tbuckley/cabot-search huggingface dataset:
Pragmatic vs Explanatory Trials—Reply
Authors: Nariman Sepehrvand, Wendimagegn Alemayehu, Justin A. Ezekowitz
Journal: JAMA Cardiology (2020)

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Adrian Bayley Gillham
Authors: Georgina Calvert
Journal: BMJ (2020)

Consultant psychiatrist (b 1948; q Cambridge/St Mary’s Hospital 1972; MRCP (UK), MRCGP, FRCPsych), died unexpectedly from severe coronary atheroma on 21 January 2020



Adrian Bayley Gillham, named after his great grandfather Dr Bayley, started his career in general medicine at St Mary’s, completing his MRCP(UK) in 1976. Wanting …
How can I explain my high blood pressure to you?
Authors: Evelyn Lawrie
Journal: BMJ (2020)

How can I explain my high blood pressure to you?Evelyn Lawrie describes what it is like to live with white coat syndrome and how health professionals can help her manage this Evelyn LawrieFor most people, having their blood pressure checked is a relatively straightforward process, but for me, living with white coat syndrome, it is more complicated.The syndrome feels like an uncontrollable physical or mental reaction when I am faced with medical professionals.Many people laugh when I try to explain my condition or think I am making it up, but it has caused me many challenges throughout my life.
Gestational Exposures to Phthalates and Folic Acid, and Autistic Traits in Canadian Children
Authors: Youssef Oulhote, Bruce Lanphear, Joseph M. Braun, Glenys M. Webster, Tye E. Arbuckle, Taylor Etzel, Nadine Forget-Dubois, Jean R. Seguin, Maryse F. Bouchard, Amanda MacFarlane, Emmanuel Ouellet, William Fraser, Gina Muckle
Journal: Environmental Health Perspectives (2020)

The etiology of autism spectrum disorder is poorly understood. Few studies have investigated the link between endocrine-disrupting chemicals and autistic traits. We examined the relationship between gestational phthalates and autistic traits in 3- to 4-y-old Canadian children. We also investigated potential effect modification by sex and folic acid supplementation. We enrolled 2,001 women>18 years of age during the first trimester of pregnancy between 2008 and 2011 from 10 cities in Canada. At 3-4 years of age, 610 children underwent neuropsychological assessments including the Social Responsiveness Scale-II (SRS-2) as a measure of autistic traits and social impairment. We measured 11 phthalate metabolites in maternal first trimester urine samples and assessed folic acid supplementation from reported intakes. We estimated covariate-adjusted differences in SRS-2 T-scores with a doubling in phthalate concentrations in 510 children with complete data. Mean total SRS T-score was 45.3 (SD=6.1). Children with higher gestational exposure to mono-n-butyl (MBP) and mono-3-carboxypropyl (MCPP) concentrations exhibited significantly higher total SRS T-scores, indicating greater overall social impairment, as well as higher scores on subdomains, indicating deficits in social cognition, social communication, social motivation, and restricted interests/repetitive behaviors. A doubling in MBP or MCPP concentrations was associated with 0.6 (95% CI: 0.1, 1.0) and 0.5 (95% CI: 0.1, 0.8) higher total SRS T-scores. Associations were consistently and significantly stronger in boys (βMBP=1.0; 95% CI: 0.4, 1.6; n=252) compared with girls (βMBP=0.1; 95% CI: -0.6, 0.7; n=258) and among children who had lower prenatal folic acid supplementation (<400μg/d) (βMBP=1.3; 95% CI: 0.4, 2.3; n=59) compared with those who had adequate folic acid supplementation (≥400μg/d) (βMBP=0.4; 95% CI: -0.1, 0.8; n=451). Higher gestational concentrations of some phthalate metabolites were associated with higher scores of autistic traits as measured by the SRS-2 in boys, but not girls; these small size effects were mitigated by first trimester-of-pregnancy folic acid supplementation. https://doi.org/10.1289/EHP5621.
Supportive care for end-stage kidney disease: an integral part of kidney services across a range of income settings around the world
Authors: Barnaby Hole, Brenda Hemmelgarn, Edwina Brown, Mark Brown, Mignon I. McCulloch, Carlos Zuniga, Sharon P. Andreoli, Peter G. Blake, Cécile Couchoud, Alfonso M. Cueto-Manzano, Gavin Dreyer, Guillermo Garcia Garcia, Kitty J. Jager, Marla McKnight, Rachael L. Morton, Fliss E.M. Murtagh, Saraladevi Naicker, Gregorio T. Obrador, Jeffrey Perl, Muhibur Rahman, Kamal D. Shah, Wim Van Biesen, Rachael C. Walker, Karen Yeates, Alexander Zemchenkov, Ming-Hui Zhao, Simon J. Davies, Fergus J. Caskey
Journal: Kidney International Supplements (2020)
Rapid organoid development, drug screening, and neoadjuvant chemotherapy response prediction for patients with locally advanced bladder cancer.
Authors: Samuel D. Kaffenberger, Jason Brown, Nathan Merrill, Kathryn Marchetti, Li Wei Bao, Xu Cheng, Aaron M. Udager, Lindsey A. Herrel, Nathalie Vandecan, Jeffrey S. Montgomery, Khaled Hafez, Alon Weizer, Todd Matthew Morgan, Ajjai Shivaram Alva, Matthew Soellner, Sofia Merajver
Journal: Journal of Clinical Oncology (2020)

543 Background: Neoadjuvant chemotherapy prior to radical cystectomy (RC) for muscle-invasive urothelial carcinoma (UCCx) is the standard of care though the absolute survival benefit is small, and some patients progress during chemotherapy. While progress has been made in the prediction of sensitivity to platinum-based chemotherapies, providing more accurate, personalized, and clinically-relevant chemotherapy response prediction is an unmet need. We present our early and ongoing experience with rapid, organoid-based drug-screening. Methods: one gram of tumor was procured from patients undergoing TURBT or RC and divided between DNA/RNA sequencing, organoid drug-screening, and patient-derived xenografts. Tissue was dissociated, filtered, and resuspended in organoid media for serial passage and drug screening. Drugs were tested at “Cmax” concentration, which is the maximum plasma concentration in human trials so as to provide physiologic relevance. Results were normalized to control such that a value of 100 indicated no drug effect compared to control, and a value of 0 indicated complete response. Number of drugs screened was dependent upon tissue available, but was often 20-30. Results: 25 patients have undergone rapid organoid development and drug testing to date. Clinical correlations with chemotherapy response are ongoing. Drug response analyses were available 5-10 days following procedure. Select drug response data from the 9 most recent patient organoid samples are presented in the Table. DNA and RNA sequencing and PDX models are in progress. Conclusions: This platform allows for the rapid determination of neoadjuvant chemotherapy response and may further guide selection of therapeutic agents in patients with locally advanced bladder cancer.[Table: see text]
Abstract 27: Implications of Legislative Efforts on Layperson CPR Education
Authors: Tyler D Alexander, Shaun K McGovern, Marion Leary, Vinay Nadkarni, Benjamin S Abella, Audrey L Blewer
Journal: Circulation (2018)

Introduction: Although bystander CPR has been shown to increase rates of survival from out-of-hospital cardiac arrest, recent work has demonstrated low rates of layperson training across the US. In an attempt to increase layperson CPR training, states have passed legislation that mandates CPR training before high school graduation. No study has assessed the impact of this legislation on likelihood of CPR training. Objectives: We assessed whether an association existed between state mandated CPR training during high school and the likelihood of young adults being currently trained or ever trained in CPR. We hypothesized younger individuals in states with required CPR training by graduation would be more likely to be currently trained or ever trained in CPR. Methods: From 09/2015-11/2015, we conducted a nationwide cross-sectional study of the US adult population using random-digit telephone dialing (n=9,022). Data were weighted by state and assessed through univariate and multivariate analyses controlling for confounding variables. Individuals age 18-24 years old were considered “young” and healthcare workers were excluded in the analysis. Subjects in the five states whose mandatory training laws began in or before the 2013-2014 school year were considered. Results: Of the 9,022 participants, individuals were classified by whether they lived in state that mandated training (n=924) or did not (n=8,084). After accounting for confounding variables, 33% of all laypeople in states with mandated training were currently trained while 27% of laypeople in states without mandated training were currently trained (OR: 1.28, 95%CI: 1.07-1.48, p=0.01). Younger adults were 59% more likely to be currently trained in states with mandated training than in states without it (OR: 1.59, 95%CI 1.34-1.89, p&lt;0.01). In addition, younger adults were also 48% more likely to be ever trained in states with mandated training (OR: 1.48, 95%CI: 1.02-2.10 p=0.04). Conclusion: Younger adults were more likely to be trained in states with laws mandating CPR training for high school graduation. In addition, younger adults were more likely to have ever been trained in states with laws requiring compulsory CPR training for high school graduation.
Botulinum toxin can help with foot symptoms in patients with pachyonychia congenita
Authors: A. Koren, E. Sprecher, E. Reider, O. Artzi
Journal: British Journal of Dermatology (2020)

Pachyonychia congenita (PC) is a rare genetic skin disease which is estimated to affect between 5,000 and 10,000 people worldwide. PC can cause severe pain, especially affecting weight-bearing areas, which accompanies thickening of the skin on the feet (keratoderma). Although there are options for treating the various symptoms of PC, most of them are not especially effective at improving the keratoderma and the pain. The successful use of botulinum toxin (Btx) injections for treating keratoderma in PC patients has been documented in three reports over the past decade. The injection technique, doses of Btx, and methods of anesthesia varied between the reports and the patients. In recent years, the authors, who are based in Israel, have adopted the same approach and refined the injection technique and anesthesia procedure, and have adjusted the Btx doses to improve the treatment. The purpose of this study was to describe the authors four-year experience during which they administered a total of 30 Btx injections to five PC patients following the protocol they have designed. The conclusions of the study were that Btx treatment of PC-associated keratoderma following an optimized protocol leads to a major change in patients’ quality of life. The best improvement scores concerned patients’ morning feet burning and ability of long-distance walking (> 500 m). The scores were significantly better if the intervals between Btx injections were less than 100 days. This is a summary of the study: A treatment protocol for botulinum toxin injections in the treatment of pachyonychia congenita-associated keratoderma
Analysis of clinical outcomes according to response status in prospective clinical trials of atezolizumab (atezo) in pretreated locally advanced/metastatic urothelial carcinoma (mUC).
Authors: Jens Bedke, Axel Stuart Merseburger, Yohann Loriot, Daniel Castellano, Ernest Choy, Ignacio Duran, Jonathan E. Rosenberg, Daniel Peter Petrylak, Robert Dreicer, Jose Luis Perez-Gracia, Jean H. Hoffman-Censits, Michiel Simon Van Der Heijden, Viraj Degaonkar, Lars Thiebach, Sabine de Ducla, Simon Fear, Thomas Powles, Cora N. Sternberg
Journal: Journal of Clinical Oncology (2020)

492 Background: Atezo is an approved therapy for mUC based on the IMvigor210 (IM210) and IMvigor211 (IM211) phase 2 and 3 trials. The single-arm phase 3b SAUL study in a broader patient (pt) population showed consistent efficacy and safety. The value of complete response to immunotherapy is well recognized, but less is known about the benefit of partial response (PR) or stable disease (SD). We performed post hoc analyses of outcomes in pts with PR/SD in atezo trials. Methods: Pts with mUC received atezo 1200 mg q3w until disease progression (PD) or unacceptable toxicity. Baseline characteristics, efficacy and safety were analyzed in pts achieving PR or SD in IM210 cohort 2 (2nd line), IM211 (atezo and chemotherapy [CT] arms analyzed separately) and SAUL. Data cutoffs were 5/5/15, 3/13/17 and 9/16/18, respectively. Results: The analysis population included 229 PR and 583 SD pts (183 and 421, respectively, treated with atezo); ~40% of pts had 0 Bellmunt risk factors. Baseline characteristics were generally similar between trials. PD-L1 IC 2/3 was more common in PR than SD pts in atezo-treated (41% vs 26%) and CT-treated (37% vs 23%) pts. Median time to best response (PR or SD) was 2.1 mo across trials and treatments. In PR pts, disease control (DC) and overall survival (OS) durations were longer with atezo than CT (Table). Durations of DC and OS were shorter in SD than PR pts; OS was numerically longer with atezo than with CT in the SD population. Presence of more Bellmunt risk factors was associated with worse OS with CT but showed only a weak (SD pts) or no (PR pts) association in atezo-treated pts. Conclusions: Pts achieving a PR or SD have meaningful OS expectancy; pts with PR on atezo have sustained DC. Clinical trial information: NCT02108652 ; NCT02302807 ; NCT02928406 . [Table: see text]
The tumor immune microenvironment of germline <i>BRCA1/2</i> and sporadic prostate cancer.
Authors: Anna S. Trigos, Anupama Pasam, Patricia Diana Banks, Roslyn Wallace, Simon P. Keam, Heather Thorne, Catherine Mitchell, David Clouston, Declan G. Murphy, Nathan Lawrentschuk, Damien M. Bolton, Daniel Moon, Elena Castro, David Olmos, Phillip K. Darcy, Ygal Haupt, Scott Williams, David L. Goode, Paul J. Neeson, Shahneen Kaur Sandhu
Journal: Journal of Clinical Oncology (2020)

152 Background: Prostate cancer (PC) is considered an immunologically ‘cold’ tumor and therefore patients are generally not considered good candidates for immunotherapy. Tumors arising in germline (g) BRCA1/2 mutation carriers are associated with higher genomic instability and levels of immune infiltration in breast and ovarian cancer. We investigated how germline mutations in DNA repair genes affect the tumor immune microenvironment (TME) of PC. Methods: Archival primary tumor samples from 26 patients with g BRCA2 mutations, 5 with g BRCA1, 5 with mutations in other DNA repair genes ( ATM, CHEK2, FANCI, PALB2 or BRCA2+ MSH2), and 26 sporadic patients were analyzed. OPAL multiplex immunohistochemistry was used to detect 7 markers (CD3, CD4, CD8, FOXP3, PDL1, AMACR, DAPI) to identify immune subsets and provide the X,Y coordinates of single cells. We developed novel computational distance-based methods to characterize the spatial distribution of cells. Gene expression was evaluated with the Nanostring panel of 770 immune genes. Results: g BRCA1/2 carriers showed lower levels of T cells (9.73% of the tumor stroma) compared to sporadic tumors (14.8%). In in both cothors the T cell population was dominated by CD4+ cells (69.5%), with CD8+ cells representing only 25.6%. Sporadic PCs displayed aggregation of T cells into large clusters in the stroma dominated by CD4+ cells and few CD8+ cells, while 77% of high-grade g BRCA2 patients were enriched in high levels of free, non-aggregated CD8+ T-cells in the tumor area. HLA-A expression was 2.37 times higher in g BRCA2 patients ( p = 3.4x10 −8 ), who also showed higher expression of genes associated with a present but suppressed immune system ( p = 1.4x10 −4 ). gBRCA2 patients with larger T-cell aggregates had an overall poorer prognosis compared to patients without (time to metastasis 55.1 vs. 85.3 months, survival time 67.3 vs. 85.0 months). Conclusions: g BRCA2 carriers displayed higher levels of HLA-A, more free CD8+ T cells infiltrating tumor regions and higher inflammatory signatures, suggesting an immune system that could potentially be harnessed. The degree of clustering of T cells (free vs. aggregated) within the TME may provide valuable prognostic information that warrants further validation.
Pleural Fluid suPAR Levels Predict the Need for Invasive Management in Parapneumonic Effusions
Authors: David T. Arnold, Fergus W. Hamilton, Karen T. Elvers, Stuart W. Frankland, Natalie Zahan-Evans, Sonia Patole, Andrew Medford, Rahul Bhatnagar, Nicholas A. Maskell
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

Rationale: Parapneumonic effusions have a wide clinical spectrum. The majority settle with conservative management but some progress to complex collections requiring intervention. For decades, physicians have relied on pleural fluid pH to determine the need for chest tube drainage despite a lack of prospective validation and no ability to predict the requirement for fibrinolytics or thoracic surgery.Objectives: To study the ability of suPAR (soluble urokinase plasminogen activator receptor), a potential biomarker of pleural fluid loculation, to predict the need for invasive management compared with conventional fluid biomarkers (pH, glucose, and lactate dehydrogenase) in parapneumonic effusions.Methods: Patients presenting with pleural effusions were prospectively recruited to an observational study with biological samples stored at presentation. Pleural fluid and serum suPAR levels were measured using the suPARnostic double-monoclonal antibody sandwich ELISA on 93 patients with parapneumonic effusions and 47 control subjects (benign and malignant effusions).Measurements and Main Results: Pleural suPAR levels were significantly higher in effusions that were loculated versus nonloculated parapneumonic effusions (median, 132 ng/ml vs. 22 ng/ml; P < 0.001). Pleural suPAR could more accurately predict the subsequent insertion of a chest tube with an area under the curve (AUC) of 0.93 (95% confidence interval, 0.89-0.98) compared with pleural pH (AUC 0.82; 95% confidence interval, 0.73-0.90). suPAR was superior to the combination of conventional pleural biomarkers (pH, glucose, and lactate dehydrogenase) when predicting the referral for intrapleural fibrinolysis or thoracic surgery (AUC 0.92 vs. 0.76).Conclusions: Raised pleural suPAR was predictive of patients receiving more invasive management of parapneumonic effusions and added value to conventional biomarkers. These results need validation in a prospective multicenter trial.
Treatment timing in localized high-risk prostate cancer treated with radiation and androgen deprivation therapy.
Authors: Shaakir Hasan, Stanislav Lazarev, Daniel Gorovets, Madhur Garg, Robert H. Press, Isabelle Choi, Charles B. Simone
Journal: Journal of Clinical Oncology (2020)

359 Background: Data regarding the impact of overall treatment time in prostate radiotherapy predate the dose escalation era and is absent in high risk disease. We hypothesize that delays in initiating androgen deprivation therapy (ADT) and in completing fractionated radiotherapy (XRT) correlate with worse outcomes in high risk prostate cancer. Methods: Using the National Cancer Database, we identified 9,611 cases of localized high risk prostate cancer, defined as Grade groups 4 and 5 (Gleason 8-10), PSA &lt; 40, and T1-T3N0M0, treated with conventionally fractionated XRT (74-81 Gy, median 78 Gy) and ADT between 2010-2014 with at least 12 months follow-up (median 40). Receiver operating characteristic (ROC) analyses determined a-priori values for days to initiation of treatment (ADT or XRT) and number of “missed” treatment days (number of days beyond the minimum required to complete XRT). Multivariable regression models with propensity matching conveyed the relative impact of these timing parameters on survival. Results: The median time from diagnosis to treatment intervention was 63 days and median missed XRT treatment days was 2.2. The greatest difference in survival was seen when intervention was initiated beyond 74 days from diagnosis (HR=1.21, P=0.045) and when more than 3 XRT treatment days were missed (HR=1.27, P=0.006). Only missed treatment days correlated with survival as a continuous variable (HR=1.028, P&lt;0.001) on multivariable analysis. On a multivariable regression model propensity-matched for missed treatment days, independent predictors for worse survival include older age, higher comorbidity score, dose below 78 Gy, grade group 5, and PSA &gt; 20. Greater than 3 missed treatment days remained an independent predictor; adjusted HR = 1.23 (P=0.002). The lone predictors of missed treatments was African American race (OR=1.21). Conclusions: Although outcomes in prostate cancer are not typically thought to be associated with treatment time, our study, the largest such analysis to date, revealed a strong independent correlation between timely completion of XRT and survival in high risk disease. The association between survival and time to initiating ADT was not nearly as strong.
Tropomyosin Is A Novel Major Fish Allergen Of Unrecognized Importance
Authors: Thimo Ruethers, Sandip Kamath, Aya Taki, Thu Le, Shaymaviswanathan Karnaneedi, Roni Nugraha, Truc Cao, Shuai Nie, Nicholas Williamson, Sam Mehr, Dianne Campbell, Andreas Lopata
Journal: Journal of Allergy and Clinical Immunology (2020)
Use of Lymphocyte Transformation Test to evaluate the recognition of synthetic Clavulanic Acid antigenic determinants by the immune system.
Authors: Ruben Fernández-Santamaría, Alba Rodriguez-Nogales, Maria Vega, Patricia Malagon Conejo, Ezequiel Perez-Inestrosa, Cristobalina Mayorga, Maria Torres Jaen, Tahia Fernandez
Journal: Journal of Allergy and Clinical Immunology (2020)
Growth Rates of Genetically Defined Renal Tumors: Implications for Active Surveillance and Intervention
Authors: Mark W. Ball, Julie Y. An, Patrick T. Gomella, Rabindra Gautam, Christopher J. Ricketts, Cathy D. Vocke, Laura S. Schmidt, Maria J. Merino, Ramaprasad Srinivasan, Ashkan A. Malayeri, Adam R. Metwalli, W. Marston Linehan
Journal: Journal of Clinical Oncology (2020)

Published series of growth rates of renal tumors on active surveillance largely consist of tumors without pathologic or genetic data. Growth kinetics of genetically defined renal tumors are not well known. Here, we evaluate the growth of genetically defined renal tumors and their association with patient clinical and genetic characteristics.
The IPBES Global Assessment: Pathways to Action
Authors: Mary H. Ruckelshaus, Stephen T. Jackson, Harold A. Mooney, Katharine L. Jacobs, Karim-Aly S. Kassam, Mary T.K. Arroyo, András Báldi, Ann M. Bartuska, James Boyd, Lucas N. Joppa, Anikó Kovács-Hostyánszki, Jill Petraglia Parsons, Robert J. Scholes, Jason F. Shogren, Zhiyun Ouyang
Journal: Trends in Ecology & Evolution (2020)
A wireless millimetre-scale implantable neural stimulator with ultrasonically powered bidirectional communication
Authors: David K. Piech, Benjamin C. Johnson, Konlin Shen, M. Meraj Ghanbari, Ka Yiu Li, Ryan M. Neely, Joshua E. Kay, Jose M. Carmena, Michel M. Maharbiz, Rikky Muller
Journal: Nature Biomedical Engineering (2020)