tbuckley/cabot-search huggingface dataset:
Endoscopic gastroplasty for weight loss: are we finally there?
Authors: Barham Abu Dayyeh
Journal: Endoscopy (2018)

The current management paradigm for obesity, or better termed adiposity-based chronic disease, focuses on caloric restriction and increased physical activity. However, this approach has insufficiently addressed the disease pathophysiology secondary to a myriad of counter-regulatory physiological responses aimed at defending homeostatic and centrally determined body fat stores by increasing hunger and decreasing energy expenditure [1]. Not surprisingly, when a redundant and evolutionary defended physiological system is disturbed, it will counterbalance the disruption in order to return to equilibrium. Successful interventions for obesity and metabolic disease, such as bariatric and metabolic surgery, disrupt these counter-regulatory responses by targeting peripheral gastric and small intestinal signals that communicate with the central nervous system and other peripheral organs including the liver, pancreas, adipose tissue, and muscle; such interventions result in significant and durable weight loss with resolution of obesity-related metabolic diseases, such as type 2 diabetes mellitus [2].
CARM1 Is Essential for Myeloid Leukemogenesis but Dispensable for Normal Hematopoiesis
Authors: Sarah M. Greenblatt, Na Man, Pierre-Jacques Hamard, Takashi Asai, Daniel Karl, Concepcion Martinez, Daniel Bilbao, Vasileios Stathias, Anna McGrew-Jermacowicz, Stephanie Duffort, Madhavi Tadi, Ezra Blumenthal, Samantha Newman, Ly Vu, Ye Xu, Fan Liu, Stephan C. Schurer, Michael T. McCabe, Ryan G. Kruger, Mingjiang Xu, Feng-Chun Yang, Daniel Tenen, Justin Watts, Francisco Vega, Stephen D. Nimer
Journal: Cancer Cell (2018)
Normal vaginal microbiome in women with primary Sjögren’s syndrome-associated vaginal dryness
Authors: Taco A van der Meulen, Jolien F van Nimwegen, Hermie J M Harmsen, Silvia C Liefers, Karin van der Tuuk, Frans G M Kroese, Marian J E Mourits, Arjan Vissink, Hendrika Bootsma
Journal: Annals of the Rheumatic Diseases (2018)

Dryness of epithelial surfaces is characteristic for patients with primary Sjogren’s syndrome (pSS). Vaginal dryness is frequently reported by pSS-women and is associated with sexual dysfunction.1 2 Recently, we showed that dysbiosis of the oral microbiome is largely similar between oral dryness patients with and without pSS when compared with healthy controls.3 4 The objective of our current study was to assess whether the vaginal microbiome of women with pSS-associated vaginal dryness differs from controls.

In a case-control design, we compared the vaginal microbiome of 10 premenopausal pSS-women with that of 10 age-matched premenopausal women without pSS, who underwent general anaesthesia for a laparoscopic procedure. Exclusion criteria were genital inflammatory or infectious comorbidity, endometriosis and use of disease modifying antirheumatic drugs, corticosteroids, vaginal oestrogens or an intrauterine contraceptive device. All patients with pSS fulfilled the 2016 ACR/EULAR classification criteria. All participants completed a questionnaire on vaginal symptoms. Patient-reported vaginal dryness was scored using a Numeric Rating Scale (NRS, range 0–10). Vaginal health was assessed with the Vaginal Health Index (VHI).5 From all participants, a cervicovaginal lavage (CVL) and endocervical swab (ES) were collected. DNA from all samples was …
Abstracts
Authors: C Evans, S Robertson, J Gracie, I Mcinnes, A Morris, R Mookerjee, S Sen, N Davies, S Hodges, R Williams, R Jalan, E Forrest, L Murray, D Shawcross, P Hayes, A Lee, I Currie, N Masson, S Dundas, J Black, R Bayne, R Parks, O Garden, J Ross, N Finlayson, S Riordan, N Skinner, A Nagree, H Mccallum, C Mciver, J Kurtovic, J Hamilton, S Bengmark, K Visvanathan
Journal: Gut (2003)

Aim and Background: IL-18 is a novel pro-inflammatory cytokine of the IL-1 family and is critical in the development of Th-1 responses.Th-1 responses have been implicated in the pathogenesis of ALD.We investigated IL-18 expression in patients with ALD and AH.Patients and Methods: We studied inpatients with ALD (n = 48, I/P ALD), outpatients with compensated ALD (n = 13, O/P ALD), and healthy volunteers (n = 15, HVs).The mean age of the I/P ALD (40 males) was 47.7 years and that of the O/P ALD group 55.2 years.Other forms of chronic liver disease were excluded by standard serological tests.IL-18 levels were measured by ELISA (Diaclone).Whole blood cell culture (WBC) +/-lipopolysaccharide (LPS) was performed to assess IL-18 production.A Childs-Pugh score and a Maddrey's Discriminant Function were calculated for all patients.The results were analysed by Mann-Whitney U test.Results: Inpatients consisted of five with Childs grade A, 17 B, and 26 C. Eighteen had a MDF < 24, 9 a MDF of 24-32, and 21 a MDF > 32.Plasma IL-18 levels were significantly elevated in the I/P ALD group when compared with O/P ALD and HVs (all units pg/ml), (174 +/-170, 45 +/-52, and 32 +/-83; p < 0.01 and p < 0.001).IL-18 levels in Child's C inpatients (226 +/-214) were significantly elevated compared to Child's A inpatients (27 +/-38; p < 0.01).Higher plasma IL-18 levels were found in inpatients with moderate/ severe AH (MDF > 24) when compared with inpatients with MDF < 24, O/P ALDs, and HVs (224 +/-203, 93 +/-89, 45 +/-83, and 32 +/-52; p < 0.02, p < 0.002, and p < 0.0001, respectively).Patients with Childs grades B/C showed no incremental rise in IL-18 production following LPS stimulation.A similar result was obtained on analysis of patients with moderate/severe AH (206 +/-190 to 217 +/-214).Conclusions: Plasma IL-18 is elevated in patients with ALD.IL-18 levels are higher in patients with increasing severity of ALD (Childs grade B/C) and AH (MDF > 24).In patients with Childs B/C ALD and AH, LPS stimulation resulted in no incremental rise in IL-18 production, suggesting prestimulation to a 'maximal' level in more severe ALD.These results support the role of immune dysregulation in moderate/ severe ALD and AH.
Thioesterase Superfamily Member 2 Promotes Hepatic VLDL Secretion by Channeling Fatty Acids Into Triglyceride Biosynthesis
Authors: Michele Alves‐Bezerra, Yingxia Li, Mariana Acuña, Anna A. Ivanova, Kathleen E. Corey, Eric A. Ortlund, David E. Cohen
Journal: Hepatology (2018)

In nonalcoholic fatty liver disease (NAFLD), triglycerides accumulate within the liver because the rates of fatty acid accrual by uptake from plasma and de novo synthesis exceed elimination by mitochondrial oxidation and secretion as very low‐density lipoprotein (VLDL) triglycerides. Thioesterase superfamily member 2 (Them2) is an acyl‐coenzyme A (CoA) thioesterase that catalyzes the hydrolysis of fatty acyl‐CoAs into free fatty acids plus CoASH. Them2 is highly expressed in the liver, as well as other oxidative tissues. Mice globally lacking Them2 are resistant to diet‐induced obesity and hepatic steatosis, and exhibit improved glucose homeostasis. These phenotypes are attributable, at least in part, to roles of Them2 in the suppression of thermogenesis in brown adipose tissue and insulin signaling in skeletal muscle. To elucidate the hepatic function of Them2, we created mice with liver‐specific deletion of Them2 ( L‐Them2 ‐/‐ ). Although L‐Them2 ‐/‐ mice were not protected against excess weight gain, hepatic steatosis or glucose intolerance, they exhibited marked decreases in plasma triglyceride and apolipoprotein B100 concentrations. These were attributable to reduced rates of VLDL secretion owing to decreased incorporation of plasma‐derived fatty acids into triglycerides. The absence of hepatic steatosis in L‐Them2 ‐/‐ mice fed chow was explained by compensatory increases in rates of fatty acid oxidation and by decreased de novo lipogenesis in high fat–fed mice. Consistent with a role for Them2 in hepatic VLDL secretion, THEM2 levels were increased in livers of obese patients with NAFLD characterized by simple steatosis. Conclusion : Them2 functions in the liver to direct fatty acids toward triglyceride synthesis for incorporation into VLDL particles. When taken together with its functions in brown adipose and muscle, these findings suggest that Them2 is a target for the management of NAFLD and dyslipidemia.
Risks and benefits of dolutegravir-based antiretroviral drug regimens in sub-Saharan Africa: a modelling study
Authors: Andrew N Phillips, Francois Venter, Diane Havlir, Anton Pozniak, Daniel Kuritzkes, Annemarie Wensing, Jens D Lundgren, Andrea De Luca, Deenan Pillay, John Mellors, Valentina Cambiano, Loveleen Bansi-Matharu, Fumiyo Nakagawa, Thokozani Kalua, Andreas Jahn, Tsitsi Apollo, Owen Mugurungi, Polly Clayden, Ravindra K Gupta, Ruanne Barnabas, Paul Revill, Jennifer Cohn, Silvia Bertagnolio, Alexandra Calmy
Journal: The Lancet HIV (2018)

BackgroundThe integrase inhibitor dolutegravir could have a major role in future antiretroviral therapy (ART) regimens in sub-Saharan Africa because of its high potency and barrier to resistance, good tolerability, and low cost, but there is uncertainty over appropriate policies for use relating to the potential for drug resistance spread and a possible increased risk of neural tube defects in infants if used in women at the time of conception. We used an existing individual-based model of HIV transmission, progression, and the effect of ART with the aim of informing policy makers on approaches to the use of dolutegravir that are likely to lead to the highest population health gains.MethodsWe used an existing individual-based model of HIV transmission and progression in adults, which takes into account the effects of drug resistance and differential drug potency in determining viral suppression and clinical outcomes to compare predicted outcomes of alternative ART regimen policies. We calculated disability adjusted life-years (DALYs) for each policy, assuming that a woman having a child with a neural tube defect incurs an extra DALY per year for the remainder of the time horizon and accounting for mother-to-child transmission. We used a 20 year time horizon, a 3% discount rate, and a cost-effectiveness threshold of US$500 per DALY averted.FindingsThe greatest number of DALYs is predicted to be averted with use of a policy in which tenofovir, lamivudine, and dolutegravir is used in all people on ART, including switching to tenofovir, lamivudine, and dolutegravir in those currently on ART, regardless of current viral load suppression and intention to have (more) children. This result was consistent in several sensitivity analyses. We predict that this policy would be cost-saving.InterpretationUsing a standard DALY framework to compare health outcomes from a public health perspective, the benefits of transition to tenofovir, lamivudine, and dolutegravir for all substantially outweighed the risks.FundingBill & Melinda Gates Foundation.
More opioids, more constipation? Evaluation of longitudinal total oral opioid consumption and self-reported constipation in patients with cancer.
Authors: Joseph Ma, Chris Sera, Eric Roeland
Journal: Journal of Clinical Oncology (2018)

211 Background: Constipation is a distressing physical symptom inadequately assessed in patients with cancer. Total opioid consumption may impact opioid-induced constipation (OIC) prevalence. This study examined total daily opioid consumption on self-reported constipation in patients with cancer. Methods: We performed a retrospective analysis in patients who had a histologically-confirmed cancer diagnosis and completed at least 2 outpatient PC visits at an academic palliative care (PC) clinic. At each PC visit, we collected self-reported constipation scores (11-point scale, 0 [no symptom] to 10 [worst symptom]) and 24-hour oral morphine equivalents (OME) for up to 5 visits. Spearman correlation examined the association between OME and presence of constipation rated ≥3 and Wilcoxan-Mann-Whitney examined OME between patients with or without constipation. Univariable logistic regression examined associations of independent variables on constipation. Results: We identified 404 patients with cancer (mean age 55.5±14.3 years, 61.9% women, 89% metastatic disease). The most common cancer types were gastrointestinal (n = 115; 31%) and gynecologic (n = 47; 13%). Stimulant laxative use was observed in 172 (44.9%) patients. Across all visits, we observed a weak association between OME and patient-reported constipation score (r = 0.16-0.24, p &lt; 0.05 for 4 of 5 visits). Mean OME increased, while mean constipation score decreased across visits. At the first visit, higher mean OME was seen in patients who self-reported constipation (128.8 vs 92.3; p &lt; 0.05). In contrast, for each subsequent clinic visit there was no difference in mean OME in patients with or without constipation. Age, sex, metastatic disease, and stimulant laxative use were not associated with constipation. Conclusions: A weak association was observed between OME and self-reported constipation in cancer patients across multiple palliative care visits. Except for the first clinic visit, there was no difference in OME and self-reported constipation scores. These results suggest a lack of a clear association between total opioid consumption and patient-reported constipation.
Daratumumab Monotherapy for Patients with Relapsed or Refractory (R/R) Natural Killer/T-Cell Lymphoma (NKTCL), Nasal Type: An Open-Label, Single-Arm, Multicenter Phase 2 Study
Authors: Won-Seog Kim, Hyeon-Seok Eom, Su-Peng Yeh, Seok-Goo Cho, Dae Seog Heo, Jin Seok Kim, Ming Yao, Jun Zhu, Grace Gao, Lijia Zhang, Ming Qi, Huiqiang Huang, Yok Lam Kwong
Journal: Blood (2018)
Annals Story Slam - A Beginning Towards a Better End
Authors: Jonathan Ailon
Journal: Annals of Internal Medicine (2018)

Web Exclusives4 December 2018Annals Story Slam - A Beginning Towards a Better EndFREEJonathan Ailon, MD, MScJonathan Ailon, MD, MScUniversity of Toronto and St. Michael's Hospital, Toronto, Ontario, Canada (J.A.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/W18-0039 SectionsAboutVisual Abstract ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Video. Annals Story Slam - A Beginning Towards a Better End "A Beginning Towards a Better End," by Jonathan Ailon, MD, MSc (Duration 4:41)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: University of Toronto and St. Michael's Hospital, Toronto, Ontario, Canada (J.A.)Current Author Address: Jonathan Ailon, MD, MSc; e-mail, [email protected]ca. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 4 December 2018Volume 169, Issue 11Page: SS1 ePublished: 4 December 2018 Issue Published: 4 December 2018 Copyright & PermissionsCopyright © 2018 by American College of Physicians. All Rights Reserved.Loading ...
Abstract 16717: My Unlimited Health Potential: 12 Month Effect of Participation in a Worksite Lifestyle Intervention Program on Significant Weight Loss and Eligibility Criteria for Bariatric Surgery Among High Risk Individuals
Authors: SameerShaharyar, LaraRoberson, EhimenAneni, MaribethRouseff, ThinhTran, HenryGuzman, SankalpDas, DorisBrown, JoannSantaigo-Charles, TeresaOchoa, JosephMora, BeatrizCastillo, EmirVeledar, TheodoreFeldman, ArthurAgatston, JanissePost, KhurramNasir
Journal: Circulation (2014)

BACKGROUND: Bariatric surgery among the morbidly obese is recommended as an option to mitigate future risk of cardiovascular disease, diabetes and hypertension. To date there is little evidence on the effect of extensive lifestyle interventions among these high-risk groups in reducing the need for such procedures in extended periods. METHODS: The purpose of the present study is assess efficacy of an intensive lifestyle workplace intervention on significant body weight across the spectrum of obesity in a worksite wellness program, called “My Unlimited Potential (MyUP)” conducted at Baptist Health South Florida. Changes in BMI are being measured from baseline to 12 months follow up, along with corresponding improvements in cardio-metabolic risk. In addition, the decrease in participants meeting criteria for bariatric surgery over the study period is examined at 6 and 12 months. Bariatric surgery criteria were defined as BMI≥40 or BMI between 35 and 40 and at least one of the following co-morbidities: diabet...
ASCO Guideline report: Palliative Care in the Global Setting—ASCO Resource-Stratified Practice Guideline.
Authors: James F. Cleary, Hibah Osman, Nahla Gafer, Sudip Shrestha, Zipporah Ali, Sarah B. Temin
Journal: Journal of Clinical Oncology (2018)

85 Background: The purpose of the new ASCO resource-stratified guideline on global palliative care (Osman H, Shrestha S, Temin S, et al, Palliative Care in the Global Setting: ASCO Resource-Stratified Practice Guideline, JGO, 2018) is to provide expert guidance to clinicians and policymakers on implementing palliative care in resource-constrained settings and was intended to complement the 2016 “Integration of Palliative Care Into Standard Oncology Care: American Society of Clinical Oncology Clinical Practice Guideline Update”. Methods: ASCO convened a multidisciplinary, multinational panel of experts. Guideline development involved a systematic review, a modified ADAPTE process of existing high-quality guidelines and a formal consensus-based process with the expert panel and additional experts (consensus ratings group), as well as open comment. Results: The systematic review included 48 full-text publications regarding palliative care in resource-constrained settings, along with cost-effectiveness analyses; the evidence for many clinical questions was limited. These provided indirect evidence to inform the formal consensus process, which resulted in agreement of ≥ 75% (by consensus ratings group including expert panel). Conclusions: The recommendations help define: the models of care, staffing requirements, and roles and training needs of team members in a variety of resource settings for palliative care. Recommendations also outline the standards for provision of psychosocial support, spiritual care, and opioid analgesics, which can be particularly challenging and often overlooked in resource-constrained settings.
Cost-Related Insulin Underuse Among Patients With Diabetes
Authors: Darby Herkert, Pavithra Vijayakumar, Jing Luo, Jeremy I. Schwartz, Tracy L. Rabin, Eunice DeFilippo, Kasia J. Lipska
Journal: JAMA Internal Medicine (2018)

methodology. 5 Combining hospital and police data may allow for a more complete picture of violence.Limitations of the study include that findings are generated from a single city.Furthermore, this study focused on violence occurring in public places only and does not provide information on reporting by injury severity.Third, this study does not include comparison with minor criminal charges such as "simple assault"; although not readily used as a criminal charge for violent injuries necessitating ED treatment in this study's jurisdictions, use of criminal charges can vary across police jurisdictions.Last, beyond the potential of misreporting by patients, only approximately 40% of violent incidents contained enough information to be mapped.Nonetheless, we hypothesize that patients declining to provide detailed information to nurses have specific reasons for nondisclosure 6 and would therefore also be unlikely to provide such information to police.This suggests that the number of incidents unreported to police may be even higher than we detected.In summary, these findings emphasize the potential of ED and police data to provide a complementary and comprehensive understanding of violent injury resulting in significant morbidity.This study provides new support for the United States on the value of cross-sectoral partnerships,
AB0485 Comparative efficacy of tofacitinib and biologic dmards in patients with rheumatoid arthritis with insufficient response to subcutaneous methotrexate in clinical practice
Authors: E.L. Luchikhina, D. Karateev, G. Loukina, M. Borisova, N. Demidova, E. Nasonov
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Tofacitinib (TOFA) – the first registered member of the group of Janus-kinase inhibitors – actively entered into practice. Some clinical trials show efficacy similar to biological DMARDs, but we still do not have enough data from the practice of post-marketing use. <h3>Objectives</h3> To evaluate the comparative effectiveness of TOFA and biological DMARDs in clinical practice. <h3>Methods</h3> Patients with RA (according to the ACR/EULAR 2010 criteria) having active disease despite treatment by subcutaneous (SC) methotrexate (MTX) were included in post-marketing observational study (REMARCA trial). The patients received a combination of MTX and biologics or TOFA. The follow-up period was 12 months. Patients received biologics in clinical practice according to national standards of care. We used SDAI as a main parameter of disease activity. <h3>Results</h3> In total 163 patients were included (81,6% females, 80,4% anti-CCP positive, 79,8 RF-positive, 74,9% with erosive disease, mean age 50,65±12,54, disease duration 30,45±41,9, BMI 27,1±5,78). All patients received SC MTX in the mean dose 22,17±3,92 mg per week, but the most of them had high activity at baseline (SDAI=32,42±14,59). After switching to a combination treatment regimen 88 patients received TNF inhibitors (70 patients – adalimumab, 18 patients – certolizumab pegol), 34 patients – abatacept (ABA), 41 patients – TOFA. Patients in the groups were comparable according to age and the main characteristics of disease severity. We found significant decrease of disease activity in every group (see table 1). In the group receiving TOFA results at 12 months were comparable with patients on anti-TNFs and significantly better than in patients on ABA. Remission (SDAI &lt;3,3) has been achieved in 35,7% of patients on TOFA, in 28,4% – on anti-TNFs and in 14,7% on ABA (p=0055 in comparison with TOFA). No significant differences in safety parameters were found. <h3>Conclusions</h3> Tofacitinib demonstrated similar efficacy in comparison to TNF inhibitors and was slightly better than abatacept in clinical practice in RA patients who did not respond to SC methotrexate. <h3>Disclosure of Interest</h3> E. Luchikhina Grant/research support from: Biocad, Speakers bureau: Abbvie, Pfizer, Biocad, D. Karateev Consultant for: Pfizer, Biocad, Egis, Novartis, Speakers bureau: Abbvie, Bristol Myers Squibb, Pfizer, Roche, Biocad, Novartis, Egis, MSD, UCB, G. Loukina: None declared, M. Borisova: None declared, N. Demidova: None declared, E. Nasonov: None declared
Smoking, symptoms, and quality of life in patients with psychosis, siblings, and healthy controls: a prospective, longitudinal cohort study
Authors: Jentien Vermeulen, Frederike Schirmbeck, Matthijs Blankers, Mirjam van Tricht, Wim van den Brink, Lieuwe de Haan, Behrooz Z Alizadeh, Therese van Amelsvoort, Agna A Bartels-Velthuis, Nico J van Beveren, Richard Bruggeman, Wiepke Cahn, Lieuwe de Haan, Philippe Delespaul, Jurjen J Luykx, Inez Myin-Germeys, Rene S Kahn, Frederike Schirmbeck, Claudia J P Simons, Neeltje E van Haren, Jim van Os, Ruud van Winkel
Journal: The Lancet Psychiatry (2018)
Scotland’s doctors: targets and funding are prioritised over patient care
Authors: Bryan Christie
Journal: BMJ (2018)

Inadequate resources, insufficient staff, and unhelpful national targets are leading to a deterioration in patient care in Scotland, say the country’s doctors.

A survey sent to 16 000 members of the BMA in Scotland and returned by nearly 1000 (response rate 6.2%) provides further evidence of a system struggling to deliver high quality care.1 Seven in 10 respondents said that patient services had worsened in the past year. Only 2% said that they had improved.

Over two thirds …