tbuckley/cabot-search huggingface dataset:
Association Between Handover of Anesthesia Care and Adverse Postoperative Outcomes Among Patients Undergoing Major Surgery
Authors: Philip M. Jones, Richard A. Cherry, Britney N. Allen, Krista M. Bray Jenkyn, Salimah Z. Shariff, Suzanne Flier, Kelly N. Vogt, Duminda N. Wijeysundera
Journal: JAMA (2018)

<h3>Importance</h3> Handing over the care of a patient from one anesthesiologist to another occurs during some surgeries and might increase the risk of adverse outcomes. <h3>Objective</h3> To assess whether complete handover of intraoperative anesthesia care is associated with higher likelihood of mortality or major complications compared with no handover of care. <h3>Design, Setting, and Participants</h3> A retrospective population-based cohort study (April 1, 2009-March 31, 2015 set in the Canadian province of Ontario) of adult patients aged 18 years and older undergoing major surgeries expected to last at least 2 hours and requiring a hospital stay of at least 1 night. <h3>Exposure</h3> Complete intraoperative handover of anesthesia care from one physician anesthesiologist to another compared with no handover of anesthesia care. <h3>Main Outcomes and Measures</h3> The primary outcome was a composite of all-cause death, hospital readmission, or major postoperative complications, all within 30 postoperative days. Secondary outcomes were the individual components of the primary outcome. Inverse probability of exposure weighting based on the propensity score was used to estimate adjusted exposure effects. <h3>Results</h3> Of the 313 066 patients in the cohort, 56% were women; the mean (SD) age was 60 (16) years; 49% of surgeries were performed in academic centers; 72% of surgeries were elective; and the median duration of surgery was 182 minutes (interquartile [IQR] range, 124-255). A total of 5941 (1.9%) patients underwent surgery with complete handover of anesthesia care. The percentage of patients undergoing surgery with a handover of anesthesiology care progressively increased each year of the study, reaching 2.9% in 2015. In the unweighted sample, the primary outcome occurred in 44% of the complete handover group compared with 29% of the no handover group. After adjustment, complete handovers were statistically significantly associated with an increased risk of the primary outcome (adjusted risk difference [aRD], 6.8% [95% CI, 4.5% to 9.1%];<i>P</i> &lt; .001), all-cause death (aRD, 1.2% [95% CI, 0.5% to 2%];<i>P</i> = .002), and major complications (aRD, 5.8% [95% CI, 3.6% to 7.9%];<i>P</i> &lt; .001), but not with hospital readmission within 30 days of surgery (aRD, 1.2% [95% CI, −0.3% to 2.7%];<i>P</i> = .11). <h3>Conclusions and Relevance</h3> Among adults undergoing major surgery, complete handover of intraoperative anesthesia care compared with no handover was associated with a higher risk of adverse postoperative outcomes. These findings may support limiting complete anesthesia handovers.
Antibiotics Dispensed to Privately Insured Pregnant Women with Urinary Tract Infections — United States, 2014
Authors: Elizabeth C. Ailes, April D. Summers, Emmy L. Tran, Suzanne M. Gilboa, Kathryn E. Arnold, Dana Meaney-Delman, Jennita Reefhuis
Journal: MMWR Morbidity and Mortality Weekly Report (2018)

Urinary tract infections (UTIs) occur in about 8% of pregnant women, and untreated UTIs can have serious consequences, including pyelonephritis, preterm labor, low birth weight, and sepsis (1). Pregnant women are typically screened for UTIs during early pregnancy, and those with bacteriuria are treated with antibiotics (1,2). Antibiotic stewardship is critical to improving patient safety and to combating antibiotic resistance. Because of the potential risk for birth defects, including anencephaly, heart defects, and orofacial clefts, associated with use of sulfonamides and nitrofurantoin during pregnancy (3), a 2011 committee opinion from the American College of Obstetricians and Gynecologists (ACOG) recommended that sulfonamides and nitrofurantoin may be prescribed in the first trimester of pregnancy only when other antimicrobial therapies are deemed clinically inappropriate (4). To assess the effects of these recommendations, CDC analyzed the Truven Health MarketScan Commercial Database* to examine antibiotic prescriptions filled by pregnant women with UTIs. Among 482,917 pregnancies in 2014, 7.2% of women had an outpatient UTI diagnosis during the 90 days before the date of last menstrual period (LMP) or during pregnancy. Among pregnant women with UTIs, the most frequently prescribed antibiotics during the first trimester were nitrofurantoin, ciprofloxacin, cephalexin, and trimethoprim-sulfamethoxazole. Given the potential risks associated with use of some of these antibiotics in early pregnancy and the potential for unrecognized pregnancy, women's health care providers should be familiar with the ACOG recommendations and consider the possibility of early pregnancy when treating women of reproductive age.
Brentuximab Vedotin with R-CHP Chemotherapy As Frontline Treatment for Patients with CD30 Positive Primary Mediastinal Large B-Cell, Diffuse Large B-Cell, and Grey Zone Lymphomas: Results of a Phase I/II Multisite Trial
Authors: Jakub Svoboda, Daniel J. Landsburg, Sunita Dwivedy Nasta, Stefan Klaus Barta, Nadia Khan, Henry C. Fung, Carlyn Rose Tan, Joanne Filicko-O'Hara, Sameh Gaballa, Lauren Elizabeth Strelec, Sarah J. Nagle, Steven M. Bair, Sheryl Mitnick, Terease S. Waite, Rachel Lynn Sargent, Agata M. Bogusz, Ziver Sahin, Anthony R. Mato, Stephen J. Schuster
Journal: Blood (2017)
A gene signature to determine metastatic behavior in thymic carcinoma.
Authors: Yesim Gokmen-Polar, Robert W. Cook, Jeffrey Wilkinson, Derek Maetzold, John F Stone, Kristen M. Oelschlager, Wei Lu, Ioan Tudor Vladislav, Kenneth Kesler, Patrick J. Loehrer, Sunil S. Badve
Journal: Journal of Clinical Oncology (2013)

7605 Background: Thymomas and thymic carcinomas (TC) are rare epithelial tumors derived from the thymic gland in the anterior mediastinum. Although all histological types of thymomas, albeit with different frequencies, can give rise to metastases, TC have a more aggressive behavior and metastasize earlier and more frequently than thymomas. We previously developed a prognostic gene signature able to accurately determine metastatic behavior of thymomas (Gökmen-Polar et al. ASCO 2012). The signature is currently used in clinical practice to identify patients at high or low risk for metastatic disease. In the current study, we sought to evaluate the utility of this signature for determining risk from TC tumors. Methods: FFPE tissue sections were macrodissected from 35 primary TC. RNA was isolated and RT-PCR was performed to assess the expression of 23 genes (19 test and four reference genes). Predictive modeling was performed using Radial Basis Machine (RBM) software from JMP Genomics (SAS), and survival analysis was done using the Kaplan-Meier method. Results: Samples from the TC cohort ranged from stage II through IVB, with a median age of 54 years. 26 samples had evidence of metastatic progression, while nine samples did not. Prediction of metastasis, based upon comparison to the previously developed thymoma training set and using a 19-gene signature, yielded an ROC = 0.66. Independent analysis of the TC cohort with the thymoma 19-gene signature resulted in a predictive model with an ROC = 0.97 (overall accuracy = 87%, sensitivity = 73% and specificity=100%). Further modeling and gene set reduction revealed a separate ten-gene signature able to segregate metastatic from non-metastatic cases with 100% accuracy. All the cases classified as high risk (n= 26) developed metastasis within 5 years while none of the cases categorized as low-risk (n= 9) had any events at 5 years of follow-up. Conclusions: A ten-gene signature was established that appears to predict metastatic behavior of TC with a high degree of accuracy; however, validation in an independent cohort is necessary. Our data suggests that the biologic determinants of the clinical course of TC maybe distinct from thymoma and could be used to improve patient management.
Loss of Paneth Cell Autophagy Causes Acute Susceptibility to Toxoplasma gondii-Mediated Inflammation
Authors: Elise Burger, Alessandra Araujo, Américo López-Yglesias, Michael W. Rajala, Linda Geng, Beth Levine, Lora V. Hooper, Ezra Burstein, Felix Yarovinsky
Journal: Cell Host & Microbe (2018)

Highlights•Basal Paneth cell autophagy is driven by the microbiota and IFN-γ•Paneth cell autophagy protects against acute infection•Loss of Paneth cell autophagy results in impaired intestinal permeability•Loss of Paneth cell autophagy leads to TNF- and IFN-γ mediated intestinal pathologySummaryThe protozoan parasite Toxoplasma gondii triggers severe small intestinal immunopathology characterized by IFN-γ- and intestinal microbiota-mediated inflammation, Paneth cell loss, and bacterial dysbiosis. Paneth cells are a prominent secretory epithelial cell type that resides at the base of intestinal crypts and releases antimicrobial peptides. We demonstrate that the microbiota triggers basal Paneth cell-specific autophagy via induction of IFN-γ, a known trigger of autophagy, to maintain intestinal homeostasis. Deletion of the autophagy protein Atg5 specifically in Paneth cells results in exaggerated intestinal inflammation characterized by complete destruction of the intestinal crypts resembling that seen in pan-epithelial Atg5-deficient mice. Additionally, lack of functional autophagy in Paneth cells within intestinal organoids and T. gondii-infected mice causes increased sensitivity to the proinflammatory cytokine TNF along with increased intestinal permeability, leading to exaggerated microbiota- and IFN-γ-dependent intestinal immunopathology. Thus, Atg5 expression in Paneth cells is essential for tissue protection against cytokine-mediated immunopathology during acute gastrointestinal infection.Graphical abstract
<i>Notes from the Field</i>: <i>Baylisascaris procyonis</i> Encephalomyelitis in a Toddler — King County, Washington, 2017
Authors: Vance Kawakami, Amanda Casto, Niranjana Natarajan, Anna Snyder, Jonathan Mosser, Jesse Bonwitt, Matthew P. Kronman, Meagan Kay
Journal: MMWR Morbidity and Mortality Weekly Report (2018)
The urgent need for a harmonized severity scoring system for acute allergic reactions
Authors: A. Muraro, M. Fernandez‐Rivas, K. Beyer, V. Cardona, A. Clark, E. Eller, J. O'B. Hourihane, M. Jutel, A. Sheikh, I. Agache, K. J. Allen, E. Angier, B. Ballmer‐Weber, M. B. Bilò, C. Bindslev‐Jensen, C. A. Camargo, A. Cianferoni, A. DunnGalvin, P. A. Eigenmann, S. Halken, K. Hoffmann‐Sommergruber, S. Lau, C. Nilsson, L. K. Poulsen, F. Rueff, J. Spergel, G. Sturm, F. Timmermans, M. J. Torres, P. Turner, R. van Ree, M. Wickman, M. Worm, E. N. C. Mills, G. Roberts
Journal: Allergy (2018)

The accurate assessment and communication of the severity of acute allergic reactions are important to patients, clinicians, researchers, the food industry, and public health and regulatory authorities. Severity has different meanings to different stakeholders with patients and clinicians rating the significance of particular symptoms very differently. Many severity scoring systems have been generated, most focusing on the severity of reactions following exposure to a limited group of allergens. They are heterogeneous in format, none has used an accepted developmental approach, and none has been validated. Their wide range of outcome formats has led to difficulties with interpretation and application. Therefore, there is a persisting need for an appropriately developed and validated severity scoring system for allergic reactions that work across the range of allergenic triggers and address the needs of different stakeholder groups. We propose a novel approach to develop and then validate a harmonized scoring system for acute allergic reactions, based on a data-driven method that is informed by clinical and patient experience and other stakeholders' perspectives. We envisage two formats: (i) a numerical score giving a continuum from mild to severe reactions that are clinically meaningful and are useful for allergy healthcare professionals and researchers, and (ii) a three-grade-based ordinal format that is simple enough to be used and understood by other professionals and patients. Testing of reliability and validity of the new approach in a range of settings and populations will allow eventual implementation of a standardized scoring system in clinical studies and routine practice.
Best Practices in Recruitment of the First US-Based Atopic Dermatitis Cohort: The Mechanisms of Progression of Atopic Dermatitis to Asthma in Children (MPAACH).
Authors: Asel Baatyrbek-kyzy, Rosario Alarcon, Alexandria Patterson, Kristina Keidel, John Kroner, Gurjit K. Khurana Hershey, Jocelyn M. Biagini Myers
Journal: Journal of Allergy and Clinical Immunology (2018)
Association of Psoriasis With Comorbidity Development in Children With Psoriasis
Authors: Megha M. Tollefson, Holly K. Van Houten, Dennis Asante, Xiaoxi Yao, Hilal Maradit Kremers
Journal: JAMA Dermatology (2018)

Children with psoriasis are at increased risk for comorbidities. Many children with psoriasis are also overweight or obese; it is unknown whether the increased risk of comorbidities in these children is independent of obesity.To determine the risk of elevated lipid levels (hyperlipidemia/hypertriglyceridemia), hypertension, metabolic syndrome, polycystic ovarian syndrome, diabetes, nonalcoholic liver disease, and elevated liver enzyme levels in children with and without psoriasis, after accounting for obesity.This was a retrospective cohort study of claims data from Optum Laboratories Data Warehouse (includes 150 million privately insured and Medicare enrollees). A cohort of 29 957 children with psoriasis (affected children) and an age-, sex-, and race-matched comparator cohort of 29 957 children without psoriasis were identified and divided into 4 groups: (1) nonobese, without psoriasis (reference cohort); (2) nonobese, with psoriasis; (3) obese, without psoriasis; and (4) obese, with psoriasis.Risk of developing comorbidities (Cox proportional hazards regression).The overall mean (SD) age of those included in the cohort was 12.0 (4.4) years, and 16 034 (53.5%) were girls. At baseline, more affected children were obese (862 [2.9%] vs 463 [1.5%]; P < .001 for all comparisons). Children with psoriasis were significantly more likely to develop each of the comorbidities than those without psoriasis (P < .01). Obesity was a strong risk factor for development of each comorbidity, even in those without psoriasis (hazard ratios [HRs] ranging from 2.26 to 18.11). The risk of comorbidities was 40% to 75% higher among nonobese children with vs without psoriasis: elevated lipid levels (HR, 1.42; 95% CI, 1.25-1.62), hypertension (HR, 1.64; 95% CI, 1.40-1.93), diabetes (HR, 1.58; 95% CI, 1.27-1.95), metabolic syndrome (HR, 1.62; 95% CI, 1.13-2.33), polycystic ovarian syndrome (HR, 1.49; 95% CI, 1.18-1.88), nonalcoholic liver disease (HR, 1.76; 95% CI, 1.16-2.65), and elevated liver enzyme levels (HR, 1.46; 95% CI, 1.27-1.67). Except for hypertension (P = .03), no significant interaction occurred between psoriasis and obesity on the risk of comorbidities.Children with psoriasis are at greater risk of developing obesity, hyperlipidemia, hypertension, diabetes, metabolic syndrome, polycystic ovarian syndrome, nonalcoholic liver disease, and elevated liver function enzyme levels than children without psoriasis. While psoriasis is a small independent risk factor for the development of these comorbidities, obesity is a much stronger contributor to comorbidity development in children with psoriasis.
A phase 1 study of azacitidine combined with chemotherapy in childhood leukemia: a report from the TACL consortium
Authors: Weili Sun, Timothy Triche, Jemily Malvar, Paul Gaynon, Richard Sposto, Xiaojing Yang, Henrique Bittencourt, Andrew E. Place, Yoav Messinger, Chris Fraser, Luciano Dalla-Pozza, Bodour Salhia, Peter Jones, Alan S. Wayne, Lia Gore, Todd M. Cooper, Gangning Liang
Journal: Blood (2018)
Layer-by-layer cell coating technique using extracellular matrix facilitates rapid fabrication and function of pancreatic β-cell spheroids
Authors: Yasunari Fukuda, Takami Akagi, Tadafumi Asaoka, Hidetoshi Eguchi, Kazuki Sasaki, Yoshifumi Iwagami, Daisaku Yamada, Takehiro Noda, Koichi Kawamoto, Kunihito Gotoh, Shogo Kobayashi, Masaki Mori, Yuichiro Doki, Mitsuru Akashi
Journal: Biomaterials (2018)
Cerebral Metabolic Stress Is Lower in Patients with Sickle Cell Anemia on Hydroxyurea Therapy
Authors: Melanie E Fields, Kristin P Guilliams, Michael M Binkley, Dustin K Ragan, Slim Fellah, Cihat Eldeniz, Yasheng Chen, Monica L Hulbert, Robert C McKinstry, Joshua S Shimony, Katie D Vo, Hongyu An, Andria L Ford, Jin-Moo Lee
Journal: Blood (2017)
AMPK–Akt Double-Negative Feedback Loop in Breast Cancer Cells Regulates Their Adaptation to Matrix Deprivation
Authors: Manipa Saha, Saurav Kumar, Shoiab Bukhari, Sai A. Balaji, Prashant Kumar, Sravanth K. Hindupur, Annapoorni Rangarajan
Journal: Cancer Research (2018)

Abstract Cell detachment from the extracellular matrix triggers anoikis. Disseminated tumor cells must adapt to survive matrix deprivation, while still retaining the ability to attach at secondary sites and reinitiate cell division. In this study, we elucidate mechanisms that enable reversible matrix attachment by breast cancer cells. Matrix deprival triggered AMPK activity and concomitantly inhibited AKT activity by upregulating the Akt phosphatase PHLPP2. The resultant pAMPKhigh/pAktlow state was critical for cell survival in suspension, as PHLPP2 silencing also increased anoikis while impairing autophagy and metastasis. In contrast, matrix reattachment led to Akt-mediated AMPK inactivation via PP2C-α-mediated restoration of the pAkthigh/pAMPKlow state. Clinical specimens of primary and metastatic breast cancer displayed an Akt-associated gene expression signature, whereas circulating breast tumor cells displayed an elevated AMPK-dependent gene expression signature. Our work establishes a double-negative feedback loop between Akt and AMPK to control the switch between matrix-attached and matrix-detached states needed to coordinate cell growth and survival during metastasis. Significance: These findings reveal a molecular switch that regulates cancer cell survival during metastatic dissemination, with the potential to identify targets to prevent metastasis in breast cancer. Cancer Res; 78(6); 1497–510. ©2018 AACR.
Designing Difference in Difference Studies: Best Practices for Public Health Policy Research
Authors: Coady Wing, Kosali Simon, Ricardo A. Bello-Gomez
Journal: Annual Review of Public Health (2018)

The difference in difference (DID) design is a quasi-experimental research design that researchers often use to study causal relationships in public health settings where randomized controlled trials (RCTs) are infeasible or unethical. However, causal inference poses many challenges in DID designs. In this article, we review key features of DID designs with an emphasis on public health policy research. Contemporary researchers should take an active approach to the design of DID studies, seeking to construct comparison groups, sensitivity analyses, and robustness checks that help validate the method's assumptions. We explain the key assumptions of the design and discuss analytic tactics, supplementary analysis, and approaches to statistical inference that are often important in applied research. The DID design is not a perfect substitute for randomized experiments, but it often represents a feasible way to learn about casual relationships. We conclude by noting that combining elements from multiple quasi-experimental techniques may be important in the next wave of innovations to the DID approach.
Clinical Utility of Flow Cytometry Immunophenotyping and Hematological Profile in Chronic Lymphoproliferative Disorders
Authors: Aldair Paiva, Gabriela Va Alves, Valéria Sf Sales, Alexandra Sj Silva, Dany Gkc Silva, Enildo Alves, Frank Bahia, Rodrigo Villar Freitas, Hugo Diogenes De Oliveira Paiva, Geraldo Barroso Cavalcanti
Journal: Blood (2017)
In vivo simultaneous transcriptional activation of multiple genes in the brain using CRISPR–dCas9-activator transgenic mice
Authors: Haibo Zhou, Junlai Liu, Changyang Zhou, Ni Gao, Zhiping Rao, He Li, Xinde Hu, Changlin Li, Xuan Yao, Xiaowen Shen, Yidi Sun, Yu Wei, Fei Liu, Wenqin Ying, Junming Zhang, Cheng Tang, Xu Zhang, Huatai Xu, Linyu Shi, Leping Cheng, Pengyu Huang, Hui Yang
Journal: Nature Neuroscience (2018)
Effect of Laparoscopic Sleeve Gastrectomy vs Laparoscopic Roux-en-Y Gastric Bypass on Weight Loss in Patients With Morbid Obesity
Authors: Ralph Peterli, Bettina Karin Wölnerhanssen, Thomas Peters, Diana Vetter, Dino Kröll, Yves Borbély, Bernd Schultes, Christoph Beglinger, Jürgen Drewe, Marc Schiesser, Philipp Nett, Marco Bueter
Journal: JAMA (2018)

<h3>Importance</h3> Sleeve gastrectomy is increasingly used in the treatment of morbid obesity, but its long-term outcome vs the standard Roux-en-Y gastric bypass procedure is unknown. <h3>Objective</h3> To determine whether there are differences between sleeve gastrectomy and Roux-en-Y gastric bypass in terms of weight loss, changes in comorbidities, increase in quality of life, and adverse events. <h3>Design, Setting, and Participants</h3> The Swiss Multicenter Bypass or Sleeve Study (SM-BOSS), a 2-group randomized trial, was conducted from January 2007 until November 2011 (last follow-up in March 2017). Of 3971 morbidly obese patients evaluated for bariatric surgery at 4 Swiss bariatric centers, 217 patients were enrolled and randomly assigned to sleeve gastrectomy or Roux-en-Y gastric bypass with a 5-year follow-up period. <h3>Interventions</h3> Patients were randomly assigned to undergo laparoscopic sleeve gastrectomy (n = 107) or laparoscopic Roux-en-Y gastric bypass (n = 110). <h3>Main Outcomes and Measures</h3> The primary end point was weight loss, expressed as percentage excess body mass index (BMI) loss. Exploratory end points were changes in comorbidities and adverse events. <h3>Results</h3> Among the 217 patients (mean age, 45.5 years; 72% women; mean BMI, 43.9) 205 (94.5%) completed the trial. Excess BMI loss was not significantly different at 5 years: for sleeve gastrectomy, 61.1%, vs Roux-en-Y gastric bypass, 68.3% (absolute difference, −7.18%; 95% CI, −14.30% to −0.06%;<i>P</i> = .22 after adjustment for multiple comparisons). Gastric reflux remission was observed more frequently after Roux-en-Y gastric bypass (60.4%) than after sleeve gastrectomy (25.0%). Gastric reflux worsened (more symptoms or increase in therapy) more often after sleeve gastrectomy (31.8%) than after Roux-en-Y gastric bypass (6.3%). The number of patients with reoperations or interventions was 16/101 (15.8%) after sleeve gastrectomy and 23/104 (22.1%) after Roux-en-Y gastric bypass. <h3>Conclusions and Relevance</h3> Among patients with morbid obesity, there was no significant difference in excess BMI loss between laparoscopic sleeve gastrectomy and laparoscopic Roux-en-Y gastric bypass at 5 years of follow-up after surgery. <h3>Trial Registration</h3> clinicaltrials.gov Identifier:NCT00356213
David Oliver: Will we now see a serious attempt to tackle social care funding?
Authors: David Oliver
Journal: BMJ (2018)

In Theresa May’s January reshuffle of her cabinet, Jeremy Hunt received an upgrade to his job title: “and social care” was appended to “secretary of state for health.”1 Is this a cosmetic change, or does it indicate a real desire to drive through meaningful reform?

For several parliaments, ministerial and civil service responsibility for social care has been shared with two other ministries, but mainly it’s been with the Department of Health. Social care will reportedly now be brought entirely into the Department of Health, with Hunt leading an inquiry into future funding and provision.2

Over the past two decades we’ve seen several …