tbuckley/cabot-search huggingface dataset:
Influence of concurrent diabetes mellitus on clinical progression and response to androgen deprivation therapy in patients with advanced prostate cancer.
Authors: Jeffrey Shevach, Emily Gallagher, Teena Kochukoshy, Victoria Gresia, Manpreet Brar, Matt D. Galsky, William K. Oh
Journal: Journal of Clinical Oncology (2015)

e16036 Background: To determine if a concurrent diagnosis of diabetes mellitus (DM) is associated with worse outcomes in advanced prostate cancer. The effect DM might have on the progression of advanced prostate cancer is not well studied. Methods: Data on 148 advanced prostate cancer patients (35 with concurrent DM) were collected from a Genitourinary Cancer Database at the Icahn School of Medicine at Mount Sinai to obtain diabetic status, data on treatment types and durations, and PSA values before, during and after treatment. Time to castration resistance following the onset of androgen deprivation therapy (ADT) and overall survival in those with and without DM were compared using univariate Cox regression analyses as the primary endpoints. Differences in PSA response to treatments were compared using chi-squared tests as secondary endpoints. Results: With a median follow-up of 29 months, the time to castration resistance did not differ significantly between patients with and without DM who underwent ADT. In a subset of patients who started ADT without radiographic evidence of metastases (N = 47), those with DM (N = 11) progressed to castration-resistant disease more quickly than those without DM in univariate Cox regression analysis (Hazard Ratio for progression with DM = 4.58; 95% CI: 1.92-10.94; p = 0.0006). In patients who underwent ADT, a higher percentage of those without DM responded with a decrease in PSA of at least 50% (p = 0.17), and a higher percentage of those without DM reached a nadir PSA < 0.2 ng/mL (p = 0.06). Overall survival did not differ based on diabetic status from the onset of ADT or from the onset of castration resistance. Median follow-up following castration resistance was 23 months. In patients who underwent a first-line therapy for castration-resistant prostate cancer, there was no observed difference in PSA response based on diabetic status. Conclusions: The findings in this study suggest that DM may have an effect on the progression of advanced prostate cancer, particularly in those without radiographic evidence of metastases. Further study in larger databases is necessary to fully elucidate the relationship between the two diseases.
Improving the quality of patient care through a collaborative maintenance of certification and next accreditation system project.
Authors: Hyun Kim, Theresa Maria Malatesta, Adam Dicker, Nicole Lynn Simone, Robert Benjamin Den, Voichita Bar Ad
Journal: Journal of Clinical Oncology (2015)

e17728 Background: The recent implementation of the Accreditation Council of Graduate Medical Education (ACGME) next accreditation system (NAS) for resident physicians, and the mandatory American Board of Medical Specialties (ABMS) maintenance of certification (MOC) for attending physicians, provide a unique opportunity for resident and attending physicians to work in collaboration to improve the quality of patient care, enhance the educational experience, and meet recertification requirements. Here we present a model for a collaborative NAS and MOC project between resident and attending physicians. Methods: Approval for project implementation was obtained from the American Board of Radiology (ABR) MOC group. Our practice quality improvement (PQI) project consisted of creating a policy on transition of care for Residents, a NAS requirement, which included a survey to assess the resident and attending perspective on resident sign-out, formal sign-out training and a post-training survey. One radiation oncology attending physician was designated as group leader and worked with a resident to organize meetings, coordinate data collection, analysis, and implement action items. Attending physicians who submitted this for MOC credit attended three group meetings at which minutes and attendance were recorded. Resident physicians presented the results of the project in a hospital quality improvement panel. Results: Six resident and nine attending physicians completed the surveys. Perception of the sign-out process improved by 20% after the formal training. A formal sign-out policy was implemented in our residency program. Three attendings and one resident received credit for the MOC PQI and ACGME quality improvement projects, respectively. Conclusions: This project shows the feasibility of a combined attending and resident physician effort to improve patient care and fulfill their respective ABR MOC PQI and ACGME NAS requirements. Attending and resident physicians can tailor collaborative projects to fulfill MOC and NAS requirements unique to their subspecialty.
Intractable Coronary Artery Disease in a Patient With Type 2 Diabetes Presenting With Triglyceride Deposit Cardiomyovasculopathy
Authors: Junji Kozawa, Masahiro Higashi, Iichiro Shimomura, Ken-ichi Hirano
Journal: Diabetes Care (2019)

The patient was a 51-year-old man who had been overweight since adolescence and was diagnosed with type 2 diabetes at age 26. He had been treated with a sulfonylurea, but his glycemic control was poor. When his medication was replaced with insulin injection at age 35, KITT, a marker of insulin sensitivity (1), was severely deteriorated to 0.87%, and resulting endogenous hyperinsulinemia was suspected from total daily urinary C-peptide excretion (242.8 μg). At that time, he was overweight by BMI (27.1 kg/m2). Lipid profiles showed mild hypertriglyceridemia with apolipoprotein E3/3 phenotype. His …
Logic-Gated ROR1 Chimeric Antigen Receptor Expression Rescues T Cell-Mediated Toxicity to Normal Tissues and Enables Selective Tumor Targeting
Authors: Shivani Srivastava, Alexander I. Salter, Denny Liggitt, Sushma Yechan-Gunja, Megha Sarvothama, Kirsten Cooper, Kimberly S. Smythe, Jarrod A. Dudakov, Robert H. Pierce, Christoph Rader, Stanley R. Riddell
Journal: Cancer Cell (2019)
Abstract MP26: Visceral Obesity and Systemic Inflammation Predict Sleep Disordered Breathing in Normal Weight, Never Obese Adolescents: A Longitudinal, Population-Based Study
Authors: Jacqueline M Danisi, Julio Fernandez-Mendoza, Fan He, Marjorie D Sawyer, Susan L Calhoun, Jason Liao, Duanping Liao, Alexandros N Vgontzas, Edward O Bixler
Journal: Circulation (2019)

Introduction: Although obesity is a known risk factor for sleep disordered breathing (SDB), a significant proportion of children with SDB are not obese or overweight as per body mass index percentile (BMI%) for age-and-sex. It is unknown whether premorbid or concurrent adiposity phenotypes are associated with SDB in normal weight youth. Hypothesis: We hypothesize that central obesity is a predictor of apnea/hypopnea index (AHI) in adolescents who have been otherwise normal weight since childhood. Methods: We analyzed data from the Penn State Child Cohort (N=421), a random population-based sample of 8.7 (1.7) year old children followed-up as 17.0 (2.3) year old adolescents. Of these, 242 subjects (49.2% female, 18.2% minority) were classified as persistently normal weight based on BMI%&lt;85 at both baseline and follow-up. Neck, hip and waist circumference (WC) were measured and “central obesity” was defined as a WC%≥85 for age-and-sex at baseline. During the follow-up exam, android and gynoid distribution and subcutaneous (SAT) and visceral (VAT) adipose tissue composition were assessed via DEXA scan, while inflammatory biomarkers were assayed from a fasting blood sample. The AHI was obtained from 9-hour, in-lab polysomnography at baseline and follow-up. Multivariable linear regression models examined the association between adiposity and inflammation with AHI at follow-up while adjusting for sex, race, adenotonsillectomy, age and AHI at baseline. Results: The average AHI at baseline was 0.7 (0.9) events/hour and 2.3 (6.3) events/hour at follow-up. Unadjusted analyses showed that WC (β=0.159) and central obesity (β=0.227) at baseline, but not BMI%, neck or hip circumference, and VAT (β=0.307), IL-6 (β=0.245), SAT (β=0.235), CRP (β=0.222), and android distribution (β=0.195) at follow-up were significantly (P&lt;0.05) associated with a higher follow-up AHI. Multivariable-adjusted analyses showed that VAT (β=0.299), IL-6 (β=0.191), central obesity (β=0.185) and CRP (β=0.163) were independently associated with a higher follow-up AHI. Conclusions: This is the first study to demonstrate that central obesity in childhood is a strong predictor of SDB in adolescence, even in individuals who have been persistently normal weight since childhood as per BMI% standards. These data support the clinical utility of simple measures of central obesity in childhood (i.e., WC) as early surrogate markers of increased risk of future development of SDB in the transition to adolescence. Furthermore, our study demonstrates that increased visceral adiposity and systemic inflammation are strong correlates of adolescent SDB, which supports the clinical utility of these biomarkers in predicting the cardiometabolic risk associated with adolescent SDB.
Real-world trends in first-line checkpoint inhibitor use (CPI) in advanced urothelial cell carcinoma (aUC).
Authors: Ravi Bharat Parikh, Matt D. Galsky, Shrujal S. Baxi, Blythe J.S. Adamson, Aaron Benjamin Cohen, Emily Feld, John Paul Christodouleas, Shimon Ben Boursi, Neal J. Meropol, Ronac Mamtani
Journal: Journal of Clinical Oncology (2019)

392 Background: Standard first-line treatment of aUC is cisplatin-based chemotherapy, with carboplatin-based chemotherapy or CPI reserved for cisplatin-ineligible individuals. However, given their favorable toxicity profile, there may be an indication drift of first-line CPI into cisplatin-eligible patients, despite no approved indication in this population. Methods: Using the Flatiron Health Database, a nationally representative electronic medical record-based dataset, we examined real-world prescribing patterns of first-line systemic therapies among 2090 patients with aUC diagnosed between the first quarter (q) of 2015 and 2018q1. Our analysis of cisplatin-eligible individuals excluded patients with pre-treatment (1) Eastern Cooperative Oncology Group performance status (ECOG PS) ≥ 2, (2) creatinine ≥ 1.5 mg/dL, or (3) diagnostic codes for chronic renal failure, congestive heart failure, hearing loss, or peripheral neuropathy. We used nonparametric tests of trend to describe first-line CPI and chemotherapy use over time. Results: Between 2015 and 2018, the quarterly proportion of patients who received first-line CPI increased from 1.4% to 43%, while the proportion who received platinum-based chemotherapy decreased from 89% to 56% (p trend &lt; 0.001) Similarly, among cisplatin-eligible patients (n = 1181), the proportion of first-line CPI users increased from 1.0% in 2015q4 to 42% in 2018q1 (p trend = 0.001), while the proportion of first-line cisplatin users fell from 53% in 2015q4 to 33% in 2018q1 (p trend = 0.018). First-line CPI initiators were older (median age 76 vs 71) and had worse performance status (PS ≥ 2 17.8% vs 11.4%) relative to platinum initiators (Table). Conclusions: Our analysis suggests a dramatic rise in first-line CPI use, even in patients who may be cisplatin-eligible, for whom first-line CPI is not evidence-based. [Table: see text]
Distinct genomic hallmarks exist between metastatic upper and lower tract urothelial carcinoma.
Authors: Brian Winters, Navonil De Sarkar, Sonali Arora, Hamid Bolouri, Funda Vakar-Lopez, MD, Heather H. Cheng, Evan Y. Yu, Lori Kollath, Petros Grivas, Lisa McFerrin, Robert B. Montgomery, Jonathan Wright, Hung-Ming Lam, Andrew Caleb Hsieh
Journal: Journal of Clinical Oncology (2019)

371 Background: Although the genomic landscape of LTUC is well studied, less is known about UTUC, including in the metastatic sites. We compared genomic features of metastatic UTUC and LTUC. Methods: We performed whole exome sequencing on 7 rapid autopsy patients with metastatic UC, with matched primary and metastatic tumor samples (N = 37). Single nucleotide variants (SNV) were identified using Mutect and Strelka. Focused analyses were performed on mutations with known significance in UC as well as mutations predicted to have functional impact using 11 mutation assessors. Genome scale copy number aberrations (CNA) were estimated using Sequenza (normalized for ploidy) to derive gene definition restricted copy number estimation outcomes. Multi-dimensional scaling (MDS) was used to visualize how copy number and mutation-derived genomic distances differed between LTUC and UTUC. Results: Three pts with UTUC (3 primary samples, 13 metastases) and four pts with LTUC (4 primary samples, 17 metastases) were examined. The majority of patients were male (5) and received cisplatin-based therapy (5). We found that SNV burden (mean mutation per megabase) was significantly higher in LTUC vs. UTUC overall (6.6 vs. 3.8, p = 0.001) and when stratified by primaries (6.1 vs. 2.9, p = 0.047); or metastases (6.7 vs. 4.1, p = 0.001). Mutational signature analysis revealed higher proportion of APOBEC signature in all LTUC vs. UTUC tumors. Both inter- and intra-individual genomic distances between primary and metastatic tissues were substantially larger in UTUC than LTUC, suggesting a wider spectrum of mutations at the level of individual nucleotides and chromosomal structure. Interestingly, Gene definition-restricted CNA analysis revealed MDM2 amplification exclusively in UTUC tumors which was associated with shallow p53 deletion. Conclusions: Metastatic UTUC appears to have a lower overall mutational burden but greater genomic variability compared to LTUC. Our relatively small dataset suggests that metastatic UTUC displays a greater spectrum of mutational divergence from LTUC which may partially explain differences in clinical behavior.
The PRESIDE trial: A randomized, double-blind, placebo-controlled phase III efficacy and safety study of continued enzalutamide plus docetaxel after disease progression on enzalutamide alone in patients with metastatic castration-resistant prostate cancer.
Authors: Simon Chowdhury, Richard Davidson, Alex Coppell, Hossein Mobasheri, Anny Stari, Robert Snijder, Cecil Treadwell, Axel S. Merseburger
Journal: Journal of Clinical Oncology (2015)

TPS5083 Background: Enzalutamide (ENZA) is an oral androgen receptor inhibitor approved in the US for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC) (US PI, 2014) and in the EU for the treatment of asymptomatic/mildly symptomatic men with mCRPC after failure of androgen deprivation therapy in whom chemotherapy is not yet clinically indicated, or those whose disease has progressed on or after doxetaxel (DTX) therapy (EU SmPC, 2014). The PRESIDE study (NCT02288247) will evaluate the efficacy and safety of continued ENZA treatment vs placebo (PBO) when starting docetaxel plus prednisolone (PRED) after disease progression on first-line ENZA in chemotherapy-naïve mCRPC patients. Methods: PRESIDE will consist of an open-label treatment period with ENZA (period 1), followed by a randomized double-blind treatment with continued ENZA or PBO in addition to DTX plus PRED (period 2). Eligibility criteria include confirmed prostate adenocarcinoma, metastatic disease, prostate-specific antigen (PSA) progression on androgen deprivation or surgical castration, Eastern Cooperative Oncology Group performance status 0–1, testosterone ≤ 50 ng/dL, and minimally symptomatic patients (Brief Pain Inventory Short Form, question 3, < 4 in the absence of opiate analgesia). In period 1, all patients will receive open-label ENZA 160 mg/day until radiographic progression and/or PSA progression with rapid PSA doubling time. In period 2, patients with confirmed disease progression on ENZA alone will be randomized to continue ENZA 160 mg/day or receive PBO. All patients will also receive therapy with DTX 75 mg/m2 every 3 weeks plus PRED 10 mg/day. The primary end point is radiographic progression-free survival. Secondary end points include PSA and pain progression, PSA and radiographic response, opiate use for cancer-related pain, skeletal related events and quality of life. Planned enrolment is 650 patients in 90 sites across Europe for period 1, with ≥ 137 patients in each randomized arm for period 2. Recruitment commenced in December 2014. Clinical trial information: NCT02288247.
Racial and Ethnic Disparities in Geographic Access to Trauma Care—A Multiple-Methods Study of US Urban Trauma Deserts
Authors: Lisa Marie Knowlton
Journal: JAMA Network Open (2019)

Elizabeth L. Tung, MD, MS; David A. Hampton, MD, MEng; Marynia Kolak, PhD, MS; Selwyn O. Rogers, MD, MPH; Joyce P. Yang, PhD; Monica E. Peek, MD, MPH, MS
Cancer-specific Twitter conversations among physicians in 2014.
Authors: Brian Bowers Reid, Kayla Nicole Rodriguez, Michael A. Thompson, Greg Dean Matthews
Journal: Journal of Clinical Oncology (2015)

e17500 Background: The use of social media in health care is growing. Small-scale analyses of the use of social media by physician communities have found that social media use by physicians can be a powerful educational tool for both professional and lay audiences. We wished to build off of our 2013 analysis of Twitter conversation by physicians on oncology-related topics to better understanding the phenomenon. Methods: Using a proprietary database of physicians on Twitter that matches individual Twitter accounts with their corresponding National Provider Identifier (NPI) and associated information (MDigitalLife, W2O Group), we examined all tweets from 17,738 validated U.S. physicians during the calendar year 2014 for overall mentions of cancer-related keywords as well as keywords related to the lung cancer, breast cancer, colon cancer, pancreatic cancer, prostate cancer, and melanoma. Results: The database search generated yielded 138,081 cancer-related tweets from 5,539 different U.S. physicians. The average number of oncology-related tweets per day by this cohort was 378, though great variation was seen. More than 1,000 tweets were recorded each day of the American Society for Clinical Oncology (ASCO) 2014 Annual Meeting (#ASCO14), as well as two days in October, during Breast Cancer Awareness Month. Tweets about breast cancer represented more than 19% of all cancer-related tweets, followed by lung cancer (9%) and prostate cancer (7%). A small number of physicians accounted for a large percentage of the Twitter activity, in qualitative agreement with a Zipf power law distribution. Conclusions: Twitter is a large and growing communication tool among doctors discussing oncology. The conversation, however, appears to be largely driven by a small group of "superusers" who are especially active during specific times of the year (e.g. medical congresses and awareness months). Future research should examine the role that physicians who frequently post on social media have on health-related conversations among both health professionals and the larger public.
Variation in Surgical Outcomes Across Networks of the Highest-Rated US Hospitals
Authors: Kyle H. Sheetz, Andrew M. Ibrahim, Hari Nathan, Justin B. Dimick
Journal: JAMA Surgery (2019)

Hospitals are rapidly consolidating into regional delivery networks. To our knowledge, whether these multihospital networks leverage their combined assets to improve quality and provide a uniform standard of care has not been explored.To evaluate the extent to which surgical outcomes varied across hospitals within the networks of the highest-rated US hospitals.This longitudinal analysis of 87 hospitals that participated in 1 of 16 networks that are affiliated with US News & World Report Honor Roll hospitals used data from Medicare beneficiaries who were undergoing colectomy, coronary artery bypass graft, or hip replacement between 2005 and 2014 to evaluate the variation in risk-adjusted surgical outcomes at Honor Roll and affiliated hospitals within and across networks. The data were analyzed between April 20, 2018, and June 25, 2018.Thirty-day postoperative complications, mortality, failure to rescue, and readmissions.Of 143 174 patients, 68 718 (48.0%) were men, 124 427 (86.9%) were white, and the mean (SD) age was 71.8 (9.9) years and 73.5 (9.1) years in Honor Roll and affiliated hospitals, respectively. Outcomes were not consistently better at Honor Roll hospitals compared with network affiliates. For example, Honor Roll hospitals had lower failure to rescue rates (13.3% vs 15.1%; odds ratio, 0.92; 95% CI, 0.86-0.98) but higher complication rates (22.1% vs 18.0%; odds ratio, 1.11; 95% CI, 1.03-1.19). Within networks, risk-adjusted outcomes varied widely across affiliated hospitals. The differences in failure to rescue varied by as little as 1.1-fold (range, 12.7%-14.3%) in some networks to as much as 4.9-fold (range, 7.6%-37.3%) in others. Similarly, complication rates varied by 1.1-fold (range, 21%-23%) to 4.3-fold (range, 6%-26%) across all networks.Surgical outcomes vary widely across hospitals affiliated with the US News & World Report Honor Roll hospitals. Public reporting mechanisms should provide patients with information on the quality of all network-affiliated hospitals. Networks should monitor variations in outcomes to characterize and improve the extent to which a uniform standard of care is being delivered.
Barriers to Use of Palliative Care and Advance Care Planning Discussions for Patients With End-Stage Liver Disease
Authors: Nneka N. Ufere, John Donlan, Lauren Waldman, Jules L. Dienstag, Lawrence S. Friedman, Kathleen E. Corey, Nikroo Hashemi, Peter Carolan, Alan C. Mullen, Michael Thiim, Irun Bhan, Ryan Nipp, Joseph A. Greer, Jennifer S. Temel, Raymond T. Chung, Areej El-Jawahri
Journal: Clinical Gastroenterology and Hepatology (2019)
Which Aspirin to Choose?—Reply
Authors: Brian Hallstrom
Journal: JAMA Surgery (2019)

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