tbuckley/cabot-search huggingface dataset:
F<scp>ifty</scp> Y<scp>ears of</scp> R<scp>esearch in</scp> ARDS.V<scp>t</scp> Selection in Acute Respiratory Distress Syndrome
Authors: Sarina K. Sahetya, Jordi Mancebo, Roy G. Brower
Journal: American Journal of Respiratory and Critical Care Medicine (2017)

Mechanical ventilation (MV) is critical in the management of many patients with acute respiratory distress syndrome (ARDS). However, MV can also cause ventilator-induced lung injury (VILI). The selection of an appropriate Vt is an essential part of a lung-protective MV strategy. Since the publication of a large randomized clinical trial demonstrating the benefit of lower Vts, the use of Vts of 6 ml/kg predicted body weight (based on sex and height) has been recommended in clinical practice guidelines. However, the predicted body weight approach is imperfect in patients with ARDS because the amount of aerated lung varies considerably due to differences in inflammation, consolidation, flooding, and atelectasis. Better approaches to setting Vt may include limits on end-inspiratory transpulmonary pressure, lung strain, and driving pressure. The limits of lowering Vt have not yet been established, and some patients may benefit from Vts that are lower than those in current use. However, lowering Vts may result in respiratory acidosis. Tactics to reduce respiratory acidosis include reductions in ventilation circuit dead space, increases in respiratory rate, higher positive end-expiratory pressures in patients who recruit lung in response to positive end-expiratory pressure, recruitment maneuvers, and prone positioning. Mechanical adjuncts such as extracorporeal carbon dioxide removal may be useful to normalize pH and carbon dioxide levels, but further studies will be necessary to demonstrate benefit with this technology.
FRI0334 What is the absolute risk of developing diabetes mellitus in patients with glucocorticoid-treated polymyalgia rheumatica and giant cell arteritis? a systematic review and meta-analysis
Authors: L Lai, E Harris, RM West, SL Mackie
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) are treated with glucocorticoids (GCs) but long-term GC use is associated with diabetes mellitus (DM). The absolute incidence of this serious complication in this patient group remains unclear. <h3>Objectives</h3> To quantify the absolute risk of GC-induced DM in PMR and GCA in published literature. <h3>Methods</h3> We identified literature from inception to February 2016 reporting diabetes following exposure to oral GC in patients with PMR and/or GCA without pre-existing diabetes. A random-effects meta-analysis was performed to summarise the literature. Risk of bias was assessed using the Cochrane Collaboration tool. <h3>Results</h3> 21 eligible publications were identified. In studies of patients with GCA, mean cumulative GC dose was almost two times higher than in studies of PMR (8.9g vs 5.0g), with slightly longer treatment duration but much longer duration of follow-up (8.8years vs 4.4years). The incidence proportion (cumulative incidence) of patients who developed new-onset DM was 6% (95% CI: 3–9%) for PMR and 12% (95% CI: 8–17%) for GCA. Heterogeneity between studies was high (I<sup>2</sup>=78.2%), as there were differences in study designs, patient population, geographical locations and treatment strategies. Based on UK data on incidence rate of DM in the general population<sup>1</sup>, the expected background incidence rate of DM over 4.4 years in PMR patients and 8.8 years in GCA patients (the duration of follow-up) would be 4.8% and 9.7%, respectively. Very little information on predictors of DM in PMR or GCA patients was found. The overall risk of bias was high for many of the observational studies, especially relating to definition and recording of outcome and prognostic variables. <h3>Conclusions</h3> Physicians should screen patients treated for PMR/GCA for DM but it remains unclear what is the time-period of greatest risk and the influence of risk factors. Our meta-analysis produced plausible estimates of DM incidence in patients with PMR and GCA but there is insufficient published data to allow precise quantification of the DM risk or, crucially, which patients are at greatest risk. <h3>References</h3> Sharma M et al. BMJ Open, 2016. 6(1): p.e010210. <h3>Disclosure of Interest</h3> None declared
Adenovirotherapy Delivering Cytokine and Checkpoint Inhibitor Augments CAR T Cells against Metastatic Head and Neck Cancer
Authors: Amanda Rosewell Shaw, Caroline E. Porter, Norihiro Watanabe, Kiyonori Tanoue, Andrew Sikora, Stephen Gottschalk, Malcolm K. Brenner, Masataka Suzuki
Journal: Molecular Therapy (2017)

In solid tumors, chimeric antigen receptor (CAR)-modified T cells must overcome the challenges of the immunosuppressive tumor microenvironment. We hypothesized that pre-treating tumors with our binary oncolytic adenovirus (CAd), which produces local oncolysis and expresses immunostimulatory molecules, would enhance the antitumor activity of HER2-specific CAR T cells, which alone are insufficient to cure solid tumors. We tested multiple cytokines in conjunction with PD-L1-blocking antibody and found that Ad-derived IL-12p70 prevents the loss of HER2.CAR-expressing T cells at the tumor site. Accordingly, we created a construct encoding the PD-L1-blocking antibody and IL-12p70 (CAd12_PDL1). In head and neck squamous cell carcinoma (HNSCC) xenograft models, combining local treatment with CAd12_PDL1 and systemic HER2.CAR T cell infusion improved survival to >100 days compared with approximately 25 days with either approach alone. This combination also controlled both primary and metastasized tumors in an orthotopic model of HNSCC. Overall, our data show that CAd12_PDL1 augments the anti-tumor effects of HER2.CAR T cells, thus controlling the growth of both primary and metastasized tumors. In solid tumors, chimeric antigen receptor (CAR)-modified T cells must overcome the challenges of the immunosuppressive tumor microenvironment. We hypothesized that pre-treating tumors with our binary oncolytic adenovirus (CAd), which produces local oncolysis and expresses immunostimulatory molecules, would enhance the antitumor activity of HER2-specific CAR T cells, which alone are insufficient to cure solid tumors. We tested multiple cytokines in conjunction with PD-L1-blocking antibody and found that Ad-derived IL-12p70 prevents the loss of HER2.CAR-expressing T cells at the tumor site. Accordingly, we created a construct encoding the PD-L1-blocking antibody and IL-12p70 (CAd12_PDL1). In head and neck squamous cell carcinoma (HNSCC) xenograft models, combining local treatment with CAd12_PDL1 and systemic HER2.CAR T cell infusion improved survival to >100 days compared with approximately 25 days with either approach alone. This combination also controlled both primary and metastasized tumors in an orthotopic model of HNSCC. Overall, our data show that CAd12_PDL1 augments the anti-tumor effects of HER2.CAR T cells, thus controlling the growth of both primary and metastasized tumors.
SAT0587 School bags weight are not associated with low back pain in schoolchildren in cameroon
Authors: F Kemta Lekpa, MS Doualla, H Namme Luma
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Data are mixed on the role of school bags in the occurrence of low back pain in pupils. <h3>Objectives</h3> Thus, we carried out this study with the aim to determine if the school bags were a factor associated with low back pain in Cameroonian schoolchildren. <h3>Methods</h3> We performed a cross-sectional study between December 2015 and April 2016 in 10 primary schools of the city of Douala, Cameroon. A questionnaire was submitted to the students of these different schools. Informed and signed consent of their parents were obtained. Sociodemographic and clinical data were collected, as well as the weight of each school bags. A p&lt;0.05 was significant. <h3>Results</h3> We included 1075 pupils (543 boys, 532 girls). The mean age was 11±1 years (8–16 years). BMI was normal in 928 children (86.5%). The prevalence of low back pain was 12.3% (132 children: 81 girls and 51 boys). Sixteen children had already met a physician for low back pain. The mean weight of the school bag was 4.9±1.9 kg, with 369 children (57.7%) with a school bags weight ≥15% of their body weight in private schools compared with 56 (12.9%) in public schools. We had 99 children with low back pain with a school bag weight ≥10% of their body weight (Table 1). We didn9t find any relationship between low back pain and the weight of the school bag, regardless of gender, BMI, age of pain, type of school, distance from home to school, way of transportation, and age (p&gt;0.05). However, the exception was found in girls aged from 8 to 10 years with a school bag weight &gt;15% of their body weight (p=0.05). Furthermore, in univariate analysis, factors associated with low back pain were (p&lt;0.05): age, history of low back pain in at least one parent, competitive sport, a bad seated position on school benches. In multivariate analysis, factors associated with low back pain were female, competitive sport, and low back pain in at least one parent (Table 2). <h3>Conclusions</h3> The weight of the school bags was not associated with low back pain in Cameroonian schoolchildren (except for girls aged from 8 to 10). However, female, competitive sport and low back pain in at least one parent were associated to low back pain. <h3>Disclosure of Interest</h3> None declared
画像誘導治療のための新しいX線不透過性塞栓術ビーズの送達に関連した長期生体適合性,画像診断所見と組織効果【Powered by NICT】
Authors: V Sharma Karun, Bascal Zainab, Kilpatrick Hugh, Ashrafi Koorosh, L Willis Sean, R Dreher Matthew, L Lewis Andrew
Journal: Biomaterials (2016)
Behavioral Economics and Health Insurance Reform
Authors: Edwin Colloff
Journal: JAMA (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Annals Story Slam - Making It Up on the Spot
Authors: Ariel Lefkowitz
Journal: Annals of Internal Medicine (2017)

Web Exclusives19 September 2017Annals Story Slam - Making It Up on the SpotFREEAriel Lefkowitz, MDAriel Lefkowitz, MDFrom University of Toronto, Toronto, Ontario, Canada.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/W17-0048 SectionsAboutVisual Abstract ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Video. Annals Story Slam - Making It Up on the Spot "Making It Up on the Spot," by Dr. Ariel Lefkowitz (Duration 06:27)Building on the popular Annals feature “On Being a Doctor,” storytellers share stories about the experience of doctoring on video.For more videos from and information on Annals Story Slam, visit go.annals.org/StorySlam. Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: From University of Toronto, Toronto, Ontario, Canada.Current Author Address: Ariel Lefkowitz, MD, University of Toronto, Toronto, Ontario, Canada; e-mail, ariel.[email protected]com. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 19 September 2017Volume 167, Issue 6Page: SS1 ePublished: 19 September 2017 Issue Published: 19 September 2017 Copyright & PermissionsCopyright © 2017 by American College of Physicians. All Rights Reserved.Loading ...
AB1134 Characteristics of autoimmune featured interstitial lung disease in korean patients
Authors: J-H Kim, J Jae Hyun, YH Seo, SJ Choi, GG Song
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Interstitial lung disease (ILD) includes a heterogeneous group of disorders that result in diffuse parenchymal lung disease, with overlapping clinical, radiographic, and physiologic manifestations. Several rheumatologic conditions are associated with the development of ILD. There are many patients who are not diagnosed as definite connective tissue disease (CTD). These patients may have an undifferentiated connective tissue disease (UCTD). <h3>Objectives</h3> The aim of this study was to compare the prevalence and characteristics of patients with CTD-ILD, UCTD-ILD and Idiopathic pulmonary fibrosis (IPF) in Korean patients. <h3>Methods</h3> We study compared the prevalence and characteristics of patients with connective tissue disease-associated interstitial lung disease (CTD-ILD), undifferentiated connective tissue disease-associated interstitial lung disease (UCTD-ILD), or idiopathic pulmonary fibrosis (IPF) between January 2015 and June 2016 in Korea university guro hospital. Clinical characteristics, laboratory tests, and high-resolution CT images were analyzed and compared among three groups. <h3>Results</h3> CTD-ILD was identified in 13.0%, UCTD-ILD in 18.2%, and IPF in 68.7% among 307 patients. Female and younger age patients were dominant in CTD-ILD group. Pulmonary symptoms were more common in IPF, while extra-pulmonary symptoms were more common in CTD-ILD and UCTD-ILD group. Patients with CTD-ILD had more abnormal antibody tests than those of UCTD-ILD and IPF. Usual interstitial pneumonia pattern was dominant in HRCT images among three groups. <h3>Conclusions</h3> CTD-ILD is not able to be diagnosed accurately in ILD patients. A systematic evaluation of extra-pulmonary symptoms and serologic tests in patients with ILD can identify CTD-ILD, UCTD-ILD, and IPF. <h3>References</h3> Vij R, Noth I, Strek ME. Autoimmune-featured interstitial lung disease: a distinct entity. Chest. 2011;140(5):1292–9. Castelino FV, Varga J. Interstitial lung disease in connective tissue diseases: evolving concepts of pathogenesis and management. Arthritis Res Ther. 2010;12(4):213. Kinder BW, Shariat C, Collard HR et al. Undifferentiated connective tissue disease-associated interstitial lung disease: changes in lung function. Lung. 2010;188(2):143–9. <h3>Disclosure of Interest</h3> None declared
SAT0484 Low magnesium intake is associated with increased pain in subjects with radiographic knee osteoarthritis: data from the osteoarthritis initiative
Authors: A Shmagel, N Onizuka, T Vo, L Langsetmo, K Ensrud, R Foley, P Valen
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Osteoarthritis pain appears to be caused, at least in part, by alterations in peripheral and/or central nociceptive pathways.[1] As magnesium is a known mediator of nociception, we hypothesized that low magnesium intake may be associated with increased pain in radiographic knee OA. <h3>Objectives</h3> To evaluate whether magnesium intake is associated with knee pain in radiographic knee osteoarthritis. <h3>Methods</h3> We investigated the associations between knee pain and magnesium intake from food and supplements in 2549 participants with prevalent radiographic knee OA (Kellgren-Lawrence score ≥2) in the Osteoarthritis Initiative cohort.[2] WOMAC pain scores in the affected knee were reported annually with total follow up period of 48 months. Magnesium intake was assessed at baseline by food frequency questionnaire and dietary supplement questionnaire, and expressed in gender-specific calorie-adjusted quintiles. Analyses used generalized linear mixed effects models with repeated measures. <h3>Results</h3> Among participants with baseline radiographic knee OA the mean total magnesium intake was 310 mg/day (SD 133) for men, and 288 mg/day (SD 118) for women, with 68% of men and 44% of women below the estimated average requirement (EAR). The mean WOMAC pain score at 0, 12, 24, 36, and 48 months of follow up was 3.5 (SD 3.8), median score 2 (IQR 0; 6). After adjustment for age, gender, BMI, caloric intake, physical activity, smoking status, alcohol use, renal insufficiency, and the use of analgesics, subjects in the lowest gender-specific quintile of magnesium intake (Q1) had, on average, 1 point higher WOMAC knee pain scores than subjects in the highest quintile (Q5): Q1 β (95% CI) 1.00 (0.61–1.39), Q2 0.69 (0.32–1.06), Q3 0.25 (-0.12–0.62), Q4 0.25 (-0.14–0.64); p&lt;0.0001. <h3>Conclusions</h3> In a cohort of adults with prevalent radiographic knee osteoarthritis, magnesium intake overall was below recommended. Low magnesium intake at baseline was associated with increased pain in the affected knee over 48 months of follow up. These findings may be of growing importance as the average dietary magnesium intake for humans is declining.[3] <h3>References</h3> Thakur M, Dickenson AH, Baron R. Osteoarthritis pain: nociceptive or neuropathic? Nat Rev Rheumatol. 2014;10(6):374–380. doi: 10.1038/nrrheum.2014.47. Fawaz-Estrup F. The osteoarthritis initiative: an overview. Med Health R I. 2004;87(6):169–171. Rosanoff A, Weaver CM, Rude RK. Suboptimal magnesium status in the United States: are the health consequences underestimated? Nutr Rev. 2012;70(3):153–164. doi:10.1111/j.1753–4887.2011.00465.x. <h3>Disclosure of Interest</h3> None declared
Female ClockΔ19/Δ19 mice are protected from the development of age-dependent cardiomyopathy
Authors: Faisal J Alibhai, Cristine J Reitz, Willem T Peppler, Poulami Basu, Paul Sheppard, Elena Choleris, Marica Bakovic, Tami A Martino
Journal: Cardiovascular Research (2017)

Abstract Aims Circadian rhythms are important for healthy cardiovascular physiology and they are regulated by the molecular circadian mechanism. Previously, we showed that disruption of the circadian mechanism factor CLOCK in male ClockΔ19/Δ19 mice led to development of age-dependent cardiomyopathy. Here, we investigate the role of biological sex in protecting against heart disease in aging female ClockΔ19/Δ19 mice. Methods and results Female ClockΔ19/Δ19 mice are protected from the development of cardiomyopathy with age, as heart structure and function are similar to 18 months of age vs. female WT mice. We show that female ClockΔ19/Δ19 mice maintain normal glucose tolerance as compared with female WT. Tissue metabolic profiling revealed that aging female ClockΔ19/Δ19 mice maintain normal cardiac glucose uptake, whereas the male ClockΔ19/Δ19 mice have increased cardiac glucose uptake consistent with pathological remodelling. Shotgun lipidomics revealed differences in phospholipids that were sex and genotype specific, including cardiolipin CL76:11 that was increased and CL72:8 that was decreased in male ClockΔ19/Δ19 mice. Additionally, female ClockΔ19/Δ19 mice show increased activation of AKT signalling and preserved cytochrome c oxidase activity compared with male ClockΔ19/Δ19 mice, which can help to explain why they are protected from heart disease. To determine how this protection occurs in females even with the Clock mutation, we examined the effects of ovarian hormones. We show that ovarian hormones protect female ClockΔ19/Δ19 mice from heart disease as ovariectomized female ClockΔ19/Δ19 mice develop cardiac dilation, glucose intolerance and reduced cardiac cytochrome c oxidase; this phenotype is consistent with the age-dependent decline observed in male ClockΔ19/Δ19 mice. Conclusions These data demonstrate that ovarian hormones protect female ClockΔ19/Δ19 mice from the development of age-dependent cardiomyopathy even though Clock function is disturbed. Understanding the interaction of biological sex and the circadian mechanism in cardiac growth, renewal and remodelling opens new doors for understanding and treating heart disease.
Circulating Cell-free DNA for Metastatic Cervical Cancer Detection, Genotyping, and Monitoring
Authors: Zhigang Kang, Sanja Stevanović, Christian S. Hinrichs, Liang Cao
Journal: Clinical Cancer Research (2017)

Circulating cell-free (ccf) human papillomavirus (HPV) DNA may serve as a unique tumor marker for HPV-associated malignancies, including cervical cancer. We developed a method to genotype and quantify circulating HPV DNA in patients with HPV16- or HPV18-positive metastatic cervical cancer for potential disease monitoring and treatment-related decision making.
AB0063 The protective effect of PFTα on alcohol-induced osteonecrosis of the femoral head
Authors: C Yixuan
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Epidemiologic studies have shown that alcohol plays a pivotal role in the development of osteonecrosis of the femoral head (ONFH). However, few studies have discussed the pathogenesis of or interventions for alcohol-induced ONFH. <h3>Objectives</h3> The aim of this study was to explore the underlying mechanism of alcohol-induced ONFH and the protective effect of pifithrin-α (PFTα). <h3>Results</h3> Through a series of <i>in vitro</i> assessments, we found that ethanol treatment significantly activated p53, suppressed Wnt/β-catenin signaling and inhibited osteogenic-related proteins, including runt-related transcription factor 2 (RUNX2), osteocalcin (OCN), osteopontin (OPN) and collagen I (COL1). Furthermore, by separating the cytoplasmic and nuclear proteins, we found that ethanol inhibited osteogenesisby impairing the accumulation of β-cateninin both the cytoplasm and nucleus in human bone mesenchymal stem cells (hBMSCs), which resulted from activating glycogen synthase kinase-3β (GSK-3β). In this <i>in vivo</i> study, we established alcohol-induced ONFH in rats and investigated the protective effect of PFTα. Micro-CT, hematoxylin &amp; eosin (H&amp;E) staining, immunohistochemical analyses, immunofluorescence staining, TUNEL staining, and fluorochrome labeling were performed to reveal the PFTα-induced therapeutic effects. H&amp;E findings combined with TUNEL, caspase-3-cleaved immunohistochemical staining, and micro-CT images revealed obvious ONFH in the alcohol-administered rats, whereas significantly less osteonecrosis developed in the rats injected with PFTα. As the initiator of osteogenesis, RUNX2 and its downstream targets OCN, OPN, COL1 were immunostained in the femoral heads. These results indicated that those osteogenic-related proteins were significantly decreased in the alcohol-administered rats, whereas these results were reversed in the PFTα-injected rats. Fluorochrome labeling showed a similar result in that alcohol significantly reduced the osteogenic activity in the rat femoral head, which was blocked by the injection of PFTα. <h3>Conclusions</h3> Pifithrin-α, a p53 inhibitor, was able to block the ethanol-triggered activation of p53 in hBMSCs and alcohol-induced ONFH in a rat model. Its antagonistic effect against ethanol9s effect on hBMSCs could be a clinical strategy to prevent the development of alcohol-induced ONFH. <h3>Acknowledgements</h3> The current study was supported by grants from the National Natural Science Foundation of China (no. 81272003 andno. 81301572) and the SMC-Chen Xing Plan for Splendid Young Investigators of Shanghai Jiao Tong University. <h3>Disclosure of Interest</h3> None declared