tbuckley/cabot-search huggingface dataset:
Glutathione S-transferase T1, M1 genetic polymorphisms in cases of acute leukemia
Authors: S. Moawia, M. Elbordiny, A. Saad
Journal: Journal of Clinical Oncology (2007)

7053 Background: Glutathione S-transferases (GSTs) are enzymes that detoxify potentially mutagenic and carcinogenic xenobiotics. The genes encoding isoenzymes M1 and T1 are polymorphic in humans and the phenotypic absence of enzyme activity is caused by a homozygous inherited deletion of the gene. The null genotype has been associated with incidence of several types of solid tumors. In addition, GSTM1 and GSTT1 polymorphisms have been considered as risk factors for developing acute leukemia in a number of studies; however the overall results of these previous reports are inconsistent and even controversial. Methods: The present study was undertaken to determine the frequencies of allelic variants in the GST genes in Egyptians and to explore the possibleinfluence of GSTT1, M1 genetic polymorphisms on the risk of acuteleukemia (myeloid and lymphoid). Results: The prevalence of the GSTM1 and GSTT1 homozygous deletions in 53 Egyptian patients with leukemia (21 ALL and 32 AML) and 87 racially,geographically, age and sex matched healthy control individuals was determined using a multiplex polymerase chain reaction (PCR)-based method. Thegenotype frequencies in the leukemia patients and normal controls were compared using Fisher's exact test. A significantly increased incidence of the GSTT1 null genotype was found in the group of patients compared to the controls (34% versus 15% P = 0.03, OR = 2.98, 95% CI 1.6–7.6). GSTM1 null genotype frequencies in cases were slightly but non-significantly higher than controls (68 % versus 49 %, respectively, P=0.07). Conclusions: In conclusion, this study has shown an increased risk of acute leukemia in adult Egyptian patients associated with the GSTT1 null genotype, as well as the combined GSTM1/T1 null genotype, particularly in AML cases. Study will be further extended to examine the relation between the GSTT1 and GSTM1 null genotypes and the patient's response to chemotherapy. No significant financial relationships to disclose.
Treat obesity with the same effort used to reduce smoking, says lead psychologist
Authors: Gareth Iacobucci
Journal: BMJ (2019)

GPs delivering weight management programmes should have regular supervision sessions with psychologists to increase their awareness of how mental health can contribute to obesity, a report has recommended.

The report1 by the British Psychological Society (BPS) said many health professionals delivering weight management interventions “lack sufficient skills and training in the design, delivery, and evaluation of behavioural support.”

Better outcomes could be achieved if staff had a greater understanding of the link between mental health conditions, psychological factors, and obesity, it argued.

The report calls on the government to develop a national training and …
Performance of Simple Fibrosis Scores in Nonobese Patients With Nonalcoholic Fatty Liver Disease
Authors: Charmaine Fu, Janae Wentong Wai, Nik Raihan Nik Mustapha, Marie Irles, Grace Lai-Hung Wong, Sanjiv Mahadeva, Sarah Shili, Anthony Wing-Hung Chan, Wassil Merrouche, Henry Lik-Yuen Chan, Juliette Foucher, Brigitte Le Bail, Vincent Wai-Sun Wong, Wah Kheong Chan, Victor de Lédinghen
Journal: Clinical Gastroenterology and Hepatology (2019)
TCT-267 A Multicenter Registry to Evaluate Drug-Coated Balloon Angioplasty After Directional Coronary Atherectomy for Coronary Bifurcation Lesions
Authors: Shunsuke Kitani, Yasumi Igarashi, Etsuo Tsuchikane, Mikihiro Kijima, Shigeru Nakamura, Yoshitane Seino, Yoshihiro Takeda, Kenichiro Shimoji, Maoto Habara, Yoshinori Yasaka, Masaru Yamaki, Junji Yajima, Nobuo Komatsu, Yoshisato Shibata, Masafumi Sugi, Takashi Uchiyama, Kazuyuki Ozaki, Katsuo Noda
Journal: Journal of the American College of Cardiology (2019)
Exon 16–Skipping HER2 as a Novel Mechanism of Osimertinib Resistance in EGFR L858R/T790M–Positive Non–Small Cell Lung Cancer
Authors: Chia-Chi Hsu, Bin-Chi Liao, Wei-Yu Liao, Aleksandra Markovets, Daniel Stetson, Kenneth Thress, James Chih-Hsin Yang
Journal: Journal of Thoracic Oncology (2019)

IntroductionOsimertinib is the current recommended treatment for EGFR T790M–positive NSCLC after EGFR tyrosine kinase inhibitor therapy. However, resistance to osimertinib therapy is inevitably acquired after a period of effective treatment. We had a patient with EGFR L858R/T790M–positive NSCLC who initially responded to osimertinib therapy but eventually experienced development of resistance. Plasma cell–free DNA analysis revealed the occurrence of exon 16–skipping HER2, which may have resulted in the erb-b2 receptor tyrosine kinase 2 gene (HER2) splice variant HER2D16. HER2D16 has never been reported in lung cancer, and HER2D16-driven signaling is known to be regulated by Src kinase in breast cancer. We investigated the role of HER2D16 as an osimertinib-resistant mechanism.MethodsWe constructed and established H1975 cells stably expressing HER2D16. The dimeric formation of HER2D16 was tested by using nonreducing polyacrylamide gel electrophoresis. The effects of the study drugs on signaling transduction were examined by using Western blot. Synergistic effect was assessed by using the Chou-Talalay method.ResultsWe found that HER2D16 can form a homodimer in NSCLC cells. HER2D16-expressing H1975 cells were resistant to osimertinib treatment. We also found that mutant EGFR and HER2D16 cooperated to activate downstream signaling for osimertinib resistance. In addition, cotreatment with osimertinib and an Src kinase inhibitor failed to reverse resistance, indicating that HER2D16-driven signaling in NSCLC did not occur through a canonical pathway. Finally, we revealed that the combination of osimertinib with the pan-HER small-molecule inhibitor afatinib could synergistically repress cell growth and signaling in H1975-HER2D16 cells.ConclusionHER2D16 can contribute to osimertinib resistance through an Src-independent pathway. HER2D16 should be included in the molecular diagnosis panel for lung cancer.
Latent tuberculosis infection among minor asylum seekers in Denmark
Authors: Banoo Bakir Ahmad, Kristina Langholz Kristensen, Jonathan Peter Glenthoej, Anja Poulsen, Ann-Gine Bryld, Franziska Grundtvig Huber, Ebbe Munk Andersen, Pernille Ravn
Journal: European Respiratory Journal (2019)

<b>Screening among minor asylum seekers in Denmark revealed a high LTBI prevalence with heterogeneity in terms of clinical evaluation and initiating preventive treatment, underlining the need for uniform management of LTBI screening and treatment</b>http://bit.ly/2m2WyJI
TCT-16 Longitudinal Distribution of Lipid-Rich Plaque in Nonculprit Lesions: A Lipid-Rich Plaque (LRP) Study Subanalysis
Authors: Evan Shlofmitz, Rebecca Torguson, Paige Craig, Kazuhiro Dan, Corey Shea, Priti Shah, Hector Garcia-Garcia, Ron Waksman
Journal: Journal of the American College of Cardiology (2019)
TCT-297 Performing Percutaneous Coronary Interventions With Pre-Dilatation Using Non-Compliant Balloons at High-Pressure Versus Conventional Pre-Dilatation With Semicompliant Balloons: Insights From 2 Randomized Studies Using Optical Coherence Tomography
Authors: Florim Cuculi, Matthias Bossard, Wojciech Zasada, Federico Moccetti, Michiel Voskuil, Miriam Brinkert, Stefan Toggweiler, Richard Kobza
Journal: Journal of the American College of Cardiology (2019)
Better fetal monitoring will reduce severe brain injury in babies, says negligence claims agency NHS Resolution
Authors: Clare Dyer
Journal: BMJ (2019)

Urgent action is needed to improve fetal monitoring to prevent babies being born with severe brain injuries, says a report from NHS Resolution, which handles negligence claims made against the health service in England.1

The call comes in a report on NHS Resolution’s new early notification scheme, which requires hospital trusts to notify the agency of all full term babies who have had a potentially severe brain injury diagnosed in the first seven days of life.

An analysis of a sample of 96 cases described as high risk from a legal point of view found that issues with fetal monitoring were a leading contributory factor in 70%. In …
Feasibility and utility of a clinician dashboard from wearable and mobile application Parkinson’s disease data
Authors: Jordan J. Elm, Margaret Daeschler, Lauren Bataille, Ruth Schneider, Amy Amara, Alberto J. Espay, Michal Afek, Chen Admati, Abeba Teklehaimanot, Tanya Simuni
Journal: npj Digital Medicine (2019)

Mobile and wearable device-captured data have the potential to inform Parkinson's disease (PD) care. The objective of the Clinician Input Study was to assess the feasibility and clinical utility of data obtained using a mobile health technology from PD patients. In this observational, exploratory study, PD participants wore a smartwatch and used the Fox Wearable Companion mobile phone app to stream movement data and report symptom severity and medication intake for 6 months. Data were analyzed using the Intel® Pharma Analytics Platform. Clinicians reviewed participants' data in a dashboard during in-office visits at 2 weeks, 1, 3, and 6 months. Clinicians provided feedback in focus groups leading to dashboard updates. Between June and August 2017, 51 PD patients were recruited at four US sites, and 39 (76%) completed the 6-month study. Patients streamed 83,432 h of movement data from their smartwatches (91% of expected). Reporting of symptoms and medication intake using the app was lower than expected, 44% and 60%, respectively, but did not differ according to baseline characteristics. Clinicians' feedback resulted in ten updates to the dashboard during the study period. Clinicians reported that medications and patient reported outcomes were generally discernable in the dashboard and complementary to clinical assessments. Movement, symptoms, and medication intake data were feasibly translated from the app into a clinician dashboard but there was substantial attrition rate over 6 months. Further enhancements are needed to ensure long-term patient adherence to portable technologies and optimal digital data transfer to clinicians caring for PD patients.
Assessment of drug causality in Stevens‐Johnson syndrome/toxic epidermal necrolysis: Concordance between lymphocyte transformation test and ALDEN
Authors: Teresa Bellón, Sara Rodríguez‐Martín, Rosario Cabañas, Elena Ramírez, Victoria Lerma, Carlos González‐Herrada, Olga González, Elena Sendagorta, Ana Fiandor, Francisco J de Abajo
Journal: Allergy (2019)

Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Population-scale hand tremor analysis via anonymized mouse cursor signals
Authors: Ryen W. White, Eric Horvitz
Journal: npj Digital Medicine (2019)

Tremors are a common movement disorder with a spectrum of benign and pathological causes, including neurodegenerative disease, alcohol withdrawal, and physical overexertion. Studies of tremors in clinical practice are limited in size and scope and depend on explicit tracking of tremor characteristics by clinicians. Data drawn from small numbers of patients observed in short-duration sessions pose challenges for understanding the nature and distribution of tremors over a large population. Methods are presented to estimate hand tremors based on anonymized computer mouse cursor movement data collected from millions of users of a web search engine. To determine the feasibility of using this signal for the estimation of the prevalence of tremors over a large population, the characteristics of tremor-like movements are computed and compared against user data that can be interpreted as self-reports, the findings of published clinical studies, and a target selection study where participants self-report hand tremors and known causes. The results demonstrate significant alignment between estimated tremors and both self-reports and clinical findings. Those with cursor tremor events are more likely to report tremor-related search interests. Variations in cursor tremor quantity and cursor tremor frequency with demographics mirror those from clinical studies. Distributions of cursor tremor frequencies vary as expected for different medical conditions. Overall, the study finds evidence for the validity of harnessing anonymized mouse cursor motion as a population-scale tremor sensor for epidemiologic studies. Feasible future applications include opt-in services for screening and for monitoring the progression of illness.
Health-related quality of life in patients with a germline BRCA mutation and metastatic pancreatic cancer receiving maintenance olaparib
Authors: P. Hammel, H.L. Kindler, M. Reni, E. Van Cutsem, T. Macarulla, M.J. Hall, J.O. Park, D. Hochhauser, D. Arnold, D.-Y. Oh, A. Reinacher-Schick, G. Tortora, H. Algül, E.M. O’Reilly, D. McGuinness, K.Y. Cui, S. Joo, H.K. Yoo, N. Patel, T. Golan
Journal: Annals of Oncology (2019)

Patients with metastatic pancreatic cancer often have a detriment in health-related quality of life (HRQoL). In the randomized, double-blind, phase III POLO trial progression-free survival was significantly longer with maintenance olaparib, a poly(ADP-ribose) polymerase inhibitor, than placebo in patients with a germline BRCA1 and/or BRCA2 mutation (gBRCAm) and metastatic pancreatic cancer whose disease had not progressed during first-line platinum-based chemotherapy. The prespecified HRQoL evaluation is reported here.
TCT-314 Inpatient Versus Outpatient PCI in Patients With Left Main Disease: Analysis From the EXCEL Trial
Authors: Prakriti Gaba, Patrick Serruys, Dimitri Karmpaliotis, Adrian Banning, Zixuan Zhang, Marie-Claude Morice, David Kandzari, Ori Ben-Yehuda, Roxana Mehran, Martin Leon, Joseph Sabik, A. Pieter Kappetein, Gregg Stone
Journal: Journal of the American College of Cardiology (2019)
Abstract 19473: Impact of Immediate Aortic Repair After Cardiopulmonary Resuscitation on Acute Type A Aortic Dissection Complicated by Cardiopulmonary Arrest
Authors: Chikashi Nakai, Tomonori Haraguchi, Yasushi Okada, Shinichi Nakayama, Takuro Tsukube
Journal: Circulation (2016)

Introduction: Management of acute type A aortic dissection (AADA) presented with cardiopulmonary arrest (CPA) remains controversial varying from aggressive cardiopulmonary resuscitation (CPR) follo...
TCT-518 Utility of Troponin and Creatine Kinase in Predicting Myocardial Infarct Size, Left Ventricular Dysfunction, and Clinical Outcomes After Acute Anterior Myocardial Infarction: The INFUSE-AMI Trial
Authors: Bahira Shahim, Shmuel Chen, Aaron Crowley, Bjorn Redfors, Ghazaleh Mehdipoor, Ori Ben-Yehuda, Bernhard Witzenbichler, Akiko Maehara, C. Michael Gibson, Gregg Stone
Journal: Journal of the American College of Cardiology (2019)
Long‐term efficacy and safety of sonidegib in patients with advanced basal cell carcinoma: 42‐month analysis of the phase II randomized, double‐blind BOLT study
Authors: R. Dummer, A. Guminksi, R. Gutzmer, J.T. Lear, K.D. Lewis, A.L.S. Chang, P. Combemale, L. Dirix, M. Kaatz, R. Kudchadkar, C. Loquai, R. Plummer, H.‐J. Schulze, A.J. Stratigos, U. Trefzer, N. Squittieri, M.R. Migden
Journal: British Journal of Dermatology (2019)

Basal cell carcinomas (BCCs) exhibit aberrant activation of the hedgehog pathway. Sonidegib is a hedgehog pathway inhibitor approved for the treatment of locally advanced BCC (laBCC) and metastatic BCC (mBCC) based on primary results of the BOLT study [Basal Cell Carcinoma Outcomes with LDE225 (sonidegib) Treatment].This is the final 42-month analysis of the BOLT study, evaluating the efficacy and safety of sonidegib.Adults with no prior hedgehog pathway inhibitor therapy were randomized in a 1 : 2 ratio to sonidegib 200 mg or 800 mg once daily. Treatment continued for up to 42 months or until disease progression, unacceptable toxicity, death, study termination or withdrawal of consent. The primary efficacy end point was the objective response rate (ORR) by central review, assessed at baseline; weeks 5, 9 and 17; then subsequently every 8 or 12 weeks during years 1 or 2, respectively. Safety end points included adverse event monitoring and reporting.The study enrolled 230 patients, 79 and 151 in the 200-mg and 800-mg groups, respectively, of whom 8% and 3.3% remained on treatment by the 42-month cutoff, respectively. The ORRs by central review were 56% [95% confidence interval (CI) 43-68] for laBCC and 8% (95% CI 0·2-36) for mBCC in the 200-mg group and 46·1% (95% CI 37·2-55·1) for laBCC and 17% (95% CI 5-39) for mBCC in the 800-mg group. No new safety concerns emerged.Sonidegib demonstrated sustained efficacy and a manageable safety profile. The final BOLT results support sonidegib as a viable treatment option for laBCC and mBCC. What's already known about this topic? Basal cell carcinoma (BCC) is usually treatable with surgery or radiation therapy, but there are limited treatment options for patients with advanced BCC. Sonidegib, a hedgehog pathway inhibitor approved for the treatment of advanced BCC, demonstrated clinically relevant efficacy and manageable safety in prior analyses of the phase II randomized, double-blind BOLT study [Basal Cell Carcinoma Outcomes with LDE225 (sonidegib) Treatment]. What does this study add? This final 42-month analysis of BOLT is the longest follow-up available for a hedgehog pathway inhibitor. Clinically relevant efficacy results were sustained from prior analyses, with objective response rates by central review of the approved 200-mg daily dose of 56% in locally advanced BCC and 8% in metastatic BCC. No new safety concerns were raised. The results confirmed sonidegib as a viable long-term treatment option for patients with advanced BCC.
TCT-259 Drug-Coated Balloon Versus Drug-Eluting Stent for the Treatment of Small-Vessel Disease: 2-Year Clinical Outcomes of the RESTORE SVD China Randomized Trial
Authors: Jian Tian, Yida Tang, Changdong Guan, Shubin Qiao, Run-Lin Gao, Bo Xu
Journal: Journal of the American College of Cardiology (2019)
Inadequate Health Care in U.S. Prisons
Authors: Terry E. Hill
Journal: Annals of Internal Medicine (2019)

Letters1 October 2019Inadequate Health Care in U.S. PrisonsTerry E. Hill, MDTerry E. Hill, MDHill Physicians Medical Group, San Ramon, California (T.E.H.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/L19-0348 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:I commend Hurst and colleagues (1) for calling much-needed attention to the issue of substandard prison health care and its implications for community health. For a time, I found myself at the center of the California court case discussed in their commentary. I have 1 concern and several additional suggestions about what can be done.Hurst and colleagues frame the problem and its solution too narrowly in emphasizing the need for hospital physicians to report medical negligence by prison physicians. We all have an obligation to report suspected negligence or incompetence to appropriate authorities; however, I hope ...References1. Hurst A, Castañeda B, Ramsdale E. Deliberate indifference: inadequate health care in U.S. prisons. Ann Intern Med. 2019;170:563-4. [PMID: 30934062]. doi:10.7326/M17-3154 LinkGoogle Scholar2. Hill TE, Martelli PF, Kuo JH. A case for revisiting peer review: implications for professional self-regulation and quality improvement. PLoS One. 2018;13:e0199961. [PMID: 29953510] doi:10.1371/journal.pone.0199961 CrossrefMedlineGoogle Scholar3. Pont J, Enggist S, Stöver H, et al. Prison health care governance: guaranteeing clinical independence. Am J Public Health. 2018;108:472-6. [PMID: 29470125] doi:10.2105/AJPH.2017.304248 CrossrefMedlineGoogle Scholar4. Hill TE. How clinicians make (or avoid) moral judgments of patients: implications of the evidence for relationships and research. Philos Ethics Humanit Med. 2010;5:11. [PMID: 20618947] doi:10.1186/1747-5341-5-11 CrossrefMedlineGoogle Scholar5. Trestman RL, Ferguson W, Dickert J. Behind bars: the compelling case for academic health centers partnering with correctional facilities [Editorial]. Acad Med. 2015;90:16-9. [PMID: 25054416] doi:10.1097/ACM.0000000000000431 CrossrefMedlineGoogle Scholar Author, Article, and Disclosure InformationAffiliations: Hill Physicians Medical Group, San Ramon, California (T.E.H.)Disclosures: The author has disclosed no conflicts of interest. The form can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=L19-0348. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoDeliberate Indifference: Inadequate Health Care in U.S. Prisons Ashley Hurst , Brenda Castañeda , and Erika Ramsdale Metrics 1 October 2019Volume 171, Issue 7Page: 523-524KeywordsConflicts of interestDisclosureHealth careHealth care facilitiesHealth disparitiesMortalityPatientsPeer reviewPrevention, policy, and public healthSystematic reviews ePublished: 1 October 2019 Issue Published: 1 October 2019 Copyright & PermissionsCopyright © 2019 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
TCT-685 Coronary Stenosis Before TAVR Are Not Necessarily Associated With Poorer 1-Year Prognosis and May Be Medically Managed
Authors: Cécile Cazé, Réda Bensaid, David Ternant, Christophe Saint Etienne, Thierry Bourguignon, Jean-Michel Clerc, Bernard Desveaux, Laurent Quilliet, Fabrice Ivanes
Journal: Journal of the American College of Cardiology (2019)
Pyoderma gangrenosum in hematologic malignancies: A systematic review
Authors: Carmen M. Montagnon, Elizabeth A. Fracica, Archna A. Patel, Michael J. Camilleri, M. Hassan Murad, David Dingli, David A. Wetter, Stanislav N. Tolkachjov
Journal: Journal of the American Academy of Dermatology (2019)