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1.
J Surg Res ; 301: 224-230, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38964012

RESUMO

INTRODUCTION: The purpose of this study is to examine and characterize patterns of injury to the upper extremity caused by fireworks in a nationally representative sample of emergency department patients from 2011 to 2020. METHODS: The National Electronic Injury Surveillance System was queried for upper-extremity injuries caused by fireworks between 2011 and 2020. RESULTS: One thousand two hundred fifty-one injuries were identified from the database representing 47,235 national cases that presented to emergency departments in the United States. Case frequency was stable during the period until 2020, which was nearly 70% higher than the previous 9-y average. Patients were generally young and male, with most cases in the 10-29-y age group and males over three times as likely to be injured as females. The most common injury was burn, and the week of July 4th accounted for 53% of cases alone. Diagnosis was also significantly associated with device type. CONCLUSIONS: These data can be used to target prevention measures and campaigns to specific patient populations most at risk of injury, specifically young males. They may also be used to highlight the impact of policy changes on availability of fireworks, the need for public health education coinciding with injury incidence peaks, and secondary pandemic effects.

2.
Brain Inj ; 38(4): 295-303, 2024 03 20.
Artigo em Inglês | MEDLINE | ID: mdl-38335326

RESUMO

INTRODUCTION: Repeat sport-related concussion (SRC) is anecdotally associated with prolonged recovery. Few studies have examined repeat concussion within the same athlete. We sought to explore differences in symptom burden and recovery outcomes in an individual athlete's initial and repeat SRC. METHODS: A retrospective within-subject cohort study of athletes aged 12-23 years diagnosed with two separate SRCs from 11/2017-10/2020 was conducted. Primary outcomes were initial symptom severity and time-to-symptom-resolution. Secondary outcomes included return-to-learn (RTL) and return-to-play (RTP) duration. RESULTS: Of 868 athletes seen, 47 athletes presented with repeat concussions. Median time between concussions was 244 days (IQR 136-395). Comparing initial to repeat concussion, no differences were observed in time-to-clinic (4.3 ± 7.3vs.3.7 ± 4.6 days, p = 0.56) or initial PCSS (26.2 ± 25.3 vs. 30.5 ± 24.1, p = 0.32). While a difference was observed in time-to-symptom resolution between initial/repeat concussion (21.2 ± 16.3 vs. 41.7 ± 86.0 days, p = 0.30), this did not reach statistical significance. No significant differences were observed in time-to-RTL (17.8 ± 60.6 vs. 6.0 ± 8.3 days, p = 0.26) and RTP (33.2 ± 44.1 vs. 29.4 ± 39.1 days, p = 0.75). Repeat concussion was not associated with symptom resolution on univariate (HR 1.64, 95% CI 0.96-2.78, p = 0.07) and multivariable (HR 0.85, 95% CI 0.49-1.46, p = 0.55) Cox regression. CONCLUSION: No significant differences in symptom duration and RTP/RTL were seen between initial/repeat concussion.


Assuntos
Traumatismos em Atletas , Concussão Encefálica , Humanos , Traumatismos em Atletas/complicações , Traumatismos em Atletas/diagnóstico , Estudos de Coortes , Estudos Retrospectivos , Concussão Encefálica/diagnóstico , Concussão Encefálica/complicações , Atletas
3.
Am J Physiol Heart Circ Physiol ; 321(1): H162-H174, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-34085842

RESUMO

Long-chain acylcarnitines (LCACs) are known to directly alter cardiac contractility and electrophysiology. However, the acute effect of LCACs on human cardiac function is unknown. We aimed to determine the effect of LCAC 18:1, which has been associated with cardiovascular disease, on the contractility and arrhythmia susceptibility of human atrial myocardium. Additionally, we aimed to assess how LCAC 18:1 alters Ca2+ influx and spontaneous Ca2+ release in vitro. Human right atrial trabeculae (n = 32) stimulated at 1 Hz were treated with LCAC 18:1 at a range of concentrations (1-25 µM) for a 45-min period. Exposure to the LCAC induced a dose-dependent positive inotropic effect on myocardial contractility (maximal 1.5-fold increase vs. control). At the 25 µM dose (n = 8), this was paralleled by an enhanced propensity for spontaneous contractions (50% increase). Furthermore, all LCAC 18:1 effects on myocardial function were reversed following LCAC 18:1 washout. In fluo-4-AM-loaded HEK293 cells, LCAC 18:1 dose dependently increased cytosolic Ca2+ influx relative to vehicle controls and the short-chain acylcarnitine C3. In HEK293 cells expressing ryanodine receptor (RyR2), this increased Ca2+ influx was linked to an increased propensity for RyR2-mediated spontaneous Ca2+ release events. Our study is the first to show that LCAC 18:1 directly and acutely alters human myocardial function and in vitro Ca2+ handling. The metabolite promotes proarrhythmic muscle contractions and increases contractility. The exploratory findings in vitro suggest that LCAC 18:1 increases proarrhythmic RyR2-mediated spontaneous Ca2+ release propensity. The direct effects of metabolites on human myocardial function are essential to understand cardiometabolic dysfunction.NEW & NOTEWORTHY For the first time, the fatty acid metabolite, long-chain acylcarnitine 18:1, is shown to acutely increase the arrhythmia susceptibility and contractility of human atrial myocardium. In vitro, this was linked to an influx of Ca2+ and an enhanced propensity for spontaneous RyR2-mediated Ca2+ release.


Assuntos
Sinalização do Cálcio/efeitos dos fármacos , Carnitina/análogos & derivados , Átrios do Coração/efeitos dos fármacos , Contração Miocárdica/efeitos dos fármacos , Miócitos Cardíacos/efeitos dos fármacos , Idoso , Idoso de 80 Anos ou mais , Carnitina/farmacologia , Feminino , Átrios do Coração/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Miócitos Cardíacos/metabolismo
4.
Am J Physiol Endocrinol Metab ; 319(3): E540-E547, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32715745

RESUMO

The adipocytokine resistin is released from epicardial adipose tissue (EAT). Plasma resistin and EAT deposition are independently associated with atrial fibrillation. The EAT secretome enhances arrhythmia susceptibility and inotropy of human myocardium. Therefore, we aimed to determine the effect of resistin on the function of human myocardium and how resistin contributes to the proarrhythmic effect of EAT. EAT biopsies were obtained from 25 cardiac surgery patients. Resistin levels were measured by ELISA in 24-h EAT culture media (n = 8). The secretome resistin concentrations increased over the culture period to a maximal level of 5.9 ± 1.2 ng/mL. Coculture with ß-adrenergic agonists isoproterenol (n = 4) and BRL37344 (n = 13) had no effect on EAT resistin release. Addition of resistin (7, 12, 20 ng/mL) did not significantly increase the spontaneous contraction propensity of human atrial trabeculae (n = 10) when given alone or in combination with isoproterenol. Resistin dose-dependently increased trabecula-developed force (maximal 2.9-fold increase, P < 0.0001), as well as the maximal rates of contraction (2.6-fold increase, P = 0.002) and relaxation (1.8-fold increase, P = 0.007). Additionally, the postrest potentiation capacity of human trabeculae was reduced at all resistin doses, suggesting that the inotropic effect induced by resistin might be due to altered sarcoplasmic reticulum Ca2+ handling. EAT resistin release is not modulated by common arrhythmia triggers. Furthermore, exogenous resistin does not promote arrhythmic behavior in human atrial trabeculae. Resistin does, however, induce an acute dose-dependent positive inotropic and lusitropic effect.


Assuntos
Arritmias Cardíacas/induzido quimicamente , Átrios do Coração/efeitos dos fármacos , Contração Miocárdica/efeitos dos fármacos , Resistina/fisiologia , Tecido Adiposo/metabolismo , Idoso , Idoso de 80 Anos ou mais , Cálcio/metabolismo , Cardiotônicos/farmacologia , Relação Dose-Resposta a Droga , Feminino , Humanos , Isoproterenol/farmacologia , Masculino , Pessoa de Meia-Idade , Pericárdio/metabolismo , Resistina/sangue , Retículo Sarcoplasmático/metabolismo , Malha Trabecular/metabolismo
5.
Am J Physiol Endocrinol Metab ; 318(2): E164-E172, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-31821041

RESUMO

Epicardial adipose tissue (EAT) deposition has a strong clinical association with atrial arrhythmias; however, whether a direct functional interaction exists between EAT and the myocardium to induce atrial arrhythmias is unknown. Therefore, we aimed to determine whether human EAT can be an acute trigger for arrhythmias in human atrial myocardium. Human trabeculae were obtained from right atrial appendages of patients who have had cardiac surgery (n = 89). The propensity of spontaneous contractions (SCs) in the trabeculae (proxy for arrhythmias) was determined under physiological conditions and during known triggers of SCs (high Ca2+, ß-adrenergic stimulation). To determine whether EAT could trigger SCs, trabeculae were exposed to superfusate of fresh human EAT, and medium of 24 h-cultured human EAT treated with ß1/2 (isoproterenol) or ß3 (BRL37344) adrenergic agonists. Without exposure to EAT, high Ca2+ and ß1/2-adrenergic stimulation acutely triggered SCs in, respectively, 47% and 55% of the trabeculae that previously were not spontaneously active. Acute ß3-adrenergic stimulation did not trigger SCs. Exposure of trabeculae to either superfusate of fresh human EAT or untreated medium of 24 h-cultured human EAT did not induce SCs; however, specific ß3-adrenergic stimulation of EAT did trigger SCs in the trabeculae, either when applied to fresh (31%) or cultured (50%) EAT. Additionally, fresh EAT increased trabecular contraction and relaxation, whereas media of cultured EAT only increased function when treated with the ß3-adrenergic agonist. An acute functional interaction between human EAT and human atrial myocardium exists that increases the propensity for atrial arrhythmias, which depends on ß3-adrenergic rather than ß1/2-adrenergic stimulation of EAT.


Assuntos
Tecido Adiposo/fisiopatologia , Arritmias Cardíacas/fisiopatologia , Átrios do Coração/fisiopatologia , Coração/fisiopatologia , Pericárdio/fisiopatologia , Agonistas de Receptores Adrenérgicos beta 3/farmacologia , Agonistas Adrenérgicos beta/farmacologia , Idoso , Etanolaminas/farmacologia , Feminino , Humanos , Isoproterenol/farmacologia , Masculino , Contração Miocárdica , Miocárdio/metabolismo
6.
Can J Surg ; 60(6): 388-393, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28930045

RESUMO

BACKGROUND: Antibiotics play an important role in the treatment of many surgical diseases that affect older adults, and the potential for inappropriate use of these drugs is high. Our objective was to describe antibiotic use among older adults admitted to an acute care surgery service at a tertiary care teaching hospital. METHODS: Detailed data regarding diagnosis, comorbidities, surgery and antibiotic use were retrospectively collected for patients 70 years and older admitted to an acute care surgery service. We evaluated antibiotic use (perioperative prophylaxis and treatment) for appropriateness based on published guidelines. RESULTS: During the study period 453 patients were admitted to the acute care surgery service, and 229 underwent surgery. The most common diagnoses were small bowel obstruction (27.2%) and acute cholecystitis (11.0%). In total 251 nonelective abdominal operations were performed, and perioperative antibiotic prophylaxis was appropriate in 49.5% of cases. The most common prophylaxis errors were incorrect timing (15.5%) and incorrect dose (12.4%). Overall 206 patients received treatment with antibiotics for their underlying disease process, and 44.2% received appropriate first-line drug therapy. The most common therapeutic errors were administration of second- or third-line antibiotics without indication (37.9%) and use of antibiotics when not indicated (12.1%). There was considerable variation in the duration of treatment for patients with the same diagnoses. CONCLUSION: Inappropriate antibiotic use was common among older patients admitted to an acute care surgery service. Quality improvement initiatives are needed to ensure patients receive optimal care in this complex hospital environment.


CONTEXTE: Les antibiotiques jouent un rôle important dans de nombreux cas de chirurgie chez les adultes âgés, et le risque d'utilisation inappropriée de ces médicaments est élevé. Notre objectif était de décrire l'utilisation des antibiotiques chez les patients âgés admis au service chirurgical d'urgence d'un centre hospitalier universitaire de soins tertiaires. MÉTHODES: Nous avons recueilli de manière rétrospective les données détaillées sur le diagnostic, les comorbidités, la chirurgie et l'utilisation d'antibiotiques chez les patients de 70 ans et plus admis dans un service chirurgical d'urgence. Nous avons évalué le bien-fondé du recours aux antibiotiques (prophylaxie et traitement périopératoire) en fonction des lignes directrices publiées. RÉSULTATS: Durant la période de l'étude, 453 patients ont été admis au service chirurgical d'urgence et 229 ont subi une chirurgie. Les diagnostics les plus fréquents étaient : occlusion de l'intestin grêle (27,2 %) et cholécystite aigüe (11,0 %). En tout, 251 interventions abdominales urgentes ont été effectuées et l'antibioprophylaxie périopératoire était justifiée dans 49,5 % des cas. Les erreurs les plus fréquentes en matière de prophylaxie ont été : moment mal choisi (15,5 %) et dose incorrecte (12,4 %). En tout, 206 patients ont reçu une antibiothérapie pour un processus pathologique sous-jacent et 44,2 % ont reçu un traitement antibiotique de première intention approprié. Les erreurs thérapeutiques les plus fréquentes concernaient l'administration d'antibiotiques de deuxième ou de troisième intention sans indication (37,9 %) et l'utilisation d'antibiotiques lorsque cela n'était pas indiqué (12,1 %). On a noté une variation considérable de la durée des traitements chez des patients porteurs de diagnostics semblables. CONCLUSION: L'utilisation inappropriée des antibiotiques a été fréquente chez les patients adultes admis dans un service chirurgical d'urgence. Des initiatives s'imposent sur le plan de l'amélioration de la qualité pour s'assurer ainsi que les patients reçoivent des soins optimaux dans cet environnement hospitalier complexe.


Assuntos
Antibacterianos/uso terapêutico , Antibioticoprofilaxia/estatística & dados numéricos , Antibioticoprofilaxia/tendências , Procedimentos Cirúrgicos Operatórios , Idoso , Idoso de 80 Anos ou mais , Cuidados Críticos , Uso de Medicamentos/estatística & dados numéricos , Feminino , Humanos , Masculino , Estudos Retrospectivos , Centro Cirúrgico Hospitalar
7.
Ann Surg ; 263(2): 274-9, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25607757

RESUMO

OBJECTIVE: To describe the change in residential status at discharge and 6 months after hospitalization among older adults who have undergone nonelective abdominal surgery and to identify risk factors associated with discharge to institution. BACKGROUND: Surgery in older adults may lead to a loss of independence that prevents them from returning to their preadmission residential status. Understanding the impact of surgery on residential status and risk factors for institutionalization is important for patient counseling, discharge planning, and resource allocation. METHODS: Community-dwelling patients aged 70 years and older who underwent nonelective abdominal surgery over a 15-month period were prospectively enrolled. Residential status before admission, at discharge, and 6 months after admission was assessed. Multiple logistic regression was used to identify factors associated with discharge to institution. RESULTS: Of the 197 patients who underwent surgery and survived to discharge, 30% were living alone before admission and 70% were living with others. At discharge, 72% of patients returned to their preadmission residential status and 22% were institutionalized. Six months after hospitalization, 55% of institutionalized patients had returned to community-living, and 79% of all patients had returned to their preadmission residential status. Change in residential status was associated with decreased quality of life. Increasing American Society of Anesthesiologists score, frailty, surgery for malignancy, and postoperative complications were associated with discharge to institution. CONCLUSIONS: The majority of older patients, including those who were discharged to an institution, returned to their preadmission residential status 6 months after nonelective abdominal surgery.


Assuntos
Abdome/cirurgia , Vida Independente/estatística & dados numéricos , Institucionalização/estatística & dados numéricos , Casas de Saúde/estatística & dados numéricos , Alta do Paciente/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Emergências , Feminino , Seguimentos , Idoso Fragilizado , Humanos , Modelos Logísticos , Masculino , Estudos Prospectivos , Qualidade de Vida
8.
Can J Surg ; 59(3): 172-9, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26999476

RESUMO

BACKGROUND: Postoperative complications have been identified as an important and potentially preventable cause of increased hospital costs. While older adults are at increased risk of experiencing complications and other adverse events, very little research has specifically examined how these events impact inpatient costs. We sought to examine the association between postoperative complications, hospital mortality and loss of independence and direct inpatient health care costs in patients 70 years or older who underwent nonelective abdominal surgery. METHODS: We prospectively enrolled consecutive patients 70 years or older who underwent nonelective abdominal surgery between July 1, 2011, and Sept. 30, 2012. Detailed patient-level data were collected regarding demographics, diagnosis, treatment and outcomes. Patient-level resource tracking was used to calculate direct hospital costs (2012 $CDN). We examined the association between complications, hospital mortality and loss of independence cost using multiple linear regression. RESULTS: During the study period 212 patients underwent surgery. Overall, 51.9% of patients experienced a nonfatal complication (32.5% minor and 19.4% major), 6.6% died in hospital and 22.6% experienced a loss of independence. On multivariate analysis nonfatal complications (p < 0.001), hospital mortality (p = 0.021) and loss of independence at discharge (p < 0.001) were independently associated with health care costs. These adverse events respectively accounted for 30%, 4% and 10% of the total costs of hospital care. CONCLUSION: Adverse events were common after abdominal surgery in older adults and accounted for 44% of overall costs. This represents a substantial opportunity for better patient outcomes and cost savings with quality improvement strategies tailored to the needs of this high-risk surgical population.


CONTEXTE: Les complications postopératoires sont une cause évitable qui contribue grandement aux coûts hospitaliers élevés. Malgré le fait que les personnes âgées courent un risque accru de subir des complications ou des événements indésirables, peu de recherches ont étudié l'incidence de ces éléments sur les coûts d'hospitalisation. Nous nous sommes penchés sur la relation entre les coûts des soins de santé assumés par les malades hospitalisés et les complications postopératoires, la mortalité hospitalière et la perte d'autonomie auprès d'une population de patients de 70 ans et plus ayant subi une intervention chirurgicale abdominale non facultative. MÉTHODES: La cohorte prospective a été formée de patients consécutifs âgés de 70 ans et plus ayant subi une intervention chirurgicale abdominale non facultative entre le 1er juillet 2011 et le 30 septembre 2012. Des données détaillées concernant leur profil démographique, leur diagnostic, leur traitement et leurs résultats ont été recueillies. Le calcul des coûts hospitaliers directs est basé sur un suivi des ressources utilisées par les patients (en dollars canadiens, 2012). Au moyen d'une régression linéaire multiple, nous avons analysé la relation entre les complications, la mortalité hospitalière et la perte d'autonomie. RÉSULTATS: Pendant la période à l'étude, 212 patients ont subi une intervention chirurgicale. Parmi eux, 51,9 % ont subi une complication non mortelle (mineure dans 32,5 % des cas; majeure dans 19,4 % des cas), 6,6 % sont décédés à l'hôpital, et 22,6 % ont subi une perte d'autonomie. Une analyse multivariable a permis de conclure que les complications non mortelles (p < 0,001), la mortalité hospitalière (p = 0,021) et la perte d'autonomie à la sortie de l'hôpital (p < 0,001) étaient indépendamment associées aux coûts des soins de santé et qu'elles représentaient respectivement 30 %, 4 % et 10 % des coûts d'hospitalisation totaux. CONCLUSION: Les événements indésirables étaient fréquents dans le contexte des interventions chirurgicales abdominales réalisées sur des personnes âgées et représentaient 44 % des coûts totaux. Nous devons saisir cette occasion et nous doter de stratégies d'amélioration de la qualité adaptées aux besoins de cette population, à risque élevé sur le plan chirurgical, afin d'améliorer les résultats pour les patients et de diminuer les coûts.


Assuntos
Abdome/cirurgia , Custos de Cuidados de Saúde/estatística & dados numéricos , Pacientes Internados/estatística & dados numéricos , Complicações Pós-Operatórias/economia , Procedimentos Cirúrgicos Operatórios/efeitos adversos , Procedimentos Cirúrgicos Operatórios/economia , Idoso , Idoso de 80 Anos ou mais , Canadá , Feminino , Mortalidade Hospitalar , Humanos , Masculino , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/mortalidade , Procedimentos Cirúrgicos Operatórios/estatística & dados numéricos
9.
Surg Endosc ; 28(2): 414-26, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24196545

RESUMO

BACKGROUND: In the United States, 37.5 % of adults (78 million) are obese. The direct medical costs of treating obesity-related disease account for more than 6 % of the national health expenditure. Robotic bariatric surgery is becoming more common, but it is unclear whether robotic procedures result in lower complication rates. Additionally, some evidence is conflicting regarding the costs of robotic Roux-en-Y gastric bypass (RYGB) compared with those of laparoscopic RYGB. This study aimed to compare complication rates, operative characteristics, and expected costs between robotic and laparoscopic RYGB. METHODS: A systematic review of the literature was performed with searches of five databases and grey literature, hand searches, and reference and forward citation searches. Studies comparing robotic versus laparoscopic RYGB involving patients ages 18-65 years who met the National Institutes of Health (NIH) criteria for bariatric surgery were included in the study if they reported overall or major complication rates. Outcomes were pooled using random-effects metaanalysis. A decision-tree economic analysis was performed to calculate expected costs associated with each technique. RESULTS: The systematic search strategy returned 1,374 potentially relevant studies. The inclusion criteria were met by 10 of these studies, which included results from 2,557 patients. The overall major and minor complications did not differ significantly between the robotic and laparoscopic groups. The rates for anastomotic leak, bleeding, stricture, and reoperation did not differ significantly. An economic analysis found that the expected costs for robotic RYGB ($15,447) were higher than for laparoscopic RYGB ($11,956). Sensitivity analyses produced similar results. CONCLUSION: The complication rates did not differ significantly between robotic and laparoscopic RYGB, but the expected costs were greater for robotic RYGB. Further cost effectiveness analyses are recommended before adoption of a robotic approach to RYGB.


Assuntos
Derivação Gástrica/métodos , Gastos em Saúde , Laparoscopia/economia , Obesidade Mórbida/cirurgia , Robótica/economia , Análise Custo-Benefício , Humanos , Obesidade Mórbida/economia
10.
Gen Comp Endocrinol ; 206: 118-29, 2014 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-25038498

RESUMO

Nitric oxide (NO) and Ca(2+) are two of the many intracellular signal transduction pathways mediating the control of growth hormone (GH) secretion from somatotropes by neuroendocrine factors. We have previously shown that the NO donor sodium nitroprusside (SNP) elicits Ca(2+) signals in identified goldfish somatotropes. In this study, we examined the relationships between NO- and Ca(2+)-dependent signal transduction mechanisms in GH secretion from primary cultures of dispersed goldfish pituitary cells. Morphologically identified goldfish somatotropes stained positively for an NO-sensitive dye indicating they may be a source of NO production. In 2h static incubation experiments, GH release responses to the NO donor S-nitroso-N-acetyl-d,l-penicillamine (SNAP) were attenuated by CoCl2, nifedipine, verapamil, TMB-8, BHQ, and KN62. In column perifusion experiments, the ability of SNP to induce GH release was impaired in the presence of TMB-8, BHQ, caffeine, and thapsigargin, but not ryanodine. Caffeine-elicited GH secretion was not affected by the NO scavenger PTIO. These results suggest that NO-stimulated GH release is dependent on extracellular Ca(2+) availability and voltage-sensitive Ca(2+) channels, as well as intracellular Ca(2+) store(s) that possess BHQ- and/or thapsigargin-inhibited sarcoplasmic/endoplasmic reticulum Ca(2+)-ATPases, as well as TMB-8- and/or caffeine-sensitive, but not ryanodine-sensitive, Ca(2+)-release channels. Calmodulin kinase-II also likely participates in NO-elicited GH secretion but caffeine-induced GH release is not upstream of NO production. These findings provide insights into how NO actions many integrate with Ca(2+)-dependent signalling mechanisms in goldfish somatotropes and how such interactions may participate in the GH-releasing actions of regulators that utilize both NO- and Ca(2+)-dependent transduction pathways.


Assuntos
Cálcio/metabolismo , Carpa Dourada/metabolismo , Hormônio do Crescimento/metabolismo , Óxido Nítrico/metabolismo , Hipófise/metabolismo , Animais , Cafeína/farmacologia , Bloqueadores dos Canais de Cálcio/farmacologia , Canais de Cálcio/química , Canais de Cálcio/metabolismo , Estimulantes do Sistema Nervoso Central/farmacologia , Inibidores Enzimáticos/farmacologia , Ácido Gálico/análogos & derivados , Ácido Gálico/farmacologia , Nifedipino/farmacologia , Hipófise/citologia , Hipófise/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Tapsigargina/farmacologia
11.
Can J Surg ; 57(6): 379-84, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25421079

RESUMO

BACKGROUND: The purpose of this research was to examine the morbidity, mortality and rate of recurrent bowel obstruction associated with the treatment of small bowel obstruction (SBO) in older adults. METHODS: We prospectively enrolled all patients 70 years or older with an SBO who were admitted to a tertiary care teaching centre between Jul. 1, 2011, and Sept. 30, 2012. Data regarding presentation, investigations, treatment and outcomes were collected. RESULTS: Of the 104 patients admitted with an SBO, 49% were managed nonoperatively and 51% underwent surgery. Patients who underwent surgery experienced more complications (64% v. 27%, p = 0.002) and stayed in hospital longer (10 v. 3 d, p < 0.001) than patients managed nonoperatively. Nonoperative management was associated with a high rate of recurrent SBO: 31% after a median follow-up of 17 months. Of the patients managed operatively, 60% underwent immediate surgery and 40% underwent surgery after attempted nonoperative management. Patients in whom nonoperative management failed underwent surgery after a median of 2 days, and 89% underwent surgery within 5 days. The rate of bowel resection was high (29%) among those who underwent delayed surgery. Surgery after failed nonoperative management was associated with a mortality of 14% versus 3% for those who underwent immediate surgery; however, this difference was not significant. CONCLUSION: These data suggest that some elderly patients with SBO may be waiting too long for surgery.


CONTEXTE: Le but de cette recherche était d'analyser la morbidité, la mortalité et le taux de récurrence de l'occlusion intestinale associés au traitement de l'occlusion intestinale grêle (OIG) chez des adultes âgés. MÉTHODES: Nous avons inscrit de manière prospective tous les patients de 70 ans ou plus présentant une OIG qui ont été admis dans un établissement de soins tertiaires entre le 1er juillet 2011 et le 30 septembre 2012. Nous avons recueilli les données concernant les tableaux cliniques, les épreuves diagnostiques, les traitements et leurs résultats. RÉSULTATS: Parmi les 104 patients admis pour OIG, 49 % ont été traités non chirurgicalement et 51 % ont subi une intervention chirurgicale. Les patients soumis à la chirurgie ont présenté davantage de complications (64 % c. 27 %, p = 0,002) et ont séjourné plus longtemps à l'hôpital (10 j. c. 3 j., p < 0,001) comparativement aux patients qui n'ont pas été opérés. La prise en charge non chirurgicale a été associée à un taux élevé de récurrences de l'OIG : 31 % après un suivi médian de 17 mois. Parmi les patients opérés, 60 % ont subi une chirurgie immédiate et 40 % ont subi leur chirurgie après une tentative de prise en charge non chirurgicale. Les patients chez qui la prise en charge non chirurgicale a échoué ont subi leur chirurgie après une période médiane de 2 jours et 89 % en l'espace de 5 jours. Le taux de résection intestinale a été élevé (29 %) chez ceux dont la chirurgie a été retardée. La chirurgie après une intervention non chirurgicale infructueuse a été associée à un taux de mortalité de 14 %, contre 3 % chez les patients immédiatement soumis à la chirurgie. Toutefois, cette différence s'est révélée non significative. CONCLUSION: Ces données laissent penser que certains patients âgés présentant une OIG attendent peut-être trop longtemps pour leur chirurgie.


Assuntos
Gerenciamento Clínico , Obstrução Intestinal/terapia , Intestino Delgado/patologia , Complicações Pós-Operatórias/terapia , Resultado do Tratamento , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Obstrução Intestinal/epidemiologia , Obstrução Intestinal/mortalidade , Intestino Delgado/cirurgia , Masculino , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/cirurgia , Estudos Prospectivos , Recidiva
12.
Heart Lung Circ ; 23(3): 217-23, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24315633

RESUMO

The mitral annulus can be rendered hostile by several uncommon clinical situations such as infective endocarditis, calcification, or previous valve surgery. These can all lead to difficulties seating a prosthesis or annuloplasty ring. The posterior mitral annulus or anteriorly the intervalvar fibrous body can be affected. These situations continue to pose a formidable technical challenge to the cardiac surgeon in the operating room. We review the evidence around solutions for these problems with the intent of giving surgeons an overview of techniques to address these issues.


Assuntos
Doenças das Valvas Cardíacas/cirurgia , Implante de Prótese de Valva Cardíaca/métodos , Próteses Valvulares Cardíacas , Anuloplastia da Valva Mitral/métodos , Valva Mitral/cirurgia , Humanos
13.
World J Surg ; 37(2): 318-32, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23052814

RESUMO

BACKGROUND: Controversy still exists on the effect that obesity has on the morbidity and mortality in severe acute pancreatitis (SAP). The primary purpose of this study was to compare the mortality rate of obese versus nonobese patients admitted to the ICU for SAP. Secondary goals were to assess the potential risk factors for abdominal compartment syndrome (ACS) and to investigate the performance of validated scoring systems to predict ACS and in-hospital mortality. METHODS: A retrospective cohort of adults admitted to the ICU for SAP was stratified by their body mass index (BMI) as obese and nonobese. The rates of morbidity, mortality, and ACS were compared by univariate and multivariate regression analyses. Areas under the curve (AUC) were used to evaluate the discriminating performance of severity scores and other selected variables to predict mortality and the risk of ACS. RESULT: Forty-five patients satisfied the inclusion criteria and 24 (53 %) were obese with similar characteristics to nonobese patients. Among all the subjects, 11 (24 %) died and 16 (35 %) developed ACS. In-hospital mortality was significantly lower for obese patients (12.5 vs. 38 %; P = 0.046) even though they seemed to develop ACS more frequently (41 vs. 28 %; P = 0.533). At multivariable analysis, age was the most significant factor associated with in-hospital mortality (odds ratio (OR) = 1.273; 95 % confidence interval (CI) 1.052-1.541; P = 0.013) and APACHE II and Glasgow-Imrie for the development of ACS (OR = 1.143; 95 % CI 1.012-1.292; P = 0.032 and OR = 1.221; 95 % CI 1.000-1.493; P = 0.05) respectively. Good discrimination for in-hospital mortality was observed for patients' age (AUC = 0.846) and number of comorbidities (AUC = 0.801). ACS was not adequately predicted by any of the clinical severity scores (AUC = 0.548-0.661). CONCLUSIONS: Patients' age was the most significant factor associated with mortality in patients affected by SAP. Higher APACHE II and Glasgow-Imrie scores were associated with the development of ACS, but their discrimination performance was unsatisfactory.


Assuntos
Cuidados Críticos , Descompressão Cirúrgica , Mortalidade Hospitalar , Hipertensão Intra-Abdominal/etiologia , Obesidade/complicações , Pancreatite Necrosante Aguda/mortalidade , Adulto , Idoso , Estudos de Coortes , Feminino , Indicadores Básicos de Saúde , Humanos , Incidência , Hipertensão Intra-Abdominal/diagnóstico , Hipertensão Intra-Abdominal/epidemiologia , Hipertensão Intra-Abdominal/cirurgia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Pancreatite Necrosante Aguda/complicações , Pancreatite Necrosante Aguda/terapia , Curva ROC , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento
14.
CJC Open ; 4(5): 466-473, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35607488

RESUMO

Background: Both the Canadian Cardiovascular Society (CCS) and the Canadian Association of Emergency Physicians (CAEP) have published documents to guide atrial fibrillation (AF) management. In 2021, the CAEP updated its AF checklist. Prior to this update, the recommendations of the 2 organizations differed in several key areas, including the suggested cardioversion timeframe, the factors determining cardioversion eligibility, and anticoagulant initiation after cardioversion. Whether emergency physicians (EPs) are aware of, or adhering to, one, both, or neither of these documents is unknown. Methods: We assessed document awareness, adherence, and EP practice using a piloted questionnaire administered to EPs at 5 emergency departments in 3 provinces. Results: Of 166 survey recipients, 123 (74.1%) responded. The majority (64.7%) worked at an academic site, 38.8% identified as female, and median years in practice was 10.0. Most (93.1%) were aware of at least one of the documents; 45.7% were aware of both. Reported awareness was higher for the CCS (77.6%) vs the CAEP (61.2%) guidelines. Respondents varied in their adherence, with 40.5% using parts of both documents. Considerable practice variability occurred when recommendations conflicted. Despite its use not being recommended by either organization, half of respondents (50.0%) reported using the CHA2DS2-VASc score as their stroke-risk assessment tool. Conclusions: Although most surveyed EPs were aware of at least one organization's AF documents, many reported using parts of both. When recommendations conflicted, EPs were divided in their decision-making. These findings emphasize the need to improve consensus between organizations and further improve knowledge translation.


Introduction: La Société canadienne de cardiologie (SCC) et l'Association canadienne des médecins d'urgence (ACMU) ont publié des documents pour orienter la prise en charge de la fibrillation auriculaire (FA). En 2021, l'ACMU a actualisé sa liste de vérification sur la FA. Avant cette actualisation, les recommandations des deux organismes différaient sur plusieurs points importants, notamment le laps de temps suggéré avant la cardioversion, les facteurs qui déterminent l'admissibilité à la cardioversion, et l'amorce du traitement anticoagulant après la cardioversion. On ignore si les médecins d'urgence (MU) connaissent ou adhère à un, à deux ou à aucun de ces documents. Méthodes: Nous avons évalué la connaissance qu'ont les MU de ces documents, leur adhésion et leur pratique grâce à un questionnaire pilote soumis aux MU de cinq services des urgences de trois provinces. Résultats: Parmi les 166 participants à l'enquête, 123 (74,1 %) y ont répondu. La majorité (64,7 %) travaillait dans un établissement universitaire, 38,8 % étaient des femmes, et le nombre médian d'années de pratique était de 10,0. La plupart (93,1 %) connaissaient au moins un des documents; 45,7 % connaissaient les deux. La connaissance rapportée était plus élevée pour les lignes directrices de la SCC (77,6 %) que pour les lignes directrices de l'ACMU (61,2 %). L'adhésion des répondants variait, mais 40,5 % utilisaient des parties des deux documents. La variabilité considérable de la pratique était observée lorsque les recommandations étaient contradictoires. Bien que son utilisation ne soit pas recommandée par l'un ou l'autre de ces organismes, la moitié des répondants (50,0 %) signalaient utiliser le score CHA2DS2-VASc comme outil d'évaluation du risque d'accident vasculaire cérébral. Conclusions: Bien que la plupart des MU interrogés connaissaient au moins un document sur la FA des organismes, plusieurs signalaient utiliser des parties des deux documents. Lorsque les recommandations étaient contradictoires, les MU étaient divisés sur la prise de décision. Ces résultats confirment la nécessité d'améliorer le consensus entre les organismes et d'améliorer davantage l'application des connaissances.

15.
J Surg Case Rep ; 2022(11): rjac503, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36389440

RESUMO

Pyomyositis is an acute bacterial infection of the skeletal muscle that is commonly associated with localized abscess formation. It is estimated that pyomyositis accounts for up to 4% of all hospital admissions throughout Asia, tropical Africa, Oceania and the Caribbean Islands. However, there has been an increasing emergence of pyomyositis in temperate climates and high-income countries. Staphylococcus aureus is the most common organism implicated. Management requires a high index of clinical suspicion, prompt diagnosis and early management to prevent sequalae that can be fatal if left untreated. We describe an interesting case of pyomyositis in an otherwise fit and immunocompetent individual causing mediastinitis; a rare sequalae of the disease. Percutaneous drainage of his left pectoral abscess and a prolonged course of antibiotics provided complete clinical and radiological resolution of the disease despite mediastinal extension. Here we discuss aetiology, associations, pathophysiology and epidemiology of pyomyositis with associated sequalae of the disease.

16.
J Neurosurg Pediatr ; : 1-8, 2022 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-35907196

RESUMO

OBJECTIVE: Adolescents sustaining sport-related concussion often experience difficulties with the return-to-learn (RTL) process. Whereas the initial symptom burden has predicted prolonged RTL, no studies have established a relationship between acute cognitive symptoms and RTL duration. The authors sought to evaluate the relationship between initial cognitive symptoms and RTL duration. METHODS: A retrospective single-institution cohort study of adolescent athletes aged 12-23 years who were evaluated within 5 days of a diagnosed sport-related concussion between November 2017 and October 2020 was conducted. Athletes missing cognitive symptom ratings and RTL data were excluded. The primary exposure variable was the Cognitive Symptom Ratio (CSR), defined as total cognitive symptom cluster score divided by total Post-Concussion Symptom Scale (PCSS) score from the initial clinic visit. Primary and secondary outcomes were time to RTL and total length of care, respectively. Multivariable Cox proportional hazards modeling was used to assess the effect of CSR on RTL duration. RESULTS: Of 653 athletes evaluated within 5 days of injury, 346 patients were included in the final cohort. Athletes reported a median initial PCSS score of 21 (interquartile range [IQR] 6-37) and a median cognitive symptom score of 4 (IQR 0-9). Most patients endorsed some degree of difficulty concentrating (n = 212, 61.3%). The median CSR was 0.18 (IQR 0.00-0.27). On multivariable regression analysis, a higher CSR was associated with prolonged RTL duration (HR 0.30, 95% CI 0.13-0.69, p = 0.004). When initial PCSS score was added to the model, the previously significant association between CSR and RTL was no longer significant (HR 0.67, 95% CI 0.29-1.59, p = 0.367). When dichotomized based on frequency distribution, a higher proportion of patients with low CSR achieved RTL by 7 days postinjury (82.2% vs 69.9%, p = 0.007), a difference not seen at 14 days (92.2% vs 87.3%, p = 0.133). CONCLUSIONS: An acute ratio of cognitive symptoms may predict patients at increased risk for prolonged RTL and those with normal PCSS scores who may experience difficulties once resuming school activities.

17.
CJEM ; 23(1): 75-79, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33683612

RESUMO

INTRODUCTION: One in nine (11.7%) people in Saskatchewan identify as First Nations. It is known that First Nations people have a higher burden of cardiovascular disease, but not whether outcomes of out of hospital cardiac arrest are different. METHODS/METHODOLOGY: We reviewed pre-hospital and inpatient records of patients with out of hospital cardiac arrest between January 1st, 2015 and December 31st, 2017. The population consisted of patients aged 18 years or older with out of hospital cardiac arrest of presumed cardiac origin occurring in the catchment area of Saskatoon's emergency medical services (EMS). Variables of interest included age, gender, First Nations status, EMS response times, bystander cardiopulmonary resuscitation (CPR), and shockable rhythm. Outcomes of interest included return of spontaneous circulation (ROSC), survival to hospital admission, and survival to hospital discharge. RESULTS: In all, 372 patients sustained out of hospital cardiac arrest, of which 27 were status First Nations. There were no differences between First Nations and non-First Nations patients in terms of shockable rhythms (24% vs 26%; p = 0.80), ROSC (42% vs 41%; p = 0.87), survival to hospital admission (27% vs 33%; p = 0.53), and survival to hospital discharge (15% vs 12%; p = 0.54). First Nations patients with out of hospital cardiac arrest were significantly younger (mean age 46 vs. 65 years; p < 0.0001) and had shorter EMS response times (median times 5.3 vs. 6.2 min; p = 0.01) when compared to non-First Nations patients. CONCLUSIONS: In Saskatoon, First Nations patients with out of hospital cardiac arrest appear to have similar survival rates when compared with non-First Nations patients. However, First Nations patients sustaining out of hospital cardiac arrest were significantly younger than their non-First Nations counterparts. This highlights a significant public health issue.


RéSUMé: INTRODUCTION: Une personne sur neuf (11,7 %) en Saskatchewan s'identifie comme membre des Premières Nations. On sait que le fardeau des maladies cardiovasculaires est plus lourd pour les membres des Premières Nations, mais on ne sait pas si les résultats d'un arrêt cardiaque en dehors de l'hôpital sont différents. MéTHODES/MéTHODOLOGIE: Nous avons examiné les dossiers pré-hospitaliers et les dossiers des patients hospitalisés ayant subi un arrêt cardiaque hors hôpital entre le 1er janvier 2015 et le 31 décembre 2017. La population était composée de patients âgés de 18 ans ou plus ayant subi un arrêt cardiaque hors de l'hôpital d'origine cardiaque présumée survenu dans la Territoire des services médicaux d'urgence (SMU) de Saskatoon. Les variables d'intérêt comprenaient l'âge, le sexe, le statut des Premières Nations, les temps de réponse des SMU, la réanimation cardiorespiratoire (RCR) des témoins et le rythme choquant. Les résultats d'intérêt comprenaient le retour de la circulation spontanée (RCS), la survie à l'admission à l'hôpital et la survie la sortie de l'hôpital. RéSULTATS : Au total, 372 patients ont subi un arrêt cardiaque hors de l'hôpital, dont 27 étaient des Premières Nations inscrites. Il n'y avait aucune différence entre les patients des Premières Nations et les patients non membres des Premières Nations en termes de rythmes choquants (24 % contre 26 %; p = 0.80), RCS (42% contre 41% ; p = 0.87), survie à l'admission à l'hôpital ( 27% contre 33%; p = 0.53) et la survie à la sortie de l'hôpital (15 % contre 12%; p = 0.54). Les patients des Premières Nations ayant subi un arrêt cardiaque hors hôpital étaient significativement plus jeunes (âge moyen 46 ans contre 65 ans ; p < 0.0001)) et avaient des temps de réponse plus courts aux SMU (temps médian 5,3 contre 6,2 minutes ; p = 0.01) par rapport aux patients des autres nations. CONCLUSIONS: À Saskatoon, les patients des Premières Nations ayant subi un arrêt cardiaque hors de l'hôpital semblent avoir des taux de survie similaires à ceux des patients non autochtones. Cependant, les patients des Premières Nations qui ont subi un arrêt cardiaque hors de l'hôpital étaient beaucoup plus jeunes que leurs homologues des autres nations. Cela met en évidence un problème de santé publique important.


Assuntos
Reanimação Cardiopulmonar , Serviços Médicos de Emergência , Parada Cardíaca Extra-Hospitalar , Hospitais , Humanos , Pessoa de Meia-Idade , Parada Cardíaca Extra-Hospitalar/terapia , Taxa de Sobrevida
18.
Int J Cardiol ; 341: 70-73, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34461161

RESUMO

BACKGROUND: The heart has an intrinsic ability to regenerate, orchestrated by progenitor or stem cells. However, the relative complexity of non-resident cardiac progenitor cell (CPC) therapy makes modulation of resident CPCs a more attractive treatment target. Thiamine analogues improve resident CPC function in pre-clinical models. In this double blinded randomised controlled trial (identifier: ACTRN12614000755639), we examined whether thiamine would improve CPC function in humans. METHODS AND RESULTS: High dose oral thiamine (one gram twice daily) or matching placebo was administered 3-5 days prior to coronary artery bypass surgery (CABG). Right atrial appendages were collected at the time of CABG, and CPCs isolated. There was no difference in the primary outcome (proliferation ability of CPCs) between treatment groups. Older age was not associated with decreased proliferation ability. In exploratory analyses, isolated CPCs in the thiamine group showed an increase in the proportion of CD34-/CD105+ (endoglin) cells, but no difference in CD34-/CD90+ or CD34+ cells. Thiamine increased maximum force developed by isolated trabeculae, with no difference in relaxation time or beta-adrenergic responsiveness. CONCLUSION: Thiamine does not improve proliferation ability of CPC in patients undergoing CABG, but increases the proportion of CD34-/CD105+ cells. Having not met its primary endpoint, this study provides the impetus to re-examine CPC biology prior to any clinical outcome-based trial examining potential beneficial cardiovascular effects of thiamine.


Assuntos
Células-Tronco , Tiamina , Idoso , Endoglina , Átrios do Coração , Humanos , Transdução de Sinais
19.
CJEM ; 23(3): 297-302, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33590443

RESUMO

OBJECTIVE: To develop pragmatic recommendations for starting, building and sustaining a program of research in emergency medicine (EM) in Canada at sites with limited infrastructure and/or prior research experience. METHODS: At the direction of the Canadian Association of Emergency Physicians (CAEP) academic section, we assembled an expert panel of 10 EM researchers with experience building programs of research. Using a modified Delphi approach, our panel developed initial recommendations for (1) starting, (2) building, and (3) sustaining a program of research in EM. These recommendations were peer-reviewed by emergency physicians and researchers from each of the panelist's home institutions and tested for face and construct validity, as well as ease of comprehension. The recommendations were then iteratively revised based on feedback and suggestions from peer review and amended again after being presented at the 2020 CAEP academic symposium. RESULTS: Our panel created 15 pragmatic recommendations for those intending to start (formal research training, find mentors, local support, develop a niche, start small), build (funding, build a team, collaborate, publish, expect failure) and sustain (become a mentor, obtain leadership roles, lead national studies, gain influence, prioritize wellness) a program of EM research in centers without an established research culture. Additionally, we suggest four recommendations for department leads aiming to foster a program of research within their departments. CONCLUSION: These recommendations serve as guidance for centres wanting to establish a program of research in EM.


RéSUMé: OBJECTIF: Développer des recommandations pragmatiques pour lancer, établir et soutenir un programme de recherche en médecine d'urgence (MU) au Canada dans des sites avec une infrastructure et / ou une expérience de recherche antérieure limitée. MéTHODES: Sous la direction de la section académique de l'Association canadienne des médecins d'urgence (ACMU), nous avons réuni un comité d'experts de 10 chercheurs en MU possédant de l'expérience dans le développement des programmes de recherche. En utilisant une approche Delphi modifiée, notre comité a mis en place des recommandations initiales pour 1) lancer, 2) établir et 3) soutenir un programme de recherche en MU. Ces recommandations ont été examinées par des médecins d'urgence et des chercheurs appartenant aux établissements d'origine des chacun des membres de comité et ont été testées pour leur validité apparente et conceptuelle, ainsi que leur facilité de compréhension. Les recommandations ont ensuite été fréquemment révisées en fonction des commentaires et suggestions de l'examen des pairs et modifiées à nouveau après avoir été présentées au symposium académique 2020 de l'ACMU. RéSULTATS: Notre comité a créé 15 recommandations pragmatiques pour ceux qui ont l'intention de lancer (formation formelle en recherche, trouver des mentors, soutien local, développer un créneau, débuter à petite échelle), d'établir (financer, constituer une équipe, collaborer, publier, s'attendre à l'échec) et de soutenir (devenir un mentor, obtenir des rôles de leadership, diriger des études nationales, gagner en influence, prioriser le bien-être) un programme de recherche en MU dans des centres sans culture de la recherche établie. De plus, nous suggérons 4 recommandations aux responsables de département visant à promouvoir un programme de recherche au sein de leur département. CONCLUSION: Ces recommandations servent de guide aux centres qui souhaitent établir un programme de recherche en MU.


Assuntos
Medicina de Emergência , Sociedades Médicas , Canadá , Humanos , Liderança , Mentores
20.
Front Cell Dev Biol ; 9: 633704, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33718369

RESUMO

The release of Ca2+ by ryanodine receptor (RyR2) channels is critical for cardiac function. However, abnormal RyR2 activity has been linked to the development of arrhythmias, including increased spontaneous Ca2+ release in human atrial fibrillation (AF). Clustering properties of RyR2 have been suggested to alter the activity of the channel, with remodeling of RyR2 clusters identified in pre-clinical models of AF and heart failure. Whether such remodeling occurs in human cardiac disease remains unclear. This study aimed to investigate the nanoscale organization of RyR2 clusters in AF patients - the first known study to examine this potential remodeling in diseased human cardiomyocytes. Right atrial appendage from cardiac surgery patients with paroxysmal or persistent AF, or without AF (non-AF) were examined using super-resolution (dSTORM) imaging. Significant atrial dilation and cardiomyocyte hypertrophy was observed in persistent AF patients compared to non-AF, with these two parameters significantly correlated. Interestingly, the clustering properties of RyR2 were remarkably unaltered in the AF patients. No significant differences were identified in cluster size (mean ∼18 RyR2 channels), density or channel packing within clusters between patient groups. The spatial organization of clusters throughout the cardiomyocyte was also unchanged across the groups. RyR2 clustering properties did not significantly correlate with patient characteristics. In this first study to examine nanoscale RyR2 organization in human cardiac disease, these findings indicate that RyR2 cluster remodeling is not an underlying mechanism contributing to altered channel function and subsequent arrhythmogenesis in human AF.

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