tbuckley/cabot-search huggingface dataset:
Polymorphisms of the serotonin transporter and Monoamine Oxidase A gene in patients with metastatic midgut carcinoid tumors
Authors: A. van der Horst-Schrivers, E. de Vries, P. Willemse, I. Kema, T. Links, H. Boezen, A. Wymenga
Journal: Journal of Clinical Oncology (2007)

4557 Background: In patients with metastatic midgut carcinoid tumors increased serotonin secretion is related to the carcinoid syndrome and mortality. Free serotonin is taken up via the serotonin transporter (5-HTT) in the liver and the lung and metabolized to 5- hydroxyindolacetic acid (5-HIAA) by Monoamine Oxidase A (MAO-A). The 5-HTT gene has a functional polymorphism in the promoter region (5-HTTPLR), with a short (S, less active) and long (L) allele and a polymorphic region in the second intron with variable number tandem repeats (VNTR-2). The MAO-A gene contains a length polymorphism in its promoter region (MAOA-LPR). To determine the clinical effects of the serotonin metabolizing capacity of individual patients, the association between different genotypes and symptoms (flushes and diarrhea) and survival was studied. Methods: 107 patients with metastatic midgut carcinoid tumors were genotyped for 5-HTTPLR, VNTR-2 and MAO-A-LPR. Differences were tested using Chi-square test and survival according to genotypes was analyzed using Kaplan Meier survival curves and tested with a log rank test. The independent effect of genotypes on survival was studied with multivariate Cox regression analysis with adjustments for the urinary 5-HIAA level, age at presentation and the presence of liver metastases. Results: The various genotypic variants were not related to flushes or diarrhea. Patients with the SS variant of 5-HTTLPR had a shorter median survival (45 months, 95% Confidence Interval (CI) 0.50–90) compared to patients with the LS (113 months, 95% CI 53–172) and the LL variant (90 months, 95% CI 64–115) (P=0.02). After adjustment, survival in patients with the SS variant remained worse with an odds ratio of 0.43 (95% CI 0.23–0.83; P=0.009) and 0.63 (95% CI 0.33–1.11; P=0.1) compared to patients with the LS and the LL variant respectively. Survival was not influenced by the VNTR-2 or MAOA-LPR. Conclusions: The SS genotype of the 5-HTTLPR is independently associated with a worse survival in patients with metastatic midgut carcinoid tumors. No significant financial relationships to disclose.
Gemcitabine oxaliplatin (GEMOX) is an active combination in heavily pretreated metastatic breast cancer (MBC)
Authors: F. M. Penault-Llorca, B. Nayl, M. Mouret-Reynier, M. Leheurteur, I. Van Praagh, X. Durando, J. Ferriere, H. Cure, P. Chollet
Journal: Journal of Clinical Oncology (2007)

1082 Background: This study was performed to evaluate retrospectively the efficacy and tolerance of gemcitabine plus oxaliplatin (GEMOX) as salvage chemotherapy in patients with metastatic breast cancer (MBC) in a mono-institutional series. Methods: From January 2003 to March 2005, 38 MBC patients were treated at disease progression according to three schedules: (a) gemcitabine 1000 mg/m 2 on day 1 and 8 and oxaliplatin 100 mg/m 2 on day 1 every three weeks (n=30); (b) gemcitabine 1,000 mg/m 2 on day 1, followed same day by oxaliplatin 100 mg/m 2 every two weeks (n=7); (c) gemcitabine 1250 mg/m 2 on days 1 and 8 and oxaliplatin 100 mg/m 2 on day 1 every four weeks (n=1). Results: All patients (median age, 58 years) received prior chemotherapy for metastatic disease (median of four lines). Radiological response was assessed in 36 patients: 12 patients (33%) experienced a partial response and 11 patients (31%) had a stable disease. The median times to progression and survival were 4 months (range, 0–21 months) and 10 months (range, 2–24 months), respectively. A total of 233 cycles were administered with a median of 5.5 cycles per patient (range, 1–21 cycles). Grade 3/4 toxicity consisted of myelotoxicity in 26% of patients and neurotoxicity in 8%. Conclusions: This retrospective study suggests that GEMOX is an effective combination with a good tolerance profile in heavily pretreated MBC. Further evaluation of this regimen is warranted in this tumor indication. No significant financial relationships to disclose.
Abstract P226: The Effect Of Isometric Exercise On Aortic Valve Function And Aortic Dimensions In Adolescents With Bicuspid Aortic Valves
Authors: Jacob C Hartz, Laura Mansfield, David Brown, Jonathan Rhodes
Journal: Circulation (2020)

Introduction: Central arterial pressure rises to much higher levels during heavy isometric exercise compared to other forms of exercise. For this reason, patients with bicuspid aortic valves (BAV) are often restricted from heavy isometric exercise. Although this approach may be theoretically appealing, no data exists regarding the efficacy of this activity restriction. Methods: Patients between the 12-19 years old with BAV were approached during a routine clinic visit. Patients were excluded if they had a diagnosed syndrome or had undergone a procedure involving the aortic valve. Patients were assumed to have been exercise restricted, regardless of aortic dimensions. Patients completed a questionnaire regarding frequency and intensity of isometric exercise during the 12-month period prior to the visit. We then compared aortic dimensions and qualitative (1-4 scale) estimates of aortic insufficiency (AI) from an echocardiogram performed during the current visit and one obtained 2-5 years previously, using paired t-tests and multivariable regression controlling for age, gender, and participation in isometric exercise. Results: In this unique data set of 37 individuals (41% female, average age 14.8 years), 6 (16%) participated in isometric exercise. There was no significant increase in the aortic root Z-score (0.004 [95 th CI -0.20, 0.21) or in the ascending aorta Z-score (0.11 [95 th CI, -0.15, 0.37], p=0.4) between the first and second visits. Further, there was no differences in the change aortic root Z-score (β=-0.39, p=0.39) and ascending aorta Z-score (β=-0.30, p-0.699) between those who participated in isometric exercise and those who did not. However, although the sample size in this preliminary group of patients was small, the increase in AI severity among those participating in isometric exercise was clinically significant and approached statistical significance (β=0.37, p=0.1). These results did not change even after controlling for age, gender, and time between echocardiograms. Conclusion: Most adolescents with BAV follow recommendations to limit isometric exercise. Time-related changes in aortic dimensions were similar among patients who refrained from isometric exercise and those who engaged in isometric exercise. AI however may have progressed more rapidly in those who participated in isometric exercise.
Abstract P102: Potential U.S. Population Impact Of Low Cardiovascular Health In Terms Of Preventable Loss Of Life-span And Health-span
Authors: Sadiya S Khan, Hongyan Ning, Norrina B Allen, Joshua D Bundy, John T Wilkins, Donald M Lloyd-Jones
Journal: Circulation (2020)

Introduction: Individuals who maintain optimal cardiovascular health (CVH) live a longer, healthier life without cardiovascular disease (CVD). In order to quantify the population burden of sub-optimal CVH, we estimated potential loss of health- and life-span in a nationally representative sample of middle-aged US black and white adults. Methods: We first calculated individual-level composite CVH scores (range 0-14 points), including all 7 AHA-defined CVH metrics (smoking, diet, physical activity, body mass index, blood pressure, glucose, and cholesterol) using data from middle-aged participants (40-49 years) from 3 population-based cohorts. We categorized participants into low (0-6), moderate (7-9), and high (10-14) CVH and used Irwin’s restricted means to estimate years lived free of and with CVD. Next, we determined the contemporary prevalence of low, moderate, and high CVH in middle-aged black and white adults (40-59 years) pooled from 3 NHANES survey cycles (2011-2016). Finally, we generated estimates of CVD-free and overall years of life lost in moderate and low CVH compared to high CVH subgroups, weighted to the US population accounting for the NHANES complex survey design. Results: Of 12,906 participants in the pooled cohort, 23% were black and 56% women. Low and moderate CVH were associated with 4.41±0.02 and 1.86±0.01 fewer healthy years lived without CVD and 2.43±0.02 and 1.09±0.01 fewer overall years of life, respectively. This resulted in a greater proportion of life lived with CVD across all race-sex groups (FIGURE). When weighted to the US population, we estimate that approximately 230.8 (203.5, 258.0) and 97.1 (95% CI 85.6, 108.6) million healthy life years will be lost due to low and moderate CVH, respectively, in middle-aged adults. Conclusions: The projected loss of healthy CVD-free years and total life years due to low and moderate CVH is substantial. Maintenance of optimal CVH into mid-life may represent a significant opportunity to extend healthspan and mitigate disparities in the US population.
Changes in estrogen receptor (ER), progesterone receptor (PR) and HER2/neu status with time: Discordance rates between primary and metastatic breast pathology samples
Authors: R. J. Broom, P. Tang, C. Simmons, L. Bordeleau, F. P. O’Malley, N. Miller, I. L. Andrulis, D. M. Brenner, M. Clemons
Journal: Journal of Clinical Oncology (2007)

1024 Background: The occurrence of changes in tumor receptor profile (ER, PR and HER-2/neu) between primary and metastatic tissue has been recognised and may have significant treatment implications. Previous reports on receptor discordance rates have tended to be from sub-studies of clinical trials. We sought to evaluate the degree of ER, PR and HER-2/neu receptor discordance in patients treated at two Canadian cancer centres. Methods: Archival data was collected on patients for whom tissue from both primary and metastatic sites was available. Patients with recurrences in the breast or axilla were excluded. ER, PR and HER-2/neu status in the primary and metastasis were compared. Additional information including adjuvant therapy and time to metastasis biopsy was gathered. Results: To date, data is available on 80 patients. Hormone receptor (HR) status was available for 96% of primaries and 56% of metastases. HR status on both the primary and the metastasis was performed in 51% of cases. The discordance rate for ER was 21% (2-sided p=0.0096). 12% of patients changed from ER+ to ER- and 9% changed from ER- to ER+. The discordance rate for PR was 37% (2-sided p=0.0001), with all of these patients changing from PR+ to PR-. No significant HR discordance was found among different adjuvant hormone therapy subgroups. There was no correlation between HR discordance and time to rebiopsy. No discordance for HER-2/neu was found. Conclusions: Significant discordance for HR status was observed, 21% for ER and 37% for PR. HER-2/neu discordance was not observed. We are currently exploring the practical implications of these discordance rates on the management of advanced breast cancer patients in a prospective trial. No significant financial relationships to disclose.
Abstract 14154: Final Report of the OSLER-1 Study: Long-Term Evolocumab for the Treatment of Hypercholesterolemia
Authors: Michael J Koren, Marc S Sabatine, Robert P Giugliano, Gisle Langslet, Stephen D Wiviott, Andrea Ruzza, Yuhui Ma, Andrew Hamer, Scott M Wasserman, Frederick J Raal
Journal: Circulation (2018)

Introduction: Evolocumab and other monoclonal antibodies against PCSK9 reduced major adverse CV outcomes in clinical trials of patients with CV disease treated up to a median of 2.8 years. OSLER-1 ...
Abstract P321: Assembly and Validation of a Heart Failure Free Cohort From the Reasons for Geographic and Racial Differences in Stroke Study
Authors: Lauren Balkan, Matthew Mefford, Ligong Chen, Madeline R Sterling, Raegan W Durant, Monika M Safford, Emily B Levitan, Parag Goyal
Journal: Circulation (2020)

Introduction: Studies of incident heart failure (HF) have provided insights into key risk factors for the disease but have been limited to select populations that often lack geographic, racial, and gender diversity. There is a need to assemble a HF-free cohort using a contemporary, geographically diverse sample. Aim: To develop and validate a strategy for assembling a HF-free cohort from the REasons for Geographic And Racial Differences in Stroke (REGARDS) study. Methods: To assemble a HF-free cohort, we identified and excluded REGARDS participants who were taking HF-specific medications at baseline including: digoxin without atrial fibrillation, angiotensin converting enzyme inhibitor/angiotensin receptor blocker plus beta-blocker in the absence of hypertension, carvedilol, spironolactone, loop diuretic or a combination of hydralazine and nitrates. We then examined the subgroup of REGARDS participants with at least 6 months of Medicare claims at the time of the baseline assessment; we evaluated diagnostic performance (negative predictive value, positive predictive value, sensitivity and specificity) using three Medicare claims-based definitions of HF as the referent standard: Hospitalization for HF, Principal Diagnosis of HF, and Any Diagnosis of HF. Results: Among 28,884 eligible participants, 3,125 used HF-specific medications at baseline, leaving 25,759 (89%) participants in the proposed HF-free cohort. Participants in the HF-free cohort had a lower prevalence of coronary disease, atrial fibrillation, and diabetes compared to excluded participants. Depending on the Medicare definition used as the referent, the percent of the HF-free cohort without evidence of HF based on Medicare claims (the negative predictive value) ranged from 95.0-99.2% (Table 1). Negative predictive value was stable across age, sex, and race strata. Conclusions: This medication-based strategy to assembling a HF-free cohort in REGARDS can serve as a basis for future studies to examine incident HF in REGARDS and similar studies.
A post-treatment individualized prescriptive exercise and recreation therapy intervention for breast cancer patients
Authors: D. G. Groff, C. L. Battaglini, J. Peppercorn
Journal: Journal of Clinical Oncology (2007)

19637 Background: The number of breast cancer survivors is increasing due to early detection and advancements in treatment leading to increased concern with long term side effects and quality of life after therapy for early stage breast cancer. The Get REAL &amp; HEEL Breast Cancer Program addresses the physiological and psychological declines experienced by breast cancer survivors post-treatment through combined exercise (EX) and recreation therapy (RT) to strengthen the body and mind of survivors and improve overall QOL. Methods: Women with early stage breast cancer within 6 months from completion of initial therapy were recruited to participate in a combined EX and RT intervention. The EX consisted of cardiovascular endurance (VO 2 Max ), muscular endurance (ME) and flexibility (FL) training. The RT included activities such as leisure counseling, bio-feedback, heart-math, crafts, and a ropes course. Each participant engaged in an individually prescribed intervention for 8 weeks, 3 times per week, for approximately 1.5 hour per therapy session. A battery of fitness and psychological assessments including, VO 2 Max , body composition (BC), ME, FL, fatigue (F), depression (D), QOL were used to assess baseline parameters and outcomes. Descriptive statistics presenting the results of baseline and final assessments were used to evaluate program outcomes. Results: Fifteen subjects, age 30 to 75, volunteered for the program. At initial analysis, clinically relevant changes in physiological and psychological parameters were observed. Improvements in VO 2 Max , BC, and ME were observed for all subjects. Positive changes in psychological parameters were also observed in all of subjects including decreased F and D accompanied by increased QOL. Conclusions: The results of this pilot program are promising and suggest that further evaluation of this novel combination of EX and RT to improve physical and emotional functioning, and overall QOL after breast cancer treatment are warranted. No significant financial relationships to disclose.
Abstract 51: Effects of Dietary Patterns on Subclinical Cardiac Damage: Results From the DASH Trial
Authors: Stephen P Juraschek, Lara C Kovell, Lawrence J Appel, Edgar R Miller, Frank M Sacks, Robert H Christenson, Heather Rebuck, Alexander R Chang, Kenneth J Mukamal
Journal: Circulation (2020)

Background: The Dietary Approaches to Stop Hypertension (DASH) diet (rich in fruit (F), vegetables (V), low-fat dairy, and fiber, and reduced in saturated fat and cholesterol) lowered blood pressure (BP) and low-density lipoprotein cholesterol after 8 weeks compared with a typical American diet. However, direct effects on cardiovascular damage are unknown. Hypothesis: The DASH diet reduces cardiac injury, strain, and inflammation compared to a typical American diet. Methods: The DASH feeding study was a 3-arm, parallel-design, randomized controlled trial of adults with systolic BP (SBP) &lt;160 mm Hg and diastolic BP (DBP) of 80-95 mm Hg, without cardiovascular disease (CVD) and not taking BP medications. Participants were randomized to 8 weeks of monitored feeding with: a typical American diet with 3.6 servings of F/V per day (ref), a F/V-enriched diet (8.5 servings of F/V per day), or the DASH diet (9.6 servings of F/V per day). Calories were adjusted to keep weight constant throughout feeding. We compared the effects of these diets on 3 cardiac biomarkers: high-sensitivity cardiac troponin I (hs-cTnI), N-terminal b-type pro natriuretic peptide (NT-proBNP), and high-sensitivity C-reactive protein (hs-CRP), measured in stored serum collected at baseline and after feeding. Results: Of the 257 participants with available specimens, 33% were aged &gt;50 yrs, 48% were women, and 56% were non-white. Mean baseline SBP/DBP was 131/85 mmHg. Compared to control, the F/V-enriched diet reduced hs-cTnI by 53% (95% CI: 18, 73; P = 0.008) and NT-proBNP by 24% (95% CI: 7, 38; P = 0.01) ( Figure ). Similarly, compared to control, DASH reduced hs-cTnI by 49% (95% CI: 11, 71; P = 0.02) and NT-proBNP by 20% (95% CI: 2, 35; P = 0.04). Hs-CRP did not differ between diets, and none of the markers differed between DASH and F/V-enriched diets. Conclusions: In adults with high BP but not CVD, both F/V-enriched and DASH diets lowered sensitive markers of cardiac injury and strain over 8 weeks. Our study demonstrates early, direct cardiovascular benefits from diets rich in F/V.
Osteonecrosis of the jaw (ONJ) in cancer patients (pts) treated with bisphosphonates (B): Results of a monoinstitutional monitoring program
Authors: N. La Verde, K. Borgonovo, M. C. Garassino, P. Sburlati, D. Pedretti, S. Perrone, D. Mihali, C. Mantica, B. Galassi, G. Farina
Journal: Journal of Clinical Oncology (2007)

19601 Background: B reduce bone metastases complications. ONJ is a serious adverse event during B treatment. Therefore, it's necessary to identify some procedures to reduce ONJ injures in a monitoring program. Patients and Methods: We retrospectively reviewed how an active program of prevention based on clinical oral cavity examination, dentists and pts education might improve ONJ outcome in pts receiving pamidronate (P) 90 mg monthly or zoledronate (Z) 4 mg monthly. Results: from October 2003 to October 2006, 154 consecutive pts were treated; 95 females, 59 males; primary tumors: 66 breast, 28 prostate, 26 lung, 9 myeloma, 4 NHL, 21 other. In June 2005 the monitoring program started on all our pts. ONJ was diagnosed in 15/154 (9.7%) pts, 8 before and 7 after June 2005; all pts were treated with Z (total 2,987 courses, range 8–43; median courses/pt 19.4) and 4 pts pretreated also with P (total 124 courses, range 12–43, median courses/pt 31. Tumors: 7 breast, 1 kidney, 2 lung, 1 head-neck, 1 thyroid, 1 NHL, 1 prostate, 1 sarcoma. Concomitant therapies: 14 pts chemotherapy; 7 hormonotherapy; 2 head-neck radiotherapy; 5 steroids. Significant anamnesis: 9 recent dentoalveolar procedures, 4 diabetes. First symptoms: multiple recurrent alveolar abscesses 9, pain 3, dental mobility 1, paresthesia of the lower lip 1, exposed bone 1. Main treatments were: antibiotics and antifungals 11, curettages 3, surgical resections 4 (1 partial maxillectomy, complicated by septic shock and oronasal communication, 2 partial mandibulectomies, 1 segmental mandibular resection). These last 4 pts, that had the worst prognosis, were diagnosed before starting the monitoring program, and they had been treated with aggressive dental procedures at the exordium. 7 new ONJ cases, diagnosed after June 2005 were successfully treated without aggressive dentist interventions, achieving a good control. Conclusions: We remark that ONJ B related is a frequent adverse event (9.7%), especially with Z. A monitoring program based on non- surgical treatment and patients and physicians education may improve its management. No significant financial relationships to disclose.
Impact of Molecular Subtyping and Immune Infiltration on Pathological Response and Outcome Following Neoadjuvant Pembrolizumab in Muscle-invasive Bladder Cancer
Authors: Andrea Necchi, Daniele Raggi, Andrea Gallina, Jeffrey S. Ross, Elena Farè, Patrizia Giannatempo, Laura Marandino, Maurizio Colecchia, Roberta Lucianò, Marco Bianchi, Renzo Colombo, Andrea Salonia, Giorgio Gandaglia, Nicola Fossati, Marco Bandini, Filippo Pederzoli, Umberto Capitanio, Francesco Montorsi, Joep J. de Jong, Ryan Dittamore, Yang Liu, Elai Davicioni, Joost L. Boormans, Alberto Briganti, Peter C. Black, Ewan A. Gibb
Journal: European Urology (2020)
Abstract 13121: Fluid Resuscitation in CHF Patients Presenting With Sepsis
Authors: Mulham Shikh Hamdon, Toribiong Uchel, Manishkumar Patel, Victoria Gonzalez, Lina Masso, Anubhav Jain
Journal: Circulation (2019)

Introduction: Sepsis is a life-threatening condition with the cardiovascular system playing a major role. Physicians often hesitate to administer liberal amounts of fluid according to guidelines, 3...
Unraveling the Architecture of Classic Hodgkin Lymphoma One Cell at a Time
Authors: Daniel A.C. Fisher, Stephen T. Oh
Journal: Cancer Discovery (2020)

Abstract Summary: Aoki and colleagues have utilized single-cell RNA sequencing and imaging mass cytometry to describe the landscape of reactive, nonmalignant immune-cell populations present in classic Hodgkin lymphoma (cHL), and delineate their spatial proximity to malignant Hodgkin–Reed–Sternberg cells. From this study, they have identified a LAG3-expressing Tr1-type Treg cell population as prevalent mainly in MHC-II–negative cHL, implying a potential functional relationship underlying the differential responsiveness of MHC-II–negative versus MHC-II–positive cHLs to immunotherapy. See related article by Aoki et al., p. 406.