lignes directrices recommandant un traitement non antibiotique pour la diverticulite non compliquée et leur application sont sous-optimales. Des activités de transfert de connaissances, des interventions éducatives et des protocoles locaux sont nécessaires pour assurer l'utilisation rationnelle des antibiotiques.

Prevalence and predictors of elder abuse among older adults attending emergency departments: a prospective cohort study.

INTRODUCTION: Elder abuse is associated with impaired physical and psychological health. It is, however, rarely identified in emergency departments (EDs). The objective was to determine the prevalence and the predictors of elder abuse among older adults visiting EDs. METHODS: This prospective cohort study was conducted in eight Canadian EDs between May and August 2021. Patients were eligible if they were ≥ 65 years old, oriented to time, and with a Canadian Triage and Acuity Scale score 3, 4 or 5. In a private setting, participants were questioned directly about abuse as part of a larger questionnaire exploring ten non-medical problems. We used multivariable logistic regression to identify predictors of elder abuse. RESULTS: A total of 1061 participants were recruited (mean age: 77.1 (SD 7.6) years, female sex: 55.7%, lived alone: 42.5%). Patients mostly attended EDs for pain (19.6%), neurologic (11.3%) or cardiovascular (8.4%) symptoms. The most frequent pre-existing comorbidities were hypertension (67.2%), mental health conditions (33.3%) and cardiac insufficiency (29.6%). Mobility issues outside (41.0%) or inside their home (30.7%) and loneliness (29.4%) were also frequent. Fifty-four (5.1%) participants reported elder abuse, of which 34.3% were aware of available community-based resources. Identified predictors of elder abuse were female sex (OR 2.8 [95%CI 1.4; 5.6]), financial difficulties (OR 3.6 [95%CI 1.8; 7.3]), food insecurity (OR 2.7 [95%CI 1.2; 5.6]), need for a caregiver (OR 2.7 [95%CI 1.5; 5.0]) and at least one pre-existing mental health condition (OR 2.6 [95%CI 1.4; 4.9]). CONCLUSION: When questioned directly, 5.1% of older adults attending EDs reported experiencing abuse. Female sex, functional impairment, social vulnerability, and mental health comorbidities are associated with elder abuse. Given its importance and relatively high prevalence, ED professionals should have a low threshold to ask directly about elder abuse.

RéSUMé: INTRODUCTION: La maltraitance des personnes âgées est associée à une détérioration de la santé physique et psychologique. Elle est cependant rarement identifiée dans les services d'urgence. L'objectif était de déterminer la prévalence et les prédicteurs de l'abus envers les aînés chez les personnes âgées qui consultent dans un service d'urgence. MéTHODES: Cette étude de cohorte prospective a été menée dans huit services d'urgence canadiens entre mai et août 2021. Les patients étaient éligibles s'ils étaient âgés de ≥ 65 ans, s'ils étaient orientés vers le temps et s'ils avaient un score de 3, 4 ou 5 sur l'échelle canadienne de triage et d'acuité. Dans un cadre privé, les participants ont été interrogés directement sur la maltraitance dans le cadre d'un questionnaire plus large explorant 10 problèmes non médicaux. Nous avons utilisé une régression logistique multivariable pour identifier les facteurs prédictifs de la maltraitance envers les personnes âgées. RéSULTATS: Au total, 1 061 participants ont été recrutés (âge moyen : 77,1 (SD 7,6) ans, sexe féminin : 55,7 %, vivant seul : 42,5 %). Les patients se sont surtout rendus aux urgences pour des douleurs (19,6 %), des symptômes neurologiques (11,3 %) ou cardiovasculaires (8,4 %). Les comorbidités préexistantes les plus fréquentes étaient l'hypertension (67,2 %), les problèmes de santé mentale (33,3 %) et l'insuffisance cardiaque (29,6 %). Les problèmes de mobilité à l'extérieur (41,0 %) ou à l'intérieur du domicile (30,7 %) et la solitude (29,4 %) sont également fréquents. Cinquante-quatre (5,1 %) participants ont signalé des cas de maltraitance des personnes âgées, dont 34,3 % connaissaient les ressources communautaires disponibles. Les facteurs prédictifs identifiés de maltraitance envers les personnes âgées étaient le sexe féminin (RC 2,8 [IC 95 % 1,4 ; 5,6]), les difficultés financières (RC 3,6 [IC 95 % 1,8 ; 7,3]), l'insécurité alimentaire (RC 2,7 [IC 95 % 1,2 ; 5,6]), besoin d'un aidant (RC 2,7 [IC 95 % 1,5 ; 5,0]) et au moins un problème de santé mentale préexistant (RC 2,6 [IC 95 % 1,4 ; 4,9]). CONCLUSION: Interrogées directement, 5,1 % des personnes âgées fréquentant les urgences ont déclaré avoir été victimes de maltraitance. Le sexe féminin, les déficits fonctionnels, la vulnérabilité sociale et les problématiques de santé mentale sont associés à la maltraitance des personnes âgées. Compte tenu de son importance et de sa prévalence relativement élevée, les professionnels des urgences ne devraient pas hésiter à poser directement des questions sur la maltraitance aux personnes âgées.

A Canadian consensus-based list of urgent and specialized in-hospital trauma care interventions to assess the accuracy of prehospital trauma triage protocols: a modified Delphi study.

BACKGROUND: Injury severity scales have traditionally been used to assess the performance of prehospital trauma triage protocols, but they correlate weakly with the urgent needs of specialized trauma care interventions. This study aimed to develop a list of in-hospital urgent and specialized trauma care interventions that require direct transport to the highest-level trauma centre within the catchment area. METHODS: Based on a list of potential participants we obtained using data on training, experience, geographic location, affiliations and role within key trauma organizations, we recruited multidisciplinary trauma experts (including prehospital, emergency, surgery and intensive care clinicians, epidemiologists and clinician/decision-makers) from across Canada to complete a 3-round modified Delphi survey. We conducted a literature review of the criteria used to define urgent and specialized trauma care, and included all diagnostic and therapeutic interventions presented in previously published studies in the list of interventions to present to the panellists. The final list was determined by our advisory committee, 5 clinicians with experience in trauma care. Participants were asked to rate their level of agreement for potentially including the 38 items as urgent and specialized trauma care interventions on a 9-point Likert scale. Interventions were retained if more than 67% of participants moderately or strongly agreed (7-9 on the Likert scale). Interventions that did not reach consensus were presented again in the subsequent round. RESULTS: Twenty-three panellists were recruited. The response rate was 91%, 96% and 83% for the 3 rounds. After the Delphi process, 30 of the 38 interventions, including endotracheal intubation, blood product administration and angioembolization, and abdominal, thoracic, neurosurgical, spinal and/or orthopedic operations (excluding hip or limb surgery, and toe or finger amputation), were selected. Hospital admission to the intensive care unit and/or for observation of brain, spinal, thoracic or abdominal injuries were also retained. CONCLUSION: We developed a Canadian consensus-based list of urgent and specialized in-hospital trauma care interventions requiring direct transportation to a major trauma centre. This list should help standardize assessments of current protocols and derive new triage tools.

Accuracy of Prehospital Trauma Triage to Select Older Adults Requiring Urgent and Specialized Trauma Care.

INTRODUCTION: This study aims to assess the sensitivity and specificity of a 5-step prehospital trauma triage protocol to identify older adults who require urgent and specialized trauma care using different age cut-offs to define an older adult (≥55, ≥65, and ≥75 y old). METHODS: Prehospital and in-hospital medical records were reviewed for injured patients transported by an ambulance to an emergency department (ED) between November 11, 2016 and March 3, 2017 in Quebec City, Canada. Sensitivities and specificities were calculated to assess the accuracy of our prehospital trauma triage protocol to identify patients who required at least one urgent in-hospital trauma intervention. RESULTS: A total of 822 patients were included of which 62.9% were ≥55 y old and 56.3% were female. Fall (65.8%) was the main trauma mechanism. Seventy-six (9.2%) patients required urgent trauma care. This proportion was similar regardless of age (8.9%-9.5%). The proportion of patients who needed to be transported to the level-1 trauma center as per the triage protocol tended to decrease with increasing age (20.6% [whole cohort], 15.3% [≥55 y old], 11.4% [≥65 y old], and 9.0% [≥75 y old]). The sensitivity of the protocol for steps 1, 2, and 3 was 56.6% (whole cohort) and 30.0% for patients aged ≥75 y. The specificity ranged between 83.1% (whole cohort) and 93.1% (≥75 y old). CONCLUSIONS: Our prehospital trauma triage protocol has insufficient sensitivity to identify patients with urgent trauma care needs, particularly in older adults.

External validation of the updated Brain Injury Guidelines for complicated mild traumatic brain injuries: a retrospective cohort study.

OBJECTIVE: Approximately 10% of patients with mild traumatic brain injury (mTBI) have intracranial bleeding (complicated mTBI) and 3.5% eventually require neurosurgical intervention, which is mostly available at centers with a higher level of trauma care designation and often requires interhospital transfer. In 2018, the Brain Injury Guidelines (BIG) were updated in the United States to guide emergency department care and patient disposition for complicated mild to moderate TBI. The aim of this study was to validate the sensitivity and specificity of the updated BIG (uBIG) for predicting the need for interhospital transfer in Canadian patients with complicated mTBI. METHODS: This study took place at three level I trauma centers. Consecutive medical records of patients with complicated mTBI (Glasgow Coma Scale score 13-15) who were aged ≥ 16 years and presented between September 2016 and December 2017 were retrospectively reviewed. Patients with a penetrating trauma and those who had a documented cerebral tumor or aneurysm were excluded. The primary outcome was a combination of neurosurgical intervention and/or mTBI-related death. Sensitivity and specificity analyses were performed. RESULTS: A total of 477 patients were included, of whom 8.4% received neurosurgical intervention and 3% died as a result of their mTBI. Forty patients (8%) were classified as uBIG-1, 168 (35%) as uBIG-2, and 269 (56%) as uBIG-3. No patients in uBIG-1 underwent neurosurgical intervention or died as a result of their injury. This translates into a sensitivity for predicting the need for a transfer of 100% (95% CI 93.2%-100%) and a specificity of 9.4% (95% CI 6.8%-12.6%). Using the uBIG could potentially reduce the number of transfers by 6% to 25%. CONCLUSIONS: The patients in uBIG-1 could be safely managed at their initial center without the need for transfer to a center with a higher level of neurotrauma care. Although the uBIG could decrease the number of transfers, further refinement of the criteria could improve its specificity.

Reducing Barriers to Optimal Automated External Defibrillator Use: An Elementary School Intervention Study.

Background: Timely use of an automated external defibrillator (AED) improves outcomes in sudden cardiopulmonary arrest (SCA). Our project aims were to: 1) identify the barriers to optimal AED use in the Québec City area elementary schools; 2) create targeted educational material regarding AEDs; and 3) measure the impact of the teaching module. Methods: Using a quality improvement in health-care framework, a survey exploring the barriers to AED use was sent to 139 elementary schools. We then developed a video teaching module on using AEDs to address these barriers. A convenience sample of 92 elementary school professionals participated in a mock scenario. Metrics related to AED use were assessed at baseline and after completing the post-teaching module. The primary outcome was the time to first shock and secondary outcomes consisted of evaluating the completion of each step required for safe and effective AED use. Results: The barrier analysis survey received a response rate of 52.5%. Most schools reported having an AED (95%), but 48.6% indicated that no formal training was offered. After the teaching module, the appropriate use of the AED in an SCA simulation improved from 53% to 92% (P < 0.001). The average time elapsed before first shock was 66 (95% confidence interval [CI], 63-70) seconds at baseline compared with 47 (95% CI, 45-49) seconds post-teaching module (P < 0.001). Conclusions: Lack of training, the main barrier to optimal use of AEDs in elementary schools, can be addressed through a brief video teaching module, thus improving the ability to deliver timely and effective defibrillation.

Contexte: L'utilisation rapide d'un défibrillateur externe automatisé (DEA) améliore les résultats en cas d'arrêt cardiorespiratoire soudain (ACS). Les objectifs de notre projet étaient les suivants : 1) déterminer les obstacles à l'utilisation optimale d'un DEA dans les écoles primaires de la région de Québec; 2) créer du matériel éducatif ciblé à propos des DEA; et 3) mesurer l'impact du module d'enseignement. Méthodologie: Dans le cadre d'un projet d'amélioration de la qualité des soins de santé, un sondage explorant les obstacles à l'utilisation des DEA a été envoyé à 139 écoles primaires. Nous avons ensuite mis au point un module d'enseignement vidéo sur l'utilisation des DEA afin de surmonter ces obstacles. Un échantillon de commodité comprenant 92 professionnels des écoles primaires a participé à un scénario fictif. Les paramètres liés à l'utilisation des DEA ont été évalués au départ et après le visionnement du module d'enseignement vidéo. Le principal critère d'évaluation était le temps écoulé entre l'ACS et l'administration du premier choc et les critères secondaires consistaient à évaluer la réalisation de chaque étape requise pour une utilisation sûre et efficace d'un DEA. Résultats: Le sondage d'analyse des obstacles a généré un taux de réponse de 52,5 %. La plupart des écoles ont signalé avoir un DEA (95 %), mais 48,6 % ont indiqué qu'aucune formation n'était offerte. Après le visionnement du module d'enseignement, l'utilisation appropriée du DEA dans le cadre d'une simulation d'ACS est passée de 53 à 92 % (P < 0,001). Le temps moyen écoulé avant l'administration du premier choc était de 66 secondes (intervalle de confiance [IC] à 95 %, 63-70) au départ, comparativement à 47 secondes (IC à 95 %, 45-49) après le visionnement du module d'enseignement (P < 0,001). Conclusions: Le principal obstacle à l'utilisation optimale d'un DEA dans les écoles primaires, soit l'absence de formation, peut être surmonté grâce à un court module d'enseignement vidéo, améliorant ainsi la capacité de procéder à une défibrillation rapide et efficace.

Predictors of neurosurgical intervention in complicated mild traumatic brain injury patients: a retrospective cohort study.

OBJECTIVES: To determine the predicting demographic, clinical and radiological factors for neurosurgical intervention in complicated mild traumatic brain injury (mTBI) patients. METHODS: Design: retrospective multicenter cohort study. Participants: patients aged ≥16 presenting to all level-I trauma centers in Quebec between 09/2016 and 12/2017 with mTBI(GCS 13-15) and complication on initial head CT (intracranial hemorrhage/skull fracture). Procedure: Consecutive medical records were reviewed and separated into two groups: no neurosurgical intervention and neurosurgical intervention (NSI). Main outcome: neurosurgical intervention. Analysis: multiple logistic regression model. RESULTS: Four hundred and seventy-eight patients were included and 40 underwent NSI. One patient had radiological deterioration but no clinical deterioration prior to surgery. Subdural hemorrhage ≥4 mm width (OR:3.755 [95% CI:1.290-10.928]) and midline shift (OR:7.507 [95% CI: 3.317-16.989]) increased the risk of NSI. Subarachnoid hemorrhage was associated with a lower risk of NSI (OR:0.312 [95% CI: 0.136-0.713]). All other intracranial hemorrhages were not associated with NSI. CONCLUSION: Radiological deterioration was not associated with the incidence of NSI. Subdural hemorrhage and midline shift should be predicting factors for neurosurgery. Some patients with isolated findings such as subarachnoid hemorrhage could be safely managed in their original center without being transferred to a level-I trauma center.

Continuous flow insufflation of oxygen compared with manual ventilation during out-of-hospital cardiac arrest: A survey of the paramedics.

INTRODUCTION: In 2018, a continuous flow insufflation of oxygen (CFIO) device (b-card™, Vygon (USA)) placed on a supraglottic airway (SGA) became the standard of care to ventilate patients during adult out-of-hospital cardiac arrest (OHCA) care in Quebec-Capitale-Nationale region, Canada. This study aims to assess the paramedics' perception as well as the disadvantages and the benefits relative to the use of CFIO during OHCA management. METHODS: An invitation to complete an online survey (Survey Monkey™) was sent to all 560 paramedics who are working in our region. The survey included 22 questions of which 9 aimed to compare the traditional manual ventilation with a bag to the CFIO using a 5-point Likert-type scale. RESULTS: A total of 244 paramedics completed the survey, of which 189 (77.5%) had used the CFIO device during an OHCA at least once. Most respondents felt that the intervention was faster (70.2%) and easier (86.5%) with the CFIO device compared with manual ventilation. CFIO was also associated with perceived increased patient safety (64.4%) as well as paramedic safety during the evacuation (88.9%) and the ambulance transport (88.9%). Paramedics reported that physical (48.1%) and cognitive (52.9%) fatigue were also improved with CFIO. The main reported barriers were the bending of the external SGA tube and the loss of capnography values. CONCLUSION: The use of CFIO during adult OHCA care allows a simplified approach and was perceived as safer for the patient and the paramedics compared with manual ventilation. Its impact on patient-centred outcomes needs to be assessed.

Continuous flow insufflation of oxygen for cardiac arrest: Systematic review of human and animal model studies.

OBJECTIVE: To synthetize the evidence regarding the effect of constant flow insufflation of oxygen (CFIO) on the rate of return of spontaneous circulation (ROSC) and other clinical outcomes during cardiac arrest (CA). METHODS: A systematic review was performed using four databases (PROSPERO: CRD42020071960). Studies reporting on adult CA patients or on animal models simulating CA and assessing the effect of CFIO on ROSC or other clinical outcomes were considered. RESULTS: A total of 3540 citations were identified, of which 16 studies were included. Four studies (two randomized controlled trials (RCT), two cohort studies), reported on humans while 12 studies used animal models. No meta-analysis was performed due to clinical heterogeneity. There were no differences in the ROSC (18.9% vs 20.8%, p = 0.99; 27.1% vs 21.3%, p = 0.51) and sustained ROSC rates (16.1% vs 17.3%, p = 0.81; 12.5% vs 14.9%, p = 0.73) with CFIO compared to intermitant positive pressure ventilation (IPPV) in the two human RCTs. Survival to ICU discharge was similar between CFIO (2.3%) and IPPV (2.3%) in the largest RCT (p = 0.96). Human studies were at serious or high risk of bias. In animal models' studies, ROSC rates were presented in seven RCTs. CFIO was superior to IPPV in one trial, but was associated with similar ROSC rates using different ventilation strategies in the remaining six studies. CONCLUSIONS: No definitive association between CFIO and ROSC, sustained ROSC or survival compared to other ventilation strategies could be demonstrated. Future studies should assess CFIO effect on post-survival neurological functions and patient-important CA outcomes.

ß1 Syntrophin Supports Autophagy Initiation and Protects against Cerulein-Induced Acute Pancreatitis.

Syntrophins are a family of proteins forming membrane-anchored scaffolds and serving as adaptors for various transmembrane and intracellular signaling molecules. To understand the physiological roles of ß1 syntrophin, one of the least characterized members, we generated mouse models to eliminate ß1 syntrophin specifically in the endocrine or exocrine pancreas. ß1 syntrophin is dispensable for the morphology and function of insulin-producing ß cells. However, mice with ß1 syntrophin deletion in exocrine acinar cells exhibit increased severity of cerulein-induced acute pancreatitis. Reduced expression of cystic fibrosis transmembrane conductance regulator and dilation of acinar lumen are potential predisposition factors. During the disease progression, a relative lack of autophagy is associated with deficiencies in both actin assembly and endoplasmic reticulum nucleation. Our findings reveal, for the first time, that ß1 syntrophin is a critical regulator of actin cytoskeleton and autophagy in pancreatic acinar cells and is potently protective against cerulein-induced acute pancreatitis.

PPARγ is a major regulator of branched-chain amino acid blood levels and catabolism in white and brown adipose tissues.

OBJECTIVE: We investigated whether PPARγ modulates adipose tissue BCAA metabolism, and whether this mediates the attenuation of obesity-associated insulin resistance induced by pharmacological PPARγ activation. METHODS: Mice with adipocyte deletion of one or two PPARγ copies fed a chow diet and rats fed either chow, or high fat (HF) or HF supplemented with BCAA (HF/BCAA) diets treated with rosiglitazone (30 or 15 mg/kg/day, 14 days) were evaluated for glucose and BCAA homeostasis. RESULTS: Adipocyte deletion of one PPARγ copy increased mice serum BCAA and reduced inguinal white (iWAT) and brown (BAT) adipose tissue BCAA incorporation into triacylglycerol, as well as mRNA levels of branched-chain aminotransferase (BCAT)2 and branched-chain α-ketoacid dehydrogenase (BCKDH) complex subunits. Adipocyte deletion of two PPARγ copies induced lipodystrophy, severe glucose intolerance and markedly increased serum BCAA. Rosiglitazone abolished the increase in serum BCAA induced by adipocyte PPARγ deletion. In rats, HF increased serum BCAA, such levels being further increased by BCAA supplementation. Rosiglitazone, independently of diet, lowered serum BCAA and upregulated iWAT and BAT BCAT and BCKDH activities. This was associated with a reduction in mTORC1-dependent inhibitory serine phosphorylation of IRS1 in skeletal muscle and whole-body insulin resistance evaluated by HOMA-IR. CONCLUSIONS: PPARγ, through the regulation of both BAT and iWAT BCAA catabolism in lipoeutrophic mice and muscle insulin responsiveness and proteolysis in lipodystrophic mice, is a major determinant of circulating BCAA levels. PPARγ agonism, therefore, may improve whole-body and muscle insulin sensitivity by reducing blood BCAA, alleviating mTORC1-mediated inhibitory IRS1 phosphorylation.