tbuckley/cabot-search huggingface dataset:
Cluster-Randomized Trial of Devices to Prevent Catheter-Related Bloodstream Infection
Authors: Steven M. Brunelli, David B. Van Wyck, Levi Njord, Robert J. Ziebol, Laurie E. Lynch, Douglas P. Killion
Journal: Journal of the American Society of Nephrology (2018)

Central venous catheters (CVCs) contribute disproportionately to bloodstream infection (BSI) and, by extension, to infection-related hospitalization, mortality, and health care costs in patients undergoing dialysis. Recent product advancements may reduce BSIs, but a sufficiently powered comparative-effectiveness study is needed to facilitate evidence-based patient care decisions. In a 13-month, prospective, cluster-randomized, open-label trial, we compared BSI rates in facilities using ClearGuard HD antimicrobial barrier caps (ClearGuard group) with those in facilities using Tego hemodialysis connectors plus Curos disinfecting caps (Tego+Curos group). Forty DaVita dialysis facilities in the United States were pair-matched by BSI rate, number of patients using CVCs, and geographic location, and then cluster randomized 1:1. We enrolled all adult patients undergoing dialysis with CVCs at these facilities, except those allergic to heparin or chlorhexidine. Overall, 1671 patients participated in the study, accruing &gt;183,000 CVC-days. The study outcome was positive blood culture (PBC) rate as an indicator of BSI rate. We calculated results at the cluster level and adjusted for the facility cluster effect. During a 3-month run-in period immediately before study interventions, the groups had similar BSI rates ( P =0.8). During the 13-month intervention period that immediately followed, the ClearGuard group had a BSI rate significantly lower than that of the Tego+Curos group (0.28 versus 0.75 PBCs per 1000 CVC-days, respectively; P =0.001). No device-related adverse events were reported. In conclusion, compared with Tego connectors plus Curos caps, ClearGuard HD antimicrobial barrier caps significantly lowered the rate of catheter-related BSIs in patients undergoing hemodialysis using CVCs, representing an important advancement in hemodialysis patient care.
Improving the reporting of tennis injuries: the use of workload data as the denominator?
Authors: Machar Reid, Stuart J Cormack, Rob Duffield, Stephanie Kovalchik, Miguel Crespo, Babette Pluim, Danielle T Gescheit
Journal: British Journal of Sports Medicine (2018)

Advances in technology have changed the way that we understand and consume sports performance.From an injury epidemiology perspective, the data generated from these technologies -particularly those related to player exposure or load -can also provide cause to reconsider accepted norms of how to report injury data.Using tennis as a case study, we highlight the opportunity for these new data to provide richer and more meaningful injury insights.
High-throughput metabolomic analysis predicts mode of action of uncharacterized antimicrobial compounds
Authors: Mattia Zampieri, Balazs Szappanos, Maria Virginia Buchieri, Andrej Trauner, Ilaria Piazza, Paola Picotti, Sébastien Gagneux, Sonia Borrell, Brigitte Gicquel, Joel Lelievre, Balazs Papp, Uwe Sauer
Journal: Science Translational Medicine (2018)

The mode of action of new antimicrobial compounds can be predicted from changes in metabolome profiles in Mycobacterium .
Tau Positron Emission Tomography in Autosomal Dominant Alzheimer Disease
Authors: Eric McDade, Randall J. Bateman
Journal: JAMA Neurology (2018)

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NHS England faces legal challenges over proposed changes to services
Authors: Clare Dyer
Journal: BMJ (2018)

NHS England faces two High Court challenges to its proposed introduction of accountable care organisations (ACOs) in England, both arguing that the move is unlawful.

Both legal actions are being brought by campaign groups that say that the plans, which they fear could lead to rationing of resources and part privatisation of the NHS, have been launched without full public consultation.

A grassroots campaign, 999 Call for the NHS, has won permission to apply for a judicial review of the proposals, with a hearing set for 24 April. The case has been brought against NHS England and NHS Improvement.

The other group, JR4NHS, which includes the renowned cosmologist …
Abstract 12842: Regional Relaxation Abnormality Does Not Precede Regional Contraction Abnormality in the Ischemic Myocardium Immediately After Coronary Occlusion
Authors: Erika Iwagami, Toshihiko Asanuma, Kasumi Masuda, Daisuke Sakurai, Toshiki Kamimukai, Satoshi Nakatani
Journal: Circulation (2015)

Background: Although it has been reported that diastolic dysfunction precedes systolic dysfunction in the whole ventricle in the ischemic cascade, it is unclear whether the relaxation abnormality precedes the contraction abnormality in the region of ischemic insult. We investigated the beat-by-beat change of contraction and relaxation parameters after coronary occlusion. Methods: In 13 open-chest dogs, left ventricular short-axis images were continuously acquired with high frame rate speckle tracking echocardiography (109.3 fps, GE Vivid E9) along with hemodynamic data before and after left circumflex coronary artery occlusion (20 consecutive heartbeats after occlusion). Circumferential strain and strain rate were analyzed in the ischemic and non-ischemic regions. Peak systolic strain (ε s ), end-systolic strain (ε es ), and contraction duration as regional contraction parameters and the first positive peak of the strain rate (SR first positive peak ) as a regional relaxation parameter were measured. Results: Negative dP/dt began to decrease and tau began to prolong after the 15th beat of occlusion. In the ischemic region, ε es and contraction duration significantly decreased after the 15th beat, and ε s significantly decreased at the 20th beat. However, SR first positive peak did not decrease during 20 consecutive heartbeats but rather significantly increased after the 15th beat (0.51 ± 0.10 vs. 1.34 ± 0.15 /s, p&lt;0.05). Because the contraction duration was prolonged in the non-ischemic region after the 15th beat, dyssynchrony during the isovolumic relaxation period became remarkable (figure, arrowheads). Conclusions: In the ischemic myocardium immediately after coronary occlusion, the regional relaxation parameter did not become abnormal before the contraction parameter became abnormal. The deterioration of diastolic parameters for the whole ventricle (negative dP/dt and tau) seemed to be due to dyssynchrony during the isovolumic relaxation period.
Abstract 20142: Impaired Intraventricular Blood Transport in Hypertrophic Cardiomyopathy
Authors: Consuelo Fernandez-Aviles, Pablo Martinez-Legazpi, Lorenzo Rossini, Candelas Pérez del Villar, Yolanda Benito, Antonia Delgado-Montero, Ana Gonzalez-Mansilla, Francisco Fernandez-Aviles, J.C. del Alamo, Javier Bermejo, Raquel Yotti
Journal: Circulation (2016)

Intraventricular blood flow patterns in the healthy left ventricle (LV) are determined by the large vortices that develop during diastole. These vortices have been proposed to enhance blood mixing and filling. Patients with hypertrophic cardiomyopathy (HCM) show concentric remodeled LVs with large wall-flow friction that impairs vortex formation. We aimed to assess whether the absence of vortex-mediated flow may alter blood transport and mixing in the LV, facilitating blood stasis and thrombogenesis in HCM.  Two-dimensional flow velocity fields from color Doppler echocardiographic sequences were obtained in 20 patients with HCM and 20 matched control healthy volunteers (LV mass (g): 441±135 vs 127±37, p  HCM group showed significantly larger VDF (0.35±0.11% vs 0.25±0.09%, p=0.006) and lower VRI and VDE (0.11±0.06% vs 0.18±0.07%, p=0.008, and 0.18±0.05% vs 0.23±0.06%, p=0.04) than the control group. Kinetic energy of these regions also showed differences between groups (Kin(VDF): 22.6 ±15.2mJ/m vs 14.6±6.7mJ/m, p=0.04, Kin(VRI): 3.7 ±4.8mJ/m vs 9.1±7.5mJ/m, p=0.01, and Kin(VDE): 7.7 ±3.7mJ/m vs 15.9±13.6 mJ/m, p=0.01). HCM patients showed larger blood apical regions with high TR in contact with the LV wall (aggregate variable C= from 2.1±0.9s to 0.7±0.8s vs 1.3±0.6s to 0.2±0.2s, p  1 to 6s).  Flow transport within the LV is impaired in HCM. In turn, abnormal transport generates regions of blood stasis near the apex that may contribute to the increased thromboembolic risk of HCM.
Abstract 93: Analysis of Serum Levels of Procalcitonin and Serum Amyloid A as Biomarkers of Intravenous immunoglobulin-resistant Kawasaki Disease
Authors: Yumi Mizuno, Kenji Furuno, Mitsuharu Fukazawa, Tomonobu Aoki
Journal: Circulation (2015)

Aim: Immune globulin is the most effective treatment of Kawasaki Disease, however, 15-20% of patients with Kawasaki disease (KD) is resistant to 2g/kg of IVIG (refractory case), and those patients are high risk for complication of coronary artery abnormalities, to detect these refractory KD before treatment of acute phase is very important to determine their treatment, but the methods to predict the refractory case is not yet established. We analyze the relation of IVIG-resistant Kawasaki disease and serum levels of procalcitonin (PCT) or serum amyloid A (SAA). Method: 192 patients with KD were involved in this study, and 48 were IVIG-resistant cases. Refractory case was defined as patients who needed additional treatment with IVIG and/or steroid after the first treatment with total 2g/kg of IVIG. Serum levels of PCT and SAA were measured before treatment, and the relationship to clinical course was analyzed. Result: Median level of PCT of patients with IVIG-resistant KD was 2.24 ng/ml and those with non- IVIG-resistant KD was 0.47 ng/ml, and median levels of PCT of patients with IVIG-resistant KD was significantly higher than those with non- IVIG-resistant KD (p&lt;0.01). Median level of SAA of patients with IVIG-resistant KD was 753.6 μg/ml and those with non- IVIG-resistant KD was 635.9μg/ml and there was no significant difference. We compared the accuracy of prediction of IVIG resistant KD by PCT and SAA using receiver operating characteristic (ROC) analysis. The areas under the receiver operating characteristic curve(AUC) of PCT, SAA and CRP was 0.75, 0.57 and 0.63 respectively. For identification of IVIG-resistant patients, a cut-off point, sensitivity and specificity of PCT, SAA and CRP were as follows, 1.5 ng/ml, 77% and 61%, 444 μg/ml, 83% and 32% and 7.7 mg/dl, 73% and 59%, respectively. Conclusion: As PCT levels of patients with IVIG-resistant Kawasaki disease were significantly higher than those with non- IVIG-resistant KD, PCT could be one of the predictor of IVIG-resistant KD.
Histopathological growth patterns as a candidate biomarker for immunomodulatory therapy
Authors: Pieter-Jan van Dam, Sofie Daelemans, Elizabeth Ross, Yannick Waumans, Steven Van Laere, Emily Latacz, Roanne Van Steen, Christel De Pooter, Mark Kockx, Luc Dirix, Peter B. Vermeulen
Journal: Seminars in Cancer Biology (2018)
Surface receptor Toso controls B cell–mediated regulation of T cell immunity
Authors: Jinbo Yu, Vu Huy Hoang Duong, Katrin Westphal, Andreas Westphal, Abdulhadi Suwandi, Guntram A. Grassl, Korbinian Brand, Andrew C. Chan, Niko Föger, Kyeong-Hee Lee
Journal: Journal of Clinical Investigation (2018)

The immune system is tightly controlled by regulatory processes that allow for the elimination of invading pathogens, while limiting immunopathological damage to the host. In the present study, we found that conditional deletion of the cell surface receptor Toso on B cells unexpectedly resulted in impaired proinflammatory T cell responses, which led to impaired immune protection in an acute viral infection model and was associated with reduced immunopathological tissue damage in a chronic inflammatory context. Toso exhibited its B cell–inherent immunoregulatory function by negatively controlling the pool of IL-10–competent B1 and B2 B cells, which were characterized by a high degree of self-reactivity and were shown to mediate immunosuppressive activity on inflammatory T cell responses in vivo. Our results indicate that Toso is involved in the differentiation/maintenance of regulatory B cells by fine-tuning B cell receptor activation thresholds. Furthermore, we showed that during influenza A–induced pulmonary inflammation, the application of Toso-specific antibodies selectively induced IL-10–competent B cells at the site of inflammation and resulted in decreased proinflammatory cytokine production by lung T cells. These findings suggest that Toso may serve as a novel therapeutic target to dampen pathogenic T cell responses via the modulation of IL-10–competent regulatory B cells.
In situ formed reactive oxygen species–responsive scaffold with gemcitabine and checkpoint inhibitor for combination therapy
Authors: Chao Wang, Jinqiang Wang, Xudong Zhang, Shuangjiang Yu, Di Wen, Quanyin Hu, Yanqi Ye, Hunter Bomba, Xiuli Hu, Zhuang Liu, Gianpietro Dotti, Zhen Gu
Journal: Science Translational Medicine (2018)

Patients with low-immunogenic tumors respond poorly to immune checkpoint blockade (ICB) targeting the programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) pathway. Conversely, patients responding to ICB can experience various side effects. We have thus engineered a therapeutic scaffold that, when formed in situ, allows the local release of gemcitabine (GEM) and an anti-PD-L1 blocking antibody (aPDL1) with distinct release kinetics. The scaffold consists of reactive oxygen species (ROS)-degradable hydrogel that releases therapeutics in a programmed manner within the tumor microenvironment (TME), which contains abundant ROS. We found that the aPDL1-GEM scaffold elicits an immunogenic tumor phenotype and promotes an immune-mediated tumor regression in the tumor-bearing mice, with prevention of tumor recurrence after primary resection.
Aspirin in Patients With Previous Percutaneous Coronary Intervention Undergoing Noncardiac Surgery
Authors: Michelle M. Graham, Daniel I. Sessler, Joel L. Parlow, Bruce M. Biccard, Gordon Guyatt, Kate Leslie, Matthew T.V. Chan, Christian S. Meyhoff, Denis Xavier, Alben Sigamani, Priya A. Kumar, Marko Mrkobrada, Deborah J. Cook, Vikas Tandon, Jesus Alvarez-Garcia, Juan Carlos Villar, Thomas W. Painter, Giovanni Landoni, Edith Fleischmann, Andre Lamy, Richard Whitlock, Yannick Le Manach, Meylin Aphang-Lam, Juan P. Cata, Peggy Gao, Nicolaas C.S. Terblanche, Pamidimukkala V. Ramana, Kim A. Jamieson, Amal Bessissow, Gabriela R. Mendoza, Silvia Ramirez, Pierre A. Diemunsch, Salim Yusuf, P.J. Devereaux
Journal: Annals of Internal Medicine (2017)

Background: Uncertainty remains about the effects of aspirin in patients with prior percutaneous coronary intervention (PCI) having noncardiac surgery. Objective: To evaluate benefits and harms of perioperative aspirin in patients with prior PCI. Design: Nonprespecified subgroup analysis of a multicenter factorial trial. Computerized Internet randomization was done between 2010 and 2013. Patients, clinicians, data collectors, and outcome adjudicators were blinded to treatment assignment. (ClinicalTrials.gov: NCT01082874) Setting: 135 centers in 23 countries. Patients: Adults aged 45 years or older who had or were at risk for atherosclerotic disease and were having noncardiac surgery. Exclusions were placement of a bare-metal stent within 6 weeks, placement of a drug-eluting stent within 1 year, or receipt of nonstudy aspirin within 72 hours before surgery. Intervention: Aspirin therapy (overall trial, n = 4998; subgroup, n = 234) or placebo (overall trial, n = 5012; subgroup, n = 236) initiated within 4 hours before surgery and continued throughout the perioperative period. Of the 470 subgroup patients, 99.9% completed follow-up. Measurements: The 30-day primary outcome was death or nonfatal myocardial infarction; bleeding was a secondary outcome. Results: In patients with prior PCI, aspirin reduced the risk for the primary outcome (absolute risk reduction, 5.5% [95% CI, 0.4% to 10.5%]; hazard ratio [HR], 0.50 [CI, 0.26 to 0.95]; P for interaction = 0.036) and for myocardial infarction (absolute risk reduction, 5.9% [CI, 1.0% to 10.8%]; HR, 0.44 [CI, 0.22 to 0.87]; P for interaction = 0.021). The effect on the composite of major and life-threatening bleeding in patients with prior PCI was uncertain (absolute risk increase, 1.3% [CI, −2.6% to 5.2%]). In the overall population, aspirin increased the risk for major bleeding (absolute risk increase, 0.8% [CI, 0.1% to 1.6%]; HR, 1.22 [CI, 1.01 to 1.48]; P for interaction = 0.50). Limitation: Nonprespecified subgroup analysis with small sample. Conclusion: Perioperative aspirin may be more likely to benefit rather than harm patients with prior PCI. Primary Funding Source: Canadian Institutes of Health Research.
Potential Confounding of Diagnosis of Rabies in Patients with Recent Receipt of Intravenous Immune Globulin
Authors: Neil M. Vora, Lillian A. Orciari, J Bradford Bertumen, Inger Damon, James A. Ellison, Vance G. Fowler, Richard Franka, Brett W. Petersen, P.S. Satheshkumar, Stephen M. Schexnayder, Todd G. Smith, Ryan M. Wallace, Susan Weinstein, Carl Williams, Pamela Yager, Michael Niezgoda
Journal: MMWR Morbidity and Mortality Weekly Report (2018)

Rabies is an acute encephalitis that is nearly always fatal. It is caused by infection with viruses of the genus Lyssavirus, the most common of which is Rabies lyssavirus. The Council of State and Territorial Epidemiologists (CSTE) defines a confirmed human rabies case as an illness compatible with rabies that meets at least one of five different laboratory criteria.* Four of these criteria do not depend on the patient's rabies vaccination status; however, the remaining criterion, "identification of Lyssavirus-specific antibody (i.e. by indirect fluorescent antibody…test or complete [Rabies lyssavirus] neutralization at 1:5 dilution) in the serum," is only considered diagnostic in unvaccinated patients. Lyssavirus-specific antibodies include Rabies lyssavirus-specific binding immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies and Rabies lyssavirus neutralizing antibodies (RLNAs). This report describes six patients who were tested for rabies by CDC and who met CSTE criteria for confirmed human rabies because they had illnesses compatible with rabies, had not been vaccinated for rabies, and were found to have serum RLNAs (with complete Rabies lyssavirus neutralization at a serum dilution of 1:5). An additional four patients are described who were tested for rabies by CDC who were found to have serum RLNAs (with incomplete Rabies lyssavirus neutralization at a serum dilution of 1:5) despite having not been vaccinated for rabies. None of these 10 patients received a rabies diagnosis; rather, they were considered to have been passively immunized against rabies through recent receipt of intravenous immune globulin (IVIG). Serum RLNA test results should be interpreted with caution in patients who have not been vaccinated against rabies but who have recently received IVIG.
Traitement endoscopique des fistules oeso-trachéales bénignes: résultats et facteurs pronostics
Authors: A Debourdeau, JM Gonzalez, A Benezech, M Barthet
Journal: Endoscopy (2018)

Les fistules oesotrachéales (= FOT) bénignes sont des affections rares à l'origine d'une morbi-mortalité importante. Le traitement chirugical est bien codifié, mais il existe peu de données concernant le traitement endoscopique de cette pathologie lorsque la chirurgie n'est pas envisageable. Nous décrivons ici les résultats et les facteurs pronostics associés au traitement endoscopique des FOT.
Self-adjuvanting nanoemulsion targeting dendritic cell receptor Clec9A enables antigen-specific immunotherapy
Authors: Bijun Zeng, Anton P.J. Middelberg, Adrian Gemiarto, Kelli MacDonald, Alan G. Baxter, Meghna Talekar, Davide Moi, Kirsteen M. Tullett, Irina Caminschi, Mireille H. Lahoud, Roberta Mazzieri, Riccardo Dolcetti, Ranjeny Thomas
Journal: Journal of Clinical Investigation (2018)

Non–antigen-specific stimulatory cancer immunotherapies are commonly complicated by off-target effects. Antigen-specific immunotherapy, combining viral tumor antigen or personalized neoepitopes with immune targeting, offers a solution. However, the lack of flexible systems targeting tumor antigens to cross-presenting dendritic cells (DCs) limits clinical development. Although antigen–anti-Clec9A mAb conjugates target cross-presenting DCs, adjuvant must be codelivered for cytotoxic T lymphocyte (CTL) induction. We functionalized tailored nanoemulsions encapsulating tumor antigens to target Clec9A (Clec9A-TNE). Clec9A-TNE encapsulating OVA antigen targeted and activated cross-presenting DCs without additional adjuvant, promoting antigen-specific CD4+ and CD8+ T cell proliferation and CTL and antibody responses. OVA-Clec9A-TNE–induced DC activation required CD4 and CD8 epitopes, CD40, and IFN-α. Clec9A-TNE encapsulating HPV E6/E7 significantly suppressed HPV-associated tumor growth, while E6/E7–CpG did not. Clec9A-TNE loaded with pooled B16-F10 melanoma neoepitopes induced epitope-specific CD4+ and CD8+ T cell responses, permitting selection of immunogenic neoepitopes. Clec9A-TNE encapsulating 6 neoepitopes significantly suppressed B16-F10 melanoma growth in a CD4+ T cell–dependent manner. Thus, cross-presenting DCs targeted with antigen–Clec9A-TNE stimulate therapeutically effective tumor-specific immunity, dependent on T cell help.