tbuckley/cabot-search huggingface dataset:
Exploring Diseases/Traits and Blood Proteins Causally Related to Expression of ACE2, the Putative Receptor of SARS-CoV-2: A Mendelian Randomization Analysis Highlights Tentative Relevance of Diabetes-Related Traits
Authors: Shitao Rao, Alexandria Lau, Hon-Cheong So
Journal: Diabetes Care (2020)

OBJECTIVE COVID-19 has become a major public health problem. There is good evidence that ACE2 is a receptor for SARS-CoV-2, and high expression of ACE2 may increase susceptibility to infection. We aimed to explore risk factors affecting susceptibility to infection and prioritize drug repositioning candidates, based on Mendelian randomization (MR) studies on ACE2 lung expression. RESEARCH DESIGN AND METHODS We conducted a phenome-wide MR study to prioritize diseases/traits and blood proteins causally linked to ACE2 lung expression in GTEx. We also explored drug candidates whose targets overlapped with the top-ranked proteins in MR, as these drugs may alter ACE2 expression and may be clinically relevant. RESULTS The most consistent finding was tentative evidence of an association between diabetes-related traits and increased ACE2 expression. Based on one of the largest genome-wide association studies on type 2 diabetes mellitus (T2DM) to date (N = 898,130), T2DM was causally linked to raised ACE2 expression (P = 2.91E−03; MR-IVW). Significant associations (at nominal level; P &amp;lt; 0.05) with ACE2 expression were observed across multiple diabetes data sets and analytic methods for T1DM, T2DM, and related traits including early start of insulin. Other diseases/traits having nominal significant associations with increased expression included inflammatory bowel disease, (estrogen receptor–positive) breast cancer, lung cancer, asthma, smoking, and elevated alanine aminotransferase. We also identified drugs that may target the top-ranked proteins in MR, such as fostamatinib and zinc. CONCLUSIONS Our analysis suggested that diabetes and related traits may increase ACE2 expression, which may influence susceptibility to infection (or more severe infection). However, none of these findings withstood rigorous multiple testing corrections (at false discovery rate &amp;lt;0.05). Proteome-wide MR analyses might help uncover mechanisms underlying ACE2 expression and guide drug repositioning. Further studies are required to verify our findings.
In acute HF, intensive and sustained vasodilation did not reduce a composite of death or HF readmission at 180 days
Authors: Gaetano Santulli
Journal: Annals of Internal Medicine (2020)

Kozhuharov N, Goudev A, Flores D, et al. Effect of a strategy of comprehensive vasodilation vs usual care on mortality and heart failure rehospitalization among patients with acute heart failure: the GALACTIC randomized clinical trial. JAMA. 2019;322:2292-302. 31846016.
Laboratory-Proven Asymptomatic SARS-CoV-2 (COVID-19) Infection on 18F-FDG PET/CT
Authors: Simone Krebs, Iva Petkovska, Alan L. Ho, Gary A. Ulaner
Journal: Clinical Nuclear Medicine (2020)

Abstract An 87-year-old man with primary salivary duct carcinoma and hepatic metastases was referred for restaging. 18 F-FDG PET/CT demonstrated new FDG-avid ground-glass opacities with intralobular septal thickening in both lungs with a peripheral dominant distribution. This was interpreted as a pattern highly suggestive of COVID-19 pneumonia, and the referring physician was contacted. The patient was currently asymptomatic and without clinical evidence of active pneumonia. However, the patient tested positive for COVID-19 using real-time reverse transcription–polymerase chain reaction. This case demonstrates that even asymptomatic outpatients undergoing PET/CT should be evaluated for radiologic findings suggestive of COVID-19 during this pandemic.
ENDOSCOPIC MANAGEMENT OF POSTOPERATIVE PANCREATIC FISTULAS (POPF) ARISING AFTER DISTAL PANCREATECTOMY OR ENUCLEATION: A TERTIARY CARE CENTER EXPERIENCE
Authors: EA Ali, M Camus, S Leblanc, F Paye, P Balladur, JC Vaillant, F Menegaux, PP Massault, M Barret, R Coriat, S Chaussade, B Dousset, S Gaujoux, F Prat
Journal: Endoscopy (2020)

Aims Only small series have described the endoscopic management of POPF. The purpose of this retrospective study was to describe the indications, technique and results of endoscopic treatment of POPF in our experience.
IDENTIFYING AMPULLA AND DIFFICULTY OF SELECTIVE CANNULATION WITH ARTIFICIAL-INTELLIGENCE ASSISTED ANALYSIS OF ERCP IMAGE
Authors: KW Lee, JM Lee, HJ Jeon, SH Kim, S Jang, SJ Choi, HS Choi, ES Kim, B Keum, YT Jeen, HS Lee, HJ Chun, CD Kim, J Kim, T Kim, J Choo, SY Han, DU Kim, S Kwon
Journal: Endoscopy (2020)

Aims The advancement of artificial intelligence (AI) made it possible to apply AI into medical fields. The aim of this study was to investigate an AI-assisted classification for ERCP through convolutional neural network (CNN) using documented endoscopic images.
Antitumor Activity of Amivantamab (JNJ-61186372), an EGFR–MET Bispecific Antibody, in Diverse Models of <i>EGFR</i> Exon 20 Insertion–Driven NSCLC
Authors: Jiyeon Yun, Soo-Hwan Lee, Seok-Young Kim, Seo-Yoon Jeong, Jae-Hwan Kim, Kyoung-Ho Pyo, Chae-Won Park, Seong Gu Heo, Mi Ran Yun, Sangbin Lim, Sun Min Lim, Min Hee Hong, Hye Ryun Kim, Meena Thayu, Joshua C. Curtin, Roland E. Knoblauch, Matthew V. Lorenzi, Amy Roshak, Byoung Chul Cho
Journal: Cancer Discovery (2020)

Abstract EGFR exon 20 insertion driver mutations (Exon20ins) in non–small cell lung cancer (NSCLC) are insensitive to EGFR tyrosine kinase inhibitors (TKI). Amivantamab (JNJ-61186372), a bispecific antibody targeting EGFR–MET, has shown preclinical activity in TKI-sensitive EGFR-mutated NSCLC models and in an ongoing first-in-human study in patients with advanced NSCLC. However, the activity of amivantamab in Exon20ins-driven tumors has not yet been described. Ba/F3 cells and patient-derived cells/organoids/xenograft models harboring diverse Exon20ins were used to characterize the antitumor mechanism of amivantamab. Amivantamab inhibited proliferation by effectively downmodulating EGFR–MET levels and inducing immune-directed antitumor activity with increased IFNγ secretion in various models. Importantly, in vivo efficacy of amivantamab was superior to cetuximab or poziotinib, an experimental Exon20ins-targeted TKI. Amivantamab produced robust tumor responses in two Exon20ins patients, highlighting the important translational nature of this preclinical work. These findings provide mechanistic insight into the activity of amivantamab and support its continued clinical development in Exon20ins patients, an area of high unmet medical need. Significance: Currently, there are no approved targeted therapies for EGFR Exon20ins–driven NSCLC. Preclinical data shown here, together with promising clinical activity in an ongoing phase I study, strongly support further clinical investigation of amivantamab in EGFR Exon20ins–driven NSCLC. This article is highlighted in the In This Issue feature, p. 1079
When viruses collide: hepatitis B virus reactivation after hepatitis C treatment
Authors: Ashwin Balagopal, Chloe L. Thio
Journal: Journal of Clinical Investigation (2020)

Treatment for hepatitis C virus (HCV) with direct-acting antivirals (DAAs) in hepatitis B virus (HBV) coinfection can result in HBV reactivation. In this issue of the JCI, Cheng and colleagues explored the role of interferon signaling in the complex interaction between HBV and HCV using cell lines, mouse models, and samples from people with coinfection. Notably, HCV enhanced interferon signaling, as measured by interferon-stimulated gene (ISG) expression, and decreased HBV transcription and replication. Blockade of interferon signaling reversed the effects on HBV replication. Further, pharmacologic inhibition of HCV replication in vitro and in coinfected humanized mice also reduced interferon signaling and, correspondingly, increased HBV replication. Intriguingly, baseline serum levels of the ISG CXCL10 predicted HBV reactivation in a cohort of coinfected people taking DAAs. Determining how interferon signaling silences HBV transcription and whether serum CXCL10 predicts HBV reactivation in a clinical setting are questions that warrant further investigation.
ENDOSCOPIC ULTRASOUND-GUIDED RADIOFREQUENCY ABLATION OF PANCREATIC METASTASIS FROM RENAL CELL CANCER: FEASIBILITY AND SAFETY
Authors: D Biasutto, S Stigliano, F Covotta, FMD Matteo
Journal: Endoscopy (2020)

Aims Renal cell carcinoma (RCC) is the most common renal cancer in adults. Up to 50% of patients will develop metastases after nephrectomy with a 5-year survival rate of 10%-15%. Pancreas is an elective site for RCC metastases. Surgery is the first choice treatment for pancreatic metastases. For not-resectable pancreatic metastases therapeutical options are limited. Radiofrequency ablation (RFA) has been successfully performed for the treatment of several not-resectable solid tumours. Previous studies have demonstrated the feasibility and safety of endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) for the treatment of pancreatic lesions. However, there are no data regarding its use in the treatment of pancreatic metastases from RCC.
Sociodemographic Factors Associated With High Risk for Firearm Suicide Among US Adults
Authors: Mark Olfson, Candace M. Cosgrove, Melanie M. Wall, Carlos Blanco
Journal: JAMA Internal Medicine (2020)

insurers should consider improving coverage for all type 1 diabetes-related services, following the approach of a 2019 rule allowing qualified high-deductible health plans to cover services such as insulin and glucometers before deductibles are met. 5his study has limitations.We did not study patients covered by Medicare or Medicaid or those without insurance.The database included patients who received insurance from medium to large firms, 3 which typically offer plans with lower deductibles compared with plans offered by small firms. 6onsequently, findings may underestimate out-of-pocket spending for patients with type 1 diabetes who receive insurance from small firms.
ULCER WITH ADHERENT CLOT: TAKE OFF OR RESPECT?
Authors: R Benjira, H Abid, S Hassoune, S Zoukal, M Lahlali, AL Sejai, N Lahmidani, M Elyousfi, M Elabkari, SA Ibrahimi, DA Benajah
Journal: Endoscopy (2020)

Aims For the adherent clot ulcers (IIb), the endoscopist has the choice between the detachment or the resepect of the clot .The aim of this work is to compare the two therapeutic attitudes while insisting on the recurrence and mortality.
ENDOSCOPIC THERAPY OF AN AFFERENT LOOP SYNDROM WITH CHOLANGITIS IN A PATIENT WITH PANCREATIC CANCER
Authors: F Straulino, N Tscherwinski, A Genthner, A Eickhoff
Journal: Endoscopy (2020)

Aims The afferent loop syndrom is a rare complication after roux-en-y gastric bypass (RYGB). Although surgical therapy is the standard, many patients are not suitable for surgery due to poor medical conditions. In those patients interventional endoscopy should be considered. We report the case of an endoscopic gastrojejunostomy in a patient with afferent loop syndrom and cholangitis.
Whole exome mutation landscape of 70 commonly used colorectal cancer cell lines
Authors: O Sieber, D Mouradov, C Sloggett, R Jorissen, C Love, S Li, A Burgess, D Arango, R Strausberg, D Buchanan, S Wormald, L O'Connor, J Wilding, D Bicknell, I Tomlinson, W Bodmer, J Mariadason
Journal: Cancer Research (2014)
QUALITY OF COLONOSCOPY «QUACOL». THE RESULTS OF THE PROSPECTIVE MULTICENTRE STUDY «QUACOL 2» COMPARED WITH RESULTS OF THE «QUACOL 1» STUDY IN RUSSIA
Authors: S Kashin, E Nikonov, N Nekhaykova, V Veselov, A Veselov, Z Galkova, D Lileev, M Korolev, Y Starkov, A Repici, C Hassan
Journal: Endoscopy (2020)

Aims In Russia, colorectal cancer (CRC) represents the second most common cancer in women, the third in men. The long-term efficacy of colonoscopy in preventing Colorectal Cancer is strictly related with the risk of interval cancer, which in turn is associated with colonoscopy quality indicators: Adenoma Detection Rate (ADR), Ceacal Intubation Rate (CIR), Colonoscopy Withdrawal Time (CWT), Bowel preparation. The aims of our «QuaCol 2» study were to assess quality of colonoscopy in Russia after performing educational project «QuaCol» and to compare the results of «QuaCol 2» and «QuaCol 1» studies.
Pulmonary rehabilitation at a time of social distancing: prime time for tele-rehabilitation?
Authors: Linzy Houchen-Wolloff, Michael C Steiner
Journal: Thorax (2020)

The global COVID-19 pandemic and the concomitant social distancing measures taken in many countries to suppress transmission of the virus has had an immediate and profound effect on the provision of pulmonary rehabilitation (PR) services. Conventional PR programmes organised around groups of people attending a rehabilitation centre have been suspended in most affected countries to ensure vulnerable people are effectively shielded from the virus. However, the need for PR has not gone away and consideration is under way about how best to provide effective therapy in the context of the current crisis.1 2 The issue of enhancing access to effective PR is not a new one. The overwhelming evidence for the effectiveness of the intervention (reducing disability, improving quality of life3 and potentially offering a survival advantage for those who complete the programme4) has been tempered by well-documented problems across many healthcare systems in ensuring PR is accessible for all who need it.5 It is this problem that has taken centre stage in the field in recent years, and the need for innovation in the delivery of PR is a clear and urgent challenge in the context of the current pandemic.

Helpfully, in the linked article, Hansen and colleagues report the results of a randomised controlled trial comparing home-based tele-rehabilitation with conventional centre-based PR in a population with severe COPD.6 Participants in the experimental arm of the study were provided with a touchscreen video-conferencing device together with basic home exercise equipment (dumbbells and a one-step …
PROGNOSIS AND CLINICAL CHARACTERISTICS OF PANCREATIC CANCER PATIENTS DIAGNOSED WITH ENDOSCOPIC ULTRASOUND BUT INDETERMINATE ON CT: A MULTI-CENTER RETROSPECTIVE COHORT STUDY
Authors: Tae Jun Song, SW Ko, JH Yoon, CM Cho, JH Cho, JH Choi, DW Lee, SH Lee, SB Yoon, SH Kim, TH Lee, TH Kim
Journal: Endoscopy (2020)

Aims Endoscopic ultrasound (EUS) has a high resolution and has shown its superiority to CT in the diagnosis of small pancreatic cancer. As a result, the role of EUS in the early detection of pancreatic cancer is attracting attention. The purpose of this study was to identify clinical and radiological characteristics of pancreatic cancer patients diagnosed with EUS but not found on CT.
In older adults with acute ischemic stroke, the Clinical Frailty Scale predicted mortality at 28 days
Authors: Calvin Hirsch
Journal: Annals of Internal Medicine (2020)

ACP Journal Club19 May 2020In older adults with acute ischemic stroke, the Clinical Frailty Scale predicted mortality at 28 daysCalvin Hirsch, MDCalvin Hirsch, MDUC Davis Medical Center, Sacramento, California, USA (C.H.)Author, Article, and Disclosure Informationhttps://doi.org/10.7326/ACPJ202005190-057 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationEvans NR, Wall J, To B, et al. Clinical frailty independently predicts early mortality after ischaemic stroke. Age Ageing. 2020. [Epub ahead of print]. https://pubmed.ncbi.nlm.nih.gov/31951248Clinical Impact RatingsHospitalists: Geriatrics: References1 Rockwood K, Song X, MacKnight C, et al. A global clinical measure of fitness and frailty in elderly people. CMAJ. 2005;173;489-95. [PMID: 16129869] Google Scholar2 Fried LP, Tangen CM, Walston J, et al. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci. 2001;56;M146-56. [PMID: 11253156] Google Scholar3 Winovich DT, Longstreth WT Jr, Arnold AM, et al. Factors associated with ischemic stroke survival and recovery in older adults. Stroke. 2017;48;1818-26. [PMID: 28526765] Google Scholar4 Wallis SJ, Wall J, Biram RW, Romero-Ortuno R. Association of the clinical frailty scale with hospital outcomes. QJM. 2015;108;943-9. [PMID: 25778109] Google Scholar Author, Article, and Disclosure InformationAffiliations: UC Davis Medical Center, Sacramento, California, USA (C.H.)Disclosures: The commentator has disclosed no conflicts of interest. The form can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M19-3042.This article was published at Annals.org on -13 May 2020. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byFrailty and outcomes in lacunar stroke 19 May 2020Volume 172, Issue 10Page: JC57KeywordsElderlyFrailtyIschemic strokeLength of stayMedical risk factorsMortalityMyocardial infarctionPhenotypesRisk managementStroke ePublished: 1 May 2020 Issue Published: 19 May 2020 Copyright & PermissionsCopyright © 2020 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
PROGRESSION OF CYSTIC PANCREATIC NEOPLASMS - A UNI-CENTER COHORT STUDY OVER 6 YEARS
Authors: M Kaess, D Amissah, Wo Schorr, J Schedel, O Pech
Journal: Endoscopy (2020)

Aims The purpose of this study was to evaluate the malignant potential of pancreatic cystic lesions and the precision of endosonographic diagnoses including the early detection of cysts with malignant potential.
APPEAL‐1: A multiple‐country European survey assessing the psychosocial impact of peanut allergy
Authors: Audrey DunnGalvin, Katharina Blumchen, Frans Timmermans, Lynne Regent, Sabine Schnadt, Marcia Podestà, Angel Sánchez, Pascale Couratier, Mary Feeney, Betina Hjorth, Ram Patel, Tessa Lush, Robert Ryan, Andrea Vereda, Montserrat Fernández‐Rivas, Helen R. Fisher
Journal: Allergy (2020)

Abstract Background Peanut allergy (PA) is a common, potentially life‐threatening and typically lifelong condition with a significant burden of illness. However, information is lacking on how persons with PA (PwPA) and their caregivers perceive the psychosocial impact of living with PA. The Allergy to Peanuts imPacting Emotions And Life 1 (APPEAL‐1) survey, conducted across Europe, investigated the experience and impact of living with PA. Here, we report data evaluating the psychosocial impact of PA on PwPA and their caregivers. Methods Allergy to Peanuts imPacting Emotions And Life study 1 was an online survey conducted in eight European countries. Representatives of eight patient advocacy groups and five healthcare‐research specialists developed the survey. Eligible respondent groups included the following: adults diagnosed with PA (self‐report); parent/nonparent caregivers (proxy‐report for a child with PA); and parent/nonparent caregivers (self‐report of PA impact on themselves). Results Of 1846 total study respondents, 419 were adults with PA (self‐report); 546 were parents/caregivers (proxy‐report); and 881 were parents/caregivers (self‐report). Most respondents reported lifestyle restrictions regarding food (84%‐93%) and additional domains including parties and socializing, holiday activities and destinations, and taking public transport (53%‐89%). Approximately 40% rated themselves as “very” frustrated and “very” stressed. Two‐thirds (65%) felt socially isolated; 43% were bullied. Less than half felt confident in knowing when to use an adrenaline autoinjector. Several intercountry differences were observed such as high levels of uncertainty and stress in respondents from Ireland, highest rates of anxiety in respondents from Germany, and social exclusion and isolation most common in respondents from France. Conclusions Peanut allergy imposes an adverse psychosocial impact on patients and caregivers, leading to frustration, stress and isolation. Attention to the impact of PA is needed in research and clinical practice to improve PA healthcare and public education programmes.
Modeling Controlled Cortical Impact Injury in 3D Brain‐Like Tissue Cultures
Authors: Volha Liaudanskaya, Joon Yong Chung, Craig Mizzoni, Nicolas Rouleau, Alexander N. Berk, Limin Wu, Julia A. Turner, Irene Georgakoudi, Michael J. Whalen, Thomas J. F. Nieland, David L. Kaplan
Journal: Advanced Healthcare Materials (2020)

Abstract Traumatic brain injury (TBI) survivors suffer long term from mental illness, neurodegeneration, and neuroinflammation. Studies of 3D tissue models have provided new insights into the pathobiology of many brain diseases. Here, a 3D in vitro contusion model is developed consisting of mouse cortical neurons grown on a silk scaffold embedded in collagen and used outcomes from an in vivo model for benchmarking. Molecular, cellular, and network events are characterized in response to controlled cortical impact (CCI). In this model, CCI induces degradation of neural network structure and function and release of glutamate, which are associated with the expression of programmed necrosis marker phosphorylated Mixed Lineage Kinase Domain Like Pseudokinase (pMLKL). Neurodegeneration is observed first in the directly impacted area and it subsequently spreads over time in 3D space. CCI reduces phosphorylated protein kinase B (pAKT) and Glycogen synthase kinase 3 beta (GSK3 β ) in neurons in vitro and in vivo, but discordant responses are observed in phosphprylated ribosomal S6 kinase (pS6) and phosphorylated Tau (pTau) expression. In summary, the 3D brain‐like culture system mimicked many aspects of in vivo responses to CCI, providing evidence that the model can be used to study the molecular, cellular, and functional sequelae of TBI, opening up new possibilities for discovery of therapeutics.
ENDOSCOPIC ULTRASONOGRAPHY GUIDED FINE-NEEDLE ASPIRATION FOR DISTAL COMMON BILE DUCT TUMORS AND STRICTURES: MORE EFFECTIVE THAN ERCP AND BRUSH CYTOLOGY
Authors: P Desai, M Kabrawala, C Patel, P Kalra, N Patel, R Prajapati
Journal: Endoscopy (2020)

Aims We aimed to determine the diagnostic yield of EUS and EUS guided fine-needle aspiration for distal CBD lesions causing obstructive jaundice as diagnostic yields with ERCP and brush cytology is not optimal.
ERCP TREATMENT OF BILIARY COMPLICATIONS AFTER LIVER TRANSPLANTATION IN MEXICO
Authors: A Diaz-Coppe, R Soto-Solis, LA Waller-Gonzalez
Journal: Endoscopy (2020)

Aims Evaluate and compare the effectiveness, safety and long-term outcomes of endoscopic treatment of biliary complications after liver transplant at a National referral center in Mexico.
DEEP SUBMUCOSAL BIOPSY ASSISTED BY ENDOSCOPIC SUBMUCOSAL DISSECTION FOR THE DIAGNOSIS OF AN INFILTRATIVE GASTRIC CANCER: A CASE-REPORT
Authors: JS Garcia, D de Frutos Rosa, BA Castillo, MGH Ruiz, AH de Tejada Echanojauregui
Journal: Endoscopy (2020)

A 57-year-old woman was admitted because of vomits and weight loss. Gastroscopy revealed thickened gastric folds and poor distension on insufflation. CT-scan and EUS showed no additional abnormalities. Two repeat sets of biopsies, sampling by unroofing technique and EUS-FNA were inconclusive.
Thrombotic occlusive vasculopathy in a skin biopsy from a livedoid lesion of a patient with <scp>COVID</scp> ‐19
Authors: M. Llamas‐Velasco, P. Muñoz‐Hernández, J. Lázaro‐González, A. Reolid‐Pérez, B. Abad‐Santamaría, J. Fraga, E. Daudén‐Tello
Journal: British Journal of Dermatology (2020)

Some authors have reported the presence of cutaneous lesions related to new COronaVirus Disease 2019 (CoViD‐19) caused by SARS‐CoV‐2, in up to 20.4% of the cases; however, these lesions are not well characterized either clinically or histopathologically.1 Recently, it has been highlighted the finding of congested and edematous blood vessels in the alveolar septum along with hyaline thrombi, and also in the heart, liver and kidney of autopsies of 3 patients deceased due to severe infection by SARS‐CoV‐2.
A RARE FINDING IN AN ATYPICAL LOCATION: COLORECTAL XANTHOMAS
Authors: P Florez-Diez, V Jimenez-Beltran, N Rodriguez-Ferreiro, M Celada-Sendino, L Carballo-Folgoso, A Gejo-Beneitez, M Fraile-Lopez
Journal: Endoscopy (2020)

Gastrointestinal xanthomas are accumulations of foam cells in the lamina propria, usually found in the gastric mucosa, although they can occur in other sections of the digestive tract.