tbuckley/cabot-search huggingface dataset:
Nivolumab + ipilimumab combination in patients with DNA mismatch repair-deficient/microsatellite instability-high (dMMR/MSI-H) metastatic colorectal cancer (mCRC): First report of the full cohort from CheckMate-142.
Authors: Thierry Andre, Sara Lonardi, Mark Wong, Heinz-Josef Lenz, Fabio Gelsomino, Massimo Aglietta, Michael Morse, Eric Van Cutsem, Raymond S. McDermott, Andrew G Hill, Michael B. Sawyer, Alain Hendlisz, Bart Neyns, Magali Svrcek, Rebecca Anne Moss, Jean-Marie Ledeine, Z. Alexander Cao, Shital Kamble, Scott Kopetz, Michael J. Overman
Journal: Journal of Clinical Oncology (2018)

553 Background: Nivolumab (NIVO) provided durable responses (investigator-assessed [INV] ORR, 31%) and disease control (DCR, 69%) in pretreated pts with dMMR/MSI-H mCRC in CheckMate-142 (NCT02060188; Overman et al Lancet Oncol 2017). An interim analysis of the NIVO + ipilimumab (IPI) combination cohort of CheckMate-142 reported a preliminary ORR of 55% and manageable safety profile in a subset of pts (n = 84) with dMMR/MSI-H mCRC and ≥ 6 mo of follow-up (André et al ASCO 2017). Here we report for the first time efficacy and safety from the complete population (N = 119) of the NIVO + IPI cohort of CheckMate-142, which is the largest single-study report of an immunotherapy regimen in pts with dMMR/MSI-H mCRC. Methods: Pts with dMMR/MSI-H mCRC received NIVO 3 mg/kg + IPI 1 mg/kg Q3W for 4 doses followed by NIVO 3 mg/kg Q2W. Primary endpoint was ORR (INV; RECIST 1.1). Other endpoints were DOR, PFS, OS, and safety/tolerability. Results: Of 119 treated pts, 76% had ≥ 2 prior lines of therapy. Median follow-up was 13.4 mo. The ORR was 55% and DCR was 80% (Table). Notably, ORR in pts with a BRAF mutation was 55%. Among all responders, median DOR was not reached (NR), with 94% of responses ongoing at data cutoff. Tumor burden was reduced from baseline in 77% of pts. The 9-mo PFS and OS rates were 76% and 87%, respectively. Gr 3–4 TRAEs occurred in 32% of pts; 13% (any gr) and 10% (gr 3–4) of pts had TRAEs that led to discontinuation. No treatment-related deaths were reported. Results including a similar follow-up of the NIVO arm will also be presented. Conclusions: In the largest cohort of dMMR/MSI-H pts treated with an immunotherapy regimen, NIVO + IPI built on the efficacy reported with NIVO monotherapy, demonstrating enhanced clinical benefit and manageable safety, and may represent a new standard of care in pts with dMMR/MSI-H mCRC. Clinical trial information: NCT02060188. [Table: see text]
Endoscopic grading of gastric intestinal metaplasia (EGGIM): a multicenter validation study
Authors: Gianluca Esposito, Pedro Pimentel-Nunes, Stefano Angeletti, Rui Castro, Diogo Libânio, Gloria Galli, Edith Lahner, Emilio Di Giulio, Bruno Annibale, Mario Dinis-Ribeiro
Journal: Endoscopy (2018)

Abstract Background Random biopsies are recommended to identify individuals at risk of gastric adenocarcinoma. Cumulative evidence suggests that narrow-band imaging (NBI) can be used to grade gastric intestinal metaplasia (GIM). We aimed to externally validate a classification of endoscopic grading of gastric intestinal metaplasia (EGGIM). Methods Consecutive patients in two centers were submitted to high resolution white-light gastroscopy followed by NBI to estimate EGGIM – a score (0 – 10) resulting from the sum of endoscopic assessments of GIM, scored as 0, 1, or 2 for no GIM, ≤ 30 %, or &gt; 30 % of the mucosa, respectively, in five areas (lesser and greater curvature of both antrum and corpus, and incisura). If GIM was endoscopically suspected, targeted biopsies were performed; if GIM was not noticeable, random biopsies were performed according to the Sydney system to estimate the operative link on gastric intestinal metaplasia (OLGIM; the gold standard). Results 250 patients (62 % female; median age 55 years) were included. GIM was staged as OLGIM 0, I, II, III, IV in 136 (54 %), 15 (6 %), 52 (21 %), 34 (14 %), and 13 (5 %) patients, respectively. All patients with GIM except three were identifiable with targeted biopsies. For the diagnosis of OLGIM III/IV, the area under the ROC curve was 0.96 (95 % confidence interval [CI] 0.93 – 0.98) and by using the cutoff &gt; 4, sensitivity, specificity, and positive likelihood ratio were 89 %, 95 %, and 16.5, respectively; results were similar (91 %, 95 %, and 18.1) when excluding patients with foveolar hyperplasia. Conclusions For the first time, an endoscopic approach was externally validated to determine the risk of gastric cancer without the need for biopsies. This can be used to simplify and individualize the management of patients with gastric precancerous conditions.
UTILITY OF DOUBLE BALLOON ENTEROSCOPY IN PATIENTS WITH SURGICALLY ALTERED BOWEL ANATOMY AFTER OBESITY SURGERY
Authors: A Martínez-Alcalá García, PT Kröner, S Peter, JP Gutierrez, AM Ahmed, I Jovanovic, K Mönkemüller
Journal: Endoscopy (2018)

To evaluate the diagnostic yield, success and complications rates of double-balloon enteroscopy (DBE) in patients with surgically altered bowel anatomy after obesity surgery and GI problems necessitating endoscopic evaluation.
INFLIXIMAB, A TNF-α INHIBITOR HAS PROTECTIVE EFFECT ON EXPERIMENTAL BENIGN ESOPHAGEAL STRICTURE IN RATS
Authors: W Jiang, L Chen, H Li, L Min, Y Wang
Journal: Endoscopy (2018)

In 3 groups (Group A - sham-operated group, Group B - benign esophageal stricture establishment goup, Group C - infliximab treatment group) consisiting of 12 SD rats each, we evaluated the efficacy of IFX whether it can alleviate the stricture degree based on histolopathology, biochemical analysis which consists of Elisa and Western Blot. To investigate whether the potential alleviation of IFX is associated with apoptosis procedure, we used Tunel staining to calculate the apoptosis index. The baseline characters such as surviving rate and body weight gain were also included.
DO ENDOSCOPISTS WITH AN ADR &gt; 20% DETECT MORE ADENOMAS IN THE PROXIMAL COLON?
Authors: A Hinterberger, D Penz, E Waldmann, B Majcher, A Dokladanska, A Szymanska, A Asaturi, M Trauner, M Ferlitsch
Journal: Endoscopy (2018)

Sessil serrated adenomas, responsible for 15%-30% of all colorectal cancers, are mostly located in proximal colon. (Ijaspeert et al., Gut. 2017). Aim was to identify, if endoscopists with an adenoma detection rate (ADR) > 20% detected more polyps in proximal colon than endoscopists with an ADR < 20%.
Equivalent Efficacies of Reverse Hybrid and Bismuth Quadruple Therapies in Eradication of Helicobacter pylori Infection in a Randomized Controlled Trial
Authors: Ping-I Hsu, Feng-Woei Tsay, David Y. Graham, Tzung-Jiun Tsai, Kuo-Wang Tsai, John Y. Kao, Nan-Jing Peng, Chao-Hung Kuo, Sung-Shuo Kao, Huay-Min Wang, Te-Fu Lin, Deng-Chyang Wu
Journal: Clinical Gastroenterology and Hepatology (2018)
PROPHYLACTIC ANTIBIOTICS FOR PREVENTION OF ELECTROCOAGULATION SYNDROME AFTER COLONIC ENDOSCOPIC SUBMUCOSAL DISSECTION: DOES IT WORKS?
Authors: G Sirin, H Yılmaz, A Erkan Duman, Z Islamoglu, A Celebi, S Hülagu
Journal: Endoscopy (2018)

Nowadays, endoscopic submucosal dissection (ESD) is performed widespread in the world even in colorectal superficial lesion treatment. Colonic ESD has some risk of adverse events like electrocoagulation (ECS) syndrome after performing ESD in that region. We aimed that to analyze whether the use of prophylactic antibiotics could be decrease the formation of ECS.
La ponction sous échoendoscopie guidée par l'élastografie en temps réel: une étude préliminaire
Authors: C Ménard, M Gasmi, JC Grimaud, M Barthet
Journal: Endoscopy (2009)

Introduction: L'élastografie échoendoscopique est une technologie récente qui permet de visualiser en temps réel les propriétés physiques d'un tissu. Cette étude préliminaire avait pour buts de vérifier la faisabilité et la performance diagnostique des ponctions échoendoscopiques sous guidance élastographique.
The Ebb and Flow of Echocardiographic Cardiac Function Parameters in Relationship to Hemodialysis Treatment in Patients with ESRD
Authors: Charalampos Loutradis, Pantelis A. Sarafidis, Christodoulos E. Papadopoulos, Aikaterini Papagianni, Carmine Zoccali
Journal: Journal of the American Society of Nephrology (2018)

Cardiovascular disease is the leading cause of mortality in patients receiving hemodialysis. Cardiovascular events in these patients demonstrate a day-of-week pattern;
OBSTRUCTIVE JAUNDICE SECONDARY TO “AFFERENT LOOP SYNDROME” IN A PATIENT WITH ENDOSCOPIC GASTROJEJUNOSTOMY RESOLVED BY EUS-GUIDED HEPATICOGASTROSTOMY
Authors: DF Gómez Nussbaumer, J Martinez Sempere, L Compañy Catala, JA Casellas Valde, FA Ruiz, O Murcia Pomares, K Cardenas Jaen, C Mangas Sanjuan, JI Cameo, M Bozhychko, S Baile, L Medina, J Ramón Aparicio Tormo
Journal: Endoscopy (2018)

In the afferent loop syndrome there is an accumulation of bile that distends the obstructed afferent loop as a complication of gastrointestinal surgery. Obstructive jaundice in these cases is a consequence of the difficulty of draining the bile due to hyperpressure in the afferent loop. We present a case of obstructive jaundice secondary to obstruction of the second portion of the duodenum due to stenosis at the tip of the bulb and third portion of the duodenum.
Implications of STAT3 and STAT5 signaling on gene regulation and chromatin remodeling in hematopoietic cancer
Authors: Bettina Wingelhofer, Heidi A. Neubauer, Peter Valent, Xiaonan Han, Stefan N. Constantinescu, Patrick T. Gunning, Mathias Müller, Richard Moriggl
Journal: Leukemia (2018)

STAT3 and STAT5 proteins are oncogenic downstream mediators of the JAK–STAT pathway. Deregulated STAT3 and STAT5 signaling promotes cancer cell proliferation and survival in conjunction with other core cancer pathways. Nuclear phosphorylated STAT3 and STAT5 regulate cell-type-specific transcription profiles via binding to promoter elements and exert more complex functions involving interaction with various transcriptional coactivators or corepressors and chromatin remodeling proteins. The JAK–STAT pathway can rapidly reshape the chromatin landscape upon cytokine, hormone, or growth factor stimulation and unphosphorylated STAT proteins also appear to be functional with respect to regulating chromatin accessibility. Notably, cancer genome landscape studies have implicated mutations in various epigenetic modifiers as well as the JAK–STAT pathway as underlying causes of many cancers, particularly acute leukemia and lymphomas. However, it is incompletely understood how mutations within these pathways can interact and synergize to promote cancer. We summarize the current knowledge of oncogenic STAT3 and STAT5 functions downstream of cytokine signaling and provide details on prerequisites for DNA binding and gene transcription. We also discuss key interactions of STAT3 and STAT5 with chromatin remodeling factors such as DNA methyltransferases, histone modifiers, cofactors, corepressors, and other transcription factors.
OVER-THE-SCOPE-CLIP IS AN EFFECTIVE ENDOSCOPIC MONOTHERAPY FOR SEVERE ACUTE UPPER NON-VARICEAL GASTROINTESTINAL BLEEDING
Authors: A Martínez-Alcalá García, PT Kröner, JP Gutierrez, K Kyanam Kabir Baig, MA D'Assuncao, I Jovanovic, K Mönkemüller
Journal: Endoscopy (2018)

The over-the-scope-clip (OTSC) has proven useful as a rescue therapy for GI bleeding. Currently, various case reports, series and studies have shown that the OTSC device is effective as a first line therapy for upper GI bleeding lesions including peptic ulcer, Dieulafoy lesions and Mallory Weiss tears.
Neuronal hypothalamic regulation of body metabolism and bone density is galanin dependent
Authors: Anna Idelevich, Kazusa Sato, Kenichi Nagano, Glenn Rowe, Francesca Gori, Roland Baron
Journal: Journal of Clinical Investigation (2018)

In the brain, the ventral hypothalamus (VHT) regulates energy and bone metabolism. Whether this regulation uses the same or different neuronal circuits is unknown. Alteration of AP1 signaling in the VHT increases energy expenditure, glucose utilization, and bone density, yet the specific neurons responsible for each or all of these phenotypes are not identified. Using neuron-specific, genetically targeted AP1 alterations as a tool in adult mice, we found that agouti-related peptide-expressing (AgRP-expressing) or proopiomelanocortin-expressing (POMC-expressing) neurons, predominantly present in the arcuate nucleus (ARC) within the VHT, stimulate whole-body energy expenditure, glucose utilization, and bone formation and density, although their effects on bone resorption differed. In contrast, AP1 alterations in steroidogenic factor 1-expressing (SF1-expressing) neurons, present in the ventromedial hypothalamus (VMH), increase energy but decrease bone density, suggesting that these effects are independent. Altered AP1 signaling also increased the level of the neuromediator galanin in the hypothalamus. Global galanin deletion (VHT galanin silencing using shRNA) or pharmacological galanin receptor blockade counteracted the observed effects on energy and bone. Thus, AP1 antagonism reveals that AgRP- and POMC-expressing neurons can stimulate body metabolism and increase bone density, with galanin acting as a central downstream effector. The results obtained with SF1-expressing neurons, however, indicate that bone homeostasis is not always dictated by the global energy status, and vice versa.
THE ADDITIVE VALUE OF ENDOSCOPIC ULTRASOUND (EUS) GUIDED FINE NEEDLE ASPIRATION (FNA) IN DIFFERENTIAL DIAGNOSIS OF PANCREATIC CYSTIC LESIONS IN A TERTIARY-CARE CENTRE
Authors: G Rossi, P Magnoni, M Traini, MC Petrone, E Dabizzi, SG Giulia Testoni, A Mariani, C Doglioni, PG Arcidiacono
Journal: Endoscopy (2018)

Literature data show a low sensitivity (30 – 50%) for endoscopic ultrasound (EUS) fine needle aspiration (FNA) in differential diagnosis of pancreatic cystic lesions (PCL).
Cold snare polypectomy: is there a limit to polyp size?
Authors: David Hewett, Nicholas Tutticci
Journal: Endoscopy (2018)

See also: Cold versus hot endoscopic mucosal resection for nonpedunculated colorectal polyps sized 6–10 mm: a randomized trialEndoscopy eFirstDOI: 10.1055/s-0043-118594
Abstract 11211: Insulin resistance is a Risk Factor for Ongoing Myocardial Damage in General Subjects: The Takahata Study
Authors: Taro Narumi, Tetsuro Shishido, Shinpei Kadowaki, Yoichiro Otaki, Yuki Honda, Shintaro Honda, Hiromasa Hasegawa, Satoshi Nishiyama, Hiroki Takahashi, Takanori Arimoto, Takehiko Miyashita, Takuya Miyamoto, Tetsu Watanabe, Isao Kubota
Journal: Circulation (2012)

Background:  The presence of metabolic disorder, such as glucose intolerance and dyslipidemia, is associated with the new onset of the cardiovascular disease (CVD) and all cause of mortality. It has been reported that each component of metabolic syndrome (Mets), which includes abdominal obesity, hypertension, impaired insulin tolerance with high fasting glucose levels, and elevated levels of triglycerides, is a risk factor for CVD and ongoing myocardial damage. These findings imply that there is a significant association between the severity of Mets and the existing organ damage. However, correlation between insulin resistance (IR) and cardiac dysfunction in general populations has not been established yet. The purpose of this study is to investigate the association between IR and myocardial damage in general normal subjects.   Methods and Results:  We retrospectively studied 2200 consecutive subjects who had been participated in a community-based health check at Takahata town in northern Japan. Mets was evaluated by using the National Cholesterol Education program Adult Treatment Panel III (NCEP-ATP III) criteria. Homeostasis model assessment ratio (HOMA-R) was estimated as suggested presence of IR. Serum level of heart type fatty acid binding protein (H-FABP) was measured as a maker of ongoing myocardial damage. Serum H-FABP level was significantly higher in subjects with Mets and IR than normal subjects. However, there were no significant difference between subjects with IR and those with Mets. To investigate the contribution of IR on ongoing myocardial damage in normal subjects, we excluded 264 subjects with Mets. 1936 subjects without Mets were examined in logistic analysis. In multivariate logistic analysis, presence of IR was independently associated with ongoing myocardial damage (OR: 1.6, 95% confidence interval 1.1 - 2.3). Furthermore, the percentage of ongoing myocardial damage was significantly higher in subjects with IR compared with those without IR.   Conclusion:  Presence of IR is related to ongoing myocardial damage in general normal subjects, which suggests that myocardial damage occurs in the early state of metabolic disorder. It is necessary in a future study to find way to ameliorate IR and get better clinical outcomes.
Transmission of HIV-1 drug resistance mutations within partner-pairs: A cross-sectional study of a primary HIV infection cohort
Authors: Joanne D. Stekler, Ross Milne, Rachel Payant, Ingrid Beck, Joshua Herbeck, Brandon Maust, Wenjie Deng, Kenneth Tapia, Sarah Holte, Janine Maenza, Claire E. Stevens, James I. Mullins, Ann C. Collier, Lisa M. Frenkel
Journal: PLoS Medicine (2018)

Background Transmission of human immunodeficiency virus type 1 (HIV-1) drug resistance mutations, particularly that of minority drug-resistant variants, remains poorly understood. Population-based studies suggest that drug-resistant HIV-1 is less transmissible than drug-susceptible viruses. We compared HIV-1 drug-resistant genotypes among partner-pairs in order to assess the likelihood of transmission of drug resistance mutations and investigate the role of minority variants in HIV transmission. Methods and findings From 1992–2010, 340 persons with primary HIV-1 infection and their partners were enrolled into observational research studies at the University of Washington Primary Infection Clinic (UWPIC). Out of 50 partner-pairs enrolled, 36 (72%) transmission relationships were confirmed by phylogenetic distance analysis of HIV-1 envelope (env) sequences, and 31 partner-pairs enrolled after 1995 met criteria for this study. Drug resistance mutations in the region of the HIV-1 polymerase gene (pol) that encodes protease and reverse transcriptase were assessed by 454-pyrosequencing. In 25 partner-pairs where the transmission direction could be determined, 12 (48%) transmitters had 1–4 drug resistance mutations (23 total) detected in their HIV-1 populations at a median frequency of 6.0% (IQR 1.5%–98.7%, range 1.0%–99.6%). Of 10 major mutations detected in five transmitters at a frequency >95%, 100% (95% CI 69.2%–100%) were detected in recipients. All of these transmitters were antiretroviral (ARV)-naïve at the time of specimen collection. Fourteen mutations (eight major mutations and six accessory mutations) were detected in nine transmitters at low frequencies (1.0%–11.8%); four of these transmitters had previously received ARV therapy. Two (14% [95% CI 1.8%–42.8%]) G73S accessory mutations were detected in both transmitter and recipient. This number is not significantly different from the number expected based on the observed frequencies of drug-resistant viruses in transmitting partners. Limitations of this study include the small sample size and uncertainties in determining the timing of virus transmission and mutation history. Conclusions Drug-resistant majority variants appeared to be commonly transmitted by ARV-naïve participants in our analysis and may contribute significantly to transmitted drug resistance on a population level. When present at low frequency, no major mutation was observed to be shared between partner-pairs; identification of accessory mutations shared within a pair could be due to transmission, laboratory artifact, or apolipoprotein B mRNA-editing enzyme, catalytic polypeptides (APOBECs), and warrants further study.
POLYP DETECTION INCREASES WITH WITHDRAWAL TIME IN COLONOSCOPY
Authors: S Jardak, M Medhioub, K Agar, L Hamzaoui, A Khsiba, M Msaddak Azzouz
Journal: Endoscopy (2018)

Polypectomy of adenomatous polyps during colonoscopy has been shown to decrease the incidence of colorectal cancer (CRC). Withdrawal time during colonoscopy is thought to improve polyp detection.
Intervention strategies to improve nutrition and health behaviours before conception
Authors: Mary Barker, Stephan U Dombrowski, Tim Colbourn, Caroline H D Fall, Natasha M Kriznik, Wendy T Lawrence, Shane A Norris, Gloria Ngaiza, Dilisha Patel, Jolene Skordis-Worrall, Falko F Sniehotta, Régine Steegers-Theunissen, Christina Vogel, Kathryn Woods-Townsend, Judith Stephenson
Journal: The Lancet (2018)
WATER EXCHANGE COLONOSCOPY INCREASES ADENOMA DETECTION RATE. A SYSTEMATIC REVIEW WITH NETWORK META-ANALYSIS OF RANDOMIZED CONTROLLED STUDIES
Authors: L Frazzoni, L Fuccio, C Hassan, M La Marca, V Paci, V Smania, N De Bortoli, F Bazzoli, A Repici, D Rex, S Cadoni
Journal: Endoscopy (2018)

Water-aided colonoscopy techniques (water immersion, WI; water exchange, WE) have shown different results regarding adenoma detection rate (ADR). We determined the impact of WI and WE on ADR and other procedural outcomes vs. gas (air, AI; carbon dioxide, CO2) insufflation colonoscopy.
Efficacité de la mucosectomie endoscopique pour les tumeurs superficielles de l'estomac
Authors: JM Canard, G Rahmi, B Landi, L Palazzo, C Cellier, R Jian
Journal: Endoscopy (2009)

Introduction: La mucosectomie endoscopique est un traitement curatif des tumeurs superficielles de l'estomac qui a essentiellement été développée dans les pays asiatiques. Le but de cette étude est d'évaluer l'efficacité de la mucosectomie endoscopique dans cette indication.
A Diagnostic Problem: Noncyanotic Heart Disease with Heart Failure in a Seven Year-Old Boy
Authors: Edgar Allen, Raymond Pruitt, D Mahlon Delp
Journal: Circulation (1955)

The Clinicopathological Conference at this school is somewhat unique. Fourth year students are responsible for the discussion of the case, interpretation of x-ray films, and of electrocardiograms. The comments of the students, in the following presentation, reflect the maturity of the modern-day senior.
Prevalence and clinical association of gene mutations through multiplex mutation testing in patients with NSCLC: results from the ETOP Lungscape Project
Authors: K.M. Kerr, U. Dafni, K. Schulze, E. Thunnissen, L. Bubendorf, H. Hager, S. Finn, W. Biernat, L. Vliegen, J.H. Losa, A. Marchetti, R. Cheney, A. Warth, E.-J. Speel, F. Blackhall, K. Monkhorst, E. Jantus Lewintre, V. Tischler, C. Clark, J. Bertran-Alamillo, P. Meldgaard, K. Gately, A. Wrona, P. Vandenberghe, E. Felip, G. De Luca, S. Savic, T. Muley, E.F. Smit, A.-M.C. Dingemans, L. Priest, P. Baas, C. Camps, W. Weder, V. Polydoropoulou, T.R. Geiger, R. Kammler, T. Sumiyoshi, M.A. Molina, D.S. Shames, R.A. Stahel, S. Peters
Journal: Annals of Oncology (2017)