tbuckley/cabot-search huggingface dataset:
Transluminal stone removal from right intrahepatic bile duct using novel basket catheter
Authors: Takeshi Ogura, Nobu Nishioka, Saori Ueno, Tadahiro Yamada, Kazuhide Higuchi
Journal: Endoscopy (2019)

Intrahepatic bile duct (IHBD) stones are usually removed under endoscopic retrograde cholangiopancreatography (ERCP) [1] [2] [3]. However, ERCP can be challenging when patients have a complicated surgical anatomy. Various intervention techniques under endoscopic ultrasound (EUS) guidance, such as antegrade stone removal, have been applied [4], but right IHBD stone removal can be difficult owing to device limitations. A novel basket catheter (Reforma; Piolax Medical Devices Inc., Kanagawa, Japan), which can be used for pancreatic stone removal under ERCP guidance [5], has recently become available ([Fig. 1]). We describe technical tips for transluminal bile duct stone removal from the right IHBD using this novel catheter ([Video 1]).
International Consortium for Health Outcomes Measurement (ICHOM): Standardized Patient-Centered Outcomes Measurement Set for Heart Failure Patients
Authors: Daniel J.P. Burns, Jason Arora, Oluwakemi Okunade, John F. Beltrame, Sabrina Bernardez-Pereira, Marisa G. Crespo-Leiro, Gerasimos S. Filippatos, Suzanna Hardman, Arno W. Hoes, Stephen Hutchison, Mariell Jessup, Tina Kinsella, Michael Knapton, Carolyn S.P. Lam, Frederick A. Masoudi, Hugh McIntyre, Richard Mindham, Louise Morgan, Luuk Otterspoor, Victoria Parker, Hans E. Persson, Claude Pinnock, Christopher M. Reid, Jillian Riley, Lynne W. Stevenson, Theresa A. McDonagh
Journal: JACC Heart Failure (2019)

Whereas multiple national, international, and trial registries for heart failure have been created, international standards for clinical assessment and outcome measurement do not currently exist. The working group's objective was to facilitate international comparison in heart failure care, using standardized parameters and meaningful patient-centered outcomes for research and quality of care assessments. The International Consortium for Health Outcomes Measurement recruited an international working group of clinical heart failure experts, researchers, and patient representatives to define a standard set of outcomes and risk-adjustment variables. This was designed to document, compare, and ultimately improve patient care outcomes in the heart failure population, with a focus on global feasibility and relevance. The working group employed a Delphi process, patient focus groups, online patient surveys, and multiple systematic publications searches. The process occurred over 10 months, employing 7 international teleconferences. A 17-item set has been established, addressing selected functional, psychosocial, burden of care, and survival outcome domains. These measures were designed to include all patients with heart failure, whether entered at first presentation or subsequent decompensation, excluding cardiogenic shock. Sources include clinician report, administrative data, and validated patient-reported outcome measurement tools: the Kansas City Cardiomyopathy Questionnaire; the Patient Health Questionnaire-2; and the Patient-Reported Outcomes Measurement Information System. Recommended data included those to support risk adjustment and benchmarking across providers and regions. The International Consortium for Health Outcomes Measurement developed a dataset designed to capture, compare, and improve care for heart failure, with feasibility and relevance for patients and clinicians worldwide.
Moving From Cancer Burden to Cancer Genomics for Smoldering Myeloma
Authors: Francesco Maura, Niccolò Bolli, Even H. Rustad, Malin Hultcrantz, Nikhil Munshi, Ola Landgren
Journal: JAMA Oncology (2019)

All patients who develop multiple myeloma have a preceding asymptomatic expansion of clonal plasma cells, clinically recognized as monoclonal gammopathy of undetermined significance or smoldering multiple myeloma (SMM). During the past decade, significant progress has been made in the classification and risk stratification of SMM.This review summarizes current clinical challenges and discusses available models for risk stratification in the context of SMM. Owing to several novel, more effective, and less toxic drugs, these aspects are becoming increasingly important to identify patients eligible for early treatment. However, all proposed criteria were built around indirect markers of disease burden and therefore are generally able to identify a fraction of patients with SMM in whom transformation to multiple myeloma and genomic subclonal diversification are already happening. In contrast, next-generation sequencing approaches have the potential to identify myeloma precursor disease that will progress even before the major clonal expansion and progression, providing a potential base for more effective treatment and better precision regarding the optimal timing of treatment initiation.Owing to modern technologies, in the near future, prognostic models derived from genomic signatures independent of the disease burden will allow better identification of the optimal timing to treat a plasma cell clonal disorder at the very early stages, when the chances of eradication are higher.
Bendamustine retreatment of CLL in the outpatient setting.
Authors: Georg Guenther, Stefan Wilhelm, Hans Werner Tessen, Rainer Goettel, Annette Sauer
Journal: Journal of Clinical Oncology (2012)

6566 Background: Several studies have proven that bendamustine is a highly active drug in the therapy of CLL (Knauf et al. J Clin Oncol. 2009;27:4378-84; Fischer et al. J Clin Oncol. 2011;29:3559-3556). Nevertheless, only few data exist about the real-life use and efficacy of bendamustine-therapies in the non-trial setting. The project group of internal oncology (p.i.o.) therefore implemented a registry for patients in the routine use of bendamustine in the therapy of CLL ( Sauer et al. Onkologie 2010;33(suppl 6):12). Since 2008 a total of 616 patients have been registered, out of which 473 have been thoroughly documented. To evaluate whether a retreatment with bendamustine in relapsed CLL is still active and well tolerable we present comparative data on therapies in patients with (group A) or without (group B) bendamustine pretreatment. Methods: 228 documented patients in relapsed situation were retrospectively appointed to one of two groups (see table below). Results: In Group A the ORR was 80 % and the median PFS lasted 15.6 month. In the patients without prior bendamustine treatment the ORR was 84% and the median PFS lasted 21.2 month. In both groups the median OS has not been reached yet. The grade 3/4 toxicities were mostly hematologic and comparable in both groups. Similar grade 3/4 toxicities were observed for neutropenia (about 25% of the patients), thrombocytopenia (16%) and infections (5%). Conclusions: Bendamustine is broadly used in the routine treatment of CLL. Bendamustine-therapies show impressionable high activity and tolerability, even in an advanced-line context with prior exposition to bendamustine. The treatment results are comparable to results of clinical trials and underline the quality and feasibility of bendamustine in the outpatient treatment. Nevertheless, it is to note that this is a registry and that both groups therefore are not composed of randomized patient-populations (cf. ECOG, patients in lines and ratio of rituximab combinations). [Table: see text]
Abstract C06: Cholesterol deprivation induces TGFβ signaling to promote basal differentiation in pancreatic cancer
Authors: Linara Gabitova, Suraj Peri, Ralph Francescone, Janusz Franco-Barraza, Neelima Shah, Emmanuelle Nicolas, Elizabeth A. Handorf, Kathy Q. Cai, Ido Sloma, Rachel Chiaverelli, Richard Moffitt, Erica A. Golemis, Carolyn Fang, Shannon Lynch, Edna Cukierman, Igor Astsaturov
Journal: Cancer Research (2019)

Abstract Oncogenic transformation alters the metabolism of cellular nutrients to sustain tumor growth. We here define a mechanism by which modifications in cholesterol metabolism control the formation of pancreatic ductal adenocarcinoma (PDAC). Disruption of distal cholesterol biosynthesis by means of conditional inactivation of Nsdhl in mice bearing a tumor-inducing Kras mutation (KrasG12D) prevented PDAC formation in the context of a heterozygous Trp53f/+ genotype without impairing normal pancreatic development. In mice with pancreatic Nsdhl ablation and homozygous loss of Trp53, the emerging tumors presented with the aggressive basal (mesenchymal) phenotype as opposed to the classic (glandular) PDAC. This paralleled significantly reduced expression of cholesterol metabolic pathway genes in human basal PDAC subtype. Mechanistically, we demonstrate that genetic or metabolic reduction in cellular cholesterol induces the expression of transforming growth factor beta (TGF) and activates pro-mesenchymal effectors in human and murine PDAC, providing a direct transcriptional mechanism by which cholesterol metabolism can condition tumor differentiation. Activity of TGF beta pathway estimated via pSMAD2 expression in surgical PDAC samples inversely correlated with patients’ blood cholesterol levels, especially in patients taking cholesterol-lowering statins. Conclusions: Low levels of cellular cholesterol induce autocrine TGF beta signaling in PDAC. Malnutrition or cholesterol-lowering statins may be mechanistically linked to basal PDAC differentiation. Citation Format: Linara Gabitova, Suraj Peri, Ralph Francescone, Janusz Franco-Barraza, Neelima Shah, Emmanuelle Nicolas, Elizabeth A. Handorf, Kathy Q. Cai, Ido Sloma, Rachel Chiaverelli, Richard Moffitt, Erica A. Golemis, Carolyn Fang, Shannon Lynch, Edna Cukierman, Igor Astsaturov. Cholesterol deprivation induces TGFβ signaling to promote basal differentiation in pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2019 Sept 6-9; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2019;79(24 Suppl):Abstract nr C06.
Neutralizing tumor-promoting inflammation with polypeptide-dexamethasone conjugate for microenvironment modulation and colorectal cancer therapy
Authors: Sheng Ma, Wantong Song, Yudi Xu, Xinghui Si, Dawei Zhang, Shixian Lv, Chenguang Yang, Lili Ma, Zhaohui Tang, Xuesi Chen
Journal: Biomaterials (2019)
In a Phase 1a escalating clinical trial, autologous mesenchymal stem cell infusion for renovascular disease increases blood flow and the glomerular filtration rate while reducing inflammatory biomarkers and blood pressure
Authors: Abdelrhman Abumoawad, Ahmed Saad, Christopher M. Ferguson, Alfonso Eirin, Sandra M. Herrmann, LaTonya J. Hickson, Busra B. Goksu, Emily Bendel, Sanjay Misra, James Glockner, Allan B. Dietz, Lilach O. Lerman, Stephen C. Textor
Journal: Kidney International (2019)
Molecular Biomarkers in Localized Prostate Cancer: ASCO Guideline
Authors: Scott E. Eggener, R. Bryan Rumble, Andrew J. Armstrong, Todd M. Morgan, Tony Crispino, Philip Cornford, Theodorus van der Kwast, David J. Grignon, Alex J. Rai, Neeraj Agarwal, Eric A. Klein, Robert B. Den, Himisha Beltran
Journal: Journal of Clinical Oncology (2019)

This guideline provides recommendations for available tissue-based prostate cancer biomarkers geared toward patient selection for active surveillance, identification of clinically significant disease, choice of postprostatectomy adjuvant versus salvage radiotherapy, and to address emerging questions such as the relative value of tissue biomarkers compared with magnetic resonance imaging.An ASCO multidisciplinary Expert Panel, with representatives from the European Association of Urology, American Urological Association, and the College of American Pathologists, conducted a systematic literature review of localized prostate cancer biomarker studies between January 2013 and January 2019. Numerous tissue-based molecular biomarkers were evaluated for their prognostic capabilities and potential for improving management decisions. Here, the Panel makes recommendations regarding the clinical use and indications of these biomarkers.Of 555 studies identified, 77 were selected for inclusion plus 32 additional references selected by the Expert Panel. Few biomarkers had rigorous testing involving multiple cohorts and only 5 of these tests are commercially available currently: Oncotype Dx Prostate, Prolaris, Decipher, Decipher PORTOS, and ProMark. With various degrees of value and validation, multiple biomarkers have been shown to refine risk stratification and can be considered for select men to improve management decisions. There is a paucity of prospective studies assessing short- and long-term outcomes of patients when these markers are integrated into clinical decision making.Tissue-based molecular biomarkers (evaluating the sample with the highest volume of the highest Gleason pattern) may improve risk stratification when added to standard clinical parameters, but the Expert Panel endorses their use only in situations in which the assay results, when considered as a whole with routine clinical factors, are likely to affect a clinical decision. These assays are not recommended for routine use as they have not been prospectively tested or shown to improve long-term outcomes-for example, quality of life, need for treatment, or survival. Additional information is available at www.asco.org/genitourinary-cancer-guidelines.
Nicotinamide Pathway-Dependent Sirt1 Activation Restores Calcium Homeostasis to Achieve Neuroprotection in Spinocerebellar Ataxia Type 7
Authors: Colleen A. Stoyas, David D. Bushart, Pawel M. Switonski, Jacqueline M. Ward, Akshay Alaghatta, Mi-bo Tang, Chenchen Niu, Mandheer Wadhwa, Haoran Huang, Alex Savchenko, Karim Gariani, Fang Xie, Joseph R. Delaney, Terry Gaasterland, Johan Auwerx, Vikram G. Shakkottai, Albert R. La Spada
Journal: Neuron (2019)
Abstract 11287: Establishment of Novel Deep Venous Thrombosis Model Suitable for In Vivo Imaging
Authors: Mitsumasa Okano, Tetsuya Hara, Makoto Nishimori, Koichi Watanabe, Toshihiko Oshita, Yasuhiro Irino, Seimi Kobayashi, Masakazu Shinohara, Ryuji Toh, Tatsuro Ishida, Ken-ichi Hirata
Journal: Circulation (2018)

Backgrounds: The pathogenesis of DVT (deep venous thrombosis) is still unclear, largely due to a lack of an appropriate animal model. Although stasis is a major cause of DVT formation, IVC (inferio...
Common barriers to healthcare for transgender people in the U.S. Southeast
Authors: Austin H. Johnson, Ivy Hill, Jasmine Beach-Ferrara, Baker A. Rogers, Andrew Bradford
Journal: International Journal of Transgender Health (2019)

Background: Transgender and non-binary people are more likely to face barriers to healthcare than their cisgender counterparts. The majority of work in this area centers on the experiences of transgender people in northern cities and urban enclaves, yet over 500,000 transgender people live in the U.S. Southeast.Aims: The purpose of this study is to explore barriers to healthcare among transgender people in the U.S. Southeast.Methods: The research team conducted four 120-minute focus groups (eligibility criteria: 18 years or older, self-identify as transgender, live in the U.S. Southeast). Participants completed a demographic questionnaire prior to the start of the focus group. Each focus group explored access to and experiences of receiving basic healthcare as a transgender person in the U.S. Southeast. Established qualitative methods were used to conduct the focus groups and data analysis.Results: Participants (n = 48) ranged in age from 19 to 65, with the majority identifying as trans women (43.8%) and non-binary (33.3%). The sample was racially diverse: White (50%), Black (37.5%), and Latinx or Multiracial (12.5%). Multiple barriers to care were identified: (1) fear and mistrust of providers; (2) inconsistency in access to healthcare; (3) disrespect from providers; and, (4) mistreatment due to intersecting experiences of gender, race, class, and location.Discussion: Transgender Southerners face barriers to care at the structural, cultural, and interpersonal levels. The study results have implications for researchers, as well as providers, practices, and health care systems throughout the region.
GP wins High Court appeal against decision to erase him from medical register
Authors: Clare Dyer
Journal: BMJ (2019)

A GP who was ordered to be struck off the UK medical register has won a High Court appeal quashing the decision.1

A medical practitioners’ tribunal decided in July to strike Olakunle Arowojolu off the register for sexually assaulting a receptionist at the health centre in Essex where he worked as an out of hours GP.

But his lawyers successfully argued at the High Court that the tribunal’s legally qualified chairman had misdirected the tribunal members about the way they should treat evidence that the receptionist, at the age of 14, had accused her grandfather of sexually abusing her for two years.

Mr Justice Julian Knowles ruled that the tribunal chairman misdirected the members in telling them that they need not try to decide whether or not the allegations about …
Females with Cystic Fibrosis Demonstrate a Differential Response Profile to Ivacaftor Compared with Males
Authors: Katharine E. Secunda, Jennifer S. Guimbellot, Borko Jovanovic, Sonya L. Heltshe, Scott D. Sagel, Steven M. Rowe, Manu Jain
Journal: American Journal of Respiratory and Critical Care Medicine (2019)
IL-33 Therapy Prevents Acute Lung Injury after Transplantation Via IL-9-Producing Type 2 Innate Lymphoid Cells Induction
Authors: Hua Jiang, Abdulraouf Ramadan, Becquet Laurine, Tu Szu-Wei, Hong Liu, Courtney Rowan, Xiaowen Liu, Huanmei Wu, Jun Wan, Sophie Paczesny
Journal: Blood (2019)
Mitochondrial Deacetylase Sirt3 Reduces Vascular Dysfunction and Hypertension While Sirt3 Depletion in Essential Hypertension Is Linked to Vascular Inflammation and Oxidative Stress
Authors: Anna E. Dikalova, Arvind Pandey, Liang Xiao, Liaisan Arslanbaeva, Tatiana Sidorova, Marcos G. Lopez, Frederic T. Billings, Eric Verdin, Johan Auwerx, David G. Harrison, Sergey I. Dikalov
Journal: Circulation Research (2019)

Rationale: Hypertension represents a major risk factor for stroke, myocardial infarction, and heart failure and affects 30% of the adult population. Mitochondrial dysfunction contributes to hypertension, but specific mechanisms are unclear. The mitochondrial deacetylase Sirt3 (Sirtuin 3) is critical in the regulation of metabolic and antioxidant functions which are associated with hypertension, and cardiovascular disease risk factors diminish Sirt3 level. Objective: We hypothesized that reduced Sirt3 expression contributes to vascular dysfunction in hypertension, but increased Sirt3 protects vascular function and decreases hypertension. Methods and Results: To test the therapeutic potential of targeting Sirt3 expression, we developed new transgenic mice with global Sirt3OX (Sirt3 overexpression), which protects from endothelial dysfunction, vascular oxidative stress, and hypertrophy and attenuates Ang II (angiotensin II) and deoxycorticosterone acetate–salt induced hypertension. Global Sirt3 depletion in Sirt3 −/− mice results in oxidative stress due to hyperacetylation of mitochondrial superoxide dismutase (SOD2), increases HIF1α (hypoxia-inducible factor-1), reduces endothelial cadherin, stimulates vascular hypertrophy, increases vascular permeability and vascular inflammation (p65, caspase 1, VCAM [vascular cell adhesion molecule-1], ICAM [intercellular adhesion molecule-1], and MCP1 [monocyte chemoattractant protein 1]), increases inflammatory cell infiltration in the kidney, reduces telomerase expression, and accelerates vascular senescence and age-dependent hypertension; conversely, increased Sirt3 expression in Sirt3OX mice prevents these deleterious effects. The clinical relevance of Sirt3 depletion was confirmed in arterioles from human mediastinal fat in patients with essential hypertension showing a 40% decrease in vascular Sirt3, coupled with Sirt3-dependent 3-fold increases in SOD2 acetylation, NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) activity, VCAM, ICAM, and MCP1 levels in hypertensive subjects compared with normotensive subjects. Conclusions: We suggest that Sirt3 depletion in hypertension promotes endothelial dysfunction, vascular hypertrophy, vascular inflammation, and end-organ damage. Our data support a therapeutic potential of targeting Sirt3 expression in vascular dysfunction and hypertension.
Dopamine metabolism by a monoamine oxidase mitochondrial shuttle activates the electron transport chain
Authors: Steven M. Graves, Zhong Xie, Kristen A. Stout, Enrico Zampese, Lena F. Burbulla, Jean C. Shih, Jyothisri Kondapalli, Tommaso Patriarchi, Lin Tian, Lars Brichta, Paul Greengard, Dimitri Krainc, Paul T. Schumacker, D. James Surmeier
Journal: Nature Neuroscience (2019)
Combination of ATRA and High-Dose Dexamethasone As First-Line Treatment in Adult Immune Thrombocytopenia:a Randomized, Phase 2, Open-Label Trial
Authors: Qiu-Sha Huang, Yi Liu, Jing-Bo Wang, Jun Peng, Ming Hou, Hui Liu, Jing-Wen Wang, Lan-Ping Xu, Kaiyan Liu, Xiao-Jun Huang, Xiao-Hui Zhang
Journal: Blood (2019)
‘Blast from the past’ colonoscopy complication treated with a novel approach
Authors: Mohamed Shiha, Stuart Laidlaw, Lesley Hunt, Andrew D Hopper
Journal: Gut (2019)

A 72-year-old man was referred for a flexible sigmoidoscopy because of transfusion-dependent rectal bleeding. The patient had undergone an allogeneic stem cell transplant for acute myeloid leukaemia and had previous radiotherapy for prostate cancer. A previous sigmoidoscopy had diagnosed a solitary rectal ulcer and diffuse bleeding from radiation proctitis treated with haemostatic powder.

Blood tests prior to the repeat sigmoidoscopy showed thrombocytopaenia (47×109/L) and neutropaenia (0.33×109/L) and normal coagulation. A platelet transfusion and a phosphate enema were administered preprocedure, and a flexible sigmoidoscopy was performed to the descending colon using carbon dioxide insufflation. There was no evidence …
High-Risk Additional Chromosomal Abnormalities in CML Herald Death By Blast Crisis Already at Low Blast Levels
Authors: Rüdiger Hehlmann, Astghik Voskanyan, Michael Lauseker, Markus Pfirrmann, Lida Kalmanti, Sébastien Rinaldetti, Katharina Kohlbrenner, Claudia Haferlach, Brigitte Schlegelberger, Alice Fabarius, Stefan W Krause, Hans-Jochem Kolb, Andreas Neubauer, Dieter K. Hossfeld, Christoph Nerl, Alois Gratwohl, Gabriela M Baerlocher, Andreas Burchert, Tim H Brümmendorf, Andreas Hochhaus, Susanne Saussele, Michele Baccarani
Journal: Blood (2019)
Identification of Immunological Parameters Related to Relapse in Patients with Chronic Myeloid Leukemia on Treatment-Free Remission
Authors: Valentín Garcia-Gutiérrez, Lorena Vigon, Laura Checa, Alejandro Luna, Miguel Piris-Villaespesa, Sara Rodriguez-Mora, Guiomar Bautista, Juan Luis Steegmann, Vicente Planelles, Jose Alcamí, Maria Rosa López-Huertas, Maria Teresa Coiras
Journal: Blood (2019)
Post-truth era is destroying society and medicine
Authors: Murray G Forsyth
Journal: BMJ (2019)

Perera and colleagues focus on an important issue of our time.1 It is not “vaxxers” versus “anti-vaxxers,” but the disaster of living in a “post truth” society.2

It pervades every aspect of our lives—from the bluster of politicians who now operate with impunity, knowing that should any of their misdemeanours be brought to light …
Safety of live attenuated influenza vaccine (LAIV) in children with moderate to severe asthma
Authors: Paul J. Turner, Louise Fleming, Sejal Saglani, Jo Southern, Nick J. Andrews, Elizabeth Miller, Alexandra Adams, Christine Doyle, Michel Erlewyn-Lajeunesse, Katy Fidler, Louise Fleming, Atul Gupta, Stephen M. Hughes, Andrew Ives, Nicola Jay, Sonal Kansra, Louise Michaelis, Samantha Moss, Clare Murray, Prasad Nagakumar, Graham Roberts, Sejal Saglani, Paul Seddon, Ian Sinha, Gary Stiefel, Huw M. Thomas, Paul J. Turner
Journal: Journal of Allergy and Clinical Immunology (2019)

Live attenuated influenza vaccine (LAIV) is recommended for annual influenza vaccination in children from age 2 years. However, some guidelines recommend against its use in children with asthma or recurrent wheeze due to concerns over its potential to induce wheezing.