An unexpected paradox: wall shear stress in the aorta is less in patients with severe atherosclerosis regardless of obesity.

BACKGROUND: Obesity is a widespread condition that is more prevalent in Western countries compared to others. Aortic atherosclerosis (AA) is a condition that frequently has been associated with obesity. An obesity paradox, where morbidly obese decedents had either no or minimal AA compared to nonobese decedents, recently has been described by some of us. The explanation for this almost counterintuitive paradox has yet to be determined, but a number of hypotheses were advanced, including hemodynamic factors producing aortic wall shear stress (WSS). The purpose of the present study was to determine if there was a relationship between AA and WSS, as determined by postmortem measurement of aortic wall diameters. METHODS: Circumferences of the aorta at the levels of the ascending, thoracic and abdominal aorta were measured in 274 consecutive autopsies over 2-year period of time. AA was assessed using a previously described grading scale as either mild or severe. Circumferences were mathematically converted to diameters and WSS was calculated using the Hagen-Poiseuille formula. Two different methods to estimate cardiac output were used, both based on literature methods, one of which was body mass index (BMI) dependent, and the other BMI independent. Univariate and multivariable analyses of the relationship between WSS, age, BMI, gender, race and severity of AA were performed. RESULTS: Of the 274 decedents, 140 had mild and 134 had moderate to severe AA. BMI <35 was associated with moderate to severe AA. WSS was inversely correlated with AA in all these segments of the aorta in each BMI subgroup with the exception of the ascending aorta for decedents with BMI ≤35 kg/m2. Contrary to what we had hypothesized, WSS was not a determinant of the obesity paradox. However, among all the variables analyzed, a history of hypertension, diabetes mellitus and age were significant factors for developing AA (relative risk [RR] 0.35, P = .039; RR 1.51, P = .0006, RR 1.19, P = .0001, respectively). CONCLUSIONS: Our data demonstrate that WSS was unexpectedly lower in decedents with moderate and severe AA as compared to those with mild AA. This observation, which requires further investigations, was seen in all BMI ranges and was confirmed by 2 methods to calculate WSS.

National Institutes of Health Funding in Rhode Island.

OBJECTIVES: We present an overview of the National Institutes of Health (NIH) funding in Rhode Island through analysis of 935 NIH grants received during the fiscal years of 2012 to 2016. RESULTS: NIH funded over 2,600 grants from 2012 to 2016, of which approximately 900 were new grant awards, and the remainder were annual grant renewals. The most funded type of research in Rhode Island is mental health and substance abuse, followed by infectious disease, neurology, and public health. Research funding of cardiovascular diseases, on a per capita basis, are on par with the rest of the nation, while cancer research funding is less than one half the national average. The largest NIH institutional funding source is the National Institute of General Medical Sciences (NIGMS), followed by National Institute of Mental Health (NIMH) and National Institute on Alcohol Abuse and Alcoholism (NIAAA). While research grants (R01s) remain the predominant source of NIH funding, investigators in Rhode Island have secured additional funding through program project (P) grants with the aim of bolstering research resources and collaboration throughout the state. [Full article available at http://rimed.org/rimedicaljournal-2017-07.asp].

Updates On Chimeric Antigen Receptor-Mediated Glioblastoma Immunotherapy.

Glioblastoma multiforme (GBM) is the most malignant of the primary central nervous system (CNS) neoplasms, accounting for nearly 80% of all primary brain tumors and is associated with high morbidity and mortality. Immunotherapy is proving to be a fertile ground for next-generation GBM therapy, with large translational research projects and clinical trials currently underway. One particularly promising area is the chimeric antigen receptors (CARs) in the context of lymphocyte adoptive cell therapy (ACT), which has achieved success in the treatment of hematological malignancies. In this review, we will discuss CARs and review current challenges facing their use in GBM therapy. [Full article available at http://rimed.org/rimedicaljournal-2017-06.asp].

The Clinical Research Landscape in Rhode Island.

OBJECTIVES: To present an overview of clinical research activity and the state of medical research funding in Rhode Island. METHODS: We utilized clinicaltrials.gov registry to profile clinical studies between 2011 to 2016. NIH RePORT and other federal databases were used to extract information on levels of federal funding. Previously published hospital financial reports were reviewed for data on hospital-specific total external research funding. RESULTS: During 2011-2016, 1651 clinical studies were registered in clinicaltrials.gov. Nearly a third of all clinical studies were in oncology (21%) and cardiovascular diseases (10%). Alzheimer's dementia, breast cancer, HIV, and hepatitis C accounted for nearly 17% of all clinical trials. Seventy-five percent (75%) of clinical trials in RI were conducted in hospitals affiliated with Lifespan or Care New England. Financial support for clinical trials largely came from industry (60%) with 23% being supported by the National Institutes of Health (NIH). The rest are funded by nonprofit organizations, charitable foundations, educational institutions, and unlisted concerns. [Full article available at http://rimed.org/rimedicaljournal-2017-01.asp].