tbuckley/cabot-search huggingface dataset:
Combination of everolimus and lu-177 PRRT in treatment of G1-2 neuroendocrine tumors (NET): Phase 1-2 study.
Authors: Ali Husain Aljubran, Mohamed Alrowaili, Hussein Raef, Shouki Bazarbashi, Ahmed M Alzahrani, Ahmed Almuhaideb, Hadeel Almanea, Ahmed ali Badran, Abdelmuniem Al-Dalee, Mahmoud Tuli
Journal: Journal of Clinical Oncology (2019)

386 Background: Everolimus and Lutetium-177 PRRT were approved as monotherapy. However, animal model research showed synergistic effect of the combination. The goal of this study is to assess the safety and efficacy of the combination in treatment of unresectable G1-2 NETs of all gastrointestinal, lung and pancreatic origins. Methods: This is a phase 1-2 study. Phase 1 part involves finding the maximum tolerating dose (MTD) of everolimus and accordingly to recommend dose for phase II part. Starting everolimus dose was 5 mg OD. Patients were treated concurrently with Lu-177 DOTATOC therapy at intervals of 8 weeks (+/-1 week) with average of 4 sessions. Sample size calculation was based on the expected response of the combination to be 30% with power of 80 and type 1 of .05, compared to the known response rate of everolimus alone of 5%. Primary end point is safety. Other end points include response rate, PFS and OS. Results: Eleven patients, with progressive disease, were enrolled. Characteristics are summarized in the table. Everolimus MTD was 10 mg once daily. However, dose was reduced to 5 mg OD in 3 patients and to 5 mg once every other day in 2 patients. Median number of sessions of Lu-177: 3 sessions, and median cumulative dose: 300 mci. Most common G1-2 toxicities: stomatitis (90.9%), Nausea (72.7%), Fatigue (63.6%), anorexia (36.4%), diarrhea (36.4%) and skin and nail changes (36.4%). G3 toxicities (36%) were infection, fatigue, pneumonitis and neutropenia. No grade 4 toxicities. Reasons of discontinuation were toxicity in 3 patients, progression in 3, stroke in 1 and due to interruption of therapy in 4 patients. ORR: 1 PD, 1 PR and 9 SD. At median FU of 18.9 months, 7 patients are still alive, 3 died, and 1 lost to FU. Median PFS: 23.3 months. Conclusions: Combination of Everolimus and the Lu-177 PRRT appear to be safe and effective. Four patients, due to strict compliance criteria in the study protocol, were removed from the study prematurely resulting in undertreatment. Larger and randomized studies are required to confirm such findings.[Table: see text]
When continuous outcomes are measured using different scales: guide for meta-analysis and interpretation
Authors: Mohammad Hassan Murad, Zhen Wang, Haitao Chu, Lifeng Lin
Journal: BMJ (2019)

It is common to measure continuous outcomes using different scales (eg, quality of life, severity of anxiety or depression), therefore these outcomes need to be standardized before pooling in a meta-analysis. Common methods of standardization include using the standardized mean difference, the odds ratio derived from continuous data, the minimally important difference, and the ratio of means. Other ways of making data more meaningful to end users include transforming standardized effects back to original scales and transforming odds ratios to absolute effects using an assumed baseline risk. For these methods to be valid, the scales or instruments being combined across studies need to have assessed the same or a similar construct
Pregnancy-Associated Plasma Protein-A (PAPP-A) in Ewing Sarcoma: Role in Tumor Growth and Immune Evasion
Authors: Sabine Heitzeneder, Elena Sotillo, Jack F Shern, Sivasish Sindiri, Peng Xu, Robert Jones, Michael Pollak, Pernille R Noer, Julie Lorette, Ladan Fazli, Anya Alag, Paul Meltzer, Ching Lau, Cheryl A Conover, Claus Oxvig, Poul H Sorensen, John M Maris, Javed Khan, Crystal L Mackall
Journal: JNCI Journal of the National Cancer Institute (2018)

Abstract Background Ewing sarcoma (EWS) manifests one of the lowest somatic mutation rates of any cancer, leading to a scarcity of druggable mutations and neoantigens. Immunotherapeutics targeting differentially expressed cell surface antigens could provide therapeutic benefit for such tumors. Pregnancy-associated plasma protein A (PAPP-A) is a cell membrane-associated proteinase produced by the placenta that promotes fetal growth by inducing insulinlike growth factor (IGF) signaling. Methods By comparing RNA expression of cell surface proteins in EWS (n = 120) versus normal tissues (n = 42), we comprehensively characterized the surfaceome of EWS to identify highly differentially expressed molecules. Using CRISPR/Cas-9 and anti-PAPP-A antibodies, we investigated biological roles for PAPP-A in EWS in vitro and in vivo in NSG xenograft models and performed RNA-sequencing on PAPPA knockout clones (n = 5) and controls (n = 3). All statistical tests were two-sided. Results EWS surfaceome analysis identified 11 highly differentially overexpressed genes, with PAPPA ranking second in differential expression. In EWS cell lines, genetic knockout of PAPPA and treatment with anti-PAPP-A antibodies revealed an essential survival role by regulating local IGF-1 bioavailability. MAb-mediated PAPPA inhibition diminished EWS growth in orthotopic xenografts (leg area mm2 at day 49 IgG2a control (CTRL) [n = 14], mean = 397.0, SD = 86.1 vs anti-PAPP-A [n = 14], mean = 311.7, SD = 155.0; P = .03; median OS anti-PAPP-A = 52.5 days, 95% CI = 46.0 to 63.0 days vs IgG2a = 45.0 days, 95% CI = 42.0 to 52.0 days; P = .02) and improved the efficacy of anti-IGF-1R treatment (leg area mm2 at day 49 anti-PAPP-A + anti-IGF-1R [n = 15], mean = 217.9, SD = 148.5 vs IgG2a-CTRL; P &lt; .001; median OS anti-PAPP-A + anti-IGF1R = 63.0 days, 95% CI = 52.0 to 67.0 days vs IgG2a-CTRL; P &lt; .001). Unexpectedly, PAPPA knockout in EWS cell lines induced interferon (IFN)-response genes, including proteins associated with antigen processing/presentation. Consistently, gene expression profiles in PAPPA-low EWS tumors were enriched for immune response pathways. Conclusion This work provides a comprehensive characterization of the surfaceome of EWS, credentials PAPP-A as a highly differentially expressed therapeutic target, and discovers a novel link between IGF-1 signaling and immune evasion in cancer, thus implicating shared mechanisms of immune evasion between EWS and the placenta.
Stripping the Fear of a Fatal Disease—The Cancer Named Herbie
Authors: Nikolaos A. Trikalinos
Journal: JAMA Oncology (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 Oncology 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 Oncology journal
Idiopathic interstitial pneumonia or idiopathic interstitial pneumonitis: what's in a name?
Authors: Athol U. Wells, Kevin K. Brown, Kevin R. Flaherty, Martin Kolb, Victor J. Thannickal
Journal: European Respiratory Journal (2019)

<b>We welcome debate on the implications of a change from "pneumonia" to "pneumonitis", but suggest that this alteration does not capture a unifying pathogenetic basis for these diverse disorders</b>http://ow.ly/yMIA30ns2q0
Real World Use of Extended Half-Life Products and the Impact on Bleeding Events and Joint Health in the United States
Authors: Lynn M. Malec, Char M Witmer, Julie Jaffray, Peter A. Kouides, Kristina M. Haley, Robert F. Sidonio, Dunlei Cheng, Thomas C. Abshire, Gilbert C. White, Margaret V. Ragni
Journal: Blood (2018)
Evaluation of intratumoral T cells in biopsies from advanced gastric cancer patients treated with andecaliximab and nivolumab.
Authors: Carrie Brachmann, Yafeng Zhang, Emon Elboudwarej, Scott Turner, Dung Thai, Pankaj Bhargava, Jean-Philippe Metges, David Cunningham, Daniel V.T. Catenacci, Eric Van Cutsem, Zev A. Wainberg, Manish A. Shah
Journal: Journal of Clinical Oncology (2019)

118 Background: Preclinical studies suggest that MMP9 inhibition relieves immune suppression and promotes T cell infiltration to potentiate checkpoint blockade. To test this hypothesis, patient tumor samples obtained in a phase 2, open-label, randomized study (NCT02864381) of previously treated advanced gastric cancer comparing the MMP9-specific inhibitor andecaliximab (ADX) plus nivolumab (N) vs N alone were evaluated for T cell biomarkers. Methods: CD8 and PD-L1 (28-8 DAKO) were assessed by immunohistochemistry. IFNg, Teffector (Teff), and activated CD8+ T cell (ActT) gene signatures (GS) were assessed by RNASeq in archival baseline (BL) and biopsies obtained between weeks 5 and 9 (on-treatment; OT). Results: For both N and ADX/N, intratumoral CD8+ cells were significantly increased in OT biopsies relative to BL. The CD8+ OT increase was significantly greater for the ADX/N treatment relative to N in the PD-L1+ subgroup. In the ADX/N group only, IFNg, Teff, and ActT GS were significantly higher in OT biopsies relative to BL. OT change from BL of ≥ 300% vs &lt;300% in CD8+ cells was associated with longer PFS (HR = 0.50, p = 0.032). The percentage of patients with increased CD8+ cells in OT biopsies was higher in the ADX/N arm. Conclusions: In the PD-L1+ ADX/N group, there was a significantly greater magnitude of CD8+ cell density increase, which was associated with gene signatures of T cell activation. More ADX/N-treated patients had an increase in tumor-associated CD8+ cells. Longer PFS was observed for patients in which CD8+ cells increased by ≥ 300%. These results are consistent with the hypothesis that ADX potentiates checkpoint inhibition by favorably altering the tumor immune microenvironment. Clinical trial information: NCT02864381. [Table: see text]
Mutation-Specific Dose Reduction in Functional SRP54 Protein Causes Isolated or Syndromic Neutropenia with Shwachman-Diamond-like Features
Authors: Martina Konantz, Christoph Schürch, Joelle S. Müller, Jonas Schärer, Raphael Carapito, Seiamak Bahram, Claudia Lengerke
Journal: Blood (2018)
Abstract 14792: Coronary Artery Disease in Patients With a Bicuspid Aortic Valve-is Routine Preoperative Catheterization Justfied?
Authors: Josephina Haunschild, Konstantin Aspern, Martin Misfeld, Farhad Bakthiary, Piroze Davierwala, Friedrich-Wilhelm Mohr, Michael A Borger, Christian D Etz
Journal: Circulation (2017)

Objective: It has been hypothesized that patients with bicuspid aortic valves (BAV) are less prone to coronary artery disease (CAD), while frequently exhibiting complex coronary anomalies—both clinically relevant risk factors for surgical (and TAVI) treatment of valve pathologies requiring optimal preoperative coronary diagnostics. Benchmark data on (1) incidence and complexity of concomitant CAD according to the Syntax score and (2) clinically relevant coronary anomalies in pts with dysfunctional BAV are not yet available. Methods: A total of 1698 consecutive patients undergoing AVR w/o concomitant tubular/ascending aortic repair between 01/2012 and 09/2015 at a high-volume institution were analyzed. Complete clinical imaging data were available for analysis in 98% of patients (N=1663), of which 65% (N=1087) had a tricuspid aortic valve (TAV), while 35% (N=576) carried different morphologies of BAV. Prior to group comparison confounders were adjusted for by propensity score matching. Results: Prior to ma...
A Nodular Lesion of the Foot Detected by 18F-FDG PET/CT in Mycosis Fungoides
Authors: Yasuyuki Fujita, Ken Natsuga, Osamu Manabe, Kenji Hirata, Hiroshi Shimizu
Journal: Clinical Nuclear Medicine (2019)

A 34-year-old Japanese woman presented with widespread scaly erythema that had enlarged over 2 years. A skin biopsy revealed the diagnosis of mycosis fungoides (patch stage, T1b N0 M0 B0), a most frequent cutaneous T-cell lymphoma. F-FDG PET/CT scan unexpectedly showed intense uptake on the left sole, which suggested a tumorous mycosis fungoides lesion (SUVmax = 6.2). Careful examination revealed the mass to be a typical plantar wart of 2 cm in diameter that the patient had not recognized. With repeated cryotherapy, the wart disappeared in 6 months, and follow-up F-FDG PET/CT showed no abnormal uptake on the left sole.
Epigenetic Dysfunction in T cells is Associated with Enhanced Type-2 and Blunted Regulatory Immunity
Authors: Onyinye I. Iweala, Lakeya C. Hardy, Shailesh Choudhary, Hsing-Hui Wang, Claire T. Addison, Nikhil Milind, Kelly A. Orgel, Michael D. Kulis, Joseph F. Urban, Cathryn R. Nagler, A. Wesley Burks, Maureen A. Su, Scott P. Commins
Journal: Journal of Allergy and Clinical Immunology (2019)
Enhanced expression of ASB6 and IFIT2 in oral squamous cell carcinoma
Authors: Kuo-Chu Lai, Kuo-Wei Chang, Chung Ji Liu, Te-Chang Lee
Journal: Cancer Research (2006)

910  Oral squamous cell carcinoma (OSCC) is the most common cancer of the head and neck region and accounts for over 300,000 new cancer cases worldwide every year. In Taiwan, OSCC accounts for the sixth leading cause of cancer mortality and the fourth most common cancer in males, while the occurrence of 80% OSCC is associated with areca chewing. To identify tumor biomarkers, we have recently identified that the expression of ankyrin repeat and SOCS box-containing 6 (ASB6) and interferon-induced protein with tetratricopeptide repeats 2 (IFIT2) were significantly enhanced in OSCC tissue samples. Using RT-PCR analysis, 60% and 95% of OSCC tissues were shown with enhanced ASB6 and IFIT2 expression, respectively, as compared to non-cancerous matched tissues. ASB6 is a member of suppressor of cytokine signaling family, while IFIT2 belongs to interferon-induced protein without a known function. Since most OSCC patients in Taiwan are areca chewers, we therefore treated OEC-M1 cells, an OSCC cell line, with various concentrations (0 to 80 μg/ml) of areca nut extracts (ANE) for 48 to 72 h. Our results demonstrated that ANE treatment remarkably elevated the expression of both ASB6 and IFIT2 genes. These results imply a possible association of elevated expression of these two genes with areca chewing. In addition, we also found that the protein levels of IFIT2 were enhanced in OEC-M1 cells following TGF-β1 treatment. Whether ASB6 and IFIT2 can serve as tumor markers for OSCC patients warrants our further investigation.
Abstract P114: Association Between Socioeconomic Position and Cardiovascular Disease Risk Factors: The Solan Surveillance Study
Authors: Anubha Agarwal, Vamadevan S Ajay, Siddhartha Mandal, Shreeparna Ghosh, Devraj Jindal, Kavita Singh, Mark D Huffman, Nikhil Tandon, Dorairaj Prabhakaran
Journal: Circulation (2017)

Introduction: Data are limited evaluating the association of socioeconomic position and cardiovascular disease risk factors in rural India, an area facing rapid economic changes. Hypothesis: We hypothesized that socioeconomic position is associated with the prevalence of abnormal cardiovascular disease risk factors in rural India. Methods: From 2013-2014, we performed multi-stage, representative, community-based sampling of the rural Solan district of Himachal Pradesh in India as part of a prospective, longitudinal cohort study enrolling 40,017 participants. We collected data on demographics, medical history, anthropometry, blood pressure, and laboratory studies. Using factor analysis for mixed data, we constructed a socioeconomic position index incorporating education, occupation, income, and household assets for each individual. We used multivariable logistic regression models adjusted for age and sex to evaluate the association between quintiles of the socioeconomic position index and cardiovascular disease risk factors. Results: Participants’ mean (SD) age was 42.7 (15.9) years, and 57% were women. Fifteen percent of participants were illiterate (n = 6081) and 24% were employed (n = 9502). The mean (SD) BMI was 22.3 (4.1) kg/m 2 . The mean (SD) systolic and diastolic blood pressures were 139.6 (21.8) mmHg and 84.3 (11.4) mmHg, respectively. After adjustment, individuals in the highest quintile of socioeconomic position index had 2.19 (95% CI 2.01, 2.38) higher odds of being overweight, 3.43 (95% CI 2.91, 4.04) higher odds of being obese, 2.45 (95% CI 2.16, 2.78) higher odds of having hypertension, and 1.62 (95% CI 1.44, 1.82) higher odds of having diabetes mellitus (Figure). Conclusion: We observed a direct, stepwise association between socioeconomic position and prevalence of abnormal cardiovascular risk factors in rural India. Primordial prevention strategies are needed for rural Indians, including those who experience increases in socioeconomic position, to improve cardiovascular health.
Initial Versus Follow-up Sequential Myocardial 123I-MIBG Scintigraphy to Discriminate Parkinson Disease From Atypical Parkinsonian Syndromes
Authors: Dong-Woo Ryu, Joong-Seok Kim, Jee-Eun Lee, Yoon-Sang Oh, Sang-Won Yoo, Ie Ryung Yoo, Kwang-Soo Lee
Journal: Clinical Nuclear Medicine (2019)

Purpose Previous single-center or meta-analysis studies analyzed myocardial 123 I-metaiodobenzylguanidine ( 123 I-MIBG) scintigraphy in a single image session and demonstrated low sensitivity and high specificity for discriminating Parkinson disease (PD) from atypical Parkinsonian syndromes (APS). This study aimed to assess diagnostic ability of myocardial 123 I-MIBG scintigraphy at 2 phases to discriminate PD from APS. Patients and Methods This hospital-based prospective study enrolled 162 PD and 26 APS patients who underwent 2 sequential 123 I-MIBG scintigraphy evaluations. Patients were stratified into normal and decreased 123 I-MIBG groups according to early and delayed heart-to-mediastinum (H/M) ratios. Patients with PD and normal 123 I-MIBG uptake (initial delayed H/M ratio, ≥1.78) were considered scans without evidence of cardiac norepinephrine deficit (SWEND). Early and delayed H/M ratios on the initial and 2-year follow-up scintigraphs were studied. The diagnostic sensitivity and specificity were calculated from these confusion matrices and were analyzed according to receiver-operating characteristic curve analysis. A repeated-measures general linear model was used to investigate differences among groups over time in H/M ratio changes and washout rates. Results Follow-up 123 I-MIBG scintigraphy analysis had a higher diagnostic sensitivity (89.5%) than the initial imaging (72.2%). The improved sensitivity was associated with a steeper decrease in H/M ratio in the SWEND group than in the APS group. Conclusions Follow-up 123 I-MIBG scintigraphy can identify cardiac sympathetic denervation and its progression in patients with PD and may be effective in discriminating PD from APS. A later decrease in myocardial 123 I-MIBG uptake in the group with SWEND meets the Braak staging threshold hypothesis for synucleinopathy.
Factors Associated With High-Quality Guidelines for the Pharmacologic Management of Chronic Diseases in Primary Care
Authors: Caroline de Godoi Rezende Costa Molino, Nathalia Celini Leite-Santos, Franciele Cordeiro Gabriel, Sheila Kalb Wainberg, Luciana Pereira de Vasconcelos, Rafael Augusto Mantovani-Silva, Eliane Ribeiro, Nicolina Silvana Romano-Lieber, Airton Tetelbom Stein, Daniela Oliveira de Melo
Journal: JAMA Internal Medicine (2019)

<h3>Importance</h3> As the rate of publication of new and sometimes conflicting medical research increases, clinicians rely heavily on clinical practice guidelines (CPGs) to inform practice. However, CPGs are of widely variable quality, and there are no existing objective measures to rate the quality of CPGs. <h3>Objective</h3> To systematically assess 421 CPGs for the management of common noncommunicable diseases in primary care using the validated Appraisal of Guidelines for Research and Evaluation Instrument, version II (AGREE-II) tool and elucidate the factors associated with quality of CPGs. <h3>Evidence Review</h3> MEDLINE, Embase, the Cochrane Library, and 12 websites for CPGs were searched for CPGs for the management of common noncommunicable diseases in primary care published between January 1, 2011, and August 30, 2017. The assessment of the quality of CPGs was performed by 3 appraisers using the 6 domains of the AGREE-II instrument. A multiple logistic regression was performed to identify factors associated with quality of CPGs. <h3>Findings</h3> Of the 421 CPGs reviewed, 23.5% (99) were classified as high quality. Among included guidelines, clarity of presentation (70%) and scope and purpose (61%) had the highest median AGREE-II scores. The domains with the lowest median scores were applicability (22%) and rigor of development (33%). Factors associated with high-quality CPGs included having more than 20 authors (odds ratio, 9.08; 95% CI, 3.35-24.62), development at governmental institutions (odds ratio, 10.38; 95% CI, 2.72-39.60), and reporting funding (odds ratio, 10.34; 95% CI, 4.77-22.39). Year of publication, region, guideline version, and scope were not associated with quality among included CPGs. <h3>Conclusions and Relevance</h3> Primary care professionals and policymakers should be aware that CPGs in primary care are of widely variable quality, with less than 25% of included CPGs rated as high quality. High-quality CPGs were associated with a higher number of authors, governmental institutions, and the report of funding. Region of origin was not associated with quality of CPGs, which suggests that the improvement of the quality of CPGs should be an international concern.
An integrative memory model of recollection and familiarity to understand memory deficits
Authors: Christine Bastin, Gabriel Besson, Jessica Simon, Emma Delhaye, Marie Geurten, Sylvie Willems, Eric Salmon
Journal: Behavioral and Brain Sciences (2019)

Humans can recollect past events in details (recollection) and/or know that an object, person, or place has been encountered before (familiarity). During the last two decades, there has been intense debate about how recollection and familiarity are organized in the brain. Here, we propose an integrative memory model which describes the distributed and interactive neurocognitive architecture of representations and operations underlying recollection and familiarity. In this architecture, the subjective experience of recollection and familiarity arises from the interaction between core systems (storing particular kinds of representations shaped by specific computational mechanisms) and an attribution system. By integrating principles from current theoretical views about memory functioning, we provide a testable framework to refine the prediction of deficient versus preserved mechanisms in memory-impaired populations. The case of Alzheimer's disease (AD) is considered as an example because it entails progressive lesions starting with limited damage to core systems before invading step-by-step most parts of the model-related network. We suggest a chronological scheme of cognitive impairments along the course of AD, where the inaugurating deficit would relate early neurodegeneration of the perirhinal/anterolateral entorhinal cortex to impaired familiarity for items that need to be discriminated as viewpoint-invariant conjunctive entities. The integrative memory model can guide future neuropsychological and neuroimaging studies aiming to understand how such a network allows humans to remember past events, to project into the future, and possibly also to share experiences.