Nonobstructive coronary artery disease and risk of myocardial infarction.

IMPORTANCE: Little is known about cardiac adverse events among patients with nonobstructive coronary artery disease (CAD). OBJECTIVE: To compare myocardial infarction (MI) and mortality rates between patients with nonobstructive CAD, obstructive CAD, and no apparent CAD in a national cohort. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study of all US veterans undergoing elective coronary angiography for CAD between October 2007 and September 2012 in the Veterans Affairs health care system. Patients with prior CAD events were excluded. EXPOSURES: Angiographic CAD extent, defined by degree (no apparent CAD: no stenosis >20%; nonobstructive CAD: ≥1 stenosis ≥20% but no stenosis ≥70%; obstructive CAD: any stenosis ≥70% or left main [LM] stenosis ≥50%) and distribution (1, 2, or 3 vessel). MAIN OUTCOMES AND MEASURES: The primary outcome was 1-year hospitalization for nonfatal MI after the index angiography. Secondary outcomes included 1-year all-cause mortality and combined 1-year MI and mortality. RESULTS: Among 37,674 patients, 8384 patients (22.3%) had nonobstructive CAD and 20,899 patients (55.4%) had obstructive CAD. Within 1 year, 845 patients died and 385 were rehospitalized for MI. Among patients with no apparent CAD, the 1-year MI rate was 0.11% (n = 8, 95% CI, 0.10%-0.20%) and increased progressively by 1-vessel nonobstructive CAD, 0.24% (n = 10, 95% CI, 0.10%-0.40%); 2-vessel nonobstructive CAD, 0.56% (n = 13, 95% CI, 0.30%-1.00%); 3-vessel nonobstructive CAD, 0.59% (n = 6, 95% CI, 0.30%-1.30%); 1-vessel obstructive CAD, 1.18% (n = 101, 95% CI, 1.00%-1.40%); 2-vessel obstructive CAD, 2.18% (n = 110, 95% CI, 1.80%-2.60%); and 3-vessel or LM obstructive CAD, 2.47% (n = 137, 95% CI, 2.10%-2.90%). After adjustment, 1-year MI rates increased with increasing CAD extent. Relative to patients with no apparent CAD, patients with 1-vessel nonobstructive CAD had a hazard ratio (HR) for 1-year MI of 2.0 (95% CI, 0.8-5.1); 2-vessel nonobstructive HR, 4.6 (95% CI, 2.0-10.5); 3-vessel nonobstructive HR, 4.5 (95% CI, 1.6-12.5); 1-vessel obstructive HR, 9.0 (95% CI, 4.2-19.0); 2-vessel obstructive HR, 16.5 (95% CI, 8.1-33.7); and 3-vessel or LM obstructive HR, 19.5 (95% CI, 9.9-38.2). One-year mortality rates were associated with increasing CAD extent, ranging from 1.38% among patients without apparent CAD to 4.30% with 3-vessel or LM obstructive CAD. After risk adjustment, there was no significant association between 1- or 2-vessel nonobstructive CAD and mortality, but there were significant associations with mortality for 3-vessel nonobstructive CAD (HR, 1.6; 95% CI, 1.1-2.5), 1-vessel obstructive CAD (HR, 1.9; 95% CI, 1.4-2.6), 2-vessel obstructive CAD (HR, 2.8; 95% CI, 2.1-3.7), and 3-vessel or LM obstructive CAD (HR, 3.4; 95% CI, 2.6-4.4). Similar associations were noted with the combined outcome. CONCLUSIONS AND RELEVANCE: In this cohort of patients undergoing elective coronary angiography, nonobstructive CAD, compared with no apparent CAD, was associated with a significantly greater 1-year risk of MI and all-cause mortality. These findings suggest clinical importance of nonobstructive CAD and warrant further investigation of interventions to improve outcomes among these patients.

BCG and Alternative Therapies to BCG Therapy for Non-Muscle-Invasive Bladder Cancer.

Bladder cancer is a heterogeneous disease. Treatment decisions are mostly decided based on disease stage (non-muscle invasive or muscle invasive). Patients with muscle-invasive disease will be offered a radical treatment combined with systemic therapy, while in those with non-muscle-invasive disease, an attempt to resect the tumor endoscopically will usually be followed by different intravesical instillations. The goal of intravesical therapy is to decrease the recurrence and/or progression of the tumor. In the current landscape of bladder cancer treatment, BCG is given intravesically to induce an inflammatory response and recruit immune cells to attack the malignant cells and induce immune memory. While the response to BCG treatment has changed the course of bladder cancer management and spared many "bladders", some patients may develop BCG-unresponsive disease, leaving radical surgery as the best choice of curative treatment. As a result, a lot of effort has been put into identifying novel therapies like systemic pembrolizumab and Nadofaragene-Firadenovac to continue sparing bladders if BCG is ineffective. Moreover, recent logistic issues with BCG production caused a worldwide BCG shortage, re-sparking interest in alternative BCG treatments including mitomycin C, sequential gemcitabine with docetaxel, and others. This review encompasses both the historic and current role of BCG in the treatment of non-muscle-invasive bladder cancer, revisiting BCG alternative therapies and reviewing the novel therapeutics that were approved for the BCG-unresponsive stage or are under active investigation.

Application of the Sleep C.A.L.M. Tool for Assessing Nocturia in a Large Nationally Representative Cohort.

PURPOSE: Nocturia significantly impacts patients' quality of life but remains insufficiently evaluated and treated. The "Sleep C.A.L.M." system categorizes the factors thought to collectively reflect most underlying causes of nocturia (Sleep disorders, Comorbidities, Actions [i.e., modifiable patient behaviors such as excess fluid intake], Lower urinary tract dysfunction, and Medications). The purpose of this study was to assess the association of nocturia with the Sleep C.A.L.M. categories using a nationally representative dataset. METHODS: Retrospective analysis of the National Health and Nutrition Examination Survey from 2013/14-2017/18 cycles was conducted. Pertinent questionnaire, laboratory, dietary, and physical examination data were used to ascertain the presence of Sleep C.A.L.M. categories in adults ≥20 years of age. Nocturia was defined as ≥2 nighttime voids. RESULTS: A total of 12,274 included subjects were included (51.6% female; median age, 49.0 years [interquartile range, 34.0-62.0 years]; 27.6% nocturia). Among subjects with nocturia, the prevalence of 0, ≥1, and ≥2 Sleep C.A.L.M. categories was 3.5% (95% confidence interval [CI], 2.8%-4.4%), 96.5% (95% CI, 95.6%-97.2%), and 81.2% (95% CI, 78.9%-83.3%), respectively. Compared to those with 0-1 Sleep C.A.L.M. categories, the adjusted odds of nocturia in subjects with 2, 3, and 4-5 Sleep C. A.L.M. categories were 1.77 (95% CI, 1.43-2.21), 2.33 (1.89-2.87), and 3.49 (2.81-4.35), respectively (P<0.001). Similar trends were observed for most age and sex subgroups. When assessed individually, each of the 5 Sleep C.A.L.M. categories were independently associated with greater odds of nocturia, which likewise persisted across multiple age and sex subgroups. CONCLUSION: Sleep C.A.L.M. burden is associated with increased odds of nocturia in a dose-dependent fashion, and potentially a relevant means by which to organize the underlying etiologies for nocturia among community-dwelling adults.

Diabetes and cardiovascular disease: Epidemiology, biological mechanisms, treatment recommendations and future research.

The incidence of diabetes mellitus (DM) continues to rise and has quickly become one of the most prevalent and costly chronic diseases worldwide. A close link exists between DM and cardiovascular disease (CVD), which is the most prevalent cause of morbidity and mortality in diabetic patients. Cardiovascular (CV) risk factors such as obesity, hypertension and dyslipidemia are common in patients with DM, placing them at increased risk for cardiac events. In addition, many studies have found biological mechanisms associated with DM that independently increase the risk of CVD in diabetic patients. Therefore, targeting CV risk factors in patients with DM is critical to minimize the long-term CV complications of the disease. This paper summarizes the relationship between diabetes and CVD, examines possible mechanisms of disease progression, discusses current treatment recommendations, and outlines future research directions.

Weight Loss Programs May Have Beneficial or Adverse Effects on Fat Mass and Insulin Sensitivity in Overweight and Obese Black Women.

OBJECTIVE: Weight loss interventions have produced little change in insulin sensitivity in black women, but mean data may obscure metabolic benefit to some and adverse effects for others. Accordingly, we analyzed insulin sensitivity relative to fat mass change following a weight loss program. DESIGN AND METHODS: Fifty-four black women (BMI range 25.9 to 54.7 kg/m2) completed the 6-month program that included nutrition information and worksite exercise facilities. Fat mass was measured by dual-energy X-ray absorptiometry, and insulin sensitivity index (SI) was calculated from an insulin-modified intravenous glucose tolerance test using the minimal model. RESULTS: Baseline SI (range 0.74 to 7.58 l/mU-1•min-1) was inversely associated with fat mass (r = -0.516, p < 0.001), independent of age. On average, subjects lost fat mass (baseline 40.8 ± 12.4 to 39.4 ± 12.6 kg [mean ± SD], P < 0.01), but 17 women (32 %) actually gained fat mass. SI for the group was unchanged (baseline 3.3 ± 1.7 to 3.2 ± 1.6, P = 0.67). However, the tertile with greatest fat mass loss (-3.6 kg, range -10.7 to -1.7 kg) improved insulin sensitivity (SI +0.3 ± 1.2), whereas the tertile with net fat mass gain (+0.9 kg, range -0.1 to +3.8 kg) had reduced insulin sensitivity (SI -0.7 ± 1.3) from baseline values (P < 0.05 by ANOVA). CONCLUSIONS: Black women in a weight loss program who lose fat mass may have improved insulin sensitivity, but fat mass gain with diminished sensitivity is common. Additional support for participants who fail to achieve fat mass loss early in an intervention may be required for success.