Disparity Outcomes in Patients Undergoing Pancreas Surgery at an Urban Tertiary Care Center

INTRODUCTION: Previous studies have shown significant disparities in pancreas cancer outcomes in African American (AA) compared to non-AA patients. Pancreas surgery continues to be associated with significant morbidity, however, there is little reported data on pancreas surgical outcomes by race. We sought to evaluate how race would affect surgical outcomes in an urban tertiary care center for patients undergoing pancreas surgery. METHODS: A retrospective single-center analysis of patients undergoing pancreas surgery between January 2013 and September 2021 was performed. Patient demographics and post-surgical complications were collected and stratified by race. Area Deprivation Index (ADI) was used to determine patient socioeconomic status. Charlson Comorbidity Index (CCI) was calculated for comorbidities. Clavien-Dindo (CD) complications, as well as postoperative pancreatic fistula (POPF), delayed gastric emptying (DGE) and postpancreatectomy hemorrhage (PPH) were evaluated. Patient reoperation, readmission, and mortality in the 30- and 90- day period were collected and univariate and multivariate analyses were performed. RESULTS: Among 461 patients, 82% (N = 378) were nonAA and 18% (N = 83) were AA. Age and sex were found to be significantly different between the two groups, while ADI and CCI were not. Length of stay (LOS), POPF, PPH, PPH grade C and intra-abdominal abscess (IAA) were found to be significant on univariate analysis in the AA cohort. On multivariate analysis, LOS (OR 4.0; 95% CI 2.0-5.7; p \u3c 0.001), POPF (OR 0.6; 95% CI 0.4-1.0; p = 0.043), PPH (OR 0.5; 95% CI 0.2-0.9; p = 0.022), PPH grade C (OR 0.2; 95% CI 0.1-0.7; p = 0.017) and IAA (OR 0.4; 95% CI 0.2-0.9; p = 0.017) were still significantly higher in the AA cohort. CONCLUSIONS: AA patients undergoing pancreas surgery were noted to have a longer LOS, higher incidence of POPF, PPH and IAA compared to non-AA patients. However, no significant difference was seen in reoperation rates, major CD complications, or 30- and 90-day readmission. Elucidating patient selection, tumor biology, and preoperative treatment algorithms may shed additional insight on the differences in surgical outcomes in this particular patient cohort

Ritonavir blocks AKT signaling, activates apoptosis and inhibits migration and invasion in ovarian cancer cells

<p>Abstract</p> <p>Background</p> <p>Ovarian cancer is the leading cause of mortality from gynecological malignancies, often undetectable in early stages. The difficulty of detecting the disease in its early stages and the propensity of ovarian cancer cells to develop resistance to known chemotherapeutic treatments dramatically decreases the 5-year survival rate. Chemotherapy with paclitaxel after surgery increases median survival only by 2 to 3 years in stage IV disease highlights the need for more effective drugs. The human immunodeficiency virus (HIV) infection is characterized by increased risk of several solid tumors due to its inherent nature of weakening of immune system. Recent observations point to a lower incidence of some cancers in patients treated with protease inhibitor (PI) cocktail treatment known as HAART (Highly Active Anti-Retroviral Therapy).</p> <p>Results</p> <p>Here we show that ritonavir, a HIV protease inhibitor effectively induced cell cycle arrest and apoptosis in ovarian cell lines MDH-2774 and SKOV-3 in a dose dependent manner. Over a 3 day period with 20 μM ritonavir resulted in the cell death of over 60% for MDAH-2774 compared with 55% in case of SKOV-3 cell line. Ritonavir caused G1 cell cycle arrest of the ovarian cancer cells, mediated by down modulating levels of RB phosphorylation and depleting the G1 cyclins, cyclin-dependent kinase and increasing their inhibitors as determined by gene profile analysis. Interestingly, the treatment of ritonavir decreased the amount of phosphorylated AKT in a dose-dependent manner. Furthermore, inhibition of AKT by specific siRNA synergistically increased the efficacy of the ritonavir-induced apoptosis. These results indicate that the addition of the AKT inhibitor may increase the therapeutic efficacy of ritonavir.</p> <p>Conclusion</p> <p>Our results demonstrate a potential use of ritonavir for ovarian cancer with additive effects in conjunction with conventional chemotherapeutic regimens. Since ritonavir is clinically approved for human use for HIV, drug repositioning for ovarian cancer could accelerate the process of traditional drug development. This would reduce risks, limit the costs and decrease the time needed to bring the drug from bench to bedside.</p

Sulforaphane induces cell cycle arrest by protecting RB-E2F-1 complex in epithelial ovarian cancer cells

<p>Abstract</p> <p>Background</p> <p>Sulforaphane (SFN), an isothiocyanate phytochemical present predominantly in cruciferous vegetables such as brussels sprout and broccoli, is considered a promising chemo-preventive agent against cancer. In-vitro exposure to SFN appears to result in the induction of apoptosis and cell-cycle arrest in a variety of tumor types. However, the molecular mechanisms leading to the inhibition of cell cycle progression by SFN are poorly understood in epithelial ovarian cancer cells (EOC). The aim of this study is to understand the signaling mechanisms through which SFN influences the cell growth and proliferation in EOC.</p> <p>Results</p> <p>SFN at concentrations of 5 - 20 μM induced a dose-dependent suppression of growth in cell lines MDAH 2774 and SkOV-3 with an IC50 of ~8 μM after a 3 day exposure. Combination treatment with chemotherapeutic agent, paclitaxel, resulted in additive growth suppression. SFN at ~8 μM decreased growth by 40% and 20% on day 1 in MDAH 2774 and SkOV-3, respectively. Cells treated with cytotoxic concentrations of SFN have reduced cell migration and increased apoptotic cell death via an increase in Bak/Bcl-2 ratio and cleavage of procaspase-9 and poly (ADP-ribose)-polymerase (PARP). Gene expression profile analysis of cell cycle regulated proteins demonstrated increased levels of tumor suppressor retinoblastoma protein (RB) and decreased levels of E2F-1 transcription factor. SFN treatment resulted in G1 cell cycle arrest through down modulation of RB phosphorylation and by protecting the RB-E2F-1 complex.</p> <p>Conclusions</p> <p>SFN induces growth arrest and apoptosis in EOC cells. Inhibition of retinoblastoma (RB) phosphorylation and reduction in levels of free E2F-1 appear to play an important role in EOC growth arrest.</p

Prediction of cardiovascular outcomes with machine learning techniques: application to the Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL) study.

Background: Data derived from the Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL) study were analyzed in an effort to employ machine learning methods to predict the composite endpoint described in the original study. Methods: We identified 573 CORAL subjects with complete baseline data and the presence or absence of a composite endpoint for the study. These data were subjected to several models including a generalized linear (logistic-linear) model, support vector machine, decision tree, feed-forward neural network, and random forest, in an effort to attempt to predict the composite endpoint. The subjects were arbitrarily divided into training and testing subsets according to an 80%:20% distribution with various seeds. Prediction models were optimized within the CARET package of R. Results: The best performance of the different machine learning techniques was that of the random forest method which yielded a receiver operator curve (ROC) area of 68.1%±4.2% (mean ± SD) on the testing subset with ten different seed values used to separate training and testing subsets. The four most important variables in the random forest method were SBP, serum creatinine, glycosylated hemoglobin, and DBP. Each of these variables was also important in at least some of the other methods. The treatment assignment group was not consistently an important determinant in any of the models. Conclusion: Prediction of a composite cardiovascular outcome was difficult in the CORAL population, even when employing machine learning methods. Assignment to either the stenting or best medical therapy group did not serve as an important predictor of composite outcome. Clinical Trial Registration: ClinicalTrials.gov, NCT00081731

Large-Scale Gene-Centric Meta-Analysis across 39 Studies Identifies Type 2 Diabetes Loci

To identify genetic factors contributing to type 2 diabetes (T2D), we performed large-scale meta-analyses by using a custom similar to 50,000 SNP genotyping array (the ITMAT-Broad-CARe array) with similar to 2000 candidate genes in 39 multiethnic population-based studies, case-control studies, and clinical trials totaling 17,418 cases and 70,298 controls. First, meta-analysis of 25 studies comprising 14,073 cases and 57,489 controls of European descent confirmed eight established T2D loci at genome-wide significance. In silico follow-up analysis of putative association signals found in independent genome-wide association studies (including 8,130 cases and 38,987 controls) performed by the DIAGRAM consortium identified a T2D locus at genome-wide significance (GATAD2A/CILP2/PBX4; p = 5.7 x 10(-9)) and two loci exceeding study-wide significance (SREBF1, and TH/INS; p <2.4 x 10(-6)). Second, meta-analyses of 1,986 cases and 7,695 controls from eight African-American studies identified study-wide-significant (p = 2.4 x 10(-7)) variants in HMGA2 and replicated variants in TCF7L2 (p = 5.1 x 10(-15)). Third, conditional analysis revealed multiple known and novel independent signals within five T2D-associated genes in samples of European ancestry and within HMGA2 in African-American samples. Fourth, a multiethnic meta-analysis of all 39 studies identified T2D-associated variants in BCL2 (p = 2.1 x 10(-8)). Finally, a composite genetic score of SNPs from new and established T2D signals was significantly associated with increased risk of diabetes in African-American, Hispanic, and Asian populations. In summary, large-scale meta-analysis involving a dense gene-centric approach has uncovered additional loci and variants that contribute to T2D risk and suggests substantial overlap of T2D association signals across multiple ethnic groups

Utility of an Oral Exam During the Third Year Surgery Clerkship

Purpose: The National Board of Medical Examiners (NBME) Surgery Shelf Exam is often criticized as not accurately reflecting surgical knowledge. As a result, medical schools implement an oral exam to better assess students’ surgical knowledge. There is no data on the correlation between performance on the shelf and oral exams. We sought to assess the utility of the oral exam as a correlate and predictor of shelf exam performance.Methods:We reviewed medical student surgery clerkship performance reports between 2012 through 2018. Students’ clinical evaluation, clinical site, clerkship dates, and exam scores were noted. Bivariate and multivariate analysis was performed to assess for the relationship between the two exams.Results:We reviewed 1,160 performance reports over four clinical sites. The average oral exam score was 20.0 [4.8]. Students with a higher clinical evaluation had a significantly higher oral exam score (21.1 [4.5] vs 19.5 [4.8], p\u3c0.001). There was a significant difference in oral exam scores among the four different clinical sites (p\u3c0.01). There was no difference in oral exam scores among the different clerkship dates (p = 0.23). Oral exam scores and shelf exam scores were positively correlated (r = 0.32, p \u3c 0.001). In multivariate analysis, oral exam performance was an independent predictor for shelf exam performance (b = 0.48, 95% CI: 0.39 – 0.57, p\u3c0.001).Conclusion:Oral exam performance correlates with and predicts shelf exam performance. Low performance on an oral exam may allow educators to intervene prior to students taking the shelf exam.https://scholarlycommons.henryford.com/merf2019edu/1006/thumbnail.jp

Medical Student Perception of Morbidity and Mortality Conference

Introduction: Morbidity and mortality (M&M) conference has long been a vital educational tool for medical students, residents, and staff. It allows for learning and quality improvement through discussion of noteworthy cases. There is, however, a paucity of data on the how M&M is perceived by medical students, especially as a function of their interest, or lack thereof, in surgery. The objective of this study was to fill this void by measuring the perceptions of medical students regarding M&M conference.Methods: Medical students in a single medical school class voluntarily took part in a survey after their surgical rotation. The survey gauged students’ interest in surgery as a career and their overall rating of M&M. Students were specifically asked to recall if specific types of cases (resident at fault, medical error, non-therapeutic operation, pre- or post-operative mismanagement, multiple levels of error, and preventable or non-preventable error) were discussed. They were also asked to recall if tenets of surgical care (patient safety, quality improvement, root cause analysis, never events, time out/critical pause, complication vs preventable error) were discussed during M&M. Responses were tabulated and descriptive statistics were performed to summarize the data. Univariate analysis with a Chi-squared test, or Fisher’s Exact test when appropriate, was performed for association.Results:A total of 251 students were surveyed over four clinical sites. Of these students, 236 (94.0%) felt they understood the purpose of M&M, and 233 (88.8%) students felt they understood quality improvement in medicine and surgery. However, only 136 (54.2%) students reported M&M as a valuable learning experience. Discussion of the following was associated with a positive experience: examples of patient safety (93.4% vs 84.3%, p=0.02), preventable (91.2% vs 75.4%, p\u3c0.01) or non-preventable (76.5% vs 55.3%, p\u3c0.01) errors, quality improvement (95.6% vs 71.9%, p\u3c0.01), and root cause analysis (59.6% vs 40.4%, p\u3c0.01). Students were less likely to have a positive experience if they perceived M&M as a resident ‘grilling session’ (31.6% vs 51.4%, p\u3c0.01). There was no association between interest in a surgical subspecialty and perceiving M&M as a positive learning experience (48.5% vs 50.5%, p = 0.29). Conclusion: Overall, only a very small majority of medical students view M&M as a positive learning experience. Introducing structured concepts focusing on quality improvement may serve as a viable strategy to enhance the learning experience. Prospective studies incorporating such a curriculum are warranted.https://scholarlycommons.henryford.com/merf2019edu/1007/thumbnail.jp

Extremes of BMI are associated with a higher risk of pancreatic fistula following pancreaticoduodenectomy: an analysis using the NSQIP database

Background: Elevated body-mass index (BMI) is a well-described risk factor for postoperative complications. Specifically, the impact of BMI on pancreatic fistula rates following pancreaticoduodenectomy (PD) has been inconsistent. The aim of this study was to investigate pancreas-specific morbidity following pancreaticoduodenectomy for patients with extremes of BMI using a large national database. Methods: The National Surgical Quality Improvement Program database (NSQIP) was queried for patients undergoing PD between 2014–2016. BMI was classified according to the WHO classification as underweight (UW) (40). Univariate and multivariable logistic regression models were used to evaluate the effects of BMI on pancreas-specific morbidity. Stepwise selection was performed and adjustments were made for comorbidities, operative factors and pancreas-specific variables. Postoperative pancreatic fistula was classified into biochemical leak (BCL), Grade B and Grade C as per the International Study Group for Pancreatic Surgery (ISGPS) 2016 definition. P \u3c.05 was considered statistically significant. All analyses were done in SAS 9.4 (SAS Institute, Cary, NC). Results: 10,526 patients were included in the analysis (UW n=302, NW n=3,721, OW n = 3,678, OBI n = 1,779, OBII n=653, OBIII n=363) (Table 1). On univariate analysis elevated BMI (OB I-III) was associated with pancreatic fistula development compared to normal weight patients. This difference persisted on multivariable analysis for OBI and OBIII (OBI vs. NW OR = 1.55 (1.13–2.12); p = 0.007) (OBIII vs. NW, OR = 1.86 (1.08–3.21); p = 0.026). The difference did not persist for OBII (OBII vs. NW OR = 1.53 (0.96–2.24); p = 0.08). Similarly, patients with higher BMI (OBI-III) had a lower odds of a lower grade pancreatic leak compared to NW patients. This difference persisted on multivariate ordinal logistic regression analysis for OBI and OBIII but not for OBII (OB I vs. NW OR = 0.65 (0.48–0.89); p = 0.008) (OBII vs. NW OR = 0.68 (0.43–1.08); p = 0.099) (OBIII vs. NW OR = 0.53 (0.31–0.90); p = 0.02). On multivariable logistic regression there was no statistically significant difference for 30-day mortality, readmission rates, morbidity, delayed gastric emptying among the BMI groups. Conclusion: Elevated BMI increases risk of pancreatic fistula but not mortality or general perioperative morbidity following pancreaticoduodenectomy. Extreme obesity is an independent risk factor for pancreatic fistula and higher fistula grade compared to patients with normal weight. It might be worth considering the incorporation of BMI into the pancreatic fistula risk score. [Figure presented