tbuckley/cabot-search huggingface dataset:
THE PALLIATIVE ENDOSCOPIC MANAGEMENT OF UGI MALIGNANT OBSTRUCTION
Authors: Y Abdirashev, N Abdiyev, S Izmagambetova, A Uzhakhov
Journal: Endoscopy (2018)

The severe stenosis and complicated malignant esophagus and gastric outlet obstruction (GOO) appears a difficult task for endoscopists. The purpose is analysis of SEMS placement of cancer obstruction of UGI.
Intravital phosphorescence lifetime imaging of the renal cortex accurately measures renal hypoxia
Authors: Yosuke Hirakawa, Kiichi Mizukami, Toshitada Yoshihara, Ippei Takahashi, Purevsuren Khulan, Tomoko Honda, Imari Mimura, Tetsuhiro Tanaka, Seiji Tobita, Masaomi Nangaku
Journal: Kidney International (2018)
Low-dose X-ray radiotherapy–radiodynamic therapy via nanoscale metal–organic frameworks enhances checkpoint blockade immunotherapy
Authors: Kuangda Lu, Chunbai He, Nining Guo, Christina Chan, Kaiyuan Ni, Guangxu Lan, Haidong Tang, Charles Pelizzari, Yang-Xin Fu, Michael T. Spiotto, Ralph R. Weichselbaum, Wenbin Lin
Journal: Nature Biomedical Engineering (2018)
Impact of adjuvant chemotherapy on recurrence-free survival in patients with pT1a/b hormone-negative and HER2-positive breast cancer.
Authors: Yazan Migdady, William M. Sikov, Bachir Joseph Sakr, Adam J. Olszewski
Journal: Journal of Clinical Oncology (2012)

1034 Background: T1ab triple-negative (TN) or Her-2-positive (H2+) breast cancers are reported to pose relatively high risk of relapse, but benefits of adjuvant chemotherapy are uncertain. We studied the impact of chemotherapy on recurrence-free survival in this group. Methods: Records of all consecutive cases diagnosed in Brown-affiliated centers in 2000 - 2010 were reviewed. Factors influencing chemotherapy decision were studied with logistic regression, and recurrence-free interval (RFI) with a Cox proportional hazard model and Kaplan-Meier estimator. Results: Among 1415 screened T1a/b N0 cases, 161 were eligible (57 TN; 104 HER2+), with a median age of 57 years; 66% tumors were T1b. 20% of patients underwent mastectomy, 76% received radiation and 30% hormonal therapy. Adjuvant chemotherapy was recommended in 53% of cases. Younger age (p&lt;10 -6 ), stage T1b (p&lt;10 -5 ), high grade (p=0.001), HER2+/ERPR- status (p=0.017) and diagnosis after 2006 (p=0.007) were significantly predictive of the medical oncology recommendation. There was a significant trend with decrease in anthracycline (p&lt;0.001) and increase in taxane use (p&lt;0.001). With a median follow up of 46 months, the 5-year rate of relapse was 6.1% (95%CI 2.7-13.9%), somewhat higher in T1b tumors (8.1%) and without detectable difference in TN/HER2+ subgroups. In a univariate analysis chemotherapy did not significantly impact the recurrence-free interval (HR=0.45; 95%CI 0.09-2.34; p=0.32), however there was a detectable benefit (p=0.02) for T1b tumors in a multivariable Cox model including age (p=0.02) and LVI (p=0.01). The histology, type of surgery and year of diagnosis were not significant. There were no relapses among ER/PR+ patients who received hormonal therapy or HER2+ patients who received trastuzumab. Conclusions: The risk of relapse in biologically aggressive T1ab breast cancers is very low with judicious use of adjuvant therapy. The benefit of chemotherapy is likely restricted to the highest-risk patients with T1b tumors, lymphovascular invasion and younger age.
Combination nivolumab and ipilimumab or nivolumab alone in melanoma brain metastases: a multicentre randomised phase 2 study
Authors: Georgina V Long, Victoria Atkinson, Serigne Lo, Shahneen Sandhu, Alexander D Guminski, Michael P Brown, James S Wilmott, Jarem Edwards, Maria Gonzalez, Richard A Scolyer, Alexander M Menzies, Grant A McArthur
Journal: The Lancet Oncology (2018)
SIGNIFICANT CAUSE FOR OCCULT ANAEMIA DEMONSTRATED WITH MACROSCOPICALLY ABNORMAL MUCOSAE FROM ROUTINE COLONOSCOPIC ILEAL INSPECTION
Authors: N Jayasooriya, R Eckersley, A Sullivan, S Musa, A Alisa, K Tang
Journal: Endoscopy (2018)

Small bowel disease is a significant cause of occult iron deficiency anaemia (IDA). Terminal ileal (TI) endoscopic examination is a recognised modality in investigating disease of the small intestine. We investigated the diagnostic value of routine TI inspection and biopsy of macroscopically abnormal terminal ileum mucosa in the investigation of anaemia.
ENDOSCOPIC TREATMENT OF THE PLUMMER VINSON SYNDROME (PATERSON-KELLY SYNDROME): CROSS-SECTIONAL STUDY (A MOROCCAN EXPERIENCE)
Authors: I Benelbarhdadi, I Nakhcha, L Lahlou, F Zehra Ajana
Journal: Endoscopy (2018)

The aim of our study is to describe the epidemiology of SPV (clinical, paraclinical, therapeutical and evolutive), to estimate the prevalence of a good evolution after dilation and to model the factors associated with this good evolution in the Moroccan context.
COMPARISON OF CLINICAL OUTCOME BETWEEN REMNANT AND ENTIRE STOMACH IN ENDOSCOPIC SUBMUCOSAL DISSECTION FOR LESIONS ON THE PROXIMAL STOMACH
Authors: SJ Kim, CW Choi, DH Kang, HW Kim, HJ Kim
Journal: Endoscopy (2018)

Tumors located on the proximal stomach are associated with the poor clinical outcome. Gastric endoscopic submucosal dissection (ESD) for lesions after distal gastrectomy is more difficult because of the narrow inner space. We aimed to compare the therapeutic outcomes of ESD for proximal gastric lesion between the remnant and entire stomach.
Electrosprayed mesoporous particles for improved aqueous solubility of a poorly water soluble anticancer agent: in vitro and ex vivo evaluation
Authors: Elshaimaa Sayed, Christina Karavasili, Ketan Ruparelia, Rita Haj-Ahmad, Georgia Charalambopoulou, Theodore Steriotis, Dimitra Giasafaki, Paul Cox, Neenu Singh, Lefki-Pavlina N. Giassafaki, Aggeliki Mpenekou, Catherine K. Markopoulou, Ioannis S. Vizirianakis, Ming-Wei Chang, Dimitrios G. Fatouros, Zeeshan Ahmad
Journal: Journal of Controlled Release (2018)

Encapsulation of poorly water-soluble drugs into mesoporous materials (e.g. silica) has evolved as a favorable strategy to improve drug solubility and bioavailability. Several techniques (e.g. spray drying, solvent evaporation, microwave irradiation) have been utilized for the encapsulation of active pharmaceutical ingredients (APIs) into inorganic porous matrices. In the present work, a novel chalcone (KAZ3) with anticancer properties was successfully synthesized by Claisen-Schmidt condensation. KAZ3 was loaded into mesoporous (SBA-15 and MCM-41) and non-porous (fumed silica, FS) materials via two techniques; electrohydrodynamic atomization (EHDA) and solvent impregnation. The effect of both loading methods on the physicochemical properties of the particles (e.g. size, charge, entrapment efficiency, crystallinity, dissolution and permeability) was investigated. Results indicated that EHDA technique can load the active in a complete amorphous form within the pores of the silica particles. In contrast, reduced crystallinity (~79%) was obtained for the solvent impregnated formulations. EHDA engineered formulations significantly improved drug dissolution up to 30-fold, compared to the crystalline drug. Ex vivo studies showed EHDA formulations to exhibit higher permeability across rat intestine than their solvent impregnated counterparts. Cytocompatibility studies on Caco-2 cells demonstrated moderate toxicity at high concentrations of the anticancer agent. The findings of the present study clearly show the immense potential of EHDA as a loading technique for mesoporous materials to produce poorly water-soluble API carriers of high payload at ambient conditions. Furthermore, the scale up potential in EHDA technologies indicate a viable route to enhance drug encapsulation and dissolution rate of loaded porous inorganic materials.
Biliary Atresia: Clinical and Research Challenges for the Twenty‐First Century
Authors: Jorge A. Bezerra, Rebecca G. Wells, Cara L. Mack, Saul J. Karpen, Jay H. Hoofnagle, Edward Doo, Ronald J. Sokol
Journal: Hepatology (2018)

Biliary atresia (BA) is a fibroinflammatory disease of the intrahepatic and extrahepatic biliary tree. Surgical hepatic portoenterostomy (HPE) may restore bile drainage, but progression of the intrahepatic disease results in complications of portal hypertension and advanced cirrhosis in most children. Recognizing that further progress in the field is unlikely without a better understanding of the underlying cause(s) and pathogenesis of the disease, the National Institutes of Diabetes and Digestive and Kidney Diseases (NIDDK) sponsored a research workshop focused on innovative and promising approaches and on identifying future areas of research. Investigators discussed recent advances using gestational ultrasound and results of newborn BA screening with serum direct (conjugated) bilirubin that support a prenatal onset of biliary injury. Experimental and human studies implicate the toxic properties of environmental toxins (e.g., biliatresone) and of viruses (e.g., cytomegalovirus) to the biliary system. Among host factors, sequence variants in genes related to biliary development and ciliopathies, a notable lack of a cholangiocyte glycocalyx and of submucosal collagen bundles in the neonatal extrahepatic bile ducts, and an innate proinflammatory bias of the neonatal immune system contribute to an increased susceptibility to damage and obstruction following epithelial injury. These advances form the foundation for a future research agenda focused on identifying the environmental and host factor(s) that cause BA, the potential use of population screening, studies of the mechanisms of prominent fibrosis in young infants, determinations of clinical surrogates of disease progression, and the design of clinical trials that target subgroups of patients with initial drainage following HPE. (Hepatology 2018; 00:000-000).
Impact of Heart Transplantation on the Functional Status of US Children With End-Stage Heart Failure
Authors: David M. Peng, Yulin Zhang, David N. Rosenthal, Michal Palmon, Sharon Chen, Beth D. Kaufman, Katsuhide Maeda, Seth A. Hollander, Nancy McDonald, Leslie B. Smoot, Daniel Bernstein, Christopher S. Almond
Journal: Circulation (2017)

There are limited data describing the functional status (FS) of children after heart transplant (HT). We sought to describe the FS of children surviving at least 1 year after HT, to evaluate the impact of HT on FS, and to identify factors associated with abnormal FS post-HT.Organ Procurement and Transplantation Network data were used to identify all US children <21 years of age surviving ≥1 year post-HT from 2005 to 2014 with a functional status score (FSS) available at 3 time points (listing, transplant, ≥1 year post-HT). Logistic regression and generalized estimating equations were used to identify factors associated with abnormal FS (FSS≤8) post-HT.A total of 1633 children met study criteria. At the 1-year assessment, 64% were "fully active/no limitations" (FSS=10), 21% had "minor limitations with strenuous activity" (FSS=9); and 15% scored ≤8. In comparison with listing FS, FS at 1 year post-HT increased in 91% and declined/remained unchanged in 9%. A stepwise regression procedure selected the following variables for association with abnormal FS at 1 year post-HT: ≥18 years of age (odds ratio [OR], 1.8; 95% confidence interval [CI], 1.2-2.7), black race (OR, 1.5; 95% CI, 1.1-2.0), support with ≥inotropes at HT (OR, 1.7; 95% CI, 1.2-2.5), hospitalization status at HT (OR, 1.5; 95% CI, 1.0-2.19), chronic steroid use at HT (OR, 1.5; 95% CI, 1.0-2.2), and treatment for early rejection (OR, 2.0; 95% CI, 1.5-2.7).Among US children who survive at least 1 year after HT, FS is excellent for the majority of patients. HT is associated with substantial improvement in FS for most children. Early rejection, older age, black race, chronic steroid use, hemodynamic support at HT, and being hospitalized at HT are associated with abnormal FS post-HT.
EUS-GUIDED CRYOTHERM ABLATION OF STAGE III PANCREATIC ADENOCARCINOMA: A PRELIMINARY RADIOLOGICAL PERSPECTIVE
Authors: E Dabizzi, SG Giulia Testoni, M Barbera, W Linzenbold, MC Petrone, M Enderle, F De Cobelli, R Nicoletti, S Gusmini, G Rossi, M Traini, A Mariani, PG Arcidiacono
Journal: Endoscopy (2018)

Cryotherm ablation is a hybrid bipolar ablative technique, combining radiofrequency thermal injury with a cryogenic gas. However, data on radiological perspectives are still lacking.
No survival benefit of extended transthoracic resection over limited transhiatal resection for adenocarcinoma of the mid/distal esophagus and gastric cardia: results of a randomized study.
Authors: J.B.F. Hulscher, A.G.E.M. de Boer, J.W. van Sandick, B.P. Wijnhoven, J.G.P. Tijssen, P. Fockens, P.F.M. Stalmeier, F.J. ten Kate, H. van Dekken, H. Obertop, H.W. Tilanus, J.J. van Lanschot
Journal: New England Journal of Medicine (2002)
438. Targeting HSV-1 Virions for Specific Binding to Epidermal Growth Factor Receptor-VIII on Tumor Cells
Authors: Paola Grandi, Juliet Fernandez, Oscar Szentirmai, Robert Carter, Xandra O. Breakefield, Miguel Sena-Esteves
Journal: Molecular Therapy (2006)

Oncolytic HSV vectors have shown promise for cancer therapy in preclinical animal models of glioma. Early phase human clinical trials have demonstrated that the use of these vectors as a therapy for recurrent malignant glioblastoma is safe without treatment-related severe adverse events and with some indication of efficacy. The safety and efficacy of oncolytic vectors should be enhanced by increasing infectivity via targeting to tumor-specific receptors. In order to target HSV-1 vectors to glial tumor cells, which typically express a mutant form of the EGFR (EGFRvIII), the virus envelope glycoprotein C (gC) was modified so as to incorporate a single chain antibody (scFv), designated MR1-1, that binds with high affinity to a novel epitope created by deletion/rearrangement in EGFRvIII. MR1-1 coding sequences were used to replace the gC sequence that normally recognizes heparan sulfate in the initial step in the natural binding of the virus to the cell surface. Wild-type and engineered HSV-1 virions expressing only modified gC were evaluated for differential infection of human glioma U87 cells and ones modified to express EGFRvIII receptors (U87EGFR) in culture. Virions bearing MR1-1-modified gC showed over 5-fold increased binding to and infection of cells expressing the EGFRvIII receptor as compared to receptor-deficient cells. Further, this MR1-1/EGFRvIII mediated infection was more efficient than that of virions expressing wild-type gC for both EGFRvIII positive and negative cells. This increased susceptibility of EGFRvIII+ cells for infection by MR1-1+ virions, as compared to wild-type virions, was also shown in subcutaneous tumors in vivo using a firefly luciferase reporter of virus infection. These data demonstrate that HSV-1 tropism can be manipulated so that virions recognize a cell specific binding site, and that this, in turn, can increase the infectivity of the virions for a specific cell type expressing the appropriate surface moiety. The retargeting of HSV virions to tumor cells should allow the use of lower vector doses to achieve greater oncolytic activity while decreasing toxicity to normal cells.
LAMS TO THE SEMS RESCUE!
Authors: P Bastos, D Libanio, J Lage, I Pita, P Pimentel-Nunes, M Dinis-Ribeiro
Journal: Endoscopy (2018)

Effective endoscopic biliary drainage may be difficult to achieve when the major papilla is inaccessible to the duodenoscope. In such cases, endoscopic ultrasound-guided biliary drainage appears to be a valid alternative to percutaneous transhepatic biliary drainage. Recently, lumen apposing metal stents (LAMS) have been used to achieve internal biliary drainage through the creation of a choledochoduodenostomy. This particular type of stent may reduce the risk of biliary leak and tends to make the procedure simpler and faster.
Abstract P051: Circulating Beta-2-microglobulin Predicts Cardiovascular, Cancer, and All-cause Mortality: The Framingham Heart Study
Authors: Shih-Jen Hwang, Joshua Keefe, Michael Mendelson, Paul Courchesne, Jennifer Ho, Martin G Larson, Asya Lyass, Chen Yao, Tianxiao Huan, Daniel Levy
Journal: Circulation (2018)

Beta-2-microglobulin (β 2 M), a multifunctional protein involved in immune function, is a filtration marker that has been reported to predict renal failure, cancer, cardiovascular disease (CVD), and all-cause mortality. Previous studies of β 2 M and mortality were limited to select study samples (elderly or patient-based) lacking information on cancer or kidney function. We examined plasma β 2 M as a predictor of all-cause and cause-specific mortality in those with and without chronic kidney disease (CKD). The study sample consisted of Framingham Heart Study participants from the 2 nd (n=3196) and 3 rd (n=3911) generations who attended an on-site examination (2001-2007). Plasma β 2 M concentration was measured using a Luminex bead-based immunoassay. Mortality events were adjudicated by a physician committee. Proportional hazard models were conducted based on standardized values of β 2 M, adjusted for CVD risk factors, prevalent CVD, cancer, and family structure. We additionally analyzed subgroups stratified for CKD (defined as GFR ckdepi &lt; 60 mL/min/1.73 m 2 ). The study sample included 7107 individuals [mean age 50 years, 54% female, 4% with prevalent CKD, mean length of follow-up: 13 years]. In the overall sample, β 2 M concentrations were associated with increased risk of CVD death (HR=1.42 [CI=1.17-1.72]), cancer death (HR=1.27 [CI=1.07-1.5]), and all-cause mortality (HR=1.27 [CI=1.16-1.4]). β 2 M performed better in participants with prevalent CKD than in those free of CKD. Adjusting for cystatin C, a filtration biomarker, did not affect the results. For all-cause mortality, including plasma β 2 M yielded a relative integrated discrimination improvement of 3% (p-value 0.03) beyond the covariate-only model. The net reclassification improvements (NRI) for all-cause mortality was 4% that was not statistically significant (p-value 0.26). We conclude that among middle-aged adults, plasma β 2 M is a predictor of all-cause and cause-specific mortality. Much of the risk associated with β 2 M is concentrated in those with CKD.
Standards and Methodological Rigor in Pulmonary Arterial Hypertension Preclinical and Translational Research
Authors: Steeve Provencher, Stephen L. Archer, F. Daniel Ramirez, Benjamin Hibbert, Roxane Paulin, Olivier Boucherat, Yves Lacasse, Sébastien Bonnet
Journal: Circulation Research (2018)

Despite advances in our understanding of the pathophysiology and the management of pulmonary arterial hypertension (PAH), significant therapeutic gaps remain for this devastating disease. Yet, few innovative therapies beyond the traditional pathways of endothelial dysfunction have reached clinical trial phases in PAH. Although there are inherent limitations of the currently available models of PAH, the leaky pipeline of innovative therapies relates, in part, to flawed preclinical research methodology, including lack of rigour in trial design, incomplete invasive hemodynamic assessment, and lack of careful translational studies that replicate randomized controlled trials in humans with attention to adverse effects and benefits. Rigorous methodology should include the use of prespecified eligibility criteria, sample sizes that permit valid statistical analysis, randomization, blinded assessment of standardized outcomes, and transparent reporting of results. Better design and implementation of preclinical studies can minimize inherent flaws in the models of PAH, reduce the risk of bias, and enhance external validity and our ability to distinguish truly promising therapies form many false-positive or overstated leads. Ideally, preclinical studies should use advanced imaging, study several preclinical pulmonary hypertension models, or correlate rodent and human findings and consider the fate of the right ventricle, which is the major determinant of prognosis in human PAH. Although these principles are widely endorsed, empirical evidence suggests that such rigor is often lacking in pulmonary hypertension preclinical research. The present article discusses the pitfalls in the design of preclinical pulmonary hypertension trials and discusses opportunities to create preclinical trials with improved predictive value in guiding early-phase drug development in patients with PAH, which will need support not only from researchers, peer reviewers, and editors but also from academic institutions, funding agencies, and animal ethics authorities.
A SURPRISING EVOLUTION OF FOCAL ESOPHAGEAL EOSINOPHIL INFILTRATION
Authors: AM Bucalau, L Verset, P Demetter, P Eisendrath, J Devière, A Lemmers
Journal: Endoscopy (2018)

A 83 years-old woman, chronically treated by PPI for gastro-esophageal reflux disease underwent an esophagogastroduodenoscopy (EGD). It showed a 30 mm Paris O-IIa verrucous esophageal lesion on 30% of the circumference at 25 cm from the incisors. The patient was not exposed to alcohol or tobacco. The lesion was lugol negative and atypical pattern with NBI and near focus examination was not in favor of squamous cell carcinoma (SCC). The biopsies revealed a dense eosinophilic infiltration associated to moderate to severe squamous dysplasia, a feature that might be reactional for our pathologist. Human papilloma virus (HPV) was not detected. Biopsies of the upper, medial and lower esophagus were negative for eosinophilic infiltration. Knowing the absence of risk factor for SCC, the atypical aspect of the lesion, the absence of symptoms and the old age of the patient, and after discussion with our pathologist, no endoscopic treatment was proposed and the patient was rescheduled for a follow-up endoscopy at 6 months. The patient came back at 15 months for control EGD. At that time, the lesion involved 30% of the esophageal circumference and its shape changed with a Paris O-Is center. Targeted biopsies revealed SCC. EUS disclosed no lymphadenopathy and was in favor of T1 lesion. Distant metastasis were excluded by thoraco-abdominal CT scan and 18F-FDG PET/CT. An endoscopic en-bloc resection by endoscopic submucosal dissection (ESD) was then performed. The patient had no symptoms after the resection. Histopathological examination of the specimen showed a moderately differentiated SCC invading the submucosa on 700 µm. Lateral and deep margins were free from malignancy and dysplasia. No lymphovascular infiltration or perineural infiltration was observed, but tumor budding was present (pT1bsm2). Considering the age of the patient endoscopic follow-up was proposed.
ENDOSCOPIC RESPONSE TO CHEMORADIOTHERAPY IN LOW RECTAL CANCER: ARE THE WAIT-AND-SEE CRITERIA TOO STRICT?
Authors: J Cortez-Pinto, R Oom, I Rosa, C Travancinha, G Fernandez, I Marques, I Miguel, J Freire, J Moleiro, J Pereira da SIlva, J Venâncio, L d'Orey, L Mirones, M Limbert, P Chaves, P Pereira, R Fonseca, R Barroca, T Ferreira, T Marques, A Dias Pereira
Journal: Endoscopy (2018)

In the wait-and-see (W&S) strategy, locally advanced low rectal adenocarcinoma patients who achieve clinical complete response (cCR) after chemoradiotherapy (CRT) undergo regular surveillance, with surgery being reserved for tumor “regrowth”. Endoscopic complete response is characterized by light/white mucosa, scar, telangiectasia or edema. Erosion and ulceration are considered an absence of response.
ASSESSING THE APPROPRIATENESS OF COLONOSCOPY REFERRALS AND POST COLONOSCOPY FOLLOW UP IN A SINGLE CENTRE
Authors: A Cotter, W Joyce
Journal: Endoscopy (2018)

The volume of referrals for colonoscopy procedures is increasing exponentially and currently healthcare systems are under extreme pressure to meet this demand. Frequently questions are raised regarding the appropriateness of referrals for these invasive procedures. There were three primary aims of this study; firstly to assess if colonoscopy referrals were appropriate, secondly to investigate if surveillance endoscopies were following guidelines and lastly to detect whether pathological findings were found for those referred with ‘red flag’ symptoms.