tbuckley/cabot-search huggingface dataset:
Response rates with pembrolizumab in combination with rituximab in patients with relapsed follicular lymphoma: Interim results of an on open-label, phase II study.
Authors: Loretta J. Nastoupil, Jason R. Westin, Nathan Hale Fowler, Michelle A. Fanale, Felipe Samaniego, Yasuhiro Oki, Chizobam Obi, JingJing Cao, Xiaoyun Cheng, Man Chun John Ma, Zhiqiang Wang, Fuliang Chu, Lei Feng, Shouhao Zhou, Richard Eric Davis, Sattva Swarup Neelapu
Journal: Journal of Clinical Oncology (2017)

7519 Background: Follicular lymphoma (FL) tumors are infiltrated with antitumor T cells, however, their function is impaired by immune checkpoints such as PD-1/PD-ligand pathway. Blocking PD-1 enhances the function of antitumor T cells in FL. In addition, blocking PD-1 on NK cells has been shown to enhance the ADCC effect of NK cells. We reasoned that the combination of pembrolizumab (P), an anti-PD-1 antibody (ab), and rituximab (R), an anti-CD20 ab that induces ADCC, is likely to be synergistic through activation of both the innate and adaptive immune systems and result in enhanced clinical activity in FL. Methods: We evaluated P and R in an open-label, non-randomized, single institution, phase II trial (N=30). Key inclusion criteria included adult (age ≥ 18 years), FL grade 1-3a, ECOG 0-1, in relapse after ≥1 prior therapy (tx) and R sensitive disease, defined as a complete (CR) or partial response lasting at least 6 months (mos) after most recent R-containing therapy. Pts received R (375 mg/m 2 IV) on days 1, 8, 15, and 22 of cycle 1 and P (200mg IV) q 3 weeks for up to 16 cycles starting on day 2 of cycle 1. Primary endpoint was overall response rate (ORR). Results: 27 pts have initiated therapy, median age 65 (range 42-79), 52% male, 76% had intermediate or high risk FLIPI, 56% met GELF criteria. Median prior tx =1 (range 1-4). Adverse events (AE) regardless of causality were mild, most grade 1-2. Grade 3 AE’s included nausea (N=2), infusion reaction (N=2), aseptic meningitis (N=1), pneumonia (N=1). Immune-related AEs included grade 2 diarrhea (N=2), grade 2 pneumonitis (N=1), grade 2 skin rash (N=1). At the pre-planned interim analysis (N=15), ORR was 80%, CR rate was 60%. With a median follow up of 7 mos (range 0.5-17), median DOR, PFS, and OS has not been reached. PD-L1 expression was tested in 8 baseline tumor samples using PD-L1 22C3 IHC pharmDx and was detected in histiocytes in all 8 tumors, present in only 1-8% of tumor cells in 5 tumors. Additional biomarker analyses are ongoing. Conclusions: The combination of P and R is well tolerated in relapsed FL and is associated with high overall and CR rate. These interim results warrant further investigation of this combination in FL. Clinical trial information: NCT02446457.
Models of epigenetic age capture patterns of DNA methylation in glioma associated with molecular subtype, survival, and recurrence
Authors: Peter Liao, Quinn T Ostrom, Lindsay Stetson, Jill S Barnholtz-Sloan
Journal: Neuro-Oncology (2018)

Models of epigenetic aging (epigenetic clocks) have been implicated as potentially useful markers for cancer risk and prognosis. Using 2 previously published methods for modeling epigenetic age, Horvath's clock and epiTOC, we investigated epigenetic aging patterns related to World Health Organization grade and molecular subtype as well as associations of epigenetic aging with glioma survival and recurrence.
Treatment trends of localized renal cell carcinoma by hospital type: A NCDB analysis.
Authors: David B. Cahn, Elizabeth Handorf, Daniel C. Edwards, Laura Kidd, Daniel M. Geynisman, Brian T. Kadow, Richard E. Greenberg, Rosalia Viterbo, David Chen, Alexander Kutikov, Robert Uzzo, Marc C. Smaldone
Journal: Journal of Clinical Oncology (2018)

641 Background: Weighing operative, oncologic and comorbid risks guide treatment recommendations for localized kidney cancers. We hypothesize that individualized surgical decision making may also be influenced by surgical center and volume. Methods: The National Cancer Database (NCDB) was queried for patients 18-80 years old with pT1a-T2bN0M0 RCC, treated by partial (PN) or radical nephrectomy (RN), or ablation (ABL) from 2004-2014. After adjusting for clinicopathologic characteristics, we evaluated the association of hospital volume (vol) and center classification with receipt of PN. High vol was defined as the top 10% in treatment volume. Results: 142,090 patients met inclusion criteria, where 58% (n = 82,498) and 41% (n = 58,873) were treated by RN and PN, respectively, and 1% (n = 719) by ABL. The utilization of PN increased over time (2004: 24% vs 2014: 53%; p &lt; 0.001). Stratified by tumor stage, 60% (n = 47,484) of pT1a and 24% (n = 9,906) of pT1b tumors were treated by PN. On multivariate analysis, patients treated at a high-vol center (OR 1.89, 95% CI 1.57-2.28) had a greater likelihood of receiving a PN when compared to treatment elsewhere. Additionally, compared to a community cancer program, treatment at a comprehensive community cancer center (OR 1.39, 95%CI 1.23-1.57), academic/research (OR 1.67, 95%CI 1.47-1.90), or integrated network cancer program (OR 1.48, 95%CI 1.24-1.77) had a higher likelihood of receiving a PN. The median distance travelled was 9.8 and 18.1 miles, for treatment at non high vol and high vol centers, respectively. An inverse correlation was noted between increasing tumor stage and receipt of PN, compared to pT1a tumors (pT1b [OR 0.22, 95%CI 0.20-0.23], pT2a [OR 0.06, 95%CI 0.05-0.06], pT2b [OR 0.03, 95%CI 0.02-0.03]). Conclusions: In the NCDB, despite increased utilization of PN at higher vol centers, the majority of localized renal tumors are still treated with RN. Smaller tumor size, treatment at a higher vol centers, comprehensive community cancer centers, academic/research programs, or integrated network cancer programs increase the likelihood of receipt of PN. Evaluation of population based trends aid in understanding localized RCC surgical management and may help quality improvement efforts.
Preclinical testing of NEDD8 and proteasome inhbitors for a treatment-refractory, metastatic high-grade mucinous colorectal cancer patient
Authors: E. Torchiaro, C. Petti, C. Isella, G. Corti, M. Montone, B. Mussolin, A. Bardelli, E. Medico
Journal: Annals of Oncology (2018)
Medical school admission criteria should be centralised to widen access, report recommends
Authors: Caroline White
Journal: BMJ (2013)

Criteria for admission to medical schools should be centralised and made more transparent to improve access for students from all walks of life, says a report from the Selecting for Excellence project.1

The project was set up earlier this year under the aegis of the Medical Schools Council. It aims to widen participation in medicine and ensure that the best candidates can apply, irrespective of their social background.

Its establishment was prompted by a growing body of evidence showing that social inequalities persist among …
Hepatic resection compared to chemoembolization in intermediate‐ to advanced‐stage hepatocellular carcinoma: A meta‐analysis of high‐quality studies
Authors: Myung Han Hyun, Young‐Sun Lee, Ji Hoon Kim, Chan Uk Lee, Young Kul Jung, Yeon Seok Seo, Hyung Joon Yim, Jong Eun Yeon, Kwan Soo Byun
Journal: Hepatology (2018)

According to the American Association for the Study of Liver Diseases (AASLD) treatment guidelines for hepatocellular carcinoma (HCC), the role of surgery has been expanded beyond the Barcelona Clinic Liver Cancer (BCLC) algorithm. We compared primary hepatectomy (PH) with transarterial chemoembolization (TACE) in patients with intermediate- to advanced-stage (BCLC stage B/C) HCC to determine the current evidence. Through a database search, we included 18 high-quality studies (one randomized controlled trial [RCT], five propensity-score matching nonrandomized comparative trials [NRCTs], and 12 NRCTs) that compared survival outcomes of 5,986 patients after PH and TACE. We found significant survival benefits for PH over TACE in BCLC stage B/C patients (hazard ratio [HR], 0.59; 95% confidence interval [CI], 0.51-0.67; P < 0.00001; I2 = 84%). According to the BCLC, both stage B and stage C patients showed significantly better overall survival (OS) for PH compared to TACE (HR, 0.53; 95% CI, 0.43-0.65; P < 0.00001; I2 = 77%; HR, 0.67; 95% CI, 0.59-0.77; P < 0.00001; I2 = 79%, respectively). Five-year survival rates for PH were significantly higher than those for TACE in BCLC stage B/C, stage B, and BCLC stage C patients (odds ratio [OR], 2.71, 2.77, and 3.03, respectively; all P < 0.00001). Survival benefits persisted across subgroup, sensitivity, and metaregression analyses; interstudy heterogeneity remained constant.This meta-analysis suggests that surgical resection provides survival benefits in patients with intermediate- to advanced-stage HCC. The evidence found herein may assist in the choice of treatment modality based on diverse definitions of operability. (Hepatology 2018).
Nanogenerator for Biomedical Applications
Authors: Hongqing Feng, Chaochao Zhao, Puchuan Tan, Ruping Liu, Xin Chen, Zhou Li
Journal: Advanced Healthcare Materials (2018)

Abstract In the past 10 years, the development of nanogenerators (NG) has enabled different systems to operate without external power supply. NG have the ability to harvest the mechanical energies in different forms. Human body motions and activities can also serve as the energy source to drive NG and enable self‐powered healthcare system. In this review, a summary of several major actual applications of NG in the biomedical fields is made including the circulatory system, the neural system, cell modulation, microbe disinfection, and biodegradable electronics. Nevertheless, there are still many challenges for NG to be actually adopted in clinical applications, including the miniaturization, duration, encapsulation, and output performance. It is also very important to further combine the NG development more precisely with the medical principles. In future, NG can serve as highly promising complementary or even alternative power suppliers to traditional batteries for the healthcare electronics.
The Role of the Physician in Patient Perceptions of Barriers to Primary Adherence With Acne Medications
Authors: Kira L. Ryskina, Erica Goldberg, Briana Lott, Davis Hermann, John S. Barbieri, Jules B. Lipoff
Journal: JAMA Dermatology (2018)

Primary nonadherence with acne medications is high but commonly underreported to prescribing physicians.To describe patient experiences with primary nonadherence to medications for acne and to identify physician-level factors that may improve adherence in this population.A qualitative analysis was conducted from structured interviews with patients reporting nonadherence with acne medications at a large academic health system in the Philadelphia, Pennsylvania, area. Three hundred eighty-five patients from 4 dermatology practices in the Philadelphia area were screened for primary nonadherence with a newly prescribed acne medication. Twenty-six patients participated in structured interviews conducted between November 30, 2016, and January 31, 2017.Thematic analysis of the transcripts was performed to detect recurrent themes and divergent ideas with a focus on modifiable physician-level factors that might improve primary adherence to medications for acne.Participants (19 [73%] women, 6 [23%] aged <26 years, 15 [58%] aged 26-40 years, and 5 [19%] aged >40 years) reported cost as the major barrier to initiating therapy. Despite anticipating this barrier, they rarely brought up costs with physicians during the initial visit and generally did not expect their physician to be knowledgeable in this area. Although patients experienced inconvenience and frustration when unable to fill their prescriptions, this experience did not appear to negatively affect their satisfaction with the prescribing physician. Nevertheless, warning patients that the preferred medication may be expensive, having a plan of action if patients were unable to fill the prescription, and securing the patient's commitment to the plan were described as actions that the physicians could take to improve primary adherence.Physician-level interventions to improve primary adherence to medications for acne may have an impact on nonadherence with costly medications, although they may not affect patient satisfaction with the prescribing physician.
POPULATION-REFERENCED CORONARY ANATOMY AND CORONARY FLOW RESERVE IN WOMEN WITH EVIDENCE OF ISCHEMIA AND NO OBSTRUCTIVE CORONARY ARTERY DISEASE: A REPORT FROM THE WOMEN'S ISCHEMIA SYNDROME EVALUATION
Authors: Christine Pacheco, Ahmed AlBadri, Janet Wei, R. David Anderson, John W. Petersen, Reddy Sailaja Marpuri, Galen Cook-Wiens, Carl J. Pepine, G.B. John Mancini, C. Noel Bairey Merz
Journal: Journal of the American College of Cardiology (2018)
Validation of a biological score to predict response in chronic lymphocytic leukemia patients treated front-line with bendamustine and rituximab
Authors: Massimo Gentile, Tait D. Shanafelt, Gianluigi Reda, Francesca Romana Mauro, Katja Zirlik, Stefania Ciolli, Luca Laurenti, Maria Ilaria Del Principe, Davide Rossi, Nicola Di Renzo, Stefano Molica, Francesco Angrilli, Marta Coscia, Annalisa Chiarenza, Annamaria Giordano, Giovanna Cutrona, Kari G. Chaffee, Sameer A. Parikh, Giuseppina Uccello, Idanna Innocenti, Giovanni Tripepi, Graziella D’Arrigo, Ernesto Vigna, Anna Grazia Recchia, Yair Herishanu, Lev Shvidel, Tamar Tadmor, Agostino Cortelezzi, Giovanni Del Poeta, Gianluca Gaidano, Francesco Di Raimondo, Antonino Neri, Manlio Ferrarini, Robin Foà, Aaron Polliack, Fortunato Morabito
Journal: Leukemia (2018)
How should clinicians integrate the findings of <i>The Lancet</i>’s 2018 placebo-controlled subacromial decompression trial into clinical practice?
Authors: Chris Littlewood, Julie Bury, Aidan O’Shea, Karen McCreesh, Kieran O’Sullivan
Journal: British Journal of Sports Medicine (2018)

This systematic review and meta-analysis aimed to determine the effect of combined beta-alanine (BA) and sodium bicarbonate (SB) supplementation on exercise capacity and performance.Four databases (PubMed, SPORTDiscus, Web Of Science and MEDLINE) were searched using relevant terms for studies involving healthy (e.g.no chronic diseases or conditions) male or female adults of any training status (athletes, physically active and nonathletes) and that investigated BA and SB in isolation and combination at any dose on an exercise outcome.Ten studies, totalling 243 individuals, met the criteria with 12 outcomes for each nutritional supplement.No ergogenic effect was detected in this meta-analysis for BA (SMD = 0.18, 95% CI: -0.06; 0.43, p = 0.13, tau² = 0, tau = 0, I² = 0.0%) or SB (SMD = 0.17, 95% CI: -0.08; 0.41, p = 0.16, tau² = 0, tau = 0, I² = 0.0%) in isolation.However, there was a beneficial effect for the combination of BA and SB (SMD = 0.32, 95% CI: 0.07; 0.57, p = 0.02, tau² = 0, tau = 0, I² = 0.0%).Meta-regression identified no differences between supplementing with BA or SB separately (F = 0.58; p = 0.57).Combining BA and SB improved exercise performance, however, there was no benefit in taking these supplements individually.
Balancing Parental Needs for Physicians’ Technical Help With Physicians’ Legal Protection
Authors: Amanda Rahman, Shetal Shah, Edmund F. La Gamma
Journal: JAMA Pediatrics (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 Pediatrics 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 Pediatrics journal
The impact of treatment at minority-serving hospitals on outcomes for bladder cancer.
Authors: Sean A. Fletcher, Philipp Gild, Alexander P Cole, Malte Vetterlein, Adam S. Kibel, Toni K. Choueiri, Guru Sonpavde, Mark A Preston, Daniel Pucheril, Mani Menon, Maxine Sun, Stuart R. Lipsitz, Quoc-Dien Trinh
Journal: Journal of Clinical Oncology (2018)

492 Background: Healthcare for racial minorities is densely concentrated at a small subset of hospitals in the United States. Understanding long-term outcomes at these minority-serving hospitals is highly relevant to elucidating the sources of racial disparities in cancer care. We investigated the impact of treatment at a minority-serving hospital on overall survival and receipt of definitive treatment for bladder cancer. Methods: Using the National Cancer Database, we identified all patients diagnosed with clinically localized, muscle-invasive bladder cancer between 2004 and 2012. Univariate and multivariable analyses were performed to assess the sociodemographic, clinical, and hospital-level factors influencing overall survival and receipt of definitive treatment (radical cystectomy with or without chemotherapy; trimodal therapy) for bladder cancer. Results: In adjusted analyses, there was no significant difference in overall survival between patients treated at minority-serving hospitals versus those treated at non-minority-serving hospitals (HR: 0.95; 95% CI: 0.90-1.01). There was also no significance in receipt of definitive treatment between the two hospital types (OR: 0.85; 95% CI: 0.68-1.06). Black race was independently associated with increased likelihood of mortality (HR: 1.08; 95% CI: 1.03-1.14) and decreased odds of receiving appropriate definitive treatment (OR: 0.73; 95% CI: 0.66-0.82). Conclusions: There was no difference between minority-serving and non-minority-serving hospitals in overall survival or receipt of definitive treatment. Black patients suffered worse survival and were less likely to receive definitive treatment for bladder cancer regardless of the type of hospital in which they were treated.
Discovery, Knowledge, and Action—Diabetes in Pregnancy Across the Translational Spectrum: The 2016 Norbert Freinkel Award Lecture
Authors: H. David McIntyre
Journal: Diabetes Care (2018)

The Norbert Freinkel Award is given in memory of Norbert Freinkel, a dedicated and insightful investigator and gifted writer, to honor a researcher who has made outstanding contributions, including scientific publications and presentations, to the understanding and treatment of diabetes in pregnancy. H. David McIntyre, MD, FRACP, Director of Obstetric Medicine at Mater Health Services and Head of the Mater Clinical Unit at The University of Queensland in Brisbane, Australia, received the prestigious award at the American Diabetes Association's 76th Scientific Sessions, 10–14 June 2016, in New Orleans, LA. He presented the Norbert Freinkel Award Lecture, “Discovery, Knowledge, and Action—Diabetes in Pregnancy Across the Translational Spectrum,” on Saturday, 11 June 2016.
Actomyosin-Mediated Tension Orchestrates Uncoupled Respiration in Adipose Tissues
Authors: Kevin M. Tharp, Michael S. Kang, Greg A. Timblin, Jon Dempersmier, Garret E. Dempsey, Peter-James H. Zushin, Jaime Benavides, Catherine Choi, Catherine X. Li, Amit K. Jha, Shingo Kajimura, Kevin E. Healy, Hei Sook Sul, Kaoru Saijo, Sanjay Kumar, Andreas Stahl
Journal: Cell Metabolism (2018)
Mutational landscape of primary and recurrent glioblastoma reveals potentially actionable SNVs including WNT pathway variation
Authors: Hayley Ellis, Felix Sahm, Daniel Schrimpf, Alexei Stupnikov, Mark Wadsley, Christopher Wragg, Darragh McArt, Kathreena Kurian
Journal: Neuro-Oncology (2018)

We used Next-Generation sequencing (NGS) panels to examine somatic variation in a cohort of 41 patients, 8 of which had matched primary biopsies and recurrent biopsies from subsequent tumour resection. 38/41 (92%) of the initial tumours harbour at least one variation in a gene which interacts with the RTK/Ras/PI(3)K pathway. 6/41 (15%) of initial tumours have an SNV in the IDH pathway. 27/41 (66%) of the initial biopsy samples have at least one SNV in the Wnt signalling pathway. 29/41 (71%) of initial tumours have at least one SNV in the p53 DNA damage repair pathway, and 12/41 (29%) have an SNV in the Rb cell-cycle regulation pathway. 3/41 (7%) of initial tumours have an SNV in the Nodal TGF-β signalling pathway for chromatin remodelling and pattern development, and 3/41 (7%) samples have a G-protein gene variation. Of the recurrent tissue samples, 6/8 (75%) have at least one somatic gene variation in the RTK/Ras/PI(3)K pathway, and 2/8 (25%) samples have an SNV in the IDH pathway. 3/8 (37.5%) have an SNV in the WNT signalling pathway, 4/8 (50%) have an SNV in the P53 pathway and no variation was identified in the Rb pathway. In 1/8 (12.5%) recurrent samples had an SNV in the Nodal TGF-β signalling pathway was identified, and 2/8 (25%) have a G-protein gene variation. Of the initial biopsy samples, 19/41 (46%) harboured at least one potentially actionable SNV. Of the recurrent tissue samples, 4/11 (36%) had at least one actionable SNV. Of the matched recurrent tumours, 6/8 (75%) contain SNVs that were present in the second tumour, as well as variation lost and gained. In 2/8 (25%) recurrent tumours,variation does not appear to correlate with the initial tumour. In conclusion, mutational analysis of primary and recurrent glioblastoma reveals potentially actionable SNVs including WNT pathway variation.
Delivery of Sonic Hedgehog Gene Repressed Irradiation-induced Cellular Senescence in Salivary Glands by Promoting DNA Repair and Reducing Oxidative Stress
Authors: Bo Hai, Qingguo Zhao, Michael A. Deveau, Fei Liu
Journal: Theranostics (2018)

Rationale: Irreversible hypofunction of salivary glands or xerostomia is common in head and neck cancer survivors treated with radiotherapy even when various new techniques are applied to minimize the irradiation (IR) damage.This condition severely impairs the quality of life of patients and can only be temporarily relieved with current treatments.We found recently that transient expression of Sonic Hedgehog (Shh) in salivary glands after IR rescued salivary function, but the underlying mechanisms are not totally clear.Methods: We generated a mouse model of IR-induced hyposalivation, and delivered adenoviral vectors carrying Shh or control GFP gene into submandibular glands (SMGs) via retrograde ductal instillation 3 days after IR.The cellular senescence was evaluated by senescence-associated beta-galactosidase assay and the expression of senescence markers.The underlying mechanisms were explored by examining DNA damage, oxidative stress, and the expression of related genes by qRT-PCR, Western blot and immunofluorescent staining.Results: Shh gene transfer repressed IR-induced cellular senescence by promoting DNA repair and decreasing oxidative stress, which is mediated through upregulating expression of genes related to DNA repair such as survivin and miR-21 and repressing expression of pro-senescence gene Gdf15 likely downstream of miR-21.Conclusion: Repressing cellular senescence contributes to the rescue of IR-induced hyposalivation by transient activation of Hh signaling, which is related to enhanced DNA repair and decreased oxidative stress in SMGs.