J Crohns Colitis. 2021 Jan 28;:
Authors: Grim C, Noble R, Uribe G, Khanipov K, Johnson P, Koltun WA, Watts T, Fofanov Y, Yochum GS, Powell DW, Beswick EJ, Pinchuk IV
Abstract
BACKGROUND AND AIMS: Little is known about the presence and function of the tissue resident mesenchymal stem cells (MtSCs) within the gastro-intestinal mucosa in health and Inflammatory Bowel Diseases (IBD). The contribution of MtSCs to the generation of inflammatory fibroblasts during IBD is also poorly understood. We hypothesized that IBD-MtSCs are impaired and contribute to the generation of the pathological myofibroblasts in IBD.
METHODS: In a cohort of clinically and endoscopic active IBD patients and normal controls, we used quantitative RT-PCR and stem cell differentiation assays, as well confocal microscopy to characterize MtSCs.
RESULTS: Expression of the stem cell markers, Oct4 and ALDH1A were increased in the inflamed IBD colonic mucosa and correlated with the increase of mesenchymal lineage marker Grem1 in ulcerative colitis (UC), but not Crohn' disease (CD). Increased proliferation and aberrant differentiation of Oct4 +Grem1 + MtSCs-like cells was observed in UC, but not in CD colonic mucosa. In contrast to normal and UC-derived MtSCs, CD-MtSCs lose their clonogenic and most of their differentiation capacities. Our data also suggests that severe damage to these cells in CD may account for the pathological PD-L1 low phenotype of CD myofibroblasts. In contrast aberrant differentiation of MtSCs appears to be involved in the appearance of pathological partially differentiated PD-L1 high myofibroblasts within the inflammed colonic mucosa in UC.
CONCLUSION: For the first time our data show that the progenitor functions of the MtSCs are differentially impaired in CD versus UC providing a scientific rationale for the use of allogeneic MSC therapy in IBD, and particularly in CD.
PMID: 33506258 [PubMed - as supplied by publisher]
J Clin Microbiol. 2021 Jan 27;:
Authors: Zhang SX, Babady NE, Hanson KE, Harrington AT, Larkin PMK, Leal SM, Luethy PM, Martin IW, Pancholi P, Procop GW, Riedel S, Seyedmousavi S, Sullivan KV, Walsh TJ, Lockhart SR, Fungal Diagnostics Laboratories Consortium (FDLC)
Abstract
Fungal infections are a rising threat to our immunocompromised patient population as well as other non-immunocompromised patients with various medical conditions. However, little progress has been made in the past decade to improve fungal diagnostics. To jointly address this diagnostic challenge, the Fungal Diagnostics Laboratory Consortium (FDLC) was recently created. The FDLC consists of 26 laboratories from the United States and Canada that routinely provide fungal diagnostic services for patient care. A survey of fungal diagnostic capacity among the 26 members of the FDLC was recently completed, identifying the following diagnostic gaps: lack of molecular detection of mucormycosis; lack of an optimal diagnostic algorithm incorporating fungal biomarkers and molecular tools for early and accurate diagnosis of Pneumocystis pneumonia, aspergillosis, candidemia, and endemic mycoses; lack of a standardized molecular approach to identify fungal pathogens directly in formalin-fixed paraffin-embedded tissues; lack of robust databases to enhance mold identification with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry; suboptimal diagnostic approaches for mold blood cultures, tissue culture processing for Mucorales, and fungal respiratory cultures for cystic fibrosis patients; inadequate capacity for fungal point-of-care testing, to detect and identify new, emerging or under-recognized, rare or uncommon fungal pathogens, and performance of antifungal susceptibility testing. In this commentary, the FDLC delineates the most pressing unmet diagnostic needs and provides expert opinion on how to fulfill them. Most importantly, the FDLC provides a robust laboratory network to tackle these diagnostic gaps and ultimately to improve and enhance the clinical laboratory's capability to rapidly and accurately diagnose fungal infections.
PMID: 33504591 [PubMed - as supplied by publisher]
Ann Thorac Surg. 2021 01;111(1):16-23
Authors: Antonoff MB, Mitzman B, Backhus L, Bradbury ST, Chatterjee S, Cooke DT, Crestanello J, Goldstone AB, Kim KM, Nguyen TC, Romano JC, Vaporciyan AA, Varghese TK
PMID: 33137298 [PubMed - indexed for MEDLINE]
J Pediatr. 2020 12;227:274-280.e2
Authors: Jalali A, Rothwell E, Botkin JR, Anderson RA, Butterfield RJ, Nelson RE
Abstract
OBJECTIVE: To evaluate the cost-effectiveness of nusinersen with and without universal newborn screening for infantile-onset spinal muscular atrophy (SMA).
STUDY DESIGN: A Markov model using data from clinical trials with US epidemiologic and cost data was developed. The primary interventions studied were nusinersen treatment in a screening setting, nusinersen treatment in a nonscreening setting, and standard care. Analysis was conducted from a societal perspective.
RESULTS: Compared with no screening and no treatment, the incremental cost-effectiveness ratio (ICER) for nusinersen with screening was $330 558 per event-free life year (LY) saved, whereas the ICER for nusinersen treatment without screening was $508 481 per event-free LY saved. For nusinersen with screening to be cost-effective at a willingness-to-pay (WTP) threshold of $50 000 per event-free LY saved, the price would need to be $23 361 per dose, less than one-fifth its current price of $125 000. Preliminary data from the NURTURE trial indicated an 85.7% improvement in expected LYs saved compared with our base results. In probabilistic sensitivity analysis, nusinersen and screening was a preferred strategy 93% of the time at a $500 000 WTP threshold.
CONCLUSION: Universal newborn screening for SMA provides improved economic value for payers and patients when nusinersen is available.
PMID: 32659229 [PubMed - indexed for MEDLINE]
Ann Thorac Surg. 2021 01;111(1):296-300
Authors: Luc JGY, Archer MA, Arora RC, Bender EM, Blitz A, Cooke DT, Hlci TN, Kidane B, Ouzounian M, Varghese TK, Antonoff MB
Abstract
BACKGROUND: The Thoracic Surgery Social Media Network (TSSMN) is a collaborative effort of leading journals in cardiothoracic surgery to highlight publications via social media. This study aims to evaluate the 1-year results of a prospective randomized social media trial to determine the effect of tweeting on subsequent citations and nontraditional bibliometrics.
METHODS: A total of 112 representative original articles were randomized 1:1 to be tweeted via TSSMN or a control (non-tweeted) group. Measured endpoints included citations at 1 year compared with baseline, as well as article-level metrics (Altmetric score) and Twitter analytics. Independent predictors of citations were identified through univariable and multivariable regression analyses.
RESULTS: When compared with control articles, tweeted articles achieved significantly greater increase in Altmetric scores (Tweeted 9.4 ± 5.8 vs Non-tweeted 1.0 ± 1.8, P < .001), Altmetric score percentiles relative to articles of similar age from each respective journal (Tweeted 76.0 ± 9.1 percentile vs Non-tweeted 13.8 ± 22.7 percentile, P < .001), with greater change in citations at 1 year (Tweeted +3.1 ± 2.4 vs Non-Tweeted +0.7 ± 1.3, P < .001). Multivariable analysis showed that independent predictors of citations were randomization to tweeting (odds ratio [OR] 9.50; 95% confidence interval [CI] 3.30-27.35, P < .001), Altmetric score (OR 1.32; 95% CI 1.15-1.50, P < .001), open-access status (OR 1.56; 95% CI 1.21-1.78, P < .001), and exposure to a larger number of Twitter followers as quantified by impressions (OR 1.30, 95% CI 1.10-1.49, P < .001).
CONCLUSIONS: One-year follow-up of this TSSMN prospective randomized trial importantly demonstrates that tweeting results in significantly more article citations over time, highlighting the durable scholarly impact of social media activity.
PMID: 32504611 [PubMed - indexed for MEDLINE]
