tbuckley/cabot-search huggingface dataset:
Are Adverse Reproductive Outcomes Associated With the Illness or Its Treatment (or Both)?—Reply
Authors: Odile Sheehy, Jin-Ping Zhao, Anick Bérard
Journal: JAMA Psychiatry (2019)

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 Psychiatry 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 Psychiatry journal
P102 High dimensional profiling of regulatory T cells in spondyloarthritis reveals cellular heterogeneity
Authors: D Simone, MH Al Mossawi, I Brough, L Chen, F Penkava, A Ridley, H Shi, L Tucker, N Yager, P Bowness
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Career situation of first and presenting author</h3> Student for a master or a PhD <h3>Introduction</h3> The Spondyloarthritides (SpA) are immune-mediated conditions characterised by spinal and joint inflammation. Numerous studies implicate Th17 lymphocytes in pathogenicity but few reports exist on the role played by regulatory T cells (Tregs) in the disease. <h3>Objectives</h3> To describe Treg frequency and phenotype in SpA patients compared to controls. To identify differential expression of trafficking molecules and activation markers within Tregs at the inflammatory site. <h3>Methods</h3> A total of 61 patients with SpA (38 with AS, 23 with PsA) and 16 age-matched healthy controls were recruited. Peripheral blood (PB) and paired synovial fluid (SF) mononuclear cells (n=8) were stained for with 3 multicolor flow cytometry panels, including a total of 35 surface and intracellular protein markers. Manual gating was done in parallel with unsupervised data analysis using FlowSOM and SPADE. <h3>Results</h3> No difference in PB Treg frequency was observed between SpA and healthy controls. In the SF Tregs were enriched relative to the blood memory (CD45RA-) compartment (mean: 11.7 vs 4.7%; p=0.01) with a higher expression of Foxp3 (p=0.04). The distribution of trafficking markers between patients and controls showed considerable heterogeneity, as visualised on SPADE analysis, but little difference in their relative frequency. Intracellular cytokine staining demonstrated that Tregs from AS and PsA patients have higher potential to secrete IL-17A compared to controls (IL-17A+Tregs mean: 2.8 vs 1.2%; p=0.02). Production of this cytokine overlapped with expression of CD161 and CCR6, both markers associated with Th17. Interestingly, this subset, despite expressing normal levels of Foxp3, expressed lower levels of TIGIT (p=0.04) and Helios (p&lt;0.001) when compared to conventional Tregs. <h3>Conclusions</h3> High-dimensional immunoprofiling in SpA patients shows normal frequency of Tregs in the PB, but increased Tregs with activated phenotype in the inflammatory site. The presence of phenotypical markers commonly associated with Th17 in Tregs of non thymic origin are intriguing findings and require further evaluation. <h3>References</h3> None. <h3>Acknowledgements</h3> None. <h3>Disclosure of Interest</h3> D. Simone: None declared, M. H. Al Mossawi Grant/research support from: UCB, I. Brough: None declared, L. Chen: None declared, F. Penkava: None declared, A. Ridley: None declared, H. Shi: None declared, L. Tucker: None declared, N. Yager: None declared, P. Bowness Grant/research support from: Merck, GSK, Celgene.
Clinical Outcomes Using Mycophenolate and Tacrolimus for Graft Versus Host Disease Prophylaxis in Patients Undergoing Allogenic Stem Cell Transplant: A Single Institution Experience
Authors: Hamza Hashmi, Shruti Bhandari, Xiaoyong Wu, Shesh Nath Rai, William Tse, Robert V.B. Emmons
Journal: Blood (2018)
A multicenter phase II study to evaluate efficacy and safety of gefitinib as the first-line treatment for Korean patients (pts) with advanced pulmonary adenocarcinoma harboring EGFR mutations
Authors: D. Kim, S. Lee, J. Lee, M. Lee, J. Kang, S. Kim, S. Shin, H. Kim, D. S. Heo
Journal: Journal of Clinical Oncology (2009)

8066 Background: This study (D7913L00056) was designed to prospectively evaluate the efficacy and safety of first-line gefitinib treatment in pts with advanced pulmonary adenocarcinoma harboring EGFR mutations and to explore the molecular factors affecting the efficacy of gefitinib. Methods: Chemo-naïve pts with advanced (stage IIIB/IV/recurrent disease) pulmonary adenocarcinoma underwent direct DNA sequencing of tumor EGFR exons 18, 19 and 21. Pts with EGFR mutations received gefitinib 250 mg/d until disease progression or unacceptable toxicity. The primary end-point was objective response rate (ORR). The protocol planned to accrue 45 pts with EGFR mutations in a single stage. Results: Out of 147 screened pts, 45 pts (31%) had EGFR mutations and received gefitinib. The most common EGFR mutations were in-frame exon 19 deletions (del 19, 29 pts, 64%) and L858R point mutations in exon 21 (L858R, 15 pts, 33%). One patient had atypical mutation of L861Q in exon 21. The ORR by RECIST was 53.3% (95% CI, 38.8 to 67.9) and disease control rate (DCR) including stable disease was 86.7%. Progression free survival (PFS) at 12 months (mo) was 74.6% (95% CI, 58.8 to 85.1). Median PFS was not reached after median 10.1 mo follow-up. Treatment was well tolerated. Six pts experienced grade 3 toxicities including rash, pruritis, and anorexia. No grade 4 toxicities were reported. Subgroup analysis according to the EGFR mutation subtypes was carried out. The ORR and DCR were higher in pts with del 19 than those with L858R (62.1% vs 33.3%; P=0.0705 and 96.6% vs 66.7%; P=0.0062, respectively). All 4 pts with progressive disease had an L858R mutation. No secondary resistant mutations such as T790M were found in those pts. In addition, PFS at 12 mo was significantly better in pts with del 19 than those with L858R (63.2% vs 23.8%, P=0.0034). Conclusions: Gefitinib as the first-line treatment for Korean pts with advanced pulmonary adenocarcinoma harboring EGFR mutations was very effective and well tolerated. Subgroup analysis suggests that the benefit from gefitinib treatment was more prominent in pts with the del 19 mutation. [Table: see text]
P093/O16 IL-36 signaling in keratinocytes is mandatory in imiquimod-induced psoriasis in mice
Authors: J Goldstein, EY Bassoy, J Palomo, E Rodriguez, C Gabay
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Career situation of first and presenting author</h3> Post-doctoral fellow. <h3>Introduction</h3> A large body of evidence indicates that IL-36R signaling plays an important role in the pathogenesis of psoriasis. For instance, IL-36 receptor (IL-36R)-deficient mice showed impaired development of imiquimod (IMQ)-induced psoriasis, but the cells in which IL-36R signaling is involved have not been identified. <h3>Objectives</h3> To assess the role of IL-36R signaling in keratinocytes in the development of IMQ-induced psoriasis. <h3>Methods</h3> We constructed an IL-36R<sup>fl/fl</sup> mouse line in which exons 1 and 2 from the <i>Il36r</i> gene are flanked by <i>loxP</i> sites. Crossing these mice with K5-Cre transgenic mice induced a progeny with a specific deletion of <i>Il36r</i> in keratinocytes (IL-36R<sup>ΔK</sup>). The selectivity of <i>Il36r</i> gene targeting in keratinocytes was confirmed by RT-qPCR and <i>ex vivo</i> cell stimulation by recombinant IL-36 using isolated keratinocytes and bone marrow differentiated dendritic cells. We then assessed the sensitivity of IL-36R<sup>ΔK</sup> mice to IMQ-induced psoriasis, and compared it to mice presenting a complete IL-36R deficiency (IL-36R<sup>-/-</sup>) and to their respective littermate controls (IL-36<sup>+/+</sup> and IL-36R<sup>fl/fl</sup>). The severity of skin inflammation was assessed by ear thickness measured with a caliper. H and E staining was performed on treated and control ears. Total RNA was extracted from ears and mRNA levels of various cytokines were assessed by RT-qPCR. <h3>Results</h3> IL-36R<sup>-/-</sup> mice were strongly resistant to the induction of IMQ-induced psoriasis as assessed by ear thickness. IL-36R<sup>ΔK</sup> mice showed a similar macroscopic protection as IL-36R<sup>-/-</sup> mice, demonstrating that IL-36 signaling in keratinocytes is critical in this model of psoriasis. Several pro-inflammatory genes upregulated by IMQ in IL-36R<sup>+/+</sup> and IL-36R<sup>fl/fl</sup> mice were not stimulated in neither IL-36R<sup>-/-</sup> nor in IL-36R<sup>ΔK</sup> mice. These genes included notably IL-17A or IL-22, both known to be crucial in psoriasis. Histological findings in IMQ-induced psoriasis include keratinocyte altered differentiation and hyperproliferation as well as inflammatory cell infiltration. Surprisingly and in contrast to IL-36R<sup>-/-</sup>mice, epidermidis thickness was not reduced in IL-36R<sup>ΔK</sup>compared to IL-36R<sup>fl/fl</sup> control mice. This finding suggests that IL-36 signaling in keratinocytes does not induce keratinocyte hyper-proliferation but rather controls the development of downstream inflammatory responses in IMQ-treated ears. <h3>Conclusions</h3> IL-36R signaling in keratinocytes is mandatory for the development of IMQ-induced psoriasis in mice. FACS studies are ongoing to characterize the inflammatory cell infiltrates in the different mouse lines. <h3>Disclosure of Interest</h3> None declared.
Quantitative analysis of intrahepatic hepatitis B (HBV) DNA and cccDNA and their impact on survival posthepatectomy in HBV-associated hepatocellular carcinoma (HCC) patients.
Authors: Qin Wang, Wei Luan, M. Isabel Fiel, Sima Blank, Ki Won Kim, Spiros P. Hiotis
Journal: Journal of Clinical Oncology (2012)

e14583 Background: Little is known about the prognostic significance of total intrahepatic HBV DNA (ihHBV DNA) and cccDNA, a stable episome that accumulates in the nuclei and serves as the template for viral replication. This study aims to quantitate ihHBV DNA and cccDNA in the non-neoplastic liver and to assess their impact on prognosis in HBV-HCC patients. Methods: 111 patients, many on HBV antivirals, who underwent liver resection for HBV-HCC from 1991 to 2008 were assessed by real time PCR for ihHBV DNA, cccDNA, and albumin. Liver fibrosis and necroinflammation was assessed using the modified Ishak method. Independent variables associated with survival were analyzed using multivariate Cox regression model, with a median follow up for survivors of 52 months. Results: Serum HBV DNA was detectable in only 42% of patients, but 106 patients (95%) had detectable ihHBV DNA (median: 0.018copy/hepatocyte); and 89 patients (80%) had detectable cccDNA (0.00058 copy/hepatocyte). Median cccDNA/ihHBV DNA ratio was 0.019. ihHBV DNA correlated with histologic activity index (p = 0.04) and serum ALT (p = 0.004). Patients in the lowest quartile of cccDNA/ihHBV DNA ratio (&lt;0.0032) trended towards poor overall 5-year survival by univariate analysis (p = 0.09), with higher mortality at 2 years (89% vs. 45%, p = 0.03). In multivariate analysis, AFP &gt; 20, Ishak fibrosis stage 6 (established cirrhosis), cccDNA/ihHBV DNA &lt; 0.0032, and large tumor diameter were independently associated with poor overall survival (Table). Conclusions: ihHBV DNA levels were associated with severity of liver necroinflammation and injury. ihHBV DNA and cccDNA levels were not associated with survival; rather, low proportion of total HBV DNA in the form of cccDNA was independently associated with poor overall survival. Thus, viral behavior at the time of liver resection influences clinical outcome for HBV-HCC patients. [Table: see text]
Isolation of T cell receptor specifically reactive with autologous tumour cells from tumour-infiltrating lymphocytes and construction of T cell receptor engineered T cells for esophageal squamous cell carcinoma
Authors: Qin Tan, Chaoting Zhang, Wenjun Yang, Ying Liu, Palashati Heyilimu, Dongdong Feng, Liying Xing, Yang Ke, Zheming Lu
Journal: Journal for ImmunoTherapy of Cancer (2019)

<h3>Background</h3> T cell receptor-engineered T cells (TCR-Ts) therapy is a promising cancer treatment strategy. Nowadays, most studies focused on identification of high-avidity T cell receptors (TCRs) directed against neoantigens derived from somatic mutations. However, few neoantigens per patient could induce immune response in epithelial cancer and additionally many tumor-specific antigens could be derived from noncoding region. Autologous tumor cells (ATCs) could be unbiased stimulators in activating and enriching tumor-reactive T cells. However, it's unknown if T cells engineered to express TCRs isolated from tumor-reactive T cells enriched by ATCs have strong antitumor response. <h3>Methods</h3> In this study, multiple TIL fragments obtained from a patient with esophageal squamous cell carcinoma (ESCC) were screened for specific recognition of ATCs. Tumor-reactive TILs were enriched by in vitro repeated stimulation of ATCs and isolated based on CD137 upregulation. Subsequently, tumor-reactive TCR was obtained by single-cell RT-PCR analysis and was introduced into peripheral blood lymphocytes to generate TCR-Ts. <h3>Results</h3> We found that phenotype and effect function of TIL fragments derived from different tumor sites were spatially heterogeneous. Of four TIL fragments, only TIL-F1 could specifically identify ATCs. Subsequently, we isolated CD8<sup>+</sup> CD137<sup>+</sup> T cells from pre- and post-stimulated TIL-F1 co-cultured with ATCs, and identified their most dominant TCR. This TCR was introduced into PBLs to generate TCR-Ts, which specifically identified and killed ATCs in vivo and in vitro. <h3>Conclusion</h3> This strategy provides the means to generate tumor-reactive TCR-Ts for ESCC, which is especially important for patients without prior knowledge of specific epitopes and might be applied for other cancers.
Botulinum Toxin to Treat Endometriosis Pain
Authors: Rita Rubin
Journal: JAMA (2019)

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
Biweekly oxaliplatin with gemcitabine and capecitabine in advanced gastrointestinal malignancies: A phase I study
Authors: B. R. Tan, W. S. Brenner, J. Picus, R. Suresh, S. Sorcher, J. S. James, C. Fournier, H. L. Mcleod
Journal: Journal of Clinical Oncology (2007)

4560 Background: Oxaliplatin (OX), gemcitabine (GEM) and capecitabine (CAP) are all active agents against various gastrointestinal and other malignancies and have different mechanisms of action and toxicity profiles. This Phase I study aims to determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLT) associated with this triplet regimen. Methods: The modified Fibonacchi 3/cohort dose escalation schema was used to determine the MTD and DLT of OX, GEM and CAP. Oxalipaltin [85–100 mg/m 2 ] IV over 2 hours and gemcitabine [800–1,000 mg/m 2 ] were given at a constant rate infusion of 10 mg/m 2 /min on days 1 &amp; 15, while CAP [600–800 mg/m 2 ] was given PO BID on days 1–7 and 15–21. 1 cycle = 28 days. Pharmacogenomic correlates including ERCC2, GSTP1, TYMS, TS del and TSER G&gt;C were also obtained. A structured neurological toxicity assessment and questionnaire was also performed. Once MTD was established, additional patients were treated at the MTD and pharmacokinetic studies were performed on these additional patients. Results: 30 patients (M:F 2:1; 23% non-caucasian) with median age of 62 (range: 38–78) and PS of 0–1 were enrolled from 3/05 to 8/06. All patients had advanced GI malignancies (19 pancreatic, 6 biliary, 2 duodenal, 1 gastric, 1 esophageal, 1 GI unknown primary). Dose levels, # patients, DLT and best responses are tabulated below. Conclusions: The MTD of this triplet regimen is OX at 100 mg/m 2 , GEM at 800 mg/m 2 days 1 &amp; 15 with CAP at 800 mg/m 2 PO BID days 1–7, 15–21. DLTs for this regimen include grade 3 fatigue and dyspnea as well as Grade 4 thrombocytopenia. CR is achieved in 2 patients (cholangiocarcinoma and pancreatic), while a patient with a GI unknown primary achieved PR. Several patients with pancreatic cancer achieved prolonged SD. An exploration of any association of toxicities and response with pharmacogenomic correlates is ongoing. A Phase II study in patients with pancreaticobiliary cancers is planned. This study is supported by Sanofi-Aventis Pharmaceuticals. [Table: see text] [Table: see text]
Feasibility and benefits of second-line chemotherapy in advanced biliary tract cancer: A large retrospective study.
Authors: Thomas Walter, Anne Horgan, Mairead Geraldine McNamara, Elizabeth McKeever, Trisha Min, David W Hedley, Stefano Serra, Monika K. Krzyzanowska, Eric Xueyu Chen, Helen Mackay, Ronald Feld, Malcolm J. Moore, Jennifer J. Knox
Journal: Journal of Clinical Oncology (2012)

e14524 Background: Chemotherapy is effective in advanced biliary tract cancer (ABTC). The benefits of second-line chemotherapy (CT2) are unclear. Methods: We retrospectively studied all patients starting at least one line of chemotherapy for ABTC at our institution between 1991 and 2011. We analyzed patient and chemotherapy characteristics in order to: 1) characterize patients eligible for CT2; 2) evaluate the efficacy of CT2. Results: Three hundred and ninety five, 100 (25%), and 25 (6%) patients received CT1, CT2, and CT3, respectively. Primary tumor location was the gallbladder (29%), intraphepatic (19%), perihilar (17%), distal common bile duct (19%), and ampulla of Vater (14%). Ninety-one percent had a baseline performance status (PS) of 0-1 prior to CT1. Females (p=0.005), age≤60 years (p=0.009), and patients with progression free survival (PFS) &gt;6 months following CT1 (p=0.01) were more likely to be offered CT2. Objective response rates and stable disease with CT2 were 10% and 35%, respectively. Median PFS and median overall survival (OS) from the beginning of CT2 were 2.8 and 8.0 months, respectively. Prognostic factors impacting PFS with CT2 were the regimen type (doublet versus monotherapy, p=0.004) and PS&lt;2 (p&lt;0.0001). Conclusions: Among patients with ABTC, 25% received CT2, typically younger patients and those with longer PFS following CT1. Disease control occurred in 45% of patients, and more often with a doublet than single agent. However, clearly more effective therapies must be found.
Consequences of Slow Progress Toward Pragmatism in Randomized Clinical Trials
Authors: Fatima Rodriguez, Robert M. Califf, Robert A. Harrington
Journal: JAMA Cardiology (2019)

Nariman Sepehrvand, MD; Wendimagegn Alemayehu, PhD; Debraj Das, MD; Arjun K. Gupta, MD; Pishoy Gouda, MBBCh, MSc; Anukul Ghimire, MSc; Amy X. Du, MSc; Sanaz Hatami, MD; Hazal E. Babadagli, PharmD; Sanam Verma, MD; Zakariya Kashour, MD; Justin A. Ezekowitz, MBBCh, MSc
Effects of Alirocumab on Cardiovascular Events After Coronary Bypass Surgery
Authors: Shaun G. Goodman, Philip E. Aylward, Michael Szarek, Vakhtang Chumburidze, Deepak L. Bhatt, Vera A. Bittner, Rafael Diaz, Jay M. Edelberg, Corinne Hanotin, Robert A. Harrington, J. Wouter Jukema, Sasko Kedev, Alexia Letierce, Angele Moryusef, Robert Pordy, Gabriel Arturo Ramos López, Matthew T. Roe, Margus Viigimaa, Harvey D. White, Andreas M. Zeiher, Ph. Gabriel Steg, Gregory G. Schwartz
Journal: Journal of the American College of Cardiology (2019)
Human resource (HR) costs of chemotherapy infusion reactions (IR) in community oncology
Authors: J. Ogle, B. V. Fortner, K. Moore, L. Zhu, L. S. Schwartzberg
Journal: Journal of Clinical Oncology (2006)

16013 Background: Chemotherapy IR are the dose limiting factor for many agents and have clinical consequences ranging from patient symptom burden to death. No work has been done to describe the provider burden of chemotherapy IR. The purpose of this analysis was to describe the clinical interventions associated with mild and severe IR and estimate the associated HR costs. Methods: Staff from a single, free standing, community oncology practice were surveyed regarding involvement in the management of mild and severe chemotherapy IR using a modified time and motion survey to identify tasks required to manage CIR and the HR time required. Mild and severe chemotherapy IR HR events were created. Salary averages for each type of staff were used to estimate HR costs. Results: 39 staff participated in the survey and were 85% (n = 33) female, average age 44, with M = 7.6 years experience. 21 distinct tasks (e.g. initial assessment, patient monitoring, infusion stopped, notify physician) were identified representing the management of the mild and severe chemotherapy IR. 11 types of staff indicated routine participation in ≥ 1 IR related task. Total HR time was 188 and 194 minutes for mild and severe IR respectively, resulting in HR cost of $124 and $187. Conclusions: The above methodology will be used in an expanded analysis of 20 outpatient practices. Recent changes in cancer treatment reimbursement have resulted increased interest in practice efficiency and provider cost. Definitions for quality care should consider minimization of unnecessary direct and indirect costs and maximization of practice efficiency. Models such as the one described are needed to understand provider costs. Clinical processes and chemotherapy agents that reduce rates and severity of CIR should reduce HR burden related to CIR. [Table: see text] [Table: see text]
Romiplostim in patients with refractory aplastic anaemia previously treated with immunosuppressive therapy: a dose-finding and long-term treatment phase 2 trial
Authors: Jong Wook Lee, Sung-Eun Lee, Chul Won Jung, Silvia Park, Hiroyuki Keta, Soo Kyeong Park, Jin-A Kim, Il-Hoan Oh, Jun Ho Jang
Journal: The Lancet Haematology (2019)