tbuckley/cabot-search huggingface dataset:
Targeting CD38 and PD-1 with isatuximab plus cemiplimab in patients with advanced solid malignancies: results from a phase I/II open-label, multicenter study
Authors: Paolo Andrea Zucali, Chia-Chi Lin, Bradley C Carthon, Todd M Bauer, Marcello Tucci, Antoine Italiano, Roberto Iacovelli, Wu-Chou Su, Christophe Massard, Mansoor Saleh, Gennaro Daniele, Alastair Greystoke, Martin Gutierrez, Shubham Pant, Ying-Chun Shen, Matteo Perrino, Robin Meng, Giovanni Abbadessa, Helen Lee, Yingwen Dong, Marielle Chiron, Rui Wang, Laure Loumagne, Lucie Lépine, Johann de Bono
Journal: Journal for ImmunoTherapy of Cancer (2022)

Background Preclinical data suggest that concurrent treatment of anti-CD38 and antiprogrammed death 1 (PD-1)/programmed death ligand 1 (PD-L1) antibodies substantially reduce primary tumor growth by reversing T-cell exhaustion and thus enhancing anti-PD-1/PD-L1 efficacy. Methods This phase I/II study enrolled patients with metastatic castration-resistant prostate cancer (mCRPC) or advanced non-small cell lung cancer (NSCLC). The primary objectives of phase I were to investigate the safety and tolerability of isatuximab (anti-CD38 monoclonal antibody)+cemiplimab (anti-PD-1 monoclonal antibody, Isa+Cemi) in patients with mCRPC (naïve to anti-PD-1/PD-L1 therapy) or NSCLC (progressed on anti-PD-1/PD-L1-containing therapy). Phase II used Simon’s two-stage design with response rate as the primary endpoint. An interim analysis was planned after the first 24 (mCRPC) and 20 (NSCLC) patients receiving Isa+Cemi were enrolled in phase II. Safety, immunogenicity, pharmacokinetics, pharmacodynamics, and antitumor activity were assessed, including CD38, PD-L1, and tumor-infiltrating lymphocytes in the tumor microenvironment (TME), and peripheral immune cell phenotyping. Results Isa+Cemi demonstrated a manageable safety profile with no new safety signals. All patients experienced ≥1 treatment-emergent adverse event. Grade≥3 events occurred in 13 (54.2%) patients with mCRPC and 12 (60.0%) patients with NSCLC. Based on PCWG3 criteria, assessment of best overall response with Isa+Cemi in mCRPC revealed no complete responses (CRs), one (4.2%) unconfirmed partial response (PR), and five (20.8%) patients with stable disease (SD). Per RECIST V.1.1, patients with NSCLC receiving Isa+Cemi achieved no CR or PR, and 13 (65%) achieved SD. In post-therapy biopsies obtained from patients with mCRPC or NSCLC, Isa+Cemi treatment resulted in a reduction in median CD38+ tumor-infiltrating immune cells from 40% to 3%, with no consistent modulation of PD-L1 on tumor cells or T regulatory cells in the TME. The combination triggered a significant increase in peripheral activated and cytolytic T cells but, interestingly, decreased natural killer cells. Conclusions The present study suggests that CD38 and PD-1 modulation by Isa+Cemi has a manageable safety profile, reduces CD38+ immune cells in the TME, and activates peripheral T cells; however, such CD38 inhibition was not associated with significant antitumor activity. A lack of efficacy was observed in these small cohorts of patients with mCRPC or NSCLC. Trial registration numbers NCT03367819 .
PYLORIC OBSTRUCTION DUE TO PEPTIC ULCER
Journal: JAMA (1964)

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
Guidelines on managing people with vitiligo
Journal: British Journal of Dermatology (2022)

Abstract Linked Article: Eleftheriadou et al. Br J Dermatol 2022; 186:18–29. Vitiligo is a common, long-term skin condition. It affects approximatively 1% of the world’s population, regardless of age, sex or race. The type of vitiligo and its stability help indicate the chance of improvement (or chance of relapse). In people with vitiligo not enough melanin is produced in the body, which leads to pale, white or light pink patches on the skin. Sometimes, these patches can merge to form larger areas. In rare cases, over 80% of the body surface can be affected. However, vitiligo appears most commonly on the face, neck, hands, body openings (nostrils, mouth, genitals, navel and around the eyes) and skinfolds (the underarms and groin area). The British Association of Dermatologists (BAD) formed a group of experts made up dermatologists, clinical psychologists, patient representatives and a technical team. They reviewed relevant articles published up to May 2019 to produce evidence-based recommendations using the rigorous GRADE system (Grading of Recommendations Assessment, Development and Evaluation) for guideline development. The guideline has 28 management recommendations, nine future research recommendations and five recommended audit points (audit points are used by health professionals to assess, evaluate and improve the quality of care received by patients in a systematic way). The management approach is presented as a flow diagram, allowing clinicians to see at a glance the key recommended actions when treating people with vitiligo. Based on the experience of the group, people with vitiligo may experience high levels of social anxiety, stigma and discrimination. They recommended, alongside the recommended treatments, routine assessment of patients’ quality of life, and mental and social wellbeing. People with vitiligo should also be offered information on self-help, and where appropriate, referred for psychological therapy. The guideline was used to update the BAD’s Patient Information Leaflet (PIL) for vitiligo, which can be accessed on the BAD website (www.skinhealthinfo.org.uk/a-z-conditions-treatments/). Linked Article: Eleftheriadou et al. Br J Dermatol 2022; 186:18–29.
circCDYL2 promotes trastuzumab resistance via sustaining HER2 downstream signaling in breast cancer
Authors: Yun Ling, Gehao Liang, Qun Lin, Xiaolin Fang, Qing Luo, Yinghuan Cen, Maryam Mehrpour, Ahmed Hamai, Zihao Liu, Yu Shi, Juanmei Li, Wanyi Lin, Shijie Jia, Wenqian Yang, Qiang Liu, Erwei Song, Jun Li, Chang Gong
Journal: Molecular Cancer (2022)

Abstract Background Approximate 25% HER2-positive (HER2 + ) breast cancer (BC) patients treated with trastuzumab recurred rapidly. However, the mechanisms underlying trastuzumab resistance remained largely unclear. Methods Trastuzumab-resistant associated circRNAs were identified by circRNAs high-throughput screen and qRT-PCR in HER2 + breast cancer tissues with different trastuzumab response. The biological roles of trastuzumab-resistant associated circRNAs were detected by cell vitality assay, colony formation assay, Edu assay, patient-derived xenograft (PDX) models and orthotopic animal models. For mechanisms research, the co-immunoprecipitation, Western blot, immunofluorescence, and pull down assays confirmed the relevant mechanisms of circRNA and binding proteins. Results We identified a circRNA circCDYL2, which was overexpressed in trastuzumab-resistant patients, which conferred trastuzumab resistance in breast cancer cells in vitro and in vivo. Mechanically, circCDYL2 stabilized GRB7 by preventing its ubiquitination degradation and enhanced its interaction with FAK, which thus sustained the activities of downstream AKT and ERK1/2. Trastuzumab-resistance of HER2 + BC cells with high circCDYL2 could be reversed by FAK or GRB7 inhibitor. Clinically, HER2 + BC patients with high levels of circCDYL2 developed rapid recurrence and had shorter disease-free survival (DFS) and overall survival (OS) following anti-HER2 therapy compared to those with low circCDYL2. Conclusions circCDYL2-GRB7-FAK complex plays a critical role in maintaining HER2 signaling, which contributes to trastuzumab resistance and circCDYL2 is a potential biomarker for trastuzumab-resistance in HER2 + BC patients.
Failure of exercise to reduce hypertension
Authors: B. Arroll
Journal: JAMA (1992)

<h3>To the Editor.</h3> —We wish to comment on the article by Blumenthal et al<sup>1</sup>that found that moderate aerobic exercise does not lower blood pressure in persons with untreated mild hypertension. We recently have reviewed the literature on physical activity and blood pressure and almost all the studies show that physical activity lowers blood pressure in spite of the majority of articles having major design flaws. Although there may be a publication bias toward studies with positive results, we believe that the study by Blumenthal et al has numerous design limitations that may explain its unusual findings. The major problems are potential contamination of the control group, cointervention of the intervention group, and lack of blind assessment of blood pressure measurement. With the passage of time, the loss of the alerting response (white-coat effect) results in a reduction of blood pressure in control groups. Also, the waiting-list participants would have
Update in Adult Asthma 2020
Authors: Andrew J. Halayko, Christopher D. Pascoe, Jessica D. Gereige, Michael C. Peters, Robyn T. Cohen, Prescott G. Woodruff
Journal: American Journal of Respiratory and Critical Care Medicine (2021)

"Update in Adult Asthma 2020." American Journal of Respiratory and Critical Care Medicine, 204(4), pp. 395–402
Ultrasound-Guided Laser Therapy for Rosacea (Clinical Observation)
Authors: I. N. Bondarenko
Journal: Radiology - Practice (2021)

The article describes a clinical case of high-resolution ultrasound (US) diagnostics of changes in the intensity of blood supply to the dermis of a patient with rosacea at different stages of treatment and early visualization of exacerbation. The presented clinical case demonstrates the possibilities of ultrasound in planning the treatment of rosacea, objective assessment of the results of systemic therapy and laser correction, personalization of the protocol, taking into account the clinical findings and instrumental methods of examination.
Effect of Urate-Elevating Inosine on Progression of Early Parkinson Disease
Authors: Steven J. Frucht
Journal: JAMA (2022)

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
Abstract 350: Construction and Validation of a New Termination-of-Resuscitation Rule for Out-of-Hospital Cardiac Arrest in the Japanese Population; JCS-ReSS Study
Authors: Katsutaka Hashiba, Yoshio Tahara, Kazuo Kimura, Tsutomu Endo, Kouichi Tamura, Naohiro Yonemoto, Hiroshi Nonogi, Hiroaki Shimokawa, Ken Nagao
Journal: Circulation (2018)

Background: Termination of resuscitation (TOR) rules for OHCA have been constructed for better utilization of hospital healthcare resources and increasing the availability of care for other patients. However, TOR rules in the prehospital settings are not legally implemented in Japan. Thus, almost all OHCA patients are transported to the hospital, regardless to the possibility of successful resuscitation. Objective: To validate the TOR-ALS rule in Japan and to establish a new TOR rule for terminating ongoing resuscitation just after hospital arrival. Methods: Data from a nationwide database of a prospective population-based cohort using an Utstein-style template for OHCA patients during January 2011 to December 2015 was used for the current analysis. We constructed a new TOR rule consisting of 5 factors (no-witness, no-return of spontaneous circulation (ROSC), asystole for the initial rhythm, no-defibrillation before hospital arrival, age&gt;75) including the patients during 2011 to 2013 (derivation cohort). Statistical values to predict death and unfavorable neurological outcome(UNO) at one-month were calculated for the TOR-ALS rule (no-witness, no-bystander CPR, no-ROSC, no-defibrillation) and the new rule, respectively. After constructing the new rule, we validated it in a cohort of patients during 2014 to 2015 (validation cohort). Results: Of the 629,471 patients documented for the study period, 466,033 adult patients with OHCA without external causes of arrest were included in the present analysis. In the derivation cohort, values (PPV/NPV/sensitivity/specificity/AUC-ROC) to predict death for each rule were; TOR-ALS rule (99.35%/6.01%/29.89%/95.87%/0.63), new rule (99.61%/6.53%/34.96%/97.05%/0.66). Values to predict UNO were, TOR-ALS rule (99.90%/3.09%/29.37%/98.75%/0.64), new rule (99.97%/3.34%/34.28%/99.49%/0.67). In the validation cohort, values to predict death were, TOR-ALS rule (99.38%/6.53%/26.97%/96.81%/0.62), new rule (99.66%/7.24%/34.00%/97.79%/0.66). Values to predict UNO were, TOR-ALS rule (99.13%/3.36%/26.43%/99.11%/0.63), new rule (99.98%/3.71%/33.24%/99.75%/0.67). Conclusion: The new TOR rule has a higher PPV and specificity to predict unfavorable outcome of OHCA in a Japanese population.
Research in brief
Authors: Sharmila Devi
Journal: The Lancet Infectious Diseases (2020)

Scientists used human white blood cell membranes to carry two drugs, an antibiotic and an anti-inflammatory, directly to infected lungs in mice. The nano-sized drug delivery method shows a potential new strategy for treating infectious diseases, including COVID-19. The researchers developed a method to essentially peel the membrane from neutrophils, the most common type of white blood cells that lead the body's immune system response. Once emptied, these membranes can be used as nanovesicles, tiny empty sacks only 100 to 200 nanometers wide, which scientists can then fill with medicine.
Usefulness of myocardial intravenous contrast echocardiography in idiopathic dilated cardiomyopathy Yoko Miyata, Hiroya Kawai, Katsuya Hata, Toshiro Shinke, Yoshiaki Ueda, Hidenari Matsumoto, Soichiro Ota, Yoshio Yamanaka, Ryohei Yoshikawa, Osamu Iseki, Mitsuhiro Yokoyama. The 1st department of internal medicine Kobe University school of medicine, Kobe, Japan
Journal: Journal of the American College of Cardiology (2001)
Deaths
Journal: JAMA (1930)

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
Systolic blood pressure at submaximal exercise predicts left ventricular hypertrophy in normotensive &amp; hypertensive women Peter Kokkinos, Andreas Pittaras, John Colleran, Puneet Narayan, Emmanuel Coutoulakis, Wassim Choucair, Daniel Fernicola, Vasillios Papademetriou. Veterans Affairs Medical Center, Washington, DC, Georgetown University Medical Center, Washington, DC
Journal: Journal of the American College of Cardiology (2001)
Effect of Fractional Carbon Dioxide Laser vs Sham Treatment on Vaginal Symptom Severity in Postmenopausal Women
Authors: Lucie Veron, Delphine Wehrer, Catherine Uzan
Journal: JAMA (2022)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
The Hospital College of Medicine of Louisville, Ky.
Journal: JAMA (1884)

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
Ethics of a randomized trial of periconceptual vitamins
Journal: JAMA (1989)

<h3>To the Editor.—</h3> Dr Holmes<sup>1</sup>offers a number of thoughtful and cogent remarks concerning the report on periconceptual use of multivitamins by Mulinare et al.<sup>2</sup>However, one comment he makes raises an important ethical issue that is worthy of further comment. Dr Holmes observes that it is fortunate that "a larger, randomized trial of the effectiveness of periconceptual vitamin supplements is under way in Great Britain at this time." This study will, Dr Holmes suggests, help answer some of the questions that remain concerning the advisability of taking vitamin supplements to prevent anencephaly and other neural tube defects. With the exception of the ongoing British study, there has not been a definitive randomized trial of the prophylactic efficacy of vitamin supplements for neural tube disorders. The issue of whether it is ethically desirable to conduct a large, randomized trial to assess the prophylactic efficacy of vitamins is one
Alternative Lengthening of Telomeres (ALT) and Telomerase Reverse Transcriptase Promoter Methylation in Recurrent Adult and Primary Pediatric Pituitary Neuroendocrine Tumors
Authors: Hiba Alzoubi, Simone Minasi, Francesca Gianno, Manila Antonelli, Francesca Belardinilli, Felice Giangaspero, Marie-Lise Jaffrain-Rea, Francesca Romana Buttarelli
Journal: Endocrine Pathology (2022)
The Cost of Tuberculosis
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