tbuckley/cabot-search huggingface dataset:
Assessment of Sepsis-3 criteria and quick SOFA in patients with cirrhosis and bacterial infections
Authors: Salvatore Piano, Michele Bartoletti, Marta Tonon, Maurizio Baldassarre, Giada Chies, Antonietta Romano, Pierluigi Viale, Elia Vettore, Marco Domenicali, Marialuisa Stanco, Chiara Pilutti, Anna Chiara Frigo, Alessandra Brocca, Mauro Bernardi, Paolo Caraceni, Paolo Angeli
Journal: Gut (2017)

Introduction Patients with cirrhosis have a high risk of sepsis, which confers a poor prognosis. The systemic inflammatory response syndrome (SIRS) criteria have several limitations in cirrhosis. Recently, new criteria for sepsis (Sepsis-3) have been suggested in the general population (increase of Sequential Organ Failure Assessment (SOFA) ≥2 points from baseline). Outside the intensive care unit (ICU), the quick SOFA (qSOFA (at least two among alteration in mental status, systolic blood pressure ≤100 mm Hg or respiratory rate ≥22/min)) was suggested to screen for sepsis. These criteria have never been evaluated in patients with cirrhosis. The aim of the study was to assess the ability of Sepsis-3 criteria in predicting in-hospital mortality in patients with cirrhosis and bacterial/fungal infections. Methods 259 consecutive patients with cirrhosis and bacterial/fungal infections were prospectively included. Demographic, laboratory and microbiological data were collected at diagnosis of infection. Baseline SOFA was assessed using preadmission data. Patients were followed up until death, liver transplantation or discharge. Findings were externally validated (197 patients). Results Sepsis-3 and qSOFA had significantly greater discrimination for in-hospital mortality (area under the receiver operating characteristic (AUROC)=0.784 and 0.732, respectively) than SIRS (AUROC=0.606) (p&lt;0.01 for both). Similar results were observed in the validation cohort. Sepsis-3 (subdistribution HR (sHR)=5.47; p=0.006), qSOFA (sHR=1.99; p=0.020), Chronic Liver Failure Consortium Acute Decompensation score (sHR=1.05; p=0.001) and C reactive protein (sHR=1.01;p=0.034) were found to be independent predictors of in-hospital mortality. Patients with Sepsis-3 had higher incidence of acute-on-chronic liver failure, septic shock and transfer to ICU than those without Sepsis-3. Conclusions Sepsis-3 criteria are more accurate than SIRS criteria in predicting the severity of infections in patients with cirrhosis. qSOFA is a useful bedside tool to assess risk for worse outcomes in these patients. Patients with Sepsis-3 and positive qSOFA deserve more intensive management and strict surveillance.
Adjuvant Dabrafenib plus Trametinib in Stage III<i>BRAF</i>-Mutated Melanoma
Authors: Georgina V. Long, Axel Hauschild, Mario Santinami, Victoria Atkinson, Mario Mandalà, Vanna Chiarion-Sileni, James Larkin, Marta Nyakas, Caroline Dutriaux, Andrew Haydon, Caroline Robert, Laurent Mortier, Jacob Schachter, Dirk Schadendorf, Thierry Lesimple, Ruth Plummer, Ran Ji, Pingkuan Zhang, Bijoyesh Mookerjee, Jeff Legos, Richard Kefford, Reinhard Dummer, John M. Kirkwood
Journal: New England Journal of Medicine (2017)

Combination therapy with the BRAF inhibitor dabrafenib plus the MEK inhibitor trametinib improved survival in patients with advanced melanoma with BRAF V600 mutations. We sought to determine whether adjuvant dabrafenib plus trametinib would improve outcomes in patients with resected, stage III melanoma with BRAF V600 mutations.In this double-blind, placebo-controlled, phase 3 trial, we randomly assigned 870 patients with completely resected, stage III melanoma with BRAF V600E or V600K mutations to receive oral dabrafenib at a dose of 150 mg twice daily plus trametinib at a dose of 2 mg once daily (combination therapy, 438 patients) or two matched placebo tablets (432 patients) for 12 months. The primary end point was relapse-free survival. Secondary end points included overall survival, distant metastasis-free survival, freedom from relapse, and safety.At a median follow-up of 2.8 years, the estimated 3-year rate of relapse-free survival was 58% in the combination-therapy group and 39% in the placebo group (hazard ratio for relapse or death, 0.47; 95% confidence interval [CI], 0.39 to 0.58; P<0.001). The 3-year overall survival rate was 86% in the combination-therapy group and 77% in the placebo group (hazard ratio for death, 0.57; 95% CI, 0.42 to 0.79; P=0.0006), but this level of improvement did not cross the prespecified interim analysis boundary of P=0.000019. Rates of distant metastasis-free survival and freedom from relapse were also higher in the combination-therapy group than in the placebo group. The safety profile of dabrafenib plus trametinib was consistent with that observed with the combination in patients with metastatic melanoma.Adjuvant use of combination therapy with dabrafenib plus trametinib resulted in a significantly lower risk of recurrence in patients with stage III melanoma with BRAF V600E or V600K mutations than the adjuvant use of placebo and was not associated with new toxic effects. (Funded by GlaxoSmithKline and Novartis; COMBI-AD ClinicalTrials.gov, NCT01682083 ; EudraCT number, 2012-001266-15 .).
Reconstruction of enhancer–target networks in 935 samples of human primary cells, tissues and cell lines
Authors: Qin Cao, Christine Anyansi, Xihao Hu, Liangliang Xu, Lei Xiong, Wenshu Tang, Myth T S Mok, Chao Cheng, Xiaodan Fan, Mark Gerstein, Alfred S L Cheng, Kevin Y Yip
Journal: Nature Genetics (2017)
FRI0480 Scoring syndesmophytes on ct spine images of patients with radiographic axial spondyloarthritis from the sensitive imaging of axial spondyloarthritis (SIAS) cohort
Authors: F de Bruin, R van den Berg, X Baraliakos, J Braun, F van Gaalen, M Reijnierse, D van der Heijde
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Low dose Computed Tomography (CT) could potentially be more sensitive than radiographs in the follow up of patients with axial spondyloarthritis (axSpA). <h3>Objectives</h3> Our first goal was to develop a scoring method for the spine and test its interreader variability and frequency of progression in the various parts of the spine. <h3>Methods</h3> Patients (pts) of the Sensitive Imaging of Axial Spondyloarthritis (SIAS) cohort fulfilled the modified New York (mNY) criteria, had ≥1 syndesmophyte in cervical or lumbar spine on radiographs and ≥1 inflammatory lesion on MRI-spine. Baseline and 2 years follow up low-dose CT scans (approximately 2–3 mSV) were performed. Syndesmophytes were scored in the coronal and sagittal planes for all "corners" per view, thus scoring 8 9quadrants9 per vertebral unit (VU). Syndesmophytes were scored as absent (score 0), &lt;50% of the intervertebral disc height (IVDH) (score 1), ≥50% of the IVDH but no bridging (score 2) or as "bridging the IDVH" (score 3). Score range 0–552. Two readers, blinded for clinical information and time order, scored the CT scans paired by patient. Scores of the 2 readers were compared using heatmaps. Interreader variability was assessed by (two-way average) ICC and smallest detectable change (SDC) for the whole spine and per segment. <h3>Results</h3> In total, 56 pts (84% male, mean age 48.6) were included. The heatmap (fig 1) presents the similarity in basseline and change scores per reader per VU (VU on the y-axis). Ankylosis (score 3) is most prevalent in the thoracic spine, and syndesmophytes in general are least prevalent in the cervical spine. Both readers use almost the entire possible range, pick up a similar magnitude of change and have high ICCs. Most change is present in the thoracic spine. A change ≥SDC is seen in 33.9% of the patients. <h3>Conclusions</h3> A fine-grained scoring system for CT spine was developed. Scoring syndesmophytes with good accuracy on CT images was feasible, picking up changes over a 2-year period in a high percentage of patients, especially in the thoracic spine, which is insufficiently visible on radiographs. <h3>Disclosure of Interest</h3> None declared
Vascular remodelling in the pulmonary circulation after major lung resection
Authors: Nina Rol, Chris Happé, Jeroen A.M. Beliën, Frances S. de Man, Nico Westerhof, Anton Vonk-Noordegraaf, Katrien Grünberg, Harm J. Bogaard
Journal: European Respiratory Journal (2017)

Lung resection is a standard treatment in patients with clinical stages I and II and selected patients with stage IIIA nonsmall cell lung cancer [1]. Major lung resection (MLR), such as (bi)lobectomy or pneumonectomy, occasionally lead to pulmonary hypertension (PH). Several studies report an increase in pulmonary artery pressures in about one-third of these patients up to 5 years postoperatively [2–4]. The development of PH after MLR may be explained simply by the fact that total cardiac output flows through a smaller vascular bed. Because there are no reports in the literature of histological studies performed after MLR, it remains unknown whether flow-induced structural changes in the remaining lung vasculature lead to progressive increases in pulmonary vascular resistance. Major lung resection results in mild pulmonary vascular remodelling <http://ow.ly/JRvW30doTC0>
<i>Mise en Place</i>
Authors: Carlos A. Rodriguez-Russo
Journal: JAMA Oncology (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 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
CCL2 and T cells in pulmonary fibrosis: an old player gets a new role
Authors: Awo D Osafo-Addo, Erica L Herzog
Journal: Thorax (2017)

Idiopathic pulmonary fibrosis (IPF) is an incurable condition characterised by progressive extracellular matrix deposition and tissue remodelling in the adult human lung.1 Because 5-year mortality rates approach 70%, new approaches to treatment are sorely needed. IPF is thought to result from an abnormal wound healing response caused by an unknown insult to the lung epithelium that results in the recruitment and activation of myofibroblasts via incompletely understood mechanisms.1 The contribution of immune activation to these processes remains unknown. While the contribution of innate cell populations such as macrophages is gaining increased acceptance, the contribution of T cell driven adaptive immune responses remain controversial.2 The paper by Milger et al 3 represents an important step forward in our understanding of this issue.

Historically, IPF has been defined as a non-immune entity due to its lack of an identifiable antigen driven immune response, lack of inflammatory infiltrate on lung biopsy, lack of benefit from conventional immunosuppressive therapies and lack of a requirement for lymphocytes for development of maximal fibrosis in commonly used animal models.1 2 However, the now seminal finding that lymphocyte modulating agents actually worsen outcomes in IPF4 combined with human and animal data demonstrating an imbalance between T helper populations in these settings suggests a critical role …
Disruption of JCAD/KIAA1462, a Coronary Artery Disease-associated Gene Product, Inhibits Angiogenic Processes in Vitro and in Vivo
Authors: Hara Tetsuya, Monguchi Tomoko, Akashi Masaya, Mori Kenta, Iwamoto Noriko, Toh Ryuji, Irino Yasuhiro, Shinohara Masakazu, Furuse Mikio, Ishida Tatsuro, Hirata Ken-Ichi
Journal: Circulation (2016)
Adjuvant Nivolumab versus Ipilimumab in Resected Stage III or IV Melanoma
Authors: Jeffrey Weber, Mario Mandala, Michele Del Vecchio, Helen J. Gogas, Ana M. Arance, C. Lance Cowey, Stéphane Dalle, Michael Schenker, Vanna Chiarion-Sileni, Ivan Marquez-Rodas, Jean-Jacques Grob, Marcus O. Butler, Mark R. Middleton, Michele Maio, Victoria Atkinson, Paola Queirolo, Rene Gonzalez, Ragini R. Kudchadkar, Michael Smylie, Nicolas Meyer, Laurent Mortier, Michael B. Atkins, Georgina V. Long, Shailender Bhatia, Celeste Lebbé, Piotr Rutkowski, Kenji Yokota, Naoya Yamazaki, Tae M. Kim, Veerle de Pril, Javier Sabater, Anila Qureshi, James Larkin, Paolo A. Ascierto
Journal: New England Journal of Medicine (2017)

Nivolumab and ipilimumab are immune checkpoint inhibitors that have been approved for the treatment of advanced melanoma. In the United States, ipilimumab has also been approved as adjuvant therapy for melanoma on the basis of recurrence-free and overall survival rates that were higher than those with placebo in a phase 3 trial. We wanted to determine the efficacy of nivolumab versus ipilimumab for adjuvant therapy in patients with resected advanced melanoma. In this randomized, double-blind, phase 3 trial, we randomly assigned 906 patients (≥15 years of age) who were undergoing complete resection of stage IIIB, IIIC, or IV melanoma to receive an intravenous infusion of either nivolumab at a dose of 3 mg per kilogram of body weight every 2 weeks (453 patients) or ipilimumab at a dose of 10 mg per kilogram every 3 weeks for four doses and then every 12 weeks (453 patients). The patients were treated for a period of up to 1 year or until disease recurrence, a report of unacceptable toxic effects, or withdrawal of consent. The primary end point was recurrence-free survival in the intention-to-treat population. At a minimum follow-up of 18 months, the 12-month rate of recurrence-free survival was 70.5% (95% confidence interval [CI], 66.1 to 74.5) in the nivolumab group and 60.8% (95% CI, 56.0 to 65.2) in the ipilimumab group (hazard ratio for disease recurrence or death, 0.65; 97.56% CI, 0.51 to 0.83; P<0.001). Treatment-related grade 3 or 4 adverse events were reported in 14.4% of the patients in the nivolumab group and in 45.9% of those in the ipilimumab group; treatment was discontinued because of any adverse event in 9.7% and 42.6% of the patients, respectively. Two deaths (0.4%) related to toxic effects were reported in the ipilimumab group more than 100 days after treatment. Among patients undergoing resection of stage IIIB, IIIC, or IV melanoma, adjuvant therapy with nivolumab resulted in significantly longer recurrence-free survival and a lower rate of grade 3 or 4 adverse events than adjuvant therapy with ipilimumab. (Funded by Bristol-Myers Squibb and Ono Pharmaceutical; CheckMate 238 ClinicalTrials.gov number, NCT02388906 ; Eudra-CT number, 2014-002351-26 .).
ハイブリッド足場上の共培養脂肪間葉系幹細胞軟骨細胞を用いた半月板組織の再生:in vivo研究【Powered by NICT】
Authors: Moradi Lida, Vasei Mohammad, M Dehghan Mohammad, Majidi Mohammad, Farzad Mohajeri Saeed, Bonakdar Shahin
Journal: Biomaterials (2017)
Estimation of seasonal influenza vaccine effectiveness using data collected in primary care in France: comparison of the test-negative design and the screening method
Authors: A.M. Vilcu, C. Souty, V. Enouf, L. Capai, C. Turbelin, S. Masse, S. Behillil, M. Valette, C. Guerrisi, L. Rossignol, T. Blanchon, B. Lina, T. Hanslik, A. Falchi
Journal: Clinical Microbiology and Infection (2017)
An immune clock of human pregnancy
Authors: Nima Aghaeepour, Edward A. Ganio, David Mcilwain, Amy S. Tsai, Martha Tingle, Sofie Van Gassen, Dyani K. Gaudilliere, Quentin Baca, Leslie McNeil, Robin Okada, Mohammad S. Ghaemi, David Furman, Ronald J. Wong, Virginia D. Winn, Maurice L. Druzin, Yaser Y. El-Sayed, Cecele Quaintance, Ronald Gibbs, Gary L. Darmstadt, Gary M. Shaw, David K. Stevenson, Robert Tibshirani, Garry P. Nolan, David B. Lewis, Martin S. Angst, Brice Gaudilliere
Journal: Science Immunology (2017)

The maintenance of pregnancy relies on finely tuned immune adaptations. We demonstrate that these adaptations are precisely timed, reflecting an immune clock of pregnancy in women delivering at term. Using mass cytometry, the abundance and functional responses of all major immune cell subsets were quantified in serial blood samples collected throughout pregnancy. Cell signaling-based Elastic Net, a regularized regression method adapted from the elastic net algorithm, was developed to infer and prospectively validate a predictive model of interrelated immune events that accurately captures the chronology of pregnancy. Model components highlighted existing knowledge and revealed previously unreported biology, including a critical role for the interleukin-2-dependent STAT5ab signaling pathway in modulating T cell function during pregnancy. These findings unravel the precise timing of immunological events occurring during a term pregnancy and provide the analytical framework to identify immunological deviations implicated in pregnancy-related pathologies.
血清ペントシジン,糖化最終産物(AGE)は心不全の危険因子
Authors: Koyama Yo, Takeishi Yasuchika, Arimoto Takanori, Niizeki Takeshi, Shishido Tetsuro, Okuyama Hidenobu, Nozaki Naoki, Hirono Osamu, Watanabe Tetsu, Nitobe Joji, Tsunoda Yuichi, Miyashita Takehiko, Takahashi Hiroki, Kubota Isao
Journal: Circulation (2006)
Report of the Inter Society Commission for Heart Disease Resources. Optimal resources for examination of the chest and cardiovascular system. A hospital planning and resource guideline
Authors: M. P. Judkins, H. L. Abrams, J. D. Bristow, E. Carlsson, J. M. Criley, L. P. Elliott, K. B. Ellis, G. C. Friesinger, R. H. Greenspan, M. Viamonte
Journal: Circulation (1976)
Comparison of Allogeneic Stem Cell Transplantation for Transformed Acute Myeloid Leukemia Derived from MDS, CMML or MPN. a Report of the Chronic Malignancies Working Party of EBMT
Authors: Nicolaus Kröger, Diderik-Jan Eikema, Liesbeth De Wreede, Anja van Biezen, Dietrich W. Beelen, Jürgen Finke, Christian Koenecke, Dietger Niederwieser, Martin Bornhäuser, Stefan Schönland, Ghulam J Mufti, Gernot Stuhler, Johan Maertens, Matthias Theobald, Guido Kobbe, Liisa Volin, Gerald Wulf, Peter Kahls, Noel Milpied, Hildegard Greinix, Tamás Masszi, Arnon Nagler, Yves Chalandon, Marie Robin
Journal: Blood (2016)
Severe fever with thrombocytopenia syndrome-associated encephalopathy/encephalitis
Authors: S.Y. Park, J.-S. Kwon, J.Y. Kim, S.-M. Kim, Y.R. Jang, M.-C. Kim, O.-H. Cho, T. Kim, Y.P. Chong, S.-O. Lee, S.-H. Choi, Y.S. Kim, J.H. Woo, S.-H. Kim
Journal: Clinical Microbiology and Infection (2017)
Diverse Cis-Regulatory Mechanisms Contribute to Expression Evolution of Tandem Gene Duplicates
Authors: Luís Baudouin-Gonzalez, Marília A Santos, Camille Tempesta, Élio Sucena, Fernando Roch, Kohtaro Tanaka
Journal: Molecular Biology and Evolution (2017)

Pairs of duplicated genes generally display a combination of conserved expression patterns inherited from their unduplicated ancestor and newly acquired domains. However, how the cis-regulatory architecture of duplicated loci evolves to produce these expression patterns is poorly understood. We have directly examined the gene-regulatory evolution of two tandem duplicates, the Drosophila Ly6 genes CG9336 and CG9338, which arose at the base of the drosophilids between 40 and 60 Ma. Comparing the expression patterns of the two paralogs in four Drosophila species with that of the unduplicated ortholog in the tephritid Ceratitis capitata, we show that they diverged from each other as well as from the unduplicated ortholog. Moreover, the expression divergence appears to have occurred close to the duplication event and also more recently in a lineage-specific manner. The comparison of the tissue-specific cis-regulatory modules (CRMs) controlling the paralog expression in the four Drosophila species indicates that diverse cis-regulatory mechanisms, including the novel tissue-specific enhancers, differential inactivation, and enhancer sharing, contributed to the expression evolution. Our analysis also reveals a surprisingly variable cis-regulatory architecture, in which the CRMs driving conserved expression domains change in number, location, and specificity. Altogether, this study provides a detailed historical account that uncovers a highly dynamic picture of how the paralog expression patterns and their underlying cis-regulatory landscape evolve. We argue that our findings will encourage studying cis-regulatory evolution at the whole-locus level to understand how interactions between enhancers and other regulatory levels shape the evolution of gene expression.
Severe leptospirosis in Morocco: comparative data from the Amazonian area
Authors: Loïc Epelboin, Paul Le Turnier, Emilie Mosnier, Roxane Schaub, Erwann Fontaine, Stéphanie Houcke, Anne Jolivet, Magalie Demar, Mathieu Nacher, Félix Djossou
Journal: Intensive Care Medicine (2017)
Abstract 211: Regulatory T cells improve healing after myocardial infarction
Authors: Stefan Frantz, Johannes Weirather, Benjamin Vogel, Niklas Beyersdorf, Thomas Kerkau, Ulrich Hofmann
Journal: Circulation Research (2013)

Background: The proinflammatory activation of innate immunity by myocardial ischemic injury has been recognized for long time. Our recent data have indicated that activation of CD4+ T cells, presumably by auto-antigen recognition, is a prerequisite for formation of a stable scar and prevention from left ventricular dilation after experimental myocardial infarction in mice. We here hypothesized that regulatory CD4+CD25+Foxp3+CD4+ T cells might improve left ventricular wound healing and prevent from adverse remodeling after myocardial infarction. Results: Experimental myocardial infarction in mice induced the proliferation and activation of CD4+CD25+Foxp3+ regulatory T cells, as demonstrated by intracellular expression of the Ikaros family transcription factor Helios, in heart draining lymph nodes. Pretreatment of mice with an anti-CD25 antibody before myocardial infarction efficiently depleted CD4+CD25+Foxp3+ regulatory T cells and increased mortality after myocardial infarction as compared to mice treated with an isotype-matched control antibody of irrelevant specificity, i.e., 25% survival in anti-CD25 treated mice vs. 55,9% survival in control antibody treated animals. Therapeutic activation of regulatory CD4+CD25+Foxp3+ T cells by a superagonistic anti-CD28 antibody (CD28-SA) applied at day 2 after myocardial infarction prevented, compared to mice treated with an isotype-matched control antibody, from left ventricular rupture and resulted in improved survival (47.1% survival in the control group vs. 76.6% survival in the CD28-SA treated group). CD28-SA treatment lead to expansion of CD4+CD25+Foxp3+ T-cells in the peripheral blood and increased their frequency in the infarcted myocardium. This was associated with increased expression of several molecules known to facilitate wound healing by promoting the formation of a stable scar such as osteopontin and coagulation factor XIII. Conclusion: CD4+CD25+Foxp3+ regulatory T-cells are a prerequisite for proper myocardial wound healing and can be therapeutically activated to improve outcome after experimental myocardial infarction.