tbuckley/cabot-search huggingface dataset:
SAT0305 PERFORMANCE OF HIGH FREQUENCY ULTRASOUND IN THE ASSESSMENT OF SKIN INVOLVEMENT IN SYSTEMIC SCLEROSIS
Authors: G. Lettieri, V. Picerno, D. Temiz Karadağ, M. C. Padula, G. A. Mennillo, A. Padula, S. D’angelo, G. Abignano
Journal: Annals of the Rheumatic Diseases (2020)

Background: The modified Rodnan skin score (mRSS) is the current gold standard for skin assessment in systemic sclerosis (SSc) both in clinical trials and practice. High frequency ultrasound (HFUS) has been suggested to offer a quantitative assessment of skin thickness in SSc by several studies, however results are inhomogeneous with regards to the machine used, number of imaged sites, as well as the various stages of skin involvement. Objectives: Aim of this cross-sectional study was to compare performance of HFUS in the assessment of skin involvement in diffuse cutaneous SSc (dcSSc) patients, at different disease stages, as compared with healthy controls (HC). Methods: Dorsal finger, hand, forearm and upper arm skin of consecutive dcSSc patients, at different disease stages, and of matched-HC were scanned bilaterally using HFUS. Two investigators, expert in MSK ultrasound, blinded to the clinical details, measured skin thickness using Esaote MyLab70 equipped with a 22 MHZ probe. Clinical involvement was assessed by a blinded operator using the mRSS and results were compared with imaging data. Statistical analysis was performed using GraphPad Prism software V.7.0. Results: A total of 704 HFUS images were obtained from 22 dcSSc patients [20 Female, mean age 49 (±11) years, 12 with ≤ 5 years disease duration] and 22 HC [20 Female, mean age 50.7 (±6.7) years]. Skin thickness was significantly higher in SSc patients than in HC at fingers (p&lt;0.0001) and hands (p&lt;0.0001), while no significant difference was found at the forearms and upper arms (p&gt;0.05). HFUS showed a good discriminative ability between SSc and HC skin at fingers and hands (AUC 0.91, 0.81, 0.6 and 0.65 for fingers, hands, forearms and upper arms respectively). When analysing the subgroup of SSc patients with ≤5 years disease duration, HFUS showed a slightly lower performance in discriminating between SSc without clinical skin involvement (site mRSS=0) and HC (AUC 0.68, 0.57, 0.68 for hands, forearms and upper arms respectively). Mean HFUS skin thickness significantly correlated with mRSS at site of analysis (hand: r=0.78, p=&lt;0.0001; forearm: r=0.47, p=0.0013; upper arm: r=0.52, p=0.0003) and total mRSS (hand: r=0.53, p=0.0002; forearm: r=0.63, p&lt;0.0001; upper arm: r=0.63, p&lt;0.0001). No significant correlation was found between finger skin thickness and mRSS (both local and total, p&gt;0.05). Interobserver reliability for skin thickness was good to excellent at all sites with intraclass correlation coefficient ranging between 0.79 and 0.94. Conclusion: HFUS of the skin is a reliable measure of skin involvement in SSc. Studies with higher number of patients with different clinical features are needed to explore the potential of HFUS to discriminate between healthy and SSc skin, including sites at a preclinical stage of involvement. Disclosure of Interests: None declared
Amyotrophic lateral sclerosis and intestinal microbiota—toward establishing cause and effect
Authors: Marc Gotkine, Denise Kviatcovsky, Eran Elinav
Journal: Gut Microbes (2020)

The intestinal microbiota may be involved, through metabolic gut–brain interactions, in a variety of neurological conditions. In this addendum, we summarize the findings of our recent study investigating the potentially modulatory influence of the microbiome in a transgenic ALS mouse model, and the possible application to human disease. We found that transgenic mice show evidence of dysbiosis, even at the pre-symptomatic stage, and have a more severe disease course under germ-free conditions or after receiving broad-spectrum antibiotics. We demonstrated that Akkermansia muciniphila ameliorated the disease in mice and that this may be due to the production of nicotinamide. We then conducted a preliminary study in human ALS and identified functionally similar alterations within the metagenome. Furthermore, we found that patients with ALS had lower systemic and CSF levels of nicotinamide, suggesting that the changes observed in the mouse model may be relevant to human disease.
Blood Test Flags Multiple Cancers in Large Study
Authors: Jennifer Abbasi
Journal: JAMA (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Restoration of miR-340 controls pancreatic cancer cell<i>CD47</i>expression to promote macrophage phagocytosis and enhance antitumor immunity
Authors: Qing Xi, Jieyou Zhang, Guangze Yang, Lijuan Zhang, Ying Chen, Chengzhi Wang, Zimu Zhang, Xiangdong Guo, Jingyi Zhao, Zhenyi Xue, Yan Li, Qi Zhang, Yurong Da, Li Liu, Zhi Yao, Rongxin Zhang
Journal: Journal for ImmunoTherapy of Cancer (2020)

Background Immune checkpoint blockade has emerged as a potential cancer immunotherapy. The “don’t eat me” signal CD47 in cancer cells binds signal regulatory protein-α on macrophages and prevents their phagocytosis. The role of miR-340 in pancreatic ductal adenocarcinoma (PDAC), especially in tumor immunity, has not been explored. Here, we examined the clinical and biological relevance of miR-340 and the molecular pathways regulated by miR-340 in PDAC. Methods CD47 and miR-340 expression and the relationship with cancer patient survival were analyzed by bioinformatics. The mechanism of miR-340 action was explored through bioinformatics, luciferase reporter, qRT-PCR and western blot analyses. The effects of miR-340 on cancer cells were analyzed in terms of apoptosis, proliferation, migration and phagocytosis by macrophages. In vivo tumorigenesis was studied in orthotopic and subcutaneous models, and immune cells from the peripheral and tumor immune microenvironments were analyzed by flow cytometry. Depletion of macrophages was used to verify the role of macrophages in impacting the function of miR-340 in tumor progression. Results miR-340 directly regulates and inversely correlates with CD47, and it predicts patient survival in PDAC. The restoration of miR-340 expression in pancreatic cancer cells was sufficient to downregulate CD47 and promote phagocytosis of macrophages, further inhibiting tumor growth. The overexpression of miR-340 promoted macrophages to become M1-like phenotype polarized in peripheral and tumor immune microenvironments and increased T cells, especially CD8 + T cells, contributing to the antitumor effect of miR-340. Conclusions miR-340 is a key regulator of phagocytosis and antitumor immunity, and it could offer a new opportunity for immunotherapy for PDAC.
Famotidine use and quantitative symptom tracking for COVID-19 in non-hospitalised patients: a case series
Authors: Tobias Janowitz, Eva Gablenz, David Pattinson, Timothy C Wang, Joseph Conigliaro, Kevin Tracey, David Tuveson
Journal: Gut (2020)

Treatment options for non-hospitalised patients with coronavirus disease 2019 (COVID-19) to reduce morbidity, mortality and spread of the disease are an urgent global need. The over-the-counter histamine-2 receptor antagonist famotidine is a putative therapy for COVID-19. We quantitively assessed longitudinal changes in patient reported outcome measures in non-hospitalised patients with COVID-19 who self-administered high-dose famotidine orally.Patients were enrolled consecutively after signing written informed consent. Data on demographics, COVID-19 diagnosis, famotidine use, drug-related side effects, temperature measurements, oxygen saturations and symptom scores were obtained using questionnaires and telephone interviews. Based on a National Institute of Health (NIH)-endorsed Protocol to research Patient Experience of COVID-19, we collected longitudinal severity scores of five symptoms (cough, shortness of breath, fatigue, headaches and anosmia) and general unwellness on a four-point ordinal scale modelled on performance status scoring. All data are reported at the patient level. Longitudinal combined normalised symptom scores were statistically compared.Ten consecutive patients with COVID-19 who self-administered high-dose oral famotidine were identified. The most frequently used famotidine regimen was 80 mg three times daily (n=6) for a median of 11 days (range: 5-21 days). Famotidine was well tolerated. All patients reported marked improvements of disease related symptoms after starting famotidine. The combined symptom score improved significantly within 24 hours of starting famotidine and peripheral oxygen saturation (n=2) and device recorded activity (n=1) increased.The results of this case series suggest that high-dose oral famotidine is well tolerated and associated with improved patient-reported outcomes in non-hospitalised patients with COVID-19.
Age-associated B Cells Appear in Patients with Granulomatous Lung Diseases
Authors: Swati Phalke, Katja Aviszus, Kira Rubtsova, Anatoly Rubtsov, Briana Barkes, Linda Powers, Brenda Warner, James L. Crooks, John W. Kappler, Evans R. Fernández-Pérez, Lisa A. Maier, Nabeel Hamzeh, Philippa Marrack
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

Rationale: A subpopulation of B cells (age-associated B cells [ABCs]) is increased in mice and humans with infections or autoimmune diseases. Because depletion of these cells might be valuable in patients with certain lung diseases, the goal was to find out if ABC-like cells were at elevated levels in such patients.Objectives: To measure ABC-like cell percentages in patients with lung granulomatous diseases.Methods: Peripheral blood and BAL cells from patients with sarcoidosis, beryllium sensitivity, or hypersensitivity pneumonitis and healthy subjects were analyzed for the percentage of B cells that were ABC-like, defined by expression of CD11c, low levels of CD21, FcRL 1-5 (Fc receptor-like protein 1-5) expression, and, in some cases, T-bet.Measurements and Main Results: ABC-like cells in blood were at low percentages in healthy subjects and higher percentages in patients with sarcoidosis as well as at high percentages among BAL cells of patients with sarcoidosis, beryllium disease, and hypersensitivity pneumonitis. Treatment of patients with sarcoidosis led to reduced percentages of ABC-like cells in blood.Conclusions: Increased levels of ABC-like cells in patients with sarcoidosis may be useful in diagnosis. The increase in percentage of ABC-like cells in patients with lung granulomatous diseases and decrease in treated patients suggests that depletion of these cells may be valuable.
Geographic Access to Transcatheter Aortic Valve Replacement Centers in the United States
Authors: Guillaume Marquis-Gravel, Amanda Stebbins, Andrzej S. Kosinski, Morgan L. Cox, J. Kevin Harrison, G. Chad Hughes, Vinod H. Thourani, Thomas G. Gleason, Ajay J. Kirtane, John D. Carroll, Michael J. Mack, Sreekanth Vemulapalli
Journal: JAMA Cardiology (2020)

<h3>Importance</h3> Geographic access to transcatheter aortic replacement (TAVR) centers varies in the United States as a result of controlled expansion through minimum volume requirements. <h3>Objective</h3> To describe the current geographic access to TAVR centers in the United States. <h3>Design, Setting, and Participants</h3> Observational study from June 1, 2015, to June 30, 2017. United States census data were used to describe access to TAVR center. Google Maps and the Society of Thoracic Surgeons American College of Cardiology Transcatheter Valve Therapy Registry were used to describe characteristics of patients undergoing successful TAVR according to proximity to implanting center. The study analyzed 47 527 537 individuals 65 years and older in the United States and 31 098 patients who underwent successful transfemoral TAVR, were linked to fee-for-service Medicare, and had a measurable driving time. <h3>Main Outcomes and Measures</h3> Median driving distance to a TAVR center. <h3>Results</h3> Among 40 537 zip codes in the United States, 490 (1.2%) contained a TAVR center, and among 305 hospital referral regions (HRR), 234 (76.7%) contained a TAVR center. Of the 31 749 patients who underwent successful transfemoral TAVR and were linked to fee-for-service Medicare, 31 098 had a measurable driving time. Mean (SD) age was 82.4 (6.9) years, 14 697 patients (47.3%) were women, and 7422 (23.87%) lived in a rural area. This translated to 1 232 568 of 47 527 537 individuals (2.6%) 65 years and older living in a zip code with a TAVR center and 43 789 169 (92.1%) living in an HRR with a TAVR center. Among 31 749 patients who underwent successful transfemoral TAVR and were linked to fee-for-service Medicare, 31 098 had a measurable driving time. All of these patients (100.0%) underwent their procedure in a TAVR center within their HRR, with 1350 (4.3%) undergoing TAVR in a center within their home zip code. Median driving time to implanting TAVR center was 35.0 minutes (IQR, 20.0-70.0 minutes), ranging from 2.0 minutes to 18 hours and 48 minutes. <h3>Conclusions and Relevance</h3> Most US individuals 65 years and older live in an HRR with a TAVR center. Among patients undergoing successful transfemoral TAVR, median driving time to implanting center was 35.0 minutes. Within the context of the US health care system, where certain advanced procedures and specialized care are centralized, TAVR services have significant penetration. More studies are required to evaluate the effect of geographic location of TAVR sites on access to TAVR procedures among individuals with an indication for a TAVR within the US population.
The Janus kinase 1/2 inhibitor ruxolitinib in COVID-19 with severe systemic hyperinflammation
Authors: F. La Rosée, H. C. Bremer, I. Gehrke, A. Kehr, A. Hochhaus, S. Birndt, M. Fellhauer, M. Henkes, B. Kumle, S. G. Russo, P. La Rosée
Journal: Leukemia (2020)

A subgroup of patients with severe COVID-19 suffers from progression to acute respiratory distress syndrome and multiorgan failure. These patients present with progressive hyperinflammation governed by proinflammatory cytokines. An interdisciplinary COVID-19 work flow was established to detect patients with imminent or full blown hyperinflammation. Using a newly developed COVID-19 Inflammation Score (CIS), patients were prospectively stratified for targeted inhibition of cytokine signalling by the Janus Kinase 1/2 inhibitor ruxolitinib (Rux). Patients were treated with efficacy/toxicity guided step up dosing up to 14 days. Retrospective analysis of CIS reduction and clinical outcome was performed. Out of 105 patients treated between March 30th and April 15th, 2020, 14 patients with a CIS ≥ 10 out of 16 points received Rux over a median of 9 days with a median cumulative dose of 135 mg. A total of 12/14 patients achieved significant reduction of CIS by ≥25% on day 7 with sustained clinical improvement in 11/14 patients without short term red flag warnings of Rux-induced toxicity. Rux treatment for COVID-19 in patients with hyperinflammation is shown to be safe with signals of efficacy in this pilot case series for CRS-intervention to prevent or overcome multiorgan failure. A multicenter phase-II clinical trial has been initiated (NCT04338958).
HIV outbreaks among people who inject drugs in Europe, North America, and Israel
Authors: Don C Des Jarlais, Vana Sypsa, Jonathan Feelemyer, Adrian O Abagiu, Vic Arendt, Dita Broz, Daniel Chemtob, Carole Seguin-Devaux, Joan M Duwve, Margaret Fitzgerald, David J Goldberg, Angelos Hatzakis, Raluca E Jipa, Eugene Katchman, Eamon Keenan, Ibrahim Khan, Stephanie Konrad, Andrew McAuley, Stuart Skinner, Lucas Wiessing
Journal: The Lancet HIV (2020)
Functional Genetic Screening Enables Theranostic Molecular Imaging in Cancer
Authors: Nicholas R. Perkons, Omar Johnson, Gabrielle Pilla, Enri Profka, Michael Mercadante, Daniel Ackerman, Terence P.F. Gade
Journal: Clinical Cancer Research (2020)

Targeted therapies for cancer have accelerated the need for functional imaging strategies that inform therapeutic efficacy. This study assesses the potential of functional genetic screening to integrate therapeutic target identification with imaging probe selection through a proof-of-principle characterization of a therapy-probe pair using dynamic nuclear polarization (DNP)-enhanced magnetic resonance spectroscopic imaging (MRSI).CRISPR-negative selection screens from a public dataset were used to identify the relative dependence of 625 cancer cell lines on 18,333 genes. Follow-up screening was performed in hepatocellular carcinoma with a focused CRISPR library targeting imaging-related genes. Hyperpolarized [1-13C]-pyruvate was injected before and after lactate dehydrogenase inhibitor (LDHi) administration in male Wistar rats with autochthonous hepatocellular carcinoma. MRSI evaluated intratumoral pyruvate metabolism, while T2-weighted segmentations quantified tumor growth.Genetic screening data identified differential metabolic vulnerabilities in 17 unique cancer types that could be imaged with existing probes. Among these, hepatocellular carcinoma required lactate dehydrogenase (LDH) for growth more than the 29 other cancer types in this database. LDH inhibition led to a decrease in lactate generation (P < 0.001) and precipitated dose-dependent growth inhibition (P < 0.01 overall, P < 0.05 for dose dependence). Intratumoral alanine production after inhibition predicted the degree of growth reduction (P < 0.001).These findings demonstrate that DNP-MRSI of LDH activity using hyperpolarized [1-13C]-pyruvate is a theranostic strategy for hepatocellular carcinoma, enabling quantification of intratumoral LDHi pharmacodynamics and therapeutic efficacy prediction. This work lays the foundation for a novel theranostic platform wherein functional genetic screening informs imaging probe selection to quantify therapeutic efficacy on a cancer-by-cancer basis.
Oncogenic Herpesvirus Engages Endothelial Transcription Factors SOX18 and PROX1 to Increase Viral Genome Copies and Virus Production
Authors: Silvia Gramolelli, Endrit Elbasani, Krista Tuohinto, Veijo Nurminen, Thomas Günther, Riikka E. Kallinen, Seppo P. Kaijalainen, Raquel Diaz, Adam Grundhoff, Caj Haglund, Joseph M. Ziegelbauer, Teijo Pellinen, Mark Bower, Mathias Francois, Päivi M. Ojala
Journal: Cancer Research (2020)

Abstract Kaposi sarcoma is a tumor caused by Kaposi sarcoma herpesvirus (KSHV) infection and is thought to originate from lymphatic endothelial cells (LEC). While KSHV establishes latency in virtually all susceptible cell types, LECs support spontaneous expression of oncogenic lytic genes, high viral genome copies, and release of infectious virus. It remains unknown the contribution of spontaneous virus production to the expansion of KSHV-infected tumor cells and the cellular factors that render the lymphatic environment unique to KSHV life cycle. We show here that expansion of the infected cell population, observed in LECs, but not in blood endothelial cells, is dependent on the spontaneous virus production from infected LECs. The drivers of lymphatic endothelium development, SOX18 and PROX1, regulated different steps of the KSHV life cycle. SOX18 enhanced the number of intracellular viral genome copies and bound to the viral origins of replication. Genetic depletion or chemical inhibition of SOX18 caused a decrease of KSHV genome copy numbers. PROX1 interacted with ORF50, the viral initiator of lytic replication, and bound to the KSHV genome in the promoter region of ORF50, increasing its transactivation activity and KSHV spontaneous lytic gene expression and infectious virus release. In Kaposi sarcoma tumors, SOX18 and PROX1 expression correlated with latent and lytic KSHV protein expression. These results demonstrate the importance of two key transcriptional drivers of LEC fate in the regulation of the tumorigenic KSHV life cycle. Moreover, they introduce molecular targeting of SOX18 as a potential novel therapeutic avenue in Kaposi sarcoma. Significance: SOX18 and PROX1, central regulators of lymphatic development, are key factors for KSHV genome maintenance and lytic cycle in lymphatic endothelial cells, supporting Kaposi sarcoma tumorigenesis and representing attractive therapeutic targets.
Abstract 12863: Rivaroxaban for Extended Thromboprophylaxis After Hospitalization for Medical Illness: Pooled Analysis of Mortality and Major Thromboembolic Events in 16,496 Patients From the MAGELLAN and MARINER Trials
Authors: Gary E Raskob, Alex Spyropoulos, Alexander T Cohen, Theodore Spiro, Wentao Lu, Bennett Levitan, Eun Young Suh, Elliot S Barnathan
Journal: Circulation (2019)

Introduction: Thromboprophylaxis extended after hospital discharge in high- risk medical patients remains controversial due to uncertainty about the benefit for preventing fatal or major thromboemb...