tbuckley/cabot-search huggingface dataset:
Work participation in spondyloarthritis across countries: analysis from the ASAS-COMOSPA study
Authors: Santiago Rodrigues Manica, Alexandre Sepriano, Sofia Ramiro, Fernando Pimentel Santos, Polina Putrik, Elena Nikiphorou, Sam Norton, Anna Molto, Maxime Dougados, Désirée van der Heijde, Robert B M Landewé, Filip E van den Bosch, Annelies Boonen
Journal: Annals of the Rheumatic Diseases (2018)

Objectives To explore the role of individual and country level socioeconomic (SE) factors on employment, absenteeism and presenteeism in patients with spondyloarthritis (SpA) across 22 countries worldwide. Methods Patients with a clinical diagnosis of SpA fulfilling the ASAS classification criteria and in working age (≤65 years) from COMOSPA were included. Outcomes of interest were employment status, absenteeism and presenteeism, assessed by the Work Productivity and Activity Impairment Specific General Health questionnaire. Three multivariable models were built (one per outcome) using mixed-effects binomial (for work status) or ordinal regressions (for absenteeism and presenteeism), with country as random effect. The contribution of SE factors at the individual-level (eg, gender, education, marital status) and country-level (healthcare expenditure (HCE) per capita, Human Development Index (HDI) and gross domestic product per capita) SE factors, independent of clinical factors, was assessed. Results In total, 3114 patients with SpA were included of which 1943 (62%) were employed. Physical function and comorbidities were related to all work outcomes in expected directions and disease activity also with absenteeism and presenteeism. Higher education (OR 4.2 (95% CI 3.1 to 5.6)) or living in a country with higher HCE (OR 2.3 (1.5 to 3.6)) or HDI (OR 1.9 (1.2 to 3.3)) was positively associated with being employed. Higher disease activity was associated with higher odds for absenteeism (OR 1.5 (1.3 to 1.7)) and presenteeism (OR 2.1 (1.8 to 2.4)). No significant association between individual-level and country-level SE factors and absenteeism or presenteeism was found. Conclusions Higher education level and higher country SE welfare are associated with a higher likelihood of keeping patients with SpA employed. Absenteeism and presenteeism are only associated with clinical but not with individual-level or country-level SE factors.
Efficacy of self-expandable metal stents compared with multiple plastic stents in benign biliary strictures
Authors: Guido Costamagna
Journal: Endoscopy (2018)

See also: Will Reflux Kill POEM?Endoscopy 2017; 49(07): 625-628DOI: 10.1055/s-0043-112490 See also: Efficacy of self-expandable metal stents in management of benign biliary strictures and comparison with multiple plastic stents: a meta-analysisEndoscopy 2017; 49(07): 682-694DOI: 10.1055/s-0043-109865
Living on a Wire
Authors: Scott Weinreb
Journal: JAMA Cardiology (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 Cardiology 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 Cardiology journal
Benefits and risks from maintenance therapy after first-line chemotherapy in patients with metastatic breast cancer.
Authors: Yunfang Yu, Ying Wang, Quanlong Gao, Qiyun Ou, Dagui Lin, Tuping Fu, Herui Yao
Journal: Journal of Clinical Oncology (2018)

1088 Background: Current guidelines lack definitive evidence regarding the clinical outcomes associated with different maintenance strategies for metastatic breast cancer (MBC). We aimed to investigate the benefits and risks of different maintenance therapy after first-line treatment of MBC. Methods: We searched for randomized clinical trials (RCTs) investigating maintenance chemotherapy, endocrine therapy or immunotherapy after first-line chemotherapy in MBC. The primary endpoint was progression-free survival (PFS); overall survival (OS) and adverse events (AEs) were secondary endpoints. Direct and indirect evidence for data were combined using random-effects meta-analysis. The GRADE system was used to assess the quality of evidence. The PROSPERO registry number is CRD42017071858. Results: A total of 3,290 patients from 16 RCTs were included. Maintenance chemotherapy resulted into a significantly prolonged PFS (hazard ratio [HR] 0.63, 95% confidence interval 0.54 to 0.73, P = 0.000; high certainty) and OS (HR 0.87, 95% CI 0.78 to 0.97, P = 0.016; high certainty) compared with observation, although higher odds of G1-G2 AEs (moderate certainty). Among patients who developed an immune response, maintenance immunotherapy combined with chemotherapy extended PFS (HR 0.57, 95% CI 0.33 to 0.97, P = 0.04; low certainty) and OS (HR 0.71, 95% CI 0.52 to 0.97, P = 0.029; low certainty) than chemotherapy alone. Hormone-receptor-positive patients who received maintenance endocrine therapy might provide similar PFS (HR 1.0, 95% CI 0.70 to 1.50, P = 0.998; very low certainty) and OS (HR 1.15, 95% CI 0.59 to 2.22, P = 0.679; very low certainty) versus chemotherapy, but with lower odds of G1-G2 AEs (moderate certainty). Conclusions: Our study provided strong evidence for OS and PFS benefits of maintenance chemotherapy over observation after first-line chemotherapy in MBC patients. Limited prospective trial indicated that maintenance endocrine therapy was noninferior to chemotherapy with less treatment-related toxicity, which was worthy of a clinical recommendation. Support: ChiCTR-IIR-17014036, SYS-C-201801.
Blocking heteromerization of platelet chemokines ccl5 and cxcl4 reduces inflammation and preserves heart function after myocardial infarction
Authors: T. Vajen, I. Werner, D. Projahn, M. Staudt, A. Curaj, T. T. Soenmez, S. Simsekyilmaz, T. M. Hackeng, P. von Hundelshausen, R. R. Koenen, C. Weber, E. A. Liehn
Journal: Cardiovascular Research (2016)
Pathway to support and growth: Feasibility of formalized peer mentoring in gynecologic cancer survivorship.
Authors: Nita Karnik Lee, Diane Anderson, Fay J. Hlubocky
Journal: Journal of Clinical Oncology (2018)

164 Background: Peer support among cancer patients is understudied. Formal peer mentoring programs matching patients with survivor peers provides emotional and social support. Gynecological cancer patients are: underserved in the survivorship community, stigmatized due to disease, suffer elevated distress. Little is known on how to design and implement a formal peer support program for gynecologic cancer. Methods: To study the effect of peer support, a novel outpatient pilot peer support program for gynecologic cancer patients was implemented. Peer mentors had prior gynecologic cancers, completed treatment 1 year prior, and had formal 6 hour training. Newly diagnosed patients were matched with a peer at: 1) initial diagnosis 2) post-surgery 3) chemotherapy/radiation initiation 4) post treatment. Patients and Peers were matched based upon demographics. Qualitative individual and group interviews were used for program evaluation. Results: To date, 38 participants are enrolled: 17 peer mentors underwent training and 21 new patients were matched with mentors. Mentor demographics include: Mean age 61.8 (range 48-80), median 62. Ethnicity 65% CA, 30% AA, 5% Latina. Diagnoses were 47% endometrial, 12% cervical and 41% ovarian cancers. 65% of mentors have been matched with patients. Majority of pairs communicated via phone followed by face-to-face encounters. Qualitative program evaluation by mentors revealed barriers including: new patient resistance, readiness, distress. Matched mentors reported themes associated with advocacy, positive patient interactions, personal growth and satisfaction, greater sense of purpose due to their mentor role. Mentors expressed desire for future programs in inpatient/ infusion settings and group education. Programmatic challenges identified included inconsistent provider referrals, matching to disease site/stage, patient readiness to participate as mentees, and management of disease recurrence in mentors. Conclusions: Formalized peer mentoring program is feasible, offers a novel approach to providing psychosocial support for newly diagnosed patients and provides mentors a pathway for positive growth as survivors.
Where are UK trained doctors? The migrant care law and its implications for the NHS–an essay by Julian M Simpson
Authors: Julian M Simpson
Journal: BMJ (2018)

Locally trained doctors tend not to want to work in areas of high deprivation and need, and we continue to rely on foreign trained doctors to fill massive gaps. Medicine should acknowledge this historical trend and tackle the dysfunction arising from its contemporary manifestations, writes <b>Julian M Simpson</b>
Comprehensive transcriptomic profiling to identify breast cancer patients that may be spared adjuvant systemic therapy.
Authors: Martin Sjostrom, S. Laura Chang, Nick Fishbane, Elai Davicioni, Linda Hartman, Erik Holmberg, Felix Y Feng, Corey Wayne Speers, Lori J. Pierce, Per Malmström, Mårten Fernö, Per Karlsson
Journal: Journal of Clinical Oncology (2018)

535 Background: Some women with early stage breast cancer (BC) may not require additional systemic therapy after breast-conserving surgery (BCS). While this subgroup of ultra low-risk women has been difficult to identify with conventional clinical metrics, transcriptomic profiling may offer improved risk stratification. Previously described genomic signatures perform well on the group level, but reports indicate that there may be substantial disagreement between signatures for an individual patient. Methods: We analyzed tumors from 765 patients in the SweBCG91-RT trial, which randomized node-negative BC patients to +/- radiation following BCS, with minimal use of adjuvant systemic treatment (9%). Median follow-up was 18.6 years for breast cancer-specific survival (BCSS). The original study demonstrated a benefit from radiation on locoregional events, but not BCSS. Tumors were profiled with the Affymetrix Human Exon 1.0 ST microarray and 14 genomic signatures from literature (including Mammaprint-like, OncotypeDX-like and PAM50-like signatures) were calculated. The average of all signatures was used as an average genomic risk (AGR), which was further used to derive a novel 141-gene signature, with independent features from the previous signatures. Results: Most previously described signatures performed well in our data and were highly prognostic for BCSS. The performance of AGR was in line with the best individual genomic signatures, and among the systemically untreated, ER+, HER2- and postmenopausal patients (N = 454, 59% of the entire study population), the BCSS at 15 years for the 50% of patients with lowest AGR was 93% (95%CI 90-97%). The 141-gene signature had a similar performance with 92% (95%CI 88-96) BCSS for the 50% of patients with lowest risk at 15 years. Conclusions: AGR, based on 14 previously published signatures, is highly prognostic for BCSS and identifies a large proportion of patients with an excellent outcome. An associated novel 141-gene signature performs similarly and identifies patients that may be spared adjuvant systemic treatment. Based on several individual signatures, AGR and the novel 141-gene signature may be more robust on an individual patient level.
<i>MET</i>-Oncogenic and <i>JAK2</i>-Inactivating Alterations Are Independent Factors That Affect Regulation of PD-L1 Expression in Lung Cancer
Authors: Maria Saigi, Juan J. Alburquerque-Bejar, Anne Mc Leer-Florin, Carolina Pereira, Eva Pros, Octavio A. Romero, Nuria Baixeras, Anna Esteve-Codina, Ernest Nadal, Elisabeth Brambilla, Montse Sanchez-Cespedes
Journal: Clinical Cancer Research (2018)

Abstract Purpose: The blockade of immune checkpoints such as PD-L1 and PD-1 is being exploited therapeutically in several types of malignancies. Here, we aimed to understand the contribution of the genetics of lung cancer to the ability of tumor cells to escape immunosurveillance checkpoints. Experimental Design: More than 150 primary non–small cell lung cancers, including pulmonary sarcomatoid carcinomas, were tested for levels of the HLA-I complex, PD-L1, tumor-infiltrating CD8+ lymphocytes, and alterations in main lung cancer genes. Correlations were validated in cancer cell lines using appropriate treatments to activate or inhibit selected pathways. We also performed RNA sequencing to assess changes in gene expression after these treatments. Results: MET-oncogenic activation tended to associate with positive PD-L1 immunostaining, whereas STK11 mutations were correlated with negative immunostaining. In MET-altered cancer cells, MET triggered a transcriptional increase of PD-L1 that was independent of the IFNγ-mediated JAK/STAT pathway. The activation of MET also upregulated other immunosuppressive genes (PDCD1LG2 and SOCS1) and transcripts involved in angiogenesis (VEGFA and NRP1) and in cell proliferation. We also report recurrent inactivating mutations in JAK2 that co-occur with alterations in MET and STK11, which prevented the induction of immunoresponse-related genes following treatment with IFNγ. Conclusions: We show that MET activation promotes the expression of several negative checkpoint regulators of the immunoresponse, including PD-L1. In addition, we report inactivation of JAK2 in lung cancer cells that prevented the response to IFNγ. These alterations are likely to facilitate tumor growth by enabling immune tolerance and may affect the response to immune checkpoint inhibitors. Clin Cancer Res; 24(18); 4579–87. ©2018 AACR.
Modulation of EZH2 expression in T cells improves efficacy of anti–CTLA-4 therapy
Authors: Sangeeta Goswami, Irina Apostolou, Jan Zhang, Jill Skepner, Swetha Anandhan, Xuejun Zhang, Liangwen Xiong, Patrick Trojer, Ana Aparicio, Sumit K. Subudhi, James P. Allison, Hao Zhao, Padmanee Sharma
Journal: Journal of Clinical Investigation (2018)

Enhancer of zeste homolog 2–mediated (EZH2-mediated) epigenetic regulation of T cell differentiation and Treg function has been described previously; however, the role of EZH2 in T cell–mediated antitumor immunity, especially in the context of immune checkpoint therapy, is not understood. Here, we showed that genetic depletion of EZH2 in Tregs (FoxP3creEZH2fl/fl mice) leads to robust antitumor immunity. In addition, pharmacological inhibition of EZH2 in human T cells using CPI-1205 elicited phenotypic and functional alterations of the Tregs and enhanced cytotoxic activity of Teffs. We observed that ipilimumab (anti–CTLA-4) increased EZH2 expression in peripheral T cells from treated patients. We hypothesized that inhibition of EZH2 expression in T cells would increase the effectiveness of anti–CTLA-4 therapy, which we tested in murine models. Collectively, our data demonstrated that modulating EZH2 expression in T cells can improve antitumor responses elicited by anti–CTLA-4 therapy, which provides a strong rationale for a combination trial of CPI-1205 plus ipilimumab.
Zinc Metallochaperones Reactivate Mutant p53 Using an ON/OFF Switch Mechanism: A New Paradigm in Cancer Therapeutics
Authors: Xin Yu, Samuel Kogan, Ying Chen, Ashley T. Tsang, Tracy Withers, Hongxia Lin, John Gilleran, Brian Buckley, Dirk Moore, Joseph Bertino, Chang Chan, S. David Kimball, Stewart N. Loh, Darren R. Carpizo
Journal: Clinical Cancer Research (2018)

Purpose: Zinc metallochaperones (ZMC) are a new class of anticancer drugs that reactivate zinc-deficient mutant p53 by raising and buffering intracellular zinc levels sufficiently to restore zinc binding. In vitro pharmacodynamics of ZMCs indicate that p53-mutant activity is ON by 4-6 hours and is OFF by 24. We sought to understand the mechanism of this regulation and to translate these findings preclinically. We further sought to innovate the formulation of ZMCs to improve efficacy.Experimental Design: We performed in vitro mechanistic studies to determine the role of cellular zinc homeostatic mechanisms in the transient pharmacodynamics of ZMCs. We conducted preclinical pharmacokinetic, pharmacodynamic, and efficacy studies using a genetically engineered murine pancreatic cancer model (KPC) to translate these mechanistic findings and investigate a novel ZMC formulation.Results:In vitro, cellular zinc homeostatic mechanisms that restore zinc to its physiologic levels function as the OFF switch in ZMC pharmacodynamics. In vivo pharmacokinetic studies indicate that ZMCs have a short half-life (< 30 minutes), which is sufficient to significantly improve survival in mice expressing a zinc-deficient allele (p53R172H) while having no effect in mice expressing a non-zinc-deficient allele (p53R270H). We synthesized a novel formulation of the drug in complex with zinc and demonstrate this significantly improves survival over ZMC1.Conclusions: Cellular zinc homeostatic mechanisms function as an OFF switch in ZMC pharmacodynamics, indicating that a brief period of p53-mutant reactivation is sufficient for on-target efficacy. ZMCs synthesized in complex with zinc are an improved formulation. Clin Cancer Res; 24(18); 4505-17. ©2018 AACR.
FRI0542 Potential nociceptive pain relief of intra-articular saline control in clinical trials of knee osteoarthritis: a systematic review and meta-analysis of randomised trials
Authors: I. Simsek, T. Phalen, A. Bedenbaugh, J. Tambiah
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Hyaluronic acid, corticosteroids and platelet-rich plasma (PRP) are widely used intra-articular (IA) therapies for the management of mild to moderate knee osteoarthritis (OA). Many trials evaluating the efficacy of IA-administered therapies commonly use IA saline injections as a placebo comparator arm. A previously published systematic review Altman et al, 2016 showed significant reductions in pain relief with IA saline in both the short- (3 months) and long-term (6–12 months). <h3>Objectives</h3> The aim of this updated systematic review and meta-analysis was to assess the clinical benefit and harm associated with use of IA saline in trials of IA therapies for patients with painful knee OA. <h3>Methods</h3> We searched MEDLINE and Embase databases for randomised controlled trials (RCTs) published up to and including October 12th, 2017. Two reviewers independently assessed the eligibility of potential reports and the risk of bias of included trials. We analysed short (≤3 months) and long-term (6–12 months) pain reduction from baseline of the saline arm of included trials using standardised mean differences (SMDs; estimated assuming a null-effect in a comparator group) that were weighted and pooled using a random-effects model. Pain scores were transformed to a 100-point scale when necessary. We summarised and presented treatment-related adverse events (AEs) descriptively. <h3>Results</h3> We included 46 RCTs, of which 44 provided sufficient data to be included in the meta-analysis for benefit. IA saline significantly improved short-term knee pain from baseline vs. a null effect for a comparator group across 36 studies involving 1908 patients (SMD −0.85, 95% CI −1.05 to −0.66; I<sup>2</sup>=87%). There was also significant reduction in long-term knee pain following IA injection with saline across 25 studies involving 1758 patients (SMD −0.78, 95% CI −1.02 to −0.55) with a substantial degree of heterogeneity (I<sup>2</sup>=90%). Thirty-three of the included trials reported on adverse events, none of which found any serious treatment-related AEs following IA injection with saline. <h3>Conclusions</h3> The pain relief observed with IA saline should prompt one to consider the added effectiveness of current IA treatments that use saline comparators in clinical studies, and challenges of classifying IA saline injection a "placebo." <h3>Reference</h3> [1] Altman RD, et al. Semin Artrhritis Rheum2016;46:151–9. <h3>Disclosure of Interest</h3> I. Simsek Shareholder of: Samumed, LLC, Employee of: Samumed, LLC, T. Phalen Shareholder of: Samumed, LLC, Employee of: Samumed, LLC, A. Bedenbaugh Shareholder of: Samumed, LLC, Employee of: Samumed, LLC, J. Tambiah Shareholder of: Samumed, LLC, Employee of: Samumed, LLC
The ageing brain in sleep apnoea: paradoxical resilience, survival of the fittest, or simply comparing apples and oranges?
Authors: David Gozal
Journal: European Respiratory Journal (2018)

The elevated prevalence of obstructive sleep apnoea (OSA) and its association with a long and ever expanding list of end-organ morbidities has prompted substantial interest in identifying mechanistic pathways underlying such deleterious consequences, and their potential reversibility with treatment. Over the last several decades, we have witnessed substantial increases in the granularity of the morbid phenotype of OSA, and such observations have prompted us to rethink some of the stricter early concepts. Among them, rather than viewing OSA as a single disease model that is applicable to all patients, we have formulated the conceptual framework of distinct phenotypes of OSA that may be driven by different mechanisms, link to different clinical manifestations, and display divergent responses to therapy [1–6]. In this contextual setting, the aspirational goals of the field are to first and foremost identify those OSA patients likely to benefit from treatment and administer the correct intervention, i.e. precision medicine [7, 8]. Preserved brain integrity in older sleep apnoea patients depends on whether underlying symptoms are present or not <http://ow.ly/O0U530jX1Xp>
Evaluation of Reasons Why Surgical Residents Exceeded 2011 Duty Hour Requirements When Offered Flexibility
Authors: Eddie Blay, Kathryn E. Engelhardt, D. Brock Hewitt, Allison R. Dahlke, Anthony D. Yang, Karl Y. Bilimoria
Journal: JAMA Surgery (2018)

This secondary analysis of data from the FIRST trial examines the reasons surgical residents work beyond the 2011 duty hour restrictions for daily shifts established by the Accreditation Council for Graduate Medical Education.