tbuckley/cabot-search huggingface dataset:
Updated Overall Survival Data and Predictive Biomarkers of Sintilimab Plus Pemetrexed and Platinum as First-Line Treatment for Locally Advanced or Metastatic Nonsquamous NSCLC in the Phase 3 ORIENT-11 Study
Authors: Yunpeng Yang, Jiya Sun, Zhehai Wang, Jian Fang, Qitao Yu, Baohui Han, Shundong Cang, Gongyan Chen, Xiaodong Mei, Zhixiong Yang, Rui Ma, Minghong Bi, Xiubao Ren, Jianying Zhou, Baolan Li, Yong Song, Jifeng Feng, Juan Li, Zhiyong He, Rui Zhou, Weimin Li, You Lu, Hui Zhou, Shuyan Wang, Luyao Sun, Oscar Puig, Christoph Mancao, Bo Peng, Wenfeng Fang, Wei Xu, Li Zhang
Journal: Journal of Thoracic Oncology (2021)

IntroductionSintilimab plus chemotherapy significantly prolonged progression-free survival (PFS) compared with chemotherapy alone in nonsquamous NSCLC in the ORIENT-11 study. Updated overall survival (OS) and PFS data and corresponding biomarker analyses are reported here.MethodsIn this study, a total of 397 patients with previously untreated, locally advanced or metastatic nonsquamous NSCLC were assigned to sintilimab plus chemotherapy combination treatment (combo) group or placebo plus chemotherapy treatment group. The patients were stratified by programmed death-ligand 1 (PD-L1) expression levels. Immune signature profiles from tumor RNA sequencing and PD-L1 immunohistochemistry were correlated with clinical outcome to identify predictive biomarkers.ResultsAs of January 2021, with median follow-up of 22.9 months, median OS was significantly improved in the combo group compared with the placebo plus chemotherapy treatment group (not reached versus 16.8 mo; hazard ratio [HR] = 0.60, 95% confidence interval [CI]: 0.45–0.79, p = 0.0003). High or medium immune cell infiltration was strongly associated with improved PFS in the combo group, in contrast to absent or low immune cell infiltration, which suggests that chemotherapy could not prime "immune deserts" to obtain benefit from programmed cell death protein-1 inhibition. In particular, high major histocompatibility complex (MHC) class II presentation pathway expression was significantly correlated with prolonged PFS (HR = 0.32, 95% CI: 0.19–0.54, p < 0.0001) and OS (HR = 0.36, 95% CI: 0.20–0.64, p = 0.0005) in the combo group. Importantly, patients with low or absent PD-L1 but high MHC class II expression could still benefit from the combo treatment. In contrast, MHC class I antigen presentation pathway was less relevant in this combination setting.ConclusionsThe addition of sintilimab to chemotherapy resulted to significantly longer OS in nonsquamous NSCLC. Expression of MHC class II antigen presentation pathway could identify patients benefiting most from this combination.
UNDERWATER- VERSUS CONVENTIONAL ENDOSCOPIC MUCOSAL RESECTION OF LARGE SESSILE OR FLAT COLONIC POLYPS: PRELIMINARY RESULTS OF A PROSPECTIVE RANDOMIZED CONTROLLED TRIAL
Authors: S Nagl, A Ebigbo, G Braun, S Gölder, L Neuhaus, A Probst, C Römmele, A Schneider, E Schnoy, T Weber, H Messmann
Journal: Endoscopy (2020)

Aims Conventional endoscopic mucosal resection (CEMR) with submucosal injection is the current standard for the resection of large, non-malignant colonic polyps. Underwater EMR (UWEMR) is a novel technique and has been shown to be more effective than CEMR for colonic polyps up to 20 mm in size. In this study, we present preliminary results of a randomized, controlled trial to demonstrate the efficacy, safety and feasibility of UWEMR for large sessile or flat colonic polyps between 20 mm and 40 mm.
Choreo-acanthocytosis
Authors: Barbara J. Bain, Peter G. Bain
Journal: American Journal of Hematology (2013)

A 38-year-old Pakistani patient presented with a 3-year history of facial grimacing, dysphagia, dysarthria, and stutter. More recently she had developed mild chorea. On examination, she had facial tics, eye twitching, excessive blinking, tongue protrusions, dystonic opening of the mouth and choreiform movement of the limbs, particularly on the right side 1. There was no family history of neurological disease but her parents were first cousins. Her full blood count was normal but a blood film showed acanthocytosis (image). A diagnosis of choreo-acanthocytosis was confirmed by demonstration of reduced chorein expression in red cell membranes. Choreo-acanthocytosis is one of four rare neurological syndromes with movement disorders linked to atrophy of the basal ganglia, acanthocytosis and normal beta lipoproteins, designated collectively neuroacanthocytosis (Table 1). The common link between the neurological and erythroid abnormality is an abnormality of cell membranes. Detection of acanthocytes in a blood film is diagnostically useful.
Abstract 15479: Global Burden of Rheumatic Heart Disease and the Shortage of Penicillin
Authors: Vikas Yellapu, Qasim Z Malik, Ileana Perez Figueroa, Avi Singh, Santo V Longo, Sudip Nanda
Journal: Circulation (2019)

Introduction: Rheumatic heart disease (RHD) is a sequela of a simple Group A streptococcal infection left untreated. It is estimated that in 2017 the global incidence of RHD was 1.3 million new cas...
Engineering liver
Authors: Linda G. Griffith, Alan Wells, Donna B. Stolz
Journal: Hepatology (2014)

Interest in "engineering liver" arises from multiple communities: therapeutic replacement; mechanistic models of human processes; and drug safety and efficacy studies. An explosion of micro- and nanofabrication, biomaterials, microfluidic, and other technologies potentially affords unprecedented opportunity to create microphysiological models of the human liver, but engineering design principles for how to deploy these tools effectively toward specific applications, including how to define the essential constraints of any given application (available sources of cells, acceptable cost, and user-friendliness), are still emerging. Arguably less appreciated is the parallel growth in computational systems biology approaches toward these same problems-particularly in parsing complex disease processes from clinical material, building models of response networks, and in how to interpret the growing compendium of data on drug efficacy and toxicology in patient populations. Here, we provide insight into how the complementary paths of engineering liver-experimental and computational-are beginning to interplay toward greater illumination of human disease states and technologies for drug development.
Appropriate Opioid Prescribing for Acute Pain
Authors: Deborah Grady, Mitchell H. Katz
Journal: JAMA Internal Medicine (2021)

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 Internal Medicine 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 Internal Medicine journal
“I feel like a spare part”
Authors: Hannah Beresford
Journal: BMJ (2021)

Stepping onto your first ward round as a medical student is undeniably terrifying. No amount of clinical skills sessions truly prepare you for entering the world of paperwork, hierarchy, and bed management. For medical students, a ward round can mean anything from being the designated “curtain-shutter-in-chief” to a consultant-led grilling. <b>Hannah Beresford</b> outlines steps you can take to get more out of the ward round.
Novel <i>NPM1</i> exon 5 mutations and gene fusions leading to aberrant cytoplasmic nucleophosmin in AML
Authors: Maria Paola Martelli, Roberta Rossi, Alessandra Venanzi, Manja Meggendorfer, Vincenzo Maria Perriello, Giovanni Martino, Orietta Spinelli, Raffaella Ciurnelli, Emanuela Varasano, Lorenzo Brunetti, Stefano Ascani, Corinne Quadalti, Valeria Cardinali, Federica Mezzasoma, Ilaria Gionfriddo, Francesca Milano, Roberta Pacini, Alessia Tabarrini, Barbara Bigerna, Francesco Albano, Giorgina Specchia, Calogero Vetro, Francesco Di Raimondo, Ombretta Annibali, Giuseppe Avvisati, Alessandro Rambaldi, Franca Falzetti, Enrico Tiacci, Paolo Sportoletti, Torsten Haferlach, Claudia Haferlach, Brunangelo Falini
Journal: Blood (2021)
Editor's Note: The Paradoxical Expression of <i>Maspin</i> in Ovarian Carcinoma
Authors: Anil K. Sood, Mavis S. Fletcher, Lynn M. Gruman, Jeremy E. Coffin, Sarvenaz Jabbari, Zhila Khalkhali-Ellis, Nancy Arbour, Elisabeth A. Seftor, Mary J.C. Hendrix
Journal: Clinical Cancer Research (2021)

The editors are publishing this note to alert readers to a concern about [this article][1] ([1][2]): in Fig. 1D, the GADPH blots appear identical in the HIO-180 and 1436N1 lanes. The authors retain original corroborative data and stand by the conclusions in the article. 1. 1.[↵][3]1. Sood AK
The Clinical Significance of Hepatic CD69+CD103+CD8+ Resident‐Memory T Cells in Autoimmune Hepatitis
Authors: Zhengrui You, You Li, Qixia Wang, Zhibin Zhao, Yikang Li, Qiwei Qian, Bo Li, Jun Zhang, Bingyuan Huang, Jubo Liang, Ruiling Chen, Zhuwan Lyu, Yong Chen, Min Lian, Xiao Xiao, Qi Miao, Jingyuan Fang, Zhexiong Lian, M. Eric Gershwin, Ruqi Tang, Xiong Ma
Journal: Hepatology (2021)

The diverse inflammatory response found in the liver of patients with autoimmune hepatitis (AIH) is well established, but identification of potentially pathogenic subpopulations has proven enigmatic.We report herein that CD69+ CD103+ CD8+ tissue-resident memory T cells (TRM ) are significantly increased in the liver of patients with AIH compared to chronic hepatitis B, NAFLD, and healthy control tissues. In addition, there was a significant statistical correlation between elevation of CD8+ TRM cells and AIH disease severity. Indeed, in patients with successful responses to immunosuppression, the frequencies of such hepatic CD8+ TRM cells decreased significantly. CD69+ CD8+ and CD69+ CD103+ CD8+ T cells, also known as CD8+ TRM cells, reflect tissue residency and are well known to provide intense immune antigenic responses. Hence, it was particularly interesting that patients with AIH also manifest an elevated expression of IL-15 and TGF-β on inflammatory cells, and extensive hepatic expression of E-cadherin; these factors likely contribute to the development and localization of CD8+ TRM cells. Based on these data and, in particular, the relationships between disease severity and CD8+ TRM cells, we studied the mechanisms involved with glucocorticoid (GC) modulation of CD8+ TRM cell expansion. Our data reflect that GCs in vitro inhibit the expansion of CD8+ TRM cells induced by IL-15 and TGF-β and with direct down-regulation of the nuclear factor Blimp1 of CD8+ TRM cells.Our data suggest that CD8+ TRM cells play a critical role in the pathogenesis of AIH, and GCs attenuate hepatic inflammation through direct inhibition of CD8+ TRM cell expansion.
Targeting<i>HER2</i>Exon 20 Insertion–Mutant Lung Adenocarcinoma with a Novel Tyrosine Kinase Inhibitor Mobocertinib
Authors: Han Han, Shuai Li, Ting Chen, Michael Fitzgerald, Shengwu Liu, Chengwei Peng, Kwan Ho Tang, Shougen Cao, Johara Chouitar, Jiansheng Wu, David Peng, Jiehui Deng, Zhendong Gao, Theresa E. Baker, Fei Li, Hua Zhang, Yuanwang Pan, Hailin Ding, Hai Hu, Val Pyon, Cassandra Thakurdin, Eleni Papadopoulos, Sittinon Tang, Francois Gonzalvez, Haiquan Chen, Victor M. Rivera, Rachael Brake, Sylvie Vincent, Kwok-Kin Wong
Journal: Cancer Research (2021)

Abstract No targeted treatments are currently approved for HER2 exon 20 insertion–mutant lung adenocarcinoma patients. Mobocertinib (TAK-788) is a potent irreversible tyrosine kinase inhibitor (TKI) designed to target human epidermal growth factor receptor 2 (HER2/ERBB2) exon 20 insertion mutations. However, the function of mobocertinib on HER2 exon 20 insertion–mutant lung cancer is still unclear. Here we conducted systematic characterization of preclinical models to understand the activity profile of mobocertinib against HER2 exon 20 insertions. In HER2 exon 20 insertion–mutant cell lines, the IC50 of mobocertinib was higher than poziotinib and comparable with or slightly lower than afatinib, neratinib, and pyrotinib. Mobocertinib had the lowest HER2 exon 20 insertion IC50/wild-type (WT) EGFR IC50 ratio, indicating that mobocertinib displayed the best selectivity profile in these models. Also, mobocertinib showed strong inhibitory activity in HER2 exon 20YVMA allograft and patient-derived xenograft models. In genetically engineered mouse models, HER2 exon 20G776&amp;gt;VC lung tumors exhibited a sustained complete response to mobocertinib, whereas HER2 exon 20YVMA tumors showed only partial and transient response. Combined treatment with a second antibody–drug conjugate (ADC) against HER2, ado-trastuzumab emtansine (T-DM1), synergized with mobocertinib in HER2 exon 20YVMA tumors. In addition to the tumor cell autonomous effect, sustained tumor growth control derived from M1 macrophage infiltration and CD4+ T-cell activation. These findings support the ongoing clinical development of mobocertinib (NCT02716116) and provide a rationale for future clinical evaluation of T-DM1 combinational therapy in HER2 exon 20YVMA insertion–mutant lung adenocarcinoma patients. Significance: This study elucidates the potent inhibitory activity of mobocertinib against HER2 exon 20 insertion–mutant lung cancer and the synergic effect of combined mobocertinib and T-DM1, providing a strong rationale for clinical investigation.
Fast-Acting Insulin Aspart Versus Insulin Aspart Using a Second-Generation Hybrid Closed-Loop System in Adults With Type 1 Diabetes: A Randomized, Open-Label, Crossover Trial
Authors: Melissa H. Lee, Barbora Paldus, Sara Vogrin, Dale Morrison, Dessi P. Zaharieva, Jean Lu, Hannah M. Jones, Emma Netzer, Lesley Robinson, Benyamin Grosman, Anirban Roy, Natalie Kurtz, Glenn M. Ward, Richard J. MacIsaac, Alicia J. Jenkins, David N. O’Neal
Journal: Diabetes Care (2021)

OBJECTIVE To evaluate glucose control using fast-acting insulin aspart (faster aspart) compared with insulin aspart (IAsp) delivered by the MiniMed Advanced Hybrid Closed-Loop (AHCL) system in adults with type 1 diabetes. RESEARCH DESIGN AND METHODS In this randomized, open-label, crossover study, participants were assigned to receive faster aspart or IAsp in random order. Stages 1 and 2 comprised of 6 weeks in closed loop, preceded by 2 weeks in open loop. This was followed by stage 3, whereby participants changed directly back to the insulin formulation used in stage 1 for 1 week in closed loop. Participants chose their own meals except for two standardized meal tests, a missed meal bolus and late meal bolus. The primary outcome was the percentage of time sensor glucose values were from 70 to 180 mg/dL (time in range [TIR]). RESULTS Twenty-five adults (52% male) were recruited; the median (interquartile range) age was 48 (37, 57) years, and the median HbA1c was 7.0% (6.6, 7.2) (53 [49, 55] mmol/mol). Faster aspart demonstrated greater overall TIR compared with IAsp (82.3% [78.5, 83.7] vs. 79.6% [77.0, 83.4], respectively; mean difference 1.9% [0.5, 3.3]; P = 0.007). Four-hour postprandial glucose TIR was higher using faster aspart compared with IAsp for all meals combined (73.6% [69.4, 80.2] vs. 72.1% [64.5, 78.5], respectively; median difference 3.5% [1.0, 7.3]; P = 0.003). There was no ketoacidosis or severe hypoglycemia. CONCLUSIONS Faster aspart safely improved glucose control compared with IAsp in a group of adults with well-controlled type 1 diabetes using AHCL. The modest improvement was mainly related to mealtime glycemia. While the primary outcome demonstrated statistical significance, the clinical impact may be small, given an overall difference in TIR of 1.9%.
P-148 Perfect concordance between blood-based and normal tissue-based dihydropyrimidine dehydrogenase polymorphisms suggests that pharmacogenetic screening could be contextual to tumour molecular profiling
Authors: C. Morelli, V. Formica, E. Doldo, S. Riondino, M. Rofei, G. Palmieri, A. Orlandi, M. Roselli
Journal: Annals of Oncology (2021)
Precision therapy for RET-altered cancers with RET inhibitors
Authors: Kyaw Z. Thein, Vamsidhar Velcheti, Blaine H.M. Mooers, Jie Wu, Vivek Subbiah
Journal: Trends in cancer (2021)

Rearranged during transfection (RET) is involved in the physiological development of some organ systems. Activating RET alterations via either gene fusions or point mutations are potent oncogenic drivers in non-small cell lung cancer, thyroid cancer, and in multiple diverse cancers. RET-altered cancers were initially treated with multikinase inhibitors (MKIs). The efficacy of MKIs was modest at the expense of notable toxicities from their off-target activity. Recently, highly potent and RET-specific inhibitors selpercatinib and pralsetinib were successfully translated to the clinic and FDA approved. We summarize the current state-of-the-art therapeutics with preclinical and clinical insights of these novel RET inhibitors, acquired resistance mechanisms, and future outlooks.
Male sex, discoid lupus erythematosus, and lower limb involvement are associated with systemic lupus in lupus panniculitis patients: A multicenter case series of 74 patients
Authors: Juliette Lemasson, Laure Frumholtz, Marie Jachiet, Cédric Lenormand, Dan Lipsker, Sophie Moulin, Christine Chiaverini, Florence Le Duff, Thierry Passeron, Florence Cordoliani, Martine Bagot, Jean-Benoît Monfort, Patricia Senet, Adèle De Masson, Charles Cassius, Antoine Petit, Laurent Misery, Philippe Moguelet, Nadège Cordel, Laurence Fardet, Edouard Begon, Camille Frances, Didier Bessis, Jean-David Bouaziz, François Chasset
Journal: Journal of the American Academy of Dermatology (2021)
Surprise Billing in Health Care
Authors: Lauren E. Miller, Roy Xiao, Vinay K. Rathi
Journal: JAMA (2021)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Breast cancer screening in patients with cancers other than breast.
Authors: Stephen M Maurer, Robin Berton Leopold, Alexander W Thomas, Kyle Francis Concannon, Alissa Dorothy Correll, Catherine M LaPenta, Brian L Sprague, Sally D. Herschorn, Claire F. Verschraegen
Journal: Journal of Clinical Oncology (2017)

e13095 Background: Screening mammography can detect early breast cancers and reduce subsequent cancer mortality. However, there is a lack of consensus as to what should trigger screening discontinuation. This absence of clear-cut guidelines means that many patients with advanced malignancies continue screening despite unclear benefit. Methods: We performed a retrospective cohort study of female patients diagnosed with a non-breast malignancy to explore the incidence and effects of screening mammography. Female patients, who were diagnosed between 2007 and 2012 with a non-breast malignancy stage II or higher, were cross-referenced with the Vermont mammography screening logs from January 1, 2007 to September 30, 2014. Additional data was collected through chart reviews, in May 2016. Results: Of 1501 women, 398 (26%) who met the above criteria had a screening mammogram within first 5 years of their cancer diagnosis. Of these 398 women, 193 (48.5%) were alive without cancer, 132 (33.2%) had died, and 73 (18.3%) were alive with cancer at the time of chart review. Of those who died, 84 (63.6%) had a stage III or IV cancer. Eighteen (4.5%) had a breast biopsy following a suspicious screening mammogram, resulting in 13 (3.3%) benign diagnoses and 5 (1.3%) breast cancer diagnoses. No patient died of breast cancer. Conclusions: Female patients diagnosed with an advanced non-breast malignancy have a mortality risk that outweighs the known breast cancer mortality benefit from screening mammography. [Table: see text]
Abstract 2437: The Interaction between Left Ventricular Apical Rotation and the Arterial Blood Pressure in Elderly Females may Reveal Mechanisms Involved in the Syndrome of Diastolic Heart Failure a Follow-Up Study
Authors: Johannes Soma, Ketil Dahl, Tor-Erik Widerøe
Journal: Circulation (2008)

LV apical short-axis loops were obtained with 2D echocardiography (80 – 110 frames/s) in 31 healthy females, age 69 to 84 years. Peak apical rotation (PAR) and peak rotation velocity (PAR-velocity) was assessed with speckle tracking (ST). Ambulatory systolic (SBP) and diastolic (DBP) blood pressures were averaged between 0600 and 2300. The difference (Δ) between measurements after four years follow-up was calculated by subtracting the first from the last assessment. Apical short-axis loops were eligible for ST in 27 subjects. SBP and DBP increased (126 ± 14 vs 133 ± 13 mm Hg, p = 0.007 and 70 ± 7 vs 73 ± 7 mm Hg, p = 0.049) and LV end-diastolic and end-systolic volumes decreased (84 ± 15 vs 74 ± 10 ml, p &lt; 0.0001 and 33 ± 9 vs 25 ± 7 ml, p &lt; 0.0001) during follow-up. ΔSBP and ΔDBP correlated inversely with the LV end-diastolic short-axis dimension (r = −0.38, p = 0.03 and r = −0.43, p = 0.02). ΔSBP, ΔDBP and DBP, correlated inversely with PAR (r = −0.51, p = 0.007; r = −0.59, p = 0.0001 and r = −0.47, p = 0.01). PAR correlated positively with LV stroke volume and with body weight (p &lt; 0.05) and with systolic and diastolic PAR-velocity (r = 0.76, p &lt; 0.0001 and r = 0.58, p = 0.001). Diastolic PAR-velocity correlated with mitral E peak velocity (r = 0.48, p = 0.01). In healthy elderly females LV peak apical rotation and peak diastolic rotation velocity correlate with indices of LV filling and ejection, indicating that suction, a key property for effective early LV filling, may be preserved in elderly subjects. Suction seems to deteriorate with BP elevations. An age- or blood pressure related reduction in LV end-diastolic volume may represent an additional impediment to LV filling. Both features may contribute to the development of LV diastolic dysfunction and to diastolic heart failure.