tbuckley/cabot-search huggingface dataset:
The impact of the National Breast and Cervical Cancer Early Detection Program (NBCCEDP) in reducing outcome disparities based on race.
Authors: Mark A Fiala, Tanya Marya Wildes
Journal: Journal of Clinical Oncology (2015)

6555 Background: The NBCCEDP, created in 1990, provides breast and cervical cancer screening and diagnostic services to low-income and uninsured women. The program’s effectiveness in reducing racial disparities in outcomes is unclear. Therefore, we examined the incidence of metastatic (distant) disease at diagnosis and the mortality rates of women with metastatic disease by race before and after the advent of the NBCCEDP. Methods: Using the SEERStat software, we extracted the case listings of all women diagnosed with breast or cervical cancer from 1981 through 2010 in Surveillance Epidemiology and End Results (SEER)-9 registries database based on the November 2013 submission. Autopsy or death certificate only cases were excluded. As the targeted ages for breast cancer screening is 50-69 years old and 16-69 years old for cervical, only cancers diagnosed during those respective ages were included. The women were divided into three cohorts based on the year of diagnosis [1981-1990; 1991-2000; 2001-2010]. Socioeconomic status was approximated by median household income of county of residence from the 2000 US census. Incidence rates of metastatic disease were compared using χ2, and mortality rates were compared using multivariate cox regression. Results: 224,183 women with breast cancer and 28,532 with cervical cancer were analyzed. Black women represented 15% of the breast cancers and 9% of the cervical. The proportion of women with metastatic disease was consistently higher for black women than white women. The mortality rate of those with metastatic disease, adjusted for year of diagnosis, age, and SES, was also consistently higher for black women than white women (Table 1); neither improved during the two most recent decades. Conclusions: Racial disparities persist between black and white women with breast or cervical cancer despite the screening efforts of the NBCCEDP. Breast Cervical White Black White Black Distant Distant aHR (95% CI) Distant Distant aHR (95% CI) 1981-1990 7% 11% 1.5 (1.4-1.6) 8% 10% 1.4 (1.3-1.5) 1991-2000 6% 9% 1.8 (1.7-1.8) 7% 9% 1.5 (1.4-1.6) 2001-2010 6% 11% 2.2 (2.1-2.3) 11% 13% 1.5 (1.3-1.6) aHR, adjusted Hazard Ratio.
Phase II study of Lutetium-177-labeled anti-Carbonic Anhydrase IX monoclonal antibody girentuximab in patients with advanced renal cell carcinoma.
Authors: Marye Boers-Sonderen, Stijn Muselaers, Tim van Oostenbrugge, Otto Boerman, Ingrid Desar, Alexander Stillebroer, Sasja Mulder, Carla M.L.- Van Herpen, Hans Langenhuijsen, Egbert Oosterwijk, Wim J.G. Oyen, Peter Mulders
Journal: Journal of Clinical Oncology (2015)

e14014 Background: Despite recent advances in treatment of metastatic clear cell renal cell carcinoma (ccRCC), the search for alternative treatment modalities, which can induce durable responses with milder toxicity profiles continues. A phase II radioimmunotherapy (RIT) trial with 177lutetium (177Lu)-girentuximab was initiated, based on the encouraging results of a phase I study, to evaluate the efficacy of this RIT approach in patients with metastatic ccRCC. Methods: In this single-center, non-randomized phase II trial, patients with progressive metastatic ccRCC received RIT with 2.4 GBq 177Lu-labeled anti-CAIX antibody, girentuximab, if targeting of the antibody was observed after a diagnostic injection with 111Indium labeled girentuximab. Patients were eligible for another treatment cycle if they had at least stable disease (SD) on evaluation after 3 months according to RECIST v.1.1 and did not have prolonged grade 4 hematological toxicity. Retreatment was at 75% of the previous activity dose with a maximum of 3 treatment cycles in total. Results: Between August 2011 and April 2014, 14 patients were enrolled in the study and received at least one infusion with 177Lu-girentuximab. After the first treatment cycle SD was observed in 8 (57%) patients, partial response (PR) was seen in 1 (7%) patient, while progressive disease (PD) was seen in the other 5 (36%) patients. The treatment was generally well tolerated, but resulted in transient grade 3-4 leucocytopenia and/or thrombocytopenia in all, but one, patients. Of the 9 patients with clinical benefit (PR,SD) after the first cycle, 3 patients were not eligible for retreatment due to prolonged hematological toxicity. After the second treatment cycle, continued SD was observed in 5 out of 6 patients. All 5 suffered from prolonged thrombocytopenia after cycle 2 and were therefore not eligible for the third treatment cycle. Conclusions: RIT with 177Lu-girentuximab resulted in disease stabilization in 9 out of 14 patients with progressive ccRCC. Apart from transient grade 3-4 myelotoxicity, RIT was well tolerated. Clinical trial information: NCT02002312.
Abstract P085: Cardiometabolic Syndrome Varies Significantly by Geography and Race/Ethnicity
Authors: Laura Houghtaling, Sarah Milder, Tom Eckstein
Journal: Circulation (2017)

Introduction: The relationship between cardiometabolic syndrome (CMS) and various risk factors has been studied in a variety of populations. Previously published research using 2007 Behavioral Risk Factor Surveillance System (BRFSS) data from Pennsylvania found that black and Hispanic adults had a significantly higher prevalence of CMS compared with whites. However, CMS has not been presented at the state level for the purpose of comparing the prevalence between states and between subpopulations within states. Hypothesis: This descriptive study examines the variation in prevalence of CMS by state and by race/ethnicity. We assessed the hypothesis that significant racial disparities exist in CMS prevalence between and within states. Methods: The sample size for this study included 2,380,047 noninstitutionalized adults aged 18 and older. A composite variable for CMS was created using BRFSS variables measuring obesity, hypercholesterolemia, angina (as a proxy for decreased high-density lipoprotein), prehypertension or hypertension, and prediabetes or diabetes. CMS was defined as having 3 or more of the 5 variables. Within BRFSS, obesity is defined as having a body mass index &gt;=30kg/m*m based on self-reported height and weight. . Self-reported diagnosis of high cholesterol was used as a surrogate for elevated triglycerides. Self-reported diagnosis of angina or CHD was used as a surrogate for reduced HDL. Five years of BRFSS data (2011-2015) were aggregated to ensure adequate sample size for stratification by demographic variables. The survey weight used in the analysis was adjusted to represent the average population over the 5-year period. Both unadjusted and age-adjusted prevalence estimates were calculated. All statistical analyses were performed using STATA v14.1. Results: Unadjusted prevalence of cardiometabolic syndrome varied from 10.5% (95% CI: 10.0%-10.9%) of adults in Colorado to 23.1% (95% CI: 22.3%-24.0%) in Mississippi. Within Colorado, prevalence of CMS was 7.7% (95% CI: 7.2%-8.1%) among adults aged 18 to 64, and 21.7% (95% CI: 20.7%-22.7%) among adults aged 65 and older. In Mississippi prevalence of CMS was 19.8% (95% CI: 18.8%-20.7%) among adults aged 18 to 64 and 34.3% (95% CI: 32.8%-35.8%) among adults aged 65 and older. CMS prevalence is significantly higher among black adults compared with whites and Hispanics in almost all states (unadjusted for age). Age-adjusted comparisons between states are presented. Conclusions: Understanding the burden of CMS relative to other states and among select demographic groups within the state is vital to prevention efforts. Black adults are disproportionately afflicted with poor cardiometabolic health and the degree of affliction is dependent on state of residence. In conclusion, when it comes to CMS, it matters where you live, your age, and your racial/ethnic status.
Penile and uterine cervical squamous cell carcinomas: A comparative genomic profiling study.
Authors: Joseph Jacob, Rubin Pinkhasov, Oleg Shapiro, Nick Liu, Laurie M. Gay, Brian Michael Alexander, Julia Andrea Elvin, Jo-Anne Vergilio, James Suh, Shakti Ramkissoon, Siraj Mahamed Ali, Alexa Betzig Schrock, Jon Chung, Venkataprasanth P. Reddy, Vincent A. Miller, Robert John Corona, Jeffrey S. Ross, Gustavo de La Roza, Gennady Bratslavsky
Journal: Journal of Clinical Oncology (2019)

514 Background: Metastatic penile (mPSCC) and uterine cervical squamous cell carcinoma (mCSCC) are aggressive forms of malignancy with limited treatment options. We used comprehensive genomic profiling (CGP) to compare the genomic alterations (GA) and their potential impact on targeted and immunotherapy options of mPSCC and mCSCC. Methods: 78 metastatic mPSCC and 604 mCSCC underwent CGP using a hybrid-capture-based next-generation sequencing assay with a mean coverage depth of &gt; 500X. Tumor mutational burden (TMB) was determined on 1.1 Mbp of sequenced DNA and microsatellite instability (MSI) was determined on 114 loci. Results: The median age of mPSCC men was higher than mCSCC women. The HPV+/CDKN2A- status was more frequent in the mCSCC than mPSCC. The GA/tumor were similar for both tumor types (table). TP53 mutations were more common in mPSCC likely linked to loss of original HPV+ status. TERT, NOTCH1 and FAT1 GA were more frequent in mPSCC whereas PIK3CA GA were more common in mCSCC. MTOR pathway targets (GA in STK11, FBXW7 and PTEN) were more common in mCSCC. MSI-High status was extremely rare in all cases, but the relatively high frequencies of TMB ≥ 10/20 mut/Mb in both mPSCC and mCSCC were noteworthy. Examples of patients with mCSCC and mPSCC responding to targeted and immunotherapies will be presented. Conclusions: Although mCSCC and mPSCC share a variety of genomic features, the 2 tumor types can nonetheless be sharply differentiated on CGP. The TP53, CDKN2A and HPV status of the tumor types differ significantly with viral identification much higher in the mCSCC group. There are opportunities for targeted therapies in both groups predominantly identified in the MTOR pathway. Numerous cases with significantly elevated TMB in both mPSCC and mCSCC suggest that immunotherapies might be of benefit in a subset of patients. [Table: see text]
Incidence of Carcinogenic Pathways in non-squamous non-small cell lung cancer (NSq-NSCLC) in a community cancer center: Actionable driven mutations and their interactions with other genomic alterations.
Authors: Edgardo S. Santos, Lilibeth del Carmen Castillero, Daniel Adam Katz, Albert Begas
Journal: Journal of Clinical Oncology (2015)

e12562 Background: Since the first report by Mok T. et al. in 2008 showing clinical benefit of tyrosine kinase inhibitor for patients (pts) whose tumors harbor EGFR mutation, personalized medicine has become a priority nowadays in oncology. To date, we are looking for new driven mutations in both squamous and NSq-NSCLC that can improve overall survival, progression-free survival, and quality of life over conventional platinum-based doublet as frontline treatment for NSCLC. Methods: From November 2012 to January 2015, we tested 132 pts with newly diagnosed NSq-NSCLC; 1 pt. was re-biopsied. We analyzed 133 tumor samples; more recently, 22 pathways have been added to our panel. In this 2-year timeframe, we evolved from FISH and PCR analyses to next generation sequencing. We analyzed the incidence of EGFR, ALK, and ROS1as well as the co-existence of these mutations with others. The rate of insufficient tumor (QNS) was also calculated. Results: Median age 75 (range, 40-92); gender: 88 female and 44 male pts; Caucasian n = 125, Hispanic n = 4, African American n = 2; and Asian n = 1. Driven mutation found: EGFR exon19/L858R, 15% (15/103; 12% QNS); ALK, 11% (10/94; 10% QNS); and ROS1, 6% (4/67; 11% QNS). Other pathways with high incidence were: K-ras 41% (34/83; 8% QNS) and c-MET 40% (25/62; 25% QNS). For K-ras, most common variants: Gly12Cys (38%), Gly12Val (29%), and Gly12Asp (9%). From the 25 cases with overexpressed c-MET, only 1 pt (1/13) was amplified; FISH analysis was not requested in 12 of these c-MET + pts. Co-existence was found as follows: EGFR/c-MET (2), ALK/K-ras (2), ROS1/K-ras (1), ROS1/c-MET (1). K-ras mutation was also found in combination with c-Met (7), PI3K (3), EGFR exon 20 (1), B-Raf (1), TP53 (1), PTPRD (1), and DDR2 (1). Conclusions: Our incidence of ALK translocation continues to be one of the higher being reported. Our ALK + pts had a median age of 76 (range, 62-86). Incidence of EGFR and K-ras are similar to other reports. c-MET has a high incidence in newly diagnosed pts. These analyses are important for development of future clinical trials targeting either single or multiple pathways.
Outcomes of Direct Oral Anticoagulants in Patients With Mitral Stenosis
Authors: Ju Youn Kim, Sung-Hwan Kim, Jun-Pyo Myong, Yoo Ri Kim, Tae-Seok Kim, Ji-Hoon Kim, Sung-Won Jang, Yong-Seog Oh, Man Young Lee, Tai-Ho Rho
Journal: Journal of the American College of Cardiology (2019)
Non-urothelial bladder cancer: Genomic alterations and patient outcomes.
Authors: Fern Anari, Benjamin Miron, Donald Henson, David Arguello, Elizabeth R. Plimack, Matthew R. Zibelman, Chethan Ramamurthy, Pooja Ghatalia, Elisabeth I. Heath, Earle Frederick Burgess, Nancy Ann Dawson, Daniel A. Vaena, Bradley G. Somer, Thomas F. Hogan, Ralph J. Hauke, Jeanny B. Aragon-Ching, Daniel M. Geynisman
Journal: Journal of Clinical Oncology (2019)

399 Background: Adenocarcinoma (ADA) and squamous cell carcinoma (SCC) are rare, aggressive subtypes of bladder cancer, for which no clear standard of care exists. We report on survival of pts with ADA and SCC and identify potential therapeutic targets using molecular profiling via next generation sequencing (NGS). Methods: Survival trends, demographics, pt characteristics were obtained from the Surveillance, Epidemiology, and End Results (SEER) Database. In a separate cohort, NGS results from 72 specimens (50% metastatic) were also analyzed, using either a hotspot 47 gene panel or a 592 gene assay (Caris Life Sciences, Phoenix, AZ). Results: In SEER, 235,537 cases of bladder cancer were extracted from 1988-2008, of which 3096 were SCC and 671 were ADA. 90% of pts were white, although more African-American patients (15%) were seen in those with ADA. Among all stages, median overall survival (mOS) and 5-yr survival rates were 17.9 mos and 58% for ADA and 15 mos and 37% for SCC. Via NGS testing, 43 patients (28 ADA, 15 SCC) were tested with a 47 gene panel and 29 (21 ADA, 8 SCC) with a 592 gene panel. In the 47 gene panel, among ADA pts, the highest mutation rates were TP53 (57.1%), KRAS (21.4%), SMAD4 (14.8%), PIK3CA (10.7%) and BRCA2 (7.7%). Among SCC pts, the highest mutation rates were TP53 (66.7%), PIK3CA (33.3%), HRAS (14.3%), FBXW7 (6.7%) and AKT1 (6.7%). In the 592 gene assay, the genes with the highest mutation rates in pts with ADA were TP53 (81%), SMAD4 (33.3%), KRAS (23.8%), KMT2C (11.8%), ARID1A (11.1%), BRAF (9.5%), CTNNB1 (9.5%), KMT2D (9.5%), TSC1 (9.5%), KDM6A (5.9%), CDKN2A (5%). Among SCC pts, the highest mutation rates were TP53 (75%), CDKN2A (42.9%), FGFR3 (25%), PIK3CA (25%), CIC (14.3%), KDM6A (14.3%), BRAF (12.5%), BRCA1 (12.5%), FH (12.5%), HRAS (12.5%) and KMT2D (12.5%). Only 1 pt had high TMB. Conclusions: Genomic profiling identifies differences in underlying tumor biology of bladder ADA and SCC, which on a population level are rare with poor survival. Overall, the alterations in the PIK3CA/ AKT/ mTOR and TP53 pathways are similar to what has been reported in UC. Future analyses of these malignancies should investigate the emerging actionable targets, such as TSC1, FGFR3, BRCA1/2 and BRAF.
Parents of US boy who survived tetanus after nearly $1m of care refuse vaccine
Authors: Janice Hopkins Tanne
Journal: BMJ (2019)

The parents of a 6 year old boy who survived tetanus after 57 days in an Oregon paediatric acute care unit in 2017 have refused the recommended second dose of tetanus vaccine.

They boy’s hospital care in 2017 cost $811 929 (£620 000; €720 000)—plus the unreported cost of emergency air transport, rehabilitation, and follow-up care, an account in Morbidity and Mortality Weekly Report said.1

This was the first case of tetanus in the state of Oregon in 30 years. A reported 7.5% of Oregon’s school age children do not receive any vaccinations because parents choose “non-medical exemptions”—that is, for personal reasons.2 The case fatality rate for tetanus is 13.2%, the Centers for Disease Control and Prevention has reported.3

Recommended protection against tetanus is five doses of the …
Abstract P041: Adipose Inflammation as Assessed by Adipose FDG Uptake is Associated With Aortic Vascular Inflammation in Psoriasis
Authors: Harry Choi, Amit Dey, Aditya Goyal, Justin Rodante, Andrew Keel, Milena Aksentijevich, Noor Khalil, Jenis Argueta-Ameya, Aarthi Reddy, Martin Playford, Mark Ahlman, Tiffany Powell-Wiley, Joel Gelfand, Nehal Mehta
Journal: Circulation (2019)

Background: Psoriasis, a chronic inflammatory disease, is associated with accelerated vascular inflammation (VI) by FDG PET/CT and increased cardiometabolic dysfunction, including adipose tissue dysregulation. Both visceral and subcutaneous adipose volume are associated with sub-clinical aortic VI as well as future cardiovascular events, however, the relationship of adipose inflammation (assessed as adipose FDG uptake) with sub-clinical aortic VI has never been characterized in psoriasis. Methods: 104 consecutive biologic naïve psoriasis patients underwent FDG PET/CT scans to measure VI and adipose FDG uptake, represented as target-to-background ratio (TBR) and standardized uptake value (SUV) respectively. After identification of anatomical location (vertebral level T10), a single 3D-volume region of interest with a fixed volume (4.0 cm 3 ) was placed in the subcutaneous adipose to measure FDG uptake as standardized uptake value (SUV) using a dedicated software (OsiriX MD, Geneva, Switzerland). Results: The cohort was middle-aged, predominantly male, low CV risk by Framingham risk score and mild-moderate psoriasis. Adipose FDG uptake significantly associated with skin disease severity as well as aortic VI even beyond traditional risk factors (β=0.33, p=0.001 and β=0.24, p=0.014 respectively). Additionally, adipose FDG uptake mediated the association between psoriasis skin disease severity and aortic VI accounting for 23% of the total effect (Figure). Conclusions: Our study demonstrated that adipose inflammation is positively associated with psoriasis severity as well as aortic VI. Moreover, adipose inflammation also mediated the relationship between skin disease severity and aortic VI, suggesting that it may contribute to the potential link between psoriasis and CV disease. However, larger studies are needed to confirm our findings.
Abstract P313: Sport Participation Associated With Fewer Anxiety Symptoms in Adult Congenital Heart Disease
Authors: Jong Ko, Kamila White, Adrienne Kovacs, Kristen Tecson, Junko Enomoto, Philip Moons, Ari Cedars
Journal: Circulation (2019)

Introduction: Physical activity (PA) has well-known benefits for mental health, which is closely related to clinical outcomes in patients with heart disease; however, little is known about the relationship between PA and anxiety. In this study, we examined their association in a large international cohort of adult congenital heart disease (ACHD) patients. Hypothesis: We hypothesize that different PA types would have differential impact on anxiety symptoms. Methods: We conducted a cross-sectional assessment of data derived from the Assessment of Patterns of Patient-Reported Outcomes in Adults with Congenital Heart Disease - International Study . This study enrolled 4,028 ACHD patients from 24 centers in 15 countries. Anxiety symptoms were assessed with the Hospital Anxiety and Depression Scale (HADS). Participants reported whether they were regular active commuters (either walk or cycle to work/school) and/or regular sport participants (either recreational or competitive). To assess the relationship between PA and anxiety, we constructed ordinal logistic mixed models, treating country as a random effect. We built an optimally-adjusted model via stepwise selection, which considered all variables having significant relations with anxiety in bivariate analyses and missing at a rate of &lt; 5%. Results: Of 3,893 patients (mean age of 35 ± 13) who completed the HADS, 53% were female; 27% reported elevated anxiety symptoms (i.e., HADS ≥ 8). No significant relationship was found between active commute and anxiety symptoms in bivariate analysis while sport participation was associated with a 40% lower risk of elevated anxiety. The benefit of sport participation on anxiety remained, even after accounting for relevant demographic and clinical variables (adjusted OR=0.769; 95% CI 0.654 - 0.906; p = 0.002) (Table 1). Conclusion: Sport participation is associated with fewer symptoms of anxiety. In conclusion, individualized sport-related exercise prescriptions may reduce anxiety symptoms in cardiac patients.
Mendelian Randomization Study of <i>ACLY</i> and Cardiovascular Disease
Authors: Brian A. Ference, Kausik K. Ray, Alberico L. Catapano, Thatcher B. Ference, Stephen Burgess, David R. Neff, Clare Oliver-Williams, Angela M. Wood, Adam S. Butterworth, Emanuele Di Angelantonio, John Danesh, John J.P. Kastelein, Stephen J. Nicholls
Journal: New England Journal of Medicine (2019)

ATP citrate lyase is an enzyme in the cholesterol–biosynthesis pathway upstream of 3-hydroxy-3-methylglutaryl–coenzyme A reductase (HMGCR), the target of statins. Whether the genetic inhibition of ATP citrate lyase is associated with deleterious outcomes and whether it has the same effect, per unit decrease in the low-density lipoprotein (LDL) cholesterol level, as the genetic inhibition of HMGCR is unclear.
MMP9 Inhibition Rescues the Erythroid Defect in RPS14-Deficient Del(5q) MDS Models
Authors: Minyoung Youn, Haigen Huang, Cheng Chen, Sharon Kam, Mark C Wilkes, Hee-Don Chae, Anupama Narla, Shuo Lin, Kathleen M. Sakamoto
Journal: Blood (2018)
Proton Pump Inhibitors Are Associated With Minimal and Overt Hepatic Encephalopathy and Increased Mortality in Patients With Cirrhosis
Authors: Silvia Nardelli, Stefania Gioia, Lorenzo Ridola, Alessio Farcomeni, Manuela Merli, Oliviero Riggio
Journal: Hepatology (2018)

Minimal hepatic encephalopathy (MHE) is a subclinical cognitive impairment frequently observable in patients with cirrhosis. Proton pump inhibitors (PPIs) can contribute to small‐bowel bacterial overgrowth, but no study has investigated the link between PPIs and MHE. We investigated the relationship between MHE and PPI use as well as the role of PPI use in the development of overt HE and survival. Consecutive patients with cirrhosis (n = 310) were included in the study and followed up for 14.1 ± 12.3 months. At entry, MHE was diagnosed when the Psychometric Hepatic Encephalopathy Score was ≤–4. Data were analyzed by logistic regression for the factors associated with MHE and by time‐related models for overt HE development and survival. At inclusion, 131 out of 310 patients with cirrhosis (42%) were affected by MHE. One hundred and twenty‐five patients (40%) were using PPIs. The variables independently associated with the presence of MHE were PPI use, previous overt HE, low albumin, low sodium, and age. During follow‐up, the development of overt HE was higher (64% versus 25%, P &lt; 0.001) and overall survival lower (41% versus 81%, P &lt; 0.001) in PPI users than in nonusers. Variables independently associated with the development of overt HE were PPIs, history of overt HE, low albumin, MHE, and age, while variables independently associated with mortality were PPIs, development of overt HE, Model for End‐Stage Liver Disease score, low sodium, and age. Conclusion: The study identifies a potentially removable factor associated with the presence of MHE and related to the development of overt HE and survival in patients with liver cirrhosis.