tbuckley/cabot-search huggingface dataset:
Estrogen receptor beta (ERβ) gene polymorphisms as a predictor of overall survival in patients with gastric cancer (GC) from Japan and Los Angeles County (LAC).
Authors: Anish Parekh, Yu Sunakawa, Shu Cao, Satoshi Matsusaka, Dongyun Yang, Wu Zhang, Takeru Wakatsuki, Yan Ning, Stefan Stremitzer, Angela Mendez, Satoshi Okazaki, Rita Elkhoueiry, Syma Iqbal, Afsaneh Barzi, Mizutomo Azuma, Masahiko Watanabe, Wasaburo Koizumi, Anna H. Wu, Heinz-Josef Lenz
Journal: Journal of Clinical Oncology (2015)

4036 Background: Use of menopausal hormones has correlated with a lower risk of colon cancer in women. Prostate cancer patients (pts) treated with estrogen have a reduced risk of developing GC as a second primary. Several ERβ gene (ESR2) polymorphisms have been associated with colorectal cancer survival (Cancer Res 2013;73:767). To better understand the role of ERβ in relation to GC outcome, we tested whether ESR2 polymorphisms will be associated with overall survival (OS) in GC pts from 2 different regions. Methods: We analyzed genomic DNA extracted from blood or tumor tissues of 169 pts from Japan (64% men, stage IB-IV of AJCC-6th, median age 67, median follow-up 3.6 years, median survival 5.7 years) and 214 pts from LAC (68% men, stage 0-IV of AJCC-6th, median age 62, median follow-up 8.2 years, median survival 2.6 years), using PCR-based direct sequencing. ESR2 polymorphisms, which were shown to be of biological significance (rs2978381, rs3020443 and rs1271572), were analyzed for association with OS in both cohorts. Multivariate Cox proportional hazard regression was conducted to test the association after adjustment for age, sex, primary tumor site, stage and other covariates. Results: ESR2 rs1271572 and rs3020443 had uni- and multivariate associations with OS in the Japanese but not LAC cohort. Any C allele of ESR2 rs2978381 (T > C) was associated with longer OS than T/T genotype in the Japanese cohort (5-year survival 63 % vs 41 %, p= 0.021) but shorter OS in the LAC cohort (5-year survival 30 % vs 51 %, p= 0.049) although these findings did not remain significant in multivariate analysis. In analysis restricted to distal GC, the ESR2 rs1271572 (C > A) correlated with OS but the effect of A allele was in the opposite direction between the Japanese (n= 121, adjusted HR 2.19, p= 0.019) and LAC cohort (n= 116, unadjusted HR 0.62, p= 0.031). Conclusions: ESR2 polymorphisms have prognostic value in pts with GC. These data also suggest that ERβ pathway may play a key role in tumor progression of GC and its prognostic impact may differ depending on histopathologic, ethnic or epidemiologic differences. Further studies to evaluate the association among different races are warranted.
Physician-driven variation in non-recommended imaging for women with early stage breast cancer.
Authors: Allison Nicole Lipitz Snyderman, Camelia S. Sima, Elena B. Elkin, Coral L. Atoria, Christopher Anderson, Victoria Susana Blinder, Peter Bach
Journal: Journal of Clinical Oncology (2015)

6507 Background: Some women at low risk for metastasis receive imaging for staging of early breast cancer, despite ASCO Choosing Wisely recommendations and NCCN guidelines supporting the contrary. The objective of this study was to assess the extent to which the observed variation in use of imaging in this context reflects physician-driven practice. Methods: Retrospective analysis using population-based SEER-Medicare data to examine the likelihood that a woman would receive a non-recommended imaging test (i.e., CT scan, PET scan, or bone scan) if her physician’s last patient received one. The cohort included women ages 66 and over diagnosed with early stage breast cancer between 2000 and 2007, who had surgery within 6 months of diagnosis (n=66,149 women). We also assessed the extent of variation in imaging between physicians using a non-linear random-effects model. Results: Fourteen percent of our cohort received at least one imaging test between diagnosis and surgery. Over 3,800 physicians had at least two patients assigned, representing approximately 98% patients, and were included in the analysis. The likelihood that a woman would receive an imaging test was over three fold higher if her physician’s prior patient received an imaging test, adjusting for patient characteristics (adjusted odds ratios ranged by imaging test from 3.05 to 6.54) (Table). From the random effects models, a test of whether the estimated variance of the random effects is significantly different from zero provides indication of significant unexplained variation across physicians (p<0.0001 for all models). Conclusions: We observed a substantial physician-driven influence on imaging for women with early stage breast cancer. Our findings support intervening at the physician level, specifically targeting high users, to help reduce the use of these potentially harmful and costly services. Adjusted odds ratio [95% confidence interval] of patient receiving non-recommended imaging test if the physician’s prior patient received imaging test. Any imaging CT scan PET scan Bone scan Prior patient received imaging test 3.27 [3.09-3.45] 3.05 [2.83-3.29] 5.79 [4.63-7.24] 6.54 [6.11-7.01]
Abstract P032: Soluble CD14 Level is a Coronary Heart Disease Risk Factor in Younger-aged Black Adults of the Reasons for Geographical and Racial Differences in Stroke (REGARDS) Study
Authors: Nels C Olson, Insu Koh, Alex P Reiner, Suzanne E Judd, Marguerite R Irvin, George Howard, Neil A Zakai, Mary Cushman
Journal: Circulation (2019)

Introduction: CD14 plays an important role in the innate immune response and promotes inflammation. Soluble CD14 (sCD14) is produced during an acute phase response and following cleavage from immune cell surfaces upon activation. Higher sCD14 may be a risk factor for cardiovascular disease, however prospective studies evaluating sCD14 with incident coronary heart disease (CHD) events are limited. We examined the association of sCD14 levels with incident CHD in black and white REGARDS participants. Methods: REGARDS enrolled 30,239 participants from across the contiguous U.S. in 2003-07. The cohort was 55% female and 41% black by design. In a nested case-cohort study, sCD14 levels were measured by ELISA in 612 participants with incident CHD and 856 in a cohort random sample; all were free of CHD at baseline. Using Cox proportional hazards models we calculated the hazards ratio (HR) of CHD for increasing sCD14, and studied interactions of sCD14 with age, sex, or race. Results: In models adjusted for Framingham risk factors, interaction terms for sCD14-by-race (p-interaction=0.02) and sCD14-by-age (p-interaction=0.02) were statistically significant but not for sCD14-by-sex (p=0.21). Stratified by race and age, each 1-SD higher sCD14 (442 ng/mL) was associated with an increased CHD risk in blacks but not whites (Table). Relationships were stronger in younger than older black participants. SCD14 was not significantly associated with CHD risk among white participants, but there was a trend for stronger relationships at younger ages. Conclusions: Higher sCD14 is associated with risk of CHD in blacks with greater risk at younger ages. These findings suggest sCD14 may be an important CHD risk factor among younger black adults.
Safety of high dose rate prostate brachytherapy in patients with high baseline international prostate symptom scores.
Authors: Tiffany Morgan, Peter John Rossi, Patrick Cutrell, Chao Zhang, Robert H. Press, Sara Rahnema, Martin George Sanda, John Pattaras, Cara B. Cimmino, Ashesh B. Jani, Pretesh R. Patel
Journal: Journal of Clinical Oncology (2019)

25 Background: Though a high baseline international prostate symptom score (IPSS) is considered a relative contraindication for low dose rate (LDR) brachytherapy, use of high dose rate (HDR) technique has several theoretical advantages including increased ability to sculpt dose and spare normal tissue via post-implant dosimetry. We report our institutional QOL data for those undergoing HDR with an IPSS score ≥15 compared to those with an IPSS score &lt;15. Methods: The charts of 95 patients with localized adenocarcinoma of the prostate treated with HDR as monotherapy or as a boost after external beam radiation (EBRT) at a single institution between 2012 and 2015 were reviewed. All patients completed the IPSS and Expanded Prostate Index for Prostate Cancer–Clinical Practice (EPIC-CP) quality of life assessments prior to treatment and at least one follow-up survey. Linear mixed models were performed to test for significant changes and differences in each outcome over time. Results: Median follow-up in the IPSS &lt;15 group (n=79) was 23 months and 16 months in the IPSS ≥15 group (n=16). Median IPSS score was 6 (range 0-14) and 19 (range 15-30), respectively. A majority of patients in both groups were diagnosed with National Comprehensive Cancer Network (NCCN) intermediate risk disease. Median prostate volume was 45.4cc in the IPSS ≥15 group and 46.3cc in the IPSS &lt;15 group (p=0.901). IPSS, incontinence, and urinary irritation/obstruction scores were significantly higher in the IPSS ≥15 group compared to the IPSS &lt;15 group at baseline (all p≤0.05). By the &gt;24 months time point, these scores had decreased below baseline and were not significantly different from those with a baseline IPSS score &lt;15 (all p&gt;0.1). 12.5% in the IPSS ≥15 group developed a new grade 2 GU toxicity requiring an alpha-blocker compared to 26.5% in the IPSS &lt;15 group (p=0.34). No patients required emergency placement of a foley catheter within 30 days of treatment. Conclusions: Given the low rates of GU toxicity, including a low risk of urinary obstruction requiring catheterization after HDR brachytherapy for those with a baseline IPSS score ≥15, this technique appears appropriate even for those with high baseline urinary symptoms.
Impact of surgical approach on perioperative complications for endometrial cancer staging.
Authors: Michael Stephen Guy, Jeanelle Sheeder, Kian Behbakht, Saketh Guntupalli
Journal: Journal of Clinical Oncology (2015)

e16507 Background: To identify predictors of reduced complications and discharge to home in patients being surgically staged for endometrial cancer. Methods: Patients were identified who were surgically treated for endometrial cancer at facilities that offered robotic and open approaches from the National Inpatient Sample from 2008-2010. Complications included intraoperative, perioperative medical/surgical complications and death. Comorbidity scores were calculated using the Charlson Comorbidity Index (CCI). T-tests and χ2 were used to compare groups. Multivariable logistic regression models adjusted for confounding variables. Results: A total of 9,674 were included (robotic, n = 2,803; laparotomy, n = 6,871). Patients undergoing robotic surgery were older (63 vs 62 years, p = 0.04) more likely to be white (83% vs 76%, p < 0.01) had lower CCI (2.4 vs 2.6, p < 0.01) and rates of obesity (28% vs 31%, p < 0.01). The rate of lymph node dissection between groups was similar (76% vs 76%, p = 0.94). There were no differences in intraoperative complications, except ureteral injuries in the robotic group were lower (0.4% vs 1.4%, p < 0.001). Rates of any perioperative surgical (7% vs 19%, p < 0.001) and medical (9% vs 21%, p < 0.001) complications were lower in the robotics group. Robotics patients were more likely to be discharged home without assistance (93% vs 79%, p < 0.001). In multivariable analysis, white race (aOR 1.4; 95% CI 1.2-1.6), non-metastatic disease (aOR 2.2; 95% CI 1.2-4.0) and a robotic approach (aOR 2.6; 95% CI 2.3-2.9) were the only predictors of having no complication and being discharged to home without assistance. Increasing age (aOR 0.96; 95% CI 0.96-0.97) obesity (aOR 0.8; 95% CI 0.7-0.9) and CCI (aOR 0.8; 95% CI 0.8-0.9) were inversely related to having no complication and being discharged home without assistance. Conclusions: After adjusting for the effect of age, race, obesity, comorbidity, presence of metastatic disease, a robotic approach was the only modifiable variable that was independently associated with patients having no complication and being discharged to home. The use of robotics for endometrial cancer staging appears to be advantageous using current selection criteria used by surgeons in the United States.
Transthyretin Stabilization by AG10 in Symptomatic Transthyretin Amyloid Cardiomyopathy
Authors: Daniel P. Judge, Stephen B. Heitner, Rodney H. Falk, Mathew S. Maurer, Sanjiv J. Shah, Ronald M. Witteles, Martha Grogan, Van N. Selby, Daniel Jacoby, Mazen Hanna, Jose Nativi-Nicolau, Jignesh Patel, Satish Rao, Uma Sinha, Cameron W. Turtle, Jonathan C. Fox
Journal: Journal of the American College of Cardiology (2019)

Transthyretin (TTR) amyloidosis is an underdiagnosed disease caused by destabilization of TTR due to pathogenic mutations or aging. Both pathogenic and protective mutations illuminate mechanisms of disease and potential interventions. AG10 is a selective, oral TTR stabilizer under development for transthyretin amyloidosis cardiomyopathy (ATTR-CM) that mimics a protective TTR mutation.This randomized, double-blind, placebo-controlled study evaluated safety, tolerability, pharmacokinetics, and pharmacodynamics of AG10 in ATTR-CM patients with symptomatic, chronic heart failure.ATTR-CM, New York Heart Association functional class II to III subjects (n = 49, mutant or wild-type) were randomized 1:1:1 to AG10 400 mg, AG10 800 mg, or placebo twice daily for 28 days. Safety and tolerability were assessed by clinical and laboratory criteria. AG10 plasma levels were measured. TTR stability was assessed by changes in serum TTR, and 2 established ex vivo assays (fluorescent probe exclusion and Western blot).AG10 treatment was well-tolerated, achieved target plasma concentrations and demonstrated near-complete stabilization of TTR. TTR stabilization was more complete and less variable at the higher dose with stabilization by fluorescent probe exclusion of 92 ± 10% (mean ± SD) at trough and 96 ± 9% at peak (both p < 10-12 vs. placebo). Average serum TTR increased by 36 ± 21% and 51 ± 38% at 400 and 800 mg, respectively (both p < 0.0001 vs. placebo). Baseline serum TTR in treated subjects was below normal in 80% of mutant and 33% of wild-type subjects. AG10 treatment restored serum TTR to the normal range in all subjects.AG10 has the potential to be a safe and effective treatment for patients with ATTR-CM. A phase 3 trial is ongoing. (Study of AG10 in Amyloid Cardiomyopathy; NCT03458130).
Phenotyping From Polysomnography Predicts Obstructive Sleep Apnea Responses To Supplemental Oxygen Therapy
Authors: S. A. Sands, B. A. Edwards, P. I. Terri, J. P. Butlerl, R. L. Owens, L. Taranto Montemurro, A. Azarbarzinl, M. Marques, C. De Meloi, D. P. White, A. Malhotra, A. Wellman
Journal: American Journal of Respiratory and Critical Care Medicine (2017)
Use of ribaxamase (SYN-004), a β-lactamase, to prevent Clostridium difficile infection in β-lactam-treated patients: a double-blind, phase 2b, randomised placebo-controlled trial
Authors: John F Kokai-Kun, Tracey Roberts, Olivia Coughlin, Chenxiong Le, Heidi Whalen, Ralph Stevenson, Vincent J Wacher, Joseph Sliman
Journal: The Lancet Infectious Diseases (2019)
Outbreaks of Escherichia coli O157:H7 Infection and Cryptosporidiosis Associated With Drinking Unpasteurized Apple Cider—Connecticut and New York, October 1996
Journal: JAMA (1997)

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Analysis of a large single center cohort demonstrates poor prognosis of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) in HIV infected patients (pts).
Authors: Justin D. Kaner, Amer Assal, Ashwin Sridharan, Rahul Polineni, Aditi Shastri, Harold Elias, Swati Goel, Murali Janakiram, Ira Braunschweig, Amit Verma
Journal: Journal of Clinical Oncology (2015)

e18077 Background: Even though HIV is associated with worse prognosis in many malignancies, the clinical course of MDS and AML in HIV+ pts has not been well studied. Determining the clinical presentation and outcomes of MDS and AML in these pts would be important for future diagnostic strategies, as anemia and other cytopenias are commonly seen in HIV+ pts. Methods: Unique data mining software was used to identify cases of MDS or AML in adult pts who were also HIV+ at Albert Einstein/Montefiore Medical Center between 1/1/2003 and 1/1/2015. Using Chi-Square and paired t-tests, characteristics of the HIV+ MDS pts were compared to 135 HIV- MDS pts from the same institution diagnosed between 1997-2011. The same statistical anaylsis was applied to HIV+ AML pts compared to known historical data. Results: 8 MDS and 9 AML pts who were HIV+ were identified. Average follow up was 404 days. Mean CD4 count was 307 cells/mm3, with only 4 pts < 200 cells/mm3. Median time to MDS or AML diagnosis from date of HIV diagnosis was 15.7 and 13.7 years (yrs) respectively. All pts were receiving anti-retroviral therapy at the time of MDS or AML diagnosis. HIV+ MDS pts presented at a younger age (59.5 vs 70.6 yrs, p = 0.002) and also had significantly higher risk (Int-2/High) disease by IPSS (85.7% vs 17.8%, p = 0.0003). Cytogenetic abnormalities were found in 5/6 (83.3%) evaluable HIV+ MDS pts, with monosomy 7 being common (67%). 4 (50%) of the HIV+ MDS pts progressed to AML, with a median time to progression of 10 months (mo). HIV+ MDS pts had poor median overall survival (OS) compared to controls (8.6 vs 58.2 mo, p = 0.001). HIV+ AML pts also presented at a younger age compared with known historical data (56 vs 69 yrs, p = 0.002). Median OS in HIV+ AML pts was 9.5 mo. Conclusions: Analysis of the largest single center cohort of HIV+ MDS and AML pts, demonstrated that these individuals present at a significantly younger age and with higher risk disease than their HIV- counterparts. In particular, HIV positivity in MDS pts portended a significantly worse overall survival. This suggests the need to aggresively search for MDS in HIV+ pts with unexplained cytopenias.
Mesothelin is a target of chimeric antigen receptor T cells for treating gastric cancer
Authors: Jiang Lv, Ruocong Zhao, Di Wu, Diwei Zheng, Zhiping Wu, Jingxuan Shi, Xinru Wei, Qiting Wu, Youguo Long, Simiao Lin, Suna Wang, Zhi Wang, Yang Li, Yantao Chen, Qing He, Suimin Chen, Huihui Yao, Zixia Liu, Zhaoyang Tang, Yao Yao, Duanqing Pei, Pentao Liu, Xuchao Zhang, Zhenfeng Zhang, Shuzhong Cui, Ren Chen, Peng Li
Journal: Journal of Hematology & Oncology (2019)

Gastric cancer (GC) is a common cancer in Asia and currently lacks a targeted therapy approach. Mesothelin (MSLN) has been reported to be expressed in GC tissue and could be targeted by chimeric antigen receptor (CAR) T cells. Mesothelin targeting CAR-T has been reported in mesothelioma, lung cancer, breast cancer, and pancreas cancer. However, the feasibility of using anti-MSLN CAR T cells to treat GC remains to be studied. We verified MSLN expression in primary human GC tissues and GC cell lines and then redirected T cells with a CAR containing the MSLN scFv (single-chain variable fragment), CD3ζ, CD28, and DAP10 intracellular signaling domain (M28z10) to target MSLN. We evaluated the function of these CAR T cells in vitro in terms of cytotoxicity, cytokine secretion, and surface phenotype changes when they encountered MSLN+ GC cells. We also established four different xenograft GC mouse models to assess in vivo antitumor activity. M28z10 T cells exhibited strong cytotoxicity and cytokine-secreting ability against GC cells in vitro. In addition, cell surface phenotyping suggested significant activation of M28z10 T cells upon target cell stimulation. M28z10 T cells induced GC regression in different xenograft mouse models and prolonged the survival of these mice compared with GFP-transduced T cells in the intraperitoneal and pulmonary metastatic GC models. Importantly, peritumoral delivery strategy can lead to improved CAR-T cells infiltration into tumor tissue and significantly suppress the growth of GC in a subcutaneous GC model. These results demonstrate that M28z10 T cells possess strong antitumor activity and represent a promising therapeutic approach to GC.
Nonmelanoma Skin Cancer Frequency and Risk Factors in Australian Heart and Lung Transplant Recipients
Authors: Nicholas De Rosa, Vanessa L. Paddon, Zhixin Liu, Allan R. Glanville, Kurosh Parsi
Journal: JAMA Dermatology (2019)

There is limited research examining the incidence of nonmelanoma skin cancer (NMSC) in heart and lung transplant recipients in Australia.To determine the frequency of and risk factors for NMSC in a cohort of Australian heart and lung transplant recipients.A retrospective cohort study was conducted at an Australian tertiary center where heart and lung transplants are performed between March 21 and December 14, 2016. A consecutive sample of 94 patients who underwent heart and/or lung transplant presenting for outpatient dermatologic review were evaluated. Data analysis was conducted between April 18 and October 30, 2017.Risk factors examined for association with posttransplantation NMSC included age at the time of transplantation, sex, skin phenotype, UV radiation exposure, history of allograft rejection, history of smoking, history of skin cancer prior to transplant, and transplant type.The primary outcome measure was the occurrence of posttransplantation NMSC. The probabilities of developing NMSC in general, and squamous cell carcinoma and basal cell carcinoma specifically, were separately summarized based on Kaplan-Meier analysis. Association of risk factors with development of NMSC was examined using univariable and multivariable Cox proportional hazards regression analysis.Of the 94 study participants, 58 (62%) were men; median age at transplantation was 51.9 years (range, 15.1-69.7 years). There were 801 posttransplantation skin cancers in 57 (61%) of the patients who underwent heart and/or lung transplant. The probabilities for NMSC were 41% (95% CI, 31%-53%) at 5 years and 67% (95% CI, 55%-78%) at 10 years; for basal cell carcinoma, 27% (95% CI, 18%-38%) at 5 years and 53% (95% CI, 40%-67%) at 10 years; and for squamous cell carcinoma, 33% (95% CI, 24%-45%) at 5 years and 62% (95% CI, 50%-74%) at 10 years. On multivariable analysis, older age at transplantation was associated with the development of NMSC (hazard ratio [HR], 1.07/1 year; 95% CI, 1.04-1.10; P < .001) and history of pretransplant skin cancer was associated with development of basal cell carcinoma (HR, 4.56; 95% CI, 1.67-12.42; P = .003). A Fitzpatrick skin type III to VI was associated with a decreased risk of NMSC (HR, 0.42; 95% CI, 0.24-0.74; P = .003). Sex, transplanted organ, UV radiation exposure, and history of allograft rejection were not associated with an increased risk of skin cancer.In this study of Australian heart and lung transplant recipients, there was a probable high frequency of NMSC. Routine dermatologic surveillance at frequent intervals is advised for similar populations.