tbuckley/cabot-search huggingface dataset:
Rational Dispersion for the Introduction of Transcatheter Mitral Valve Repair Into Clinical Practice
Authors: David R. Holmes, Michael J. Mack
Journal: JAMA (2019)

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Abstract 036: Derivation and Validation of a Novel Risk Equation for 10-year Risk of Incident Heart Failure in the General US Population
Authors: Sadiya S Khan, Hongyan Ning, Sanjiv J Shah, Clyde W Yancy, John T Wilkins, Donald M Lloyd-Jones
Journal: Circulation (2018)

Background: Identification of individuals at risk for heart failure (HF) is necessary for implementation of primary prevention strategies. However, currently no validated prediction models exist for assessment of HF risk in a broad-based general population (ACC/AHA Stage 0 and Stage A individuals) based on routinely available clinical data. Methods: Estimation of 10-year risk equations for developing a HF event were derived from community-based cohorts representative of the U.S. population of Whites and Blacks. Participants were included from ARIC (Atherosclerosis Risk in Communities) study, Cardiovascular Health Study, the CARDIA (Coronary Artery Risk Development in Young Adults) study, Multi-Ethnic Study of Atherosclerosis, and Framingham Offspring Study cohorts who were recruited between 1985-2000, between the ages of 30 to 80 years, free of cardiovascular disease at baseline, and had 12-years of follow-up. Sex- and race-specific 10-year risk equations were derived in a random pre-specified subset of the pooled sample (n=11,771) and subsequently validated in the remaining participants (n=11,770). Harrell’s C-statistic and Greenwood-Nam-D'Agostino chi-square were used to determine discrimination and calibration of these models. Results: In the derivation cohort, 58% were women, 22% black, and mean age 52.7±11.9 years. HF occurred in 1,339 participants. Independent predictors of HF included in the model were age, blood pressure (treated or untreated), fasting glucose (treated or untreated), body mass index, cholesterol, smoking status, and QRS duration. The data-derived model had excellent discrimination in the 11,770 distinct participants in the validation cohort (C-statistics 0.71-0.85) and was well-calibrated ( Figure) . Conclusions: A 10-year HF risk score that incorporates readily available clinical parameters in the primary care setting can be used to identify individuals with higher likelihood of developing HF who may merit intensive screening and/or targeted prevention strategies.
Abstract P138: Private School Attendance and Later Life Hypertension
Authors: Debbie Barrington
Journal: Circulation (2019)

Introduction: Black Americans have the highest prevalence of hypertension in the United States (US). Higher educational attainment has been found to have an inverse association with hypertension, yet research examining the association between hypertension and components of education not captured by quantity of education, such as type of school attended, private vs. public, has been limited. The positive relationship between private school attendance and academic achievement, with effects particularly robust among Black Americans, suggests a potential role for private school attendance as a protective factor in hypertension. Hypothesis: Private school attendance compared with public school attendance is hypothesized to be associated with a lower prevalence of hypertension among African American and Afro-Caribbean men and women in the United States. Methods: Multiple logistic regression models were used to examine type of school attended, private vs. public, and its independent association between hypertension among African American (N = 2693) and Afro-Caribbean (N = 1308) men and women, 18 years and older, in the National Survey of American Life (2001-2003). Odds ratios (OR) of the association between type of school attended and adult hypertension were estimated after adjusting for age, socioeconomic factors, health and lifestyle measures within the models. Adult socioeconomic factors included marital status, education, occupation, home ownership and poverty status. Adult health and lifestyle covariates included obesity, diabetes, smoking, alcohol use and physical activity. Results: Private school attendance was a risk factor for hypertension among African American men; age-adjusted OR = 2.11; 95%CI: (1.07, 4.15). Conversely, private school attendance was a protective factor for Afro-Caribbean men; age-adjusted OR = 0.34; 95%CI: (0.13, 0.89). After adjusting for adult socioeconomic, health and lifestyle factors, the two-fold higher odds of hypertension compared to those who attended public schools remained among African American men who attended private schools; adjusted OR = 2.11; 95%CI: (0.97, 4.60). After covariate adjustment, private school attendance remained a statistically significant protective factor for Afro-Caribbean men; those who attended private schools had 68% decreased odds of hypertension compared to those men who attended public schools, adjusted OR = 0.32; 95%CI: (0.11, 0.94). No association between hypertension and school-type was found for either African American or Afro-Caribbean women. Conclusions: These findings suggest that type of school attended is another dimension of education relevant for the cardiovascular health of African American and Afro-Caribbean men. Additionally, it exerts a differential effect on hypertension by ethnicity.
Abstract P336: Predictors of High Intensity Statin Initiation for Primary Prevention in Veterans With Familial Hypercholesterolemia Phenotype
Authors: Saadia Qazi, Laura M Tarko, Yuk-Lam Ho, Ariela R Orkaby, Yan V Sun, Themistocles L Assimes, David R Gagnon, Kelly Cho, Luc Djousse, J. Michael Gaziano, Christopher J O’Donnell, Peter W Wilson
Journal: Circulation (2019)

Introduction: Familial hypercholesterolemia (FH) phenotype, defined in part by LDL-Cholesterol (LDL-C) ≥190mg/dL, is a strong risk factor for cardiovascular disease (CVD). The 2013 ACC/AHA cholesterol guidelines recommend high intensity statins for primary prevention irrespective of global risk assessment. We sought to determine predictors of high intensity statin initiation in patients with FH phenotype in the Veteran’s Health Administration (VHA). Methods: Inclusion criteria consisted of VHA care (2002-2014), age ≥21 years, absence of prevalent CVD, baseline maximum LDL-C ≥190 mg/dL, no prior statin use, and statin initiation within 90 days of outpatient LDL-C measurement. Baseline characteristics were obtained from the electronic health record. We defined baseline LDL-C using quartile cutoffs. High intensity statin definitions were based on the 2013 cholesterol guidelines plus high dose simvastatin when it was available. Multivariable logistic regression models were constructed to determine the odds of high intensity statin initiation versus low or moderate intensity. Results: A total of 88,878 Veterans (age=53.7±11.6, men=91%; white race=74%, LDL-C mean=209.5±23.9, Q1=195, median=202, Q3=215) met inclusion criteria. High intensity statin was initiated in 29,533 (33%) of patients. Comorbidities included smoking history (80%), hypertension (39%), diabetes (10%), and chronic kidney disease (3%). Significant predictors were age &gt;40 years, male sex, diabetes, hypertension, black race, smoking, higher baseline LDL-C quartile, and recent calendar year. Veterans with cancer and white race had lower odds of statin initiation. Conclusion: Nearly 1/3 of the Veteran population with the FH phenotype was started on high intensity statins. They were more likely to be older, black, smokers, hypertensive, diabetic, and have a higher baseline LDL-C. The odds of high intensity statin initiation increased in recent years, which may partly reflect practice changes concordant with recent cholesterol guidelines.
Stemness Signature in AML: GEP with 17 Genes Score Versus Leukemic Stem Cell (LSC) Quantification By Multiparameter Flow Cytometry (MFC)
Authors: Adriana Plesa, Christophe Roumier, Florent Dumezy, Delphine Manzoni, Pierre Sujobert, Sandrine Hayette, Isabelle Tigaud, Claude Preudhomme, Karine Celli-Lebras, Yves Bertrand, Herve Dombret, Xavier Thomas, Meyling Cheok
Journal: Blood (2018)
What is the clinical utility of next generation sequencing (NGS) in advanced urologic malignancies?
Authors: James Ryan Mark, Victor Kucherov, Michael Pintauro, Joon Yau Leong, Mark Mann, Edouard John Trabulsi, Costas D. Lallas, Thenappan Chandrasekar, Nathan Handley, William Kevin Kelly, Leonard G. Gomella
Journal: Journal of Clinical Oncology (2019)

285 Background: Widespread availability of NGS and an expanding repertoire of targeted therapies has garnered significant enthusiasm for the concept of NGS directed therapy. FoundationOne (Foundation Medicine, Cambridge, MA) is a validated comprehensive genomic profiling (CGP) assay intended to guide therapy decisions based upon tumor specific genetic variations. We reviewed our experience with FoundationOne testing in advanced genitourinary (GU) cancer and examined whether NGS effected therapy in a meaningful way. Methods: Retrospective review of patients with advanced GU cancer seen between 2/1/2013–8/13/2018 who had FoundationOne CGP testing. We then compared the duration patients were maintained on NGS directed therapy to the duration of each non-NGS therapy. Results: A total of 73 patients were identified with NGS testing for prostate (25, 34%), urothelial (30, 41%), and kidney (18, 25%) cancer. 11 (15%) of these patients had therapy directed against a genetic alteration indicated by NGS. Of the treated patients, 46% (5) had urothelial, 36% (4) had kidney, and 18% (2) had prostate cancer. The average duration that each non-NGS therapy was effective in patients with urothelial, kidney, and prostate cancer was 165, 417, and 382 days respectively. Duration of NGS directed therapy averaged 226, 367, and 278 days for urothelial, kidney, and prostate cancer. The range of the duration of response to NGS directed therapy for urothelial, kidney, and prostate cancer was 66-616 days, 106-467 days, and 28-528 days. Four (36%) patients treated with NGS directed therapy achieved a duration of response greater than the average duration of all other non-NGS directed therapy they had received (Table). Conclusions: A minority of patients received NGS directed therapy following NGS testing. Treated patients demonstrated varying responses with 4 patients experiencing a longer duration of response compared to non-NGS directed therapy. Our experience illustrates that NGS has a limited but evolving role in the management of advanced GU malignancies at this time while also demonstrating a benefit to a subset of patients. Future studies should focus on identifying which patients are most likely to benefit from this technology.
Recurrence factors of stage I ovarian clear cell carcinoma.
Authors: Yuji Takei, Hiroyuki Fujiwara, Shizuo Machida, Akiyo Taneichi, Suzuyo Takahashi, Yoshifumi Takahashi, Yasushi Saga, Mitsuaki Suzuki
Journal: Journal of Clinical Oncology (2015)

e16577 Background: Ovarian clear cell carcinoma (CCC) is relatively resistant to anticancer drugs, and its prognosis is poor even in stage I compared to other histologic types. Generally, it is indicated for postoperative chemotherapy, but many points remain unclear with regard to recurrence factors. We investigated recurrence factors of stage I CCC. Methods: Between January 1988 and December 2011, patients diagnosed with stage I CCC by staging laparotomy were registered. Age, stage, tumor diameter, presence or absence of endometriosis, number of excised lymph nodes, and presence or absence of postoperative chemotherapy were investigated, and their associations with recurrence were retrospectively investigated. We diagnosed recurrence by image or pathology. The cut-off value of the number of excised lymph nodes to predict recurrence was calculated from the receiver operating characteristic curve. Cox regression analysis was used to determine the risk factors for recurrence with hazard ratios (HR). Results: 59 patients were enrolled. The median age was 52 (31-77) years old. 15 patients had stage IA, 25 IC(1), 5 IC(2), 14 IC(3). The median tumor diameter was 12 (5-28) cm, 38 patients (67%) were complicated by endometriosis, and postoperative chemotherapy was performed in 46 (78%). The median number of excised lymph nodes was 54 (6-135), and the cut-off value to predict recurrence was 34. Recurrence occurred in 18 patients (31%). On univariate analysis, IC(2,3) (vs. IA+IC(1); p = 0.007) and the number of excised lymph nodes being 34 or lower (vs. 35 or greater; p = 0.004) were extracted as significant recurrence factors. The HR of these 2 factors on multivariate analysis were 3.28 [95% confidence interval (CI): 1.28-8.45] and 3.57 [95% CI: 1.37-9.30], respectively. Conclusions: Stage and number of excised lymph nodes were independent recurrence factors of stage I CCC. Staging laparotomy with sufficient lymph node dissection could lead to recurrence prevention as well as accurate staging.
Estimation of KRAS and EGFR status among Slavic patients with pancreatic cancer.
Authors: Alexey Kashintsev, Evgeny Imyanitov, Nikolay Kokhanenko, Aglaya Iyevleva, Maria Dmitrieva
Journal: Journal of Clinical Oncology (2015)

e15247 Background: Recent clinical trials demonstrated benefits for overall survival (OS) and progression-free survival with addition of the tyrosine kinase inhibitor to gemcitabine among the patients with pancreatic adenocarcinoma (PA) in the case with positive EGFR tumor expression and wild type KRAS Methods: We had analyzed 52 FFPE samples from patients with PA. EGFR status was determined by electrophoresis and in 32 cases KRAS mutation status was evaluated by the real-time PCR sequencing. The results were correlated with age, tumor size and differentiation and OS Results: We hadn’t reveal EGFR amplification in all 52 cases. KRAS mutations were identified in 14 patients (43,8%), in this group median age was 61,4±14,5 years and in the cases with the wild-type RAS it was 72,1±10,03 years. The median OS for patients with KRAS was 4,08 month (3,08 - 5,09; CI 95 %), whereas the median OS for patients with wild-type KRAS was 9,47 months (7,07 – 11,58, CI – 95 %). In histological type the low-differentiated adenocarcinoma prevailed (55,6 %) among the patients with defected KRAS gene. There were not statistically significant differences in KRAS mutation prevalence by the tumor size or stage of the disease. Conclusions: The presence of KRAS mutations is the negative prognostic factor, but the frequencies of it mutated variant among Slavic population was low and negative EGFR status had become for us a disappointment and therefore it is necessary to increase the number of cases
Phase II study of radiation therapy combined with weekly nedaplatin in locally advanced uterine cervical carcinoma: Kitasato Gynecologic Radiation Oncology Group (KGROG 0501) - an initial analysis
Authors: Yuzuru Niibe, Shimpei Tsunoda, Toshiko Jobo, Yukihiro Hamada, Kazushige Hayakawa
Journal: Cancer Research (2007)

5057  Background: Locally advanced uterine cervical carcinoma (LAUCC) treated with chemoradiotherpaty is considered to be the standard treatment regimen. However, no evidence of its efficacy and safety has been obtained from a Japanese population. Futhermore, The total dose of Japanese radiation therapy protocol is lesser than that of US and Canada, which indicated that chemoradciotherapy for LAUCC is better than radiation therapy alone by phase III clinical trials. Thus, the current phase II study was designed to evaluate chemoradiotherapy with lesser radiation dose for LAUCC using weekly nedaplatin to be effective and safety in a Japanese population. Nedaplatin is a platitum drug and is required to no hydration to infuse patients because less toxic to renal function,which was produced by Shionogi Pharmaceutical Co., Japan. If this phase II trial success, chemoradiotherapy for LAUACC in out-patient clinic could be possible.  Patients and Methods: :Patients registered in the current study are found to have LAUCC including following criteria i) pathological proven of squamous cell carcinoma or adenocarcinom, ii) clinical stage according to FIGO is Ib, IIa, IIb with bulky tumor (diameter: 40 > mm assessed by pelive magnetic resonace imaging) or pelvic lymph node swelling (diameter: >10mm assessed by pelvic computed tomography), ) iii) clinical stage IIIa, IIIb and IVa according to FIGO with no para-aortic lymph node swelling (diameter: > 10 mm) observed by abdominal computed tomography. iv) Age: 20-75 years. v) perfomance Status: 0-2. Treatement Protocol is as follows. Radiation therapy is a combination of external beam radiation therapy (total dose: 50 Gy-52 Gy /25-27 fractions with central shielding after 30-32 Gy) with high-dose rate intracavitary irradiation (24-30 Gy/4-6 fractions to point A). Chemothrapy applied in the current study is weekly nedaplatin infused by intravenous (30 mg/mm2/time, once a week, total 150mg/mm2/5weeks) Sample size in the current study is 45 LAUCC patients recruiting for 3-years at a single institution. This protocol was permitted by ethics committee at Kitasato University Hospital.  Results: Ten patients were registered in this study between June 2005 and March 2006. The median age was 57.5 years (range; 36-73). PS0 was 5 and PS1 was 5. As for Clinical stage, 9 was IIIb and the only one was IIb. 9 patients have benn proven to be squamous cell carcinoma and the one to be adenocarcinoma. The median maximum tumor diameter was 62.5 mm (range; 30 - 100 mm). As for Initial response, 8 was CRs and 2 was PRs (100% of response rate). As for hematological acute morbidity, 3 was grade 3, 6 was grade 6, 1 was grade 4.  Conclusions:This initial analysis of phase II study confirmed that concurrent chemoradiotherapy using nedaplatin was safe and efficacy and we decided to undergo the further study.
The success of fecal microbial transplantation in <i>Clostridium difficile</i> infection correlates with bacteriophage relative abundance in the donor: a retrospective cohort study
Authors: Heekuk Park, Michael R. Laffin, Juan Jovel, Braden Millan, Jae E. Hyun, Naomi Hotte, Dina Kao, Karen L. Madsen
Journal: Gut Microbes (2019)

Background Fecal microbial transplantation (FMT) is used in the treatment of relapsing Clostridium difficile infection (rCDI). Failure rate for FMT is as high as 10% but the mechanisms contributing to a failed FMT are not understood. We utilized metagenomic data to identify the role of bacteria and bacteriophages on FMT success.Results Subjects with rCDI (n = 19) received FMT from volunteer donors (n = 7) via colonoscopy. Twelve patients fully recovered after a single FMT, while seven patients required a subsequent FMT. DNA was extracted from patient and donor stool samples for shotgun metagenomic analysis. Metagenomics libraries were analyzed focusing on bacterial taxonomy and bacteriophage sequences. Gammaproteobacteria were dominant in rCDI patients prior to FMT largely due to elevated levels of Klebsiella and Escherichia. A successful FMT led to increased levels of Clostridia and Bacteroidia and a reduction in Gammaproteobacteria. In contrast, a failed FMT led to no significant changes in bacterial composition. Bacteriophages were classified during whole metagenomic analysis of each sample and were markedly different between rCDI patients, donors, and a healthy control cohort (n = 96). Bacteriophage sequence reads were increased in CDI patients compared with donors and healthy controls. Successful FMT donors had higher bacteriophage α-diversity and lower relative abundance compared to the donors of a failed initial FMT.Conclusions In this retrospective analysis, FMTs with increased bacteriophage α-diversity were more likely to successfully treat rCDI. In addition, the relative number of bacteriophage reads was lower in donations leading to a successful FMT. These results suggest that bacteriophage abundance may have some role in determining the relative success of FMT.
Efficacy of locoregional treatment for hepatocellular carcinoma prior to living donor liver transplantation.
Authors: Kenta Inomata, Hiroshi Yagi, Masahiro Shinoda, Kentaro Matsubara, Taizo Hibi, Yuta Abe, Minoru Kitago, Hideaki Obara, Osamu Itano, Yuko Kitagawa
Journal: Journal of Clinical Oncology (2015)

e15131 Background: It has been reported that pre-operative treatment before liver transplantation (LT) for hepatocellular carcinoma (HCC) improves the long-term outcome. The aim of this study was to review our experience in single institution for multidisciplinary pre-transplant treatment of HCC and the impact of its efficacy on downstaging within Milan criteria (MC) prior to LT. Methods: From April 2000 to December 2013, we performed living donor LT for 34 patients who were pathologically diagnosed as HCC, including four patients who were detected HCC incidentally by post-operative pathological evaluation. We retrospectively evaluated the clinicopathological features of HCC and the long-term outcome after LT. Results: The over-all survival of patients with HCC, which was determined pre-operatively as beyond MC, was significantly lower than that with HCC within MC. Interestingly, there is no significant difference in overall survival between patients within and MC by pathological evaluation. Over-all survival of the patients who were downstaged pre-operatively within MC by locoregional treatment was improved. More interestingly, if the Patients were successfully downstaged within MC by pre-operative loco-regional treatment, survival rate was statistically similar to that of the patients who were within MC pre-operatively and got no locoregional treatment prior to LT. The predictive factors associated with over-all survival rate were pre-transplant diagnosis being beyond MC and vascular invasion. Conclusions: Pre-transplant clinical diagnosis based on MC is still valuable for exclusive criteria of the candidate for LT to achieve long-term survival. In this context, locoregional treatment prior to LT was significantly effective for downstage therapy.
Machine Learning Using CT-FFR Predicts Proximal Atherosclerotic Plaque Formation Associated With LAD Myocardial Bridging
Authors: Fan Zhou, Chun Xiang Tang, U. Joseph Schoepf, Christian Tesche, Jonathan D. Rollins, Hui Liu, Chang Sheng Zhou, Jing Yan, Meng Jie Lu, Guang Ming Lu, Qian Qian Ni, Long Jiang Zhang
Journal: JACC. Cardiovascular imaging (2019)