Impact of Racial Disparities in Preoperative Cardiovascular Evaluation and Surgical Outcomes in Patients Undergoing Metabolic and Bariatric Surgery: A Retrospective Cohort Analysis.

Background We investigated preoperative referral patterns, rates of cardiovascular testing, surgical wait times, and postoperative outcomes in White versus Black, Hispanic, or other racial or ethnic groups of patients undergoing metabolic and bariatric surgery. Methods and Results This was a single center retrospective cohort analysis of 797 consecutive patients undergoing metabolic and bariatric surgery from January 2014 to December 2018; 86% (n=682) were Black, Hispanic, or other racial or ethnic groups. White versus Black, Hispanic, or other racial or ethnic groups had similar baseline comorbidities and were referred for preoperative cardiovascular evaluation in similar proportion (65% versus 68%, P=0.529). Black, Hispanic, or other racial or ethnic groups of patients were less likely to undergo preoperative cardiovascular testing (unadjusted odds ratio [OR], 0.56; 95% CI, 0.33-0.95; P=0.031; adjusted for Revised Cardiac Risk Index OR, 0.59; 95% CI, 0.35-0.996; P=0.049). White patients had a shorter wait time for surgery (unadjusted hazard ratio [HR], 0.7; 95% CI, 0.58-0.87; P=0.001; adjusted HR, 0.7; 95% CI, 0.56-0.95; P=0.018). Reduction in body mass index at 6 months was greater in White patients (12.9 kg/m2 versus 12.0 kg/m2, P=0.0289), but equivalent at 1 year (14.9 kg/m2 versus 14.3 kg/m2, P=0.330). Conclusions White versus Black, Hispanic, or other racial or ethnic groups of patients were referred for preoperative cardiovascular evaluation in similar proportion. White patients underwent more preoperative cardiac testing yet had a shorter wait time for surgery. Early weight loss was greater in White patients, but equivalent between groups at 12 months.

Changes in Antihypertensive Medication Following Bariatric Surgery.

Obesity is a leading cause of hypertension (i.e., high blood pressure [BP]). While hypertension can be managed with antihypertensive medication, substantial weight loss can also lower BP, reducing the need for antihypertensive medication. Articles in this review (n = 60) presented data on antihypertensive medication use among adults pre- and postoperatively. Roux-en-Y gastric bypass was the most studied surgical approach followed by Laparoscopic Sleeve Gastrectomy. Antihypertensive medication was discontinued in a large proportion of patients after surgery, and the mean number of antihypertensive medications decreased by approximately one. In almost a third of the studies, over 75% of participants experienced hypertension remission. All articles aside from two reported a decrease in systolic BP, with about 40% reporting a decrease of ≥ 10 mm Hg.

The effects of the COVID-19 pandemic on patients with obesity undergoing bariatric care.

BACKGROUND: Patients with obesity are at increased risk of developing severe COVID-19. The pandemic has caused delays in preoperative preparation, progression, and completion of bariatric surgeries. OBJECTIVES: The aim of this study was to evaluate the impact of COVID-19 restrictions on bariatric surgery patients and assess their concern of COVID-19 as they continue the preoperative process. SETTING: Philadelphia, Pennsylvania METHODS: A questionnaire was administered to patients to assess the impact of COVID-19 on their weight loss goals, physical activity, and diet. Time points assessed were initial bariatric consultation (T1), as well as the beginning (T2), and the end (T3) of lockdown restrictions in the region. RESULTS: Seventy-four participants were invited and 50 completed the survey, for a response rate of 67.6%. The average age of participants was 44.1 years. Two-thirds of patients reported significant concern that COVID-19 would affect their weight loss goals. Patients reported significant improvements in their diet from T1 to T2 (P < .01). However, at T3, some patients returned to behaviors held at T1, with snacking behaviors significantly increasing between T2 and T3 (P < .01). Physical activity decreased in 60% of patients between T2 to T3. The vast majority (90%) wanted to have their surgery as soon as possible; 56% reported low levels of concern for COVID-19 infection. CONCLUSION: Bariatric patients were highly motivated to proceed with bariatric surgery despite the risks imposed by the pandemic.

A Provocative Molecular Link between Mammographic Density and BRCA1-loss associated TNBC.

Triple-negative breast cancer (TNBC) is a highly aggressive form of breast cancer that has a high mortality rate and disproportionately affects young African American (AA) women who carry mutations in the BRCA1 gene. Approximately 80% of breast cancers which develop in BRCA1-mutant carriers will have TNBC and the molecular mechanism facilitating tumor development is unclear. Our earlier work suggested Ubc9 to play a critical role in BRCA1 loss mediated TNBC cell migration and metastasis. Collagen is one of the major components of the stromal extracellular matrix (ECM) network that influences tissue density. Its re-organization act as a scaffold aiding cancer cells to migrate causing metastasis. Ubc9 is known to increase the production of collagen, a key component of fibroglandular breast tissue, as well as tumorigenesis. Our work is based on the hypothesis that loss of BRCA1 in women with high breast density causes abnormal Ubc9 levels which upregulates collagen, fibronectin and inhibits SIRT1, ß-catenin expression facilitating TNBC. We tested this hypothesis by studying the expression of total collagen, fibronectin, Ubc9, SIRT1, ß-catenin in BRCA1 mutant TNBC cells and tumor sample derived from patient with dense breasts using immunofluorescence, immunohistochemistry, and collagen assay. Our results suggest for the first time that mutation or loss of BRCA1 function in women with fibrocystic breasts can lead to over expression of Ubc9, induction of collagen and; fibronectin, inhibition of SIRT1 and nuclear accumulation of ß-catenin which could contribute to TNBC development. This network will aid not only in the identification of potential mechanism-based biomarkers that could detect disease early, but also enforce preventive measures that could reduce the risk for TNBC in women with high MD thus reducing the mortality associated with these cancers to achieve health equity.

Effect of dietary vitamin D and calcium on the growth of androgen-insensitive human prostate tumor in a murine model.

Vitamin D deficiency has been associated with increased risk of prostate cancer (PC) in epidemiologic and prospective studies. An association has also been made between high dietary calcium and increased PC risk. In this study, we evaluated the effect of dietary vitamin D and calcium on the growth of human androgen-insensitive prostate tumor in an athymic mouse model. We observed highest tumor growth in the normal calcium - vitamin D-deficient group, while tumor growth between the normal calcium - vitamin D-sufficient, high calcium - vitamin D-sufficient and high calcium - vitamin D-deficient diet-groups did not significantly differ but was significantly lower than that in the normal calcium - vitamin D-deficient group. Our results suggest an important role of dietary vitamin D as a preventive agent in androgen-insensitive PC.

A vitamin D receptor-alkylating derivative of 1α,25-dihydroxyvitamin D3 inhibits growth of human kidney cancer cells and suppresses tumor growth.

1,25-Dihydroxyvitamin D3 [1,25(OH)2D3] has shown strong promise as an antiproliferative agent in several malignancies, yet its therapeutic use has been limited by its toxicity leading to search for analogues with antitumor property and low toxicity. In this study, we evaluated the in vitro and in vivo properties of 1,25-dihydroxyvitamin D3-3-bromoacetate [1,25(OH)2D3-3-BE], an alkylating derivative of 1,25(OH)2D3, as a potential therapeutic agent for renal cancer. Dose response of 1,25(OH)2D3-3-BE in 2 kidney cancer cell lines was evaluated for its antiproliferative and apoptotic properties, and mechanisms were evaluated by Western blot and FACS analyses. Therapeutic potential of 1,25(OH)2D3-3-BE was assessed both by determining its stability in human serum and by evaluating its efficacy in a mouse xenograft model of human renal tumor. We observed that 1,25(OH)2D3-3-BE is significantly more potent than an equivalent concentration of 1,25(OH)2D3 in inhibiting growth of A498 and Caki 1 human kidney cancer cells. 1,25(OH)2D3-3-BE-mediated growth inhibition was promoted through inhibition of cell-cycle progression by downregulating cyclin A and induction of apoptosis by stimulating caspase activity. Moreover, 1,25(OH)2D3-3-BE strongly inhibited Akt phosphorylation and phosphorylation of its downstream target, caspase-9. 1,25(OH)2D3-3-BE seemed to be stable in human serum. In xenograft mouse model of human renal tumor, 1,25(OH)2D3-3-BE was more potent at reducing tumor size than 1,25(OH)2D3, which was accompanied by an increase in apopotosis and reduction of cyclin A staining in the tumors. These results suggest a translational potential of this compound as a therapeutic agent in renal cell carcinoma. Data from this study and extensive studies of vitamin D for the prevention of many malignancies support the potential of 1,25(OH)2D3-3-BE for preventing renal cancer and the development of relevant in vivo prevention models for assessing this potential, which do not exist at present.

Anti-growth effect of 1,25-dihydroxyvitamin D3-3-bromoacetate alone or in combination with 5-amino-imidazole-4-carboxamide-1-beta-4-ribofuranoside in pancreatic cancer cells.

1,25-Dihydroxyvitamin D(3)-3-bromoacetate (1,25(OH)(2)D(3)-3-BE) is a vitamin D receptor-alkylating derivative of 1,25(OH)(2)D(3). The strong dose-dependent antiproliferative and apoptotic effects of this compound in androgen-sensitive and androgen-insensitive prostate cancer cells have been reported. In this communication, it is reported that 1,25(OH)(2)D(3)-3-BE strongly inhibits the growth of several pancreatic cancer cell lines. This effect is further accentuated by combination with 5-amino-imidazole-4-carboxamide-1-beta-4-ribofuranoside (AICAR), an activator of AMP-activated protein kinase (AMPK)/acetyl-Co-enzyme A carboxylase (ACC) phosphorylation pathways and an inhibitor of Akt phosphorylation. It was observed that the anti-growth property of 1,25(OH)(2)D(3)-3-BE, either alone or in combination with AICAR resulted in the inhibition of Akt phosphorylation in BxPC-3 cells. In conclusion, 1,25(OH)(2)D(3)-3-BE displays a strong therapeutic potential, alone and in combination with AICAR, in pancreatic cancer.