HLA and AB0 Polymorphisms May Influence SARS-CoV-2 Infection and COVID-19 Severity

alexandrossfakianakis shared this article with you from Inoreader HLA and AB0 Polymorphisms May Influence SARS-CoV-2 Infection and COVID-19 Severity Via Transplantation - Published Ahead-of-Print Background: SARS-CoV-2 infection is heterogeneous in clinical presentation and disease evolution. To investigate whether immune response to the virus can be influenced by genetic factors, we compared HLA and AB0 frequencies in organ transplant recipients and waitlisted patients according to presence or absence of SARS-CoV-2 infection. Methods: A retrospective analysis was performed on an Italian cohort composed by transplanted and waitlisted patients in a January 2002-March 2020 time frame. Data from this cohort were merged with the Italian registry of COVID+ subjects, evaluating infection status of transplanted and waitlisted patients. A total of 56304 cases were studied with the aim of comparing HLA and AB0 frequencies according to the presence (n=265, COVID+) or absence (n=56 039, COVID-) of SARS-CoV-2 infection. Results: The cumulative incidence rate of COVID-19 was 0.112% in the Italian population and 0.462% in waitlisted/transplanted patients (OR=4.2, 95%CI [3.7-4.7], P View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Summary of International Recommendations for Donation and Transplantation Programs During the Coronavirus Disease (COVID-19) Pandemic

alexandrossfakianakis shared this article with you from Inoreader Summary of International Recommendations for Donation and Transplantation Programs During the Coronavirus Disease (COVID-19) Pandemic Via Transplantation - Published Ahead-of-Print Background: The COVID-19 pandemic has disrupted all aspects of the international organ donation and transplantation (ODT) system. Multiple organizations have developed guidance, but to date, no comparative summary has emerged to understand differences in existing recommendations. Methods: We developed and applied a comparative methodology to a convenience sample of recommendations available on The Transplantation Society website. Document types were classified according to characteristics such as type of organization (e.g. governing body or professional society) and geographic region. Recommendations were grouped according to content and summaries were posted on a public website. This process is ongoing and will be updated as new recommendations become available. Results: 18 documents were extracted in the initial review. All documents were based on expert opinion, and none described a formal literature review or adherence with clinical guideline development processes. Recommendation categories included screening of potential donors, risk assessment of potential recipients, post-transplant risk, living/paired donation, protection of ODT professionals, and ethics/logistics. While many documents included similar recommendations, such as the need to screen and test patients who are potential donors, there was variation on some topics. Type of recommended laboratory testing varied with 64% recommending nasopharyngeal swabs, 43% oropharyngeal, and 24% bronchial aspirates. Updated results are available at https://cdtrp.ca/en/covid-19-international-recommendations-for-odt/ Conclusion: The current state of COVID-19 ODT recommendations are limited to expert opinion. Substantial variation exists regarding recommendations, which are based on emerging, but currently low-quality evidence. This summary of existing recommendations will serve to inform priorities for evidence-based recommendations. Funding: This work was supported by financial and in-kind contributions from Canadian Blood Services and the Canadian Donation and Transplant Research Program. Disclosure: The authors declare no conflicts of interest. No author has a conflicting interest with a for-profit entity. All authors are either employees or consultants for not-for profit, governmental organ donation organizations or research organizations as listed in the affiliations. Authorship: All authors have reviewed and approve of the final manuscript, which represents original work. All authors participated in the design of the review. MJW, JL, LH, and AH participated in the performance of the research and analysis of the results. MJW and JL prepared the original draft. Corresponding Author: Matthew Weiss, M.D., FRCPC Pediatric Intensivist at the Centre Mère-Enfant Soleil du CHU de Québec Medical Director of Organ Donation at Transplant Québec 3-880 Calixa-Lavallée Québec, Québec, G1S 3G9 Canada Cell: 418-717-6418 Email: matthew-john.weiss@chudequebec.ca Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

COVID-19 Therapeutics for Solid Organ Transplant Recipients; 6 Months Into the Pandemic: Where Are We Now?

alexandrossfakianakis shared this article with you from Inoreader COVID-19 Therapeutics for Solid Organ Transplant Recipients; 6 Months Into the Pandemic: Where Are We Now? Via Transplantation - Published Ahead-of-Print As in the general population with COVID-19 infection, therapeutic interventions in solid organ transplant (SOT) recipients have evolved over time. The preceding 6 months of the pandemic can be divided into 2 main therapeutic eras: the early era and the later era. The first era was characterized by widespread use of drugs such as hydroxychloroquine with or without azithromycin, lopinavir-ritonavir, and tocilizumab. More recently, with the publication of larger trials, there has been increasing use of remdesivir, dexamethasone, and convalescent plasma, with rapid proliferation of clinical trials including a wide variety of investigational and repurposed agents with antiviral or immunomodulatory effects. This overview focuses on what is known about the effects of different therapie s in SOT recipients with COVID-19, mainly from case series and, more recently, larger multicenter registries; as well as outlining the information that will be needed in order to optimize management and outcomes in SOT recipients with COVID-19 in the future. Conflicts of Interest: None Funding: None Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Race, Education, and Gender Disparities in Transplantation of Kidneys from Hepatitis C Viremic Donors

alexandrossfakianakis shared this article with you from Inoreader Race, Education, and Gender Disparities in Transplantation of Kidneys from Hepatitis C Viremic Donors Via Transplantation - Published Ahead-of-Print Background: Transplantation of kidneys from hepatitis C virus (HCV)-viremic donors into HCV-negative patients followed by direct-acting antiviral therapy was an important breakthrough to increase the number of lifesaving kidney transplants. Data suggest these transplants offer several benefits, however it is unknown whether adoption of this practice has been shared equitably, especially among disadvantaged groups. Methods: We evaluated United Network for Organ Sharing data on HCV-seronegative adult deceased-donor kidney transplant (DDKT) recipients from 1/1/2017-6/12/2020. We compared recipients of a kidney from an HCV Ab-/nucleic acid test -(NAT-), HCV Ab+/NAT-, and HCV NAT+ donor. The primary covariates were: 1) race/ethnicity; 2) female sex; and 3) highest level of education. Models included variables associated with being offered an HCV NAT+ kidney. We fit mixed-effects multinomial logistic regression models with center as a random effect to account for patient clustering. Results: Of 48,255 adult kidney-alone DDKT HCV-seronegative recipients, 1,641 (3.4%) donors were HCV NAT+-, increasing from 0.3% (1/2017-6/2017) to 6.9% (1/2020-6/2020). In multivariable models, racial/ethnic minorities, women, and those with less education were significantly less likely to receive a kidney from an HCV NAT+ donor relative to an HCV Ab-/NAT- and HCV Ab+/NAT- donor. The disparities were most pronounced among Hispanic and Asian patients with less educational attainment (grade school, high school, or some college/tech school). Discussion: Despite an increase in transplants from HCV NAT+ donors, we found substantial racial/ethnic disparities in transplantation of these kidneys. These data highlight how the benefits of a scientific breakthrough are often made less available to disadvantaged patients. Disclosure: Dr. Goldberg receives research grant support paid to his institution from Gilead, Abbvie and Merck, and has received consulting fees from Pfizer for topics unrelated to this manuscript. Dr. Sise receives research grant support, paid to her institution, from Gilead, Abbvie and Merck, and has been a scientific advisory board member for Gilead and Abbvie, and has received funding from NIH K23 DK117014. Dr. Reese receives research grant support, paid to his institution, from Abbvie and Merck. Funding: No funding source for this work Corresponding Author: David Goldberg, MD, MSCE Don Soffer Clinical Research Building 1120 NW 14th Street, Office # 807 Miami, FL 33136 USA Tel: 305-243-7956 E-mail: dsgoldberg@med.miami.edu Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Peripheral Vascular Disease and Kidney Transplant Outcomes: Rethinking an Important Ongoing Complication

alexandrossfakianakis shared this article with you from Inoreader Peripheral Vascular Disease and Kidney Transplant Outcomes: Rethinking an Important Ongoing Complication Via Transplantation - Published Ahead-of-Print Peripheral vascular disease (PVD) is highly prevalent in patients on the waiting list for kidney transplantation (KT) and after transplantation and is associated with impaired transplant outcomes. Multiple traditional and non-traditional risk factors, as well as uremia- and transplant-related factors, affect two processes that can coexist, atherosclerosis and arteriosclerosis, leading to PVD. Some pathogenic mechanisms, such as inflammation-related endothelial dysfunction, mineral metabolism disorders, lipid alterations, or diabetic status, may contribute to the development and progression of PVD. Early detection of PVD before and after KT, better understanding of the mechanisms of vascular damage, and application of suitable therapeutic approaches could all minimize the impact of PVD on transplant outcomes. This review focuses on the following issues: a) definition, epidemiological data, diagnosis, risk factors and pathogenic mechanisms in KT candidates and recipients; b) adverse clinical consequences and outcomes; and c) classical and new therapeutic approaches Disclosures: The authors declare no conflicts of interest Funding: This study was supported in part by the Spanish Ministry of Economy and Competitiveness (grant PI17/02043) from the Instituto de Salud Carlos III co-funded by the Fondo Europeo de Desarrollo Regional-FEDER (REDinREN, RD16/0009/0006). Author for correspondence: Domingo Hernández Nephrology Department, Carlos Haya Regional University Hospital Avda. Carlos Haya s/n., E-29010 Málaga, Spain Phone: +34 952907411; Fax: +34 951291557 E-mail:domingohernandez@gmail.com Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Long-term Outcomes After Facial Allotransplantation: Systematic Review of the Literature

alexandrossfakianakis shared this article with you from Inoreader Long-term Outcomes After Facial Allotransplantation: Systematic Review of the Literature Via Transplantation - Published Ahead-of-Print Background: Facial vascularized composite allotransplantation (fVCA) represents a reconstructive approach that enables superior improvements in functional and esthetic restoration compared to conventional craniomaxillofacial reconstruction. Outcome reports of fVCA are usually limited to short-term follow-up or single-center experiences. We merge scientific literature on reported long-term outcome data to better define the risks and benefits of fVCA. Methods: We conducted a systematic review of PubMed/MEDLINE databases in accordance with PRISMA guidelines. English full-text articles providing data on at least 1 unique fVCA patient, with ≥ 3 years follow-up, were included. Results: The search yielded 1812 articles, of which 28 were ultimately included. We retrieved data on 23 fVCA patients with mean follow-up of 5.3 years. More than half of the patients showed improved quality of life, eating, speech, and motor and sensory function following fVCA. On average, the patients had 1 acute cell-mediated rejection and infectious episode per year. The incidence rates of acute rejection and infectious complications were high within first year posttransplant but declined thereafter. Sixty-five percent of the patients developed at least 1 neoplastic and/or metabolic complication after transplantation. Chronic vascular rejection was confirmed in 2 patients, leading to allograft loss after 8 and 9 years. Two patient deaths occurred 3.5 and 10.5 years after transplant due to suicide and lung cancer, respectively. Conclusions: Allograft functionality and improvements in quality of life suggest a positive risk-benefit ratio for fVCA. Recurrent acute rejection episodes, chronic rejection, immunosuppression related complications, and heterogeneity in outcome reporting present ongoing challenges in this field. * Drs Kollar and Pomahac contributed equally to the study as last authors Financial Disclosure: Drs Kauke, Haug and Safi received financial support from the DFG ("Deutsche Forschungsgemeinschaft"). Dr Kollar was the recipient of the Plastic Surgery Foundation Research Fellowship Grant. Dr Pomahac received partial salary support from the U.S. Department of Defense under the award #W911QY-09-C-0216. Opinions, interpretations, conclusions, and recommendations are those of the authors and not of the Department of Defense. Disclaimer: The authors declare no conflicts of interest. Correspondence: Bohdan Pomahac, MD Roberta and Stephen R. Weiner Distinguished Chair in Surgery Director, Plastic Surgery Transplantation Professor of Surgery, Harvard Medical School Brigham and Women's Hospital Department of Surgery, Division of Plastic Surgery 75 Francis Street Boston, MA 02115, USA Telephone: +1-617-732-7796 E-mail: bpomahac@bwh.harvard.edu Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Integrative Analysis of Prognostic Biomarkers for Acute Rejection in Kidney Transplant Recipients

alexandrossfakianakis shared this article with you from Inoreader Integrative Analysis of Prognostic Biomarkers for Acute Rejection in Kidney Transplant Recipients Via Transplantation - Published Ahead-of-Print Background: Non-invasive biomarkers may predict adverse events such as acute rejection after kidney transplantation and may be preferable to existing methods because of superior accuracy and convenience. It is uncertain how these biomarkers, often derived from a single study, perform across different cohorts of recipients. Methods: Using a cross-validation framework that evaluates the performance of biomarkers, the aim of this study was to devise an integrated gene signature set that predicts acute rejection in kidney transplant recipients. Inclusion criteria were publicly available datasets of gene signatures that reported acute rejection episodes after kidney transplantation. We tested the predictive probability for acute rejection using gene signatures within individual datasets and validated the set using other datasets. Eight eligible studies of 1454 participants, with a total of 512 acute rejections episodes were included. Results: All sets of gene signatures had good positive and negative predictive values (79-96%) for acute rejection within their own cohorts, but the predictability reduced to less than 50% when tested in other independent datasets. By integrating signatures sets with high specificity scores across all studies, a set of 150 genes (included CXCL6, CXCL11, OLFM4 and PSG9) which are known to be associated with immune responses, had reasonable predictive values (varied between 69-90%). Conclusions: A set of gene signatures for acute rejection derived from a specific cohort of kidney transplant recipients do not appear to provide adequate prediction in an independent cohort of transplant recipients. However, integration of gene signatures sets with high specificity scores may improve the prediction performance of these markers. # Equal contributions Funding: The authors disclosed receipt of the following financial support for this article. Australian Research Council Discovery Project Grant and Australia NHMRC Career Developmental Fellowship to JY. NHMRC Ideas Grant, Career Development Fellowships, Medical Research Future Fund and Trials and Cohort, and Investigator Grant to GW. Research Training Program Tuition Fee Offset and University of Sydney Postgraduate Award to YC. Disclosure: The authors declare no conflicts of interest. Corresponding Author: Jean Yang School of Mathematics and Statistics, Faculty of Science, Carslaw Building F07, NSW 2006, Australia jean.yang@sydney.edu.au Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Influence of Sex and Age on Ratings of Confidence and Relevance in Continuing Certification Longitudinal Assessment – A Pilot Study

alexandrossfakianakis shared this article with you from Inoreader Influence of Sex and Age on Ratings of Confidence and Relevance in Continuing Certification Longitudinal Assessment – A Pilot Study Via American Journal of Physical Medicine & Rehabilitation - Published Ahead-of-Print Objective Longitudinal assessments use spaced repetition of items to facilitate learning. Algorithms selecting repetition items can prioritize various properties for future presentation. The purpose of this pilot study is to evaluate the relationship between participant ratings of item-specific confidence and/or practice relevance and participant age, sex, and response correctness. Design Prospective quality improvement study of 403 American Board of Physical Medicine and Rehabilitation (ABPMR) diplomates with time-limited certificates. Participants answered 20 items quarterly over four quarters, rating each item on its relevance to their practice and their confidence in their response. Results The relationship between sex and ratings of response confidence was significant, with women less likely than men to be confident in their responses, regardless of correctness. Younger physicians were significantly more confident in their responses and rated items as more practice relevant. Conclusion Women physicians were less confident than men in their item-specific confidence ratings, regardless of correctness, on the ABPMR continuing certification longitudinal knowledge assessment. Older physicians were less confident in their responses than younger physicians. The findings supported the ABPMR prioritization of response correctness and practice relevance, rather than response confidence, to select items for spaced repetition in ABPMR's continuing certification longitudinal assessment. Disclosure: employed by the American Board of Physical Medicine and Rehabilitation Mikaela M. Raddatz, PhD, American Board of Physical Medicine and Rehabilitation, Rochester, Minnesota. Disclosure: employed by the American Board of Physical Medicine and Rehabilitation Lawrence R. Robinson, MD, Division of Physical Medicine and Rehabilitation, University of Toronto, Toronto, Ontario, Canada. Disclosure: no disclosures No funding was received for this study. Corresponding author: Carolyn L. Kinney, MD, American Board of Physical Medicine and Rehabilitation, 3015 Allegro Park Ln SW, Rochester, MN 55902. Phone : 502-282-1776, Extension 1743. Email : ckinney@abpmr.org. Fax: 507-282-9242 Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

How does the measurement of disability in low back pain map unto the International Classification of Functioning, Disability and Health (ICF)? A scoping review of the manual medicine literature

alexandrossfakianakis shared this article with you from Inoreader How does the measurement of disability in low back pain map unto the International Classification of Functioning, Disability and Health (ICF)? A scoping review of the manual medicine literature Via American Journal of Physical Medicine & Rehabilitation - Published Ahead-of-Print The objective of this study was to catalogue items from instruments used to measure functioning, disability, and contextual factors in patients with low back pain (LBP) treated with manual medicine (manipulation and mobilization) according to the International Classification of Functioning, Disability and Health (ICF). This catalogue will be used to inform the development of an ICF-based assessment schedule for LBP patients treated with manual medicine. In this scoping review we systematically searched MEDLINE, Embase, PsycINFO and CINAHL. We identified instruments (questionnaires, clinical tests, single questions) used to measure functioning, disability and contextual factors, extracted the relevant items and then linked these items to the ICF. We included 95 articles and identified 1510 meaningful concepts. All but 70 items were linked to the ICF. Of the concepts linked to the ICF, body functions accounted for 34.7%, body structures accounted for 0%, activities and participation accounted for 41%, environmental factors accounted for 3.6%, and personal factors accounted for 16%. Most items used to measure functioning and disability in LBP patient treated with manual medicine focus on body functions, and activities and participation. The lack of measures that address environmental factors warrants further investigation. Corresponding author: Pierre Côté, UOIT-CMCC Centre for Disability Prevention and Rehabilitation, University of Ontario Institute of Technology, Oshawa, Canada. Pierre.Cote@uoit.ca The project received funding from: The European Centre for Chiropractic Research Excellence (ECCRE), Contract No. 19-2017-NO-EA And ELiB – et liv i bevegelse, Oslo, Norway, Reference No. 234068-2500 Richard Nicol has a financial relationship with ELIB, as a consultant. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Developing a Framework for Designing and Deploying Technology-Assisted Rehabilitation Post Stroke: A Qualitative Study

alexandrossfakianakis shared this article with you from Inoreader Developing a Framework for Designing and Deploying Technology-Assisted Rehabilitation Post Stroke: A Qualitative Study Via American Journal of Physical Medicine & Rehabilitation - Published Ahead-of-Print Objective Many unmet rehabilitation needs of patients with stroke can be addressed effectively using technology. However, technological solutions have not yet been seamlessly incorporated into clinical care. The purpose of this pilot study was to examine how to bridge the gaps between the recovery process, technology, and clinical practice to impact stroke rehabilitation meaningfully. Design Semi-structured interviews using a grounded theory approach with purposive sampling of 17 diverse expert providers in acute care, inpatient, and outpatient stroke rehabilitation settings. Common themes were identified from qualitative analyses of the transcribed conversations to develop a guiding framework from the emerging concepts. Results Four core themes emerged that addressed major barriers in stroke rehabilitation and technology-assisted solutions to overcome these barriers: 1) accessibility to quality rehabilitation, 2) adaptability to patient differences, 3) accountability or compliance with rehabilitation, and 4) engagement with rehabilitation. Conclusion The results suggest a four-pronged framework, the A3E framework which stands for Accessibility, Adaptability, Accountability and Engagement, to comprehensively address existing barriers in providing rehabilitation services. This framework can guide technology developers and clinicians in designing and deploying technology-assisted rehabilitation solutions for post-stroke rehabilitation, particularly using tele-rehabilitation. Corresponding author: Preeti Raghavan, MD, Address: 600 North Wolfe Street, Phipps Bldng. Suite 182, Baltimore, MD 21287. Phone number: 410-955-0703. Email: praghav3@jhmi.edu Acknowledgement of Funding: This work is supported in part by the National Science Foundation grants DRK-12 DRL: 1417769, ITEST DRL: 1614085, and RET Site EEC: 1542286; and NY Space Grant Consortium grant 76156-10488. Conflict(s)-of-Interest/Disclosure(s): All authors have completed the ICMJE uniform disclosure and declare no support from any organization for the submitted work; VK and PR have an issued patent on Game-based Sensorimotor Rehabilitator; PR reports consulting for Mirrored Motion Works, Inc., outside the submitted work. No other relationships or activities appear to have influenced the submitted work. Anna Palumbo is in training. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Circular RNA circTP63 enhances estrogen receptor-positive breast cancer progression and malignant behaviors through the miR-873-3p/FOXM1 axis

alexandrossfakianakis shared this article with you from Inoreader Circular RNA circTP63 enhances estrogen receptor-positive breast cancer progression and malignant behaviors through the miR-873-3p/FOXM1 axis Via Anti-Cancer Drugs - Published Ahead-of-Print Circular RNAs (circRNAs) have been shown to play a functional role in a variety of cancers. However, few studies on circRNAs in estrogen receptor-positive breast cancer have been conducted. Here, we investigated the role of circRNA circTP63 in estrogen receptor-positive breast cancer progression and malignant behaviors. First, we observed increased expression of circTP63 in MCF7 cells relative to normal human mammary epithelial cell lines, such as DU4475 and MCF-10A, and the changed oncogenicity of MCF7 cells correlated with circTP63 overexpression and downregulation. Interestingly, a series of gain- and loss-of-function assays revealed that a higher level of FOXM1 was closely associated with MCF7 malignant behaviors induced by circTP63 overexpression. Further investigations showed that c ircTP63 sponged to miR-873-3p, which targeted FOXM1 mRNA and inhibited its expression. Mechanistically, circTP63 binds to miR-873-3p and prevents the targeting of FOXM1, thus inducing the progression and malignant behaviors of estrogen receptor-positive breast cancer, such as cell proliferation, cell cycle dysregulation, invasion, migration and even tumor growth. CircTP63 might be a potential biomarker or target to treat estrogen receptor-positive breast cancer patients in the future. Received 2 July 2020 Revised form accepted 25 September 2020 Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website, www.anti-cancerdrugs.com. Correspondence to Yue-e Xu, Department of Thyroid and Breast Surgery, The Affiliated Huai'an Hospital of Xuzhou Medical University and The Second People's Hospital of Huai'an, 62 Huaihai Road(S), Huai'an 223002, China, Tel: +86 15195387009; e-mail: yueexu1206@163.com Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.