tbuckley/cabot-search huggingface dataset:
Talking about risk in the context of genomic tests (TARGET): Evaluation of an educational program
Authors: V.A. Jenkin, L.J. Fallowfield
Journal: Annals of Oncology (2019)

Background: Decision-making about adjuvant chemotherapy in node neg, ER+, HER2- EBC requires balancing likely absolute benefits with treatment-related side effects. Health literacy and numeracy in general populations are often poor and many clinicians find explaining risk and uncertainty challenging especially when set against a backdrop of fear and anxiety. We developed and evaluated an educational program to aid discussions about gene expression profiling test (GEP) results from OncotypeDx and EndoPredict. Methods: The 8 hr workshop contained: - a section on the science behind GEP tests, an interactive lecture on the psychology of risk and facilitated group discussions about different strategies demonstrated in 7 filmed scenarios showing doctors talking to patients with high and low risk scores (RSs). Pre and post workshop participants were recorded discussing RSs with trained patient simulators. Recordings were coded using a study specific scoring system by experienced researchers blinded to time-point. A priori hypotheses were that post workshop (a) participants' communication skills discussing risk of recurrence would improve i.e. competence would be measurably better, (b) participants would feel more confident handling such consultations i.e. self-confidence/self–efficacy would be enhanced. Results: 65 UK cancer healthcare professionals (HCPs) attended workshops. The rate re-rate reliability and inter-rater reliability for researchers coding the digital pre and post course recordings showed kappa statistics of 0.8101, SE.=0.1517 and 0.9123, SE = 0.0712 respectively. Conditional logistic regression models comparing the 2 scores observed at each time-point showed significant and positive changes in odds ratios for every key information area. HCPs' self-rated confidence levels increased significantly post intervention for each key topic (P < 0.001). Average workshop satisfaction ratings were 9.6/10 All attendees stated they would 'definitely' recommend workshops to colleagues. Conclusions: TARGET workshops significantly improved the communication skills and confidence of HCPs discussing risk and GEP test results in ways likely to assist patient decision-making about adjuvant chemotherapy in EBC. Legal entity responsible for the study: University of Sussex. Funding: Breast Cancer Research Foundation (BCRF). Disclosure: All authors have declared no conflicts of interest.
Diagnosis and outcome of acute respiratory failure in immunocompromised patients after bronchoscopy
Authors: Philippe R. Bauer, Sylvie Chevret, Hemang Yadav, Sangeeta Mehta, Peter Pickkers, Ramin B. Bukan, Jordi Rello, Andry van de Louw, Kada Klouche, Anne-Pascale Meert, Ignacio Martin-Loeches, Brian Marsh, Lorenzo Socias Crespi, Gabriel Moreno-Gonzalez, Nina Buchtele, Karin Amrein, Martin Balik, Massimo Antonelli, Martine Nyunga, Andreas Barratt-Due, Dennis C.J.J. Bergmans, Angélique M.E. Spoelstra-de Man, Anne Kuitunen, Florent Wallet, Amelie Seguin, Victoria Metaxa, Virginie Lemiale, Gaston Burghi, Alexandre Demoule, Thomas Karvunidis, Antonella Cotoia, Pål Klepstad, Ann M. Møller, Djamel Mokart, Elie Azoulay
Journal: European Respiratory Journal (2019)

We wished to explore the use, diagnostic capability and outcomes of bronchoscopy added to noninvasive testing in immunocompromised patients. In this setting, an inability to identify the cause of acute hypoxaemic respiratory failure is associated with worse outcome. Every effort should be made to obtain a diagnosis, either with noninvasive testing alone or combined with bronchoscopy. However, our understanding of the risks and benefits of bronchoscopy remains uncertain.This was a pre-planned secondary analysis of Efraim, a prospective, multinational, observational study of 1611 immunocompromised patients with acute respiratory failure admitted to the intensive care unit (ICU). We compared patients with noninvasive testing only to those who had also received bronchoscopy by bivariate analysis and after propensity score matching.Bronchoscopy was performed in 618 (39%) patients who were more likely to have haematological malignancy and a higher severity of illness score. Bronchoscopy alone achieved a diagnosis in 165 patients (27% adjusted diagnostic yield). Bronchoscopy resulted in a management change in 236 patients (38% therapeutic yield). Bronchoscopy was associated with worsening of respiratory status in 69 (11%) patients. Bronchoscopy was associated with higher ICU (40% versus 28%; p<0.0001) and hospital mortality (49% versus 41%; p=0.003). The overall rate of undiagnosed causes was 13%. After propensity score matching, bronchoscopy remained associated with increased risk of hospital mortality (OR 1.41, 95% CI 1.08-1.81).Bronchoscopy was associated with improved diagnosis and changes in management, but also increased hospital mortality. Balancing risk and benefit in individualised cases should be investigated further.
Diarrhee chronique liquidienne chez les jeunes: pertinence de la coloscopie
Authors: M Ben Abdelwahed, A Guediche, R Baklouti, F Aissaoui, M Zakhama, W Bouhlel, W Ben Mansour, HL Mohamed, BC Nabil, L Safer
Journal: Endoscopy (2019)

Les étiologies des diarrhées chroniques liquidiennes du sujet jeune sont dominées par les troubles fonctionnels intestinaux. Toutefois, la hantise du clinicien est de méconnaitre une pathologie organique en particulier néoplasique, d'où le recours aux explorations endoscopiques notamment la coloscopie. Le but de notre étude est de déterminer la pertinence de la coloscopie dans l'exploration des diarrhées chroniques liquidiennes chez les sujets jeunes.
Home-Based Cardiac Rehabilitation
Authors: Randal J. Thomas, Alexis L. Beatty, Theresa M. Beckie, LaPrincess C. Brewer, Todd M. Brown, Daniel E. Forman, Barry A. Franklin, Steven J. Keteyian, Dalane W. Kitzman, Judith G. Regensteiner, Bonnie K. Sanderson, Mary A. Whooley
Journal: Journal of the American College of Cardiology (2019)
Myocarditis in Cynomolgus Monkeys Following Treatment with Immune Checkpoint Inhibitors
Authors: Changhua Ji, Marc D. Roy, Jonathan Golas, Allison Vitsky, Sripad Ram, Steven W. Kumpf, Matthew Martin, Frank Barletta, William A. Meier, Andrea T. Hooper, Puja Sapra, Nasir K. Khan, Martin Finkelstein, Magali Guffroy, Bernard S. Buetow
Journal: Clinical Cancer Research (2019)

Immune checkpoint inhibitors (ICI) targeting PD1, PDL1, or CTLA4 are associated with immune-related adverse events (irAE) in multiple organ systems including myocarditis. The pathogenesis and early diagnostic markers for ICI-induced myocarditis are poorly understood, and there is currently a lack of laboratory animal model to enhance our understanding. We aimed to develop such a model using cynomolgus monkeys.Chinese-origin cynomolgus monkeys were dosed intravenously with vehicle or nivolumab 20 mg/kg plus ipilimumab 15 mg/kg once weekly and euthanized on day 29.Multiple organ toxicities were observed in cynomolgus monkeys, and were characterized by loose feces, lymphadenopathy, and mononuclear cell infiltrations of varying severity in heart, colon, kidneys, liver, salivary glands, and endocrine organs. Increased proliferation of CD4+ and CD8+ T lymphocytes as well as an increase in activated T cells and central memory T cells in the blood, spleen, and lymph nodes, were observed. Transcriptomic analysis suggested increased migration and activation of T cells and increased phagocytosis and antigen presentation in the heart. Mononuclear cell infiltration in myocardium was comprised primarily of T cells, with lower numbers of macrophages and occasional B cells, and was associated with minimal cardiomyocyte degeneration as well as increases in cardiac troponin-I and NT-pro-BNP. Morphologically, cardiac lesions in our monkey model are similar to the reported ICI myocarditis in humans.We have developed a monkey model characterized by multiple organ toxicities including myocarditis. This model may provide insight into the immune mechanisms and facilitate biomarker identification for ICI-associated irAEs.
Common oral opportunistic infections in Human Immunodeficiency Virus infection/Acquired Immunodeficiency Syndrome: Changing epidemiology; diagnostic criteria and methods; management protocols
Authors: Kannan Ranganathan, Krishna Mohan Rao Umadevi
Journal: Periodontology 2000 (2019)

Abstract There were 36.9 million in the world living with human immunodeficiency virus (HIV) infection/acquired immunodeficiency syndrome (AIDS) as of 2017, and new infections have seen a reduction by 18% since 2010. But this rate of decline is not sufficient for the goal of eradication of AIDS by 2030. Only 21.7 million people infected with HIV have accesses to antiretroviral therapy, with the rest at risk of the potential complications of HIV infection. It has been shown that oral lesions are diagnostic and prognostic of HIV infection, and many oral opportunistic infections continue to be a major problem, particularly in developing countries. It is therefore important that dental surgeons be aware and updated to recognize and manage the oral effects of HIV infection/AIDS. This chapter describes the classification, diagnosis, and management of oral lesions in these patients, based on our current understanding of the infection. This review also discusses the standardization of diagnosis of oral lesions in HIV infection/AIDS patients, immune reconstitution inflammatory syndrome case definition, and the research priorities formulated at the 7th World Workshop on Oral Health and Disease in AIDS.
Hep par 1 immunohistochemistry in glycogen-rich clear cell carcinoma of the breast
Authors: M.C. Chang, J.M. Wu, G.C. Bethune
Journal: Annals of Oncology (2019)

Background: Glycogen-rich clear cell carcinoma of the breast (GRCCC) is an uncommon variant of invasive breast cancer with abundant tumor-cell glycogen and thought to have poor outcome. There are conflicting reports on the prognosis of GRCCC and its pathologic/diagnostic criteria. Some features overlap with carcinomas having hepatoid features. We hypothesize that immunomarkers of hepatic differentiation may help distinguish GRCCC from more common breast cancers. Methods: As approved by the institutional research ethics board, cases diagnosed as "glycogen-rich clear cell carcinoma" or "invasive carcinoma with clear cell features" were identified from lab archives. A control cohort of non-GRCCC cases was also identified. All diagnoses were confirmed by pathologist review. Tumor grade, size, and ER/PgR/HER2 status were recorded. Freshly cut 4-μm sections from FFPE tumor blocks were mounted on charged slides and immunostained with Hep Par 1, alpha-fetoprotein (AFP) and GATA3 using standard clinical protocols. Stains were reviewed by 2 pathologists (MCC, JMW). Results: Eight cases had "clear cell features", and 5/8 met all WHO morphologic criteria for GRCCC (high-grade nuclei, polygonal cells, PAS-positive granules/globules). All GRCCCs had weak to moderate ER staining in 33- 66% of cells, were negative for PgR and HER2, and were positive for Hep Par 1 with a diffuse, strong granular cytoplasmic pattern. GRCCCs were also positive for GATA3 and negative for AFP. The remaining 3 cases "with clear cell features" had grade 2 nuclei, were GATA3-positive, had >90% strong positivity for ER and PgR, and were negative for HER2, Hep Par1 and AFP. The control cohort included 16 "luminal-like" (ER+/HER2 -), 21 HER2+, and 24 triple-negative tumors (total N = 61). GATA3 was positive in 51/61 (84%) of tumors. All tumors in the control cohort were negative for Hep Par 1 and AFP. Conclusions: True GRCCC of the breast is likely a distinct high-grade tumor with strong granular-cytoplasmic Hep Par 1 staining. GRCCCs tend to be PgR and HER2-negative, and demonstrate weak-to-moderate ER positivity. Criteria for GRCCC should be applied strictly to exclude other tumors with "clear cell features". Further work is warranted to establish the prognostic significance of this diagnosis. Legal entity responsible for the study: Martin C. Chang. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
Abstract 3670: Reduced expression of p27 and the occurrence of CpG island methylator phenotype in insulinomas
Authors: Yuan-Jia Chen, Qiao Zhou, Yuan-Fang Chen, Hai-Yan Wu, Yu Xiao
Journal: Cancer Research (2010)

Abstract Aim Little is known about the molecular pathogenesis of sporadic insulinoma which is a type of rare endocrine tumors, and there is a lack of reliable biomarkers to differentiate benign from malignant tumors. Thus we analysed the CpG island methylator phenotype (CIMP) of multiple genes in sporadic insulinamas, as well as the expression of p27 and the relationship between p27 and CIMP. Materials and Methods Using methylation specific PCR, we examined the methylation status of p16, MLH1, RAR-β, O6-MGMT, THBS1 in 33 sporadic insulinomas and 20 paired pancreatic tissues. The expression of p27 was detected by immunohistochemistry staining. The experimental data were correlated with clinical-pathological characteristics, and were analysed by t-test, chi-square test or Fisher's exact test. Results The incidence of CIMP-High was found in 33% of insulinomas, higher than its rate in the paired pancreatic tissues, but the difference was not significant (P=0.209). The methylation status of O6-MGMT and p16 were inversely correlated (P=0.003). Compared with the paired pancreaticl tissues, the expression of p27 was reduced in tumors (85% vs. 39%, P=0.008). Moreover, the reduced expression of p27 was significantly related to the methylation of O6-MGMT (P=0.016). The reduced expression of p27 might be related with higher rate of CIMP, but the difference did not reach significance due to the limited number of tumors. The experimental data were not significantly associated with clinical-pathological characteristics in this study. Conclusion CIMP-High and reduced expression of p27 were observed in a subtype of insulinomas, and these molecular alterations might play a role in tumorigenesis of insulinoma. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3670.
ENDOSCOPIC TRANSPAPILLARY ANTEGRADE SPHINCTEROTOMY
Authors: O Dovbenko
Journal: Endoscopy (2019)

ERCP has become the "Gold" standard in the diagnostics and management of pancreaticobiliary diseases. The possibilities in treating the entire spectrum of diseases of this zone are increasing. However, the level of major complications of ERCP remains high (from 5.4% to 23.0% and the overall mortality from 0.1 to 1%). The vast majority of them related to interventions on the sph Oddi. The aim of the research has become to create a sphincterotome and a method that takes into account the anatomical structure of the sph Oddi. Sph. Oddi consists of a longitudinal and circular smooth muscle layers. Circular muscle fibers form the pancreatic and duodenal parts. Anatomical justification was cutting of only the circular layer of sph Oddi by special sphincterotome. Papilary stenosis and stenosis terminal part of common bile duct due to damage only circular layer sph Oddi. Anterograde direction and hooked form of sphincterotome (endoscopic antegrade sphincterotomy- EASD) allows to capture only need layer and control depth. Also EASD was performed patient with SOD (I-III) with preservation of the longitudinal muscular layer sph Oddi and septum of papilla. 273 patient underwent EASD within 7 years (age is 44.3 ± 12.7 years, 43.8% male, 65,7% in urgent cases). Postoperative bleeding and perforation wasn't. 5 (1,83%) cases of postEASD pancreatitis manifested by increased blood enzymes and abdominal pain, successfully cured medication for 3 days. The use of EASD with preservation of the closure function of the sph. Oddi allowed to avoid cholecystectomy in 71.2%. ASD can be performed with a standart or a new design of sphincterotome. It takes into account the anatomical structure of sph. Oddi and is recommended as an alternative to standard sphincterotomy, balloon dilatation and drainage interventions (RR 0,55 [95% CI 0,18 to 1,67]). EASD must be performed by an endoscopist with experience in transpapillary intervention.
DOUBLE STENTING SEEMS TO BE BETTER THAN DOUBLE BYPASS IN CASE OF COMBINED MALIGNANT BILIARY AND DUODENAL OBSTRUCTION: META-ANALYSIS AND SYSTEMATIC REVIEW
Authors: A Fábián, R Bor, N Gede, P Bacsur, D Pécsi, P Hegyi, B Tóth, Z Szakács, Á Vincze, I Ruzsics, Z Rakonczay, B Erőss, R Sepp, Z Szepes
Journal: Endoscopy (2019)

To assess feasibility and optimal method of double stenting of malignant duodenal and biliary obstruction compared to surgical double bypass.
THE EFFICACY OF CARBON DIOXIDE INSUFFLATION FOR PERCUTANEOUS ENDOSCOPIC GASTROSTOMY PLACEMENT
Authors: S Kim, HY Lee, YI Choi, JW Chung, JH Kim, EJ Kim, YJ Kim, KO Kim, KA Kwon, DK Park
Journal: Endoscopy (2019)

We aimed to assess the effects of CO2 insufflation with percutaneous endoscopic gastrostomy (PEG) insertion compared of room air.
Abstract 15613: Plin2 Protects Against Palmitate-mediated Lipotoxicity in a Cardiomyoblast Cell Line
Authors: Ali Akoumi, Taha Haffar, Nicolas Bousette
Journal: Circulation (2016)

Introduction: We have previously shown that palmitate causes ER stress in primary cardiomyocytes and this is associated with a diffuse lipid staining histology. This is in contrast to oleate which ...
Long lasting major response to pembrolizumab in a thoracic malignant rhabdoid-like SMARCA4-deficient tumor
Authors: C. Henon, J.-Y. Blay, C. Massard, O. Mir, R. Bahleda, S. Dumont, S. Postel-Vinay, J. Adam, J.-C. Soria, A. Le Cesne
Journal: Annals of Oncology (2019)
Impact of the 21-gene assay on treatment decisions in high-risk patients with ER-positive HER2-negative early breast cancer: Results of the KARMA Dx study
Authors: A. Llombart, R. Andrés, A. Anton Torres, N. Martinez, C. Rodriguez, P. Sánchez-Rovira, B. Rojas, M. Ruiz Borrego, B. Bermejo, E. Martinez de Dueñas
Journal: Annals of Oncology (2019)

Background: Patients (pts) with ER+, HER2– early breast cancer (EBC) do not universally benefit from adding adjuvant chemotherapy (CT) to hormonal treatment (HT). The 21-gene Oncotype DX Breast Recurrence Score® (RS) assay is uniquely designed and validated to guide CT treatment decisions in this population. Methods: The primary objective of the KARMA Dx study was to assess the impact of the RS result on treatment recommendations in high-risk patients for whom CT benefit was uncertain. Secondary objective was the evaluation of physicians' confidence in their recommendation. This study was performed before the recent publication of the TAILORx trial that definitively determined RS cut-points for CT benefit. Eligible EBC pts were ER+, HER2– candidates for CT based on high-risk clinicopathologic features: · Cohort A: grade 3, N0/N1mic · Cohort B: grade 1-2, N1-3, or · Cohort C: cT > 2 cm N0 by imaging (not T4) and planned for neoadjuvant CT Recommendations were captured before and after availability of individual RS results. Primary outcome was the percent change in CT recommendations post- vs. pre-RS results. Results: 219 pts with median age of 55 years were recruited in 7 Spanish centers and 209 pts were included in the final analysis. Recommendations changed from CT + HT to HT alone for 67% (140) of patients. The table shows changes in recommendations by cohort and RS group. Considering that 85% of patients had RS 0-25, using these TAILORx cut-points might further affect CT reduction. Physicians' confidence in their final recommendation increased in 34% of cases. Conclusions: RS testing resulted in an overall 67% reduction in CT recommendation in pts considered candidates for CT based on clinicopathologic criteria. These results reached 76% for patients in cohort C. The findings of the present study indicate the significant potential of the 21-gene assay to spare CT in high-risk EBC pts. Legal entity responsible for the study: Hospital Arnau de Vilanova. Funding: Genomic Health Inc. Disclosure: A. Llombart: Grants/research support: Genomic Health Inc.; Stock shareholder: MedSIR. All other authors have declared no conflicts of interest. Table28PCohortChanges in recommendationRecurrence Score (RS) groupsTotal n0-1718-3031-100All patients (n = 209)CT + HT to HT alone99 (86%)39 (53%)2 (10%)140 (67%)No change16 (14%)35 (47%)18 (90%)69 (33%)Total n1157420209A: N0, grade 3 (n = 30)CT + HT to HT alone5 (56%)3 (27%)1 (10%)9 (30%)No change4 (44%)8 (73%)9 (90%)21 (70%)Total n9111030B: N1 (1-3), grade 1-2 (n = 150)CT + HT to HT alone78 (91%)31 (54%)0109 (73%)No change8 (9%)26 (46%)7 (100%)41 (27%)Total n86577150C: Neoadjuvant (n = 29)CT + HT to HT alone16 (80%)5 (83%)1 (33%)22 (76%)No change4 (20%)1 (17%)2 (67%)7 (24%)Total n206329 Open table in a new tab
EUS-GUIDED, RFA ABLATION OF BENIGN AND MALIGNANT PANCREATIC NEOPLASMS AND EXTRA PANCREATIC METASTASIS IS FEASIBLE AND SAFE
Authors: A Dancour, M Rottenstreich, G Sheynkman, E Tahover, D Wengrower, E Goldin, T Golan, D Livovsky
Journal: Endoscopy (2019)

New therapeutic alternatives are needed for patients with pancreatic tumors not suitable for surgery or in order to avoid surgical morbidity. We present our data on the use of a new, through- the-echoendoscope radiofrequency ablation (RFA) device.
Sky-High Mortality Rates From Cesarean Delivery in Africa
Authors: M.J. Friedrich
Journal: JAMA (2019)

Women in Africa are 50 times more likely to die as a result of a cesarean delivery as women in high-income countries, a team of investigators from several African countries has reported. Neonates fare poorly, too. Their mortality rate after cesarean delivery is high—44 per 1000 live births.
TMAO and Heart Disease: The New Red Meat Risk?
Authors: Jennifer Abbasi
Journal: JAMA (2019)

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