tbuckley/cabot-search huggingface dataset:
Review: Opioids improve chronic noncancer pain, but difference may not be clinically meaningful in most patients
Authors: Roger Chou
Journal: Annals of Internal Medicine (2019)

ACP Journal Club16 April 2019Review: Opioids improve chronic noncancer pain, but difference may not be clinically meaningful in most patientsRoger Chou, MDRoger Chou, MDOregon Health & Science University, Portland, Oregon, USA (R.C.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/ACPJ201904160-041 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationBusse JW, Wang L, Kamaleldin M, et al. Opioids for chronic noncancer pain: a systematic review and meta-analysis. JAMA. 2018;320:2448-60. https://pubmed.ncbi.nlm.nih.gov/30561481Clinical Impact RatingsGIM/FP/GP: References1 Olsen MF, Bjerre E, Hansen MD, et al. Minimum clinically important differences in chronic pain vary considerably by baseline pain and methodological factors: systematic review of empirical studies. J Clin Epidemiol. 2018;101:87-106.e2. [PMID: 29793007] Google Scholar2 Moore RA, Derry S, Simon LS, Emery P. Nonsteroidal anti-inflammatory drugs, gastroprotection, and benefit-risk. Pain Pract. 2014;14:378-95. [PMID: 23941628] Google Scholar3 Krebs EE, Gravely A, Nugent S, et al. Effect of opioid vs nonopioid medications on pain-related function in patients with chronic back pain or hip or knee osteoarthritis pain: the SPACE randomized clinical trial. JAMA. 2018;319:872-82. [PMID: 29509867] Google Scholar Author, Article, and Disclosure InformationAffiliations: Oregon Health & Science University, Portland, Oregon, USA (R.C.)This article was published at Annals.org on 2 April 2019. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byMind-body approaches targeting the psychological aspects of opioid use problems in patients with chronic pain: evidence and opportunities 16 April 2019Volume 170, Issue 8Page: JC41Keywords36 item short form health surveyAdverse eventsGrading of Recommendations Assessment Development and EvaluationNeuropathic painOpioidsPainRelative riskSleepSystematic reviewsVomiting ePublished: 16 April 2019 Issue Published: 16 April 2019 Copyright & PermissionsCopyright © 2019 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Abstract 19676: A Positive Genotype Predicts Clinical Outcomes in a Large Cohort With Dilated Cardiomyopathy
Authors: Marta Gigli, Sharon Graw, Gianfranco Sinagra, Teisha Rowland, Marco Merlo, Dobromir Slavov, Davide Stolfo, Mary Sweet, Matteo Dal Ferro, Francesca Brun, Alessandro Altinier, Federica Ramani, Giulia Barbati, Matthew Rg Taylor, Luisa Mestroni
Journal: Circulation (2017)

Introduction: Expansion of genetic testing in Dilated Cardiomyopathy (DCM) has increased mutation detection in patients. Nevertheless, genotype-phenotype correlations are still poorly understood. Hypothesis: To explore the genetic landscape of a large DCM cohort, assessing the effect of carrier status and association between specific genotypes and outcomes. Methods: Four hundred eighty-seven patients with available genetic testing analysis were analyzed and grouped into “gene clusters” with similar functions. Primary prognostic measures included all causes of mortality, heart transplantation or ventricular assist device implantation (D/HTx/VAD). Two secondary end-points were also considered: heart failure (HF)-related death/HTx/VAD (DHF/HTx/VAD) and sudden death (SCD)/major ventricular arrhythmias (MVA). Results: A total of 186 pathogenic/likely pathogenic variants were found in 180 patients (37%). The genetic clusters identified were: 55 (11%) TTNtv; 19 (4%) LMNA; 24 (5%) Structural Cytoskeleton-Z Disk g...
FRI-322-Metabolic inflammation: The role of chemokine C-C motif ligan 2 in the crosstalk between liver tissue and muscle
Authors: Fedra Luciano-Mateo, Noemí Cabré, Gerard Baiges, Elizabet Rodríguez-Tomàs, Salvador Fernández-Arroyo, Anna Hernández-Aguilera, Jordi Camps, Jorge Joven
Journal: Journal of Hepatology (2019)
SAT-392-Dickkopf-1 from hepatocellular carcinoma cells promotes the angiogenic potential of endothelial cells by activating the VEGFR-2 signaling pathway
Authors: Bora Jin, Yechan Jeong, Beom Kyung Kim, Jun Yong Park, Do Young Kim, Kwang-Hyub Han, simon W Ro, Seung Up Kim, Sang Hoon Ahn
Journal: Journal of Hepatology (2019)
Clinical Ethicists Awakened: Addressing Two Generations of Clinical Ethics Issues Involving Undocumented Patients
Authors: Mark Kuczewski
Journal: The American Journal of Bioethics (2019)

Because the United States has failed to provide a pathway to citizenship for its long-term undocumented population, clinical ethicists have more than 20 years of addressing issues that arise in caring for this population. I illustrate that these challenges fall into two sets of issues. First-generation issues involve finding ethical ways to treat and discharge patients who are uninsured and ineligible for safety-net resources. More recently, ethicists have been invited to help address second-generation issues that involve facilitating the presentation for care of undocumented patients. In the current environment of widespread fear of deportation in the immigrant community, ethicists are working with health care providers to address patient concerns that prevent them from seeking care. I illustrate that in both generations of issues, values implicit within health care, namely, caring, efficiency, and promotion of public health, guide the strategies that are acceptable and recommended.
Analysis of the <i>CDKN2A</i> Gene in FAMMM Syndrome Families Reveals Early Age of Onset for Additional Syndromic Cancers
Authors: Candace D. Middlebrooks, Mark L. Stacey, Qing Li, Carrie Snyder, Trudy G. Shaw, Tami Richardson-Nelson, Marc Rendell, Claire Ferguson, Peter Silberstein, Murray J. Casey, Joan E. Bailey-Wilson, Henry T. Lynch
Journal: Cancer Research (2019)

Familial atypical multiple mole melanoma (FAMMM) syndrome is a hereditary cancer syndrome that results from mutations in several genes, including the CDKN2A gene. In addition to melanoma, certain other malignancies such as pancreatic cancer are known to occur more frequently in family members who carry the mutation. However, as these families have been followed over time, additional cancers have been observed in both carriers and noncarriers. We sought to determine whether these additional cancers occur at higher frequencies in carriers than noncarriers. We performed survival analyses using 10 FAMMM syndrome families (N = 1,085 individuals) as well as a mixed effects Cox regression, with age at last visit to the clinic or age at cancer diagnosis as our time variable. This analysis was done separately for the known FAMMM-related cancers and "other" cancer groups. The survival curves showed a significant age effect with carriers having a younger age at cancer onset than noncarriers for FAMMM-related cancers (as expected) as well as for newly associated cancers. The Cox regression reflected what was seen in the survival curves, with all models being highly significant (P = 7.15E-20 and P = 5.00E-13 for the FAMMM-related and other cancers, respectively). These analyses support the hypothesis that CDKN2A mutation carriers in FAMMM syndrome families have increased risk for early onset of several cancer types beyond the known cancers. Therefore, these individuals should be screened for additional cancers, and mutation screening should be extended to more than first-degree relatives of an index carrier patient. SIGNIFICANCE: This study shows that carriers of mutations in the CDKN2A gene in FAMMM syndrome are at increased risk for early onset of several cancer types beyond the known cancers.
Associations between High Temperature, Heavy Rainfall, and Diarrhea among Young Children in Rural Tamil Nadu, India: A Prospective Cohort Study
Authors: Andrew Mertens, Kalpana Balakrishnan, Padmavathi Ramaswamy, Paramasivan Rajkumar, Prabhakar Ramaprabha, Natesan Durairaj, Alan E. Hubbard, Ranjiv Khush, John M. Colford, Benjamin F. Arnold
Journal: Environmental Health Perspectives (2019)

The effects of weather on diarrhea could influence the health impacts of climate change. Children have the highest diarrhea incidence, especially in India, where many lack safe water and sanitation.In a prospective cohort of 1,284 children under 5 y of age from 900 households across 25 villages in rural Tamil Nadu, India, we examined whether high temperature and heavy rainfall was associated with increased all-cause diarrhea and water contamination.Seven-day prevalence of diarrhea was assessed monthly for up to 12 visits from January 2008 to April 2009, and hydrogen sulfide ([Formula: see text]) presence in drinking water, a fecal contamination indicator, was tested in a subset of households. We estimated associations between temperature and rainfall exposures and diarrhea and [Formula: see text] using binomial regressions, adjusting for potential confounders, random effects for village, and autoregressive-1 error terms for study week.There were 259 cases of diarrhea. The prevalence of diarrhea during the 7 d before visits was 2.95 times higher (95% CI: 1.99, 4.39) when mean temperature in the week before the 7-d recall was in the hottest versus the coolest quartile of weekly mean temperature during 1 December 2007 to 15 April 2009. Diarrhea prevalence was 1.50 times higher when the 3 weeks before the diarrhea recall period included [Formula: see text] (vs. 0 d) with rainfall of [Formula: see text] (95% CI: 1.12, 2.02), and 2.60 times higher (95% CI: 1.55, 4.36) for heavy rain weeks following a 60-d dry period. The [Formula: see text] prevalence in household water was not associated with heavy rain prior to sample collection.The results suggest that, in rural Tamil Nadu, heavy rainfall may wash pathogens that accumulate during dry weather into child contact. Higher temperatures were positively associated with diarrhea 1-3 weeks later. Our findings suggest that diarrhea morbidity could worsen under climate change without interventions to reduce enteric pathogen transmission through multiple pathways. https://doi.org/10.1289/EHP3711.
Abstract 14936: Circular Rna CircularFNDC3b Modulates Cardiac Repair After Myocardial Infarction
Authors: Venkata N Garikipati, Suresh K Verma, Zhongjian Cheng, Dongming Liang, May M Truongcao, Maria Cimini, Mohsin Khan, Erhe Gao, David Goukassian, Jeremy E Wilusz, Steven Houser, Walter J Koch, Raj Kishore
Journal: Circulation (2017)

Introduction: Circular RNAs (CircRNAs) are a new addition to the list of growing body of non-coding RNAs. Recent studies highlighted that CircRNA can play an important role in cardiac hypertrophy. ...
Abstract 20287: Tbx6 is Critical for Mesoderm Induction and Specification Into Cardiovascular and Somite Lineages
Authors: Taketaro Sadahiro, Mari Isomi, Naoto Muraoka, Hidenori Kojima, Sho Haginiwa, Shota Kurotsu, Fumiya Tamura, Hidenori Tani, Shugo Tohyama, Kazutaka Miyamoto, Hiroyuki Yamakawa, Keiichi Fukuda, Masaki Ieda
Journal: Circulation (2017)

Mesoderm arises from pluripotent epiblasts and differentiates into multiple lineages. However, the molecular mechanisms underlying this process remain unclear. Tbx6 is enriched in paraxial mesoderm...
SAT-077-Intraperitoneal activation of blood coagulation via tissue factor-exposing extracellular vesicles in patients with advanced chronic liver disease
Authors: Mattias Mandorfer, Johannes Thaler, Lena Hell, Philipp Schwabl, Lukas Wisgrill, Cihan Ay, Peter Quehenberger, Ton Lisman, Rienk Nieuwland, Ingrid Pabinger, Thomas Reiberger
Journal: Journal of Hepatology (2019)
FRI-196-The development of HCC in chronic hepatitis B patients with nucleos (t)ide analogs: Focus on hepatitis B surface antigen and core-related antigen
Authors: Itaru Ozeki, Hirokazu Suii, Ryoji Tatsumi, Masakatsu Yamaguchi, Mutsuumi Kimura, Tomohiro Arakawa, Tomoaki Nakajima, Yasuaki Kuwata, Takumi Ohmura, Shuhei Hige, Yoshiyasu Karino, Joji Toyota
Journal: Journal of Hepatology (2019)
PS-113-Analysis of the HSD17B13: TA allelic variant as a putative protective factor towards hepatocellular carcinoma in patients with and without chronic hepatitis C
Authors: Martina Fazio, Carla De Benedittis, Michela Emma Burlone, Matteo Nazzareno Barbaglia, Ramana Mallela Venkata, Antonio Panero, Rosalba Minisini, Mario Pirisi
Journal: Journal of Hepatology (2019)
Carfilzomib, a second-generation proteasome inhibitor, to enhance the activity of ibrutinib in rituximab-chemotherapy sensitive or resistant B-cell lymphoma cell lines and primary patient samples.
Authors: Qunling Zhang, Juan J Gu, Cory Mavis, Ye Guo, Francisco J. Hernandez-Ilizaliturri, Myron Stefan Czuczman
Journal: Journal of Clinical Oncology (2015)

e19524 Background: Identification of critical signaling pathways required for the development, maintenance and progression of specific subtypes of B-cell lymphoma is essential in order to develop or optimize novel therapeutic agents. We previously demonstrated that the ubiquitin proteasome system (UPS) plays an important role in altering the balance of Bcl-2 family members leading to chemotherapy resistance in rituximab-resistant pre-clinical models. Defining the role of combined targeted agents in the treatment of relapsed/refractory lymphoma or those patients not eligible for high-dose chemotherapy and autologous stem cell support (HDC-ASCT) is necessary. Methods: To this end we studied if carfilzomib (CFZ), an irreversible inhibitor of the UPS could potentiate ibrutinib (IBT) activity in lymphoma pre-clinical models. A panel of rituximab sensitive or resistant lymphoma cell lines and primary tumor cells isolated from lymphoma patients were exposed to CFZ and/or ibrutinib. Changes in cell viability, apoptosis, and expression of Bcl-2 family members were evaluated using the presto blue viability assay, flow cytometry and western blotting respectively. Coefficient of synergy was calculated using the CalcuSyn software. Results: As single agents, CFZ and IBT decreased the cell viability of lymphoma cell lines and primary tumor cells in a dose-dependent manner. Additive effects were observed by combining CFZ and IBT in rituximab-resistant cell lines and primary tumor cells. In addition, in vitro exposure of CFZ and IBT resulted in the up-regulation of pro-apoptotic proteins and PARP cleavage. Conclusions: Our data suggests that multi-step targeting of NFκB signaling pathway (using CFZ and IBT) alter the balance of Bcl-2 family members and results in additive effects. Our data supports further in vivo pre-clinical studies and clinical studies in relapsed/refractory B-cell lymphoma patients.
GS-05-MHC-II invariant chain adjuvanted chimpanzee adenoviral and MVA hepatitis C vaccines elicit unprecedented levels of anti-viral T-cell immune responses in humans
Authors: Ilaria Esposito, Paola Cicconi, Stefania Capone, Anthony Brown, Maria Luisa Esposito, Federica Mori, Ventzislav Vassilev, Loredana Siani, Emma Ghaffari, Claire Gardiner, Celia Mitton, Annette von Delft, Lan Li, Wenqin Li, Paul Klenerman, Stefano Colloca, Alfredo Nicosia, Lucy Dorrell, Antonella Folgori, Ellie Barnes
Journal: Journal of Hepatology (2019)
THU-050-Genetic variants of innate immunity receptors are associated with mortality but not with bacterial infections in liver cirrhosis
Authors: Jelte Schaapman, Amoros Alex, Johannes van der Reijden, Wim Laleman, Stefan Zeuzem, Rafael Bañares, Rajiv Jalan, Vicente Arroyo, H.w. Verspaget, Minneke Coenraad
Journal: Journal of Hepatology (2019)
Langerhans cells mediate the skin‐induced tolerance to ovalbumin via Langerin in a murine model
Authors: Yang Luo, Su Wang, Xiaochun Liu, He Wen, Wei Li, Xu Yao
Journal: Allergy (2019)

Abstract Background Epicutaneous sensitization is an important route of immunization for allergens in atopic diseases; however, studies have also shown that application with protein on the intact skin induces antigen‐specific tolerance. Langerhans cells (LCs) play an immunosuppressive role in several inflammatory skin diseases and mouse models, and the role of LCs in the skin‐induced tolerance is not fully understood. Methods Langerin‐DTA mice that were deficient in LCs were utilized to produce the model of skin‐induced tolerance to ovalbumin (OVA). Binding of Langerin to OVA was analyzed by enzyme‐linked immunosorbent assay, flow cytometry, and immunofluorescence. Homozygous Langerin‐DTR mice that were deficient in Langerin were introduced to assess the role of Langerin in the skin‐induced tolerance. Results Application with OVA onto the intact, but not tape‐stripped, skin attenuated the production of OVA‐specific IgE, IgG1, and IgG2a induced by subsequent subcutaneous immunization with OVA, and the inhibitory effects were abolished in Langerin‐DTA mice. In contrast to the tape‐stripped skin, the intact skin induced the production of IL‐10 by LCs in draining lymph node after application with OVA. Langerin could bind OVA, and homozygous Langerin‐DTR mice demonstrated similar humoral and cellular immune responses in the model of skin‐induced tolerance compared to wide‐type mice. Conclusion Our data suggested that LCs were critical in the intact skin‐induced tolerance to protein antigen via Langerin, and LCs might be targeted via Langerin to regulate the immune responses in systemic and (or) skin inflammatory diseases.
FRI-338-Mitochondrial uncoupler HU6 reduces hepatic oxidative stress in the DIAMOND (TM) mouse model, thus abrogating NASH development
Authors: Francisco Portell, Stephen Eaton, Jameel Dennis, Rebecca Caffrey, Jonathon Marioneaux, Isaac Onyango, Omer Khan, Shaharyar Khan, Arun Sanyal
Journal: Journal of Hepatology (2019)
Campaigners criticise Home Office’s use of child’s medical records to reject family’s asylum request
Authors: Elisabeth Mahase
Journal: BMJ (2019)

The Home Office has used a child’s medical notes to reject her family’s asylum request, claiming that the notes showed that the family were not telling the truth about why they had come to the UK.

The family now faces being removed from the UK, after the Home Office argued that a comment made by the daughter to a psychiatric nurse “significantly undermined” the reason for asylum stated on their application.

The move—revealed by the Sunday Times 1—has been condemned by human rights organisations, which argue that it “breaches doctor-patient confidentiality” and could prevent vulnerable people from seeking medical help.

The issue arose after the Home Office learnt that the daughter had medical issues, which prompted it to request access to her full medical records …
Transforming growth factor (TGF)-beta induces pancreatic cancer cell invasion and epithelial to mesenchymal transition (EMT) in side-population (SP) cells but not in non-SP cells
Authors: Ayano Kabashima, Hajime Higuchi, Yumi Matsuzaki, Go Hasegawa, Naoko Kuriyama, Hiromasa Takaishi, Motoko Izumiya, Hideko Iizuka, Gen Sakai, Toshifumi Hibi
Journal: Cancer Research (2007)

1274  Pancreatic cancer is an aggressive tumor with high invasion potential and metastatic tendency. The epithelial-mesenchymal transition (EMT) describes a process occurring during cancer development by which epithelial cells obtain fibroblast-like properties and show reduced cell adhesion and increased motility. Current concept of cancer stem cell is understood that a small fraction of cancer stem cells exhibit not only a capacity for self-renewal but also a capacity for invasion and metastasis. Recently, a subset of stem cells, termed side population (SP) cells, has been identified and characterized in several mammalian cancers including gastrointestinal carcinomas. Therefore, we formulated a HYPOTHESIS that SP-cells from pancreatic cancer predominantly mediate their malignant potential. Thus, our AIM is to compare the capacity of EMT and invasion between SP cells and non-SP cells in pancreatic cancer. METHODS: A poorly differentiated pancreatic adenocarcinoma cell line, Panc-1, was used in this study. SP cells and non-SP cells were isolated and cultured by a technology using Hoechst 33342 staining and flow cytometry. Both SP cells and non-SP cells were incubated in the presence or absence of TGF-beta (7.5ng/ml) for 3 days. Realtime PCR experiments were performed to identify mRNA expression levels of E-cadherin, Snail, Slug, Vimentin and matrixmetalloproteinase (MMP)-2. Immunoblot analysis was performed to observe protein expression levels of these molecules. A capacity of invasion was assessed by a matrigel invasion assay. RESULTS: Approximately 8% of SP cells were able to be isolated from total Panc-1 cells. Viability and proliferation status were equal between SP-cells and non-SP cells. Incubation with TGF-beta induced significant reduction of E-cadherin mRNA in SP cells (91.0% reduction by realtime PCR). In contrast, Slug, Snail and MMP-2 mRNA increased by incubation with TGF-beta (2.1 fold, 6.7 fold and 2.7 fold increase of baseline, respectively). Immunoblot analysis revealed that E-cadherin protein expression level was dramatically reduced by TGF-beta in SP cells. Surprisingly, all these alterations were minimal or not observed in non-SP cells. An ability of matrigel invasion was significantly increased in SP cells incubated in the presence of TGF-beta, whereas no significant increase in cellular invasion was observed in non-SP cells. In CONCLUSION, these results suggest that SP cells from pancreatic cancer cell line are more responsive to TGF-beta-mediated EMT and invasion, as compare to non-SP cells. SP cells would be attractive target cells for preventing cancer invasion and metastasis.
Association of melanoma expression of matrix metalloproteinase-23 with blunted tumor immunity and poor responses to immunotherapy.
Authors: Duane Moogk, Tianqi Li, Chelsea Lee, Ines Esteves Domingues Pires Da Silva, Michelle W. Ma, Erica Brooke Friedman, Eleazar Vega-Saenz de Miera, Farbod Darvishian, Patrick Scanlon, Arianne Perez-Garcia, Anna C. Pavlick, Nina Bhardwaj, Paul J. Christos, Iman Osman, Michelle Krogsgaard
Journal: Journal of Clinical Oncology (2015)

e20057 Background: Matrix metalloproteinase-23 (MMP-23) can inhibit T cell activation by selectively blocking the voltage-gated potassium channel Kv1.3, and may also alter T cell activity and phenotype through cleavage of proteins affecting cytokine and chemokine signaling. We therefore tested the hypothesis that MMP-23 can negatively regulate the anti-tumor T cell response in human melanoma. Methods: We characterized MMP-23 expression in primary melanoma patients who received adjuvant immunotherapy. We examined the association of MMP-23 with the intrinsic anti-tumor immune response - as assessed by the prevalence of tumor-infiltrating lymphocytes and Foxp3+ regulatory T-cells. Further, we examined the association between MMP-23 expression and response to immunotherapy. We used in vitro 3D culture assays to assess T cell lysis of tumor cells expressing MMP-23, and mutagenesis of MMP-23 functional domains to identify the molecular mechanism of MMP-23 inhibition of T cell responses. Results: Our data revealed an inverse association between primary melanoma MMP-23 expression and the anti-tumor T-cell response, as demonstrated by decreased tumor-infiltrating lymphocytes (TIL) (P= 0.05), in particular brisk TILs (P= 0.04), and a trend towards an increased proportion of immunosuppressive Foxp3+ regulatory T-cells (P= 0.07). High melanoma MMP-23 expression is also associated with recurrence in patients treated with immune biologics (P= 0.037). Further, high melanoma MMP-23 expression is associated with shorter periods of progression-free survival for patients receiving immune biologics. In vitro data supports a role for MMP-23 in blocking Kv1.3 channels on activated effector memory T cells. Conclusions: Our data suggest that MMP-23 may affect Kv1.3-dependent effector memory T cells. This support a potential role for MMP-23 as a biomarker and immunotherapeutic target in melanoma.