tbuckley/cabot-search huggingface dataset:
Specific Hepatic Sphingolipids Relate to Insulin Resistance, Oxidative Stress, and Inflammation in Nonalcoholic Steatohepatitis
Authors: Maria Apostolopoulou, Ruth Gordillo, Chrysi Koliaki, Sofia Gancheva, Tomas Jelenik, Elisabetta De Filippo, Christian Herder, Daniel Markgraf, Frank Jankowiak, Irene Esposito, Matthias Schlensak, Philipp E. Scherer, Michael Roden
Journal: Diabetes Care (2018)

OBJECTIVE Insulin resistance and nonalcoholic fatty liver disease have been linked to several lipid metabolites in animals, but their role in humans remains unclear. This study examined the relationship of sphingolipids with hepatic and peripheral metabolism in 21 insulin-resistant obese patients without (NAFL−) or with (NAFL+) nonalcoholic fatty liver and nonalcoholic steatohepatitis (NASH) and 7 healthy lean individuals undergoing tissue biopsies during bariatric or elective abdominal surgery. RESEARCH DESIGN AND METHODS Hyperinsulinemic-euglycemic clamps with d-[6,6-2H2]glucose were performed to quantify tissue-specific insulin sensitivity. Hepatic oxidative capacity, lipid peroxidation, and the phosphorylated-to-total c-Jun N-terminal kinase (pJNK-to-tJNK) ratio were measured to assess mitochondrial function, oxidative stress, and inflammatory activity. RESULTS Hepatic total ceramides were higher by 50% and 33% in NASH compared with NAFL+ and NAFL−, respectively. Only in NASH were hepatic dihydroceramides (16:0, 22:0, and 24:1) and lactosylceramides increased. Serum total ceramides and dihydroceramides (hepatic dihydroceramides 22:0 and 24:1) correlated negatively with whole-body but not with hepatic insulin sensitivity. Hepatic maximal respiration related positively to serum lactosylceramide subspecies, hepatic sphinganine, and lactosylceramide 14:0. Liver lipid peroxides (total ceramides, sphingomyelin 22:0) and the pJNK-to-tJNK ratio (ceramide 24:0; hexosylceramides 22:0, 24:0, and 24:1) all positively correlated with the respective hepatic sphingolipids. CONCLUSIONS Sphingolipid species are not only increased in insulin-resistant humans with NASH but also correlate with hepatic oxidative stress and inflammation, suggesting that these lipids may play a role during progression of simple steatosis to NASH in humans.
Substance-Induced Psychosis: An Indicator of Development of Primary Psychosis?
Authors: Subroto Ghose
Journal: American Journal of Psychiatry (2018)

Drugs of abuse and alcohol are known to acutely induce psychosis.Distinguishing between substance-induced psychosis, primary psychotic illnesses, and psychotic illnesses with comorbid substance use is clinically challenging.If the psychotic symptoms diminish as the psychoactive substance is metabolized and excreted, a diagnosis of substance-induced psychosis is typically made and substance use treatment is recommended, but, unfortunately, these patients are often lost to follow-up (1).There is growing recognition that this patient group may constitute a high-risk group for the development of a primary psychotic illness.Recent studies provide evidence that individuals with substance-induced psychosis are more likely to develop a schizophrenia spectrum disorder (1) or a primary psychotic disorder (2, 3).A recent large register-based study from Finland reported an increased risk of conversion to schizophrenia following an episode of substance-induced psychosis (4).In this issue, Starzer et al. ( 5) report on a register-based study designed to determine whether individuals diagnosed with substance-induced psychosis and no prior record of schizophrenia spectrum or bipolar disorder converted to either schizophrenia or bipolar disorder over a 20-year period.The authors delved into the Danish Civil Registration System and the Psychiatric Research Registry and identified 6,788 individuals with substance-induced psychosis and 67,227 matched control subjects for between-substance comparisons.The main results demonstrate that 32% of individuals with any substanceinduced psychosis later converted to either schizophrenia or bipolar disorder, with a majority (26%) given the former diagnosis.Half of those who converted to schizophrenia or bipolar disorder did so within 3 years or 4.5 years, respectively, after the incident substance-induced episode.This cohort included large numbers of cases with alcohol-induced (N52,315), cannabis-induced (N51,492), and amphetamine-induced (N5555) incident psychotic episodes and smaller numbers of other drug-induced incident psychoses (Ns from 114 to 158), which allowed the authors to meaningfully examine the influence of individual drugs on rates of conversion.Individuals using more than one drug were classified separately.When conversion rates over 20 years were calculated, cannabis was associated with the highest conversion rate to schizophrenia or bipolar disorder, 47%, followed by amphetamines, with a conversion rate of 32.3%.Conversion rates for alcohol, hallucinogens, cocaine, opioids, and sedatives were in the 20%228% range.
HEPATICO-DUODENOSTOMY WITH A LUMEN-APPOSING METAL STENT (LAMS) TO ACHIEVE COMPLETE BILIARY DRAINAGE IN A METASTATIC BILATERAL HILAR STRICTURE
Authors: R Torres-Yuste, L Siu-Tong, R Sanchez-Ocana, M Cimavilla-Roman, A Carbajo-Lopez, M de Benito-Sanz, J Garcia-Alonso, S Sevilla-Ribota, C De la Serna-Higuera, M Perez-Miranda
Journal: Endoscopy (2018)

Retrograde complete biliary drainage by means of ERCP in complex hilar strictures is not always feasible. Metastasis to the liver often result in complex strictures. Chemotherapy usually requires adequate biliary drainage.
ENDOSCOPIC PAPILLECTOMY: LONG TERM RESULTS IN 110 CONSECUTIVE PATIENTS
Authors: G Valerii, A Tringali, V Bove, R Landi, F Barbaro, I Boškoski, P Familiari, V Perri, G Costamagna
Journal: Endoscopy (2018)

Ampullary adenomas represents 5% of the neoplasia of the gastrointestinal tract with a premalignant nature. Aim of this study is to evaluate the results and the long-term follow-up of endoscopic papillectomy (EP) of adenoma of the ampulla of Vater.
PRODIGE 34 ADAGE: Adjuvant chemotherapy in elderly patients with resected stage III colon cancer—A randomized phase III trial.
Authors: Thomas Aparicio, Pierre-Luc Etienne, Olivier Bouche, Laurent Mineur, Sandrine Hiret, Jean Martin, Romain Desgrippes, Emilie Maillard, Gilles Breysacher, Roger Faroux, Laurent Cany, Eric Francois, Laurence Cristol-Dalstein, Elisabeth Carola, Elena Paillaud, Frédérique Retornaz, Jean Francois Seitz
Journal: Journal of Clinical Oncology (2017)

TPS3628 Background: Colon cancer (CC) occurs in around 50% of the patients after 70 years. Adjuvant chemotherapy (CT) has demonstrated a benefit on disease-free survival (DFS) and overall survival after a stage III CC resection. Nevertheless, adjuvant CT is poorly used in elderly patients. There is still concern about the efficacy of doublet CT with oxaliplatin in fit elderly patients and the usefulness of fluoropyrimidine monotherapy in unfit elderly patients. The selection of patients that should be treated remains a challenge. Geriatric evaluation and tumor biology should be explored to help for patient selection. Methods: ADAGE is a multicenter, randomized phase III study comparing 3-years DFS of 2 therapeutic strategies in 2 groups of patients aged over 70 with completely resected stage III CC. Patients are included in one of the 2 groups after a multidisciplinary team evaluation; Group 1 (arm A and B) is defined as “able” to be treated with doublet CT; Group 2 (arm C and D) is defined as “unable” to be treated with doublet CT. In each group, patients are randomized according to a 1:1 ratio. Randomization is stratified according to center, gender, stage (IIIA vs IIIB vs IIIC), occlusion and/or perforation (yes vs no) and independent activity of daily living score (IADL: normal vs abnormal). Arm A and D receive LV5FU2 or capecitabine, arm B FOLFOX4 or XELOX and arm C is an observation arm. The treatment is planned for 6 months. Adjuvant CT should start within 12 weeks after surgery. Geriatric questionnaires and Lee score must be completed before randomization. Radiological assessment is performed every 6 months for 3 years after randomization and then annually for 2 years. Hypotheses (α two-sided = 5%, power = 80%) are to improve 3-years DFS from 65% (arm A) to 72% (arm B) in group 1 (756 patients required) and from 40% (arm C) to 55% (arm D) in group 2 (226 patients required). Safety is evaluated based on laboratory and clinical tests before each cycle. Exploratory analysis are planned to determine geriatric prognostic factors for DFS. A biological ancillary study is planned to allow prognostic evaluation of mismatch repair status and other molecular signatures. At the 1 st of February 2017 the accrual was 246 patients. Clinical trial information: NCT02355379.
Short term bailouts will not help “perilous state” of NHS funding, MPs warn
Authors: Gareth Iacobucci
Journal: BMJ (2018)

The government must set out a long term plan to tackle the “perilous state” of NHS funding and must stop relying on short term bailouts to keep the service running, an influential group of MPs has urged.

In a new report the House of Commons public accounts committee highlighted the pressing need for a long term funding settlement for the NHS.1 The MPs argued that one-off funding injections had proved inadequate for tackling financial pressures, as the £1.8bn (€2.05bn; $2.54bn) rescue fund committed in 2016-17 was used to plug existing deficits rather than improve and develop services.

It said that the Department of Health and Social Care, …
Abstract P284: ClusterAnalysis of Objectively Measured Physical Activity Patterns in Women in the mPEDTrial
Authors: Yoshimi Fukuoka, Mo Zhou, Eric Vittinghoff, William Haskell, Ken Goldberg, Anil Aswani
Journal: Circulation (2018)

Background: Determining patterns of physical activity throughout the day could assist in developing more personalized interventions or physical activity guidelines in general, and in particular for women, who are less likely to be physically active than men. Objective: The aims of this report are to identify clusters of women based on accelerometer measured raw metabolic equivalent values (METs) and a normalized version of the METs ≥ 3 data and to compare sociodemographic and cardio metabolic risks among these identified clusters. Methods: 215 women wearing an accelerometer for at least 8 hours per day for the last 7 days prior to the randomization visit were analyzed. A K-means clustering method, the Lloyd’s algorithm, was used. To choose the number of clusters, we used the elbow method, looking at the percentage of variance explained as a function of the number of clusters. Results: The results of k means cluster analyses of raw METs revealed three different clusters (Figure 1) and the Low Active Group (n=102) had the highest depressive symptoms score compared to the Afternoon Active (n=65) and Morning Active (n=48) groups (overall P &lt; .001). Based on a normalized version of the METs ≥ 3 data Figure 2), the moderate to vigorous physical activity (MVPA) Evening Peak group (n = 108) had higher BMI, and waist and hip circumference than the MVPA Noon Peak group (n=61) (overall P =.03, .02, and .03 respectively). Conclusions: Categorizing physical inactive individuals into more specific activity patterns could aid in creating timing, frequency, duration, and intensity of physical activity interventions for women. Further research is needed to confirm these cluster groups using a large national dataset.
PREDICTORS OF SUCCESS AND RESCUE OPTIONS OF EUS-GUIDED RENDEZVOUS (EUS-RV) FOR BILIARY ACCESS AFTER FAILED ERCP CANNULATION
Authors: M Cimavilla, J García-Alonso, R Torres, A Carbajo, M De Benito, I Peñas, S Sevilla, N Mora, P GIl-Simon, C De la Serna, M Pérez-Miranda
Journal: Endoscopy (2018)

Failed cannulation occurs in 3% of ERCPs. EUS-RV can overcome failure. We aimed to identify predictors of success and rescue options of EUS-RV.
TWENTY-THREE YEARS OF SELF-EXPANDABLE METAL STENTS PLACEMENT FOR MALIGNANT ESOPHAGEAL STRICTURES
Authors: A Reijm, P Didden, S Schelling, P Siersema, M Bruno, M Spaander
Journal: Endoscopy (2018)

Self-expandable metal stents (SEMS) are effective for improving dysphagia in incurable esophageal cancer patients. In the past decades, various SEMS have been designed with the intention to minimize recurrent dysphagia and stent-related complications. However, it is uncertain whether these design changes indeed improves clinical outcome.
Abstract 15180: Renal Sympathetic Nerve Activity Mediates Natriuretic Peptide Metabolism via Neprilysin: A Novel Role of Renal Denervation in Heart Failure
Authors: David J Polhemus, Rishi K Trivedi, Zhen Li, Juan Gao, Hiroshi Koiwaya, Amy Scarborough, Craig Zibilich, Traci T Goodchild, Frank Smart, Daniel R Kapusta, David J Lefer
Journal: Circulation (2017)

Introduction:  Clinical trials previously reported that beta-blockers augment circulating natriuretic peptide (NP) in heart failure (HF). Furthermore, studies in our laboratory demonstrated that renal sympathetic denervation (RDN) attenuates renal neprilysin (NEP) activity, increases systemic NP levels, and improves cardiac function in HF. We hypothesized that renal sympathetic nerves acting on the renal beta 1  adrenergic receptor promote NP metabolism by activating the endopeptidase, NEP during HF. Rats subjected to HF were treated with either RDN or the beta 1 specific antagonist, Bisoprolol, and their effects on the synthesis and metabolism of NPs were evaluated.   Methods:  Wistar-Kyoto (WKY) rats were subjected to 45 min of LAD coronary artery ligation followed by reperfusion for 12w. At 4w following reperfusion, rats were treated with radiofrequency (RF)-RDN, Bisoprolol (1 mg/kg/day), or Sham-RDN. LV ejection fraction (EF) was assessed using echo. At 12w, plasma brain natriuretic peptide-32 (BNP) and renal cortex NEP activity were measured.   Results:  RDN and Bisoprolol significantly preserved LV EF compared to Sham-RDN (  Figure A  ). Meanwhile, RDN and Bisoprolol increased BNP levels and inhibiting renal NEP activity (  Figures B, C  ). RDN and Bisporolol had no impact on the transcription and translation of BNP.   Conclusions:  Our data demonstrate that decreased efferent sympathetic nerve activity to the kidney via RDN or renal beta 1  blockade via Bisporolol, inhibits renal NEP activity and leads to prolonged increases in NPs in the setting of HF. Our data suggest an important link between the sympathetic nervous system and NP metabolism in the pathobiology of HF.
Things We “kNOw” and Do Not “kNOw” about Pulmonary Hypertension
Authors: Jarrod W. Barnes, Rakesh P. Patel
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

Things We "kNOw" and Do Not "kNOw" about Pulmonary Hypertension Pulmonary hypertension (PH) is a devastating disease affecting .100 million people worldwide and defined by increased pulmonary artery pressure (.25 mm Hg) and pulmonary vascular resistance, which often results in right ventricular failure and premature death (1, 2).The World Health Organization classifies patients with PH into five groups on the basis of etiology (3).Multiple phenotypes such as vasoconstriction, dysregulated pulmonary vascular cell proliferation and remodeling, and inflammation contribute to the PH disease process (4-6) making therapeutic design complicated (7,8).Nitric oxide (NO) regulates pulmonary vascular tone and remodeling, inflammation, and coagulation.Three different nitric oxide synthase (NOS) isoforms control enzymatic formation of NO that differ in catalytic activity, location, and regulation.These are neuronal NOS (nNOS; NOS I), inducible NOS (iNOS; NOS II), and endothelial NOS (eNOS; NOS III) (9, 10).Several studies have shown that loss of eNOS-derived NO contributes to PH.This can occur by lower eNOS levels or lower NO bioavailability as a result of eNOS uncoupling despite no changes, or even increased eNOS expression (11,12).Mice genetically deficient in eNOS spontaneously develop PH and right ventricular failure (13, 14), and NO metabolite levels are lower in patients with pulmonary arterial hypertension (PAH) compared with control patients (15, 16), with the levels inversely correlating with the severity of disease.Moreover, therapies that increase NO in the pulmonary vasculature (e.g., inhaled NO or nitrite), or those that enhance downstream cyclic guanosine monophosphate-dependent signaling, are among the few available therapies to counter vasoconstriction in group 1 PAH (1,(17)(18)(19)(20).Treatment options for the other PH groups, however, are currently limited or lacking.In this issue of the Journal, Ogoshi and colleagues (pp.232-244) confirmed a critical role for eNOS in PH, using a mouse model of hypoxia-induced PH (21).Indices of PH including elevated right systolic pressure and hypertrophy, pulmonary vascular remodeling, and decreased survival were more prominent in eNOS-deficient mice compared with wild-type mice or mice lacking either nNOS or iNOS.These data further support a functional role for eNOS in protection against PH (13,14,22).The most intriguing findings by Ogoshi and colleagues were that mice devoid of all three NOS isoforms (triple NOS knockouts) had a greater degree of PH compared with mice lacking only eNOS; mortality was approximately twofold higher in triple NOS knockouts.This result reveals an unexpected interaction between NO produced by eNOS and either nNOS and/or iNOS.Although this aspect was not investigated in detail in the current study, it is notable that iNOS expression was increased in hypoxia-exposed eNOS-deficient mice, suggesting iNOS may offer compensatory
Guidelines for management of urgent symptoms in cholangiocarcinoma (CC) patients (pts) with biliary stents or catheters using the modified RAND/UCLA Delphi process.
Authors: Renuka V. Iyer, Susan G. Acquisto, John A. Bridgewater, Michael A. Choti, Theodore S. Hong, Bela Kis, Peter A Mead, Lewis R. Roberts, Rebecca Roberts, Neehar D. Parikh, Jason K. Sicklick, Richard S. Siegel, Jonathan R. Whisenant, Dasha Cherepanov, Michael Broder, Juan W. Valle
Journal: Journal of Clinical Oncology (2017)

e15641 Background: CC pts with biliary stents or catheters are prone to have obstruction/infection and studies show 20-40% present with fever/or jaundice requiring urgent treatment for which there is no uniform guideline. We aimed to develop an expert panel consensus on this topic using the modified RAND/UCLA Delphi process to rate treatment appropriateness. Methods: We recruited 13 physician experts from relevant specialty, geography, and practice settings. Patient scenarios were developed and panelists rated the therapies before and after a face-to-face discussion. The appropriateness of various therapies was rated on a 1-9 scale and classified as appropriate, inappropriate, or uncertain. Scenarios with &gt; 2 ratings of 1-3 (inappropriate) and &gt; 2 ratings of 7-9 (appropriate) were considered to have disagreement and were not assigned an appropriateness rating. Results: Panelists were from all US regions (92%) and the UK (8%); had practiced for a mean 16.5 years (4-33 years). Panelists rated 480 scenarios before the meeting, but re-rated only 288 clinical scenarios as they felt that ongoing treatment with chemotherapy did not influence decision-making. Disagreement decreased from 37.5% before the meeting to 10.4% after. Consensus statements are summarized in the table below. Conclusions: The Delphi process produced consensus guidelines to fill an unmet need in urgent management of ascending cholangitis in pts with CC. (Support: The Cholangiocarcinoma Foundation). [Table: see text]
A NEWLY DEVELOPED INTRAGASTRIC BALLOON FOR WEIGHT LOSS: A PRELIMINARY ANALYSIS OF IMPROVED EMPLOYMENT
Authors: HJ Chun, G Min, SJ Choi, W Kim, JM Lee, JM Lee, SH Kim, HS Choi, ES Kim, B Keum, YT Jeen, HS Lee, CD Kim
Journal: Endoscopy (2018)

Endoscopic bariatric approaches are gaining traction as possible treatment modalities for obesity. Especially, intragastric balloon was demonstrated to be associated with a significant weight loss in obese patients. Despite many advances in the design and material of intragastric balloon devices, there still remains a need for improved devices which is safer, faster, and less expensive than before. In the present study, we evaluated feasibility of newly developed intragastric balloon.
3D Interconnected Mesoporous Alumina with Loaded Hemoglobin as a Highly Active Electrochemical Biosensor for H<sub>2</sub>O<sub>2</sub>
Authors: Xuanyu Yang, Xiaowei Cheng, Hongyuan Song, Junhao Ma, Panpan Pan, Ahmed A. Elzatahry, Jiacan Su, Yonghui Deng
Journal: Advanced Healthcare Materials (2018)

Abstract Alumina is one of the most common and stable metal oxides in nature, which has been developed as a novel adsorbent in enrichment of biomolecules due to its excellent affinity to phosphor or amino groups. In this study, ordered mesoporous alumina (OMA) with interconnected mesopores and surface acidic property is synthesized through a solvent evaporation induced co‐assembly process using poly(ethylene oxide)‐ b ‐polystyrene (PEO‐ b ‐PS) diblock copolymer as a template and aluminium acetylacetonate (Al(acac) 3 ) as the aluminium source. The pore size (12.1–19.7 nm), pore window size (3.5–9.0 nm) and surface acidity (0.092–0.165 mmol g −1 ) can be precisely adjusted. The highly porous structure endows the OMA materials with high hemoglobin (Hb) immobilization capacity (170 mg g −1 ). The obtained Hb@OMA composite is used as an electrocatalyst of biosensor for convienet and fast detection of hydrogen peroxide (H 2 O 2 ) with a low H 2 O 2 detection limit of 1.7 × 10 −8 m and a wide linear range of 2.5 × 10 −8 to 5.0 × 10 −5 m . Moreover, the Hb@OMA sensors show a good performance in real time detection of H 2 O 2 released from Homo sapiens bone osteosarcoma, indicating their potential application in complex biological processes.
DOUBLE-BALLOON ENTEROSCOPY IN PATIENTS WITH LEFT VENTRICULAR ASSIST DEVICE (LVAD)
Authors: S Orlando, A Apostolo, F Ferretti, F Branchi, F Righini, M Vecchi, L Elli
Journal: Endoscopy (2018)

Patients with left ventricular assist device (LVAD) have an increased risk of gastrointestinal bleeding, mainly from angiodysplasia. In these patients, evaluation of the small bowel appears important for identification of bleeding and therapeutic management. However, data about deep enteroscopy in LVAD patients are limited. The aim of this study was to evaluate the safety and efficacy of double-balloon enteroscopy (DBE) in patients with LVAD.
Vaut-il mieux avoir une hémorragie digestive haute (HDH) le jour et en semaine ou la nuit ou le week-end? Résultats d'une enquête prospective de l'ANGH
Authors: S Nahon, A Peter, H Hagège, JP Latrive, B Nalet, I Rosa Hezode, B Bour, R Faroux, P Gower, JP Arpurt, J Denis, J Henrion, EA Pariente
Journal: Endoscopy (2009)

But: La réalisation d'une endoscopie digestive haute en urgence la nuit ou le week-end est souvent difficile au cours des HDH en raison de l'absence le plus souvent d'une aide spécialisée pour la réalisation des gestes techniques. Le but de notre travail était d'étudier les conditions de réalisations et les facteurs pronostiques des HDH survenant la nuit ou le week-end comparativement au jour et en semaine.