tbuckley/cabot-search huggingface dataset:
ABLE: Phase 2, single-arm, two-stage study of nabpaclitaxel with anti-PD1/PDL1 in advanced urothelial cancer.
Authors: Irene Tsung, Edward Green, Phillip Lee Palmbos, Zachery R Reichert, Ulka N. Vaishampayan, David C. Smith, Megan Veresh Caram, Sarah Elizabeth Yentz, Stephanie Daignault-Newton, Zachery Sloan, Laura Hurley, Ajjai Shivaram Alva
Journal: Journal of Clinical Oncology (2022)

502 Background: Anti-PD/PDL1 immune checkpoint inhibitor monotherapy is standard in select PDL1 expressing advanced urothelial cancer (aUC) and platinum-refractory aUC. Nab-paclitaxel (NAB) previously showed encouraging activity in platinum-refractory aUC. We conducted a single-arm trial of the combination of NAB and pembrolizumab in platinum-refractory or cisplatin-ineligible aUC. Methods: Eligible patients (pts) had RECIST 1.1 measurable urothelial cancer, grade ≤1 neuropathy, and ECOG PS 0-2. Study therapy consisted of NAB at starting dose of 125 mg/m 2 IV on days 1 and 8 and pembrolizumab 200 mg IV on day 1 in 21-day cycles until progression, intolerable toxicity, death, or consent withdrawal. Continuing NAB after 6 cycles was optional. NAB starting dose was reduced to 100 mg/m 2 after planned interim analysis on the first 17 subjects. Primary endpoint was overall response rate (ORR) by RECIST 1.1. Secondary endpoints included safety/toxicity, progression free survival (PFS), overall survival, complete response proportion, duration of response (DOR), and duration of therapy (DOT). Results: Between 2/2018 and 4/2021, 36 response evaluable pts were enrolled; 11 of upper tract origin, 32 men, mean age 71.5 years (range 52 – 88), 25 pure urothelial, 15 platinum-refractory, 21 cisplatin-ineligible by Galsky criteria, and ECOG PS was 0, 1 or 2 in 9, 20, and 7 pts, respectively. Unconfirmed best ORR was 58.3% (95% CI: 42-74) including 3 CR and 18 PR, confirmed ORR 50% (18/36); 31/36 pts experienced some tumor shrinkage. Median DOR was 19 weeks (95% CI: 15.6-34.8), and median PFS 5.4 months (95% CI: 4.6-7.9). Pts received a median of 6 cycles (range 1-14) with median DOT 4.2 months (range 0.6-9.6). Grade ≥3 adverse events (AE) occurred in 25 pts including fatigue (n = 6), anemia (n = 6), peripheral neuropathy (n = 3), and oral mucositis (n = 3); 6 discontinued treatment due to AEs. Ten pts had immune mediated AEs including 1 with encephalitis. Archival tumor NGS revealed TMB ≥10 in 5/21 available. Conclusions: The combination of NAB and pembrolizumab exhibited promising activity in advanced urothelial cancer with no unexpected toxicity. Clinical trial information: NCT03240016.
Network Analysis of Cardiac Remodeling by Primary Mitral Regurgitation Emphasizes the Role of Diastolic Function
Authors: You-Jung Choi, Jaemin Park, Doyeon Hwang, Woong Kook, Yong-Jin Kim, Hidekazu Tanaka, Takeshi Hozumi, Toshinori Yuasa, Lieng Hsi Ling, Cheuk-Man Yu, Seung Woo Park, Jong-Won Ha, Yutaka Otsuji, Jae-Kwan Song, Dae-Won Sohn, Seon-Hee Lim, Seung-Pyo Lee
Journal: JACC. Cardiovascular imaging (2022)
Association of leucocyte levels in urine with tissue PD-L1 status and immune infiltration into basal bladder cancer subtype in the prospective real-world clinicopathological register trial Bladder BRIDGister.
Authors: Thorsten Ecke, Frank Friedersdorff, Elke Veltrup, Ergin Kilic, Roland Hake, Sebastian Eidt, Jenny Roggisch, Stefan Koch, Ralph M. Wirtz
Journal: Journal of Clinical Oncology (2022)

560 Background: The objective of the present study was to evaluate whether preoperative standard urine parameters such as leucocyte count in urine samples dominate in particular molecular subtypes of bladder cancer and reflect the immune infiltration status in the tissue in matched urine and TUR biopsy samples from patients being suspicious of bladder cancer and undergoing first TURB within the prospective Real World Experience registry trial "BRIDGister". Methods: For this pilot study paraffin fixed pretreatment tissue samples from the first TURB of 48 pts participating in the BRIDGister trial and matched urine samples were prospectively collected and analyzed. RNA from FFPE tissues were extracted by commercial kits- Relative gene expression of subtyping markers (KRT5, KRT20) by standardized RT-qPCR systems for PD-1, PD-L1, CTLA4 (STRATIFYER Molecular Pathology GmbH, Cologne). In addition urine samples were analyzed for leucocyte and erythrocyte count. Spearman correlation, Kruskal-Wallis, MannWhitney and Sensitivity/Specificity tests were done by JMP 9.0.0 (SAS software). Results: The pilot cohort of the BRIDGister trial consisted of 48 patients (median age: 77, male 65% vs. female 35%) of diverse clinical stages (Benign lesions/no tumor 38%, pTa 23%, pT1 20%, pT2 19%) and WHO 1973 grade (G1 11%, G2 43%, G3 23%). Presence of leucocytes but not erythrocytes was negatively associated with KRT20 (r=-0.4249, p=0.0216) but positive with KRT5 (r=0.3704, p=0.0479). Moreover high levels of leucocytes in urine were positively associated with tumor expression of PD-L1 (r=0.5081, p=0.0041), PD-1 (r=0.5342, p=0.00024) and CTLA4 (r=0.4244, p=0.0194). In contrast there was no significant association of tumor PDL-1, PD-1 and CTLA4 expression with erythrocyte count in urine. Conclusions: Presence of leucotytes in urine is strongly associated with basal subtype and immune cell infiltration into early bladder cancer. As the presence of erythrcytes did not reveal these significant associations, the presence of leucocytes is not due to simple bleeding or tissue vulnerability. Moreover, the strong tumor subtype specificity further demonstrate the basal tumor specificity of urine leucocytes and therefore may be helpful for detecting and monitoring basal bladder cancer in a non invasive fashion. Given the prognostic value of tissue determination of PD-L1, PD-1 and CTLA4 quantitation on mRNA level, these results warrant further investigation to conclude on its impact on outcome prediction (BCG responsiveness, recurrence, progression, etc.), which will be prospectively analyzed in the framework of the ongoing multicenter BRIDGister Real World Experience trial.
Reexamination of Patient Autonomy and Prior Therapies in Oncology Clinical Trial Eligibility Criteria
Authors: Jennifer J. Gao, Richard Pazdur, Julia A. Beaver
Journal: JAMA Oncology (2022)

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Abstracts of the 24th Annual Northeast Regional Scientific Meeting of the Greater New York and New England Chapters of the Society of Nuclear Medicine
Journal: Clinical Nuclear Medicine (2011)

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Atezolizumab (atezo) with or without Bacille Calmette-Guérin (BCG) in patients (pts) with high-risk nonmuscle-invasive bladder cancer (NMIBC): Results from a phase Ib/II study.
Authors: Noah M. Hahn, Gary D. Steinberg, Kelly Lynn Stratton, Ryan P. Kopp, Alexander Sankin, Eila C. Skinner, Kamal S. Pohar, Benjamin Adam Gartrell, Song Pham, Deepali Rishipathak, Sanjeev Mariathasan, Nicole N. Davarpanah, Corey Carter, Brant Allen Inman
Journal: Journal of Clinical Oncology (2022)

493 Background: Standard treatment (tx) for high-risk NMIBC is transurethral resection of bladder tumor (TURBT) followed by BCG induction and maintenance. However, ≈50% of pts experience recurrence and/or progression after tx and may be ineligible for or refuse cystectomy. The PD-L1/PD-1 pathway may be involved with immune escape in NMIBC following BCG exposure. Here, we report results of atezo (antiPD-L1) ± BCG in BCG-unresponsive, high-risk NMIBC. Methods: This multicenter study (NCT02792192) enrolled pts with BCG-unresponsive NMIBC with carcinoma in situ who had repeat TURBT. Cohort 1A and 1B pts received atezo 1200 mg IV q3w for ≤96 wk. Cohort 1B pts also received standard BCG induction (qw × 6 doses) and maintenance (qw × 3 doses at 3 mo), with optional maintenance courses at 6, 12, 18, 24, and 30 mo. For cohort 1B only, de-escalation was allowed for ≤3 BCG dose levels (full dose 50 mg, 66% and 33% of full dose). Co-primary outcomes were safety and complete response (CR) rate at 6 mo (6-mo bladder biopsy required). Duration of CR and 3-mo CR rate (key secondary outcomes) and 12-mo CR rate (exploratory) were also shown. Results: Cohorts 1A and 1B enrolled 12 pts each. Median age was 74 y; most pts had ECOG PS 0 (n = 7 [58%] in each cohort). At data cutoff (Sep 29, 2020), median atezo tx duration was 22.7 wk in cohort 1A and 31.6 wk in 1B. Following dose de-escalation in cohort 1B, the recommended BCG dose was 50 mg. BCG dose modification/interruption occurred in 4 pts (33%) due to an AE. The most common reason for tx discontinuation was disease recurrence or progression in both cohorts. Three pts (25%) in cohort 1A had atezo-related Gr 3 AEs (most common: maculopapular rash, n = 2); no atezo- or BCG-related Gr ≥3 AEs were seen in cohort 1B. Three dose-limiting toxicities occurred (1 [8%] in cohort 1A and 2 [17%] in cohort 1B), all reported as AEs of special interest. No Gr 4/5 AEs were reported. CRs, which appeared durable, were seen in both cohorts (Table). Conclusions: In this first report of atezo + BCG in NMIBC, atezo as mono- and combination therapy was well tolerated, with no new safety signals or tx-related deaths. Preliminary data suggested clinically meaningful activity, especially with atezo + BCG, requiring confirmation in a larger setting. Clinical trial information: NCT02792192. [Table: see text]
Mechanisms and molecules: What are the treatment targets for primary biliary cholangitis?
Authors: Marlyn J. Mayo
Journal: Hepatology (2022)

Abstract Treatment of primary biliary cholangitis (PBC) with ursodeoxycholic acid (UDCA) is not always sufficient to prevent progression to hepatic decompensation and/or need for liver transplant. Adjuvant therapy with obeticholic acid may provide additional biochemical improvements in some patients, but it is not well‐tolerated by patients with significant itch or advanced cirrhosis. Thus, new and creative approaches to treating patients with PBC are important to identify. This review discusses major potential therapeutic targets in PBC and provides examples of some specific agents currently in development for the treatment of PBC. Targets are broadly classified into those which strive to modify bile, inflammation, cell survival, or fibrosis. In bile, shrinking the size of the bile acid pool or modifying the quality of the bile by making it more hydrophilic or enriched in phosphatidylcholine may ameliorate cholestatic injury. Biliary epithelial cell survival may be extended by fortifying the bicarbonate umbrella or improving cell membrane integrity. Autoimmunity and cholangitis have the potential to be improved via regulation of the immune system. Targeting cytokines, immune checkpoints, and anti‐mitochondrial antibodies are examples of a more focused immunosuppression approach. Stem cell therapy and lymphocyte trafficking inhibition are more novel methods of broad immune regulation. Anti‐fibrotic therapies are also potentially useful for preventing progression of PBC. The nuclear hormone receptors, farnesoid X receptor (FXR) and peroxisome proliferator–activated receptor (PPAR) regulate many of these pathways: cholestasis, inflammation, and fibrosis, which is why they are being enthusiastically pursued as potential therapeutic targets in PBC.
Miscellanea Medica
Journal: JAMA (1997)

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
NEUROTIC ECZEMA.
Authors: L. DUNCAN BULKLEY
Journal: JAMA (1898)

The recognition and management of eczema must ever be an interesting and profitable study to the physician, because practically it forms a very large share of the cases of skin disease coming under his care. Even. in dermatologic practice, where the rarer diseases and also the minor ailments of the skin contribute to make a considerable proportion of the whole number, it constitutes nearly one-third of all cases. In a recent analysis of 10,000 miscellaneous skin cases in the writer's private practice, there were 3201 patients with eczema, they forming 32.01 per cent. of the whole number. In ordinary private general practice, where many infantile? cases occur, this disease undoubtedly forms over one-half of all the cutaneous diseases coming for treatment. Neurotic eczema is particularly interesting to the general physician, because if recognized and rightly treated not only are the results commonly very satisfactory, but the patient also receives much
Blepharospasm
Authors: W. G. Shakespeare
Journal: BMJ (1947)

pitocin " can be given after the third dose of ascorbic acid if desirable, often with a very notable oxytocic effect.Higher doses of ascorbic acid are useless.Intravenous use may lead to tonic contractions.Intramuscular administration is of no advantage.Ascorbic acid proved especially useful in patients with uterine inertia, in which posterior-pituitary extracts were contraindicated.There were no ill effects in mother or baby.In malpresentation, trial labour, antepartum haemorrhage, and foetal distress, where the use of other oxytocics needs greatest supervision and caution in dosage, ascorbic acid is safe and deserves a trial before any other oxytocic agent.Toxaemias of pregnancy are a great field for the use of ascorbic acid as an oxytocic.It is worth noting that, with the above qualifications, ascorbic acid seems to me an active oxytocic drug which is preferable to posterior-pituitary extract, especially for patients with hypo- tonia in the dilatation period.The object of this communication is to call for further experimental and practical investigations of a relatively simple and safe chemical substance which appears to yegulate and stimulate contractions on the already active gravid uterus.-Iam, etc.,
O4.09 * IN SITU METABOLIC PROFILING SHEDS LIGHT ON OXIDATIVE STRESS PATHWAYS IN IDH1 MUTANT OLIGODENDROGLIOMA
Authors: F. Fack, G. Hochart, A. Oudin, O. Keunen, W. P. Leenders, E. Gottlieb, R. Bjerkvig, J. Stauber, S. P. Niclou
Journal: Neuro-Oncology (2014)

BACKGROUND: The oncometabolite D-2-hydroxyglutarate (2-HG) is strongly increased in glial tumors presenting a heterozygous point mutation in isocitrate dehydrogenase (IDH) and is a key indicator of aberrant metabolic circuitries in these tumors. IDH1 is a dimeric enzyme converting isocitrate to α-ketoglutarate (α-KG), a metabolite involved in energy production, macromolecule biosynthesis and an important enzyme co-factor. In IDH1-mutated tumors, α-KG is processed to 2-HG in a NADPH consuming reaction, leading to a hypermethylation phenotype through inhibition of α-KG-dependent demethylases. However the direct effect of the IDH mutation on metabolic dysregulation remains poorly understood. A limitation in the analysis of IDH mutated tumors is the lack of appropriate pre-clinical models. Indeed glioma cells carrying the IDH mutation are notoriously difficult to grow in vitro and only a handful of laboratories, including ours, have been able to generate patient derived orthotopic xenograft models. Thus, current studies addressing the role of 2-HG are mostly based on cell lines overexpressing mutant IDH1 in a wildtype background, with unknown consequences for the function of the oncogenic enzyme. Here we aimed to get insight into the major metabolic aberrations observed in human IDH mutant gliomas with a special emphasis on oxidative stress and glutamine/glutamate pathways. METHODS: In situ high resolution mass spectrometric imaging (MSI) was performed on IDH1 mutant xenografts derived from human oligodendroglial tumors with 1p19q deletion. This allows a detailed metabolic profiling with anatomical localization in tumor sections. Key enzymes of the perturbed metabolic pathways were monitored by Western blot and immunohistochemistry. Liquid chromatography mass spectrometry (LC-MS) was applied to validate our findings in fresh clinical specimen. RESULTS: 2-HG was specifically localized in the tumor bed but not in the surrounding brain parenchyma, while α-KG levels were not significantly altered in IDH1 mutated tumors. We identified a large set of differentially present metabolites in IDH1-mutant tumors, including the anti-oxidant glutathione. Importantly we reveal significant differences in metabolite levels between human glioma samples with an endogenous IDH mutation compared to previously reported data on mutant IDH1 overexpressing cell lines. CONCLUSIONS: We provide for the first time a detailed metabolic profiling of human IDH mutant gliomas with high anatomical resolution in situ. Our data point to the importance of oxidative stress regulation and its possible link to epigenetic dysregulation in IDH mutant oligodendrogliomas.
Arteriographic diagnosis of coronary disease
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
LPAR1 regulates enteric nervous system function through glial signaling and contributes to chronic intestinal pseudo-obstruction
Authors: Mohammad M. Ahmadzai, Jonathon L. McClain, Christine Dharshika, Luisa Seguella, Fiorella Giancola, Roberto De Giorgio, Brian D. Gulbransen
Journal: Journal of Clinical Investigation (2022)

Gastrointestinal motility disorders involve alterations to the structure and/or function of the enteric nervous system (ENS) but the causal mechanisms remain unresolved in most cases. Homeostasis and disease in the ENS are processes that are regulated by enteric glia. Signaling mediated through type I lysophosphatidic acid receptors (LPAR1) has recently emerged as an important mechanism that contributes to disease, in part, through effects on peripheral glial survival and function. Enteric glia express LPAR1 but its role in ENS function and motility disorders is unknown. We used a combination of genetic, immunohistochemical, calcium imaging, and in vivo pharmacological approaches to investigate the role of LPAR1 in enteric glia. LPAR1 was enriched in enteric glia in mice and humans and LPA stimulated intracellular calcium responses in enteric glia, subsequently recruiting activity in a subpopulation of myenteric neurons. Blocking LPAR1 in vivo with AM966 attenuated gastrointestinal motility in mice and produced marked enteric neuro- and gliopathy. Samples from humans with chronic intestinal pseudo-obstruction (CIPO), a severe motility disorder, showed reduced glial LPAR1 expression in the colon and ileum. These data suggest that enteric glial LPAR1 signaling regulates gastrointestinal motility through enteric glia and could contribute to severe motility disorders in humans such as CIPO.
Tetanus Immunization in Adults
Authors: Benjamin Littenberg
Journal: JAMA (1994)

<h3>To the Editor.</h3> —The report of the two cases of tetanus occurring in Kansas in 1993<sup>1</sup>serves as an important reminder that this disease, rare in the United States, still occurs; that primary immunization is not universal; that appropriate wound management is necessary for secondary prevention; and that older Americans are particularly vulnerable. The epidemiology of tetanus in the United States has remained fairly stable over the last decade with about 50 to 60 cases yearly, with higher attack rates and higher mortality rates among older Americans, many of whom never received primary immunization.<sup>2,3</sup> Using formal decision analysis, we found that primary immunization in childhood and a single tetanus booster for elderly adults is a cost-effective alternative to the decennial booster policy for primary prevention of tetanus.<sup>4</sup>While the costs (charges) of care for two persons with tetanus may fund as many as 90 000 doses of