tbuckley/cabot-search huggingface dataset:
Effects of Bariatric Surgery in Obese Patients With Hypertension
Authors: Carlos Aurelio Schiavon, Angela Cristine Bersch-Ferreira, Eliana Vieira Santucci, Juliana Dantas Oliveira, Camila Ragne Torreglosa, Priscila Torres Bueno, Julia Caldas Frayha, Renato Nakagawa Santos, Lucas Petri Damiani, Patricia Malvina Noujaim, Helio Halpern, Frederico L.J. Monteiro, Ricardo Vitor Cohen, Carlos H. Uchoa, Marcio Gonçalves de Souza, Celso Amodeo, Luiz Bortolotto, Dimas Ikeoka, Luciano F. Drager, Alexandre Biasi Cavalcanti, Otavio Berwanger
Journal: Circulation (2017)

Background: Recent research efforts on bariatric surgery have focused on metabolic and diabetes mellitus resolution. Randomized trials designed to assess the impact of bariatric surgery in patients with obesity and hypertension are needed. Methods: In this randomized, single-center, nonblinded trial, we included patients with hypertension (using ≥2 medications at maximum doses or &gt;2 at moderate doses) and a body mass index between 30.0 and 39.9 kg/m 2 . Patients were randomized to Roux-en-Y gastric bypass plus medical therapy or medical therapy alone. The primary end point was reduction of ≥30% of the total number of antihypertensive medications while maintaining systolic and diastolic blood pressure &lt;140 mm Hg and 90 mm Hg, respectively, at 12 months. Results: We included 100 patients (76% female, mean age 43.8±9.2 years, mean body mass index 36.9±2.7 kg/m2), and 96% completed follow-up. Reduction of ≥30% of the total number of antihypertensive medications while maintaining controlled blood pressure occurred in 41 of 49 patients from the gastric bypass group (83.7%) compared with 6 of 47 patients (12.8%) from the control group with a rate ratio of 6.6 (95% confidence interval, 3.1–14.0; P &lt;0.001). Remission of hypertension was present in 25 of 49 (51%) and 22 of 48 (45.8%) patients randomized to gastric bypass, considering office and 24-hour ambulatory blood pressure monitoring, respectively, whereas no patient submitted to medical therapy was free of antihypertensive drugs at 12 months. A post hoc analysis for the primary end point considering the SPRINT (Systolic Blood Pressure Intervention Trial) target reached consistent results, with a rate ratio of 3.8 (95% confidence interval, 1.4–10.6; P =0.005). Eleven patients (22.4%) from the gastric bypass group and none in the control group were able to achieve SPRINT levels without antihypertensives. Waist circumference, body mass index, fasting plasma glucose, glycohemoglobin, low-density lipoprotein cholesterol, triglycerides, high-sensitivity C-reactive protein, and 10-year Framingham risk score were lower in the gastric bypass than in the control group. Conclusions: Bariatric surgery represents an effective strategy for blood pressure control in a broad population of patients with obesity and hypertension. Clinical Trial Registration: URL: https://clinicaltrials.gov . Unique identifier: NCT01784848.
Guías clínicas del Grupo BICHAT sobre agentes utilizados como armas biológicas
Authors: P Bossi, F van Loock, A Tegnell, G Gouvras
Journal: Eurosurveillance (2004)

La emision deliberada de esporas de B. anthracis en los Estados Unidos poco tiempo despues del ataque terrorista del 11 de Septiembre de 2001, supuso un cambio radical en la percepcion del riesgo de bioterrorismo por parte de la poblacion.
Improved outcome for AML patients over the years 2000–2014
Authors: Sarah Bertoli, Suzanne Tavitian, Anne Huynh, Cécile Borel, Sarah Guenounou, Isabelle Luquet, Eric Delabesse, Audrey Sarry, Guy Laurent, Michel Attal, Françoise Huguet, Emilie Bérard, Christian Récher
Journal: Blood Cancer Journal (2017)

Abstract Few recent studies from registries have reported an improvement in overall survival of younger patients with acute myeloid leukemia (AML). However, reasons for this improvement are not defined. We analyzed the therapeutic course and outcome of 976 patients treated by intensive chemotherapy between 2000 and 2014. The number of patients receiving allogeneic stem cell transplantation in first or second response significantly increased over time whereas autologous transplantation was progressively abandoned. In the 513 younger patients, there were no differences in first complete response, induction failure, incidence of relapse, or non-relapse mortality over time. The period of time was significantly associated with a better overall survival especially in 2010–2014. The 2010–2014 period effect was still significant in multivariate analysis and was independent of allogeneic stem cell transplantation. In the 463 older patients, there was a significant interaction between the period and leukocytosis in multivariate analysis meaning that the 2010–2014 period had only an impact in patients with white blood cell count &gt;50 giga/L for response and overall survival. Progresses have been made in each phase of the therapeutic course of younger AML patients resulting in survival improvement. In older patients, the outcome of hyperleukocytic patients has significantly improved in 2010–2014.
Clinical comparison of ABP 215 and bevacizumab in patients with NSCLC: Pharmacokinetic results and justification for extrapolation across bevacizumab indications.
Authors: Nick Thatcher, Michael Thomas, Zhiying Pan, Jerome H. Goldschmidt, Michael Schenker, Rebeca Melara, Vladimir Hanes
Journal: Journal of Clinical Oncology (2017)

9050 Background: Approval of biosimilars is based on totality of evidence (TOE) that includes demonstration of analytical, functional, and pharmacokinetic (PK) similarity, and comparable clinical efficacy, safety, and immunogenicity. The TOE supports scientific justification for extrapolation across other indications that a share common mechanism of action (MOA). The proposed biosimilar ABP 215 is similar to bevacizumab (BEV) with respect to inhibition of vascular endothelial growth factor (VEGF)-induced signaling; PK in healthy adults; and clinical efficacy, safety, and immunogenicity in patients with non-small cell lung cancer (NSCLC). The PK results from the NSCLC study are reported here. Methods: In this double-blind study, adults with non-squamous NSCLC receiving first-line chemotherapy with carboplatin and paclitaxel were randomized 1:1 to ABP 215 or BEV (15 mg/kg IV Q3W for 6 cycles). Trough (pre-dose) PK samples were collected at baseline, at weeks 4, 7, and 13, and at end of study. Clinical evaluations included efficacy, safety, and immunogenicity. Results: 642 patients (ABP 215, n = 328; BEV, n = 314) were randomized. Demographic and baseline characteristics were well balanced. The primary endpoint of risk ratio for objective response rate was 0.93 (2-sided 90% CI, 0.80-1.09), which was contained within the pre-specified equivalence margin. The incidence of adverse events was comparable between ABP 215 and BEV. During the study, 4 (1.4%) and 7 (2.5%) patients in the ABP 215 and BEV group, respectively, developed binding antibodies; no patient tested positive for neutralizing antibodies. Steady-state trough serum concentrations for both ABP 215 and BEV were reached by week 13 (median 124.9 vs 124.4 µg/mL, respectively) and were consistent between ABP 215 and BEV throughout the study. Conclusions: ABP 215 is similar to BEV in multiple analytical, functional, and clinical assessments. PK results in patients presented here provide further evidence for similarity between ABP 215 and BEV and contribute to the TOE supporting extrapolation of clinical similarity across BEV indications based on its common MOA. Clinical trial information: NCT01966003.
SELECT-4: Phase I dose escalation trial of selumetinib (AZD6244, ARRY-142886) in combination with durvalumab (MEDI4736) in patients with advanced solid tumors.
Authors: Pasi A. Janne, Dana C. Ghiorghiu, Paul D. Smith, Riccardo Belli, Phillip A. Dennis, Gabriella Lucia Mariani
Journal: Journal of Clinical Oncology (2016)

TPS2607 Background: Preclinical studies suggest that intermittent dosing with selumetinib, an oral, potent and highly selective, allosteric MEK1/2 inhibitor with a short half-life, should be evaluated in combination with durvalumab, a selective, high-affinity human IgG1 mAb, that blocks PD-L1 binding to PD-1 and CD80. Selumetinib may prime the immune response and also potentially inhibit T-cell function, thereby maximizing tumor cell damage and antigen presentation during the period of MEK inhibition; intermittent dosing with selumetinib will allow maximal relief of T-cell checkpoint blockade by durvalumab. The SELECT-4 study (NCT02586987) aims to evaluate this combination for the first time in pts. Methods: SELECT-4 is a Phase I, open-label, multicenter, dose escalation study investigating the safety and tolerability of intermittent doses of selumetinib combined with durvalumab in pts with advanced solid tumors for which no standard therapy exists. Selumetinib (starting dose 50 mg po bid, increasing until the maximum tolerated dose is reached) will be given for a 7-day monotherapy run in, then on a 1 week on, 1 week off schedule, every 4 weeks in combination with durvalumab (1500 mg, iv) administered once every 4 weeks. Approximately 20–30 evaluable pts will be enrolled, with up to 6 pts in each dose escalation cohort and 6–10 evaluable pts in a paired biopsy expansion cohort. Additional cohorts may be explored as determined by the Safety Review Committee. Pts must have a WHO performance status of 0‒1 and measurable disease at baseline (RECIST 1.1). Tumor assessments will be performed at screening, then every 8 weeks until confirmed disease progression. The primary objective is to investigate the safety and tolerability of intermittent dosing of selumetinib combined with durvalumab. Secondary objectives include defining the recommended dose for selumetinib combined with durvalumab, preliminary assessment of anti-tumor activity, characterization of population pharmacokinetics for each drug when in combination, and assessment of the immunogenicity of durvalumab. Biomarkers will be assessed as an exploratory objective. Recruitment is ongoing. Clinical trial information: NCT02586987.
Abstract 24061: Targeting Trpv4 Channels Protects Heart From Pathological Remodeling Following Myocardial Infarction
Authors: Ravi K Adapala, Ashot Minasyan, Anantha K Kanugula, Holly C Cappelli, Sailaja Paruchuri, Gary J Meszaros, Charles K Thodeti
Journal: Circulation (2017)

Heart failure is one of the leading causes of death which is often characterized by pathological fibrosis. Cardiac remodeling following myocadial infarction is a multiphase reparative process which involves replacement of damaged tissue with physiological (reparative) fibrosis to form scar that limit the expansion of the infarct. Myofibroblasts are critical mediator of this reparative fibrosis, however, hyperactivation of these cells can cause pathological fibrosis leading to heart failure. We have previously demonstrated that the mechanosensitive ion channel TRPV4 (transient receptor potential vanilloid channel 4) regulates cardiac fibroblast differentiation into myofibroblasts. However, the physiological or translational significance of TRPV4 in cardiac remodeling following MI is unknown. To explore this, we have induced MI (permanent LAD ligation) in WT and TRPV4KO mice and measured cardiac function for 8 weeks. Separately, WT mice were given an orally active TRPV4 antagonist GSK2193874, immediately after MI surgery and followed for 5 weeks. 2D-echocardiography revealed that the cardiac function (ejection fraction and fractional shortening) is preserved post-MI in both TRPV4KO and GSK2193874-treated WT mice compared to either WT or vehicle treated mice. Further, we found reduced cardiac fibrosis at infarcted and remote zones in TRPV4KO and GSK2193874-treated WT mice compared to their MI counter parts. Furthermore, TRPV4KO hearts exhibited decreased cardiomyocyte apoptosis (TUNEL assay) and increased capillary density (CD31 staining) post-MI compared to WT hearts. Our results thus suggest that targeting TRPV4 protects heart from myocardial infarction-induced damage by preserving cardiac structure and function via reduced myocyte apoptosis, diminished fibrosis and increased revascularization, and identifies TRPV4 as a novel therapeutic target for heart failure.
Abstract 20463: Why Do Physicians Not Attend Hospital Resuscitation Training? A Survey Investigating Barriers for Participation
Authors: Kasper G Lauridsen, Rikke Højbjerg, Bo Løfgren
Journal: Circulation (2016)

Introduction:  Cardiopulmonary Resuscitation (CPR) training is important to provide high-quality CPR. CPR training is therefore mandatory in many hospitals. Despite this, some hospital staff does not attend CPR training on a regular basis. Barriers for attending CPR training are sparsely investigated. This study aimed to investigate CPR course attendance, barriers for participating in CPR training and possible initiatives to increase CPR course attendance among hospital physicians.   Methods:  This study included physicians from one university hospital and one regional hospital in the Central Denmark Region. Questionnaires were handed out to physicians at morning staff meeting at departments of internal medicine and surgery. Physicians were grouped as junior physicians (residents) and senior physicians (fellows, attending and chief physicians).   Results:  In total, 138 physicians responded (response rate: 86%, male: 49%). Median postgraduate clinical experience was 11.5 (IQR: 7-22) years. Overall, 36% of physicians had not attended CPR training at the hospital. Median time since last CPR course participation was 24 (12-48) months. Junior physicians had more recent training than senior physicians ((5 (2-12) months versus 25 (14-60) months p   Conclusions:  A significant part of physicians have not attended hospital CPR training. Several barriers for course participation exist of which course registration seems to be a crucial factor. Alternative CPR training methods may help improve training participation.
Abstract 21095: Medical Emergency Team (MET) Criteria in the Intensive Care Unit Setting
Authors: Logan Denny, Adam Deane, Peter T Morley
Journal: Circulation (2017)

Introduction: MET criteria are widely used in the hospital setting to provide an early warning system to facilitate escalation of care. We aimed to determine the proportion of RMH Intensive Care Unit (ICU) patients who have met MET call criteria within several separate 24-hour snapshot periods. The RMH ICU has over 2500 admissions per year (73.6% emergency admissions), with a mean age of 56.4 years, a mean length of stay of 79.6 hours, a mean APACHE 3 score 58.9, and an overall ICU mortality of 8%. Methods: This prospective study collected information retrospectively from a convenience sample, during the period from 01/03/2017 to 08/06/2017. Snapshots were collected at a set time by review of all the current RMH ICU inpatient observation charts, on separate occasions at least two days apart. Observation charts were examined for the prior 24 hours of data, or fewer hours if the patient had been more recently admitted to the ICU. Each of these discrete episodes was examined to determine whether or not specific MET criteria had been met. MET criteria occurring multiple times within one episode were not additionally recorded. The data below is from 10 separate days of data collection. Results: Over 10 separate snapshots examining 237 patient episodes, 230 observation charts could be reviewed. Of the 230 patients, 147 were mechanically ventilated (63.9%), while 116 were receiving vasopressor/inotrope infusions (50.4%). Of the 230 patients, 177 (77%) met at least one MET call criteria in the previous 24-hour period. The most common MET criterion was a spontaneous respiratory rate of &lt;8 breaths/minute (87/230, 37.8%); 86 of these 87 patients were mechanically ventilated. Other MET criteria detected were systolic blood pressure &lt;90 mmHg (60/230, 26.1%), respiratory rate &gt;30 breaths/minute (55/230, 23.9%), heart rate &gt;130 beats/minute (32/230, 13.9%), and pulse oximetry saturation &lt;90% (27/230, 11.7%). 175 of the patients (76.1%) had adjusted daily physiological aims recorded on their observation charts. Conclusions: ICU patients commonly meet standard MET criteria. Unadjusted MET criteria by themselves cannot be used to activate an escalation of care in Intensive Care.
Relative Performance of HPV and Cytology Components of Cotesting in Cervical Screening
Authors: Mark Schiffman, Walter K Kinney, Li C Cheung, Julia C Gage, Barbara Fetterman, Nancy E Poitras, Thomas S Lorey, Nicolas Wentzensen, Brian Befano, John Schussler, Hormuzd A Katki, Philip E Castle
Journal: JNCI Journal of the National Cancer Institute (2017)

The main goal of cervical screening programs is to detect and treat precancer before cancer develops. Human papillomavirus (HPV) testing is more sensitive than cytology for detecting precancer. However, reports of rare HPV-negative, cytology-positive cancers are motivating continued use of both tests (cotesting) despite increased testing costs. We quantified the detection of cervical precancer and cancer by cotesting compared with HPV testing alone at Kaiser Permanente Northern California (KPNC), where 1 208 710 women age 30 years and older have undergone triennial cervical cotesting since 2003. Screening histories preceding cervical cancers (n = 623) and precancers (n = 5369) were examined to assess the relative contribution of the cytology and HPV test components in identifying cases. The performances of HPV testing and cytology were compared using contingency table methods, general estimating equation models, and nonparametric statistics; all statistical tests were two-sided. HPV testing identified more women subsequently diagnosed with cancer (P < .001) and precancer (P < .001) than cytology. HPV testing was statistically significantly more likely to be positive for cancer at any time point (P < .001), except within 12 months (P = .10). HPV-negative/cytology-positive results preceded only small fractions of cases of precancer (3.5%) and cancer (5.9%); these cancers were more likely to be regional or distant stage with squamous histopathology than other cases. Given the rarity of cancers among screened women, the contribution of cytology to screening translated to earlier detection of at most five cases per million women per year. Two-thirds (67.9%) of women found to have cancer during 10 years of follow-up at KPNC were detected by the first cotest performed. The added sensitivity of cotesting vs HPV alone for detection of treatable cancer affected extremely few women.
Clinical Juvenile Arthritis Disease Activity Score proves to be a useful tool in treat-to-target therapy in juvenile idiopathic arthritis
Authors: Joost F Swart, E H Pieter van Dijkhuizen, Nico M Wulffraat, Sytze de Roock
Journal: Annals of the Rheumatic Diseases (2017)

To assess if the Juvenile Arthritis Disease Activity Score (JADAS71) could be used to correctly identify patients with juvenile idiopathic arthritis (JIA) in need of antitumour necrosis factor therapy (anti-TNF) therapy 3 and 6 months after start of methotrexate (MTX).Monocentric retrospective cohort study from 2011 to 2015 analysing all patients with oligoarticular JIA (OJIA) (n=39) and polyarticular course JIA (PJIA) (n=74) first starting MTX. Three and 6 months after MTX start, clinical and laboratory features and the 2011 American College of Rheumatology (ACR) JIA treatment recommendations (ACR clinical practice guideline (ACR-CPG)) were compared between groups starting and not starting anti-TNF therapy. The sensitivity and specificity of the ACR-CPG, JADAS71 and the clinical JADAS to identify non-responders after 12 months were calculated.Physicians escalated patients with significantly higher physician global assessment, clinical JADAS (cJADAS) and patient Visual Analogue Scale (VAS). The decision not to escalate was correct in 70%-75% as shown by MTX response. The implementation of the ACR-CPG would increase the current anti-TNF use from 12% to 65%. The use of (c)JADAS in identifying patients in need of anti-TNF therapy outperformed the ACR-CPG with a much higher sensitivity, specificity and accuracy. The cJADAS threshold for treatment escalation at month 3 and 6 was >5 and >3 for OJIA and >7 and >4 for PJIA, respectively. The performance of the cJADAS decreased when the patient VAS contribution to the total score was restricted and overall did not improve by adding the erythrocyte sedimentation rate.The cJADAS identifies patients in need of anti-TNF and is a user-friendly tool ready to be used for treat to target in JIA. The patient VAS is a critical item in the cJADAS for the decision to escalate to anti-TNF.
A man with paraesthesia, headache, and vertigo
Authors: Jacob O Day, Pragnesh Bhatt
Journal: BMJ (2017)

A 35 year old man presented to hospital with three months’ progressive paraesthesia of his right arm, leg, and torso. He also complained of intermittent headaches, particularly after coughing, and episodes of vertigo. Examination revealed hyperreflexia and numbness, with preserved joint position sense, in the right limbs. Magnetic resonance imaging (MRI) was performed (fig 1). What is the diagnosis?



Fig 1 
Sagittal T2 weighted MRI scan of the neck and cervical spine



Chiari malformation type 1. The MRI scan shows tonsillar descent characteristic of Chiari malformation type 1, and a resulting syringomyelia (fig 2).



Fig 2 
Sagittal T2 MRI scan …
CD4+ and B Lymphocyte Expression Quantitative Traits at Rheumatoid Arthritis Risk Loci in Patients With Untreated Early Arthritis
Authors: Nishanthi Thalayasingam, Nisha Nair, Andrew J. Skelton, Jonathan Massey, Amy E. Anderson, Alexander D. Clark, Julie Diboll, Dennis W. Lendrem, Louise N. Reynard, Heather J. Cordell, Stephen Eyre, John D. Isaacs, Anne Barton, Arthur G. Pratt
Journal: Arthritis & Rheumatology (2017)

Objective Rheumatoid arthritis ( RA ) is a genetically complex disease of immune dysregulation. This study sought to gain further insight into the genetic risk mechanisms of RA by conducting an expression quantitative trait locus ( eQTL ) analysis of confirmed genetic risk loci in CD 4+ T cells and B cells from carefully phenotyped patients with early arthritis who were naive to therapeutic immunomodulation. Methods RNA and DNA were isolated from purified B and/or CD 4+ T cells obtained from the peripheral blood of 344 patients with early arthritis. Genotyping and global gene expression measurements were carried out using Illumina BeadChip microarrays. Variants in linkage disequilibrium ( LD ) with non‐ HLA RA single‐nucleotide polymorphisms (defined as r 2 ≥ 0.8) were analyzed, seeking evidence of cis ‐ or trans ‐ eQTL s according to whether the associated probes were or were not within 4 Mb of these LD blocks. Results Genes subject to cis ‐ eQTL effects that were common to both CD 4+ and B lymphocytes at RA risk loci were FADS 1 , FADS 2 , BLK , FCRL 3 , ORMDL 3 , PPIL 3 , and GSDMB . In contrast, those acting on METTL 21B , JAZF 1 , IKZF 3, and PADI 4 were unique to CD 4+ lymphocytes, with the latter candidate risk gene being identified for the first time in this cell subset. B lymphocyte–specific eQTL s for SYNGR 1 and CD 83 were also found. At the 8p23 BLK – FAM 167A locus, adjacent genes were subject to eQTL s whose activity differed markedly between cell types; in particular, the FAM 167A effect displayed striking B lymphocyte specificity. No trans ‐ eQTL s approached experiment‐wide significance, and linear modeling did not identify a significant influence of biologic covariates on cis ‐ eQTL effect sizes. Conclusion These findings further refine the understanding of candidate causal genes in RA pathogenesis, thus providing an important platform from which downstream functional studies, directed toward particular cell types, may be prioritized.
Feasibility study of preoperative chemotherapy for esophageal cancer with naso-gastric ED tube for patients with difficulty of oral ingestion
Authors: T. Ogata, H. Osakabe, S. Nagasawa, K. Hara, M. Nakazono, Y. Kumazu, T. Hayashi, T. Yamada, T. Yoshikawa
Journal: Annals of Oncology (2017)