RESUMO
Essentially all biological processes fluctuate over the course of the day, manifesting as time-of-day-dependent variations with regards to the way in which organ systems respond to normal behaviors. For example, basic, translational, and epidemiologic studies indicate that temporal partitioning of metabolic processes governs the fate of dietary nutrients, in a manner in which concentrating caloric intake towards the end of the day is detrimental to both cardiometabolic and cardiovascular parameters. Despite appreciation that branched chain amino acids impact risk for obesity, diabetes mellitus, and heart failure, it is currently unknown whether the time-of-day at which dietary BCAAs are consumed influence cardiometabolic/cardiovascular outcomes. Here, we report that feeding mice a BCAA-enriched meal at the end of the active period (i.e., last 4 h of the dark phase) rapidly increases cardiac protein synthesis and mass, as well as cardiomyocyte size; consumption of the same meal at the beginning of the active period (i.e., first 4 h of the dark phase) is without effect. This was associated with a greater BCAA-induced activation of mTOR signaling in the heart at the end of the active period; pharmacological inhibition of mTOR (through rapamycin) blocked BCAA-induced augmentation of cardiac mass and cardiomyocyte size. Moreover, genetic disruption of the cardiomyocyte circadian clock abolished time-of-day-dependent fluctuations in BCAA-responsiveness. Finally, we report that repetitive consumption of BCAA-enriched meals at the end of the active period accelerated adverse cardiac remodeling and contractile dysfunction in mice subjected to transverse aortic constriction. Thus, our data demonstrate that the timing of BCAA consumption has significant implications for cardiac health and disease.
Assuntos
Aminoácidos de Cadeia Ramificada/metabolismo , Metabolismo Energético , Miocárdio/metabolismo , Miócitos Cardíacos/metabolismo , Vigília , Fatores de Transcrição ARNTL/deficiência , Animais , Biomarcadores , Relógios Circadianos , Suscetibilidade a Doenças , Ingestão de Alimentos , Camundongos , Camundongos Knockout , Biossíntese de Proteínas , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Remodelação Ventricular/genéticaRESUMO
OBJECTIVES: To assess the relationship between patient smoking status and fracture-related infection (FRI) characteristics including patient symptoms at FRI presentation, bacterial species of FRI, and rates of fracture union. DESIGN: Retrospective cohort study. SETTING: Urban level 1 trauma center. PATIENT SELECTION CRITERIA: All patients undergoing reoperation for FRI from January 2013 to April 2021 were identified through manual review of an institutional database. OUTCOME MEASURES AND COMPARISONS: Data including patient demographics, fracture characteristics, infection presentation, and hospital course were collected through review of the electronic medical record. Patients were grouped based on current smoker versus nonsmoker status. Hospital course and postoperative outcomes of these groups were then compared. Risk factors of methicillin-resistant Staphylococcus aureus (MRSA) infection, Staphylococcus epidermidis infection, and sinus tract development were evaluated using multivariable logistic regression. RESULTS: A total of 301 patients, comprising 155 smokers (51%) and 146 nonsmokers (49%), undergoing FRI reoperation were included. Compared with nonsmokers, smokers were more likely male (69% vs. 56%, P = 0.024), were younger at the time of FRI reoperation (41.7 vs. 49.5 years, P < 0.001), and had lower mean body mass index (27.2 vs. 32.0, P < 0.001). Smokers also had lower prevalence of diabetes mellitus (13% vs. 25%, P = 0.008) and had higher Charlson Comorbidity Index 10-year estimated survival (93% vs. 81%, P < 0.001). Smokers had a lower proportion of S. epidermidis infections (11% vs. 20%, P = 0.037), higher risk of nonunion after index fracture surgery (74% vs. 61%, P = 0.018), and higher risk of sinus tracts at FRI presentation (38% vs. 23%, P = 0.004). On multivariable analysis, smoking was not found to be associated with increased odds of MRSA infection. CONCLUSIONS: Among patients who develop a FRI, smokers seemed to have better baseline health regarding age, body mass index, diabetes mellitus, and Charlson Comorbidity Index 10-year estimated survival compared with nonsmokers. Smoking status was not significantly associated with odds of MRSA infection. However, smoking status was associated with increased risk of sinus tract development and nonunion and lower rates of S. epidermidis infection at the time of FRI reoperation. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.
Assuntos
Diabetes Mellitus , Fraturas Ósseas , Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Humanos , Masculino , Estudos Retrospectivos , Fumar/efeitos adversos , Infecções Estafilocócicas/microbiologia , HospitaisRESUMO
OBJECTIVES: To analyze demographics, comorbidities, fracture characteristics, presenting characteristics, microbiology, and treatment course of patients with fracture-related infections (FRIs) to determine risk factors leading to amputation. DESIGN: Retrospective cohort. SETTING: Single Level I Trauma Center (2013-2020). PATIENT SELECTION CRITERIA: Adults with lower extremity (femur and tibia) FRIs were identified through a review of an institutional database. Inclusion criteria were operatively managed fracture of the femur or tibia with an FRI and adequate documentation present in the electronic medical record. This included patients whose primary injury was managed at this institution and who were referred to this institution after the onset of FRI as long as all characteristics and risk factors assessed in the analysis were documented. Exclusion criteria were infected chronic osteomyelitis from a non-fracture-related pathology and a follow-up of less than 6 months. OUTCOME MEASURES AND COMPARISONS: Risk factors (demographics, comorbidities, and surgical, injury, and perioperative characteristics) leading to amputation in patients with FRIs were evaluated. RESULTS: A total of 196 patients were included in this study. The average age of the study group was 44±16 years. Most patients were men (63%) and White (71%). The overall amputation rate was 9.2%. There were significantly higher rates of chronic kidney disease (CKD; P = 0.039), open fractures (P = 0.034), transfusion required during open reduction internal fixation (P = 0.033), Gram-negative infections (P = 0.048), and FRI-related operations (P = 0.001) in the amputation cohort. On multivariate, patients with CKD were 28.8 times more likely to undergo amputation (aOR = 28.8 [2.27 to 366, P = 0.010). A subanalysis of 79 patients with either a methicillin-sensitive Staphylococcus aureus or methicillin-resistant S. aureus (MRSA) infection showed that patients with MRSA were significantly more likely to undergo amputation compared with patients with methicillin-sensitive Staphylococcus aureus (P = 0.031). MRSA was present in all cases of amputation in the Staphylococcal subanalysis. CONCLUSIONS: Findings from this study highlight CKD as a risk factor of amputation in the tibia and femur with fracture-related infection. In addition, MRSA was present in all cases of Staphylococcal amputation. Identifying patients and infection patterns that carry a higher risk of amputation can assist surgeons in minimizing the burden on these individuals. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.