tbuckley/cabot-search huggingface dataset:
Conservative management of low-risk prostate cancer among young versus older men in the United States: Trends and outcomes from a novel national database.
Authors: Amandeep R Mahal, Santino Butler, Idalid Ivy Franco, Luke Roy George Pike, Shuang Zhao, Nina Niu Sanford, Robert Timothy Dess, Felix Y Feng, Anthony Victor D'Amico, Daniel Eidelberg Spratt, James B. Yu, Paul L. Nguyen, Timothy Rebbeck, Brandon Arvin Virgil Mahal
Journal: Journal of Clinical Oncology (2019)

12 Background: The optimal management for men age ≤55 with low-risk prostate cancer (PCa) is debated given quality of life implications with definitive treatment versus potential missed opportunity for cure with conservative management. We sought to define rates of conservative management for low-risk PCa and associated short-term outcomes in young versus older men in the United States (U.S.). Methods: The Surveillance, Epidemiology, and End Results (SEER) Prostate with Active Surveillance/Watchful Waiting (AS/WW) Database identified 50,302 men diagnosed with low-risk PCa from 2010-2015. AS/WW rates in the U.S. were stratified by age (≤55 versus ≥56). Prostate cancer-specific mortality (PCSM)and overall mortality were defined by initial management type (AS/WW versus definitive treatment [referent]) and age. This non-public data was released by the SEER custom data group. Results: AS/WW utilization increased from 8.61% in 2010 to 34.56% in 2015 among men age ≤55 (P trend &lt; 0.001) and from 15.99% to 43.81% among men age ≥56 (P trend &lt; 0.001). Among patients with ≤2 positive biopsy cores, AS/WW rates increased from 12.90% to 48.78% for men age ≤55 and from 21.85% to 58.01% for men age ≥56. Among patients with ≥3 positive biopsy cores, AS/WW rates increased from 3.89% to 22.45% for men age ≤55 and from 10.05% to 28.49% for men age ≥56 (all P trend &lt; 0.001). Five-year PCSM rates were below 0.30% across age and initial management type subgroups. Conclusions: AS/WW rates quadrupled for patients age ≤55 from 2010-2015, with favorable short-term outcomes. These findings demonstrate the short-term safety and increasing acceptance of AS/WW for both younger and older patients. However, there are still higher absolute rates of AS/WW in older patients (P &lt; 0.001), suggesting some national ambivalence toward AS/WW in younger patients.
Pulmonary rehabilitation is effective in patients with tuberculosis pulmonary sequelae
Authors: Dina Visca, Elisabetta Zampogna, Giovanni Sotgiu, Rosella Centis, Laura Saderi, Lia D'Ambrosio, Valentina Pegoraro, Patrizia Pignatti, Marcela Muňoz-Torrico, Giovanni Battista Migliori, Antonio Spanevello
Journal: European Respiratory Journal (2019)

We read with interest the study reported by Collin et al . [1], who carried out a survey on organisation and priorities of national tuberculosis (TB) programmes in Europe. With an estimated annual incidence of 10 million cases, TB is considered one of the three global infectious disease priorities, together with HIV/AIDS and malaria. However, TB incidence has significantly declined in the general European population during the past two decades, with a relative increase in vulnerable groups [2, 3]. The majority of patients completing anti-tuberculosis treatment have sequelae and benefit from pulmonary rehabilitation <http://ow.ly/WyOH30nFQLV> This article belongs to the scientific activities of the WHO Collaborating Centre for Tuberculosis and Lung Diseases, Tradate, ITA-80, 2017-2020- GBM/RC/LDA and of the GTN (Global Tuberculosis Network) Working Group on TB and Pulmonary Rehabilitation, TB Treatment Committee (Chair: Marcela Muňoz Torrico).
Abstract P062: The Benefits of Preemptive Transplant Vary by Cause of End-stage Renal Disease
Authors: Alvin Thomas, Courtenay Holscher, Christine Haugen, Kyle Jackson, Allan Massie, Dorry Segev, Macey Henderson, Fawaz Al Ammary, Daniel Brennan, Jacqueline Garonzik Wang
Journal: Circulation (2019)

Introduction: Cardiovascular events, i.e. cardiac arrest and arrhythmia, are the leading cause of death among patients with end-stage renal disease (ESRD). Kidney transplantation (KT) reduces mortality and is the preferred treatment for ESRD. Generally, preemptive KT, especially with a living donor, reduces mortality over KT after dialysis initiation. Mortality reduction by preemptive KT may vary by cause of ESRD. Hypothesis: Decreased all-cause mortality after preemptive KT varies by cause of ESRD. Methods: We studied 56,927 adult living donor KT recipients from 2000 to 2017 using the Scientific Registry of Transplant Recipients. We compared all-cause mortality in preemptive living donor KT recipients to those who underwent living donor KT within a year of starting dialysis, stratifying by cause of ESRD. We estimated the adjusted hazard ratio (aHR) of mortality comparing KT with &lt;1 year on dialysis to preemptive KT recipients accounting for recipient and transplant factors using inverse probability weights. Results: Compared to recipients on &lt;1 year of dialysis, preemptive KT recipients were more often female, older, college educated, employed, and had higher BMI (all p&lt;0.001). The association between preemptive KT and post-KT mortality did vary by cause of ESRD (Figure 1). For example, among recipients with ESRD caused by type I diabetes, &lt;1 year on dialysis was associated with a higher hazard of mortality (aHR: 1.32 (1.17-1.50), p&lt;0.001). However, among recipients with ESRD caused by hypertension (p=0.1) or type II diabetes (p=0.3), there was not a statistically significantly difference in mortality comparing KT with &lt;1 year on dialysis vs. preemptive KT. Conclusions: Our findings suggest that for particular ESRD patients, like those with type I diabetes, early counseling regarding preemptive KT and finding a living donor are imperative. Future studies should assess whether expedited review of potential living donors for these patients reduces mortality in this population at high risk of cardiovascular events.
Abstract P335: Greater Frequency of Olive Oil Consumption is Associated with Lower Platelet Activation in Obesity
Authors: Ruina Zhang, Manish Parikh, Christine J Ren-Fielding, Sally M Vanegas, Melanie R Jay, Karry Calderon, Edward A Fisher, Jeffrey S Berger, Sean P Heffron
Journal: Circulation (2019)

Healthy lifestyle behaviors, including maintenance of normal weight, are associated with lower risk of atherothrombotic events. In the general population, consumption of olive oil and a Mediterranean diet are associated with reduced risk of cardiovascular disease (CVD). However, less is known about how this affects individuals with obesity. We investigated whether olive oil intake is associated with reduced platelet activation in a cohort of obese, non-smoking, non-diabetic subjects without known CVD. As part of a larger prospective study of platelet function in obesity, we assessed platelet activation (surface P-selectin and PAC1 MFI) with and without agonist (0.025U thrombin, 0.1uM ADP, 0.4uM epinephrine) exposure via flow cytometry. Food frequency surveys were used to estimate diet composition. Subjects were stratified by food intake frequency and platelet activation was compared using ANOVA, with post-hoc independent samples t-testing. Among 63 subjects, the mean age was 32.2 ± 8.0 years and BMI 44.1 ± 8.5 kg/m 2 . Olive oil intake frequency was stratified into 3 groups: ≤ 1 time/wk, n=21; 1 - 3 times/wk, n=18; ≥ 4 times/wk, n=24. The groups did not differ by age, weight, BMI, waist and hip circumferences, platelet count or mean platelet volume. Subjects with more frequent olive oil intake showed lower platelet activation to agonists than those consuming olive oil ≤ 1 time/wk (Figure). Non-agonized platelet activity did not differ significantly by olive oil intake frequency. Notably, we did not observe associations between platelet activity and consumption of red meat, eggs, butter, or margarine. In metabolically healthy obese individuals, more frequent olive oil intake is associated with suppressed platelet activation. We hypothesize that phenolic compounds in olive oil may alter platelet membrane phospholipid content, making platelets less susceptible to activation. For obese individuals, olive oil intake may lower risk of cardiovascular events.
Connections Between Clonal Hematopoiesis, Cardiovascular Disease, and Cancer
Authors: Oscar Calvillo-Argüelles, Siddhartha Jaiswal, Liran I. Shlush, Javid J. Moslehi, Aaron Schimmer, Ana Barac, Paaladinesh Thavendiranathan
Journal: JAMA Cardiology (2019)

Clonal hematopoiesis (CH) has been recently described as a novel driver for cancer and cardiovascular disease (CVD). Clonal hematopoiesis is a common, age-associated disorder marked by expansion of hematopoietic clones carrying recurrent somatic mutations. Current literature suggests that patients with CH have a higher risk of subsequent hematological malignant conditions and mortality attributable to excess CVD. This review discusses the association of cancer with CVD with CH as a potential unifying factor.The prevalence of CH varies based on the sequencing depth, diagnostic criteria, and patient age and ranges from less than 1% in those younger than 40 years to more than 15% to 20% in those 90 years and older. Clonal hematopoiesis is associated with a 0.5% to 1.0% absolute annual risk of hematological malignant condition and a 2-fold to 4-fold higher risk of coronary artery disease, stroke, and CVD deaths, independent of traditional cardiovascular risk factors. In fact, CH appears to have a relative risk similar to that of traditional cardiovascular risk factors for CVD. Experimental studies suggest that the link between CVD and CH is causal, with inflammation as 1 potential mechanism. There may be also a link between CH and CVD in survivors of cancer; however, data to support this association are currently limited.Clonal hematopoiesis represents a premalignant state, with carriers having an increased risk of hematological malignant conditions. Although most carriers will not develop a malignant condition, CH confers an increased risk of CVD, possibly via inflammation. Clonal hematopoiesis may also contribute to CVD in survivors of cancer, although this hypothesis requires validation. Clinically, as advanced sequencing techniques become available, CH may pave the way for precision medicine in the field of cardio-oncology.
Association between Oncologic Drugs Advisory Committee (ODAC) members’ financial conflicts of interest (FCOIs) and recommendations for drug approval by the U.S. Food and Drug Administration (FDA).
Authors: Ariadna Tibau Martorell, Alberto Ocana, Bostjan Seruga, Arnoud J. Templeton, Agusti Barnadas, Eitan Amir
Journal: Journal of Clinical Oncology (2015)

6582 Background: FDA advisory committees influence decisions relating to the regulatory approval of drugs in the United States. Little is known about whether ODAC members’ FCOIs affect the FDA’s oncologic drug approval process. Methods: We consulted the FDA website for transcripts from ODAC meetings between January 2000 and December 2014. We included all meetings at which drugs used for prevention, treatment, or palliation of cancer were discussed. We restricted our analysis to meetings at which yes/no votes were cast for at least one question relating to an oncologic drug. We collected data on drug name, prevalence of self-reported FCOIs of voting members, type of FCOIs (with sponsor or competitor) and the number of members recused or with waivers allowing discussion but no voting. Association between votes favoring a drug, final drug approval and FCOIs of ODAC members were explored using logistic regression. Results: Eighty transcripts were available for analysis. ODAC voted favouring the drug in 50% of cases. In 6% of cases, ODAC voted against a drug, but it was subsequently approved. At least one FCOI was declared for at least one voting committee member in 59% of votes. At least one member was recused or given a waiver in 14% and 6% of votes, respectively. There has been a significant reduction in the proportion of voting members with FCOIs over time (41% in 2000 vs. 0% in 2014, trend p < 0.001). Voting members with any FCOIs were more likely to vote in favor of a drug (OR 1.34, p = 0.04). There was a near-significant interaction between the presence and type of FCOIs; FCOIs with the sponsor were associated with higher odds of voting in favor of a drug compared to FCOIs with a competitor (OR 1.89 vs. 0.97, interaction p = 0.052). Similar results were seen for the association of ODAC members’ FCOIs and final FDA approval (OR 1.42, p = 0.03). Conclusions: FCOIs among voting members of ODAC are common, but have decreased significantly over time. FCOIs, especially with the sponsor, are associated with higher odds of ODAC recommendation and of final FDA approval of oncologic drugs.
Abstract P234: Social Coherence and Religious/Spiritual Coping Skills Modify Associations Between Weight-Related Discrimination and Risk of Multi-System Physiological Dysregulation Among US Adults
Authors: Maya Vadiveloo, Josiemer Mattei
Journal: Circulation (2019)

Background: Weight discrimination is associated with higher multi-system physiological dysregulation, referred to as allostatic load (AL), which increases cardiovascular risk. While reducing weight discrimination is critical for reducing its negative consequences, it is unclear whether individual-level factors can attenuate associations between weight discrimination and AL. This study examined whether religious and spiritual coping practices as well as beliefs about societal complexity modified the effect of weight discrimination on AL among adults aged 25-75y over 10-years. Hypothesis: Individual-level factors may attenuate associations between weight discrimination and AL. Methods: Participants from the national Midlife Development in the US (MIDUS) Biomarker Substudy with self-reported information on weight discrimination, individual-level factors, and perceptions about social coherence were analyzed (n=953). Social coherence (i.e. degree to which the world makes sense) and religious/spiritual coping (i.e. seeking religious/spiritual support for comfort and guidance) were assessed via 4 self-reported Likert items at baseline, with higher scores indicative of higher coherence and coping. Self-reported perceived discrimination across 9 scenarios at baseline and 10-years follow-up were summed and averaged to compute long-term discrimination. The proportion of 24 dysregulated biomarkers within 7 systems was summed to compute AL (range 0-7). Interactions between social coherence and religious/spiritual coping were tested using a threshold of p&lt;0.05. Median splits for social coherence, religious/spiritual coping, and weight discrimination were computed and AL ≥3 was deemed high. Estimated relative risks (RR) were obtained from multivariable models adjusted for age, household income, sex and baseline BMI. Results: Obesity was present in 41% of the sample, 8% reported weight discrimination, and 19% had high AL. Both social coherence (p=0.048) and religious/spiritual coping (p=0.03) modified associations between weight discrimination and AL. In stratified analyses, participants with high social coherence experienced triple the risk of high AL (RR:3.11; 95% CI: 1.82,5.30) while weight discrimination was not associated with AL among individuals with low social coherence (RR:1.35, 95% CI: 0.71,2.61). Conversely, high religious/spiritual coping attenuated associations between weight discrimination and AL (RR: 0.98, 95% CI: 0.27,3.55), while low religious/spiritual coping was associated with AL (RR: 2.46, 95%CI: 1.61, 3.77). Conclusions: Some individual-level factors may modify associations between weight discrimination and high AL. Mindfulness and tools that adjust internalization of societal messages about weight status have the potential to produce beneficial metabolic effects that could improve cardiovascular outcomes.
Management of low-risk prostate cancer in a population-based cohort of Australian men between 2008 and 2016.
Authors: Wee Loon Ong, Farshad Foroudi, Susan M. Evans, Jeremy Laurence Millar
Journal: Journal of Clinical Oncology (2019)

13 Background: The aim of this study is to evaluate the practice pattern of management of NCCN low-risk prostate cancer (LRPC) in a population-based cohort of Australian men. Methods: This is prospective cohort of men captured in Prostate Cancer Outcomes Registry Victoria (PCOR-Vic), who were diagnosed with LRPC between Aug 2008 and Dec 2016. Conservative management was defined as no active treatment (surgery, radiotherapy, or other local therapy) within 12-month of LRPC diagnosis. Chi-squared test for trend was used to evaluate change in practice over time. Multivariate logistics regressions were used to patient-, tumour- and institutional factors influencing the likelihood of conservative management for LRPC. Results: A total of 3238 men with LRPC were identified in the PCOR-Vic database. The median age was 62.6 (range:37-94). The median PSA level was 5.1ng/mL (range: 0.01-9.96). Overall, 1934 (60%) had conservative management, of which 1668 (86%) were documented as being on active surveillance. Of the 1304 (40%) men who active treatment within 12-month of diagnosis, 977 (30%) had surgeries, 289 (9%) had radiotherapy, and 38 (1%) had other local treatment. Overall, there is increasing trend in conservative management for LRPC from 52% in 2009 to 73% in 2016 (P&lt;0.001). In multivariate analyses, age, PSA, clinical stage, institutions and year of diagnosis were all independently associated with conservative management. Men diagnosed in private and regional centres were 26% (95%CI=0.63-0.88, P=0.001) and 40% (95% CI=0.51-0.72, P&lt;0.001) less likely to have conservative management for LRPC. Conclusions: This is the largest Australian series on management of LRPC to date. We observe increasing use of conservative management for LRPC over time, however, there is large institutional variations in care with men diagnosed in private and regional centres more likely to have active local management for LRPC.
Modeling time from bone metastasis to death in a racially diverse cohort of military health care beneficiaries.
Authors: Jennifer Cullen, Yongmei Chen, Huai-Ching Kuo, Kevin R. Rice, Inger L. Rosner, Jonathan Forsberg
Journal: Journal of Clinical Oncology (2019)

246 Background: Development of prostate cancer (PCa) metastasis, while uncommonly observed in US men, typically occurs to bone and ultimately leads to disease-specific death. The goal of this study was to estimate OS in a racially diverse cohort of military health care beneficiaries diagnosed with metastatic PCa to bone, to enhance understanding of factors such as patient race and receipt of palliative treatment, that potentially affect OS in advanced PCa patients. Methods: A retrospective cohort study was conducted, examining men consented to participate in the CPDR multi-center national database who underwent biopsy for suspicion of prostate cancer between 1989-2017 and subsequently diagnosed with bone metastasis, confirmed by bone scan, bone biopsy and/or MRI. Multivariable Cox proportional hazards (PH) analysis was used to model OS as a function of race and palliative treatment, controlling for clinical covariates. Hazard ratios (HR) and 95% Confidence intervals (CI) are reported. Results: Among 17,356 patients diagnosed with prostate cancer (PCa) between 1989 and 2017, 869 (5.0%) developed bone metastasis. Median patient age was 67 years; median follow-up time following diagnosis with bone metastasis was 2.4 years. Over one-fifth of patients (22.5%) self-reported as African American. Only 11.5% of all patients with metastasis received palliative treatment (radiation (RT) only, RT+ hormone therapy (HT), RT+HT, or RT+HT+chemotherapy). While race did not predict OS, receipt of palliative treatment was strongly predictive of better OS (p&lt;0.0005). Conclusions: Patient race did not predict OS among those with distant metastatic PCa but receipt of palliative care and slower PSADT were critical factors in lengthening OS. This work is being extended to examine the combinations and sequencing of palliative care on OS, to provide improved patient-tailored prediction tools for men with advanced prostate cancer. [Table: see text]
Paediatrician is criticised for failing to report on care cases
Authors: Clare Dyer
Journal: BMJ (2019)

A family court judge has criticised a consultant paediatrician in an open judgment after becoming “deeply concerned” about her behaviour as an expert witness in a child care case.1

Judge Clifford Bellamy said that Kathryn Ward, the expert jointly instructed by all the parties in the case of two brothers, had produced a series of excuses for not producing her reports and promises that she then failed to keep.

Six months after she was asked to report on one child, and four months after the instructions to report on the other, she had still not produced her reports or even seen the brothers and seemed to have spent “little if any time” reading their medical …
Activity of the alkylating histone-deacetylase inhibition fusion molecule EDO-S-101 in preclinical models of human glioblastoma independent from MGMT expression.
Authors: Thomas Mehrling, Enrico Ricevuto, Giovanni Luca Gravina, Andrea Mancini, Claudio Festuccia
Journal: Journal of Clinical Oncology (2015)

e13031 Background: EDO-S101 combines the DNA damaging effect of bendamustine with the pan-histone deacetylase inhibitor vorinostat. The molecule was tested in models of human MGMT negative and positive glioblastoma. Methods: Eight glioblastoma cell lines and five patient derived glioblastoma stem cell lines were studied in vitro. In vivo studies were performed in cell line xenografts using U251 (MGMT-neg.), U87MG (partially methylated MGMT), T98G (MGMT-pos.) and orthotopically, using luciferase transfected U87MG. Tumour volumes were measured to calculate time to progression (TTP), and imaging to estimate overall survival. Results: EDO-S101 demonstrated bi-functional properties in vitro by showing hyperacetylation of H3, tubulin and p53 while elevation of p21, p19 and p27, CRM1-mediated reduction of survivin and cyclin D1 activity as well as the suppression of Bcl-2 and Mcl-1 indicated cell cycle arrest and apoptosis. Differentiation of GBM and glioblastoma stem cells was indicated by increased expression of glial fibrillary acid protein (GFAP) and N-cadherin and reduced expression of nestin. Antiangiogenic activity was demonstrated in vitro in human brain endothelial cells and radio sensitizing activity on clonogenic cells treated with RT. EDO-S101 versus RT or temozolamide (TMZ) and the combination of both were studied in U251, U87MG and T98G xenografts. EDO-S101 significantly increased TTP compared to TMZ irrespective of MGMT expression. TTP was significantly longer in EDO-S101 treated animals compared to RT (HR > 15.0). Similar TTPs were recorded for EDO-S101 single agent compared to the combination of RT+TMZ in U87MG and U251 models, except in T98G where EDO-S101 showed moderately higher TTP. Finally, combination of EDO-S101 with RT showed superior TTPs compared with TMZ+RT.In the orthotopic U251 model, overall survival was higher for EDO-S101 compared to TMZ and RT alone, but lower than the RT+TMZ combination Conclusions: EDO-S101 is effective in models of human glioblastoma irrespective of MGMT status and in combination with RT. The data supports studying EDO-S101 in patients with glioblastoma in a first in FIH study.