Irini Youssef

Obesity, Cardiovascular Disease and Sleep Disorders: Insights into the RisingEpidemic

Cardiovascular disease (CVD) is the main cause of death among adult men and women in the USA and impacts millions around the globe. Traditional risk factors for CVD include obesity, diabetes, hypertension and dyslipidemia. The modern-day epidemic of obesity not only increased the rate of CVD but also ushered in an additional CVD risk factor to be added to the list; that is obstructive sleep apnea (OSA). In this review, we discuss the growing epidemic of obesity and OSA, highlighting the common pathogenic hypotheses linking these risk factors to CVD. We will also highlight the therapeutic rationale of OSA as a way to reduce CVD risk.

The utilization of MGMT promoter methylation testing in United States hospitals for glioblastoma and its impact on prognosis

Multiple studies have identified O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status to be an important prognostic factor in glioblastoma (GBM). We used the National Cancer Data Base (NCDB) to analyze completeness of coding for MGMT as well as to compare outcomes of GBM patients treated with adjuvant chemoradiation based on MGMT promoter methylation status (positive, negative, unknown). Patients diagnosed with GBM from 2010 to 2012 who received adjuvant chemoradiation were identified. MGMT promoter methylation status was obtained. The Kaplan-Meier method was used to assess overall survival (OS) by coding status of MGMT promoter methylation (positive, negative, unknown) and Cox regression analysis was used to assess impact of covariables on OS. There were 12,725 patients who met the study criteria, of which 626 (4.9%) were MGMT+, 1,037 (8.1%) were MGMT- and 11.062 (86.9%) were coded as unknown/not coded. Treatment at academic centers was strongly associated with MGMT promoter status testing (OR 2.23, p < 0.001), as well as hospital facility within the Northeast (OR 1.55, p < 0.001). The median and 2-year OS was 20 months and 40.2% for MGMT+ compared to 15 months and 24.1% for MGMT-, respectively (p < 0.001). For those coded as MGMT unknown, median and 2-year OS was 14.6 months and 27.5%, which was significantly worse compared to MGMT+ (p < 0.001) but not compared to MGMT- (p = 0.78). On multivariable analysis, MGMT+ was strongly associated with improved OS (HR 0.74, p < 0.001). Despite convincing evidence that MGMT promoter methylation status has a strong influence on prognosis; it appears to be a highly underutilized test in United States hospitals.

Obstructive Sleep Apnea as a Risk Factor for Atrial Fibrillation: A Meta-Analysis

Objectives To conducted a meta-analysis assessing the relationship between Obstructive Sleep Apnea (OSA) and the risk of Atrial Fibrillation (AF) Methods We searched PUBMED, Medline, and Cochrane Library using the keywords “atrial fibrillation”, “obstructive sleep apnea” and “sleep disordered breathing (SDB)”. All subjects included had established diagnosis of OSA/SDB. We then compared the occurrence of AF versus no AF. Analysis done with Comprehensive Meta-Analysis package V3 (Biostat, USA). Results A total of 579 results were generated. Duplicates were removed and 372 records were excluded based on irrelevant abstracts, titles, study design not consistent with the stated outcome, or full-text unavailable. Twelve studies meeting the inclusion criteria were reviewed in full-text; 2 of these articles were eventually removed due to unconfirmed OSA diagnostic modality, and one was also removed based on a control group inconsistent with the other studies. Therefore, a total of 9 studies were included (n=19,837). Sample sizes ranged from n=160 patients to n=6841 patients. The risk of AF was found to be higher among OSA/SDB versus control group (OR; 2.120, C.I: 1.845–2.436, Z; 10.598 p: <0.001). The heterogeneity observed for the pooled analysis was Q-value; 22.487 df (Q); 8 P-value; 0.004, I-squared; 64.424 Tau2; 0.098, suggesting appropriate study selection and moderate heterogeneity. Conclusion OSA/SDB is strongly associated with AFib confirming the notion that OSA/SDB populations are high risk for development of AF. Prospective studies are needed to ascertain the effect of the treatment of OSA/SDB for the prevention of AF, a growing health burden with serious consequences.

Survival benefits in colorectal adenocarcinoma with the use of metformin among a black diabetic inner city population

We assessed the association of metformin use with survival in colorectal cancer in a population consists mostly of African-American and Afro-Caribbean patients. We identified 585 colorectal cancer patients, 167 (28.6%) and 418 (71.5%) were as diabetic (DM) and nondiabetic, respectively. The diagnosis of diabetes did not impact cancer survival or extent of disease. Overall, DMs with metformin use (D+M+) have better overall survival than both DMs without metformin use (D+M∼) and nondiabetics (D∼M∼), with a mean survival of 109.9 months compared with 95.7 and 106.1 months, respectively (log-rank p < 0.05). The use of metformin shows significant reduction of risk of mortality compared with nonusers (hazard ratio: 0.34; 95% CI: 0.15-0.81; p = 0.01). Use of insulin and status of diabetes did not have a significant impact on overall cancer survival.

Cardiovascular Disease Risk in Obstructive Sleep apnea: An Update

Cardiovascular disease (CVD) is the number one cause of death globally, accounting for 31% of all deaths in the world, and one out of every three deaths in the United States, in 2017 [1]. It is estimated that 90% of CVD is preventable, with traditional risk factors including tobacco use, excessive alcohol consumption, and unhealthy diet and physical inactivity, leading to hypertension, diabetes, dyslipidemia, and obesity. The epidemic of obesity has increased over the past decade, affecting an estimated 37.7% of adults, and 18% of children, in the US, and projected to rise to 51% of the population, a 130% increase, by 2030 [2]. This obesity epidemic has ushered in a new, highly prevalent, but largely underdiagnosed CVD risk factor: obstructive sleep apnea (OSA). OSA affects 34% of men, and 17% of women in the United States [3]. It is characterized by repetitive episodes of hypoventilation and complete apnea during sleep caused by total pharyngeal collapse and airway obstruction, despite normal breathing effort and drive. OSA’s impact on CVD appears to be due to recurrent cardio metabolic perturbations experienced when repetitively attempting to breath against an occluded airway, precipitating nightly episodes of hypoxia, sleep disturbance, and sympathetic nervous system surges, culminating in elevated blood pressure and heart rate, endothelial dysfunction, systemic inflammation and insulin resistance-all mechanisms involved in the pathogenesis of CVD (Figure 1) [4]. Accumulating evidence has linked OSA to multiple cardiovascular disorders including hypertension, type 2 DM, coronary artery disease, heart failure and cardiac arrhythmias (Figure 2). Open in a separate window Figure 1 Pathophysiological mechanisms linking obstructive sleep apnea to cardiovascular disease.

Association of Nadir Prostate-specific Antigen >0.5 ng/mL after Dose-escalated External Beam Radiation with Prostate Cancer-specific Endpoints

Objective Prior studies have suggested that prostate-specific antigen (PSA) nadir of 0.5 ng/mL is an important surrogate endpoint for prostate cancer-specific and all-cause mortality. This study analyzed our well-followed patient cohort to assess whether this endpoint was associated with differences in prostate cancer-specific endpoints in patients receiving dose-escalated radiation. Methods Patients with intermediate- or high-risk prostate cancer (≥T2b, or prostate-specific antigen >10 ng/mL, or Gleason score ≥7) who were treated with external beam radiation to a minimum dose of 7560 cGy +/- androgen deprivation between 2003 and 2011 were identified. Biochemical control, distant metastasis-free survival (DMFS), prostate cancer-specific survival (PCSS), and overall survival (OS) were compared between those who achieved a nadir PSA ≤0.5 ng/mL with those who did not via Kaplan-Meier analysis. Univariable and multivariable Cox regression was performed on all endpoints to assess their impact on OS. Results There were 367 patients identified with a median follow-up of 99.5 months. Two hundred five patients (55.9%) received androgen deprivation for a median of 24 months (range 1-81 months). Most patients (n = 308, 83.9%) achieved a nadir PSA ≤0.5 ng/mL, which was associated with improvement across all endpoints at 10 years. This included biochemical control (68.0% versus 24.0%, p < 0.001), DMFS (89.6% versus 80.8%, p = 0.019), PCSS (91.1% versus 85.7%, p = 0.01), and OS (55.7% versus 45.8%, p = 0.048). On multivariable analysis, nadir PSA >0.5 ng/mL remained strongly associated with worse outcomes across all endpoints. Conclusions Achievement of nadir PSA ≤0.5 ng/mL after completion of dose-escalated radiation therapy was associated with improvement of all prostate cancer endpoints.

Statins and New-Onset Diabetes in Cardiovascular and Kidney Disease Cohorts: A Meta-Analysis

Background: Statins have long been prescribed for the primary and secondary prevention of cardiovascular disease (CVD) and kidney disease. Their benefits and efficacy are widely accepted in current clinical practice, but like any other therapeutic agents, they have adverse effects. One of the emerging concerns with statin therapy is the development of new-onset diabetes mellitus (NODM), a dreaded risk factor for CVD and kidney disease and widely viewed as CVD equivalent. Accumulating evidence indicates that NODM is a consequence of statin use. Methods: We conducted a meta-analysis of studies reporting on associations between NODM and statin use. Based on strict exclusion criteria, a total of 11 studies were selected. Their data were analyzed using Comprehensive Meta-Analysis® statistical software and reported as odds ratios (OR) with 95% confidence intervals (CI). Results: The cumulative fixed effect for use of statin therapy and incident NODM was an OR of 1.61 (95% CI 1.55–1.68, p < 0.001). Our results suggest that statin therapy is associated with NODM, such that there is a small but significant risk of NODM among patients receiving statin for CVD prevention therapy. However, this high-risk population also has other diabetes risk factors (such as obesity and hypertension) contributing to the development of NODM. Conclusions: It is imperative that patients on statin therapy be monitored carefully for NODM. However, it can be argued that the risk of statin therapy is offset by the multitude of cardiovascular and kidney-protective effects provided by such an important and highly effective therapeutic agent.

Moderating effects of sleep duration on diabetes risk among cancer survivors: analysis of the National Health Interview Survey in the USA

Background Growing evidence suggests that cancer and diabetes may share common risk factors such as age, race/ethnicity, obesity, insulin resistance, sedentary lifestyle, smoking, and alcohol consumption. However, little is known about how habitual sleep duration (a known cardiometabolic risk factor) may affect the relationship between cancer and diabetes. The aim of this study was to investigate whether sleep duration moderated the relationship between history of cancer and diabetes. Methods Data were extracted from the National Health Interview Survey dataset from 2004 to 2013 containing demographics, chronic diseases, and sleep duration (N=236,406). Data were analyzed to assess the moderating effect of short and long sleep durations on cancer and diabetes mellitus. Results Our findings indicate that short sleep (odds ratio [OR] =1.07, 95% CI =1.03–1.11, P<0.001) and long sleep (OR =1.32, 95% CI =1.26–1.39, P<0.001) were associated with diabetes mellitus in fully adjusted models. However, only long sleep duration significantly moderated the relationship between cancer and diabetes (OR =0.88, 95% CI =0.78–0.98, P<0.05). Conclusion Our findings indicate that for cancer survivors, short sleep was associated with higher self-reported diabetes and long sleep duration may act as a buffer against diabetes mellitus, as the likelihood of self-reported diabetes was lower among cancer survivors who reported long sleep duration. Impact Findings from the current study have clinical and public health implications. Clinically, comprehensive sleep assessments and sleep interventions to improve sleep are needed for cancer survivors who have comorbid diabetes. Our findings can also spur public health reform to make sleep an important component of standard cancer survivorship care, as it reduces other chronic disease like diabetes.

The Utility of Endoscopic Ultrasound–Guided Brachytherapy in Liver Metastasis: A Case Report and Review of the Literature

Endoscopic ultrasound guided brachytherapy (EGBT) has been reported to be useful in certain malignancies including esophageal and pancreatic cancers. Percutaneous or surgical placement of radioactive seeds into the liver secondaries (brachytherapy) has been done successfully, however, the utility of EGBT in liver metastasis remains largely unclear. In this case report, we demonstrate the safety, efficacy and feasibility of EUS guided brachytherapy (EGBT) in liver metastasis secondary to leiomyosarcoma.