tbuckley/cabot-search huggingface dataset:
Effect of Antibiotic Prophylaxis on Surgical Site Infections Following Removal of Orthopedic Implants Used for Treatment of Foot, Ankle, and Lower Leg Fractures
Authors: Manouk Backes, Siem A. Dingemans, Marcel G. W. Dijkgraaf, H. Rogier van den Berg, Bart van Dijkman, Jochem M. Hoogendoorn, Pieter Joosse, Ewan D. Ritchie, W. Herbert Roerdink, Judith P. M. Schots, Nico L. Sosef, Ingrid J. B. Spijkerman, Bas A. Twigt, Alexander H. van der Veen, Ruben N. van Veen, Jefrey Vermeulen, Dagmar I. Vos, Jasper Winkelhagen, J. Carel Goslings, Tim Schepers
Journal: JAMA (2017)

<h3>Importance</h3> Following clean (class I, not contaminated) surgical procedures, the rate of surgical site infection (SSI) should be less than approximately 2%. However, an infection rate of 12.2% has been reported following removal of orthopedic implants used for treatment of fractures below the knee. <h3>Objective</h3> To evaluate the effect of a single dose of preoperative antibiotic prophylaxis on the incidence of SSIs following removal of orthopedic implants used for treatment of fractures below the knee. <h3>Design, Setting, and Participants</h3> Multicenter, double-blind, randomized clinical trial including 500 patients aged 18 to 75 years with previous surgical treatment for fractures below the knee who were undergoing removal of orthopedic implants from 19 hospitals (17 teaching and 2 academic) in the Netherlands (November 2014-September 2016), with a follow-up of 6 months (final follow-up, March 28, 2017). Exclusion criteria were an active infection or fistula, antibiotic treatment, reimplantation of osteosynthesis material in the same session, allergy for cephalosporins, known kidney disease, immunosuppressant use, or pregnancy. <h3>Interventions</h3> A single preoperative intravenous dose of 1000 mg of cefazolin (cefazolin group, n = 228) or sodium chloride (0.9%; saline group, n = 242). <h3>Main Outcomes and Measures</h3> Primary outcome was SSI within 30 days as measured by the criteria from the US Centers for Disease Control and Prevention. Secondary outcome measures were functional outcome, health-related quality of life, and patient satisfaction. <h3>Results</h3> Among 477 randomized patients (mean age, 44 years [SD, 15]; women, 274 [57%]; median time from orthopedic implant placement, 11 months [interquartile range, 7-16]), 470 patients completed the study. Sixty-six patients developed an SSI (14.0%): 30 patients (13.2%) in the cefazolin group vs 36 in the saline group (14.9%) (absolute risk difference, −1.7 [95% CI, −8.0 to 4.6],<i>P</i> = .60). <h3>Conclusions and Relevance</h3> Among patients undergoing surgery for removal of orthopedic implants used for treatment of fractures below the knee, a single preoperative dose of intravenous cefazolin compared with saline did not reduce the risk of surgical site infection within 30 days following implant removal. <h3>Trial Registration</h3> clinicaltrials.gov Identifier:NCT02225821
In vitro and in vivo analysis of T cell-induced bronchoconstriction
Authors: Akio Mori, Satoshi Kouyama, Miyako Yamaguchi, Chiemi Kumitani, Akemi Ohtomo, Yuto Nakamura, Yasuhiro Tomita, Hamada Hamada, Yosuke Kamide, Hiroaki Hayashi, Kentaro Watai, Chihiro Mitsui, Kiyoshi Sekiya, Yuma Fukutomi, Masami Taniguchi, Takayuki Ohtomo, Osamu Kaminuma
Journal: Journal of Allergy and Clinical Immunology (2018)
Abstract 17183: Association Between Level of Hospital Resources for Out-of-Hospital Cardiac Arrest and Outcome in Gyeonggi Province
Authors: Kim Joo-yeong, Sungwoo Moon, Jong Hak Park, Sang Do Shin, Young Sun Ro, Eui Jung Lee, Ki Ok Ahn, Woochan Jeon, Ju Ok Park, Dae-Han Wi, Jeong Joo, Kyoung Mi Lee
Journal: Circulation (2016)

Introduction:  Post arrest care is important for favorable outcome in cardiac arrest. There are growing evidences about advantages of regionalization in the system of care for the out-of-hospital cardiac arrest (OHCA).   Hypothesis:  In this study, we aimed to categorize cardiac arrest care centers (CAC) according to their level of resources and verify if there are outcome differences in Gyeonggi Province, South Korea.   Methods:  This is an observational study performed in Gyeonggi (approximately 12 million of population). Survey via email was conducted to all 90 hospitals where OHCAs were transferred from 2013 to 2014 by EMS. Questionnaire included resources, standardized cardiac arrest management strategies and quality management statements. Hospitals were categorized into 3 groups based on the result of the survey. Definite CAC (D-CAC) was defined as a comprehensive center where multidisciplinary approach and post arrest care could be provided. Primary CAC (P-CAC) was defined as a center with a standardized cardiac arrest resuscitation and transfer protocol. None CAC(N-CAC) was defined as neither of the two. Good neurologic outcome (defined as cerebral performance category 1-2) was compared using Nationwide OHCA data base constructed by Korean CDC.   Results:  From total 90 CACs in Gyeonggi, 77 centers replied to the survey. Fifteen centers were categorized as D-CAC, 32 centers as P-CAC and 30 centers as N-CAC. Total 11,941 OHCAs were transferred to hospitals by EMS during study period and 10,212 patients to CACs where replied to the survey. Among them 4342 (42.9%) were transferred to D-CAC, 2906 (28.7%) to P-CAC and 2873 (28.4%) to N-CAC. D-CAC showed better neurologic outcome (5.0%) than P-CAC (1.6%, p   Conclusions:  About 57% of OHCAs occurred in Gyeonggi were transferred to non D-CAC. There was significant difference in favorable neurologic outcome between D-CAC and others centers. Further study is needed to define the causes of difference and implement measures including regionalization of system of care.
A multicenter randomized phase II trial of erlotinib with and without hydroxychloroquine (HCQ) in TKI-naive patients (pts) with epidermal growth factor receptor (EGFR) mutant advanced non-small cell lung cancer (NSCLC).
Authors: Joel W. Neal, Heather A. Wakelee, Josephine Louella Feliciano, Sarah B. Goldberg, Daniel Morgensztern, Millie Snigdha Das, Rebecca Suk Heist, Inga Tolin Lennes, Alona Muzikansky, Martin J. Edelman, Scott N. Gettinger, Lecia V. Sequist
Journal: Journal of Clinical Oncology (2014)

8088 Background: Erlotinib (E) is widely used in the treatment of advanced EGFR mutant NSCLC, with a historical progression free survival of about 9 months. Preclinical data showed HCQ prevented the development of resistance to E putatively via chromatin state modulation, and a prior phase I trial established safety of E+HCQ (EQ). This randomized phase II trial tested the efficacy of EQ in delaying acquired resistance to E. Methods: EGFR-TKI naïve pts with metastatic or recurrent EGFR mutant NSCLC were randomized to E (150 mg daily) with or without HCQ (1,000 mg daily). Tumor assessments were performed every 8 weeks until disease progression. With a sample size of 76 pts, the study was powered for a primary endpoint of improvement in 9-month progression free survival (PFS) from 50% in the E arm compared with 77% in the EQ arm. Results: 76 pts were enrolled at 4 sites between 12/09 and 1/13, 38 on each arm. Age, sex, race, histology, and prior chemotherapy were well balanced between the arms, but an excess of patients with a smoking history (26% E vs 47% EQ) and brain metastases (29% E vs 42% EQ) was observed on the EQ arm. E-related toxicities were mostly balanced among treatment arms, but EQ patients had an excess of grade (G) 3 fatigue (3% E vs 18% EQ) and nausea (28% G1/2 + no G3 for E, and 53% G1/2 + 3% G3 for EQ). No drug-attributed G4/5 toxicities were observed. Among 37 evaluable pts on arm E and EQ, respectively, confirmed response rates were 65% and 57% and disease control rates were 92% and 84%. 9-month PFS was 71% for E and 52% for EQ (p=NS), but median PFS was identical in each arm (10.8 months). Preliminary median overall survival (OS) was 33.5 months on E and 27.8 months on EQ (p=0.06) though OS data are not yet mature. Conclusions: EQ did not improve 9 month PFS compared with arm E. OS numerically favored the E arm, which may reflect imbalances between the arms. Despite strong preclinical evidence, hydroxychloroquine does not appear to delay the development of resistance to erlotinib in pts with EGFR mutant NSCLC. Clinical trial information: NCT00977470.
Abstract 13041: Worsening Renal Function in Early Phase of Hospitalization Indicates Poor Prognosis of Patients With Acute Heart Failure
Authors: Yuichi Kawase, Reo Hata, Keiichiro Iwasaki, Takeshi Tada, Takeshi Maruo, Harumi Katoh, Kazushige Kadota
Journal: Circulation (2016)

Background: Worsening renal function (WRF, serum creatinine rise ≥0.3 mg/dl from admission) has been consistently shown to be among the important prognostic variables in patients admitted for acute heart failure (AHF). However, the relation between the timing of WRF and prongnosis remains unclear. Methods: We investigated 464 consecutive patients admitted for AHF between February 2015 and October 2015. After having eliminated patients with acute coronary syndrome and end stage renal disease, we enrolled 377 patients in this study sample (mean age 79.1±12.4 years). The median follow-up period was 225 (interquartile range, 88-330) days. WRF was dichotomized into early or late WRF by using the median of the occurrence day (day 3). The primary end points were all-cause death and a composite of all-cause death or rehospitalization for HF. Results: WRF occurred in 42% (n=160: early, 56%; late, 44%). The figure shows the Kaplan-Meier curves of death and death/rehospitalization for heart failure. By multivariate analysis, early phase WRF was an independent predictor of poor prognosis (see Table). Conclusion: Only early phase WRF is associated with poor prognosis. Therefore, its prevention remains an important target for treatment of AHF.
mTORC1 Inactivation Promotes Colitis-Induced Colorectal Cancer but Protects from APC Loss-Dependent Tumorigenesis
Authors: Marta Brandt, Tatiana P. Grazioso, Mohamad-Ali Fawal, Krishna S. Tummala, Raul Torres-Ruiz, Sandra Rodriguez-Perales, Cristian Perna, Nabil Djouder
Journal: Cell Metabolism (2017)
Response-Adapted Lenalidomide Maintenance in Newly Diagnosed, Transplant-Eligible Multiple Myeloma: Results from the Multicenter Phase III GMMG-MM5 Trial
Authors: Hartmut Goldschmidt, Elias K Mai, Jan Dürig, Christof Scheid, Katja C. Weisel, Christina Kunz, Uta Bertsch, Thomas Hielscher, Markus Munder, Hans-Walter Lindemann, Barbara Huegle-Doerr, Dirk Hose, Anja Seckinger, Stefanie Huhn, Anna Jauch, Bernhard Rabold, Ahmet Elmaagacli, Christian Gerecke, Peter Brossart, Martin Goerner, Helga Bernhard, Martin Hoffmann, Jens Hillengass, Marc-Steffen S Raab, Igor Wolfgang Blau, Mathias Hänel, Hans Jürgen Salwender
Journal: Blood (2017)
Abstract 19306: Phosphorylation of Cardiac Myosin Binding Protein C Abolishes Myosin Binding and Preserves Actin Binding to Accelerate Relaxation Kinetics in Engineered Cardiac Tissue
Authors: Sumit Kar, Dan Smelter, Willem de Lange, Richard L Moss, J Carter Ralphe
Journal: Circulation (2016)

Cardiac myosin binding protein-C (cMyBP-C) is a sarcomeric protein that regulates contractility in response to increased circulatory demand. Phosphorylation of cMyBP-C during adrenergic stimulation...
Platelet activation is a preoperative risk factor for the development of thromboembolic complications in patients with continuous‐flow left ventricular assist device
Authors: Filippo Consolo, Giulia Sferrazza, Giulia Motolone, Rachele Contri, Lorenzo Valerio, Rosalba Lembo, Loris Pozzi, Patrizia Della Valle, Michele De Bonis, Alberto Zangrillo, Gianfranco B. Fiore, Alberto Redaelli, Marvin J. Slepian, Federico Pappalardo
Journal: European Journal of Heart Failure (2017)
Abstract 11906: Heart Failure Admissions to General Medicine Services are Associated With Increased 30-day Readmission Rate
Authors: Parag Goyal, Madeline Sterling, Ashley N Beecy, Savira Kochhar, John T Ruffino, Erica C Jones, Evelyn M Horn
Journal: Circulation (2015)

Introduction: Hospitalists are increasingly caring for patients with heart failure (HF) at a time when there is need to identify modifiable factors associated with 30-day readmission rates. Hypothesis: Patients admitted to General Medicine services (GM) will have higher 30-day readmission rates than those admitted to Cardiology services. Methods: This retrospective cohort comprised patients with a principal diagnosis of HF discharged from GM or Cardiology services in 2013-2014 at an urban academic hospital. Patients discharged with hospice were excluded. Index hospitalizations and 30-day readmissions were identified via query of the electronic medical records. Demographics, clinical indices, and hospitalization characteristics were collected by chart review. Results: Among 926 patients admitted with HF, 40% were admitted to GM and 60% were admitted to a Cardiology service. Patients on GM were slightly older, more likely female, and more likely to have Medicare (Table). They also had higher LVEF, less RV dysfunction, and less ventricular tachycardia (VT). Rates of non-cardiac comorbidities were comparable between groups. Patients on GM experienced a 1.4-fold increased 30-day readmission rate compared to those on Cardiology services (32% vs. 23%, p=0.023). Multivariate regression analysis showed that admission to GM remained a predictor for 30-day readmission (OR 1.37, [1.01 to 1.87], p=0.048) after controlling for key differences between groups including age, sex, insurance, LVEF, RV dysfunction, VT, and admission blood pressure and hemoglobin. Conclusions: HF patients admitted to General Medicine have less structural heart disease, and yet have a higher rate of 30-day readmission compared to those admitted to Cardiology services. This underscores the importance of ensuring that hospitalists obtain adequate heart failure training (related to both inpatient care and optimization of discharge regimens), so as to avoid un-necessary readmissions.
Pharmacologic Interventions to Prevent Cognitive Decline, Mild Cognitive Impairment, and Clinical Alzheimer-Type Dementia
Authors: Howard A. Fink, Eric Jutkowitz, J. Riley McCarten, Laura S. Hemmy, Mary Butler, Heather Davila, Edward Ratner, Collin Calvert, Terry R. Barclay, Michelle Brasure, Victoria A. Nelson, Robert L. Kane
Journal: Annals of Internal Medicine (2017)

Optimal treatment to prevent or delay cognitive decline, mild cognitive impairment (MCI), or dementia is uncertain.To summarize current evidence on the efficacy and harms of pharmacologic interventions to prevent or delay cognitive decline, MCI, or dementia in adults with normal cognition or MCI.Several electronic databases from January 2009 to July 2017, bibliographies, and expert recommendations.English-language trials of at least 6 months' duration enrolling adults without dementia and comparing pharmacologic interventions with placebo, usual care, or active control on cognitive outcomes.Two reviewers independently rated risk of bias and strength of evidence; 1 extracted data, and a second checked accuracy.Fifty-one unique trials were rated as having low to moderate risk of bias (including 3 that studied dementia medications, 16 antihypertensives, 4 diabetes medications, 2 nonsteroidal anti-inflammatory drugs [NSAIDs] or aspirin, 17 hormones, and 7 lipid-lowering agents). In persons with normal cognition, estrogen and estrogen-progestin increased risk for dementia or a combined outcome of MCI or dementia (1 trial, low strength of evidence); high-dose raloxifene decreased risk for MCI but not for dementia (1 trial, low strength of evidence); and antihypertensives (4 trials), NSAIDs (1 trial), and statins (1 trial) did not alter dementia risk (low to insufficient strength of evidence). In persons with MCI, cholinesterase inhibitors did not reduce dementia risk (1 trial, low strength of evidence). In persons with normal cognition and those with MCI, these pharmacologic treatments neither improved nor slowed decline in cognitive test performance (low to insufficient strength of evidence). Adverse events were inconsistently reported but were increased for estrogen (stroke), estrogen-progestin (stroke, coronary heart disease, invasive breast cancer, and pulmonary embolism), and raloxifene (venous thromboembolism).High attrition, short follow-up, inconsistent cognitive outcomes, and possible selective reporting and publication.Evidence does not support use of the studied pharmacologic treatments for cognitive protection in persons with normal cognition or MCI.Agency for Healthcare Research and Quality.
The 17,18-epoxyeicosatetraenoic acid–G protein–coupled receptor 40 axis ameliorates contact hypersensitivity by inhibiting neutrophil mobility in mice and cynomolgus macaques
Authors: Takahiro Nagatake, Yumiko Shiogama, Asuka Inoue, Junichi Kikuta, Tetsuya Honda, Prabha Tiwari, Takayuki Kishi, Atsushi Yanagisawa, Yosuke Isobe, Naomi Matsumoto, Michiko Shimojou, Sakiko Morimoto, Hidehiko Suzuki, So-ichiro Hirata, Pär Steneberg, Helena Edlund, Junken Aoki, Makoto Arita, Hiroshi Kiyono, Yasuhiro Yasutomi, Masaru Ishii, Kenji Kabashima, Jun Kunisawa
Journal: Journal of Allergy and Clinical Immunology (2017)

Metabolites of eicosapentaenoic acid exert various physiologic actions. 17,18-Epoxyeicosatetraenoic acid (17,18-EpETE) is a recently identified new class of antiallergic and anti-inflammatory lipid metabolite of eicosapentaenoic acid, but its effects on skin inflammation and the underlying mechanisms remain to be investigated.We evaluated the effectiveness of 17,18-EpETE for control of contact hypersensitivity in mice and cynomolgus macaques. We further sought to reveal underlying mechanisms by identifying the responsible receptor and cellular target of 17,18-EpETE.Contact hypersensitivity was induced by topical application of 2,4-dinitrofluorobenzene. Skin inflammation and immune cell populations were analyzed by using flow cytometric, immunohistologic, and quantitative RT-PCR analyses. Neutrophil mobility was examined by means of imaging analysis in vivo and neutrophil culture in vitro. The receptor for 17,18-EpETE was identified by using the TGF-α shedding assay, and the receptor's involvement in the anti-inflammatory effects of 17,18-EpETE was examined by using KO mice and specific inhibitor treatment.We found that preventive or therapeutic treatment with 17,18-EpETE ameliorated contact hypersensitivity by inhibiting neutrophil mobility in mice and cynomolgus macaques. 17,18-EpETE was recognized by G protein-coupled receptor (GPR) 40 (also known as free fatty acid receptor 1) and inhibited chemoattractant-induced Rac activation and pseudopod formation in neutrophils. Indeed, the antiallergic inflammatory effect of 17,18-EpETE was abolished in the absence or inhibition of GPR40.17,18-EpETE inhibits neutrophil mobility through GPR40 activation, which is a potential therapeutic target to control allergic inflammatory diseases.
Facile Synthesis of Lipid–Perfluorocarbon Nanoemulsion Coated with Silica Shell as an Ultrasound Imaging Agent
Authors: Qiang Yang, Huali Chen, Yan Bai, Yang Cao, Wenjing Hu, Liangke Zhang
Journal: Advanced Healthcare Materials (2017)

A novel organic/inorganic hybrid nanovesicle as an ultrasound imaging agent is synthesized via facile emulsion and silica deposition methods. This nanovesicle, hyaluronate (HA)-docetaxel (DTX)/perfluoro-n-pentane (PFP)@SNC, consists of an encapsulated liquid PFP core, loaded DTX, and an HA-decorated silica shell. The HA-DTX/PFP@SNC has a narrow size distribution of 274.5 ± 3.25 nm, a negative zeta potential of -11.6 ± 0.47 mV, and an entrapment efficiency of 86.70% ± 1.42%. HA-DTX/PFP@SNC possesses an ultrasound (US)-triggered drug release and a temperature-dependent size change behavior. Compared with DTX/PFP@soybean phosphatidylcholine (SPC), which has no silica shell, the HA-DTX/PFP@SNC is more stable under various conditions. The MTT assay indicates that the blank HA-PFP@SNC vehicle has no cytotoxicity to A549 cells. Furthermore, due to the HA-mediated tumor-targeting ability, the HA-DTX/PFP@SNC shows obvious cytotoxicity to A549 cells. In vitro and in vivo US imaging results indicate that HA-DTX/PFP@SNC has a stronger and more durable echo signal than DTX/PFP@SPC. Moreover, the in vivo echo signal of HA-DTX/PFP@SNC is stronger than that of DTX/PFP@SNC due to the HA-mediated tumor targeting. Therefore, this novel organic/inorganic hybrid vesicle is a US contrast agent candidate.
Microglia ablation alleviates myelin-associated catatonic signs in mice
Authors: Hana Janova, Sahab Arinrad, Evan Balmuth, Marina Mitjans, Johannes Hertel, Mohamad Habes, Robert A. Bittner, Hong Pan, Sandra Goebbels, Martin Begemann, Ulrike C. Gerwig, Sönke Langner, Hauke B. Werner, Sarah Kittel-Schneider, Georg Homuth, Christos Davatzikos, Henry Völzke, Brian L. West, Andreas Reif, Hans Jörgen Grabe, Susann Boretius, Hannelore Ehrenreich, Klaus-Armin Nave
Journal: Journal of Clinical Investigation (2017)

The underlying cellular mechanisms of catatonia, an executive "psychomotor" syndrome that is observed across neuropsychiatric diseases, have remained obscure. In humans and mice, reduced expression of the structural myelin protein CNP is associated with catatonic signs in an age-dependent manner, pointing to the involvement of myelin-producing oligodendrocytes. Here, we showed that the underlying cause of catatonic signs is the low-grade inflammation of white matter tracts, which marks a final common pathway in Cnp-deficient and other mutant mice with minor myelin abnormalities. The inhibitor of CSF1 receptor kinase signaling PLX5622 depleted microglia and alleviated the catatonic symptoms of Cnp mutants. Thus, microglia and low-grade inflammation of myelinated tracts emerged as the trigger of a previously unexplained mental condition. We observed a very high (25%) prevalence of individuals with catatonic signs in a deeply phenotyped schizophrenia sample (n = 1095). Additionally, we found the loss-of-function allele of a myelin-specific gene (CNP rs2070106-AA) associated with catatonia in 2 independent schizophrenia cohorts and also associated with white matter hyperintensities in a general population sample. Since the catatonic syndrome is likely a surrogate marker for other executive function defects, we suggest that microglia-directed therapies may be considered in psychiatric disorders associated with myelin abnormalities.