tbuckley/cabot-search huggingface dataset:
The change in the status of MGMT methylation and IDH mutation in initial and recurrent glial tumors and its relation with prognosis.
Authors: Basak Oyan, Mehmet Akif Ozturk, Ferda Ozkan, Orhan Onder Eren, Ozlem Sonmez
Journal: Journal of Clinical Oncology (2015)

e13058 Background: Both 06- methylguanine DNA methyltransferase (MGMT) promoter methylation status and isocitrate dehydrogenase (IDH) gene mutation are known to affect prognosis in gliomas. The aims of this study are to determine whether MGMT methylation status and IDH mutation status changes during progression and to demonstrate any possible effect of this change on survival. Methods: 52 patients with relapsed/progressed glial tumors were screened in this retrospective cross-sectional study and 44 of them were included as they had pathology slides suitable for pathological evaluation. MGMT methylation status and IDH mutation status was evaluated by an expert pathologist using immunohistochemical staining. Results: At initial diagnosis, 36% of the patients had grade 1-2 glial tumors, %14 had grade 3 glial tumor and %50 had glioblastoma. MGMT was methylated in 14 of 44 patients (31.8%) at initial diagnosis. In 6 of 14 (42.9%) patients with methylated MGMT, conversion to unmethylated status was observed, and in 6 of 30 (20%) patients with unmethylated MGMT, conversion to methylated status was observed at relapse/progression. Median overall survival (OS) was 29 vs. 52 months in patients with methylated and unmethylated MGMT at initial diagnosis, respectively. Alteration in MGMT methylation status at relapse/progression did not cause a significant difference in OS both in patients with glioblastoma and those with grade 1-3 glial tumors. IDH1 was found to be mutated in 12 of 44 (27.3%) patients at initial diagnosis. One of these patients (8.3%) converted to IDH1-unmutated state, while 5 of 32 (15.6%) IDH non-mutant patients were found to be IDH mutant at relapse/progression. Median OS was 77 vs. 33 months (P = 0.033) in patients with IDH1 mutated and non-mutated status at initial diagnosis, respectively. Conclusions: MGMT methylation and IDH1 mutation status did not change significantly at progression in glial tumors. In contrast to literature, MGMT methylation status at initial diagnosis was not prognostic for OS. However, IDH mutated patients had longer OS than non-mutated patients. Alteration in MGMT methylation status at relapse/progression did not cause a significant difference in OS.
Abstract P209: Trends in Presenting Symptoms Among Acute Myocardial Infarction Patients in Community Surveillance: the Atherosclerosis Risk in Communities Study
Authors: Bailey M DeBarmore, Jessica K Zègre-Hemsey, Anna M Kucharska-Newton, Wayne D Rosamond
Journal: Circulation (2019)

Introduction: Recent research shows changing incidence rates of AMI by subtype (ST segment elevation [STEMI] and non-ST segment elevation [NSTEMI]), anatomical location, and severity. However, trends in AMI symptom presentation are less well examined. Not all AMI patients present with classic chest pain of cardiac origin. Presentation without cardiac chest pain has been associated with delayed hospital arrival, lower likelihood of receiving medical therapies and cardiac procedures, and higher mortality, as well as female sex, black race/ethnicity, and diabetes. Objective: We examined trends in symptom presentation in subsets of STEMI and NSTEMI by sex and race in the community surveillance of the ARIC Study from 2005 to 2014. Methods: Poisson regression was used to estimate sex- and race-specific event rates for AMI with and without classic chest pain of cardiac origin stratified by NSTEMI and STEMI. Events were defined as definite or probable MI with an assigned NSTEMI or STEMI subtype. Event rates were age-standardized to the US 2010 Census population. We examined average annual percent change in event rates over time, and compared comorbidities, in-hospital complications, and 28-day case-fatality of CHD death by symptom presentation, sex, and race, evaluating heterogeneity between sex and race via interaction terms. All analyses were weighted using ARIC sampling fractions. Results: Between 2005 and 2014, we observed 12,184 AMI events without classic chest pain and 39,512 events with classic chest pain. Events without chest pain were more often NSTEMI vs. STEMI (22% vs. 13%). The decline in event rates over time was similar among NSTEMI patients regardless of presentation symptoms; however, this decline was greater among STEMI patients without classic cardiac pain (-8.03, 95% CI: -10.12, -5.89) than among STEMI patients presenting with classic cardiac pain (-3.02, 95% CI: -4.83, -1.18). The average annual percent decline in event rates differed by race for STEMI but not NSTEMI. Presentation without classic cardiac chest pain was associated with comorbidities such as diabetes, as well as in-hospital complications in both NSTEMI and STEMI patients. Twenty-eight-day case fatality was greater among STEMI patients presenting without classic cardiac chest pain (9.4%, 95% CI: 5.8, 12.9) compared to those with classic cardiac chest pain (4.8%, 95% CI: 3.7, 5.9). Conclusion: AMI without classic chest pain comprised a larger percent of NSTEMI than STEMI events, and while event rates declined over 2005 to 2014, AMI without classic cardiac chest pain was associated with greater 28-day case fatality and in-hospital complications. Future research should explore care pathways and other reasons why these outcomes may differ by cardiac pain presentation.
Identification of tropomyosin kinase receptor (TRK) mutations in cancer.
Authors: Nisha Nanda, Tim Fennell, Jennifer A. Low
Journal: Journal of Clinical Oncology (2015)

1553 Background: TRK A, B and C, (encoded by NTRK1, NTRK2, and NTRK3 genes, respectively) and their neurotrophin ligands regulate growth, differentiation and survival of neurons. Chromosomal rearrangements resulting in kinase fusions have been described across the NTRK gene family, and may contribute to tumorigenesis in diverse clinical settings. We searched for potentially activating mutations in the NTRK gene family by applying biologically driven ranking criteria to an anonymized next-generation sequencing dataset, sourced from Foundation Medicine (FMI) and Compendia BioSciences (Compendia). Methods: Approximately 10,000 patient samples were analyzed for mutations in NTRK1, NTRK2 or NTRK3. Mutation data in other known cancer-related genes were also captured for these tumors. Data were reconciled data across the disparate sources by mapping mutations to the canonical transcript for each gene where possible, or to a representative non-canonical transcript when the mutation occurred in a region not contained within the canonical transcript. Mutations were clustered together based on sequence proximity. Mutation groups were ranked by likelihood of oncogenic-activating potential using six biologically-driven component scores. Results: 732 distinct mutation clusters were identified across > 20 tumors. NTRK1, NTRK2 and NTRK3 represented 33%, 30% and 37%, respectively, of these mutation clusters. A disproportionate number of the most promising mutation clusters were in NTRK3: 59% of the top 5%, 58% of the top 10%, and 46% of the top 25%. In addition, the top 3 mutation clusters were in the NTRK3 kinase domain, and were observed in head and neck, lung, upper gastrointestinal, melanoma and colon cancers. Conclusions: This heuristic identified mutations in the NTRK family, especially in NTRK3, that hold promise as oncogenic activating mutations. The highest ranked mutations deserve further study, as they are clonally present in the kinase domain, exist in the absence of other known oncogenic drivers, and are infrequent in germline databases.
Novel score to predict outcome in resected pancreatic neuroendocrine tumors (pNET).
Authors: Antonio Viudez, Daniel A. Laheru, Alejandro Stark, Nilofer Saba Azad, Christopher Lee Wolfgang, Stephen Baylin, James Gordon Herman, Zahra Maleki, Ana De Jesus-Acosta
Journal: Journal of Clinical Oncology (2015)

4093 Background: MGMT expression can predict response to temozolomide-based treatment. In pNET PHLDA-3 silencing is a common event while the expression of NDRG-1 and its functional role is unknown. We conducted a retrospective review of immunohistochemistry (IHC) expression of MGMT, NDRG-1 and PHLDA-3 in pNET and investigated their potential role as prognostic biomarkers. Methods: IHC nuclear staining for MGMT and PHLDA-3 was scored as 0, 1-5%, 6-50% and ≥ 51%. For NDRG-1, we used a cytoplasmic score from 0 to 3 based on staining intensity. Based on the long-rank test result between 2 clusters for each IHC staining, we designed an IHC score (IHC-S, score from 0 to 3). Finally a Global Score (GS) was developed with those variables that showed most significant differences in the univariate analysis (IHC-S and margin). Results: 92 samples from patients (pts) with resected pNET and follow-up > 24 moths were analyzed. Median follow-up was 55.5 months (mo). Pts had a median age of 56.5 y (16-88) and R0 resection occurred in 84.8%. Median DFS was 77 mo while median OS has not been reached yet. Significant statistical differences were observed in DFS based on surgical margin status (R0: 118 m vs R1: 34 m; p = .005), ypN0 vs ypN1 (p = .004) and ki67 < 2% ( < 2% vs 2-20% p = .015). DFS was significantly poorer in pts without any expression of MGMT (p = 0.045), in pts with low-expression of NDRG-1 (0 or 1, p = 0.03), and in pts with high-expression of PHLDA-3 ( ≥ 51%, p = 0.01). Significant differences were observed between pts with IHC-S = 0 vs IHC-S = 1 (p = 0.009), IHC-S = 2 (p = 0.012) or IHC-S = 3 (p = 0.0001). Pts with IHC-S = 0 never recurred while up to 70% of pts with IHC-S = 3 progressed during follow up. Using the Cox proportional hazards regression, GS was found as independent prognosis factor for DFS (HR: 5.043; 95%CI: 1.278-19.901). Conclusions: Our results suggest the potential use of MGMT, NDRG-1 and PHLDA-3 IHC expression as predictor of outcome in pNET. Our Global Score may be able to discriminate between pts that will be cured after surgery from those with high risk of relapse.
Tumor Mutation Load and Frequently Mutated Genes in Gastric Cancer—In Reply
Authors: Xiangchun Li, Wei Zhang, Kexin Chen
Journal: JAMA Oncology (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
Same-Day Discharge After Percutaneous Coronary Intervention—An Elusive Bargain—Reply
Authors: Amit P. Amin, Hemant Kulkarni, John A. Spertus
Journal: JAMA Cardiology (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Cardiology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Cardiology journal
Abstract 15350: Exercise Training With and Without Ranolazine in Chronic Stable Angina Patients: Effects on Peak Oxygen Consumption, Daily Physical Activity and Quality of Life: A Randomized, Placebo-Controlled, Double-Blind Pilot Study
Authors: Leslie H Willis, Cris A Slentz, Johanna L Johnson, Leslie S Kelly, Karen P Craig, Andrew L Hoselton, William E Kraus
Journal: Circulation (2017)

Introduction: An estimated seven million American adults live with coronary artery disease and chronic angina. Many continue to experience angina despite revascularization and antianginal medicatio...
Real-world outcomes of genetic testing in a GU genetics clinic and evaluation of current guidelines.
Authors: Annelise Pace, Ashley Henriksen Woodson, Rebecca Slack-Tidwell, Molly S. Daniels, Patrick Glen Pilie, Jennifer Keating Litton, Jennifer M. Hoskovec, Eric Jonasch
Journal: Journal of Clinical Oncology (2019)

668 Background: Several known hereditary cancer syndromes confer an increased risk for genitourinary (GU)-related malignancies. Various guidelines indicate when to refer patients to genetic counseling for GU cancers, but there are limited data on the performance of these guidelines in clinical practice, and the association between testing outcome and clinical and familial features that may delineate a heritable syndrome. The purpose of this study is to determine the most common indications for ordering genetic testing in a GU Genetics Clinic and evaluate the relationship between the indication for germline testing and outcome. Methods: An IRB-approved retrospective chart review was performed for 350 patients seen in a GU Genetics Clinic at a single comprehensive cancer center from 2014-2018. Subgroups of patients were formed based on their indication for genetic testing. Exact binomial tests were used to compare the proportion of patients with a positive (pathogenic or likely pathogenic) germline variant for those with vs. without each indication. Results: All patients had a genetic evaluation due to a personal or family history of GU cancer. The majority (324 of 350, 92.5%) were evaluated for either renal cell carcinoma (RCC) or prostate cancer (PrCa). Among patients seen for RCC-related evaluation (n = 159), 23 patients (14.5%) tested positive. Meeting published clinical criteria for a hereditary RCC syndrome significantly predicted positive testing ( P&lt; 0.001). No other indication for testing, including RCC diagnosis ≤ 46 years, predicted for positive germline genetic test results. No positive patients were identified by age of RCC onset alone. Among patients seen for PrCa-related evaluation (n = 173), 13 (7.5%) individuals tested positive; all positive variants were in ATM or BRCA2. A single patient (1/13) was identified by metastatic PrCa status alone. Conclusions: Our data suggest current algorithms lack specificity for selecting individuals with RCC or PrCa at risk for germline mutations, and need to be revised. Evaluation of pedigrees and identifying presence of syndromic features are essential and increase the probability of identifying individuals at risk for harboring a germline mutation.
NKTR-214 + nivolumab in first-line advanced/metastatic urothelial carcinoma (mUC): Updated results from PIVOT-02.
Authors: Arlene O. Siefker-Radtke, Mayer N. Fishman, Arjun Vasant Balar, Giovanni Grignani, Adi Diab, Jianjun Gao, Mary Ann Tagliaferri, Alison L. Hannah, Erin E. Karski, Jonathan Zalevsky, Ute Hoch, Ahsan NAQI Rizwan, Mehmet Asim Bilen
Journal: Journal of Clinical Oncology (2019)

388 Background: Single-agent checkpoint inhibitors have changed the mUC treatment landscape; however, unmet need remains in first-line (1L) cisplatin ineligible mUC, particularly for PD-L1 negative (–) patients (pts). NKTR-214 is a CD122-biased agonist designed to provide sustained signaling through the IL-2 βγ receptor. PIVOT-02 is an ongoing study of NKTR-214 + nivolumab (nivo) in pts with advanced cancers, including mUC. Methods: Pts with mUC who were 1L cisplatin ineligible or refused standard of care (SOC) received NKTR-214 IV 0.006 mg/kg + nivo IV 360 mg q3w. Responses were assessed every 8 wks. Matched blood and tumor biopsies were evaluated for biomarkers including PD-L1 expression (assessed by Dako 28-8 PharmaDx IHC; PD-L1+ defined as ≥ 1% tumor cell staining). Results: As of 11 Oct. 2018, 34 pts received ≥ 1 dose of treatment (cisplatin ineligible [n=22]; refused SOC [n=12]). Median age was 70. Of 34 pts, 23 were efficacy evaluable (defined per protocol as having ≥ 1 post-treatment scan), 7 were pending a first scan, 1 pt was excluded for non-eligibility (no target lesion), and 3 discontinued prior to first scan. Thresholds for efficacy were exceeded in all 1L mUC cohorts under a pre-specified Fleming ORR analysis. In the efficacy evaluable population, overall ORR was 48% (11/23; 95% CI 27–69%) with a 17% CR rate (4/23) and 70% (16/23) DCR. The ORR was 50% in PD-L1– pts (5/10; 95% CI 19–81%) and 56% in PD-L1+ pts (5/9; 95% CI 21–86%). PD-L1 status was unknown in 4 efficacy-evaluable pts. The most common treatment-related AEs (TRAE, &gt;30%) were fatigue (59%), pyrexia (38%), chills (32%), and flu-like symptoms (32%). Grade ≥ 3 TRAEs occurred in 18% of pts and 8.8% discontinued due to TRAEs. No G4/G5 TRAEs occurred. 22 pts had available baseline PD-L1 results (PD-L1+ [n=11]; PD-L1– [n=11]). 10 of the 11 PD-L1– baseline samples had matched wk 3 biopsies. Of these, 6/10 (60%) converted to PD-L1+ at wk 3. Updated results will be presented. Conclusions: NKTR-214 + nivo showed encouraging clinical activity, including CRs, and an acceptable preliminary safety profile in pts with mUC. Efficacy appears independent of PD-L1 status with a similar ORR in PD-L1– and + tumors. These data support further evaluation of the combination. Clinical trial information: NCT02983045.
Loss of bronchoprotection with ICS plus LABA treatment, β-receptor dynamics, and the effect of alendronate
Authors: Juan Carlos Cardet, Xiaofeng Jiang, Quan Lu, Norma Gerard, Kristen McIntire, Homer A. Boushey, Mario Castro, Vernon M. Chinchilli, Christopher D. Codispoti, Anne-Marie Dyer, Fernando Holguin, Monica Kraft, Stephen Lazarus, Robert F. Lemanske, Njira Lugogo, Dave Mauger, Wendy C. Moore, James Moy, Victor E. Ortega, Stephen P. Peters, Lewis J. Smith, Julian Solway, Christine A. Sorkness, Kaharu Sumino, Michael E. Wechsler, Sally Wenzel, Elliot Israel
Journal: Journal of Allergy and Clinical Immunology (2019)
Abstract 016: Lower Levels of County Housing Affordability Are Linked to Worse Cardiometabolic Risk Profiles in Middle-Aged and Older Adults
Authors: Justin Rodgers, Robert B Wallace, Becky A Briesacher, Christopher F Baum, Daniel Kim
Journal: Circulation (2019)

Introduction: Housing is a fundamental social determinant of health. Past studies have shown that high levels of unaffordable housing raise residents’ chances of moving, often redistributing individuals into socioeconomically disadvantaged neighborhoods and dwellings. This may simultaneously expose individuals to health-detrimental factors while limiting their exposure to health-promoting factors. Residents within unaffordable housing areas may also experience adverse physical and mental health outcomes through various psychosocial, behavioral and material pathways. Yet few studies have examined the relationship between housing affordability and risk factors for cardiovascular disease, the leading cause of morbidity and mortality among Americans. Hypothesis: We investigated the hypothesis that lower levels of county housing affordability are linked to higher odds of incident hypertension, diabetes, obesity, and depression. Methods: Using a nationally-representative sample of 3,722 middle-aged to older adults from the National Longitudinal Survey of Youths 1979 and exploiting quasi-experimental variation before and after the Great Recession, we estimated the associations between the change in median county-level percentage of household income spent on housing (rent, mortgage) between 2000 and 2008 and individual-level odds of incident hypertension, obesity, diabetes, and depression during the follow-up period 2008-2014. Incidence of hypertension and diabetes was assessed through survey-reported physician diagnosis. Obesity was defined as a BMI ≥ 30 kg/m 2 , and depression was measured using the 7-item Center for Epidemiologic Studies Depression Scale and designated based on a cut-off score of 7. We employed fixed effects logistic regression models to reduce bias due to time-invariant confounding. Results: Each percentage point increase in the median county-level percentage of household income spent on rent or mortgage was associated with a 17% increase in the odds (OR = 1.17, 95% CI = 1.00 to 1.39; p = 0.047) of incident hypertension, a 37% increase in the odds (OR = 1.37, 95% CI = 1.00 to 1.87; p = 0.049) of obesity, and a 15% increased odds (OR = 1.15, 95% CI = 1.01 to 1.31; p = 0.030) of depression, controlling for individual- and area-level demographic and socioeconomic factors. No association was observed for diabetes. These associations were stronger among renters than among homeowners, and in men compared to women. In sensitivity analyses, these findings were robust when we limited the sample to non-movers and when we used alternative depression score cut-points. Conclusions: Our findings suggest that lower levels of housing affordability contribute to worse risk profiles for cardiovascular disease. Policies that make housing more affordable may help to reduce the population burden of cardiovascular disease.