tbuckley/cabot-search huggingface dataset:
Non-invasive ventilation as a strategy for weaning from invasive mechanical ventilation: a systematic review and Bayesian meta-analysis
Authors: Joyce Yeung, Keith Couper, Elizabeth G. Ryan, Simon Gates, Nick Hart, Gavin D. Perkins
Journal: Intensive Care Medicine (2018)

A systematic review and meta-analysis was conducted to answer the question 'In adults with respiratory failure requiring invasive ventilation for more than 24 h, does a weaning strategy with early extubation to non-invasive ventilation (NIV) compared to invasive ventilation weaning reduce all-cause hospital mortality?'We included randomised and quasi-randomised controlled trials that evaluated the use of non-invasive ventilation, compared to invasive ventilation, as a weaning strategy in adults mechanically ventilated for at least 24 h. The EMBASE, MEDLINE and Cochrane Central Register of Controlled Trials (CENTRAL) bibliographic databases were searched from inception to February 2018. Bayesian hierarchical models were used to perform the meta-analysis. The primary outcome was mortality at hospital discharge. Secondary outcomes included mortality (30, 60, 90 and 180 days), quality of life, duration of invasive ventilation, weaning failure, length of stay [intensive care unit (ICU) and hospital] and adverse events.Twenty-five relevant studies involving 1609 patients were included in the quantitative analysis. Studies had moderate to high risk of bias due to risk of performance and detection bias. Mortality at hospital discharge was lower in the NIV weaning group compared to the invasive weaning group [pooled odds ratio (OR) 0.58, 95% highest density interval (HDI) 0.29-0.89]. Subgroup analyses showed lower pooled mortality at hospital discharge rates in NIV weaning than those in the control group in chronic obstructive pulmonary disease (COPD) patients (pooled OR 0.43, 95% HDI 0.13-0.81) and the effect is less certain in the mixed ICU population (pooled OR 0.88, 95% HDI 0.25-1.48). NIV weaning reduced the duration of invasive ventilation in patients [standardised mean difference (SMD) - 1.34, 95% HDI - 1.92 to - 0.77] and ICU length of stay (SMD - 0.70, 95% HDI - 0.94 to - 0.46). Reported rates of ventilator associated pneumonia (VAP) were lower in the NIV group. NIV weaning did not reduce overall hospital length of stay or long-term mortality. There were insufficient data to compare other adverse events and health-related quality of life.The use of NIV in weaning from mechanical ventilation decreases hospital mortality, the incidence of VAP and ICU length of stay. NIV as a weaning strategy appears to be most beneficial in patients with COPD.
Abstract 14895: Catheter-Based Treatment for Pulmonary Embolism With Concomitant Use of Intrapulmonary Thrombolysis Improves In-Hospital Mortality Rates
Authors: Rajat Kalra, Navkaranbir S Bajaj, Jason L Guichard, Sameer Ather, William J Lancaster, Fabio Raman, Pankaj Arora, Donald T Clark, David C McGiffin, Mustafa I Ahmed
Journal: Circulation (2015)

Introduction: In-hospital mortality rates after catheter-based treatment (CBT) of high-risk pulmonary embolism (PE) are variable. Use of intrapulmonary thrombolytics with other CBT may result in rapid clearance of obstruction, prevent extremis and lead to improved mortality rates. Hypothesis: We hypothesized that the concomitant use of intrapulmonary thrombolysis in conjunction with CBT may affect mortality and explain the heterogeneity among in-hospital mortality rates. Methods: We searched SCOPUS since inception to November 2014 using predefined criteria. Studies reporting in-hospital mortality in patients with massive PE or a combination of massive and submassive PE, as defined by the American Heart Association, were included. In-hospital all-cause mortality rates were estimated in these high-risk patients using standard meta-analytic methods. Heterogeneity in mortality rates was explored with meta-regression. Results: In 54 eligible studies with 1,333 patients, 1357 CBT procedures were performed. All CBT modalities were studied. In-hospital mortality rates varied widely amongst studies (Figure, Panel A). On meta-regression with Logit-in hospital mortality rate as the dependent variable, studies that had a higher proportion of patients who received concomitant intrapulmonary thrombolysis had lower Logit in-hospital mortality rate (β = - 0.01, p &lt;0.001; Figure, Panel B). Conclusions: Concomitant use of intrapulmonary thrombolytics is associated with lower in-hospital mortality rate in patients undergoing CBT for high-risk PE.
microRNA diagnostic panel for Alzheimer’s disease and epigenetic trade-off between neurodegeneration and cancer
Authors: Siranjeevi Nagaraj, Katarzyna Marta Zoltowska, Katarzyna Laskowska-Kaszub, Urszula Wojda
Journal: Ageing Research Reviews (2018)

microRNAs (miRNAs) have been extensively studied as potential biomarkers for Alzheimer's disease (AD). Their profiles have been analyzed in blood, cerebrospinal fluid (CSF) and brain tissue. However, due to the high variability between the reported data, stemming from the lack of methodological standardization and the heterogeneity of AD, the most promising miRNA biomarker candidates have not been selected. Our literature review shows that out of 137 miRNAs found to be altered in AD blood, 36 have been replicated in at least one independent study, and out of 166 miRNAs reported as differential in AD CSF, 13 have been repeatedly found. Only 3 miRNAs have been consistently reported as altered in three analyzed specimens: blood, CSF and the brain (hsa-miR-146a, hsa-miR-125b, hsa-miR-135a). Nonetheless, all 36 repeatedly differential miRNAs in AD blood are promising as components of the diagnostic panel. Given their predicted functions, such miRNA panel may report multiple pathways contributing to AD pathology, enabling the design of personalized therapies. In addition, the analysis revealed that the miRNAs dysregulated in AD overlap highly with miRNAs implicated in cancer. However, the directions of the miRNA changes are usually opposite in cancer and AD, indicative of an epigenetic trade-off between the two diseases.
PI3 kinase-AKT-mTOR pathway is essential for neuroendocrine differentiation of prostate cancer
Authors: Chengyu Wu, Jiaoti Huang
Journal: Cancer Research (2007)

124  Hormonal therapy (androgen ablation and/or anti-androgen) is initially effective in treating patients with advanced prostate cancer, but the tumor eventually recurs with the tumor cells growing in the androgen-deprived environment (hormone-  refractory or androgen-independent (AI) stage). The mechanism of AI proliferation of prostate cancer is unknown. Hormonal therapy induces neuroendocrine (NE) differentiation (NED) of cancer cells, which may contribute to AI growth of prostate cancer. The mechanism of NED is unclear. We studied signal transduction pathways in NED of the LNCaP prostate cancer cells after androgen withdrawal, and showed that both the PI3 kinase-AKT-mTOR pathway and ERK are activated but only the former is required for NED. A constitutively active AKT promotes NED while a dominant negative AKT inhibits NED. Activation of AKT by IGF-1 also leads to NED; and NED induced by epinephrine requires AKT activation. Therefore, we have demonstrated a novel function of the PI3 kinase-AKT-mTOR pathway in prostate cancer progression. Our study has also identified potential molecular targets which may be explored for designing novel therapeutic strategies for the prevention and treatment of AI prostate cancer.
GWAS of Complete Blood Count (CBC) Measures in 13,403 Blood Donors in the Multi-Racial RBC-Omics Study Reveal Novel Genetic Loci in Minority Populations Which Provide Insights into the Pathways That May Connect Them to Disease
Authors: Yuelong Guo, Grier Page, Alan E. Mast, Richard G. Cable, Bryan R Spencer, Joseph Kiss, Stacey Endres, Steven Kleinman, Michael Paul Busch
Journal: Blood (2017)
An inhaled “bifunctional” dual PDE3/4 inhibitor provides additional short-term improvements in lung function compared to existing classes of bronchodilator: implications for future treatment of COPD
Authors: Mario Cazzola, Clive Page
Journal: European Respiratory Journal (2018)

<b>RPL554 showed substantial bronchodilation in COPD patients but far more information from more appropriate investigations is required before we have a proper understanding of the real role that RPL554 could have in the treatment of COPD</b>http://ow.ly/pjte30m128c
Tocilizumab in patients with adult-onset Still’s disease refractory to glucocorticoid treatment
Authors: Young Ho Lee
Journal: Annals of the Rheumatic Diseases (2018)

Tocilizumab in patients with adult-onset Still's disease refractory to glucocorticoid treatment I was pleased to read the article by Kaneko and colleagues 1 on the efficacy and safety of tocilizumab in patients with adult-onset Still's disease, because the current information on its biologic efficacy has been mainly obtained from small retrospective case series and not from prospective randomised trials.The authors have presented a randomised controlled trial in which they suggest that tocilizumab is effective in adult-onset Still's disease refractory to glucocorticoid treatment.Information on biologic therapy for the management of adult-onset Still's disease is scarce.In this regard, there is a noteworthy issue.At present, the treatment of patients with adult-onset Still's disease remains empirical. 2Corticosteroids are the cornerstones of the initial treatment, and conventional disease-modifying antirheumatic drugs (DMARDs), such as methotrexate, hydroxychloroquine, leflunomide, ciclosporin, tacrolimus and azathioprine, are generally used alone or in combination.DMARDs are effective means of inducing remission, lowering the risk of relapse and minimising glucocorticoid therapy and toxicity in adult-onset Still's disease. 3Thus, DMARDs are therapeutic options in addition to the standard-of-care treatment with glucocorticoids for this disease. 4Biologic agents are generally used as the secondline treatment because of their high cost and potential toxicity. 5iologics may be considered in case of failure of DMARDs to control the disease.Although adult-onset Still's disease is a rare systemic inflammatory disorder, biologic therapy represents a major breakthrough in the management of patients with adult-onset Still's disease refractory to DMARDs.For example, anakinra induced more beneficial responses than DMARDs did in patients with refractory adult-onset Still's disease in a randomised study. 6However, there is no strong evidence regarding the comparative efficacy of tocilizumab and DMARDs in the management of adult-onset Still's disease.Currently, no randomised trial has shown that tocilizumab is superior to DMARDs in treating adult-onset Still's disease refractory to glucocorticoid treatment.Thus, treatment for adult-onset Still's disease continues to be a challenge.Further randomised studies are warranted to determine the benefits of tocilizumab in terms of its glucocorticoid-sparing effect, remission and reduction in relapse, compared with DMARD therapy.
Abstract P136: Adherence to the Mediterranean Diet is Associated With Lower Pericardial Fat in African-Caribbean Men
Authors: Curtis Tilves, Allison L Kuipers, Joseph M Zmuda, J J Carr, James G Terry, Sangeeta Nair, Akira Sekikawa, Dylan Falk, Dan Ramdath, Clareann H Bunker, Victor Wheeler, Iva Miljkovic
Journal: Circulation (2018)

Introduction: Adherence to a Mediterranean-style diet pattern has been associated with altered body fat distribution among African Americans. To further evaluate these relationships, we investigated associations of adherence to the Alternative Mediterranean Diet (aMED) pattern with fat deposition in an ongoing cohort study of African-Caribbean men. Methods: Diet was assessed from 2014-2017 using a 146-item semi-quantitative food frequency questionnaire in the Tobago Health Study (N = 800, mean age=64.1, mean BMI=27.7). Adherence to the aMED pattern (score range 0-9) was calculated as the following: +1 for intake above the population median for fruits, vegetables, whole grains, nuts, legumes, fish, and monounsaturated:saturated fat ratio; +1 for intake below the population median for red and processed meats; and +1 for alcohol intake between 10-25 grams per day. Walking, TV watching, and smoking were assessed by interviewer-administered questionnaires. Abdominal subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), and pericardial adipose tissue (PAT) depot volumes were measured in a subset of this cohort (N = 679) using computed tomography. Multiple linear regressions were performed across adherence groups. Results: The average age was 64.1 ± 8.8 years old. After adjusting for age, walking, TV watching, total energy intake, and BMI (for VAT and PAT models only), PAT significantly decreased across increasing aMED adherence groups (P=0.0174), with median PAT being 8% lower in the high-adherence versus low-adherence group. No other fat measure significantly differed by adherence group (Table). Conclusion: Higher adherence to the aMED pattern was significantly associated with reduced PAT, but not with measures of general or central fat, in middle-aged and older African Caribbean men. Further studies are needed on dietary patterns and ectopic fat distribution to fully describe the potential impact of race/ethnicity.
Abstract 18844: Diagnosis of Thin-capped Fibroatheromas in Intravascular Optical Coherence Tomography Images: Effects of Light Scattering
Authors: Taylor Hoyt, Jennifer Phipps, Deborah Vela, Tianyi Wang, Maximillian Buja, Ik-Kyung Jang, Thomas Milner, Marc Feldman
Journal: Circulation (2015)

Objectives: Intravascular optical coherence tomography (IVOCT) images are recorded by detecting light backscattered within coronary arteries. We hypothesize that non- thin-cap fibroatheroma (TCFA) etiologies may scatter light to create the false appearance of IVOCT TCFA. Background: Conflicting reports are recognized about the accuracy of IVOCT for TCFA detection. Methods: Ten human cadaver hearts were imaged with IVOCT (N=14 arteries). Coronary arteries were sectioned at 120 μm intervals. IVOCT and histologic TCFA were co-registered and compared. Results: Of 21 IVOCT TCFAs identified by two independent IVOCT core labs (fibrous cap &lt;65 μm, lipid arc &gt;90°), only 8 were true histologic TCFA. Foam cell infiltration was responsible for 62% of cases in which either thick-capped fibroatheromas (ThKFAs) appeared like TCFAs or arterial tissue appeared like TCFAs when no lipid core was present. Other false IVOCT TCFA etiologies included SMC-rich fibrous tissue (15%) and loose connective tissue (8%). If the lipid arc &gt;90° criterion was disregarded, 45 IVOCT TCFAs were identified, and sensitivity of IVOCT TCFA detection increased from 53% to 88%; specificity remained high at 93%, and the presence of a new IVOCT image feature called “bright streaks” increased positive predictive value (PPV) to 53%. New mechanisms for light scattering are proposed to explain the low PPV of IVOCT to identify true TCFA (44%), and explain why other plaque components can masquerade as IVOCT TCFA. Conclusions: IVOCT can exhibit up to 88% sensitivity and 98% specificity to detect TCFA, but PPV is limited due to multiple etiologies that cause light scattering similar to true TCFA. Disregarding the lipid arc &gt;90° IVOCT TCFA requirement, and the identification of a new feature, bright steaks, can enhance the ability of IVOCT to detect TCFA. Combining IVOCT with another imaging modality that more specifically recognizes lipid will be important for increasing PPV in the future.
Ethnic, Racial, and Sex Differences in Etiology, Symptoms, Treatment, and Symptom Outcomes of Patients With Gastroparesis
Authors: Henry P. Parkman, Goro Yamada, Mark L. Van Natta, Katherine Yates, William L. Hasler, Irene Sarosiek, Madhusudan Grover, Ron Schey, Thomas L. Abell, Kenneth L. Koch, Braden Kuo, John Clarke, Gianrico Farrugia, Linda Nguyen, William J. Snape, Laura Miriel, James Tonascia, Frank Hamilton, Pankaj J. Pasricha, Richard W. McCallum
Journal: Clinical Gastroenterology and Hepatology (2018)
Identification of new molecular targets for PET imaging of the microglial anti-inflammatory activation state
Authors: Alessandro Villa, Barbara Klein, Bieneke Janssen, Jordi Pedragosa, Giovanna Pepe, Bastian Zinnhardt, Danielle J. Vugts, Paolo Gelosa, Luigi Sironi, Wissam Beaino, Annelaure Damont, Frédéric Dollé, Benoit Jego, Alexandra Winkeler, Dieter Ory, Olof Solin, Johnny Vercouillie, Uta Funke, Sandra Laner-Plamberger, Linda V. Blomster, Palle Christophersen, Elisabetta Vegeto, Ludwig Aigner, Andreas Jacobs, Anna M. Planas, Adriana Maggi, Albert D. Windhorst
Journal: Theranostics (2018)

Microglia are potential targets for therapeutic intervention in neurological and neurodegenerative diseases affecting the central nervous system. In order to assess the efficacy of therapies aimed to reduce the tissue damaging activities of microglia and/or to promote the protective potential of these cells, suitable pre-clinical and clinical tools for the in vivo analysis of microglia activities and dynamics are required. The aim of this work was to identify new translational markers of the anti-inflammatory / protective state of microglia for the development of novel PET tracers. Methods: New translational markers of the anti-inflammatory/protective activation state of microglia were selected by bioinformatic approaches and were in vitro and ex vivo validated by qPCR and immunohistochemistry in rodent and human samples. Once a viable marker was identified, a novel PET tracer was developed. This tracer was subsequently confirmed by autoradiography experiments in murine and human brain tissues. Results: Here we provide evidence that P2RY12 expression increases in murine and human microglia following exposure to anti-inflammatory stimuli, and that its expression is modulated in the reparative phase of experimental and clinical stroke. We then synthesized a novel carbon-11 labeled tracer targeting P2RY12, showing increased binding in brain sections of mice treated with IL4, and low binding to brain sections of a murine stroke model and of a stroke patient. Conclusion: This study provides new translational targets for PET tracers for the anti-inflammatory/protective activation state of microglia and shows the potential of a rationale-based approach. It therefore paves the way for the development of novel non-invasive methodologies aimed to monitor the success of therapeutic approaches in various neurological diseases.
Prisoners’ health: government must do more, say MPs
Authors: Gareth Iacobucci
Journal: BMJ (2018)

Ministers must take urgent action to improve the health of inmates in UK prisons, MPs have urged.

The House of Commons health and social care select committee said that poor conditions, driven by staff shortages and overcrowding, were limiting prisoners’ access to healthcare and their ability to lead healthy lives. It concluded in a report that many UK prisons are currently unsafe, with incidences of violence and self harm at a record high.1

The report noted that mortality in prison is 50% higher than in the general population. The …
Updated Analysis of a Phase 1, Open-Label Study of LCAR-B38M, a Chimeric Antigen Receptor T Cell Therapy Directed Against B-Cell Maturation Antigen, in Patients with Relapsed/Refractory Multiple Myeloma
Authors: Wan-Hong Zhao, Jie Liu, Bai-Yan Wang, Yin-Xia Chen, Xing-Mei Cao, Yun Yang, Yi-Lin Zhang, Fang-Xia Wang, Peng-Yu Zhang, Bo Lei, Liu-Fang Gu, Jian-Li Wang, Nan Yang, Ru Zhang, Hui Zhang, Ying Shen, Ju Bai, Yan Xu, Xu-Geng Wang, Rui-Li Zhang, Li-Li Wei, Zong-Fang Li, Zhen-Zhen Li, Yan Geng, Qian He, Qiu-Chuan Zhuang, Frank Xiao-Hu Fan, Ai-Li He, Wang-Gang Zhang
Journal: Blood (2018)
Attenuated Psychophysiological Reactivity following Single-Session Group Imagery Rescripting versus Verbal Restructuring in Social Anxiety Disorder: Results from a Randomized Controlled Trial
Authors: Matthew P. Hyett, Samantha R. Bank, Ottmar V. Lipp, David M. Erceg-Hurn, Gail A. Alvares, Ellen Maclaine, Emily Puckridge, Sarra Hayes, Peter M. McEvoy
Journal: Psychotherapy and Psychosomatics (2018)

&lt;b&gt;&lt;i&gt;Background:&lt;/i&gt;&lt;/b&gt; The effectiveness of psychotherapies for social anxiety disorder (SAD) is typically evaluated using self- and clinician-reported symptom change, while biomarkers of treatment response are rarely measured. The current study aimed to compare biomarkers of response following two brief group interventions for SAD. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; This randomized controlled trial evaluated the effectiveness of single-session group interventions for SAD (&lt;i&gt;n&lt;/i&gt; = 58) – imagery rescripting (IR) and verbal restructuring (VR) versus waitlist control (WC). The IR intervention guided participants to rescript autobiographical memories through visualization whilst the VR intervention focused on thought challenging. Trial outcomes included change in psychophysiological reactivity (heart rate variability (HRV) and electrodermal responding) to social stress, and symptom-based measures (social interaction anxiety, negative self-portrayal, cognitive avoidance, repetitive negative thinking, memory modification, anxious behaviors). &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; Psychophysiological reactivity was selectively attenuated following IR treatment, compared to VR and WC groups. The specific influence of the imagery-based intervention in modulating autonomic reactivity was evident across HRV parameters, including the standard deviation of intervals between heartbeats (IR vs. WC, &lt;i&gt;d&lt;/i&gt; = 0.67, &lt;i&gt;p&lt;/i&gt; = 0.021; IR vs. VR, &lt;i&gt;d&lt;/i&gt; = 0.58, &lt;i&gt;p&lt;/i&gt; = 0.041), and high frequency power – an indicator of parasympathetically mediated emotion regulation (IR vs. WC, &lt;i&gt;d&lt;/i&gt; = 0.75, &lt;i&gt;p&lt;/i&gt; = 0.034; IR vs. VR, &lt;i&gt;d&lt;/i&gt; = 0.95, &lt;i&gt;p&lt;/i&gt; = 0.006). Few group differences were observed across self-report measures. &lt;b&gt;&lt;i&gt;Conclusion:&lt;/i&gt;&lt;/b&gt; The current study highlights the specificity of brief imagery-based interventions in influencing psychophysiological reactivity in SAD and establishes the sensitivity of objective markers of treatment response in quantifying change over symptom-based measurements.