tbuckley/cabot-search huggingface dataset:
At the Leading Edge in Morphea—New Insights Into Disease Course and Management Options
Authors: Carla N. Cruz-Diaz, Anna K. Haemel
Journal: JAMA Dermatology (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Dermatology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Dermatology journal
Relationship Between Response and Dose in Published, Contemporary Phase I Oncology Trials
Authors: Antonious Hazim, Gordon Mills, Vinay Prasad, Alyson Haslam, Emerson Y. Chen
Journal: Journal of the National Comprehensive Cancer Network (2020)

As progress continues in oncology drug development, this study aimed to examine whether the previously established association between drug dose and efficacy in the era of cytotoxic therapies remains true in today's phase I dose-escalation oncology trials.A systematic review of early-phase dose-finding trials of single-agent oncology drugs from 2015 to 2018 was conducted to examine the relationship between drug dose and objective responses. Cancer-specific trials were included if they determined maximum tolerated dose (MTD) and/or recommended phase II dose (RP2D). Data related to the study drug, study design, treatment response, cancer type, dose levels, MTD, and RP2D were all collected. Dose level was categorized into 4 categories (≤40%, 41%-80%, 81%-120%, and >120% of the RP2D) and was further analyzed by class of drug.A total of 175 phase I studies were identified, with a total of 7,330 patients showing a median response rate of 5% (range, 0%-83%) across trials. A total of 93 trials with 2,506 participants had response data corresponding to drug dose level. In this subset, the median response rate was 5% (range, 0%-83%) across trials. Across all participants in this subset, the response rate was 12% (57 of 491) among those in the dose range of ≤40% of RP2D, 17% (95 of 562) among those in 41% to 80% of RP2D, 23% (272 of 1,206) among those in 81% to 120% of RP2D, and 29% (71 of 247) among those in >120% of RP2D (P<.001). The response rate at ≤40% of RP2D for targeted antibody was 5%, 4% for cellular therapy, 19% for immunotherapy, and 21% for small-molecule targeted inhibitors.Whereas our study of published phase I trials continued to show a low response rate consistent with earlier studies, the relationship between response and dose does not always peak at 81% to 120% of RP2D anymore, likely due to the use of novel immunotherapy and targeted agents with distinct efficacy and toxicity patterns.
POLYSEROSITIS AS THE MAIN MANIFESTATION OF EFFUSIVE-CONSTRICTIVE PERICARDITIS IN A POST-TRAUMATIC PATIENT
Authors: Jiang Yixiao, Yuxi Li, Ying Yang, Wei Ma, Yang Yu, Rongyue Liang, Ziguang Yan, Jianxing Qiu, Meilin Liu, Wenhui Ding, Jianping Li
Journal: Journal of the American College of Cardiology (2020)
Dasatinib vs. imatinib in patients with chronic myeloid leukemia in chronic phase (CML-CP) who have not achieved an optimal response to 3 months of imatinib therapy: the DASCERN randomized study
Authors: Jorge E. Cortes, Qian Jiang, Jianxiang Wang, Jianyu Weng, Huanling Zhu, Xiaoli Liu, Andreas Hochhaus, Dong-Wook Kim, Jerald Radich, Michael Savona, Patricia Martin-Regueira, Oumar Sy, Renuka Gurnani, Giuseppe Saglio
Journal: Leukemia (2020)

Early molecular response is associated with improved probability of deep molecular response and superior survival in patients with CML-CP. However, ~1 in 3 patients on first-line imatinib do not achieve this threshold. The phase 2b DASCERN trial (NCT01593254) assessed the outcome of early switch to dasatinib in patients with suboptimal response to first-line imatinib. Adult patients with CML-CP were randomized (2:1) to receive 100 mg dasatinib (n = 174) or continue imatinib at ≥400 mg (n = 86). The primary endpoint was the rate of major molecular response (MMR) at 12 months, which was 29% (dasatinib) and 13% (imatinib; P = 0.005). After ≥2 years of follow-up, 45 patients (52%) randomized to continue imatinib had crossed over to dasatinib. Considering treatment crossover, the 2-year cumulative MMR rate was 64% with dasatinib and 41% with imatinib (66% and 67%, respectively by intent-to-treat). Adverse events were consistent with the established safety profiles of both drugs. The results of this first prospective study support early monitoring of patients treated with first-line imatinib, and suggest that switching to dasatinib in cases of suboptimal response may offer clinical benefit. Further follow-up is needed to assess the long-term clinical benefit of early switching.
Postdiagnosis Body Mass Index, Weight Change, and Mortality From Prostate Cancer, Cardiovascular Disease, and All Causes Among Survivors of Nonmetastatic Prostate Cancer
Authors: Alyssa N. Troeschel, Terryl J. Hartman, Eric J. Jacobs, Victoria L. Stevens, Ted Gansler, W. Dana Flanders, Lauren E. McCullough, Ying Wang
Journal: Journal of Clinical Oncology (2020)

To investigate the association of postdiagnosis body mass index (BMI) and weight change with prostate cancer-specific mortality (PCSM), cardiovascular disease-related mortality (CVDM), and all-cause mortality among survivors of nonmetastatic prostate cancer.Men in the Cancer Prevention Study II Nutrition Cohort diagnosed with nonmetastatic prostate cancer between 1992 and 2013 were followed for mortality through December 2016. Current weight was self-reported on follow-up questionnaires approximately every 2 years. Postdiagnosis BMI was obtained from the first survey completed 1 to < 6 years after diagnosis. Weight change was the difference in weight between the first and second postdiagnosis surveys. Deaths occurring within 4 years of the follow-up were excluded to reduce bias from reverse causation. Analyses of BMI and weight change included 8,330 and 6,942 participants, respectively.Postdiagnosis BMI analyses included 3,855 deaths from all causes (PCSM, n = 500; CVDM, n = 1,155). Using Cox proportional hazards models, hazard ratios (HRs) associated with postdiagnosis obesity (BMI ≥ 30 kg/m2) compared with healthy weight (BMI 18.5 to < 25.0 kg/m2) were 1.28 for PCSM (95% CI, 0.96 to 1.67), 1.24 for CVDM (95% CI, 1.03 to 1.49), and 1.23 for all-cause mortality (95% CI, 1.11 to 1.35). Weight gain analyses included 2,973 deaths (PCSM, n = 375; CVDM, n = 881). Postdiagnosis weight gain (> 5% of body weight), compared with stable weight (± < 3%), was associated with a higher risk of PCSM (HR, 1.65; 95% CI, 1.21 to 2.25) and all-cause mortality (HR, 1.27; 95% CI, 1.12 to 1.45) but not CVDM.Results suggest that among survivors of nonmetastatic prostate cancer with largely localized disease, postdiagnosis obesity is associated with higher CVDM and all-cause mortality, and possibly higher PCSM, and that postdiagnosis weight gain may be associated with a higher mortality as a result of all causes and prostate cancer.
Personalization of Treatment is the Way Forward in Care and Trials
Authors: Laura J. Esserman
Journal: Clinical Cancer Research (2020)

It has been demonstrated that, in early breast cancer, there is no survival benefit to additional treatment once a patient has achieved a pathologic complete response (pCR). Together with the well-established prognostic association between pCR and survival, this presents a strong rationale for escalation/deescalation of neoadjuvant treatment based upon response.See related article by Spring et al., p. 2838.
Patient-reported outcomes in survivors of childhood hematologic malignancies with hematopoietic stem cell transplant
Authors: Hsiu-Ju Yen, Hesham M. Eissa, Neel S. Bhatt, Sujuan Huang, Matthew J. Ehrhardt, Nickhill Bhakta, Kirsten K. Ness, Kevin R. Krull, D. Kumar Srivastava, Leslie L. Robison, Melissa M. Hudson, I-Chan Huang
Journal: Blood (2020)
Wolff-Parkinson-White Syndrome
Authors: CHARLES FISCH, SHELDON T. PINSKY, J. PAUL SHIELDS
Journal: Circulation (1957)

It is the purpose of this communication to present a case of pre-excitation (Wolff-Parkinson-White syndrome) associated with various arrhythmias, some hitherto not described, and to stress the many features of this unusual case that support the bypass concept of the origin of this syndrome.
Personalised medicine for non-classic cystic fibrosis resulting from rare CFTR mutations
Authors: Matthew S. McCravy, Nancy L. Quinney, Deborah M. Cholon, Susan E. Boyles, Timothy J. Jensen, Andrei A. Aleksandrov, Scott H. Donaldson, Peadar G. Noone, Martina Gentzsch
Journal: European Respiratory Journal (2020)

<b>Using a precision medicine approach to define a rare CFTR mutation, we demonstrated that CF patients with this mutation may benefit from available therapies. This study illustrates the power of laboratory techniques for optimising patient treatments.</b>https://bit.ly/2WtBHiL
Coronary Thermodilution to Assess Flow Reserve
Authors: Nico H.J. Pijls, Bernard De Bruyne, Leif Smith, Wilbert Aarnoudse, Emanuele Barbato, Jozef Bartunek, G. Jan Willem Bech, Frans Van De Vosse
Journal: Circulation (2002)

Background — Guide wire–based simultaneous measurement of fractional flow reserve (FFR) and coronary flow reserve (CFR) is important to understand microvascular disease of the heart. The aim of this study was to investigate the feasibility of simultaneous measurement of FFR and CFR by one pressure-temperature sensor-tipped guide wire with the use of coronary thermodilution and to compare CFR by thermodilution (CFR thermo ) with simultaneously measured Doppler CFR (CFR Doppl ). Methods and Results — In 103 coronary arteries in 50 patients, a pressure-temperature sensor-tipped 0.014-inch floppy guide wire and a 0.014-inch Doppler guide wire were introduced. Both normal vessels and a wide range of stenotic vessels were included. With 3 mL of saline at room temperature used as an indicator, by hand-injection, thermodilution curves in the coronary artery were obtained in triplicate, both at baseline and at intravenous adenosine-induced maximum hyperemia. After adequate curve-fitting, CFR thermo was calculated from the ratio of inverse mean transit times and compared with CFR Doppl calculated by velocities at hyperemia and baseline. Adequate sets of thermodilution curves and corresponding CFR thermo could be obtained in 87% of the arteries versus 91% for Doppler CFR and 100% for FFR. CFR thermo correlated fairly well to CFR Doppl (CFR thermo =0.84 CFR Doppl +0.17; r =0.80; P &lt;0.001), although individual differences of &gt;20% between both indexes were seen in a quarter of all arteries. Conclusions — This study shows the feasibility of simultaneous measurement of FFR (by coronary pressure) and CFR (by coronary thermodilution) in humans by one single guide wire in a practical and straightforward way and will facilitate assessment of microvascular disease.
Circulating uromodulin inhibits vascular calcification by interfering with pro-inflammatory cytokine signalling
Authors: Ioana Alesutan, Trang T D Luong, Nadeshda Schelski, Jaber Masyout, Susanne Hille, Markus P Schneider, Delyth Graham, Daniel Zickler, Nicolas Verheyen, Misael Estepa, Andreas Pasch, Winfried Maerz, Andreas Tomaschitz, Stefan Pilz, Norbert Frey, Florian Lang, Christian Delles, Oliver J Müller, Burkert Pieske, Kai-Uwe Eckardt, Juergen Scherberich, Jakob Voelkl
Journal: Cardiovascular Research (2020)

Abstract Aims Uromodulin is produced exclusively in the kidney and secreted into both urine and blood. Serum levels of uromodulin are correlated with kidney function and reduced in chronic kidney disease (CKD) patients, but physiological functions of serum uromodulin are still elusive. This study investigated the role of uromodulin in medial vascular calcification, a key factor associated with cardiovascular events and mortality in CKD patients. Methods and results Experiments were performed in primary human (HAoSMCs) and mouse (MOVAS) aortic smooth muscle cells, cholecalciferol overload and subtotal nephrectomy mouse models and serum from CKD patients. In three independent cohorts of CKD patients, serum uromodulin concentrations were inversely correlated with serum calcification propensity. Uromodulin supplementation reduced phosphate-induced osteo-/chondrogenic transdifferentiation and calcification of HAoSMCs. In human serum, pro-inflammatory cytokines tumour necrosis factor α (TNFα) and interleukin-1β (IL-1β) co-immunoprecipitated with uromodulin. Uromodulin inhibited TNFα and IL-1β-induced osteo-/chondrogenic signalling and activation of the transcription factor nuclear factor kappa-light-chain-enhancer of activated β cells (NF-kB) as well as phosphate-induced NF-kB-dependent transcriptional activity in HAoSMCs. In vivo, adeno-associated virus (AAV)-mediated overexpression of uromodulin ameliorated vascular calcification in mice with cholecalciferol overload. Conversely, cholecalciferol overload-induced vascular calcification was aggravated in uromodulin-deficient mice. In contrast, uromodulin overexpression failed to reduce vascular calcification during renal failure in mice. Carbamylated uromodulin was detected in serum of CKD patients and uromodulin carbamylation inhibited its anti-calcific properties in vitro. Conclusions Uromodulin counteracts vascular osteo-/chondrogenic transdifferentiation and calcification, at least in part, through interference with cytokine-dependent pro-calcific signalling. In CKD, reduction and carbamylation of uromodulin may contribute to vascular pathology.
Physical Therapy versus Glucocorticoid Injection for Osteoarthritis of the Knee
Authors: Gail D. Deyle, Chris S. Allen, Stephen C. Allison, Norman W. Gill, Benjamin R. Hando, Evan J. Petersen, Douglas I. Dusenberry, Daniel I. Rhon
Journal: New England Journal of Medicine (2020)

Both physical therapy and intraarticular injections of glucocorticoids have been shown to confer clinical benefit with respect to osteoarthritis of the knee. Whether the short-term and long-term effectiveness for relieving pain and improving physical function differ between these two therapies is uncertain.We conducted a randomized trial to compare physical therapy with glucocorticoid injection in the primary care setting in the U.S. Military Health System. Patients with osteoarthritis in one or both knees were randomly assigned in a 1:1 ratio to receive a glucocorticoid injection or to undergo physical therapy. The primary outcome was the total score on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) at 1 year (scores range from 0 to 240, with higher scores indicating worse pain, function, and stiffness). The secondary outcomes were the time needed to complete the Alternate Step Test, the time needed to complete the Timed Up and Go test, and the score on the Global Rating of Change scale, all assessed at 1 year.We enrolled 156 patients with a mean age of 56 years; 78 patients were assigned to each group. Baseline characteristics, including severity of pain and level of disability, were similar in the two groups. The mean (±SD) baseline WOMAC scores were 108.8±47.1 in the glucocorticoid injection group and 107.1±42.4 in the physical therapy group. At 1 year, the mean scores were 55.8±53.8 and 37.0±30.7, respectively (mean between-group difference, 18.8 points; 95% confidence interval, 5.0 to 32.6), a finding favoring physical therapy. Changes in secondary outcomes were in the same direction as those of the primary outcome. One patient fainted while receiving a glucocorticoid injection.Patients with osteoarthritis of the knee who underwent physical therapy had less pain and functional disability at 1 year than patients who received an intraarticular glucocorticoid injection. (ClinicalTrials.gov number, NCT01427153.).
The Transcription Factor Bhlhe40 Programs Mitochondrial Regulation of Resident CD8+ T Cell Fitness and Functionality
Authors: Chaofan Li, Bibo Zhu, Young Min Son, Zheng Wang, Li Jiang, Min Xiang, Zhenqing Ye, Kathryn E. Beckermann, Yue Wu, James W. Jenkins, Peter J. Siska, Benjamin G. Vincent, Y.S. Prakash, Tobias Peikert, Brian T. Edelson, Reshma Taneja, Mark H. Kaplan, Jeffrey C. Rathmell, Haidong Dong, Taro Hitosugi, Jie Sun
Journal: Immunity (2020)
The validity of surface EMG of extra-diaphragmatic muscles in assessing respiratory responses during mechanical ventilation: A systematic review
Authors: H.Y. AbuNurah, D.W. Russell, J.D. Lowman
Journal: Pulmonology (2020)

Evidence supporting the utilization of surface EMG (sEMG) of extra-diaphragmatic muscles for monitoring of mechanical ventilation (MV) assistance is unclear. The purpose of this review was to assess the quality of literature available on using extra-diaphragmatic sEMG as an assessment technique of respiratory responses during MV. Studies using sEMG of extra-diaphragmatic respiratory muscles during MV were selected by two independent researchers after performing a database search of PubMed, CINAHL, GOOGLE SCHOLAR. Exclusion criteria were studies of patients with neuromuscular disorders, receiving neuromuscular blocking agents, receiving non-invasive MV, using needle EMG, and studies written in languages other than English. Quality of identified studies was assessed with the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2). This study is registered with PROSPERO, number (CRD42018081341). 596 references were identified. Of the identified studies, 7 studies were included in the review. Findings demonstrate that sEMG of extra-diaphragmatic muscle activity is a valid and applicable tool to evaluate mechanical loading/unloading of respiratory muscles and respiratory drive or sensation. However, the quality of literature supporting sEMG as monitoring tool of respiratory responses were characterized by a high and unclear risk of bias. Although it appears to be a valid and applicable tool, there is a scarcity of literature that directly demonstrates the diagnostic accuracy of sEMG of extra-diaphragmatic muscles in monitoring respiratory mechanics and respiratory drive or sensation during MV assistance across wide populations and conditions.
Coronary Artery Calcium for Personalized Allocation of Aspirin in Primary Prevention of Cardiovascular Disease in 2019
Authors: Miguel Cainzos-Achirica, Michael D. Miedema, John W. McEvoy, Mahmoud Al Rifai, Philip Greenland, Zeina Dardari, Matthew Budoff, Roger S. Blumenthal, Joseph Yeboah, Daniel A. Duprez, Martin Bødtker Mortensen, Omar Dzaye, Jonathan Hong, Khurram Nasir, Michael J. Blaha
Journal: Circulation (2020)

Background: Recent American College of Cardiology/American Heart Association Primary Prevention Guidelines recommended considering low-dose aspirin therapy only among adults 40 to 70 years of age who are at higher atherosclerotic cardiovascular disease (ASCVD) risk but not at high risk of bleeding. However, it remains unclear how these patients are best identified. The present study aimed to assess the value of coronary artery calcium (CAC) for guiding aspirin allocation for primary prevention by using 2019 aspirin meta-analysis data on cardiovascular disease relative risk reduction and bleeding risk. Methods: The study included 6470 participants from the MESA Study (Multi-Ethnic Study of Atherosclerosis). ASCVD risk was estimated using the pooled cohort equations, and 3 strata were defined: &lt;5%, 5% to 20%, and &gt;20%. All participants underwent CAC scoring at baseline, and CAC scores were stratified as =0, 1 to 99, ≥100, and ≥400. A 12% relative risk reduction in cardiovascular disease events was used for the 5-year number needed to treat (NNT 5 ) calculations, and a 42% relative risk increase in major bleeding events was used for the 5-year number needed to harm (NNH 5 ) estimations. Results: Only 5% of MESA participants would qualify for aspirin consideration for primary prevention according to the American College of Cardiology/American Heart Association guidelines and using &gt;20% estimated ASCVD risk to define higher risk. Benefit/harm calculations were restricted to aspirin-naive participants &lt;70 years of age not at high risk of bleeding (n=3540). The overall NNT 5 with aspirin to prevent 1 cardiovascular disease event was 476 and the NNH 5 was 355. The NNT 5 was also greater than or similar to the NNH 5 among estimated ASCVD risk strata. Conversely, CAC≥100 and CAC≥400 identified subgroups in which NNT 5 was lower than NNH 5 . This was true both overall (for CAC≥100, NNT 5 =140 versus NNH 5 =518) and within ASCVD risk strata. Also, CAC=0 identified subgroups in which the NNT 5 was much higher than the NNH 5 (overall, NNT 5 =1190 versus NNH 5 =567). Conclusions: CAC may be superior to the pooled cohort equations to inform the allocation of aspirin in primary prevention. Implementation of current 2019 American College of Cardiology/American Heart Association guideline recommendations together with the use of CAC for further risk assessment may result in a more personalized, safer allocation of aspirin in primary prevention. Confirmation of these findings in experimental settings is needed.
Health surveillance during covid-19 pandemic
Authors: Rafael A Calvo, Sebastian Deterding, Richard M Ryan
Journal: BMJ (2020)

Societies are responding to the covid-19 pandemic at breathtaking speed.Many of these ad hoc responses will have long lasting consequences, and we must make sure that today's efforts do not threaten our future wellbeing.The most consequential transformations may come from new health surveillance technologies that use machine learning and automated decision making to parse people's digital footprints, identify those who are potentially infected, trace their contacts, and enforce social distancing.Some have argued that such digital contact tracing could be more effective in
Triage Based on Preclinical Scores—Low-Cost Strategy for Accelerating Time to Thrombectomy
Authors: Anne W. Alexandrov, Klaus Fassbender
Journal: JAMA Neurology (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Neurology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Neurology journal