tbuckley/cabot-search huggingface dataset:
Temporal associations between national outbreaks of meningococcal serogroup W and C disease in the Netherlands and England: an observational cohort study
Authors: Mirjam J Knol, Susan J M Hahné, Jay Lucidarme, Helen Campbell, Hester E de Melker, Stephen J Gray, Ray Borrow, Shamez N Ladhani, Mary E Ramsay, Arie van der Ende
Journal: The Lancet Public Health (2017)

Since 2009, the incidence of meningococcal serogroup W disease has increased rapidly in the UK because of a single strain (the so-called original UK strain) belonging to the hypervirulent sequence type-11 clonal complex (cc11), with a variant outbreak strain (the so-called 2013 strain) emerging in 2013. Subsequently, the Netherlands has had an increase in the incidence of meningococcal serogroup W disease. We assessed the temporal and phylogenetic associations between the serogroup W outbreaks in the Netherlands and England, and the historical serogroup C outbreaks in both countries.For this observational cohort study, we used national surveillance data for meningococcal serogroup W and serogroup C disease in the Netherlands and England for the epidemiological years (July to June) 1992-93 to 2015-16. We also did whole genome sequencing and core genome multilocus sequence typing (1546 loci) on serogroup W disease isolates from both countries for surveillance years 2008-09 to 2015-16. We used Poisson regression to compare the annual relative increase in the incidence of serogroup W and serogroup C between both countries.In the Netherlands, the incidence of meningococcal serogroup W disease increased substantially in 2015-16 compared with 2014-15, with an incidence rate ratio of 5·2 (95% CI 2·0-13·5) and 11% case fatality. In England, the incidence increased substantially in 2012-13 compared with 2011-12, with an incidence rate ratio of 1·8 (1·2-2·8). The relative increase in the Netherlands from 2014-15 to 2015-16 was 418% (95% CI 99-1248), which was significantly higher than the annual relative increase of 79% (61-99) per year in England from 2011-12 to 2014-15 (p=0·03). Cases due to meningococcal serogroup W cc11 (MenW:cc11) emerged in 2012-13 in the Netherlands. Of 29 MenW:cc11 cases found up to 2015-16, 26 (90%) were caused by the 2013 strain. For both the current serogroup W outbreak and the historical serogroup C outbreak, the increase in incidence started several years later in the Netherlands than in England, the rate of increase was higher in the Netherlands, and age distributions were similar in both countries.Given the historical similarities of meningococcal serogroup W with meningococcal serogroup C emergence, the rapid expansion of the MenW:cc11 2013 strain in the Netherlands, its high case fatality, and the availability of a safe and effective vaccine, urgent consideration is needed for public health interventions in the Netherlands and other affected countries to prevent further serogroup W cases and deaths.National Institute for Public Health and the Environment (Netherlands), Academic Medical Center (Netherlands), and Public Health England.
SAT0375 Metabolomics of sera reveals potential biomarkers of skin fibrosis in systemic sclerosis that correlate with pro-fibrotic gene expression in skin biopsies
Authors: S Ahmed, MK Rai, D Dubey, A Rawat, DP Misra, D Kumar, V Agarwal
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> There is an unmet need for biomarkers in Systemic Sclerosis (SSc). Despite its shortcomings, the modified Rodnan skin score (mRSS) has remained the standard disease assessment tool for SSc. Expression of certain genes, cartilage oligomeric matrix protein (<i>COMP</i>), thrombospondin-1 (<i>THS1</i>), interferon-induced 44 (<i>IFI44</i>) and sialoadhesin (<i>SIG1</i>), and, more recently, Tenascin-C (<i>TNSC</i>), have been shown to correlate with skin fibrosis. However, assessment of the expression of these genes requires a skin biopsy. Hence, we used an open-ended approach to identify a serum-based biomarker of SSc. <h3>Objectives</h3> To identify small molecules in serum that correlate with mRSS and profibrotic genes that are upregulated in skin of SSc patients <h3>Methods</h3> We obtained serum and skin biopsies from 25 consenting adult patients with SSc and serum from 25 age- and sex-similar controls. mRNA levels of five genes: <i>COMP</i>, <i>THS1</i>, <i>IFI44</i>, <i>SIG1</i>, and <i>TNSC</i> were estimated as fold-change relative to Glyceraldehyde 3-phosphate dehydrogenase (<i>GAPDH)</i>, a housekeeping gene. H<sup>1</sup>NMR (Nuclear Magnetic Resonance) based metabolomics studies were performed on the sera using standard protocols. Principal component analysis (PCoA) and Partial Least Squares Discriminant Analysis (PLSDA) were used to delineate metabolites that were different between patients and healthy controls. Then spearman correlations (ρ) of these metabolites with mRSS and the fold-expression of the five pro-fibrotic genes were estimated. <h3>Results</h3> H<sup>1</sup>NMR based metabolomics identified 126 peaks that were different between patients and controls. Out of these, the levels of glycine had the best correlation with pro-fibrotic gene expression (ρ=0.5, p&lt;0.05 for <i>IFI44</i>; ρ=0.44, p&lt;0.05 for <i>TNSC</i>). Choline inversely correlated with <i>SIG1</i> (ρ=-0.41; p=0.05) while Glycerophosphocholine correlated with mRSS (ρ=0.50, p&lt;0.05). <h3>Conclusions</h3> H<sup>1</sup>NMR based metabolomics identified glycine, choline and their metabolites as potential biomarkers for skin fibrosis in SSc. These findings require validation in a larger cohort. <h3>References</h3> Farina G, Lafyatis D, Lemaire R, Lafyatis R. A four-gene biomarker predicts skin disease in patients with diffuse cutaneous systemic sclerosis. Arthritis Rheum. 2010 Feb;62(2):580–8. Bhattacharyya S, Wang W, Morales-Nebreda L, Feng G, Wu M, Zhou X, Lafyatis R, Lee J, Hinchcliff M, Feghali-Bostwick C, Lakota K, Budinger GR, Raparia K, Tamaki Z, Varga J.Tenascin-C drives persistence of organ fibrosis. Nat Commun. 2016 Jun 3;7:11703. <h3>Disclosure of Interest</h3> None declared
Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease
Authors: Paul M Ridker, Brendan M. Everett, Tom Thuren, Jean G. MacFadyen, William H. Chang, Christie Ballantyne, Francisco Fonseca, Jose Nicolau, Wolfgang Koenig, Stefan D. Anker, John J.P. Kastelein, Jan H. Cornel, Prem Pais, Daniel Pella, Jacques Genest, Renata Cifkova, Alberto Lorenzatti, Tamas Forster, Zhanna Kobalava, Luminita Vida-Simiti, Marcus Flather, Hiroaki Shimokawa, Hisao Ogawa, Mikael Dellborg, Paulo R.F. Rossi, Roland P.T. Troquay, Peter Libby, Robert J. Glynn
Journal: New England Journal of Medicine (2017)

Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved.We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death.At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P=0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P=0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P=0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P=0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P=0.31).Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846 .).
Clinical outcomes of patients undergoing antiviral therapy while awaiting liver transplantation
Authors: Juan Manuel Pascasio, Carmen Vinaixa, María Teresa Ferrer, Jordi Colmenero, Angel Rubin, Lluis Castells, María Luisa Manzano, Sara Lorente, Milagros Testillano, Xavier Xiol, Esther Molina, Luisa González-Diéguez, Elena Otón, Sonia Pascual, Begoña Santos, José Ignacio Herrero, Magdalena Salcedo, José Luis Montero, Gloria Sánchez-Antolín, Isidoro Narváez, Flor Nogueras, Álvaro Giráldez, Martín Prieto, Xavier Forns, María-Carlota Londoño
Journal: Journal of Hepatology (2017)
Role of c-MET pathway in the outcome prediction of cetuximab-based therapy in patients with recurrent or metastatic squamous cell carcinoma of the head and neck.
Authors: Victoria Casado, Juan Luis Arranz, Sandra Zazo, Jose Ignacio Martin Valades, Juan Madoz, Manuel Domine, Nuria Perez-Gonzalez, Francisco Lobo, Raul Rincon, Gustavo Rubio, Carmen Canadas, Ana Leon, Yann Izarzugaza, Angel Campos, Gloria Serrano, Cristina Carames, Federico Rojo, Jesus Garcia-Foncillas
Journal: Journal of Clinical Oncology (2012)

5520 Background: Activation of the c-MET oncogene promotes tumor growth, invasion and metastasis in several tumor types. In addition, c-MET has been reported in consort with EGFR and/or be activated as a compensatory pathway in the presence of EGFR blockade resulting a mechanism of acquired resistance to EGFR inhibitors in lung and colorectal carcinoma. We investigated the impact on cetuximab sensitivity of HGF, c-MET, c-MET activation and c-MET gene status in recurrent or metastatic squamous cell carcinoma of the head and neck (HNSCC) patients. Methods: A single-institution retrospective analysis including 50 HNSCC patients was carried out. For each case, formalin-fixed tumor specimens were assayed for HGF, total and phosphorylated Y1234/35 c-MET (p-c-MET) by immunohistochemistry and c-MET gene by FISH. Overexpression criteria were defined by ROC curves for each protein and amplification was defined by &gt;2 copies in at least two of the three studied tumor areas. Results were analyzed for association with clinico-pathological features and survival outcomes for cetuximab-treated patients (median follow-up 75 months). Results: c-MET overexpression was detected in 26 (52%) of patients, c-MET amplification in 15 (30%) and p-c-MET in 12 (24%). Amplification was associated with c-MET overexpression (p=0.004). HGF overexpression was observed in 8 (12%) associated with c-MET phosphorylation (p=0.001), suggesting a paracrine activation of receptor. No significant association with clinico-pathological parameters was detected. Log-rank test showed significantly worse outcome in c-MET overexpressing patients for progression-free (PFS) (p=0.002) and overall survival (OS) (p=0.045); p-c-MET was correlated with worse PFS (p=0.014) and OS (p&lt;0.001). In multivariate logistic regression analysis, p-c-MET was an independent prognostic factor for PFS (HR 6.5; 95% CI 1.5-8.9). Conclusions: HGF/c-MET pathway correlated with worse outcome in cetuximab-based regimen treated HNSCC patients, acting as a resistance mechanism for EGFR inhibitors and supporting a dual blocking HGF/c-MET and EGFR pathways for treatment of these patients.
Adult Hemoglobin Production, Chain Rebalance, and Splice Correction in IVS2-745 Beta-Thalassemia Patient Cells Using 2'-O-Methoxyethyl Splice-Switching Oligos
Authors: Alisa Cheung Dong, Valentina Ghiaccio, Irene Motta, Shuling Guo, Raechel Peralta, Coralea Stephanou, Paola Delbini, Connie Chen, Soteroula Christou, Marina Kleanthous, Maria Domenica Cappellini, Osheiza Abdulmalik, Laura Breda, Stefano Rivella
Journal: Blood (2016)
Man versus Nature — <i>Also Sprach Zarathustra</i> and an End-of-Life House Call
Authors: Maxwell M. Krem
Journal: New England Journal of Medicine (2017)

Reluctantly leaving an end-of-life house call with a patient who has decided to avail himself of his state’s death-with-dignity law, a physician hears a musical composition that reframes the experience in terms of the dialectic of Man versus Nature.
RNA interference efficiently targets human leukemia driven by a fusion oncogene in vivo
Authors: N Jyotsana, A Sharma, A Chaturvedi, M Scherr, F Kuchenbauer, L Sajti, A Barchanski, R Lindner, F Noyan, K-W Sühs, D Grote-Koska, K Brand, H-P Vornlocher, M Stanulla, B Bornhauser, J-P Bourquin, M Eder, F Thol, A Ganser, R K Humphries, E Ramsay, P Cullis, M Heuser
Journal: Leukemia (2017)
Effective treatment of drug resistant recurrent breast tumors harboring cancer stem-like cells by staurosporine/epirubicin co-loaded polymeric micelles
Authors: Juanjuan Zhang, Hiroaki Kinoh, Louise Hespel, Xueying Liu, Sabina Quader, John Martin, Tsukasa Chida, Horacio Cabral, Kazunori Kataoka
Journal: Journal of Controlled Release (2017)
Catheter-based renal denervation in patients with uncontrolled hypertension in the absence of antihypertensive medications (SPYRAL HTN-OFF MED): a randomised, sham-controlled, proof-of-concept trial
Authors: Raymond R Townsend, Felix Mahfoud, David E Kandzari, Kazuomi Kario, Stuart Pocock, Michael A Weber, Sebastian Ewen, Konstantinos Tsioufis, Dimitrios Tousoulis, Andrew S P Sharp, Anthony F Watkinson, Roland E Schmieder, Axel Schmid, James W Choi, Cara East, Anthony Walton, Ingrid Hopper, Debbie L Cohen, Robert Wilensky, David P Lee, Adrian Ma, Chandan M Devireddy, Janice P Lea, Philipp C Lurz, Karl Fengler, Justin Davies, Neil Chapman, Sidney A Cohen, Vanessa DeBruin, Martin Fahy, Denise E Jones, Martin Rothman, Michael Böhm, Jiro Aoki, Bryan Batson, Michael Böhm, James W Choi, Debbie L Cohen, George Dangas, Shukri David, Justin Davies, Chandan M Devireddy, David Kandzari, Kazuomi Kario, David P Lee, Philipp C Lurz, Manesh Patel, Kiritkumar Patel, Roland E Schmieder, Andrew S P Sharp, Jasvindar Singh, Konstantinos Tsioufis, Anthony Walton, Thomas Weber, Joachim Weil, Thomas Zeller, Khaled Ziada, Kengo Tanabe, Robert Wilkins, Felix Mahfoud, Cara East, Robert Wilensky, Johanna Contreras, Susan Steigerwalt, Neil Chapman, Janice P Lea, Denise Reedus, Satoshi Hoshide, Adrian Ma, Karl Fengler, Laura Svetkey, Anjani Rao, Axel Schmid, Anthony F Watkinson, Angela Brown, Dimitrios Tousoulis, Ingrid Hopper, Markus Suppan, Tolga Agdirlioglu, Elias Noory, Craig Chasen
Journal: The Lancet (2017)
THU0642 There is a communication problem between patient and physician during pre-conceptional period: hur-bio real life results
Authors: OA Uyaroglu, E Seyhoglu, A Erden, L Kılıç, B Armagan, A Sarı, Ö Karadağ, A Akdoğan, S Bilgen Apraş, S Kiraz, I Ertenli, U Kalyoncu
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> A significant part of patients with inflammatory arthritis are at their reproductive ages. Biological drugs are one of the important treatment options for inflammatory artritis which can cause fetal morbidity and mortality. Management of arthritis during pre-conceptional period is one of the challenges in rheumatology. <h3>Objectives</h3> This study aims to assess whether patients under biological treatment share their conception intents with their physicians. <h3>Methods</h3> 1580 patients admitted to our outpatient clinic between July 2015 and July 2016 who were received biological treatment. A questionnaire was performed to 373 patients who are at their reproductive ages. Patients were asked whether they or their wifes had got pregnant after the start of biological agent. If they had got, they were asked; 1. Was the pregnancy intented? 2. Did your physician know if you were going to get pregnant while taking a biological agent? <h3>Results</h3> There were total of 79 patients who or whose wifes had got pregnant after the start of biological agent. 34 (%43) out of 79 were female and 45 (%57) out of were male. Mean age of patients were 35.1 (5.3). Median disease duration was 10 (IQR=9) years. 24 (30.4%) pregnancies out of 79 were not planned [15 female (44.1%), 9 male (20%), p=0.021]. In addition, 43 (54.4%) out of 79 patients did not share their pregnancy plans with their physicians [15 (44,1%) female and 28 (62,2%) male (p=0.110)]. 28 (35.4%) of all patients stated that their disease was active during pre-conceptional period [20 (58,8%) female patients, 8 (17,8%) male patients, (p&lt;0,001)]. <h3>Conclusions</h3> In our study group, almost one third of the patients had unplanned pregnancies particularly with in female patients. One third of the patients were in active state before conception according to patients9 report. Almost half of the patients did not share their plan of pregnancy with their physicians. We suggest that in routine practise, physicians should ask plan of pregnancy in every clinical visit. <h3>Disclosure of Interest</h3> None declared
Clinical features and outcomes of extramedullary myeloid sarcoma in the United States: analysis using a national data set
Authors: G Goyal, A C Bartley, M M Patnaik, M R Litzow, A Al-Kali, R S Go
Journal: Blood Cancer Journal (2017)

3][4][5] The prognostic factors and outcomes of extramedullary MS are unclear.Similar to AML, the current National Comprehensive Cancer Network guidelines recommend initial treatment with induction chemotherapy for all patients diagnosed with extramedullary MS. 6 In this study, we utilized the National Cancer Database (NCDB) to describe the clinical features, prognostic factors and early treatment outcomes in extramedullary MS.We identified patients with a histologically confirmed diagnosis of extramedullary MS from 2004 to 2013 using International Classification of Diseases for Oncology version 3 (ICD-O-3) code 9930 from the NCDB.The NCDB is a joint program of the Commission on Cancer of the American College of Surgeons and the American Cancer Society that collects outcomes data for over 1500 Commission-accredited cancer programs in the nation, and accounts for 470% of new cancer diagnoses. 7 Primary site codes were used to group extramedullary MS patients by location.We excluded patients whose primary site code was bone marrow.We analyzed overall survival (OS) using Kaplan-Meier estimates and their differences between race and sex using log-rank tests.To allow for ⩾ 1 year of follow-up, we excluded patients diagnosed in 2013 from OS analysis.To ascertain accuracy of follow-up, the OS analysis also excluded patients whose treatment decisions were made at a facility outside of the reporting facility.Multivariate analysis was performed adjusting for age, sex, race and disease location.Because NCDB records only the initial treatment and not subsequent therapies, we performed a landmark OS analysis among those patients who survived ⩾ 1 month according to treatments received during the first month after diagnosis.We investigated the effect of early chemotherapy, surgery and radiation on survival using Cox regression models.This analysis was done separately for patients older and younger than 70years of age.A total of 94 185 cases of AML were reported from 2004 to 2013.During this time period, there were 746 patients diagnosed with extramedullary MS and comprised 0.8% of all AML diagnoses.The median age was 59 years (range, 41-73), and 56.1% were male.The distribution by race was 80.2% White, 9.1% Black, 2.9% Asian, and 7.8% others/unknown.Primary site was divided into 11 categories based on organ involved at presentation of extramedullary MS (Table 1).The three most common sites of presentation were connective/soft tissues (31.3%), skin/breast (12.3%) and digestive system (10.3%).The median OS for the entire cohort was 12.8 months.According to OS, we categorized the patients into three prognostic groups: good (OS 430 months: reproductive and digestive systems), intermediate (OS 15-30 months: head/neck, skin/breast and kidney/bladder/retroperitoneum/adrenal) and poor (OS o 15 months: nervous system,
The FGF21-CCL11 Axis Mediates Beiging of White Adipose Tissues by Coupling Sympathetic Nervous System to Type 2 Immunity
Authors: Zhe Huang, Ling Zhong, Jimmy Tsz Hang Lee, Jialiang Zhang, Donghai Wu, Leiluo Geng, Yu Wang, Chi-Ming Wong, Aimin Xu
Journal: Cell Metabolism (2017)
High-Altitude Illness
Authors: Peter H. Hackett, Robert C. Roach
Journal: New England Journal of Medicine (2001)

The term “high-altitude illness” is used to describe the cerebral and pulmonary syndromes that can develop in unacclimatized persons shortly after ascent to high altitude. Acute mountain sickness and high-altitude cerebral edema refer to the cerebral abnormalities, and high-altitude pulmonary edema to the pulmonary abnormalities. Because millions of visitors travel to high-altitude locations each year, acute mountain sickness is a public health problem and has economic consequences, especially for the ski industry. High-altitude pulmonary edema and high-altitude cerebral edema, though uncommon, are potentially fatal. High-altitude illness also provides a useful model for studying the pathophysiological process of hypoxia in an . . .
Comprehensive evaluation of the revised international staging system in multiple myeloma patients treated with novel agents as a primary therapy
Authors: Hyungwoo Cho, Dok Hyun Yoon, Jung Bok Lee, Sung‐Yong Kim, Joon Ho Moon, Young Rok Do, Jae Hoon Lee, Yong Park, Ho Sup Lee, Hyeon Seok Eom, Ho‐Jin Shin, Chang‐Ki Min, Jin Seok Kim, Jae‐Cheol Jo, Hye Jin Kang, Yeung‐Chul Mun, Won Sik Lee, Je‐Jung Lee, Cheolwon Suh, Kihyun Kim
Journal: American Journal of Hematology (2017)

Abstract The revised International Staging System (R‐ISS) has recently been developed to improve the risk stratification of multiple myeloma (MM) patients over the ISS. We assessed the R‐ISS in MM patients who were treated with novel agents as a primary therapy and evaluated its discriminative power and ability to reclassify patients from the ISS. A total of 514 newly diagnosed MM patients treated with novel agents including thalidomide, bortezomib, and lenalidomide as a primary therapy were included in this retrospective analysis. With a median follow‐up duration of 42.3 months (range, 40.5–44.1), the median overall survival (OS) was 61.0 months. There was a significant difference in median OS (not reached, 60.9, and 50.1 months for stages 1, 2, and 3, respectively, P &lt; 0.001) among the three stages of R‐ISS. The C‐statistic was significantly greater for R‐ISS than for ISS (0.769 vs. 0.696, P &lt; 0.001). The event NRI was −0.08 (95% confidence interval [CI], −0.18–0.01) and the non‐event NRI was 0.05 (95% CI, −0.03–0.10), resulting in a total NRI of −0.03 (95% CI, −0.14–0.08, P = 0.602). The R‐ISS performs well and has significantly better discriminative power than the ISS in MM patients treated with novel agents as a primary therapy. However, it does not better reclassify patients from the ISS, suggesting that there is still room to improve the staging system. Moreover, new statistical measures for assessing and quantifying the risk prediction of new prognostic models are necessary in future studies.