tbuckley/cabot-search huggingface dataset:
Cerebral white matter disease and functional decline in older adults from the Northern Manhattan Study: A longitudinal cohort study
Authors: Mandip S. Dhamoon, Ying-Kuen Cheung, Yeseon Moon, Janet DeRosa, Ralph Sacco, Mitchell S. V. Elkind, Clinton B. Wright
Journal: PLoS Medicine (2018)

Cerebral white matter hyperintensities (WMHs) on MRI are common and associated with vascular and functional outcomes. However, the relationship between WMHs and longitudinal trajectories of functional status is not well characterized. We hypothesized that whole brain WMHs are associated with functional decline independently of intervening clinical vascular events and other vascular risk factors.In the Northern Manhattan Study (NOMAS), a population-based racially/ethnically diverse prospective cohort study, 1,290 stroke-free individuals underwent brain MRI and were followed afterwards for a mean 7.3 years with annual functional assessments using the Barthel index (BI) (range 0-100) and vascular event surveillance. Whole brain white matter hyperintensity volume (WMHV) (as percentage of total cranial volume [TCV]) was standardized and treated continuously. Generalized estimating equation (GEE) models tested associations between whole brain WMHV and baseline BI and change in BI, adjusting for sociodemographic, vascular, and cognitive risk factors, as well as stroke and myocardial infarction (MI) occurring during follow-up. Mean age was 70.6 (standard deviation [SD] 9.0) years, 40% of participants were male, 66% Hispanic; mean whole brain WMHV was 0.68% (SD 0.84). In fully adjusted models, annual functional change was -1.04 BI points (-1.20, -0.88), with -0.74 additional points annually per SD whole brain WMHV increase from the mean (-0.99, -0.49). Whole brain WMHV was not associated with baseline BI, and results were similar for mobility and non-mobility BI domains and among those with baseline BI 95-100. A limitation of the study is the possibility of a healthy survivor bias, which would likely have underestimated the associations we found.In this large population-based study, greater whole brain WMHV was associated with steeper annual decline in functional status over the long term, independently of risk factors, vascular events, and baseline functional status. Subclinical brain ischemic changes may be an independent marker of long-term functional decline.
Abstract 15910: Evaluation of Prehospital Hypotension Depth-duration Dose and Mortality in Major Traumatic Brain Injury
Authors: Daniel W Spaite, Chengcheng Hu, Bentley J Bobrow, Vatsal Chikani, Bruce J Barnhart, Joshua B Gaither, Kurt R Denninghoff, P. David Adelson, Samuel M Keim, Chad Viscusi, Terry Mullins, Duane Sherrill
Journal: Circulation (2016)

Objective: Prehospital hypotension [systolic BP (SBP) <90 mmHg] dramatically increases mortality in Traumatic Brain Injury (TBI). The literature supporting this concept is based upon a simple dicho...
P008 Methotrexate and baff interaction prevents immunisation against TNF-Α inhibitors by increasing adenosine and regulatory B-cells
Authors: S Bitoun, G Nocturne, B Ly, R Krzysiek, A Pruvost, A Paoletti, J Pascaud, P Dönnes, K Florence, A Gleizes, A Hincelin-Mery, M Allez, S Hacein Bey, M Pallardy, X Mariette
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Introduction</h3> TNFα inhibitors (TNFi), frequently used in patients with autoimmune diseases, can induce anti-drug antibodies (ADA) in one third of cases, leading to secondary resistance. Methotrexate (MTX) is known to decrease immunisation against TNFi. In BAFFtg mice, a model of autoimmune disease in which immunisation against biologic drugs is high, we investigated a new way of tolerization using a single course of MTX and we identified the mechanisms involved in this tolerization. <h3>Objectives</h3> To assess the potential interaction between BAFF and tolerizaion induced by MTX. <h3>Methods</h3> BAFFtg mice treated with TNFi with or without MTX were monitored for drug concentration and ADA. WT and BAFFtg mice were compared for B-Cell surface markers involved in MTX-related purinergic metabolism, adenosine production or B-regulatory cells (Bregs). Then, BAFF levels, MTX treatment and ADA were assessed in the human ABIRISK cohort of patients with chronic inflammatory diseases. <h3>Results</h3> In BAFFtg but not in WT mice, a single course of MTX prevented immunisation against TNFi and maintained drug concentration for over 52 weeks. BAFFtg mice B-cells expressed more CD73 and CD39 leading to more adenosine production and to increase in Breg. MTX-induced tolerization was reversed <i>in vivo</i> using anti-CD73 antibodies. In patients treated with TNFi for chronic inflammatory diseases, high BAFF serum level was protective against ADA formation to TNFi only in patients co-treated with MTX but not in patients on TNFi monotherapy. <h3>Conclusions</h3> This data supports an interaction between MTX and BAFF via increase in CD73 to prevent ADA formation in mice and humans. Treatment increasing CD73 could potentialize the role of MTX to prevent immunisation. <h3>Disclosure of interest</h3> S. Bitoun: None declared, G. Nocturne: None declared, B. Ly: None declared, R. Krzysiek: None declared, A. Pruvost: None declared, A. Paoletti: None declared, J. Pascaud: None declared, P. Dönnes: None declared, K. Florence Employee of: GSK, A. Gleizes: None declared, A. Hincelin-Mery Employee of: Sanofi, M. Allez: None declared, S. Hacein Bey: None declared, M. Pallardy: None declared, X. Mariette: None declared
Global Prevalence of Fetal Alcohol Spectrum Disorder in Italy
Authors: Simona Pichini, Roberta Pacifici, Francesco Paolo Busardò
Journal: JAMA Pediatrics (2018)

To the Editor We read with interest the article by Lange et al,1 who aimed to estimate fetal alcohol spectrum disorder (FASD) among children and young patients in the general population by country, by World Health Organization region, and globally.
Observing dyspnoea in others elicits dyspnoea, negative affect and brain responses
Authors: Michaela Herzog, Josef Sucec, Ilse Van Diest, Omer Van den Bergh, Cecile Chenivesse, Paul Davenport, Thomas Similowski, Andreas von Leupoldt
Journal: European Respiratory Journal (2018)

Dyspnoea is usually caused by diagnosable cardiorespiratory mechanisms. However, frequently dyspnoea relates only weakly or not at all to cardiorespiratory functioning, suggesting that additional neuropsychosocial processes contribute to its experience. We tested whether the mere observation of dyspnoea in others constitutes such a process and would elicit dyspnoea, negative affect and increased brain responses in the observer. In three studies, series of pictures and videos were presented, which either depicted persons suffering from dyspnoea or nondyspnoeic control stimuli. Self-reports of dyspnoea and affective state were obtained in all studies. Additionally, respiratory variables and brain responses during picture viewing (late positive potentials in electroencephalograms) were measured in one study. In all studies, dyspnoea-related pictures and videos elicited mild-to-moderate dyspnoea and increased negative affect compared to control stimuli. This was paralleled by increased late positive potentials for dyspnoea-related pictures while respiratory variables did not change. Moreover, increased dyspnoea correlated modestly with higher levels of empathy in observers. The present results demonstrate that observing dyspnoea in others elicits mild-to-moderate dyspnoea, negative affect, and increased brain responses in the absence of respiratory changes. This vicarious dyspnoea has clinical relevance, as it might increase suffering in the family and medical caregivers of dyspnoeic patients.
Prospective clinical study of a prostate cancer (PCa) rule-out blood test for PSA gray zone patients using a sensitive circulating tumor cell assay.
Authors: SEE-TONG Pang, Ying-Hsu Chang, Po-Hung Lin, Ying Chang, Drew Watson, Oscar Segurado, Si-Hong Lu, Jen-chia Wu, Jr-Ming Lai, Hung-Jen Shao, Shih-En Chang, Ben Hsieh, Mana Javey, Rui Mei
Journal: Journal of Clinical Oncology (2018)

143 Background: The diagnostic confirmation of prostate cancer in patients with a PSA in the gray zone (4–10 ng/ml) is controversial, often leading to unnecessary biopsies. The sensitivity of the PSA test at a 4 ng/mL cut-off can be as low as 21%. We introduce a new test for prostate cancer detection in PSA gray zone patients, with the potential to decrease the number of unnecessary prostate biopsies. Methods: A single-center, multi-year, IRB-approved, prospective, blinded clinical study was conducted in 200 high-risk subjects. 4 mL of blood was drawn and processed for CTC analysis using the CellMax biomimetic platform (CMx). The CMx CTC test uses a proprietary microfluidic biochip that accurately captures and enumerates CTCs with antibodies to EpCAM, CK18 and PSMA. All patients underwent routine screening including PSA and digital rectal exam (DRE). Gray zone and those diagnosed as ‘diseased’ based on PSA &amp; DRE also underwent a biopsy. Multivariate generalized linear models incorporating CMx test results were utilized to derive age adjusted CTC scores predictive of clinical outcomes. Results: A subset of 84 subjects with PSA levels in the gray zone (4–10 ng/ml) were included in this study. Prostate biopsy results were available for 42 patients; 10 had confirmed cancer. A CTC Score was calculated as a nonlinear weighted combination of the CTCs captured with CK18 and PSMA antibodies. After adjustment for age and PSA, the CTC score remained a significant predictor of clinical outcome in the PSA “gray zone” (likelihood ratio p-value = .015) whereas PSA was not. The sensitivity and specificity of the CTC Score were 80.0% (95% CI: 44.4%, 97.5%) and 93.8% (95% CI: 79.2%, 99.2%). Negative % agreement and Positive % agreement was 93.8% (95% CI: 79.2%, 99.2%) and 80.0% (95% CI: 44.4%, 97.5%). Given the observed odds ratio for CTC score in the study- approximately 0.90 (95% CI 0.79, 0.98), the study is appropriately powered. Conclusions: The CMx CTC assay is an accurate, affordable blood based assay, with the potential to reduce unnecessary biopsies in PSA gray-zone patients by up to 90%.
Benzodiazepines as a Monotherapy in Depressive Disorders: A Systematic Review
Authors: Giada Benasi, Jenny Guidi, Emanuela Offidani, Richard Balon, Karl Rickels, Giovanni A. Fava
Journal: Psychotherapy and Psychosomatics (2018)

Background: The aim of this paper was to perform a systematic review and, when feasible, a meta-analysis of randomized controlled trials (RCT) which used benzodiazepines (BZD) as a monotherapy versus placebo, antidepressant drugs (AD), or both. Methods: Keyword searches were conducted for identifying RCT comparing BZD and AD, and/or placebo in the treatment of depression, using electronic databases from their inception up to April 2017. We selected reports of RCT in which BZD were compared to AD and/or placebo in the treatment of adult patients with a primary diagnosis of depressive disorder or anxious depression. When feasible, data were subjected to meta-analysis. Results: A total of 38 studies met the criteria for inclusion and were then included in the systematic review. Only 1 study concerned a newer AD, fluvoxamine. For the meta-analysis, we submitted data on response rate from 22 RCT, considering BZD versus placebo (8 comparisons) and BZD versus tricyclic antidepressants (TCA) (20 comparisons). There was a lack of significant differences as to response rate between BZD and placebo, as well as between BZD and TCA. Analysis of individual studies disclosed that, in more than half of the studies comparing BZD to TCA and/or placebo, BZD were significantly more effective than placebo and as effective as TCA. Conclusions: BZD are a therapeutic option in anxious depression and there are no indications that AD are preferable. There is a pressing need for RCT of adequate methodological quality and follow-up comparing BZD to second-generation AD and placebo in anxious depression.
PULMONARY VASOREACTIVITY TESTING WITH ADENOSINE PREDICTS LONG TERM HEMODYNAMIC RESPONSE TO PROSTACYCLIN MONOTHERAPY, AND PROSTACYCLIN AND PHOSPHODIESTERASE-5 INHIBITOR COMBINATION THERAPY IN PULMONARY ARTERIAL HYPERTENSION
Authors: Ramsey Wehbe, Jonathan Rich, Stuart Rich
Journal: Journal of the American College of Cardiology (2018)
Prophylactic Low-Dose Oxygen for Patients With Acute Stroke
Authors: Hamidreza Saber, Hamid-Reza Moein, Kumar Rajamani
Journal: JAMA (2018)

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Core skills in laparoscopic surgery
Authors: David Bosanquet
Journal: BMJ (2010)

Core skills in laparoscopic surgery is a three day course for junior surgical trainees (core trainees years 1-2 and specialty trainees years 3-5) who are interested in improving their laparoscopic surgical skills. It covers the theoretical basis of general laparoscopic surgery, alongside a considerable amount of time spent on laparoscopic trainers.

I took this course during my second year of core surgical training.

Laparoscopic surgery is increasingly becoming the standard approach for a wide range of surgical procedures. Despite this, it can be difficult to gain sufficient experience in laparoscopic surgery, and often junior surgical trainees are left “holding the camera.” I had already had some experience of laparoscopic surgery from a basic surgical skills course and from my own surgical experience. Despite this, laparoscopic surgery remained a daunting prospect, and I wanted to improve my skills as well as my …
Working while fasting
Authors: Ahmed Kassem
Journal: BMJ (2004)

Fasting in Ramadan is one of the five basics of Islam and is not just about abstaining from food and drink from the break of dawn ( fajr ) until sunset ( maghreb ). The main objective is to tame any unwanted habits and change your behaviour in order to become a better person.

Because fasting is done during the daytime, it usually means …
The Heterogeneity Between Lynch-Associated and Sporadic MMR Deficiency in Colorectal Cancers
Authors: Guo-Chen Liu, Ran-Yi Liu, Jun-Ping Yan, Xin An, Wu Jiang, Yi-Hong Ling, Jie-Wei Chen, Jin-Xin Bei, Xiao-Yu Zuo, Mu-Yan Cai, Ze-Xian Liu, Zhi-Xiang Zuo, Ji-Hong Liu, Zhi-Zhong Pan, Pei-Rong Ding
Journal: JNCI Journal of the National Cancer Institute (2018)

Previous studies demonstrated that prognosis of germline deficiency in mismatch repair protein (dMMR) was different from that of sporadic dMMR. The underlying mechanism has not been studied. From a prospectively maintained database, we collected dMMR colorectal cancer (CRC) patients identified by postoperative immunohistochemistry screening. According to genetic test, patients were grouped as Lynch-associated or sporadic dMMR. We compared the clinical-pathological features, prognosis, and immunoreactive differences between the two groups. By whole-exome sequencing and neoantigen detection pipeline, mutational frequencies and neoantigen burdens were also compared. All statistical tests were two-sided. Sixty-seven sporadic dMMR and 85 Lynch-associated CRC patients were included in the study. Sporadic dMMR patients were older (P < .001) and their tumors were poorly differentiated (P = .03). The survival was better in the Lynch-associated group (P = .001). After adjustment, the difference still remained statistically significant (hazard ratio = 0.29, 95% confidence interval = 0.09 to 0.95, P = .04). The scores of Crohn's-like reaction (CRO; P < .001), immunoreactions in the invasive margin (IM; P = .01), tumor stroma (TS; P = .009), and cancer nest (CN; P = .02) of the Lynch-associated group were statistically significantly higher. The numbers of CD3+, CD8+, Foxp3+ tumor-infiltrating lymphocytes (TILs) in IM; CD3+, CD4+ TILs in TS; and CD3+, CD4+, CD8+ TILs in CN were statistically significantly higher in Lynch-associated dMMR patients. Based on the 16 patients who under went whole-exome sequencing, there were also more somatic mutations and neoantigen burdens in the Lynch-associated group compared with the sporadic dMMR group (439/pt vs 68/pt, P = .006; 628/pt vs 97/pt, P = .009). There are heterogeneities in dMMR CRCs. Lynch-associated dMMR patients present with more somatic mutations and neoantigens compared with sporadic dMMR, which probably results in stronger immunoreactions and survival improvement.
Clinicopathological features of lipid cell variant of urothelial carcinoma.
Authors: Tatsuro Hayashi, Go Kimura, Keigo Takahashi, Keita Shibayama, Kotaro Obayashi, Masayuki Sano, Kuniaki Tanabe, Jun Akatsuka, Yuka Toyama, Tsutomu Hamasaki, Yukihiro Kondo
Journal: Journal of Clinical Oncology (2018)

487 Background: Lipid cell variant (LCV) of urothelial carcinoma (UC) which was first described by Mostofi et al in 1999 is a very rare variant of UC. Because it has only been documented in occasional case reports and a small series about this variant since then, clinicopathological characteristics of LCV are not yet clarified. In this study, we assessed the clinicopathological characteristics of LCV experienced in our hospital. Methods: The medical records of patients with LCV, who were treated in our hospital between September 2015 and September 2017, were retrospectively reviewed and analyzed. Results: In this period, of 301 patients undergoing TURBT and 42 patients undergoing nephroureterectomy, 13 patients including 10 patients with bladder cancer and 3 with pelvic ureter cancer, were found to be diagnosed as LCV of UC at our hospital. The median observation period of these patients was 6 months (IQR, 4-9 months). Among 10 bladder cancer patients who had confirmed this variant in transurethral resection of bladder tumor (TURBT) specimens, all cases had concurrent high-grade UC and the most cases had tumor features including pT2 or more local stages and lympho-vascular invasion (LVI) positive. Co-existence of micropapillary and/or plasmacytoid variant were seen in 5 patients. Lymph node metastases were observed in 3 patients, and this variant was histologically confirmed within the lymph node metastatic tissue in one case. No patient had distant metastasis. Among 3 pelvic ureter cancer patients who had undergone nephroureterectomy, all cases had concurrent high-grade UC and the most cases had tumor features including pT3 local stage and LVI positive. Micropapillary variant was coexisted in one patient. No patient had distant metastasis. 7 patients were no evidence of disease and 6 were alive with disease. The estimated median time from surgery to recurrence was not reached. The 6-months disease-free survival rate was 59%. Conclusions: LCV is seen in the patients who have high-grade UC, and tends to be accompanied with other aggressive variants including micropapillary and plasmacytoid. All patients with this variant had advanced stage cancer at presentation with high recurrence rates.
Cap training posts in trauma and orthopaedics, government advisers say
Authors: Abi Rimmer
Journal: BMJ (2014)

Numbers of recruits to training in the trauma and orthopaedic surgery specialty should be capped until 2016, government advisers on workforce planning have said.

Recruitment into trauma and orthopaedic surgery in the third year of specialty training (ST3) should be capped at 122 posts a year in 2014-15 and 2015-16, the Centre for Workforce Intelligence has said in a report on the specialty’s workforce.1 The centre is commissioned by the Department of Health in England, Health Education England, and Public Health England to inform policy decisions on health workforce planning.

The report said …
Role of the health system in influencing uptake of human papillomavirus vaccine among adolescent girls in Mbale District, eastern Uganda: a cross-sectional, mixed-methods study
Authors: Juliet Nabirye, Juliet Babirye, Okwi Andrew, Waniaye Johnbaptist
Journal: The Lancet Global Health (2018)

BackgroundCervical cancer ranks as the most common cancer among women in Uganda, and prevalence has increased by 1·8% per annum over the past 20 years. Human papillomavirus (HPV) is responsible for more than 90% of cases of cervical cancer. The availability of an HPV vaccine presents an opportunity to prevent cervical cancer; however, national coverage stands at 17% against target coverage of 80% since the vaccine's introduction in 2015. This study assessed the role of the health system in influencing uptake of the HPV vaccine so as to inform vaccine implementation in Uganda.MethodsWe did a cross-sectional study that employed qualitative and quantitative methods. We did structured interviews among 407 adolescents aged 9–15 years systematically selected using Bennet's cluster survey method from five subcounties in Mbale district and six key informants (district health officials) in May 2017. Adolescents were involved in decision making about where to receive the vaccine. We used the WHO six building blocks framework to assess health system factors. Nine health facilities were assessed using a WHO checklist for vaccine service delivery. Quantitative data were analysed using Stata version 13. Qualitative data were analysed using MAXQDA version 12. Uptake was defined as receiving two doses of the vaccine.Findings56 (14%) of 407 adolescents self-reported vaccine uptake. 182 (52·3%) of 348 reported lack of awareness about the HPV vaccine as the major reason for not having received it. Receiving vaccines from outreach clinics (p=0·02), having many options from which to receive the vaccine (p=0·002), getting an explanation on possible side-effects (p=0·024), and receiving the vaccine alongside other services (p=0·024) were positively associated with uptake. Key informants reported inconsistency in vaccine supply, inadequate training on HPV vaccine, and the lack of a clear target for HPV vaccine coverage as the health system factors that contribute to low uptake.InterpretationUptake was well below the Ministry of Health target of 80%. We recommend training of health workers to provide adequate information on HPV vaccine, raising awareness of the vaccine in markets, schools, and radio talk shows, and communicating the target to health workers.FundingNone.
LONG-TERM MORTALITY PREDICTORS IN ISCHAEMIC OR NON-ISCHAEMIC PATIENTS UNDERGOING VT ABLATION
Authors: Klaudia Vivien Nagy, Nandor Szegedi, Gábor Széplaki, Tamás Tahin, István Osztheimer, Szilvia Herczeg, Zoltán Salló, Bela Merkely, Laszlo Geller
Journal: Journal of the American College of Cardiology (2018)