tbuckley/cabot-search huggingface dataset:
Final results of a multicenter prospective phase II clinical trial of gemcitabine and cisplatin as neoadjuvant chemotherapy in patients with high-grade upper tract urothelial carcinoma.
Authors: Wesley Yip, Jonathan Coleman, Nathan Colin Wong, Daniel D. Sjoberg, Bernard H. Bochner, Guido Dalbagni, S. Machele Donat, Harry W. Herr, Eugene J. Pietzak, A. Ari Hakimi, Kwanghee Kim, Hikmat A. Al-Ahmadie, Hebert Alberto Vargas, Anoop M. Meraney, Angelo Angelino Baccala, Andrea B. Apolo, Gopa Iyer, Min Yuen Teo, Jonathan E. Rosenberg, Dean F. Bajorin
Journal: Journal of Clinical Oncology (2022)

440 Background: Neoadjuvant chemotherapy (NAC) has proven survival benefits for invasive urothelial carcinoma of the bladder, yet its role in upper tract urothelial carcinoma (UTUC) remains undefined. We conducted a phase II multicenter trial of NAC with gemcitabine and cisplatin (GC) in patients with high-risk UTUC prior to extirpative surgery to evaluate major outcomes of response, survival, and tolerability. Methods: Eligible patients with defined criteria for high-risk localized UTUC received four cycles of GC prior to surgical resection and lymph node dissection. The primary study endpoint was pathologic response rate (defined as &lt; pT2N0). Patients with progressive disease prior or unable to proceed to surgery were considered treatment failures. Secondary endpoints included time to disease progression (PFS), overall survival (OS), and safety and tolerability. Results: Among 57 patients evaluated, 36 (63%) demonstrated pathologic response, meeting the primary endpoint of the study. A complete response was noted in 11 patients (19%), defined as pT0N0. Forty patients (70%) tolerated all four cycles of GC, and all patients proceeded to surgery. The 90-day ≥ grade 3 surgical complication rate was 7.0%. With a median follow up of 42.3 months among survivors, six patients succumbed to disease. Two and five-year PFS were 76% (95% CI 66, 89) and 61% (95% CI 47, 78). Two and five-year OS were 93% (95% CI 86, 100) and 79% (95% CI 67, 94). Patients demonstrating pathologic response had improved PFS and OS compared to those who did not (two-year PFS 91% vs 52%, log-rank p &lt; 0.001, two-year OS 100% vs 80%, log-rank p &lt; 0.001). Conclusions: NAC for high-risk UTUC demonstrates outcomes of favorable pathologic response, is well tolerated requiring minimal delay to surgery without significant perioperative complication risk, and thus should be considered a new standard of care option for patients with high-risk UTUC. Better survival outcomes in patients with favorable pathologic features after NAC indicate a potential clinical benefit to this approach. Clinical trial information: NCT01261728.
Annals Graphic Medicine - How to Lie During a Pandemic: An Illustrated Exercise in Cognitive Dissonance
Authors: Ryan Montoya
Journal: Annals of Internal Medicine (2020)

Web Exclusives21 July 2020Annals Graphic Medicine - How to Lie During a Pandemic: An Illustrated Exercise in Cognitive DissonanceFREERyan Montoya, MDRyan Montoya, MDArlington, Virginia (R.M.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/G20-0057 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Download figure Download PowerPoint Download figure Download PowerPoint Download figure Download PowerPoint Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: Arlington, Virginia (R.M.)Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=G20-0057.Author/Illustrator Information: Ryan Montoya, MD; e-mail, [email protected]com.This article was published at Annals.org on 9 June 2020. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 21 July 2020Volume 173, Issue 2Page: W40-W43KeywordsDisclosureHealth careSports and exercise medicine ePublished: 9 June 2020 Issue Published: 21 July 2020 Copyright & PermissionsCopyright © 2020 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Eye Surgery
Authors: R. F. Moore
Journal: BMJ (1947)

BEICTISHAt a time when parts of the lay Press are more than usually critical of our profession it seems a pity that these accusations are made by our own colleagues against men and women who also " like time to examine their patients," but do not always find it necessary to exalt their own " professional consciences."-I am, etc., Waddesdon, Bucks.
Ephedrine
Authors: J. H. Gaddum
Journal: BMJ (1938)

The alkaloid ephedrine is-present in extracts of various plants belonging to the genus Ephedra, which all grow in roughly the same latitude in Northern China, Northern India, and Spain.One species has been used as a drug in China for about 5,000 years under the name Qf " ma huang."The plant consists almost entirely of bundles of green stems lying parallel without much branching.The leaves are reduced to small dry scales arranged in twos or threes round the stem at intervals, so that the plant looks rather like an equisetum.In actual fact the ephedras are gymnosperms, and are therefore related to the pines and firs, whereas the equisetums are not flowering plants at all, and are very distant relations of the ephedras.The chemical structures of ephedrine and pseudo- ephedrine are here shown.These alkaloids, both of which H CH, CH, CH,
Identification/Chief Complaint
Authors: M. Ehrlich
Journal: JAMA (2002)

played by Cary Grant, is followed everywhere by a large, silent man.The man is with him as he addresses an anatomy class, as he conducts the student orchestra, as he stands over a patient in the operating room.The man speaks only at rare moments, each crucial, coming to Noah's aid as the voice of wisdom, of conscience, or of the past.When Noah is finally challenged by a university tribunal to defend his relationship with the odd man he calls "my friend," the story comes out: the man is a convicted murderer, executed by hanging and sent 20 years earlier to Noah, a medical student who needed "a cadaver of my own."The "cadaver" awakened as soon as Noah stuck a gloved finger in his mouth, and has never since left his side.Early experiences in the anatomy laboratory underpin later practice in ways that are not easy to articulate.The knowledge gained there guides diagnosis, allows us to link phenomena that seem on the body's surface to be unrelated, and gives us fluency in a discourse that lets us to describe what is happening to our patients.Visualizing the structures hidden beneath the skin allows us to identify conditions otherwise beyond our grasp.Although the overwhelming bulk of the knowledge we use to care for patients is learned outside the lab, and the centrality of the experience wanes even by the end of first year, what we learn in anatomy lab is somehow, quietly, always there.In this issue of MSJAMA, literature professor John Bender recounts his season as an outsider in the lab and describes how the process serves as a ritual entry into the medical profession.Beyond the technical knowledge it affords, anatomy lab links us to the past and begins our socialization to future practice.We dissect knowing that we are making the same cuts and seeking the same structures as physicians centuries earlier.But today, we pride ourselves on taking more from the experience, on engaging with the gift that is the donation.Samantha Stewart and Rita Charon describe anatomy study as an initial confrontation with life and death that will follow us throughout our careers, and discuss a way these early lessons might be retrieved.S. Ryan Gregory and Thomas Cole describe the history of dissection across centuries, while Aaron Tward and Hugh Patterson account for the shift from grave robbing to cadaver donation in the United States.Finally, to launch our new creative writing section murmur, Matthew Ehrlich evaluates his cadaver's chief complaint.The first body in our care has neither the needs nor the agency of a patient, and yet for many of us, it is the body we will envision as we examine the intact surface of each patient who comes to us.Whether it is our initiation into "the professional tribe of physicians" (Bender), "the scientific method" (Gregory and Cole), or "the use of affective responses" (Stewart and Charon), anatomy lab is as much a part of how we see as what we know."The trouble with you, Elwell," Noah's ally says to his accuser at the end, "is you've never had a cadaver of your own."
Toripalimab plus axitinib in patients with metastatic mucosal melanoma: 3-year survival update and biomarker analysis
Authors: Siming Li, Xiaowen Wu, Xieqiao Yan, Li Zhou, Zhihong Chi, Lu Si, Chuanliang Cui, Bixia Tang, Lili Mao, Bin Lian, Xuan Wang, Xue Bai, Jie Dai, Yan Kong, Xiongwen Tang, Hui Feng, Sheng Yao, Keith T Flaherty, Jun Guo, Xinan Sheng
Journal: Journal for ImmunoTherapy of Cancer (2022)

Mucosal melanoma is an aggressive melanoma subtype with poor response to antiprogrammed cell death-1 (PD-1) monotherapy. Axitinib in combination with toripalimab, a humanized IgG4 mAb against PD-1, showed a promising response rate in patients with metastatic mucosal melanoma (MM) in a phase Ib study. Here, we report the updated overall survival (OS), duration of response (DoR), and biomarker analysis results.Patients with advanced MM received toripalimab 1 or 3 mg/kg intravenously every 2 weeks combined with axitinib 5 mg orally two times per day until disease progression or unacceptable toxicity. Tumor programmed cell death ligand-1 (PD-L1) expression, tumor mutational burden (TMB), and gene expression profile (GEP) by messenger RNA sequencing were evaluated for correlation with survival.As of April 2, 2021, the median follow-up was 42.5 months. Among 29 chemotherapy-naïve patients with metastatic MM, the median OS was 20.7 months (95% CI 9.7 to 32.7 months); the median progression-free survival (PFS) was 7.5 months (95% CI 3.8 to 14.8 months); and the median DoR was 13.4 months (95% CI 5.5 to 20.6 months). The OS rates of 1, 2, and 3 years were 62.1%, 44.8%, and 31.0%, respectively. Biomarker analysis found that PD-L1 expression and TMB level were not associated with survival benefits. In contrast, a 12-GEP signature correlated with improved PFS (17.7 vs 5.7 months, p=0.0083) and OS (35.6 vs 17.6 months, p=0.039).The 3-year survival update confirmed the antitumor activity and long-term survival benefit of the toripalimab plus axitinib combination in patients with advanced MM. The 12-gene GEP is of value in predicting the outcomes of vascular endothelial growth factor receptor-tyrosine kinase inhibitor and PD-1 blockade combination therapy, but requires further validation.NCT03086174.
Multimodal treatment of radiation-induced esophageal cancer: Results of a case-matched comparative study from a single center
Authors: Elisa Sefora Pierobon, Giovanni Capovilla, Lucia Moletta, Anna Laura De Pasqual, Caterina Fornasier, Renato Salvador, Gianpietro Zanchettin, Sara Lonardi, Sara Galuppo, Edin Hadzijusufovic, Peter P. Grimminger, Matteo Stocchero, Mario Costantini, Stefano Merigliano, Michele Valmasoni
Journal: International Journal of Surgery (2022)
A comprehensive profile of TCF1+ progenitor and TCF1− terminally exhausted PD-1+CD8+ T cells in head and neck squamous cell carcinoma: implications for prognosis and immunotherapy
Authors: Dikan Wang, Juan Fang, Shuqiong Wen, Qunxing Li, Jinming Wang, Lisa Yang, Wenxiao Dai, Huanzi Lu, Junyi Guo, Zhongyan Shan, Wenqiang Xie, Xiangqi Liu, Liling Wen, Jie Shen, Anxun Wang, Qianming Chen, Zhi Wang
Journal: International Journal of Oral Science (2022)

Abstract The heterogeneity of exhausted T cells (Tex) is a critical determinant of immune checkpoint blockade therapy efficacy. However, few studies have explored exhausted T cell subpopulations in human cancers. In the present study, we examined samples from two cohorts of 175 patients with head and neck squamous cell cancer (HNSCC) by multiplex immunohistochemistry (mIHC) to investigate two subsets of Tex, CD8 + PD1 + TCF1 + progenitor exhausted T cells (TCF1 + Tex prog ) and CD8 + PD1 + TCF1 − terminally exhausted T cells (TCF1 − Tex term ). Moreover, fresh tumor samples from 34 patients with HNSCC were examined by flow cytometry and immunohistochemistry to further investigate their properties and cytotoxic capabilities and their correlation with regulatory T cells (Tregs) in the tumor immune microenvironment (TIME). mIHC and flow cytometry analysis showed that TCF1 − Tex term represented a greater proportion of CD8 + PD1 + Tex than TCF1 + Tex prog in most patients. TCF1 + Tex prog produced abundant TNFα, while TCF1 − Tex term expressed higher levels of CD103, TIM-3, CTLA-4, and TIGIT. TCF1 − Tex term exhibited a polyfunctional TNFα + GZMB + IFNγ + phenotype; and were associated with better overall survival and recurrence-free survival. The results also indicated that larger proportions of TCF1 − Tex term were accompanied by an increase in the proportion of Tregs. Therefore, it was concluded that TCF1 − Tex term was the major CD8 + PD1 + Tex subset in the HNSCC TIME and that these cells favor patient survival. A high proportion of TCF1 − Tex term was associated with greater Treg abundance.
Adaptation to Space
Journal: JAMA (1966)

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
NCAPG promotes the oncogenesis and progression of non-small cell lung cancer cells through upregulating LGALS1 expression
Authors: Huanhuan Sun, Hong Zhang, Yan Yan, Yushi Li, Gang Che, Cuiling Zhou, Christophe Nicot, Haiqing Ma
Journal: Molecular Cancer (2022)

Abstract Background Numerous common oncogenic driver events have been confirmed in non-small cell lung cancer (NSCLC). Although targeted therapy has revolutionized NSCLC treatment, some patients still do not respond. NCAPG, also known as non-SMC condensin I complex subunit G, was positively associated with proliferation and migration in several tumor types. Methods We used transcriptional sequencing and TCGA database analysis to identify NCAPG as a new therapeutic target for NSCLC. The oncogenic roles of NCAPG in NSCLC tumor growth and metastasis were detected in vitro and in vivo. Ncapg +/+ or Ncapg +/− mice with urethane treatment were analyzed for oncogenesis of NSCLC. Results We investigated NCAPG as a new oncogenic driver which promoted NSCLC tumorigenesis and progression. We used transcriptome sequencing and the Cancer Genome Atlas (TCGA) database analysis to screen and found that NCAPG was negatively correlated with NSCLC survival. Using immunohistochemistry, we demonstrated that NCAPG overexpression was an independent risk factor for NSCLC survival. Functionally, NCAPG knockdown inhibited proliferation, migration, and invasion of NSCLC cells in vitro and in vivo. We exposed wildtype or Ncapg +/− mice to urethane and discovered that urethane-induced lung tumors were reduced in Ncapg +/− mice. Mechanistically, the function of NCAPG in promoting initiation and progression of NSCLC was closely related to LGALS1, which was also upregulated in NSCLC and might interact directly with NCAPG. Conclusions This study indicates that NCAPG is one of the essential factors for NSCLC oncogenesis and progression, providing a new target for prognosis prediction and treatment of NSCLC.
Strengthening a Study of Diabetes Progression After Statin Use
Authors: Rahul B. Ganatra, Anish Bhatnagar, Shoshana J. Herzig
Journal: JAMA Internal Medicine (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 Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Journals 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
Dental Anaesthetics
Authors: A. M. Danziger
Journal: BMJ (1963)

BOURNr L drug she noted a marked increase in libido, which she could only relieve by masturba- tion.She stopped taking the tablets and the effect dwindled within a day or two, but the whole episode led to a great deal of guilt and self-reproach in subsequent depressive phases (the patient being a devout Roman Catholic).At the time, however, it was considered that this might have been a purely manic symptom and not due to chlorprothixene.Her " manic" phases were later partially controlled with prothipendyl hydrochloride (" tolnate ") 40 mg.t.d.s.In July, 1963, chlorprothixene 30 mg. t.d.s. was again prescribed and within a few days she noticed increased libido and she again resorted to masturbation.The effect dwindled rapidly once she stopped taking the drug, even though her manic phase continued for another week, hence one must conclude that it was an effect of the drug.I am, etc.,
First data for sotorasib in patients with pancreatic cancer with <i>KRAS</i> p.G12C mutation: A phase I/II study evaluating efficacy and safety
Authors: John H Strickler, Hironaga Satake, Antoine Hollebecque, Yu Sunakawa, Pascale Tomasini, David Lawrence Bajor, Martin H. Schuler, Rona Yaeger, Thomas J. George, Ignacio Garrido-Laguna, Andrew L. Coveler, Mark David Vincent, Gerald Steven Falchook, Timothy F. Burns, Sun Young Rha, Charlotte Rose Lemech, Dejan Juric, Pegah Jafarinasabian, Qui Tran, David S. Hong
Journal: Journal of Clinical Oncology (2022)

360490 Background: KRAS mutation is present in 90% of pancreatic ductal adenocarcinomas with p.G12C accounting for 1% to 2% of these mutations. Sotorasib, a small molecule that specifically and irreversibly inhibits KRAS G12C , has been investigated in the CodeBreaK100 trial in patients with KRAS G12C -mutated advanced solid tumors. Herein, we report on the largest dataset evaluating efficacy and safety of a KRAS G12C inhibitor in patients with pretreated KRAS G12C -mutated pancreatic cancer. Methods: CodeBreaK100 (NCT03600883) is an international, single arm, phase I/II study evaluating the efficacy and safety of sotorasib in patients with KRAS G12C -mutated advanced solid tumors with ≥ 1 prior systemic therapy unless intolerant or ineligible for available therapies. The primary efficacy endpoint is confirmed objective response rate (ORR), assessed by blinded independent central review (BICR) per RECIST 1.1. Secondary endpoints include duration of response (DoR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). Results: As of November 1, 2021, 38 patients with pancreatic cancer (mean age: 65 years, 76.3% male) from the combined phase I/II study received sotorasib 960 mg once daily. Stage IV disease was present in 55.3% of patients at diagnosis, and in all patients at enrollment. Baseline ECOG scores were 0, 1, or 2 in 31.6%, 57.9%, and 10.5% of patients, respectively. Most patients (79%) had ≥ 2 prior lines of therapy (median: 2 [range: 1-8]). Median treatment duration was 4.1 months with a median follow-up of 16.8 months. Eight patients had confirmed partial response by BICR with a resulting ORR of 21.1% (95% CI: 9.55%-37.32%). DCR was 84.2% (Table 1). Treatment-related adverse events (TRAEs) of any grade occurred in 16 (42.1%) patients. Grade ≥ 3 TRAEs occurred in 6 patients: diarrhea (2); fatigue (2); abdominal pain, ALT increase, AST increase, pleural effusion, and pulmonary embolism (1 each). No TRAEs were fatal or resulted in sotorasib discontinuation. Conclusions: Sotorasib demonstrated clinically meaningful anticancer activity and tolerability in patients with heavily pretreated KRAS G12C -mutated advanced pancreatic cancer, who have limited treatment options and poor prognosis. Clinical trial information: NCT03600883. [Table: see text]
NATIONAL DIET AND ITS CHANGES.
Journal: JAMA (1905)

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
Allergic bronchopulmonary aspergillosis.
Authors: R J White
Journal: BMJ (1978)

reported by Professor Morris and his colleagues with high fibre intake (and lower incidence of ischaemic heart disease) would obtain 200mg magnesium per week more than the low-fibre group from their brown bread alone, and this is 5-100% of the weekly total required to stay in magnesium balance.4It may be the metal content of brown bread rather than the fibre which protects the consumer from ischaemic heart disease.The data collected by Professor Morris and his colleagues could be used to estimate the weights of magnesium, potassium, and iron consumed by their subjects, and this would be worth further investigation.