tbuckley/cabot-search huggingface dataset:
Markedly Reduced Risk of Internal Malignancies in Patients With Vitiligo: A Nationwide Population-Based Cohort Study
Authors: Jung Min Bae, Kee Yang Chung, Sook Jung Yun, Heesu Kim, Byung Cheol Park, Joung Soo Kim, Soo Hong Seo, Hyo Hyun Ahn, Dong-Youn Lee, You Chan Kim, Hyang Joon Park, Miri Kim
Journal: Journal of Clinical Oncology (2019)

Recent studies indicated that the autoimmunity of vitiligo exerts effects on cells other than melanocytes, which confer reduced risks of both melanoma and nonmelanoma skin cancers in patients with vitiligo. However, the risk of internal malignancy in patients with vitiligo has not been elucidated.We conducted a population-based retrospective cohort study using data from the Korean National Health Insurance claims database obtained from January 2007 to December 2016. All patients age 20 years or older with vitiligo who had at least two contacts with a physician from 2009 to 2016, during which a principal diagnosis was made, were identified (vitiligo group). Controls were randomly selected (two per patient with vitiligo) after frequency matching with the vitiligo group for age and sex during the same period (control group).A total of 101,078 patients with vitiligo and 202,156 controls without vitiligo were included. The incidence rates of internal malignancies were 612.9 and 708.9 per 100,000 person-years in the vitiligo and control groups, respectively. Patients with vitiligo showed a significantly reduced risk of overall internal malignancies (hazard ratio [HR], 0.86; 95% CI, 0.82 to 0.89; P < .001) compared with controls without vitiligo after adjustments for age, sex, and comorbidities. With regard to organ-specific malignancies, patients with vitiligo showed a remarkably decreased risk of cancer in the colon and rectum (HR, 0.62; 95% CI, 0.55 to 0.69; P < .001), ovary (HR, 0.62; 95% CI, 0.46 to 0.83; P < .001), and lung (HR, 0.75; 95% CI, 0.65 to 0.86; P < .001).Vitiligo was associated with a reduced risk of overall internal malignancies. These findings suggest that autoimmune diseases, including vitiligo, may provide immune surveillance for the development of cancer beyond the targeted organ.
Reality of Care for Patients with Multiple Myeloma 1995-2016. New Drugs in Routine Care Lead to Improved Survival
Authors: Rudolf Weide, Stefan Feiten, Geothy Chakupurakal, Vera Friesenhahn, Kristina Kleboth, Julia Lutschkin, Jörg Thomalla, Christoph van Roye, Jochen Heymanns
Journal: Blood (2017)
A Systems Biology Approach to Identify Mechanisms of Therapy Resistance in Multiple Myeloma
Authors: Rafael Renatino Canevarolo, Praneeth Reddy Sudalagunta, Maria D Coelho Siqueira Silva, Mark B. Meads, Priscilla Granados, Anders Berglund, Amit Kulkarni, Hongyue Dai, William S. Dalton, Ion Petre, Kenneth H. Shain, Ariosto Siqueira Silva
Journal: Blood (2018)
The BMJ Awards 2017: Outstanding Contribution to Health
Authors: Nigel Hawkes
Journal: BMJ (2017)

Ben Goldacre, a doctor with a visible public presence as a newspaper columnist who relished taking on quacks and charlatans, says the experience has proved valuable in his new role as a defender of evidence based medicine.

“I’ve been attacked and threatened, I’ve been sued, I’ve had people try to bully me, I’ve been followed and harassed at work,” he says. “That’s lucky because now I feel comfortable that facing down bad behaviour is part of the job.” Those who fall short in abiding by the well established rules of evidence based medicine should know that the winner of this year’s BMJ Award for Outstanding Contribution to Health is unlikely to allow their transgressions to go unnoticed.

Goldacre’s books Bad Science , which sold half a million copies, and Bad Pharma show his sure touch. When Bad Pharma was criticised by the drug industry—which argued that the practices he criticised were all in the past and had now been fixed—Goldacre’s supporters rallied behind him, providing the impetus for the formation of the AllTrials campaign, in which The BMJ has been strongly …
Plasma Neurotransmitters and Functional Illness (Part 3 of 3)
Authors: Fuad Lechin, Bertha van der Dijs, Marcel E. Lechin
Journal: Psychotherapy and Psychosomatics (1996)

Although the concept of functional illness has blurred boundaries, some consensus exists on its understanding among clinicians. In short, it is easier to conceive than to define functional illness. Semantic and conceptual discussion concerning this issue have been endless. Many links exist that connect brain and body (mind and organs, psyche and soma). Amongst them, neurotransmitters, released by peripheral neurons and some glandular cells (adrenal, enterochromaffm cells, mast cells), are diverted into the bloodstream. Although neurotransmitters cannot cross the blood-brain barrier, basic and clinical research has progressively established the relationship between central and peripheral neurochemical activities. Hence, it is possible to obtain some approach to the central profile through the measurement of circulating neurotransmitters. However, this approach is more reliable if we can measure all circulating factors and, in addition, test the responses to different kinds of challenges (stressors, drugs, etc.). All diseases (somatic, psychiatric and psychosomatic) present some kind of plasma neurotransmitter disturbance; however, only in some has the whole abnormal profile been established. Technical difficulties as well as expensive procedures have interfered with the generalization of this research area. In the present review article, we summarize data quoted from current scientific literature reporting exhaustive research in this area.
Abstract 16268: Adherence to Secondary Prevention Guidelines and Mortality After Acute Myocardial Infarction
Authors: Matthew D Solomon, Thomas K Leong, Sue Hee Sung, Marc Jaffe, Eleanor Levin, Jamal S Rana, Alan S Go
Journal: Circulation (2017)

Introduction: The long-term mortality impact from the cumulative achievement of multiple guideline targets for secondary prevention after acute myocardial infarction (AMI) is unknown. Methods: We i...
Abstract P2-08-05: Phase I/II trial of palbociclib in combination with bicalutamide for the treatment of androgen receptor (AR)+ metastatic breast cancer (MBC)
Authors: A Gucalp, AD Corben, S Patil, KN Feigin, LA Boyle, CA Hudis, TA Traina
Journal: Cancer Research (2017)

Abstract This abstract was withdrawn by the authors.
<i>Notes from the Field</i>: Lead and Cadmium Exposure in Electronic Recyclers — Two States, 2015 and 2017
Authors: Reed Grimes, Catherine Beaucham, Jessica Ramsey
Journal: MMWR Morbidity and Mortality Weekly Report (2019)

In 2012, the National Institute for Occupational Safety and Health (NIOSH) became aware of the potential for occupational and take-home exposures to lead and cadmium in the electronics recycling industry and contacted electronics industry stakeholders to discuss these exposures and provide information about NIOSHâs ability to investigate workplace hazards.
Spikes in acute:chronic workload ratio (ACWR) associated with a 5–7 times greater injury rate in English Premier League football players: a comprehensive 3-year study
Authors: Laura Bowen, Aleksander Stephan Gross, Mo Gimpel, Stewart Bruce-Low, Francois-Xavier Li
Journal: British Journal of Sports Medicine (2019)

We examined the relation between global positioning system (GPS)-derived workloads and injury in English Premier League football players (n=33) over three seasons.Workload and injury data were collected over three consecutive seasons. Cumulative (1-weekly, 2-weekly, 3-weekly and 4-weekly) loads in addition to acute:chronic workload ratios (ACWR) (acute workload (1-week workload)) divided by chronic workload (previous 4-week average acute workload) were classified into discrete ranges by z-scores. Relative risk (RR) for each range was then calculated between injured and non-injured players using specific GPS variables: total distance, low-intensity distance, high-speed running distance, sprint distance, accelerations and decelerations.The greatest non-contact injury risk was when the chronic exposure to decelerations was low (<1731) and the ACWR was >2.0 (RR=6.7). Non-contact injury risk was also 5-6 times higher for accelerations and low-intensity distance when the chronic workloads were categorised as low and the ACWR was >2.0 (RR=5.4-6.6), compared with ACWRs below this. When all chronic workloads were included, an ACWR >2.0 was associated with a significant but lesser injury risk for the same metrics, plus total distance (RR=3.7-3.9).We recommend that practitioners involved in planning training for performance and injury prevention monitor the ACWR, increase chronic exposure to load and avoid spikes that approach or exceed 2.0.
Boxing Should Be Banned in Civilized Countries—Round 2
Authors: George D. Lundberg
Journal: JAMA (1984)

On Jan 14, 1983,The Journalpublished two major articles<sup>1,2</sup>and two editorials<sup>3,4</sup>on the subject of boxing.The Journal's editor took the position that boxing should be banned in civilized countries based on moral, ethical, and medical grounds. The hullabaloo that followed was instantaneous, massive, and prolonged. It included major network television coverage, newspaper articles and editorials, magazine stories, letters of support, debate, and criticism toThe Journal, and numerous interviews with the various media for authors of all four publications inThe Journal. A Congressional hearing was spurred, and several state legislatures considered actions. With the exception of some closely tied to amateur boxing, virtually no one defended the "sport" as it is. The overwhelming majority of correspondents, witnesses, and authors stated that there was much wrong with boxing. Typical comments in articles, letters, and telephone calls included those decrying the situation: "Boxing is an exhibition of
Survival Outcomes of Patients with Therapy-Related Acute Myeloid Leukemia in the United States
Authors: Raffi Tchekmedyian, Tomas Radivoyevitch, Aaron T. Gerds, Aziz Nazha, Hetty E. Carraway, Anjali S. Advani, Jaroslaw P. Maciejewski, Matt Kalaycio, Navneet S. Majhail, Mikkael A. Sekeres, Sudipto Mukherjee
Journal: Blood (2018)
FDA Approval Summary: Pembrolizumab for the Treatment of Microsatellite Instability-High Solid Tumors
Authors: Leigh Marcus, Steven J. Lemery, Patricia Keegan, Richard Pazdur
Journal: Clinical Cancer Research (2019)

The FDA approved pembrolizumab on May 23, 2017, for the treatment of adult and pediatric patients with unresectable or metastatic, microsatellite instability-high (MSI-H), or mismatch repair deficient (dMMR) solid tumors that have progressed following prior treatment and who have no satisfactory alternative treatment options and for the treatment of unresectable or metastatic MSI-H or dMMR colorectal cancer that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan. The FDA granted the approval based on an understanding of the biology of MSI-H/dMMR across different tumors along with the clinically important effects on overall response rate (ORR) observed in patients who were enrolled in 1 of 5 single-arm clinical trials. The ORR was 39.6% among 149 patients with 15 different tumor types (95% confidence interval, 31.7-47.9), with a 7% complete response rate. The duration of response ranged from 1.6+ months to 22.7+ months, with 78% of responses lasting ≥6 months. Overall, the adverse event profile of pembrolizumab was similar to the adverse event profile observed across prior trials that supported the approval of pembrolizumab in other indications. This approval of pembrolizumab is the first time that the FDA has approved a cancer treatment for an indication based on a common biomarker rather than the primary site of origin.
Analysis of time to castration-resistant prostate cancer (CRPC) after initiating primary androgen depletion therapy (PADT) of prostate cancer.
Authors: Hideyuki Akaza, Shiro Hinotsu
Journal: Journal of Clinical Oncology (2012)

e15106 Background: Recent clinical trials for developing new drugs for castration resistant prostate cancer (CRPC) have been done for the patients who are surgically or medically castrated, with castration level of testosterone. Although patients who received combined androgen blockade (CAB) with anti-androgen must have shown PSA progression after discontinuing the anti-androgen prior to study enrollment, such patients are analyzed together with patients with castration monotherapy. Methods: We analyzed the time to CRPC among the patients with primary androgen depletion therapy (PADT); LH-RH agonist or CAB (LH-RH agonist + anti-androgen) who have registered to the J-CaP study and were followed up for &gt;10 years. Time to CRPC was defined as PSA progression or other disease progression. Patients were stratified into three risk groups using JCAPRA score (JCO 2009; 26: 4309). In addition to the time to CRPC, overall survival length (OS) after initiating PADT was analyzed. Results: Time to CRPC was significantly longer in the CAB group than monotherapy group in intermediate and high risk groups (Table). In addition, in the intermediate and high risk groups, OS was significantly longer for the patients with CAB (Log-rank test). Conclusions: The significant differences of the time to CRPC and OS will influence to the outcome of clinical trials of CRPC. It is important to take the type of ADT in to consideration when we analyze the results of clinical study of CRPC. [Table: see text]
Bariatric Surgery versus Intensive Medical Therapy for Diabetes — 5-Year Outcomes
Authors: Philip R. Schauer, Deepak L. Bhatt, John P. Kirwan, Kathy Wolski, Ali Aminian, Stacy A. Brethauer, Sankar D. Navaneethan, Rishi P. Singh, Claire E. Pothier, Steven E. Nissen, Sangeeta R. Kashyap
Journal: New England Journal of Medicine (2017)

Long-term results from randomized, controlled trials that compare medical therapy with surgical therapy in patients with type 2 diabetes are limited.We assessed outcomes 5 years after 150 patients who had type 2 diabetes and a body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) of 27 to 43 were randomly assigned to receive intensive medical therapy alone or intensive medical therapy plus Roux-en-Y gastric bypass or sleeve gastrectomy. The primary outcome was a glycated hemoglobin level of 6.0% or less with or without the use of diabetes medications.Of the 150 patients who underwent randomization, 1 patient died during the 5-year follow-up period; 134 of the remaining 149 patients (90%) completed 5 years of follow-up. At baseline, the mean (±SD) age of the 134 patients was 49±8 years, 66% were women, the mean glycated hemoglobin level was 9.2±1.5%, and the mean BMI was 37±3.5. At 5 years, the criterion for the primary end point was met by 2 of 38 patients (5%) who received medical therapy alone, as compared with 14 of 49 patients (29%) who underwent gastric bypass (unadjusted P=0.01, adjusted P=0.03, P=0.08 in the intention-to-treat analysis) and 11 of 47 patients (23%) who underwent sleeve gastrectomy (unadjusted P=0.03, adjusted P=0.07, P=0.17 in the intention-to-treat analysis). Patients who underwent surgical procedures had a greater mean percentage reduction from baseline in glycated hemoglobin level than did patients who received medical therapy alone (2.1% vs. 0.3%, P=0.003). At 5 years, changes from baseline observed in the gastric-bypass and sleeve-gastrectomy groups were superior to the changes seen in the medical-therapy group with respect to body weight (-23%, -19%, and -5% in the gastric-bypass, sleeve-gastrectomy, and medical-therapy groups, respectively), triglyceride level (-40%, -29%, and -8%), high-density lipoprotein cholesterol level (32%, 30%, and 7%), use of insulin (-35%, -34%, and -13%), and quality-of-life measures (general health score increases of 17, 16, and 0.3; scores on the RAND 36-Item Health Survey ranged from 0 to 100, with higher scores indicating better health) (P<0.05 for all comparisons). No major late surgical complications were reported except for one reoperation.Five-year outcome data showed that, among patients with type 2 diabetes and a BMI of 27 to 43, bariatric surgery plus intensive medical therapy was more effective than intensive medical therapy alone in decreasing, or in some cases resolving, hyperglycemia. (Funded by Ethicon Endo-Surgery and others; STAMPEDE ClinicalTrials.gov number, NCT00432809 .).
Substantial Cardiovascular Morbidity in Adults With Lower-Complexity Congenital Heart Disease
Authors: Priyanka Saha, Praneetha Potiny, Joseph Rigdon, Melissa Morello, Catherine Tcheandjieu, Anitra Romfh, Susan M. Fernandes, Doff B. McElhinney, Daniel Bernstein, George K. Lui, Gary M. Shaw, Erik Ingelsson, James R. Priest
Journal: Circulation (2019)

Although lower-complexity cardiac malformations constitute the majority of adult congenital heart disease (ACHD), the long-term risks of adverse cardiovascular events and relationship with conventional risk factors in this population are poorly understood. We aimed to quantify the risk of adverse cardiovascular events associated with lower-complexity ACHD that is unmeasured by conventional risk factors.A multitiered classification algorithm was used to select individuals with lower-complexity ACHD and individuals without ACHD for comparison among >500 000 British adults in the UK Biobank. ACHD diagnoses were subclassified as isolated aortic valve and noncomplex defects. Time-to-event analyses were conducted for the primary end points of fatal or nonfatal acute coronary syndrome, ischemic stroke, heart failure, and atrial fibrillation and a secondary combined end point for major adverse cardiovascular events. Maximum follow-up time for the study period was 22 years with retrospectively and prospectively collected data from the UK Biobank.We identified 2006 individuals with lower-complexity ACHD and 497 983 unexposed individuals in the UK Biobank (median age at enrollment, 58 [interquartile range, 51-63] years). Of the ACHD-exposed group, 59% were male, 51% were current or former smokers, 30% were obese, and 69%, 41%, and 7% were diagnosed or treated for hypertension, hyperlipidemia, and diabetes mellitus, respectively. After adjustment for 12 measured cardiovascular risk factors, ACHD remained strongly associated with the primary end points, with hazard ratios ranging from 2.0 (95% CI, 1.5-2.8; P<0.001) for acute coronary syndrome to 13.0 (95% CI, 9.4-18.1; P<0.001) for heart failure. ACHD-exposed individuals with ≤2 cardiovascular risk factors had a 29% age-adjusted incidence rate of major adverse cardiovascular events, in contrast to 13% in individuals without ACHD with ≥5 risk factors.Individuals with lower-complexity ACHD had a higher burden of adverse cardiovascular events relative to the general population that was unaccounted for by conventional cardiovascular risk factors. These findings highlight the need for closer surveillance of patients with mild to moderate ACHD and further investigation into management and mechanisms of cardiovascular risk unique to this growing population of high-risk adults.
SS18-SSX–Dependent YAP/TAZ Signaling in Synovial Sarcoma
Authors: Ilka Isfort, Magdalene Cyra, Sandra Elges, Sareetha Kailayangiri, Bianca Altvater, Claudia Rossig, Konrad Steinestel, Inga Grünewald, Sebastian Huss, Eva Eßeling, Jan-Henrik Mikesch, Susanne Hafner, Thomas Simmet, Agnieszka Wozniak, Patrick Schöffski, Olle Larsson, Eva Wardelmann, Marcel Trautmann, Wolfgang Hartmann
Journal: Clinical Cancer Research (2019)

Abstract Purpose: Synovial sarcoma is a soft tissue malignancy characterized by a reciprocal t(X;18) translocation. The chimeric SS18-SSX fusion protein acts as a transcriptional dysregulator representing the major driver of the disease; however, the signaling pathways activated by SS18-SSX remain to be elucidated to define innovative therapeutic strategies. Experimental Design: Immunohistochemical evaluation of the Hippo signaling pathway effectors YAP/TAZ was performed in a large cohort of synovial sarcoma tissue specimens. SS18-SSX dependency and biological function of the YAP/TAZ Hippo signaling cascade were analyzed in five synovial sarcoma cell lines and a mesenchymal stem cell model in vitro. YAP/TAZ-TEAD–mediated transcriptional activity was modulated by RNAi-mediated knockdown and the small-molecule inhibitor verteporfin. The effects of verteporfin were finally tested in vivo in synovial sarcoma cell line-based avian chorioallantoic membrane and murine xenograft models as well as a patient-derived xenograft. Results: A significant subset of synovial sarcoma showed nuclear positivity for YAP/TAZ and their transcriptional targets FOXM1 and PLK1. In synovial sarcoma cells, RNAi-mediated knockdown of SS18-SSX led to significant reduction of YAP/TAZ-TEAD transcriptional activity. Conversely, SS18-SSX overexpression in SCP-1 cells induced aberrant YAP/TAZ-dependent signals, mechanistically mediated by an IGF-II/IGF-IR signaling loop leading to dysregulation of the Hippo effectors LATS1 and MOB1. Modulation of YAP/TAZ-TEAD–mediated transcriptional activity by RNAi or verteporfin treatment resulted in significant growth inhibitory effects in vitro and in vivo. Conclusions: Our preclinical study identifies an elementary role of SS18-SSX–driven YAP/TAZ signals, highlights the complex network of oncogenic signaling pathways in synovial sarcoma pathogenesis, and provides evidence for innovative therapeutic approaches.
LMO2 Facilitates Synthetic Lethality after PARP Inhibition (PARPi) in Diffuse Large B-Cell Lymphoma (DLBCL)
Authors: Ramiro E Verdun, Salma Parvin, Ariel Ramirez Labrada, Gabriel Emmanuel Santiago, Cortizas M Elena, Sharabi Eden, Aumann Shlomzion, Zhang Yu, Isidro Sanchez-Garcia, Francisco Vega, Jennifer Rose Chapman-Fredricks, Izidore S. Lossos
Journal: Blood (2018)
No deal Brexit: allowing pharmacists to substitute doctors’ prescriptions may be unlawful, says public interest group
Authors: Clare Dyer
Journal: BMJ (2019)

A legal challenge to emergency “no deal Brexit” rules that would allow UK pharmacists to substitute doctors’ prescriptions in cases of drug shortages has been launched at the High Court in London.

A regulation came into force on 9 February that allows the health and social care secretary, Matt Hancock, to issue “serious shortage protocols” as and when a shortage of medicines arises.1 The move is part of preparations for the possibility that parliament does not agree a deal for leaving the EU and crashes out without one. …