A Cohort Study
AUDIENCE: Internal Medicine, Cardiology
KEY FINDINGS: Postoperative AF after noncardiac surgery is associated with similar risk for thromboembolism compared with nonoperative AF. Our findings have potentially important implications for the early postsurgical and subsequent management of postoperative AF.
BACKGROUND: Postoperative atrial fibrillation (AF) after noncardiac surgery confers increased risks for ischemic stroke and transient ischemic attack (TIA). How outcomes for postoperative AF after noncardiac surgery compare with those for AF occurring outside of the operative setting is unknown. Purpose of this study is to compare the risks for ischemic stroke or TIA and other outcomes in patients with postoperative AF versus those with incident AF not associated with surgery.
DETAILS: Patients were categorized as having AF occurring within 30 days of a noncardiac surgery (postoperative AF) or having AF unrelated to surgery (nonoperative AF). The population consisted predominantly of White patients; caution should be used when extrapolating the results to more racially diverse populations. Of 4231 patients with incident AF, 550 (13%) had postoperative AF as their first-ever documented AF presentation. Over a mean follow-up of 6.3 years, 486 patients had an ischemic stroke or TIA and 2462 had subsequent AF; a total of 2565 deaths occurred. The risk for stroke or TIA was similar between those with postoperative AF and nonoperative AF (absolute risk difference [ARD] at 5 years, 0.1% [95% CI, -2.9% to 3.1%]; hazard ratio [HR], 1.01 [CI, 0.77 to 1.32]). A lower risk for subsequent AF was seen for patients with postoperative AF (ARD at 5 years, -13.4% [CI, -17.8% to -9.0%]; HR, 0.68 [CI, 0.60 to 0.77]). Finally, no difference was seen for cardiovascular death or all-cause death between patients with postoperative AF and nonoperative AF.
Copyright © American College of Physicians. All Rights Reserved.
Source: Siontis, K. C., Gersh, B. J., Weston, S. A., et al. (2022). Associations of Atrial Fibrillation After Noncardiac Surgery With Stroke, Subsequent Arrhythmia, and Death: A Cohort Study. Annals of Internal Medicine. Published: July 26, 2022. DOI: 10.7326/M22-0434.
A Randomized Clinical Trial
AUDIENCE: Internal Medicine
KEY FINDINGS: In this randomized clinical trial, eTRE was more effective for losing weight and improving diastolic blood pressure and mood than eating over a window of 12 or more hours at 14 weeks.
BACKGROUND: It is unclear how effective intermittent fasting is for losing weight and body fat, and the effects may depend on the timing of the eating window. This randomized trial compared time-restricted eating (TRE) with eating over a period of 12 or more hours while matching weight-loss counseling across groups. Aim of this study is to determine whether practicing TRE by eating early in the day (eTRE) is more effective for weight loss, fat loss, and cardiometabolic health than eating over a period of 12 or more hours.
DETAILS: The study was a 14-week, parallel-arm, randomized clinical trial conducted between August 2018 and April 2020. Participants were adults aged 25 to 75 years with obesity and who received weight-loss treatment through the Weight Loss Medicine Clinic at the University of Alabama at Birmingham Hospital. All participants received weight-loss treatment (energy restriction [ER]) and were randomized to eTRE plus ER (8-hour eating window from 7:00 to 15:00) or control eating (CON) plus ER (>=12-hour window). The co–primary outcomes were weight loss and fat loss. Secondary outcomes included blood pressure, heart rate, glucose levels, insulin levels, and plasma lipid levels. Ninety participants were enrolled (mean [SD] body mass index, 39.6 [6.7]; age, 43  years; 72 [80%] female). The eTRE+ER group adhered 6.0 (0.8) days per week. The eTRE+ER intervention was more effective for losing weight (-2.3 kg; 95% CI, -3.7 to -0.9 kg; P = .002) but did not affect body fat (-1.4 kg; 95% CI, -2.9 to 0.2 kg; P = .09) or the ratio of fat loss to weight loss (-4.2%; 95% CI, -14.9 to 6.5%; P = .43). The effects of eTRE+ER were equivalent to reducing calorie intake by an additional 214 kcal/d. The eTRE+ER intervention also improved diastolic blood pressure (-4 mm Hg; 95% CI, -8 to 0 mm Hg; P = .04) and mood disturbances, including fatigue-inertia, vigor-activity, and depression-dejection. All other cardiometabolic risk factors, food intake, physical activity, and sleep outcomes were similar between groups. In a secondary analysis of 59 completers, eTRE+ER was also more effective for losing body fat and trunk fat than CON+ER.
Copyright © American Medical Association. All Rights Reserved.
Source: Jamshed, H. Steger, F. L., Bryn, D. R., et al. (2022). Effectiveness of Early Time-Restricted Eating for Weight Loss, Fat Loss, and Cardiometabolic Health in Adults With Obesity: A Randomized Clinical Trial. JAMA Intern Med.. Published: August 8, 2022. DOI: 10.1001/jamainternmed.2022.3050.
AUDIENCE: Endocrinology, Neurology, Family Medicine
KEY FINDINGS: Middle-aged and older adults with T1DM showed brain volume loss and increased vascular injury in comparison with control subjects without diabetes, equivalent to 4-9 years of brain aging.
BACKGROUND: Individuals with type 1 diabetes mellitus (T1DM) are living to ages when neuropathological changes are increasingly evident. Hypothesized that middle-aged and older adults with long-standing T1DM will show abnormal brain structure in comparison with control subjects without diabetes.
DETAILS: MRI was used to compare brain structure among 416 T1DM participants in the Epidemiology of Diabetes Interventions and Complications (EDIC) study with that of 99 demographically similar control subjects without diabetes at 26 U.S. and Canadian sites. Assessments included total brain (TBV) (primary outcome), gray matter (GMV), white matter (WMV), ventricle, and white matter hyperintensity (WMH) volumes and total white matter mean fractional anisotropy (FA). Biomedical assessments included HbA1c and lipid levels, blood pressure, and cognitive assessments of memory and psychomotor and mental efficiency (PME). Among EDIC participants, HbA1c, severe hypoglycemia history, and vascular complications were measured longitudinally. Mean age of EDIC participants and control subjects was 60 years. T1DM participants showed significantly smaller TBV (least squares mean ± SE 1,206 ± 1.7 vs. 1,229 ± 3.5 cm3, P < 0.0001), GMV, and WMV and greater ventricle and WMH volumes but no differences in total white matter mean FA versus control subjects. Structural MRI measures in T1DM were equivalent to those of control subjects who were 4-9 years older. Lower PME scores were associated with altered brain structure on all MRI measures in T1DM participants.
Copyright © American Diabetes Association. All rights reserved.
Source: Jacobson, A. M., Braffett, B. H., Erus, G., et al. (2022). Brain Structure Among Middle-aged and Older Adults With Long-standing Type 1 Diabetes in the DCCT/EDIC Study. Diabetes Care. 2022; 45(8): 1779-1787. Published: July 26, 2022. DOI: 10.2337/dc21-2438.
AUDIENCE: Gastroenterology, Internal Medicine
KEY FINDINGS: The results indicate that CPT1A plays a critical role in the activation of HSCs and is implicated in the development of liver fibrosis, making it a potentially actionable target for fibrosis treatment.
BACKGROUND: The pathogenesis of liver fibrosis requires activation of hepatic stellate cells (HSCs); once activated, HSCs lose intracellular fatty acids but the role of fatty acid oxidation and carnitine palmitoyltransferase 1A (CPT1A) in this process remains largely unexplored.
DETAILS: CPT1A was found in HSCs of patients with fibrosis. Pharmacological and genetic manipulation of CPT1A were performed in human HSC cell lines and primary HCSs. Finally, induced fibrosis in mice lacking CPT1A specifically in HSCs. Herein, study shows that CPT1A expression is elevated in HSCs of patients with non-alcoholic steatohepatitis, showing a positive correlation with the fibrosis score. This was corroborated in rodents with fibrosis, as well as in primary human HSCs and LX-2 cells activated by transforming growth factor ß1 (TGFß1) and fetal bovine serum (FBS). Furthermore, both pharmacological and genetic silencing of CPT1A prevent TGFß1- and FBS-induced HSC activation by reducing mitochondrial activity. The overexpression of CPT1A, induced by saturated fatty acids and reactive oxygen species, triggers mitochondrial activity and the expression of fibrogenic markers. Finally, mice lacking CPT1A specifically in HSCs are protected against fibrosis induced by a choline-deficient high-fat diet, a methionine- and choline-deficient diet, or treatment with carbon tetrachloride.
Copyright © Elsevier Inc. All rights reserved.
Source: Fondevila, M. F., Fernandes, U., Heras, V., et al. (2022). Inhibition of Carnitine Palmitoyltransferase 1A in Hepatic Stellate Cells Protects Against Fibrosis. J Hepatology. 2022; 77(1): 15-28. Published: July, 2022. DOI: 10.1016/j.jhep.2022.02.003.
AUDIENCE: Oncology, Nephrology
KEY FINDINGS: Cabozantinib plus nivolumab showed promising efficacy in most non–clear-cell RCC variants tested in this trial, particularly those with prominent papillary features, whereas treatment effects were limited in chromophobe RCC. Genomic findings in non–clear-cell RCC variants warrant further study as predictors of response.
BACKGROUND: Objective of this trial is to assess the efficacy and safety of cabozantinib plus nivolumab in a phase II trial in patients with non–clear-cell renal cell carcinoma (RCC).
DETAILS: Patients had advanced non–clear-cell renal carcinoma who underwent 0-1 prior systemic therapies excluding prior immune checkpoint inhibitors. Patients received cabozantinib 40 mg once daily plus nivolumab 240 mg once every 2 weeks or 480 mg once every 4 weeks. Cohort 1 enrolled patients with papillary, unclassified, or translocation-associated RCC; cohort 2 enrolled patients with chromophobe RCC. The primary end point was objective response rate (ORR) by RECIST 1.1; secondary end points included progression-free survival, overall survival, and safety. Next-generation sequencing results were correlated with response. A total of 47 patients were treated with a median follow-up of 13.1 months. Objective response rate for cohort 1 (n= 40) was 47.5% (95% CI, 31.5 to 63.9), with median progression-free survival of 12.5 months (95% CI, 6.3 to 16.4) and median overall survival of 28 months (95% CI, 16.3 to not evaluable). In cohort 2 (n= 7), no responses were observed; one patient had stable disease > 1 year. Grade 3/4 treatment-related adverse events were observed in 32% treated patients. Cabozantinib and nivolumab were discontinued because of toxicity in 13% and 17% of patients, respectively. Common mutations included NF2 and FH in cohort 1 and TP53 and PTEN in cohort 2. Objective responses were seen in 10/12 patients with either NF2 or FH mutations.
Copyright © American Society of Clinical Oncology. All rights reserved.
Source: Lee, C., Voss, M. H., Carlo, M. I., et al. (2022). Phase II Trial of Cabozantinib Plus Nivolumab in Patients With Non–Clear-Cell Renal Cell Carcinoma and Genomic Correlates. Journal of Clinical Oncology. 2021; 40(21): 2333-2341. Published: July 20, 2022. DOI: 0.1200/JCO.21.01944.
Prevalence and Correlation to Visual Field Loss
AUDIENCE: Ophthalmology, Family Medicine
KEY FINDINGS: Charles Bonnet Syndrome was not a rare condition in patients with glaucoma. Patients with a combination of advanced VFL and low BCVA had the highest risk of CBS; however, 1 of 3 patients with CBS had a BCVA of >=0.5 in both eyes. These findings emphasize the importance of being attentive to symptoms of CBS in patients with glaucomatous VFL even when visual acuity is preserved.
BACKGROUND: Objective of this study is to determine the prevalence and characteristics of Charles Bonnet Syndrome (CBS) and its relation to visual field loss (VFL) in patients with open-angle glaucoma (OAG).
DETAILS: Patients attending the glaucoma outpatient department of the Skane University hospital, Malmo, Sweden, between April 1, 2018, and December 31, 2018, were consecutively evaluated for inclusion. Potentially eligible patients admitting to having complex visual hallucinations were interviewed to explore the characteristics of their hallucinatory experiences. Recent automated visual field examinations were available for all participants, and swept-source OCT was performed in participants with CBS to rule out previously undiagnosed macular pathology. The correlation between potential risk factors and CBS was evaluated with logistic regression analysis. Charles Bonnet Syndrome was not a rare condition in patients with glaucoma. Patients with a combination of advanced VFL and low BCVA had the highest risk of CBS; however, 1 of 3 patients with CBS had a BCVA of >=0.5 in both eyes. These findings emphasize the importance of being attentive to symptoms of CBS in patients with glaucomatous VFL even when visual acuity is preserved.
Copyright © The American Academy of Ophthalmology. All rights reserved.
Source: Peters, D., Molander, S., Lomo, T., et al. (2022). Charles Bonnet Syndrome in Patients with Open-Angle Glaucoma: Prevalence and Correlation to Visual Field Loss. Ophthalmology Glaucoma. 2022; 5(3): 337-344. Published: May 1, 2022. DOI: Charles Bonnet Syndrome in Patients with Open-Angle Glaucoma.