tbuckley/cabot-search huggingface dataset:
Obeticholic Acid Impact on Quality of Life in Patients With Nonalcoholic Steatohepatitis: REGENERATE 18-Month Interim Analysis
Authors: Zobair M. Younossi, Maria Stepanova, Fatema Nader, Rohit Loomba, Quentin M. Anstee, Vlad Ratziu, Stephen Harrison, Arun J. Sanyal, Jörn M. Schattenberg, A. Sidney Barritt, Mazen Noureddin, Martin Bonacci, Gail Cawkwell, Bruce Wong, Mary Rinella
Journal: Clinical Gastroenterology and Hepatology (2021)

Nonalcoholic steatohepatitis (NASH) affects patients' health-related quality of life (HRQoL). Patient-reported outcomes (PROs) evaluating HRQoL were assessed in the RandomizEd Global Phase 3 Study to Evaluate the Impact on NASH with FibRosis of Obeticholic Acid TreatmEnt (REGENERATE) study, which showed that obeticholic acid (OCA) significantly improved fibrosis in patients with NASH. Noncirrhotic NASH patients in a phase 3, double-blind, randomized, placebo-controlled, multicenter, international study of OCA were enrolled. The Chronic Liver Disease Questionnaire-NASH and EuroQol EQ-5D-5L were administered at baseline, 6, 12, and 18 months. There were 1218 patients (age, 54.1 ± 11.5 y; 57% women; 43% stage F3) in the expanded intent-to-treat population (stages, F1-F3) assigned randomly to 10 mg (N = 407) or 25 mg (N = 404) OCA or placebo (N = 407). Baseline measurements were balanced across treatment groups for EuroQol EQ-5D-5L and Chronic Liver Disease Questionnaire-NASH, including Itch score: 5.75 ± 1.53 (scale 1-7, with 7 representing no itching). Nineteen (1.6%) patients discontinued therapy (protocol mandated) because of grade 3 pruritus. Patients receiving 25 mg OCA experienced mild worsening of itch scores primarily in the first months of treatment: mean ± SE change from baseline -0.66 ± 0.12, -0.44 ± 0.12, and -0.42 ± 0.13 at 6, 12, and 18 months, respectively (all P < .01). No other PRO worsening was associated with 25 mg OCA. Patients experiencing fibrosis improvement, Nonalcoholic Fatty Liver Disease Activity Score decrease (by ≥2 points), or NASH resolution had greater PRO improvements in some domains. NASH patients evaluated in REGENERATE had impaired quality of life and underlying pruritus at baseline. Improvement of NASH corresponded with improvement in several HRQoL domains. Generally mild pruritus occurs early after OCA therapy initiation and does not worsen over time. gov: NCT02548351.
Filgotinib Induces and Maintains Ulcerative Colitis Remission
Authors: Anita Slomski
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
MO35-4 Impact of omitting fluorouracil from FOLFIRI plus bevacizumab in second-line treatment of metastatic colorectal cancer
Authors: Yuki Matsubara, Toshiki Masuishi, Takatsugu Ogata, Taiko Nakazawa, Kyoko Kato, Kazuki Nozawa, Yukiya Narita, Kazunori Honda, Hideaki Bando, Shigenori Kadowaki, Masashi Ando, Masahiro Tajika, Kei Muro
Journal: Annals of Oncology (2021)
P-63 MATTERHORN: A phase 3 study of efficacy and safety of neoadjuvant-adjuvant durvalumab and FLOT chemotherapy in resectable gastric and gastroesophageal junction cancer
Authors: Y. Janjigian, E. Van Cutsem, K. Muro, Z. Wainberg, S. Al-Batran, W. Hyung, D. Molena, B. Evans, D. Ruscica, S. Robbins, A. Negro, J. Tabernero
Journal: Annals of Oncology (2021)
Endothelial Reprogramming Stimulated by Oncostatin M Promotes Inflammation and Tumorigenesis in<i>VHL</i>-Deficient Kidney Tissue
Authors: Hieu-Huy Nguyen-Tran, Thi-Ngoc Nguyen, Chen-Yun Chen, Tien Hsu
Journal: Cancer Research (2021)

Abstract Clear-cell renal cell carcinoma (ccRCC) is the most prevalent subtype of renal cell carcinoma (RCC), and its progression has been linked to chronic inflammation. About 70% of the ccRCC cases are associated with inactivation of the von Hippel–Lindau (VHL) tumor-suppressor gene. However, it is still not clear how mutations in VHL, encoding the substrate-recognition subunit of an E3 ubiquitin ligase that targets the alpha subunit of hypoxia-inducible factor-α (HIFα), can coordinate tissue inflammation and tumorigenesis. We previously generated mice with conditional Vhlh knockout in kidney tubules, which resulted in severe inflammation and fibrosis in addition to hyperplasia and the appearance of transformed clear cells. Interestingly, the endothelial cells (EC), although not subject to genetic manipulation, nonetheless showed profound changes in gene expression that suggest a role in promoting inflammation and tumorigenesis. Oncostatin M (OSM) mediated the interaction between VHL-deficient renal tubule cells and the ECs, and the activated ECs in turn induced macrophage recruitment and polarization. The OSM-dependent microenvironment also promoted metastasis of exogenous tumors. Thus, OSM signaling initiates reconstitution of an inflammatory and tumorigenic microenvironment by VHL-deficient renal tubule cells, which plays a critical role in ccRCC initiation and progression. Significance: A novel mechanism of cross-talk between ECs and VHL-deficient kidney tubules that stimulates inflammation and tumorigenesis is discovered, suggesting OSM could be a potential target for ccRCC intervention.
FLASH Proton Radiotherapy Spares Normal Epithelial and Mesenchymal Tissues While Preserving Sarcoma Response
Authors: Anastasia Velalopoulou, Ilias V. Karagounis, Gwendolyn M. Cramer, Michele M. Kim, Giorgos Skoufos, Denisa Goia, Sarah Hagan, Ioannis I. Verginadis, Khayrullo Shoniyozov, June Chiango, Michelle Cerullo, Kelley Varner, Lutian Yao, Ling Qin, Artemis G. Hatzigeorgiou, Andy J. Minn, Mary Putt, Matthew Lanza, Charles-Antoine Assenmacher, Enrico Radaelli, Jennifer Huck, Eric Diffenderfer, Lei Dong, James Metz, Constantinos Koumenis, Keith A. Cengel, Amit Maity, Theresa M. Busch
Journal: Cancer Research (2021)

Abstract In studies of electron and proton radiotherapy, ultrahigh dose rates of FLASH radiotherapy appear to produce fewer toxicities than standard dose rates while maintaining local tumor control. FLASH-proton radiotherapy (F-PRT) brings the spatial advantages of PRT to FLASH dose rates (&amp;gt;40 Gy/second), making it important to understand if and how F-PRT spares normal tissues while providing antitumor efficacy that is equivalent to standard-proton radiotherapy (S-PRT). Here we studied PRT damage to skin and mesenchymal tissues of muscle and bone and found that F-PRT of the C57BL/6 murine hind leg produced fewer severe toxicities leading to death or requiring euthanasia than S-PRT of the same dose. RNA-seq analyses of murine skin and bone revealed pathways upregulated by S-PRT yet unaltered by F-PRT, such as apoptosis signaling and keratinocyte differentiation in skin, as well as osteoclast differentiation and chondrocyte development in bone. Corroborating these findings, F-PRT reduced skin injury, stem cell depletion, and inflammation, mitigated late effects including lymphedema, and decreased histopathologically detected myofiber atrophy, bone resorption, hair follicle atrophy, and epidermal hyperplasia. F-PRT was equipotent to S-PRT in control of two murine sarcoma models, including at an orthotopic intramuscular site, thereby establishing its relevance to mesenchymal cancers. Finally, S-PRT produced greater increases in TGFβ1 in murine skin and the skin of canines enrolled in a phase I study of F-PRT versus S-PRT. Collectively, these data provide novel insights into F-PRT-mediated tissue sparing and support its ongoing investigation in applications that would benefit from this sparing of skin and mesenchymal tissues. Significance: These findings will spur investigation of FLASH radiotherapy in sarcoma and additional cancers where mesenchymal tissues are at risk, including head and neck cancer, breast cancer, and pelvic malignancies.
Gastrodin Improves Nonalcoholic Fatty Liver Disease Through Activation of the Adenosine Monophosphate–Activated Protein Kinase Signaling Pathway
Authors: Juan Wan, Yanyan Zhang, Diqi Yang, Yongjie Liang, Ling Yang, Sha Hu, Zhen Liu, Qian Fang, Song Tian, Yi Ding
Journal: Hepatology (2021)

Background and Aims NASH is currently one of the most common causes of liver transplantation and hepatocellular carcinoma. Thus far, there is still no effective pharmacological therapy for this disease. Recently, Gastrodin has demonstrated hepatoprotective effects in a variety of liver diseases. The aim of this study is to investigate the function of Gastrodin in NASH. Approach and Results In our study, Gastrodin showed potent therapeutic effects on NASH both in vivo and in vitro. In high-fat diet or high-fat and high-cholesterol diet–fed mice, the liver weight, hepatic and serum triglyceride and cholesterol contents, and serum alanine aminotransferase and aspartate aminotransferase activity levels were markedly reduced by Gastrodin treatment as compared with the corresponding vehicle groups. Notably, Gastrodin showed minimal effects on the function and histological characteristics of other major organs in mice. We further examined the effects of Gastrodin on lipid accumulation in primary mouse hepatocytes and human hepatocyte cell line and observed that Gastrodin showed a significant decrease in lipid accumulation and inflammatory response in hepatocytes under metabolic stress. Furthermore, RNA-sequencing analysis systemically indicated that Gastrodin suppressed the pathway and key regulators related to lipid accumulation, inflammation, and fibrosis in the pathogenesis of NASH. Mechanistically, we found that Gastrodin protected against NASH by activating the adenosine monophosphate–activated protein kinase (AMPK) pathway, which was supported by the result that the AMPK inhibitor Compound C or AMPK knockdown blocked the Gastrodin-mediated hepatoprotective effect. Conclusions Gastrodin attenuates steatohepatitis by activating the AMPK pathway and represents a therapeutic for the treatment of NASH.
Association of Facial Pustular Neutrophilic Eruption With Messenger RNA–1273 SARS-CoV-2 Vaccine
Authors: Eric Dean Merrill, Sakeen W. Kashem, Erin H. Amerson, Laura B. Pincus, Ursula E. Lang, Kanade Shinkai, Aileen Y. Chang
Journal: JAMA Dermatology (2021)

diagnostic and therapeutic challenge.Cytotoxic Tlymphocyte antigen-4 is expressed on regulatory T cells and binds ligands CD80 and CD86 on antigen-presenting cells to halt T-lymphocyte activation. 2 When dysfunctional, the T-cell activation leads to lymphoproliferation and autoimmunity and clinically presents with common recurrent infections, such as sinus, ear, respiratory (61%), hypogammaglobinemia (84%), autoimmune cytopenias (62%), gastrointestinal symptoms (59%), endocrinopathies (33%), neurological features (including headaches) (29%), and arthritis (14%). 1,2Nonmalignant Tcell lymphoproliferation, such as hepatosplenomegaly, lymphadenopathy, and lymphocytic lung infiltrates, can be seen in 73% of patients. 1,3Symptom onset occurs at a mean age of 11 years, but disease manifestations may occur as late as age 50 years. 3Treatment of CTLA-4 haploinsufficiency includes management of autoimmune symptoms with standard therapies.Abatacept, a fusion protein comprising human CTLA-4 that is linked to a modified Fc portion of IgG1, acts as a selective Tcell costimulation modulator that can be useful in disease regulation. 1 Cytotoxic T-lymphocyte antigen-4 haploinsufficiency cutaneous findings are still poorly characterized, despite being present in 56% of patients. 3Atopic dermatitis (AD) is the most commonly described skin comorbidity, with recent reports of vitiligo, psoriasis, and alopecia. 3Cytotoxic T-lymphocyte antigen-4 variations have been associated with childhood AD and the severity of AD symptoms, and it can be the initial presenting symptom in 2% of patients. 4Similarly, CTLA-4 variations have been associated with AA in European populations and psoriasis in Eurasian populations. 5,6 This case highlights the occurrence of novel immunodeficiency syndromes and alerts dermatologists to the clinical constellation of chronic relapsing skin diseases, frequent respiratory infections, and autoimmune conditions.
Analysis of 82 Cases of Flt3/ITD Positive Acute Myeloid Leukemia Treated with Allogeneic Stem Cell Transplantation in Single Center
Authors: Wei Zhijie, Peggy (Pei-Hua) Lu, Yang Rong, Pan Fei, Nan Hua, Yue Guanlan, Gao Kang
Journal: Blood (2017)
Risk of Inflammatory Bowel Disease in Patients With Psoriasis and Psoriatic Arthritis/Ankylosing Spondylitis Initiating Interleukin‐17 Inhibitors: A Nationwide <scp>Population‐Based</scp> Study Using the French National Health Data System
Authors: Laetitia Penso, Christina Bergqvist, Antoine Meyer, Philippe Herlemont, Alain Weill, Mahmoud Zureik, Rosemary Dray‐Spira, Emilie Sbidian
Journal: Arthritis & Rheumatology (2021)

To investigate whether the initiation of treatment with an interleukin-17 inhibitor (IL-17i) in real life is associated with a higher risk of inflammatory bowel disease (IBD) in patients who had both psoriasis (PsO) and psoriatic arthritis (PsA)/ankylosing spondylitis (AS).This nationwide cohort study was conducted using the French National Health Data System database. All adult patients with PsO and PsA/AS who were identified as having newly initiated treatment with an IL-17i during 2016-2019 were included. As controls, patients with PsO and PsA/AS who had newly initiated either 1) apremilast or 2) etanercept (ETN) during this period but had not received IL-17i were included. The follow-up end date was September 30, 2019. The primary end point was the risk of occurrence of IBD associated with exposure to an IL-17i compared to exposure to the other treatments, as determined in a time-to-event analysis with propensity score-weighted Cox and Fine-Gray proportional hazards models.The study included a total of 16,793 new IL-17i users (mean ± SD age 48.4 ± 13 years, 45% men), 20,556 new apremilast users (age 52.6 ± 15 years, 54% men), and 10,294 new ETN users (age 46.3 ± 15 years, 44% men). New IL-17i users and new ETN users had received more biologics for their underlying disease compared to new apremilast users. IBD occurred in 132 patients: 72 new IL-17i users (0.43%), 11 new apremilast users (0.05%), and 49 new ETN users (0.48%). Most IBD cases occurred after 6 months of exposure (82%, 55%, and 76%, respectively). After propensity score weighting, the risk of IBD was significantly greater among patients initiating an IL-17i compared to those initiating apremilast (weighted hazard ratio [HR] 3.8 [95% confidence interval (95% CI) 2.1-6.8]). No difference in the risk of IBD between new IL-17i users and new ETN users was observed (weighted HR 0.8 [95% CI 0.5-1.2]).Patients with PsO and PsA/AS who initiate treatment with an IL-17i do not have a higher risk of developing IBD when compared to patients initiating ETN who display the same severity of underlying disease. These results need to be confirmed in other large studies of patients with PsO and PsA/AS.
MegaLMM: Mega-scale linear mixed models for genomic predictions with thousands of traits
Authors: Daniel E. Runcie, Jiayi Qu, Hao Cheng, Lorin Crawford
Journal: Genome biology (2021)

Large-scale phenotype data can enhance the power of genomic prediction in plant and animal breeding, as well as human genetics. However, the statistical foundation of multi-trait genomic prediction is based on the multivariate linear mixed effect model, a tool notorious for its fragility when applied to more than a handful of traits. We present MegaLMM, a statistical framework and associated software package for mixed model analyses of a virtually unlimited number of traits. Using three examples with real plant data, we show that MegaLMM can leverage thousands of traits at once to significantly improve genetic value prediction accuracy.
OCaMIR—A Noninvasive, Diagnostic Signature for Early-Stage Ovarian Cancer: A Multi-cohort Retrospective and Prospective Study
Authors: Raju Kandimalla, Wei Wang, Fan Yu, Nianxin Zhou, Feng Gao, Monique Spillman, Lucie Moukova, Ondrej Slaby, Bodour Salhia, Shengtao Zhou, Xin Wang, Ajay Goel
Journal: Clinical Cancer Research (2021)

Abstract Purpose: Due to the lack of effective screening approaches and early detection biomarkers, ovarian cancer has the highest mortality rates among gynecologic cancers. Herein, we undertook a systematic biomarker discovery and validation approach to identify microRNA (miRNA) biomarkers for the early detection of ovarian cancer. Experimental Design: During the discovery phase, we performed small RNA sequencing in stage I high-grade serous ovarian cancer (n = 31), which was subsequently validated in multiple, independent data sets (TCGA, n = 543; GSE65819, n = 87). Subsequently, we performed multivariate logistic regression-based training in a serum data set (GSE106817, n = 640), followed by its independent validation in three retrospective data sets (GSE31568, n = 85; GSE113486, n = 140; Czech Republic cohort, n = 192) and one prospective serum cohort (n = 95). In addition, we evaluated the specificity of OCaMIR, by comparing its performance in several other cancers (GSE31568 cohort, n = 369). Results: The OCaMIR demonstrated a robust diagnostic accuracy in the stage I high-grade serous ovarian cancer patients in the discovery cohort (AUC = 0.99), which was consistently reproducible in both stage I (AUC = 0.96) and all stage patients (AUC = 0.89) in the TCGA cohort. Logistic regression-based training and validation of OCaMIR achieved AUC values of 0.89 (GSE106817), 0.85 (GSE31568), 0.86 (GSE113486), and 0.82 (Czech Republic cohort) in the retrospective serum validation cohorts, as well as prospective validation cohort (AUC = 0.92). More importantly, OCaMIR demonstrated a significantly superior diagnostic performance compared with CA125 levels, even in stage I patients, and was more cost-effective, highlighting its potential role for screening and early detection of ovarian cancer. Conclusions: Small RNA sequencing identified a robust noninvasive miRNA signature for early-stage serous ovarian cancer detection.
Clinical Implementation of Biologics and Small Molecules in the Treatment of Hidradenitis Suppurativa
Authors: Pim Aarts, Koen Dudink, Allard R. J. V. Vossen, Kelsey R. van Straalen, Christine B. Ardon, Errol P. Prens, Hessel H. van der Zee
Journal: Drugs (2021)

Hidradenitis suppurativa (HS) is a chronic, recurrent, auto-inflammatory skin disease originating from the hair follicles. The typical inflammatory nodules, abscesses, and draining sinus tracts (tunnels) are characterized by a massive influx of neutrophils, macrophages, B-cells, plasma cells, T helper (Th)1, Th17 cells and upregulation of pro-inflammatory cytokines such as IL-1, IL-17, IL-12/23, and TNF-α. Over the last decades, several clinical trials evaluated the clinical efficacy of different biologics targeting these pro-inflammatory cytokines, in particular TNF-α and IL-1. However, adalimumab is still the only registered drug for HS. This review discusses biologics and small molecules with high level of evidence for their clinical application, provides guidance on when and how to use these biologics and small molecules in clinical practice, and elaborates on the combination with medical and surgical treatment options beyond the current guidelines. Furthermore this review provides an overview of potential biologics and small molecules currently under investigation for novel targets in HS such as IL-36, C5a, Janus kinase family members, CD-40, LTA4 and CXCR1/2.
ESMO consensus conference on malignant lymphoma: general perspectives and recommendations for prognostic tools in mature B-cell lymphomas and chronic lymphocytic leukaemia
Authors: M. Ladetto, C. Buske, M. Hutchings, M. Dreyling, G. Gaidano, S. Le Gouill, S. Luminari, C. Pott, A. Zamò, E. Zucca
Journal: Annals of Oncology (2017)
Timely Family Meetings or Time-Limited Trials?—Reply
Authors: Dong W. Chang, Jennifer Parrish, Hal F. Yee
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
Longitudinal assessment of lung clearance index to monitor disease progression in children and adults with cystic fibrosis
Authors: Alex R Horsley, John Belcher, Katie Bayfield, Brooke Bianco, Steve Cunningham, Catherine Fullwood, Andrew Jones, Anna Shawcross, Jaclyn A Smith, Anirban Maitra, Francis J Gilchrist
Journal: Thorax (2021)

Background Lung clearance index (LCI) is a valuable research tool in cystic fibrosis (CF) but clinical application has been limited by technical challenges and uncertainty about how to interpret longitudinal change. In order to help inform clinical practice, this study aimed to assess feasibility, repeatability and longitudinal LCI change in children and adults with CF with predominantly mild baseline disease. Methods Prospective, 3-year, multicentre, observational study of repeated LCI measurement at time of clinical review in patients with CF &gt;5 years, delivered using a rapid wash-in system. Results 112 patients completed at least one LCI assessment and 98 (90%) were still under follow-up at study end. The median (IQR) age was 14.7 (8.6–22.2) years and the mean (SD) FEV 1 z-score was −1.2 (1.3). Of 81 subjects with normal FEV 1 (&gt;−2 z-scores), 63% had raised LCI (indicating worse lung function). For repeat stable measurements within 6 months, the mean (limits of agreement) change in LCI was 0.9% (−18.8% to 20.7%). A latent class growth model analysis identified four discrete clusters with high accuracy, differentiated by baseline LCI and FEV 1 . Baseline LCI was the strongest factor associated with longitudinal change. The median total test time was under 19 min. Conclusions Most patients with CF with well-preserved lung function show stable LCI over time. Cluster behaviours can be identified and baseline LCI is a risk factor for future progression. These results support the use of LCI in clinical practice in identifying patients at risk of lung function decline.