tbuckley/cabot-search huggingface dataset:
Is Computed Tomography Airway Count Related to Asthma Severity and Airway Structure and Function?
Authors: Rachel L. Eddy, Sarah Svenningsen, Miranda Kirby, Danielle Knipping, David G. McCormack, Christopher Licskai, Parameswaran Nair, Grace Parraga
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

Rationale: In patients with asthma, X-ray computed tomography (CT) has provided evidence of thickened airway walls and airway occlusions, but the total number of CT-visible airways and its relationship with disease severity is unknown.Objectives: To measure CT total airway count (TAC) in asthma and evaluate relationships with asthma severity, airway morphology, pulmonary function, and magnetic resonance imaging (MRI) ventilation.Methods: Participants underwent post-bronchodilator inspiratory CT, and prebronchodilator and post-bronchodilator spirometry and hyperpolarized 3He MRI. CT TAC was quantified as the sum of airways in the segmented airway tree, and airway wall area percent (WA%) and lumen area were measured. MRI ventilation abnormalities were quantified as the ventilation defect percent.Measurements and Main Results: We evaluated 70 participants, including 15 Global Initiative for Asthma (GINA) steps 1 to 3, 19 GINA 4, and 36 GINA 5 participants with asthma. As compared with GINA 1 to 3, TAC was significantly diminished in GINA 4 (P = 0.03) and GINA 5 (P = 0.045). Terminal airway intraluminal occlusion was present in 5 (2 GINA 4 and 3 GINA 5) of 70 participants. Sub-subsegmental airways were CT-invisible or missing in 69 out of 70 participants; the most common number of missing sub-subsegments was 10. Participants with ≥10 missing subsegments had worse WA% (P < 0.0001), lumen area (P < 0.0001), and ventilation defect percent (P = 0.03) than those with <10 missing subsegments. In a multivariable model, TAC (standardized regression coefficient = 0.50; P = 0.001) independently predicted FEV1 (R2 = 0.27; P = 0.003) and, in a separate model, TAC (standardized regression coefficient = −0.53; P < 0.0001) independently predicted airway WA% (R2 = 0.32; P = 0.0001).Conclusions: TAC was significantly diminished in participants with greater asthma severity and was related to airway wall thickness and ventilation defects. Fewer airways in severe than in mild asthma challenges our understanding of airway disease in asthma.Clinical trial registered with www.clinicaltrials.gov (NCT02351141).
High expression of B7-H3 on stromal cells defines tumor and stromal compartments in epithelial ovarian cancer and is associated with limited immune activation
Authors: Heather L. MacGregor, Azin Sayad, Andrew Elia, Ben X. Wang, Sarah Rachel Katz, Patricia A. Shaw, Blaise A. Clarke, Sarah Q. Crome, Celine Robert-Tissot, Marcus Q. Bernardini, Linh T. Nguyen, Pamela S. Ohashi
Journal: Journal for ImmunoTherapy of Cancer (2019)

<h3>Background</h3> B7-H3 and B7-H4 are highly expressed by many human malignancies making them attractive immunotherapeutic targets. However, their expression patterns and immune contexts in epithelial ovarian cancer have not been well characterized. <h3>Methods</h3> We used flow cytometry, immunohistochemistry, and genomic analyses to determine the patterns of B7-H3, B7-H4, and PD-L1 expression by tumor, stromal, and immune cells in the ovarian tumor microenvironment (TME). We analyzed immune cell frequency and expression of PD-1, TIM3, LAG3, ICOS, TIA-1, granzyme B, 2B4, CD107a, and GITR on T cells; CD20, CD22, IgD, BTLA, and CD27 on B cells; CD16 on monocytes; and B7-H3, B7-H4, PD-L1, PD-L2, ICOSL, CD40, CD86, and CLEC9a on antigen-presenting cells by flow cytometry. We determined intratumoral cellular location of immune cells using immunohistochemistry. We compared differences in immune infiltration in tumors with low or high tumor-to-stroma ratio and in tumors from the same or unrelated patients. <h3>Results</h3> On non-immune cells, B7-H4 expression was restricted to tumor cells whereas B7-H3 was expressed by both tumor and stromal cells. Stromal cells of the ovarian TME expressed high levels of B7-H3 compared to tumor cells. We used this differential expression to assess the tumor-to-stroma ratio of ovarian tumors and found that high tumor-to-stroma ratio was associated with increased expression of CD16 by monocytes, increased frequencies of PD-1<sup>high</sup> CD8<sup>+</sup> T cells, increased PD-L1 expression by APCs, and decreased CLEC9a expression by APCs. We found that expression of PD-L1 or CD86 on APCs and the proportion of PD-1<sup>high</sup> CD4<sup>+</sup> T cells were strongly correlated on immune cells from tumors within the same patient, whereas expression of CD40 and ICOSL on APCs and the proportion of PD-1<sup>high</sup> CD8<sup>+</sup> T cells were not. <h3>Conclusions</h3> This study provides insight into the expression patterns of B7-H3 and B7-H4 in the ovarian TME. Further, we demonstrate an association between the tumor-to-stroma ratio and the phenotype of tumor-infiltrating immune cells. We also find that some but not all immune parameters show consistency between peritoneal metastatic sites. These data have implications for the design of immunotherapies targeting these B7 molecules in epithelial ovarian cancer.
Abstract 16082: Changes in the Expression of MicroRNAs From Spontaneously Hypertensive Rats Submitted to Aerobic Swimming Training May Be Involved in Coronary Artery Vascular Remodeling
Authors: Fernanda R Roque, Tiago Fernandes, Henrique Cho, Vander J das Neves, Glória de Fátima A Mota, Luciana V Rossoni, Edilamar M Oliveira
Journal: Circulation (2018)

We investigated in Spontaneously Hypertensive Rats (SHR) the expression of microRNAs and coronary artery vascular remodeling after 10 weeks of aerobic swimming training (SHR-t: 60 min/ day - 4% ove...
68Ga-PMSA Uptake in the Lung
Authors: Sharjeel Usmani, Alya'a Sadeq, Fahad Marafi, Abdulredha Esmail, Fareeda al Kandari, Najeeb Ahmed
Journal: Clinical Nuclear Medicine (2019)

Abstract 68 Ga-PSMA is a promising tracer for both primary staging and detection of biochemical recurrence in prostate cancer. PSMA is also expressed in the neovascular endothelium of various solid malignancies possibly due to tumor-associated angiogenic factors and endothelial cell sprouting. We report a case of a 73-year-old man of prostate cancer with rising prostate-specific antigen levels. 68 Ga-PSMA PET/CT was performed, which showed a focal lung lesion, with subsequent histological confirmation of adenocarcinoma of the lung. Incidental lung lesions on 68 Ga-PSMA in prostate cancer patients should elicit a differential of primary lung malignancy, especially if clinical and morphological suspicion is high.
Anti–B-Cell Maturation Antigen BiTE Molecule AMG 420 Induces Responses in Multiple Myeloma
Authors: Max S. Topp, Johannes Duell, Gerhard Zugmaier, Michel Attal, Philippe Moreau, Christian Langer, Jan Krönke, Thierry Facon, Alexey V. Salnikov, Robin Lesley, Karl Beutner, James Kalabus, Erik Rasmussen, Kathrin Riemann, Alex C. Minella, Gerd Munzert, Hermann Einsele
Journal: Journal of Clinical Oncology (2020)

PURPOSE The anti–B-cell maturation antigen BiTE molecule AMG 420 was assessed in patients with relapsed/refractory multiple myeloma. PATIENTS AND METHODS In this first-in-human study, up to 10 cycles of AMG 420 were given (4-week infusions/6-week cycles). Patients had progression after ≥ 2 lines of prior therapy and no extramedullary disease. Minimal residual disease (MRD) response was defined as &lt; 1 tumor cell/10 4 bone marrow cells by flow cytometry. RESULTS Forty-two patients received AMG 420 at 0.2-800 μg/d. Median age was 65 years, and median disease duration was 5.2 years. Median exposure was 1 cycle (range, 1-10 cycles) and 7 cycles (range, 1-10 cycles) for responders. Patients discontinued for disease progression (n = 25), adverse events (AEs; n = 7), death (n = 4), completion of 10 cycles (n = 3), and consent withdrawal (n = 1). Two patients remain on treatment. There were 2 nontreatment-related deaths from AEs, influenza/aspergillosis and adenovirus-related hepatitis. Serious AEs (n = 20; 48%) included infections (n = 14) and polyneuropathy (n = 2); treatment-related serious AEs included 2 grade 3 polyneuropathies and 1 grade 3 edema. There were no grade ≥ 3 CNS toxicities or anti-AMG 420 antibodies. In this study, 800 μg/d was considered to not be tolerable because of 1 instance each of grade 3 cytokine release syndrome and grade 3 polyneuropathy, both of which resolved. The overall response rate was 31% (n = 13 of 42). At the maximum tolerated dose (MTD) of 400 μg/d, the response rate was 70% (n = 7 of 10). Of these, five patients experienced MRD-negative complete responses, and 1 had a partial response, and 1 had a very good partial response; all 7 patients responded during the first cycle, and some responses lasted &gt; 1 year. CONCLUSION In this study of AMG 420 in patients with relapsed/refractory multiple myeloma, the response rate was 70%, including 50% MRD-negative complete responses, at 400 μg/d, the MTD for this study.
Changes in Quality of Care after Hospital Mergers and Acquisitions
Authors: Nancy D. Beaulieu, Leemore S. Dafny, Bruce E. Landon, Jesse B. Dalton, Ifedayo Kuye, J. Michael McWilliams
Journal: New England Journal of Medicine (2020)

The hospital industry has consolidated substantially during the past two decades and at an accelerated pace since 2010. Multiple studies have shown that hospital mergers have led to higher prices for commercially insured patients, but research about effects on quality of care is limited.
Essential Ingredients and Innovations in the Design and Analysis of Group-Randomized Trials
Authors: David M. Murray, Monica Taljaard, Elizabeth L. Turner, Stephanie M. George
Journal: Annual Review of Public Health (2019)

This article reviews the essential ingredients and innovations in the design and analysis of group-randomized trials. The methods literature for these trials has grown steadily since they were introduced to the biomedical research community in the late 1970s, and we summarize those developments. We review, in addition to the group-randomized trial, methods for two closely related designs, the individually randomized group treatment trial and the stepped-wedge group-randomized trial. After describing the essential ingredients for these designs, we review the most important developments in the evolution of their methods using a new bibliometric tool developed at the National Institutes of Health. We then discuss the questions to be considered when selecting from among these designs or selecting the traditional randomized controlled trial. We close with a review of current methods for the analysis of data from these designs, a case study to illustrate each design, and a brief summary.
Performance of PD-L1 immunohistochemistry (IHC) assays in unresectable locally advanced or metastatic triple-negative breast cancer (mTNBC): Post-hoc analysis of IMpassion130
Authors: H.S. Rugo, S. Loi, S. Adams, P. Schmid, A. Schneeweiss, C.H. Barrios, H. Iwata, V.C. Dieras, E.P. Winer, M. Kockx, D. Peeters, S.Y. Chui, J.C. Lin, A. Nguyen Duc, G. Viale, L. Molinero, L.A. Emens
Journal: Annals of Oncology (2019)
Ibrutinib Regimens in Older Patients with Untreated CLL
Authors: Manju Sengar, Nithya Gogtay, Hasmukh Jain
Journal: New England Journal of Medicine (2019)

Ibrutinib Regimens in Older Patients with Untreated CLLTo the Editor: Woyach et al. (Dec.27 issue) 1 report that in their trial involving patients who were 65 years of age or older with previously untreated chronic lymphocytic leukemia (CLL), treatment with ibrutinib was superior to bendamustine plus rituximab with regard to progression-free survival.The authors also report that the rate of grade 5 adverse events was higher than expected with the ibrutinib-containing regimens.They thought this finding might be due to the crossover design and short follow-up.However, in the Adverse Events section of the article, the authors mention that they excluded events that occurred after crossover, so I think this finding could not have been related to the crossover design.The rate of grade 5 adverse events, especially unexplained or unwitnessed death, appears to be significantly higher in this trial than in similar trials. 2,3However, the rate of grade 5 adverse events other than unexplained or unwitnessed death was consistent with that in previous reports.I think this finding might be related to lethal ventricular tachyarrhythmias that may develop in patients who receive ibrutinib. 4
A Novel Composition of Endogenous Metabolic Modulators, AXA4010, Impacts Adhesion, Inflammation and RBC Membrane Deformability in Preclinical Models of Sickle Cell Disease
Authors: Michael Hamill, Sean Carroll, Revati Wani, Matthew Russell, Zoe Steuert, Arianna Nitzel, Andrew Downey, Murat Cokol, Raffi Afeyan, Svetlana Marukian, Tony Tramontin
Journal: Blood (2019)
Outcomes of elderly stage I lung cancer patients treated with segmentectomy via video assisted thoracoscopic surgery or open resection.
Authors: Cardinale B. Smith, Grace Mhango, Juan P. Wisnivesky
Journal: Journal of Clinical Oncology (2013)

7543 Background: Video-assisted thoracic surgery (VATS) is considered an alternative to open lobectomy for the treatment of non-small cell lung cancer (NSCLC). Limited data is available however, regarding the equivalence of open vs. VATS segmental resections, particularly among elderly patients. In this study, we used population-based data to compare postoperative and oncologic outcomes following open vs. VATS segmentectomy for early NSCLC. Methods: We identified all stage I NSCLC patients &gt;65 year treated with VATS or open segmentectomy from the Surveillance, Epidemiology, and End Results registry linked to Medicare claims. We used propensity score methods to control for differences in the baseline characteristics of patients. Overall and lung cancer-specific survival of patients treated with VATS vs. open segmentectomy was compared after adjusting, stratifying, or matching patients based on their propensity score. We performed secondary analyses evaluating perioperative complications, need for intensive care unit (ICU) admission, extended length of stay, and perioperative mortality. These were repeated adjusting for physician characteristics (sociodemographics, specialty, and procedure volume). Results: Of the 577 study patients, 27% underwent VATS resection. VATS were mostly performed by high volume surgeons (p&lt;0.001). Overall (hazard ratio [HR]: 0.80, 95% CI: 0.60-1.06) and lung cancer-specific (HR: 0.71, 95% CI: 0.45-1.12) survival was similar among treatment groups. VATS-treated patients had lower rates of postoperative complications (odds ratio [OR]: 0.55, 95% confidence interval [CI]: 0.37-0.83), need for ICU admission (OR: 0.18, 95% CI: 0.12-0.28), and decreased length of stay (OR: 0.41, 95% CI: 0.41-0.81) after adjusting for propensity scores. The distribution of all postoperative complications, ICU admission, extended length of stay, and perioperative mortality was not significantly different across groups after adjusting for surgeon characteristics. Conclusions: VATS segmentectomy can be safely performed among elderly patients with early stage NSCLC and is associated with equivalent postoperative and long-term oncologic outcomes.
Abstract 235: The Association Between No-Flow Interval and Neurological Outcomes in Out-Of-Hospital Cardiac Arrest: Implications for Rescuer Response, Initiating Resuscitation, and ECPR Candidacy Evaluation
Authors: Brian E Grunau, Andrew Guy, Takahisa Kawano, Frank Scheuermeyer, Floyd Besserer, Hussein Kanji, James Christenson
Journal: Circulation (2019)

Introduction: The benefits of early CPR are evident, however the relationship between the no-flow interval and neurological outcomes may assist clinicians with resuscitation management. Methods: We examined emergency medical system-treated non-traumatic out-of-hospital cardiac arrests from two clinical trials (PRIMED and CCC; 2006-2015), including only bystander witnessed cases without bystander resuscitation. We created a subgroup to simulate ECPR-treated cases (witnessed, age ≤65, non-asystole initial rhythm, and ROSC &gt;30 minutes). We fit an adjusted logistic regression model to estimate the relationship between the “no-flow” interval (911 call-to-initiation of CPR) and favorable neurological outcome (MRS ≤3) at hospital discharge, and created a cubic spline curve. Results: Of 43,593 trial cases, 7299 were included; 616 (8.4%; 95% CI 7.8-9.1%) favourable neurological outcomes. The no-flow interval (per minute) was associated favorable neurological outcomes (adjusted OR 0.88, 95% CI 0.85-0.91). The adjusted probability of a favorable neurological outcome decreased by 0.52% (95% CI 0.39-0.65) per no-flow minute. No patients (0%; 1-sided 97.5% CI 0-0.051%) had both a no-flow duration &gt;20 minutes and a favorable neurological outcome. In the ECPR group, 15 (9.9%; 95% CI 5.1-15%) had favourable neurological outcomes; 0/152 (0%; 1-sided 97.5% CI 0-2.4%) had both a no-flow interval &gt;10 minutes and a favourable neurological outcome. Conclusions: The odds of a favorable neurological outcome decrease as the no-flow interval increases, highlighting the urgency of rescuer response. We found no favorable outcomes among cases with &gt;20 minutes of no-flow duration, which may assist providers with decisions of starting or terminating resuscitation. Among ECPR-eligible cases with prolonged resuscitative efforts there were no favourable neurological outcomes among those with a no flow-interval &gt;10 minutes, which may assist with ECPR candidacy assessment.
Climate change brings the specter of new infectious diseases
Authors: Arturo Casadevall
Journal: Journal of Clinical Investigation (2020)

Climate change will bring major changes to the epidemiology of infectious diseases through changes in microbial and vector geographic range.Human defenses against microbial diseases rely on advanced immunity that includes innate and adaptive arms and endothermy, which creates a thermal restriction zone for many microbes.Given that microbes can adapt to higher temperatures, there is concern that global warming will select for microbes with higher heat tolerance that can defeat our endothermy defenses and bring new infectious disease.
Limited Conclusions Can Be Reached From Danish Randomized Clinical Trial of Supported Employment
Authors: Kim T. Mueser, Susan R. McGurk
Journal: JAMA Psychiatry (2019)

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 Psychiatry 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 Psychiatry journal
Translating the Secondary Prevention Therapeutic Boom Into Action
Authors: Michael G. Nanna, Eric D. Peterson
Journal: JAMA Cardiology (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 Cardiology 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 Cardiology journal
Only one in 10 outpatient appointments use video despite appetite for greater use of the technology, survey finds
Authors: Abi Rimmer
Journal: BMJ (2019)

Most UK physicians have not conducted any outpatient consultations by video recently, despite 70% thinking at least some could have been done this way, a survey conducted by the Royal College of Physicians (RCP) has found.

The college’s Barriers to Care survey was open to its UK members and fellows across all grades and specialties, and …
A phase II trial of pazopanib in relapsed/refractory small cell lung cancer (SCLC).
Authors: Leena Gandhi, Rebecca Suk Heist, Joan Vern Lucca, Jennifer S. Temel, Panos Fidias, Linda K. Morse, Bruce E Johnson
Journal: Journal of Clinical Oncology (2012)

7099 Background: Despite response to initial therapy, SCLC has high rates of relapse or distant metastasis and limited 2nd-line therapeutic options. Angiogenesis is an essential part of cell invasion, dissemination, and outgrowth of distant metastases and therefore is a potential therapeutic target in SCLC. Pazopanib (Votrient, GSK) is a potent, competitive inhibitor of the tyrosine kinase activity of VEGFR-1, VEGFR-2, VEGFR-3, PDGF, and c-kit. We initiated a phase II single-arm trial of pazopanib in relapsed or refractory SCLC to determine impact on disease progression. Methods: Patients were eligible if they had progressive disease following up to two lines of prior therapy. Patients were treated at the FDA-approved dose of 800 mg pazopanib once daily. The primary endpoint was progression-free rate (PFR) at 8 weeks. Secondary endpoints included median progression-free survival, overall survival, and safety. The trial followed a Simon 2-stage design to limit accrual if no therapeutic benefit was observed. Results: To date, 27 of 30 planned subjects have been enrolled since October 2010. Two did not complete cycle 1 and were considered inevaluable for response. Major toxicities (mostly grade 1/2) were those previously described including nausea, fatigue, hypertension, electrolyte abnormalities, and AST/ALT elevations (grade 3 in 4 subjects). Three subjects were removed from study due to toxicity: 1 with grade 3 nausea, 1 with grade 3 drop in the cardiac ejection fraction, and 1 with multiple grade 2 toxicities including diarrhea, fatigue, and nausea. A fourth was removed due to grade 1 hemoptysis despite clinical response. The PFR at 8 weeks of 21 subjects evaluable for response to date was 52%; 4 of these 11 subjects had chemo-refractory disease. There were no confirmed responses, but tumor regressions ranged from 2-20%. Median progression-free survival is 14.1 weeks. Conclusions: In patients with SCLC, single-agent pazopanib demonstrated a notable rate of stable disease (including among chemo-refractory patients) and a median PFS that exceeds that of historical PFS rates of &lt; 2 months on ineffective 2nd-line therapies. These data suggest that the potential for pazopanib in SCLC treatment should be further investigated.