tbuckley/cabot-search huggingface dataset:
Serial changes in PD1/PDL1 expression in metastatic urothelial carcinoma (mUC) patients (pts) treated with immune checkpoint blockade (CPB).
Authors: Alice Tzeng, C. Marcela Diaz-Montero, Patricia A. Rayman, Jin Sub Kim, Paul G Pavicic, James Finke, Pedro C. Barata, Marcelo Lamenza, Sarah Devonshire, Kim Schach, Hamid Emamekhoo, Marc S. Ernstoff, Christopher J. Hoimes, Brian I. Rini, Jorge A. Garcia, Timothy D. Gilligan, Moshe Chaim Ornstein, Petros Grivas
Journal: Journal of Clinical Oncology (2018)

109 Background: Since CPB may alter immune marker expression in key immunomodulatory populations such as myeloid-derived suppressor cells (MDSC) and CD8 + cytotoxic T lymphocytes (CTL), we evaluated PD1/PDL1 expression in longitudinal samples from mUC pts treated with CPB. Methods: Serial peripheral blood samples were collected from mUC pts who received CPB. PD1/PDL1 and VISTA expression was measured in MDSC (CD33 + HLADR − ) and CTL (CD8 + CD4 − ) from live peripheral blood mononuclear cells using flow cytometry. MDSC subsets were further defined as (G)ranulocytic (CD15 + CD14 − ), (M)onocytic (CD15 − CD14 + ), and (I)mmature (CD15 − CD14 − ). PD1/PDL1 and VISTA expression was presented as % of each MDSC subset or CTL. Wilcoxon signed-rank tests and mixed-model regression analyses were performed to assess changes in immune marker expression after CPB. Results: Of 30 CPB-treated pts with ≥ 2 blood samples for analysis, 21 received anti-PDL1 (20 atezolizumab/1 avelumab; [A]) and 9 received anti-PD1 (pembrolizumab [P]). Median age at diagnosis was 69.5 (4681), 77% men, 33% never smokers, 63% pure UC, 70% bladder primary, 20% prior intravesical BCG, 37% prior neoadjuvant chemotherapy, 63% prior cystectomy. Best overall responses to CPB were 3 PR/13 SD/5 PD (A) and 1 CR/1 PR/4 SD/3 PD (P). Successive doses of A correlated with decreased %PDL1 + M-MDSC, while those of P correlated with decreased %PD1 + M- and I- MDSC (Table). No significant changes in VISTA expression were detected. In 11 A-treated pts with samples before/after the 1st dose, %PDL1 + M- and I- MDSC decreased (median change −25.5 and −5.7; p = 0.02 and 0.03) and %PD1 + CTL increased (median change +2.4; p = 0.02) between 1st and 2nd samples. Conclusions: In this mUC pt cohort, distinct post-tx changes in %PD1/PDL1 in MDSC subsets and CTL occurred based on CPB (anti-PD1 vs anti-PDL1). Further analysis of correlations between CPB, immune marker expression, clinicopathologic factors, and outcomes is ongoing in a larger cohort. Mean absolute change in marker expression per dose in pts treated with CPB. [Table: see text]
Life Expectancy of Patients With Low-Normal Thyroid Function
Authors: Kosuke Inoue, Tetsuro Tsujimoto, Takehiro Sugiyama
Journal: JAMA Internal Medicine (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Preliminary results for avelumab plus axitinib as first-line therapy in patients with advanced clear-cell renal-cell carcinoma (JAVELIN Renal 100): an open-label, dose-finding and dose-expansion, phase 1b trial
Authors: Toni K Choueiri, James Larkin, Mototsugu Oya, Fiona Thistlethwaite, Marcella Martignoni, Paul Nathan, Thomas Powles, David McDermott, Paul B Robbins, David D Chism, Daniel Cho, Michael B Atkins, Michael S Gordon, Sumati Gupta, Hirotsugu Uemura, Yoshihiko Tomita, Anna Compagnoni, Camilla Fowst, Alessandra di Pietro, Brian I Rini
Journal: The Lancet Oncology (2018)
Pembrolizumab and chemoradiotherapy for muscle invasive bladder cancer: The ANZUP 1502 PCR-MIB trial.
Authors: Andrew James Weickhardt, Farshad Foroudi, Shomik Sengupta, Laura Galletta, Alan Herschtal, Peter S. Grimison, Nitya Patanjali, Siobhan Ng, Colin Tang, Robert Goodwin, Elizabeth J. Hovey, Tom Jarvis, Colin Chen, Shahneen Kaur Sandhu, Keen Hun Tai, Nathan Lawrentschuk, Ian D. Davis
Journal: Journal of Clinical Oncology (2018)

TPS531 Background: Pembrolizumab leads to responses in ~20% of metastatic bladder cancer patients. Irradiation of bladder cancer cells in-vitro and in-vivo leads to upregulation of PD-L1, and in immunocompetent mouse models blockade of PD-L1 leads to delayed tumour growth following irradiation. Randomised data from PACIFIC trial in NSCLC shows the addition of PD-L1 inhibition to chemoradiation significantly prolongs PFS. A trial of chemoradiotherapy with pembrolizumab will assess safety and synergy of the combination in localised bladder cancer. Methods: This pilot study enrols patients with maximally resected non-metastatic muscle invasive bladder cancer, who either wish for bladder preservation or are ineligible for cystectomy. This study will assess the safety and feasibility of combining pembrolizumab with chemoradiotherapy in ECOG 0-1 patients without contraindications to pembrolizumab. The study has enrolled 4 of a planned 30 patients. All patients treated with 64Gy of radiation therapy in 32 fractions over 6 weeks, 2 days. Cisplatin 35mg/m 2 IV concurrently weekly for 6 doses with radiation. Pembrolizumab commences concurrently with radiation and is given 200mg IV q21 days for 7 doses. Surveillance cystoscopy is performed 12 &amp; 24 weeks after the commencement of chemoradiotherapy to assess response to therapy. Patients will enter follow up with clinical assessment, cystoscopy and CT staging performed at intervals until close of study. The primary endpoint assessed will be safety, as defined by a satisfactorily low rate of unacceptable toxicity (G3-4 adverse events or failure of completion of planned chemotherapy and radiotherapy according to defined parameters). The secondary endpoint will be efficacy, as assessed by the proportion of patients achieving a best response of complete response based on the first two 12 and 24 week post chemoradiotherapy cystoscopic assessments. Exploratory analysis will include assessment of tumour histopathological, molecular, genetic and immunological parameters. It is expected that it will take two years to accrue the 30 patients across 5 Australian centres. NCT02662062. Clinical trial information: NCT02662062.
HEE offers £100 000 for trainee led education projects
Authors: Helen Jaques
Journal: BMJ (2013)

Health Education England’s Better Training, Better Care programme is offering £100 000 to fund trainee led projects that aim to improve education and training of junior doctors.

The programme’s “Inspire Improvement” project is seeking ideas that will help the NHS meet the recommendations set out in John Temple’s 2010 report Time for Training . …
A novel ASXL1–OGT axis plays roles in H3K4 methylation and tumor suppression in myeloid malignancies
Authors: Daichi Inoue, Takeshi Fujino, Paul Sheridan, Yao-zhong Zhang, Reina Nagase, Sayuri Horikawa, Zaomin Li, Hirotaka Matsui, Akinori Kanai, Makoto Saika, Rui Yamaguchi, Hiroko Kozuka-Hata, Kimihito Cojin Kawabata, Akihiko Yokoyama, Susumu Goyama, Toshiya Inaba, Seiya Imoto, Satoru Miyano, Mingjiang Xu, Feng-Chun Yang, Masaaki Oyama, Toshio Kitamura
Journal: Leukemia (2018)
Perceptions about cancer clinical trials among prostate cancer survivors.
Authors: Joanne S. Buzaglo, Melissa F Miller, Shauna McManus, Jamese Johnson, Alexandra Katherine Zaleta
Journal: Journal of Clinical Oncology (2018)

42 Background: Recruitment into cancer clinical trials (CCTs) remains challenging despite efforts to enhance patient understanding of and access to CCTs. We examined perceptions of CCTs among prostate cancer (PC) survivors. Methods: 86 PC survivors enrolled in Cancer Support Community’s Cancer Experience Registry online research platform, provided demographic and disease history, and rated their agreement (0 = strongly disagree; 4 = strongly agree) with 8 CCT statements. We examined bivariate associations between CCT counseling and individual factors via Spearman’s rank correlation and chi-square tests. Results: Participants were 95% White; mean (SD) age = 65 (7) years; time since diagnosis 4 (4) years. 24% had surgery, 34% underwent radiation, 20% both; 31% currently and 18% previously received hormone therapy. 32% were diagnosed 5+ years ago; 22% reported recurrence, 31% metastatic disease. 33% reported that their health care team spoke to them about participating in a CCT, with a non-significant trend for lower prevalence if all or part of care was received at a community hospital/cancer center (24%) vs. at an academic or comprehensive cancer center or private oncology practice (47%; χ 2 = 3.03, p = .082). 25% did not receive information about CCTs from the health care team prior to making a treatment decision. 21% reported there was a CCT available to them; 35% considered a CCT for treatment; 11% participated in a CCT. Regarding beliefs about CCTs (% agree or strongly agree): 64% felt uncomfortable with treatment random assignment; 52% feared receiving a placebo; 40% feared treatment side effects; 23% believed health insurance would not cover a CCT; 16% believed no clinical trials are available in their community; 16% felt mistrust and fear of being used as a “guinea pig” for research; 11% had concern about logistical barriers, e.g., transportation; 6% did not understand what CCTs are. Conclusions: Many prostate cancer survivors are uncomfortable with random assignment to treatment in a CCT and fear receiving a potentially ineffective placebo. Our findings underscore the need for comprehensive treatment decision counseling and patient education via health care providers and patient advocacy organizations.
Colleges pledge to reduce bullying in obstetrics and gynaecology
Authors: Matthew Limb
Journal: BMJ (2013)

Two royal colleges have pledged to reduce undermining and bullying behaviour in obstetrics and gynaecology and to foster a respectful working culture.

The Royal College of Obstetricians and Gynaecologists and the Royal College of Midwives said that they were acting to tackle problems faced by trainees and fully qualified staff. The colleges said that consultants’ mistreatment of trainees was a long established problem in obstetrics and gynaecology, as shown …
AUTOMATED DETERMINATION OF PULSE AMPLITUDE CHANGES IN FINGER PHOTOPLETHYSMOGRAPHY WAVEFORM DURING THE VALSALVA MANEUVER HAS HIGH SENSITIVITY AND SPECIFICITY FOR IDENTIFYING ELEVATED LEFT VENTRICULAR END DIASTOLIC PRESSURE
Authors: Panagis Galiatsatos, Jennifer Monti, Theingi Win, Peter Johnston, William Herzog, Jeffrey Trost, Chao-Wei Hwang, Harry Silber
Journal: Journal of the American College of Cardiology (2018)
Junior contract will be imposed, Jeremy Hunt announces
Authors: Abi Rimmer
Journal: BMJ (2016)

A new contract will be imposed on junior doctors in England, the health secretary has announced.

Speaking in the House of Commons on Thursday 11 February, Jeremy Hunt said that David Dalton, the government’s chief negotiator during negotiations, had said that a breakdown of negotiations meant that a negotiated agreement was unlikely to be reached.

Hunt said that Dalton had asked him to “end the uncertainty” and proceed in introducing a new contract for junior doctors, which Dalton considered to be safer for patients and fair for junior doctors. “I have therefore today decided to do that,” Hunt said.

He said that, under the new contract, the maximum hours in a week that junior doctors could work would reduce from 91 to 72 and the number of nights from seven to four, and that the maximum consecutive days a junior doctor could work would reduce from seven to five.

“We will also introduce a new guardian role into every trust, who will have the authority to impose fines for breaches to agreed working hours, based on excess hours worked,” he said.

Hunt said that …
MSc in health economics and health policy
Authors: Matthew Weller
Journal: BMJ (2008)

It is a part time MSc course run at the Health Services Management Centre at the University of Birmingham. It is a modular course taking two years to complete, and most modules can be taken either as a block lasting for one week or as weekly half day sessions. This flexibility helps to fit the course in with the normal working week. The course gives a valuable insight into the world of health economics, including how the National Institute for Health and Clinical Excellence (NICE) makes some of its very difficult rationing decisions, and also into how health policy develops and is put into practice.

The course obviously attracts a lot of NHS staff interested in pursuing a …
Impact of late Medicaid expansion on prostate cancer screening.
Authors: Daniel Pucheril, Dimitar V. Zlatev, Matthew Mossanen, Alexander P Cole, Matthew D. Ingham, Steven Lee Chang, Adam S. Kibel, Quoc-Dien Trinh
Journal: Journal of Clinical Oncology (2018)

141 Background: A key provision of the Affordable Care Act (ACA) was the expansion of Medicaid to childless adults living &lt; 138% of the federal poverty level (FPL). Aside from a few early expansion states, the majority of states adopting the provision expanded coverage in January 2014, and are categorized as late expansion states (LES). Non-expansion states (NES) opposed expansion and did not adopt these broader provisions. Our objective was to determine the effects of this policy change on prostate cancer screening (PSAS) trends in LES and NES. Methods: The 2014 and 2016 Behavioral Risk Factor Surveillance System surveys reflect 2013 and 2015 health behaviors, and were queried for men 40-64, without history of prostate cancer, with a household income &lt; 138% FPL, and residing in NES or LES. Descriptive statistics, stratified by expansion status and year, were generated for covariates. The Chi-Square test was used to compare proportions between years within state categories. Difference-in-differences (DID) analyses were employed to compare trends in men with health insurance, a personal physician, and undergoing PSAS. Within a multivariable logistic regression model, the interaction term year*state expansion status was used to determine the significance of DID estimates. Results: A weighted 8.8 million (n = 14,979) men met inclusion criteria. PSAS significantly declined from 2014 to 2016 in both NES (22.6% to 16.4%, p = 0.0006) and LES (20.5% to 15.8%, p = 0.003). In LES, the proportion of men with health insurance significantly increased from 2014 to 2016 (75.5% to 82.7%, p = 0.0002), however the proportion of insured men in NES was constant. Additionally, the proportion of respondents with a personal physician was unchanged from 2014 to 2016 in both NES and LES. DID analysis determined a significant difference in health insurance trends between 2014 and 2016 for LES compared to NES (+6.9%, p = 0.008). DID estimates were not significant for comparisons of trends for PSAS or access to a personal physician. Conclusions: The ACA’s Medicaid expansion provision has led to significant gains in insurance coverage for eligible persons in LES compared to NES, however, these gains have not translated into significantly different rates of access to a personal physician or PSAS.
Interdisciplinary training in cardiovascular imaging
Authors: Victoria St Noble, Niall G Keenan, Julia Hillier, Simon P G Padley, Edward D Nicol
Journal: BMJ (2013)

Although healthcare is now delivered across multidisciplinary teams, training continues to be delivered within the confines of each specialty. <b>Victoria St Noble</b> and colleagues describe a scheme that pairs radiologists with cardiologists to train in cardiovascular computed tomography.
An Asymmetric Wall-Thickening Pattern Predicts Response to Cardiac Resynchronization Therapy
Authors: David R. Warriner, Tom Jackson, Ernesto Zacur, Eva Sammut, Paul Sheridan, David Rod Hose, Patricia Lawford, Reza Razavi, Steve Alexander Niederer, Christopher Aldo Rinaldi, Pablo Lamata
Journal: JACC. Cardiovascular imaging (2018)

Cardiac morphology changes in heart failure and provides information on the state of the heart. We hypothesized that pre-implant left ventricular (LV) morphology differs significantly between responders and nonresponders to cardiac resynchronization therapy (CRT). To this end, the LV morphology of
THE ROSS PROCEDURE VERSUS PROSTHETIC VALVE REPLACEMENT: TOWARDS BETTER SOLUTIONS IN YOUNG AND MIDDLE-AGED ADULTS - SYSTEMATIC REVIEW, META-ANALYSIS AND VALUE OF INFORMATION ANALYSIS
Authors: Alexandru C. Visan, Howard Thom, Dan M. Dorobantu, Daniel Fudulu, Edna Keeney, Mansour T.A. Sharabiani, Jeff Round, Serban C. Stoica
Journal: Journal of the American College of Cardiology (2018)
LEFT ATRIAL REMODELING IS A PROGRESSIVE PHENOMENON ACCELERATED BY ATRIAL FIBRILLATION: COMPARISON BETWEEN PATIENTS WITHOUT AND WITH ATRIAL FIBRILLATION
Authors: Christian Mahnkopf, Marcel Mitlacher, Mathias Forkmann, Sonia Busch, Johannes Brachmann, Klinikum Coburg
Journal: Journal of the American College of Cardiology (2018)
Pilot trial of ibrutinib plus nivolumab in patients (pts) with metastatic renal cell cancer (mRCC): Results from a dose-finding cohort.
Authors: Primo Lara, Mamta Parikh, Daniel Robles, Frances Lara, Frederick J. Meyers, Chong-xian Pan
Journal: Journal of Clinical Oncology (2018)

600 Background: Immune checkpoint inhibitor therapy (CPI) has transformed the management of pts with mRCC, with a fraction experiencing durable tumor responses. However, most eventually develop disease progression after either an initial response to CPI or while on CPI. Newer agents that modulate immune response can possibly potentiate CPI therapy. The ITK/ETK/BTK inhibitor ibrutinib has been reported to inhibit myeloid derived suppressor cells in preclinical models and to potentiate CPI. We conducted an investigator-initiated pilot trial of ibrutinib plus the PD1 inhibitor nivolumab in mRCC pts, particularly in those previously exposed to CPI. Here we report initial safety and efficacy results from the dose-finding cohort. Methods: Pts with mRCC of any histologic subtype and who have completed at least one line of prior systemic therapy including prior CPI were eligible. Pts must have acceptable end-organ function and Zubrod PS of 0-2. Treatment consisted of nivolumab 240 mg IV q2 weeks plus ibrutinib 560 mg (dose level 0) or 420 mg (dose level -1) orally once daily. Cycle length was 28 days. Dose limiting toxicity (DLT) was defined as any Grade(Gr) 3+ adverse event (AE) attributable to therapy. Results: As of 9/18/17, 12 pts have been enrolled, six to each dose level. Patient characteristics: Mean age = 62 years (range 44-78); Male sex = 7 (58%); White race = 9 (75%); Prior CPI = 11 (92%). Three pts experienced one DLT each in dose level 0 (all Gr3): elevated lipase, hypoalbuminemia, &amp; nausea. Only 1 DLT has been seen thus far in dose level -1 (Gr3 infection). The most common Gr3+ AEs include anemia (n = 5), ALT elevation (4), AST elevation (3), nausea (3), hypoalbuminemia (2), esophagitis, infection, lipase increase, and vomiting (1 each). Two pts with prior CPI had partial tumor response (1 confirmed, 1 unconfirmed). Conclusions: Ibrutinib at a dose of 420mg orally once daily in combination with nivolumab 240mg IV q 2 weeks appears feasible and tolerable in mRCC patients. No unique immune-related AEs have been seen thus far. Anti-tumor activity was seen in 2 pts previously exposed to PD1-targeted therapy. Further evaluation of this combination is warranted. (Supported by Pharmacyclics and UCDCCC). Clinical trial information: NCT02899078.
Germline <i>BRCA1/2</i>, <i>PALB2,</i> and <i>ATM</i> mutations in 3,030 patients with pancreatic adenocarcinoma: Survival analysis of carriers and noncarriers.
Authors: Pashtoon Murtaza Kasi, Fergus Couch, William R Bamlet, Chunling Hu, Steven Hart, Eric Polley, Gloria M. Petersen, Robert R. McWilliams
Journal: Journal of Clinical Oncology (2018)

280 Background: Patients with pancreatic adenocarcinoma (PDAC) can have mutations in breast cancer associated genes ( BRCA1/2) and other homologous recombination (HR) pathway genes. The therapeutic significance of these mutations for PDAC patients is not yet established. We performed a comprehensive survival analysis of 3,030 unselected PDAC patients comparing non-carriers and carriers of BRCA1/2, PALB2, and ATM mutations. Methods: We analyzed germline DNA samples and outcomes from confirmed PDAC patients recruited from 1999-2014 into the Mayo Clinic SPORE in Pancreatic Cancer registry. A total of 3,046 genomic DNA samples were analyzed by next generation sequencing. All pathogenic variants were validated by Sanger sequencing. Survival analysis of PDAC patients with and without BRCA1, BRCA2, PALB2, or ATM germline mutations was performed using the Kaplan-Meier method and log-rank tests. Hazard ratios (HR) were calculated using Cox proportional hazard modeling adjusted for co-variates including age, sex, and stage. A p-value &lt; 0.05 was considered statistically significant. Pre- and post-FOLFIRINOX eras were defined as before and after June 1, 2011. Results: A total of 139 (4.6%) patients were noted to have deleterious mutations in BRCA1, BRCA2, PALB2, or ATM genes. After exclusion of patients with missing data, final analysis was restricted to 2,452 PDAC patients. Overall survival was slightly better (14.2 months versus 11.3 months) in patients with mutations as compared to those without mutations, although this finding was not statistically significant (p = 0.07). When stratified by FOLFIRINOX era, 40 patients with these mutations in the post-FOLFIRINOX era had better outcomes than 668 non-carriers (adjusted HR 0.62; 95% CI 0.43-0.89; p = 0.0062). Conclusions: Deleterious germline BRCA1/2, PALB2, and ATM mutations were seen in approximately 5% of patients with PDAC. Post-FOLFIRINOX era patients with these mutations had improved outcomes, possibly secondary to exposure to DNA-damaging chemotherapies. Germline screening of PDAC patients and development of trials incorporating this information (e.g., PARP inhibitors) has potential value for PDAC patients.