tbuckley/cabot-search huggingface dataset:
Abstract P344: Temporal Trends of Cardiovascular Health Metrics and Population Attributable Risk for Mortality Among 366,270 French adults.
Authors: Bamba Gaye, Maxime Vignac, Frédérique Thomas, Lucile Offredo, Thomas V Sloten, Xavier Jouven
Journal: Circulation (2019)

Background: Current time trends of objectively measured cardiovascular health and their relation with population attributable risk for mortality over time -in Western Europe are unknown.We aimed to investigate time trends in cardiovascular health metrics and estimate the population attributable risks of these metrics in relation to all-cause mortality in the population at large, as well as in important subgroups. Methods: In this study, we used a community-based sample of 366,270 adults from France who had a standardized examination to assess cardiovascular risk factors between 1992 and 2011 and with outcome surveillance spanning until 2016 (25 years), Temporal trends of cardiovascular health metrics were computed using metrics defined by the American Heart Association:smoking, body mass index, total cholesterol, blood glucose and blood pressure and physical activity. Population attributable fraction for all-cause mortality over 25 years were measure. Results: Mean age was 44.7 (SD 13) years and 38% (138,228) were women. Overall, few participants (≤3.5%) met all 6 ideal cardiovascular health metrics at any timepoint. The prevalence of meeting ≥5 ideal cardiovascular health metrics increased from 6.2% in 1992-1996 to 16.6% in 2007-2011 (P&lt;.001). An improvement in cardiovascular health was observed in all subgroups, i.e. younger (from 7.1% to 18.5%) and older individuals (from 1.2% to 4.2%), men (from 3.9% to 12.2%) and women (from 10.1% to 22.5%), those with low (from 8.6% to 11.6%) and high education status (from 14.0% to 19.5%) and those with (from 4.7% to 14.8%)and without depressive symptoms (from 6.5% to 16.8%). However, the rate of improvement was steepest in the most affluent group in comparison with those with lower socio-economic status. Furthermore, the improvement in overall cardiovascular health plateaued between 2002-2006 and 2007-2011, and the population attributable risks for all-cause mortality remained high over time. Conclusions and relevance: Overall cardiovascular health improved from 1992 until 2011 in French adults from the community who benefited from a free standardized health examination. However, the improvement in cardiovascular health was less strong in those with low socio-economic status as compared to those with a higher socio-economic status. Furthermore, the fraction of all-cause mortality attributable to cardiovascular health remained high throughout the study period.
Abstract MP23: Heart Failure is Associated With Incident Venous Thromboembolism: the Atherosclerosis Risk in Communities (ARIC) Study
Authors: Faye L Norby, Christina L Fanola, Amil M Shah, Patricia P Chang, Pamela L Lutsey, Wayne D Rosamond, Mary Cushman, Aaron R Folsom
Journal: Circulation (2019)

Background: Heart failure (HF) hospitalization places patients at increased short-term risk of venous thromboembolism (VTE). However, the degree to which incident HF is a long-term risk factor for VTE is less clear, and it is unknown if the association differs by type of HF. We assessed the association between HF and VTE in the ARIC study. Methods: Our analysis included 10,495 participants (22% black race, 59% female, mean age 62) who were initially free of HF, cancer, and VTE in 2005. We identified incident HF from hospitalization records starting in 2005, and when possible HF was further subcategorized from hospital record review as HF with preserved ejection fraction ≥50% (HFpEF) or reduced ejection fraction of &lt;50% (HFrEF). Incident VTE was adjudicated by physician review and classified as pulmonary embolism (PE) or deep venous thrombosis (DVT), and provoked or unprovoked. We used Cox proportional hazards models to evaluate the association between time-dependent HF and incident VTE. Follow-up time accrued from 2005 until date of VTE, loss to follow-up, death, or the end of 2015, whichever came first. Results: During a mean follow-up of 10 years, we identified 1005 participants who developed hospitalized HF (28% HFpEF; 27% HFrEF) and 262 who had incident VTE events. Incident HF was associated with a significantly higher risk of subsequent incident VTE: multivariable hazard ratio (HR) 5.15, 95% confidence interval (CI) 3.80-6.98. The risk of VTE was similar for HFpEF and HFrEF; HR (95% CI) = 4.71 (2.94-7.52) and 5.53 (3.42-8.94), respectively. The risk was similar when the VTE outcome was subclassified as PE or DVT or as provoked or unprovoked. Conclusion: In this large population-based study, incident HF was associated with a greatly increased risk of VTE, and the risk was similar in participants with HFpEF and HFrEF. Health care providers should consider possible evidence-based strategies to prevent VTE in HF patients, regardless of HF classification.
Idiopathic pulmonary fibrosis and asbestos use
Authors: Christopher M Barber, David Fishwick
Journal: BMJ (2019)

Salciccioli and colleagues note the high mortality from interstitial lung disease in the United Kingdom.1 We found a significant association between mortality from the commonest form of interstitial lung disease (idiopathic pulmonary fibrosis) and mesothelioma.2 Such a relationship is unexpected, as idiopathic pulmonary fibrosis has no identifiable cause, whereas most deaths due to mesothelioma can be explained by …
Phase II study with conventional radiotherapy (RT) + cetuximab in patients with advanced larynx cancer who responded to induction chemotherapy (IC): An organ preservation TTCC study.
Authors: Ricard Mesia, Jose Angel Garcia Saenz, Alicia Lozano, Miguel Pastor, Juan José Grau, Javier Martinez Trufero, Julio Jose Lambea- Sorrosal, Joaquina Martinez Galan, Jose Ramón Mel, Belen Gonzalez, Silvia Vazquez, Manel Manos Pujol, Miren Taberna, Beatriz Cirauqui, Elvira del Barco, Esther Casado, Jordi Rubió, Angeles Rodriguez Jaraiz, Juan J. Cruz
Journal: Journal of Clinical Oncology (2015)

6037 Background: IC with docetaxel/cisplatin/fluorouracil (TPF) is superior to PF in organ preservation. Bioradiotherapy (BRT) is superior to RT alone in the loco-regional control of locally-advanced head and neck tumors. The aim of our study was to evaluate the efficacy and safety of IC followed by BRT for functional larynx preservation. Methods: Phase II, open-label, multicenter study in patients with stage III-IVA laryngeal carcinoma candidates to total laryngectomy (TL). Study was designed to evaluate the laryngo-esophageal dysfunction–free survival (LEDFS) rate at 3 years. Using the one arm survival sample size program (SWOG), calculated recruitment: 94 patients (α .05; ß .1). Critical value > 59%. Patients received 3 cycles of IC with TPF (75/75/750 mg/m2): those who responded received conventional BRT (70 Gy/7 weeks) with cetuximab. Patients without response underwent TL + RT. Neck dissection was planned in patients with residual nodal disease at 2 months after BRT. Results: A total of 93 patients started TPF from October/2008 to February/2011: median age 59.4; 92% male; all PS: 0-1; 35% glottis / 65% supraglottis; 51% stage III / 49% IVA. Response to IC on larynx target lesion: 37 (40%) CR, 34 (37 %) PR, 8 (9 %) SD, 2 (2%) PROG and 12 (13%) not evaluated (2 death, 6 AEs, 3 missing, 1 lost follow-up). Overall response 72 (86 %). 73 (78%) patients followed by BRT: 68 as per protocol, but 2 with only SD and 3 without any response evaluation. Median follow-up: 48 months. 3-year actuarial rates: LEDFS: 69.5% (95%CI: 60-79%); laryngectomy-free survival: 71.2% (95% CI: 61-81%); overall survival: 77.2% (95%CI: 69-86%); disease-free survival: 47.9% (95%CI: 38-58%). TL was performed in 18 patients: 9 (9.7 %) after preservative treatment failure and 9 (9.7 %) in the follow-up (recurrences). The toxicity observed during both IC and BRT were as expected, with only 1 toxic related death (local bleeding during BRT). Conclusions: LEDFS rate was clearly higher than the critical value and with an acceptable toxicity with this protocol, so it is warranted to move to a phase III trial. Clinical trial information: 2008-000332-40.
Short-Term Exposure to Ambient Air Pollution and Asthma Mortality
Authors: Yuewei Liu, Jingju Pan, Hai Zhang, Chunxiang Shi, Guo Li, Zhe Peng, Jixuan Ma, Yun Zhou, Lan Zhang
Journal: American Journal of Respiratory and Critical Care Medicine (2019)

Rationale: Short-term exposure to air pollution has been associated with asthma exacerbation and increased healthcare use caused by asthma, but its effect on asthma mortality remains largely unknown.Objectives: To quantitatively assess the association between short-term exposure to air pollution and asthma mortality.Methods: We investigated 4,454 individuals who lived in Hubei province, China, and died from asthma between 2013 and 2018. A case-crossover design and conditional logistic regression models were applied for data analyses. Exposures to particulate matter ≤2.5 μm in aerodynamic diameter (PM2.5), particulate matter ≤10 μm in aerodynamic diameter (PM10), sulfur dioxide (SO2), nitrogen dioxide (NO2), carbon monoxide (CO), and ozone (O3) were estimated by inverse distance weighted averages of all monitoring stations within 50 km from each case’s home address.Measurements and Main Results: Each interquartile range (IQR) increase of PM2.5 (lag 3; IQR, 47.1 μg/m3), NO2 (lag 03; IQR, 26.3 μg/m3), and O3 (lag 3; IQR, 52.9 μg/m3) were positively associated with asthma mortality, with odds ratios of 1.07 (95% confidence interval, 1.01–1.12), 1.11 (95% confidence interval, 1.01–1.22), and 1.09 (95% confidence interval, 1.01–1.18), respectively. There was no evidence of departure from linearity for these associations. Further adjustment for other pollutants did not change the associations materially. We did not observe significant associations between PM10, SO2, and CO exposures and asthma mortality. Overall, the estimates remained consistent in various sensitivity analyses.Conclusions: Our results provide new evidence that short-term exposures to PM2.5, NO2, and O3 may increase asthma mortality risk. Further studies are needed to confirm our findings in other populations.
Sleep and Alertness in a Duty-Hour Flexibility Trial in Internal Medicine
Authors: Mathias Basner, David A. Asch, Judy A. Shea, Lisa M. Bellini, Michele Carlin, Adrian J. Ecker, Susan K. Malone, Sanjay V. Desai, Alice L. Sternberg, James Tonascia, David M. Shade, Joel T. Katz, David W. Bates, Orit Even-Shoshan, Jeffrey H. Silber, Dylan S. Small, Kevin G. Volpp, Christopher G. Mott, Sara Coats, Daniel J. Mollicone, David F. Dinges
Journal: New England Journal of Medicine (2019)

A purpose of duty-hour regulations is to reduce sleep deprivation in medical trainees, but their effects on sleep, sleepiness, and alertness are largely unknown.
Impact of pure versus mixed metastatic urothelial carcinoma (mUC) histology on response with immune checkpoint inhibitors (ICIs).
Authors: Archana Agarwal, Amin Nassar, Gregory Russell Pond, Justine A. Barletta, Andres Acosta, Sarah Abou Alaiwi, Catherine Curran, Guru Sonpavde
Journal: Journal of Clinical Oncology (2019)

479 Background: PD1/PD-L1 inhibitors have been evaluated in trials enrolling patients (pts) with pure urothelial or mixed urothelial histology containing non-urothelial components. However, any differential impact of pure vs. mixed urothelial histology on ICI benefit is unclear. We conducted a retrospective study to evaluate the impact of pure vs. mixed urothelial carcinoma histology on outcomes with ICIs in pts with metastatic urothelial carcinoma (mUC). Methods: We obtained data from 120 pts with mUC from a single institution (DFCI) who received ICI therapy. Demographic, clinical variables and outcomes (overall response rate [ORR], overall survival [OS]) were collected. Histology was reviewed at DFCI for all pts and recorded as pure urothelial if only urothelial carcinoma was seen or mixed urothelial if components of any other histology were observed in addition to urothelial. A Cox regression analysis was done to study the association of prognostic variables and histology with objective response. Results: Data was obtained from 120 pts, of whom 110 (91.7%) received a single agent PD1/PD-L1 inhibitor (pembrolizumab=58, atezolizumab=52, nivolumab=4, nivolumab + ipilimumab=3, nivolumab + vaccine=2, durvalumab+tremelimumab=1). The median age was 66, 70.8% were male and 72.5% had received prior chemotherapy. 79 (65.8%) tumors originated from the bladder, 39 (32.5%) from the upper tract, 2 (1.67%) had unknown site of origin. 91 (76.6%) had pure urothelial and 28 (23.3%) had mixed urothelial histology. On univariable analysis, pure vs. mixed urothelial histology was not associated with response (HR 1.52 [95% CI 0.59-3.98, p=0.39]). On multivariable analysis, upper tract vs. bladder primary (HR 3.06 [95% CI 1.10-8.49], p=0.032) and higher blood neutrophil to lymphocyte ratio (HR 0.35 [95% CI 0.17-0.72], p=0.004) were associated with lower response rate. Conclusions: In this hypothesis-generating study, pure vs. mixed urothelial carcinoma histology did not appear to significantly impact response to ICI therapy for mUC. The impact of proportion of non-urothelial histology, pure non-urothelial histology and site of primary on response warrants further study.
Lung cancer screening in the first year following US Preventive Services Task Force (USPSTF) recommendation.
Authors: Lalit Aneja, Amishi Desai, Karen Alisa Braithwaite, Corinne Liu, Jeffrey Gary Schneider
Journal: Journal of Clinical Oncology (2015)

e17512 Background: On December 31 2013, USPSTF recommended that all persons age 55 - 80 with 30 pack-year smoking within past 15 years should undergo low-dose computed tomography (LDCT) screening, but adoption of this recommendation has been slow. Methods: Charts of newly diagnosed lung cancer patients presenting to the Winthrop-University Hospital medical oncology practice after January 1, 2014, were reviewed to assess: means of diagnosis, screening eligibility criteria, lung cancer stage and histology. Results: As shown in the table below, just 6 of the first 100 cases were diagnosed on the basis of screening even though 50 of these patients were eligible for screening. Four patients in the age 75 – 80 group were eligible by USPSTF criteria, but their scans would not be covered by Medicare. Other factors that would have limited screening eligibility included age 50-54 (n = 5) and smoking cessation greater than 15 years prior to diagnosis (n = 14). Conclusions: Despite having a LDCT screening program in place at our hospital prior to USPSTF recommendation for lung cancer screening, only a minority of eligible patients are being screened. Increased awareness of screening recommendations amongst primary care givers and broadening of eligibility criteria would enhance the potential benefits of LDCT screening programs. Means of Cancer Diagnosis Total Screen Eligible Stage I Stage II Stage III Stage IV Symptomatic 58 29 7 4 8 39 Incidental 36 16 11 5 6 14 Screening 6 5 3 2 0 1
The effect of VERU-111, a novel oral inhibitor of α and β tubulin, on tumor growth in the human castration-resistant, AR-variant prostate cancer (PCa) model 22Rv1.
Authors: Mark Christopher Markowski, Robert H. Getzenberg, Mitchell S. Steiner, Nilofer Saba Azad, Mario A. Eisenberger, Emmanuel S. Antonarakis
Journal: Journal of Clinical Oncology (2019)

167 Background: VERU-111 is a novel, oral α and β tubulin inhibitor that blocks tubulin polymerization and is not a substrate for multi-drug resistance. In xenograft mouse models of taxane responsive and resistant cancers, VERU-111 results in tumor inhibition at ≤20 mg/kg orally dosed infrequently as 1/week. VERU-111 and docetaxel were tested in the human PCa model, 22Rv1, which expresses androgen receptor splice variants, including AR-V7, and is resistant to abiraterone and enzalutamide. Methods: Human 22Rv1 cells were implanted into SCID mice. When tumors reached 150-200 mm , the animals were randomized into 4 groups (n = 10 per group): PO vehicle; PO VERU-111 5 or 20 mg/kg; or IP docetaxel 10 mg/kg 3X per week. Animal weights and tumor volumes were measured 2X week and at study end. Animals were removed from study when the tumor volume exceeded 2000 mm or upon treatment for 28 days. Results: VERU-111 (PO 5 and 20 mg/kg) 3X/week significantly reduced tumors by 31% (p = 0.049) and 49% (p = 0.010), respectively, compared to vehicle. Administration of 10 mg/kg docetaxel IP had a nonsignificant reduction in tumor size. With respect to toxicity, mice treated with oral VERU-111 either significantly gained (5 mg/kg) or maintained their weight (20 mg/kg), whereas the docetaxel treated mice lost weight (p = 0.013). There was a significantly greater weight in mice treated with VERU-111 versus docetaxel (p = 0.014). Conclusions: VERU-111, a next generation, orally α and β tubulin inhibitor, has significant anti-tumor activity against PCa and other tumors. In the human PCa model 22Rv1, VERU-111 had a statistically significant reduction in tumor growth and was well tolerated. In contrast, IP docetaxel did not significantly reduce tumor growth and had greater toxicity. A phase 1/2 trial evaluating VERU-111 in men with metastatic castration and novel androgen blocking agent (abiraterone or enzalutamide) resistant prostate cancer is in progress. [Table: see text]
Fecal microbiota transplantation for TKI-induced diarrhea in patients with metastatic renal cell carcinoma.
Authors: Ernesto Rossi, Gianluca Ianiro, Brigida Anna Maiorano, Roberto Iacovelli, Loris Lopetuso, Carlo Romano Settanni, Luca Masucci, Gianluca Quaranta, Maurizio Sanguinetti, Emilio Bria, Antonio Gasbarrini, Giampaolo Tortora, Giovanni Cammarota, Giovanni Schinzari
Journal: Journal of Clinical Oncology (2019)

615 Background: Diarrhea is a common adverse event of tyrosine kinase inhibitors (TKI). No standard treatment for TKI-induced diarrhea has been established, although probiotics are commonly used. In several patients TKI dose reduction is necessary. Data showing the interplay between microbiota and TKI-induced diarrhea are reported. The therapeutic modulation of gut microbiota could be useful to ameliorate TKI-related diarrhea. Our study aims to explore the efficacy and safety of fecal microbiota transplantation (FMT), compared with current clinical practice approach, for the treatment of TKI-associated diarrhea in patients with metastatic renal cell carcinoma. Methods: Patients on treatment with Pazopanib/Sunitinib as first line therapy for metastatic renal cell carcinoma and TKI-associated diarrhea (³ 4 stools per day over baseline) were randomize to receive FMT from healthy donor by colonoscopy (fresh faeces) or probiotics (L. casei DG). The primary endpoint was the resolution of TKI-related diarrhea. Baseline fecal samples were collected from all patients and donors. All patients were followed up 7, 15, 30 and 60 days after the treatment for diarrhea. Results: 21 subjects, 10 in FMT arm and 11 in control arm, have been enrolled. At 7 day-follow-up, TKI-related diarrhea disappeared in 10 patients of the FMT group and in 6 patients of the control group (100% vs 54.5%, p = 0.02). At 15-day and 30-day, 9 patients in the FMT group and 0 patients in the control group experienced resolution of diarrhea (90% vs 0%, p = 0.0001). At 60-days 8/10 patients in FMT arm did not have diarrhea. Dose reduction was necessary in 4 patients of the control group. No serious adverse events associated with any of the two treatment protocols were observed. Metagenomic analyses on collected stool samples are ongoing. Conclusions: This open-label randomised controlled trial showed the effectiveness and safety of FMT compared with probiotics in curing TKI-related diarrhea in patients with metastatic renal cell carcinoma, avoiding the necessity of dose reduction. Considering the increasing evidence, the modulation of microbiota trough FMT could also affect the efficacy of immunotherapy for metastatic renal cell carcinoma.
Predictors of renal dysfunction during everolimus treatment in patients with metastatic renal cell carcinoma.
Authors: Ryuichi Mizuno, Ryohei Takahashi, Toshiaki Shinojima, Takeo Kosaka, Akira Miyajima, Mototsugu Oya
Journal: Journal of Clinical Oncology (2015)

e15584 Background: Treatments for metastatic renal cell cancer (mRCC) have evolved impressively over the past decades following the development of targeted drug therapies. Everolimus is an orally administered inhibitor of the mammalian target of rapamycin (mTOR) for the treatment of mRCC. Renal toxicity following targeted agents is one of the adverse events observed in some patients. In the present study, we investigated predictors of decrease in renal function during everolimus treatment in patients with mRCC. Methods: A total of 31 patients with mRCC were evaluated retrospectively. After treatment failure with vascular endothelial growth factor receptor-tyrosine kinase inhibitor (VEGFR-TKI) therapy, all patients received treatment with everolimus 5-10 mg once daily. Serum creatinine levels were measured at baseline before treatment. The estimated Glomerular Filtration Rate (eGFR) was calculated from serum creatinine levels using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Measurement of these parameters was repeated every four weeks over the treatment duration. The correlation between clinicopathological variables and changes in serum creatinine levels or eGFR were examined. Results: One patient (3.2%) achieved a partial response (PR) and 18 patients (58.1%) presented with stable disease (SD), whereas 7 patients (22.6%) showed progressive disease (PD). Five patients were considered not assessable for efficacy. Median PFS was 5.2 months (95% CI 1.9–8.6), and median OS was 25.8 months (95% CI 7.5–44.0). During everolimus treatment, eGFR significantly decreased compared with baseline (p < 0.05). A significant increase in serum creatinine levels during everolimus treatment were also found (p < 0.05). Among those clinicopathological factors studied, renal dysfunction during prior VEGFR-TKI treatment was significantly correlated with changes in serum creatinine levels or eGFR during everolimus treatment (p < 0.05). Conclusions: Everolimus could be nephrotoxic in patients with mRCC who presented with renal dysfunction during prior VEGFR-TKI treatment.