tbuckley/cabot-search huggingface dataset:
Analysis of learning curves in gastroscopy training: the need for composite measures for defining competence
Authors: Keith Siau, Toshio Kuwai, Sauid Ishaq
Journal: Gut (2017)

We read with interest and commend the study by Ward and colleagues which explores the learning curve in gastroscopy.1 The authors apply a D2 intubation rate of >95% as a proxy marker of trainee competency, and conclude that 187–200 procedures are sufficient to achieve this, in line with Joint Advisory Group (JAG) certification criteria.2 We would like to debate the following points with the authors.

While we agree that D2 intubation and J-maneouvre reflect procedural completion and rely on motor skill, we argue that this stand-alone measure is insufficient to define competence. Competence is defined by the American Society for Gastrointestinal Endoscopy as the ’minimal level of skill, knowledge and/or expertise derived through training and experience that is required to safely and proficiently perform …
Effects of Ultraviolet Radiation on Sodium Thymonucleate
Authors: Alexander Hollaender, Jesse P. Greenstein, Wendell V. Jenrette
Journal: JNCI Journal of the National Cancer Institute (1941)

Effects of Ultraviolet Radiation on Sodium Thymonucleate Get access Alexander Hollaender, Alexander Hollaender senior biophysicist Division of Industrial Hygiene Search for other works by this author on: Oxford Academic PubMed Google Scholar Jesse P. Greenstein, Jesse P. Greenstein research fellow Search for other works by this author on: Oxford Academic PubMed Google Scholar Wendell V. Jenrette Wendell V. Jenrette junior physiologist National Cancer Institute, National Institute of Health, United States Public Health Service Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 2, Issue 1, August 1941, Pages 23–28, https://doi.org/10.1093/jnci/2.1.23 Published: 01 August 1941
Meeting the Needs of Patients for Specialty Care
Authors: Mitchell H. Katz
Journal: JAMA Internal Medicine (2017)

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
Image Gallery: Secondary cutaneous involvement of the ear with systemic small lymphocytic lymphoma: a rare manifestation
Authors: M. de Brito, P. Gazzani, R. Amel-Kashipaz, B. Vydianath, J.J. Scarisbrick
Journal: British Journal of Dermatology (2017)

Funding sources: none. Conflicts of interest: none declared. Dear Editor, A 67‐year‐old man with known systemic small lymphocytic lymphoma (SLL) under observation presented with a 7‐month history of biauricular, tender, red‐to‐purple induration (a, b). Histology revealed dermal infiltration by small atypical lymphocytes (c, d). Immunophenotyping confirmed the same small clonal B‐cell population in skin and blood (e, CD20+). Cutaneous involvement of SLL, the lymph node counterpart of chronic lymphocytic leukaemia (CLL), is rare; this is the second reported case affecting both ears symmetrically.1,2 Following localized radiotherapy there was partial symptomatic response at 15 months. This is the first report of biauricular SLL demonstrating partial response to radiotherapy monotherapy.
Celiac Disease and Nonceliac Gluten Sensitivity
Authors: Maureen M. Leonard, Anna Sapone, Carlo Catassi, Alessio Fasano
Journal: JAMA (2017)

<h3>Importance</h3> The prevalence of gluten-related disorders is rising, and increasing numbers of individuals are empirically trying a gluten-free diet for a variety of signs and symptoms. This review aims to present current evidence regarding screening, diagnosis, and treatment for celiac disease and nonceliac gluten sensitivity. <h3>Observations</h3> Celiac disease is a gluten-induced immune-mediated enteropathy characterized by a specific genetic genotype (<i>HLA-DQ2</i>and<i>HLA-DQ8</i>genes) and autoantibodies (antitissue transglutaminase and antiendomysial). Although the inflammatory process specifically targets the intestinal mucosa, patients may present with gastrointestinal signs or symptoms, extraintestinal signs or symptoms, or both, suggesting that celiac disease is a systemic disease. Nonceliac gluten sensitivity is diagnosed in individuals who do not have celiac disease or wheat allergy but who have intestinal symptoms, extraintestinal symptoms, or both, related to ingestion of gluten-containing grains, with symptomatic improvement on their withdrawal. The clinical variability and the lack of validated biomarkers for nonceliac gluten sensitivity make establishing the prevalence, reaching a diagnosis, and further study of this condition difficult. Nevertheless, it is possible to differentiate specific gluten-related disorders from other conditions, based on currently available investigations and algorithms. Clinicians cannot distinguish between celiac disease and nonceliac gluten sensitivity by symptoms, as they are similar in both. Therefore, screening for celiac disease must occur before a gluten-free diet is implemented, since once a patient initiates a gluten-free diet, testing for celiac disease is no longer accurate. <h3>Conclusions and Relevance</h3> Celiac disease and nonceliac gluten sensitivity are common. Although both conditions are treated with a gluten-free diet, distinguishing between celiac disease and nonceliac gluten sensitivity is important for long-term therapy. Patients with celiac disease should be followed up closely for dietary adherence, nutritional deficiencies, and the development of possible comorbidities.
Deletion of 11q in Neuroblastomas Drives Sensitivity to PARP Inhibition
Authors: Elena Sanmartín, Lisandra Muñoz, Marta Piqueras, J. Antoni Sirerol, Pablo Berlanga, Adela Cañete, Victoria Castel, Jaime Font de Mora
Journal: Clinical Cancer Research (2017)

Purpose: Despite advances in multimodal therapy, neuroblastomas with hemizygous deletion in chromosome 11q (20%-30%) undergo consecutive recurrences with poor outcome. We hypothesized that patients with 11q-loss may share a druggable molecular target(s) that can be exploited for a precision medicine strategy to improve treatment outcome.Experimental Design: SNP arrays were combined with next-generation sequencing (NGS) to precisely define the deleted region in 17 primary 11q-loss neuroblastomas and identify allelic variants in genes relevant for neuroblastoma etiology. We assessed PARP inhibitor olaparib in combination with other chemotherapy medications using both in vitro and in vivo models.Results: We detected that ATM haploinsufficiency and ATM allelic variants are common genetic hallmarks of 11q-loss neuroblastomas. On the basis of the distinct DNA repair pathways triggered by ATM and PARP, we postulated that 11q-loss may define a subgroup of neuroblastomas with higher sensitivity to PARP inhibitors. Noteworthy, concomitant treatment with olaparib and DNA alkylating agent temozolomide potently inhibited growth of cell lines harboring 11q-loss. This drug synergism was less potent when temozolomide was exchanged for cisplatin or irinotecan. Intact 11q cells concomitantly treated with ATM inhibitor displayed growth arrest and enhanced apoptosis, revealing a role for ATM in the mechanism that mediates sensitivity to temozolomide-olaparib. Interestingly, functional TP53 is required for efficacy of this treatment. In an in vivo model, coadministration of temozolomide-olaparib resulted in sustained xenograft regression.Conclusions: Our findings reveal a potent synergism between temozolomide and olaparib in treatment of neuroblastomas with 11q-loss and provide a rationale for further clinical investigation. Clin Cancer Res; 23(22); 6875-87. ©2017 AACR.
Tumor- and class-specific patterns of immune-related adverse events (irAEs) of immune checkpoint inhibitors (ICIs): A systematic review (SR).
Authors: Daphne Day, Leila Khoja, Tom Wei-Wu Chen, Lillian L. Siu, Aaron Richard Hansen
Journal: Journal of Clinical Oncology (2016)

3065 Background: ICIs targeting cytotoxic T-lymphocyte antigen 4 (CTLA-4), programmed cell death protein 1 (PD-1) and its ligand (PD-L1) produce a unique profile of toxicities driven by T cell tissue infiltration. The objective of this SR was to identify patterns and incidence of irAEs based on tumor type and ICI class. Methods: A SR was performed in MEDLINE, EMBASE and COCHRANE databases to identify prospective trials investigating single agent ICIs up to Nov 2015. Paired reviewers selected studies for inclusion and extracted data. Odds ratio (OR) with 95% confidence interval (CI) was used to quantify the effect of variables on the incidence of irAEs and contingency table p values were calculated using the chi-squared test. Results: We identified 48 clinical trials with a total of 6872 patients (pts), including 27 CTLA-4, 17 PD-1, 2 CTLA-4 vs PD-1 and 2 PD-L1 monoclonal antibody (mAb) trials. Nine were phase III and 39 were phase I/II trials. Grade 3/4 irAEs were more common with CTLA-4 mAbs compared with PD-1 mAbs (31% vs 10%). All grades colitis (OR 8.7, 95% CI 5.8-12.9), hypophysitis (6.5, 3.0-14.3) and rash (2.0, 1.8-2.3) were more common with CTLA-4 mAbs; whereas pneumonitis (6.4, 3.2-12.7), hypothyroidism (4.3, 2.9-6.3), arthralgia (3.5, 2.6-4.8) and vitiligo (3.5, 2.3-5.3) were more common with PD-1 mAbs. Comparison of irAEs from the 3 most studied tumor types in PD-1 mAbs trials [melanoma (n = 2048), non-small cell lung cancer (NSCLC, n = 1030) and renal cell carcinoma (RCC, n = 573)] showed that melanoma pts had a higher frequency of gastrointestinal and skin irAEs and lower frequency of pneumonitis (Table). Conclusions: We demonstrated that CTLA-4 and PD-1 mAbs have distinct irAE profiles presumably by checkpoint-specific immune modulation. Different immune microenvironments may drive histology-specific irAE patterns. Other tumor-dependent irAE profiles may be identified as data emerge from ICI trials. irAE Melanoma vs NSCLC Melanoma vs RCC OR 95% CI pvalue OR 95% CI pvalue Colitis 4.2 1.3-14.0 0.01 No event in RCC Diarrhea 1.9 1.5-2.5 < 0.001 1.3 1.1-1.8 0.04 Pruritus 2.4 1.9-3.1 1.5 1.2-2.0 0.003 Rash 1.8 1.4-2.3 1.6 1.2-2.1 0.002 Pneumonitis 0.4 0.3-0.7 0.3 0.2-0.6 < 0.001
Divergent Epigenomes in Pediatric and Adult Acute Myeloid Leukemia Implicate Cell of Origin and Transcriptional Silencing of Immune Responses As Sources of Clinically Relevant Heterogeneity: A Report from the Children's Oncology Group and NCI/COG Therapeutically Applicable Research to Generate Effective Treatments (TARGET) Initiative
Authors: Timothy Junius Triche, Jason E Farrar, Hamid Bolouri, Rhonda E. Ries, Emilia L. Lim, Todd A. Alonzo, Yussanne Ma, Richard Moore, Andrew J. Mungall, Marco A. Marra, Jaime M. Guidry Auvil, Tanja M. Davidsen, Patee Gesuwan, Leandro C. Hermida, E. Anders Kolb, Alan Gamis, Malcolm A. Smith, Stephen R Piccolo, Daniela S Gerhard, Soheil Meshinchi
Journal: Blood (2016)
Response by Veerman et al to Letter Regarding Article, “The Brugada Syndrome Susceptibility Gene <i>HEY2</i> Modulates Cardiac Transmural Ion Channel Patterning and Electrical Heterogeneity”
Authors: Christiaan C. Veerman, Ronald Wilders, Arthur A. Wilde, Ruben Coronel, Carol Ann Remme, Arie O. Verkerk, Connie R. Bezzina
Journal: Circulation Research (2017)
Comparative efficacy of multiple myeloma therapies for treatment of first relapse: A systematic literature review and network meta-analysis.
Authors: Eric M Maiese, Jean-Gabriel Le Moine, Claire Ainsworth, Outi Ahdesmäki, Emma Howe
Journal: Journal of Clinical Oncology (2017)

8042 Background: Treatment for multiple myeloma (MM) in the US has undergone significant advances, with several new therapies recently FDA approved for relapse/refractory MM (RRMM), including carfilzomib+lenalidomide+dex (KRd), carfilzomib+dex (Kd), daratumumab+lenalidomide+dex (DRd), daratumumab+bortezomib+dex (DVd), ixaxomib+lenalidomide+dex (IRd), and elotuzumab+lenalidomide+dex (ERd). These new therapies have shown improvements in clinical outcomes in randomized controlled trials (RCTs). However, with few head-to-head RCTs, there is little comparative evidence to determine the most effective treatment for specific patients. A systematic literature review (SLR) and network meta-analysis (NMA) was conducted to determine the comparative efficacy (progression free survival (PFS)) of MM therapies for treating first relapse. Methods: The SLR searched MEDLINE, Embase, and the Cochrane Library for RCTs investigating the efficacy of treatments for RRMM (to August 2016). NMA was conducted on the PFS hazard ratios (HR), where available in RCTs for patients with one prior line of treatment, using Bayesian fixed effects mixed treatment comparisons. Results: Data formed two evidence networks. Network 1: RCTs with Rd; Network 2: RCTs with Vd. Analyses found DRd and DVd had the highest probability of being the best treatment (0.96 and 0.89, respectively). Compared to other MM therapies, DRd and DVd had the lowest risk of progression or death (PFS HR &lt;1.0) (Table 1). For example, compared to KRd, DRd had a 41% (PFS HR 0.59) reduced risk of progression or death. Conclusions: This analysis provides comparative evidence among treatments where head-to-head RCTs have not been conducted. For treating first relapse, compared to other MM treatments, this analysis found that DRd and DVd had the highest probability of providing the longest progression free survival. [Table: see text]
ReACT: Overall survival from a randomized phase II study of rindopepimut (CDX-110) plus bevacizumab in relapsed glioblastoma.
Authors: David A. Reardon, James Schuster, David Dinh Tran, Karen L. Fink, Louis B. Nabors, Gordon Li, Daniela Annenelie Bota, Rimas Vincas Lukas, Annick Desjardins, Lynn Stuart Ashby, J Paul Duic, Maciej M. Mrugala, Andrea Werner, Thomas Hawthorne, Yi He, Jennifer A Green, Michael Jay Yellin, Christopher D. Turner, Thomas A. Davis, John H. Sampson
Journal: Journal of Clinical Oncology (2015)

2009 Background: EGFRvIII, a constitutively active EGFR deletion driver mutation, is associated with poor long-term survival in glioblastoma (GB). The investigational vaccine rindopepimut consists of a peptide sequence unique to EGFRvIII conjugated to keyhole limpet hemocyanin (KLH), delivered intradermally with GM-CSF. Three phase II studies of rindopepimut in newly diagnosed, resected, EGFRvIII+ GB demonstrated encouraging progression-free survival (PFS), overall survival (OS) and safety profile. Compassionate use experience suggests that rindopepimut may also provide benefit in relapsed GB, particularly with agents such as bevacizumab (BV). Methods: In the Phase II "ReACT" study, BV-naïve pts in 1st or 2nd relapse with EGFRvIII+ GB were randomized 1:1 to BV plus double-blinded injection of rindopepimut or control (KLH). Endpoints: 6-month PFS (PFS6; primary), objective response rate (ORR), PFS, OS and safety. Results: Accrual is complete (n = 72); study follow-up continues (n = 30). Primary rindopepimut toxicity is Grade 1-2 injection site reaction. For rindopepimut+BV vs. KLH+BV (per investigator; RANO criteria): PFS6 = 27% (9/33) vs. 11% (4/35) (p = 0.048, 1-side chi-square test); ORR = 24% (7/29) vs. 17% (5/30). Central PFS/ORR assessment is underway. Median (95% CI) OS = 12.0 (9.7, -) vs. 8.8 (6.8, 11.4) months (HR = 0.47 [0.25, 0.91]; p = 0.0208), with 8 vs 4 pts progression-free on study. OS analyses favor rindopepimut including when adjusted for various prognostic factors. Rindopepimut induced robust anti-EGFRvIII titers (1:12,800 to 1:6,553,600) in 80% of pts. Rapid anti-EGFRvIII titer generation was associated with prolonged OS (HR = 0.47 [0.18, 1.27]; p = 0.128) within the rindopepimut arm, and was most frequent in pts with KPS ≥ 90 (odds ratio = 9.75; p = 0.007). Additional evaluation of humoral response quality and HLA typing vs. outcome are underway. In an additional cohort of BV-exposed pts (n = 53), four pts experienced objective tumor response. Conclusions: These near-final data show that rindopepimut induces potent EGFRvIII-specific immune response and tumor regression, and appears to significantly prolong survival when administered with BV, in pts with relapsed GB. Clinical trial information: NCT01498328.
Type I interferons and the cytokine TNF cooperatively reprogram the macrophage epigenome to promote inflammatory activation
Authors: Sung Ho Park, Kyuho Kang, Eugenia Giannopoulou, Yu Qiao, Keunsoo Kang, Geonho Kim, Kyung-Hyun Park-Min, Lionel B Ivashkiv
Journal: Nature Immunology (2017)
Use is declining and may peak again around 1999
Authors: J. J Ferguson, M. G V Jenkins
Journal: BMJ (1996)

The continuation rates and satisfaction among the women suggest that our counselling was adequate, although there is no room for compla- cency: despite having been counselled separately, none of the 100 women thought that they had had too much information and 18 thought that they had not had enough.The main things that they thought they were uninformed about were irregular bleeding and discomfort over the site of the implant.The lack of problems with removal vindicates the insistence on adequate training.No method of contraception is completely free of problems, but correct, complete, understandable information and, in this case, appropriate training for insertion and removal are essential so as not to restrict women's choices unnecessarily.
Neuropsychiatric adverse effects of montelukast in children
Authors: Pierre Ernst, Geneviève Ernst
Journal: European Respiratory Journal (2017)

Asthma is the most common chronic disease of childhood. It is associated with significant morbidity and costs including missed time from school and work for children and their parents. For those children ≥5 years of age with persistent symptoms or frequent exacerbations, inhaled corticosteroids (ICS) provide an effective and safe treatment, at least at low doses. However, parents are often concerned about their systemic absorption. Common adverse drug reactions with ICS include oropharyngeal thrush and slowing in growth; the latter results, on average, in a 1-cm decrement in adult height [1]. Partly as a result of the fear of adverse events with corticosteroids, ICS may be underprescribed and adherence to sustained treatment with these agents is poor. Furthermore, adolescents may find that one pill a day is less obtrusive and easier to remember. In this context, leukotriene receptor antagonists such as montelukast are attractive. Montelukast, as a daily controller medication, provides efficacy similar, although less potent, than ICS with the possibility of improved adherence such that the overall clinical benefit may be equal [2]. Montelukast is therefore frequently used as the initial controller therapy as well as in addition to low-dose ICS. The latter indication is the one recognised by asthma guidelines [3]. Neuropsychiatric ADRs of montelukast are common and difficult to recognise in children <http://ow.ly/wlzW30cQn0f>
Adherence to NCCN survivorship guidelines in non-small cell lung cancer (NSCLC) and colorectal cancer (CRC).
Authors: Crystal Shereen Denlinger, Kelly Filchner, Margaret Anne O'Grady, Elaine Sein, Elyse Slater, Michael Slifker, Samuel Litwin, Hossein Borghaei, Steven J. Cohen
Journal: Journal of Clinical Oncology (2014)

e20593 Background: NCCN guidelines on NSCLC and CRC include principles of survivorship care. We assessed adherence to survivorship guidelines in an academic cancer center and community practice network prior to delivery of an educational initiative on survivorship care. Methods: Retrospective chart audits evaluated adherence to survivorship guidelines in four elements: surveillance, prevention, intervention, and care coordination. Each element included multiple components per NCCN guidelines. Tumor registry identified charts. Eligibility: stage I-III CRC/NSCLC, curative therapy completed > 6 months prior to audit, no metastatic disease, and receiving surveillance care at participating site (> 1 visit 2009-2013). Optimal care was defined as documentation of discussion/review of all four elements. Strict adherence included documentation of all components in an element. Liberal adherence included documentation of > 1 component in an element. Up to 20 charts/disease site/practice were audited. Additional audits after an educational initiative presentation are planned. Results: 151 NSCLC and 221 CRC (167 colon/54 rectal) charts at 16 sites were audited. Patient (pt) characteristics: NSCLC 59%F/41%M, CRC 52%F, 48%M. Tumor characteristics: NSCLC clinical stage IA 21%, IB 9%, IIA 14%, IIB 10%, IIIA 33%, IIIB 9%, any TNxM0 3%; CRC pathologic stage 0 1%, I 18%, IIA 30%, IIB 2%, IIC 2%, IIIA 9%, IIIB 29%, IIIC 9%. 62% (93/151) NSCLC pts had surgery and 44% (66/151) received chemoradiation. 64% (141/221) CRC pts received adjuvant chemotherapy; 61% (9/167 colon, 52/54 rectal) received chemoradiation. Conclusions: Comprehensive survivorship care with strict adherence to NCCN guideline recommendations is uncommon. Most survivors receive some components of all four survivorship care elements. NSCLC survivors may be at higher risk of receiving incomplete survivorship care. The impact of provider education on optimal care delivery is being evaluated. Chart documentation of adherent care. Optimal (4 elements) Satisfactory (3 elements) Inadequate (< 2 elements) Strict Liberal Strict Liberal Strict Liberal Colon 5% 84% 65% 16% 30% 0 Rectal 6% 93% 4% 7% 90% 0 Colorectal 5% 86% 50% 14% 44% 0 NSCLC 2% 24% 7% 71% 91% 5%