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BackgroundThe cytomegalovirus (CMV) mismatch rate in deceased donor kidney transplant (DDKT) recipients in the US remains above 40%. Since CMV mismatching is common in DDKT recipients, the cumulative effects may be significant in the context of overall patient and graft survival. Our primary objective was to describe the short- and long-term risks associated with high-risk CMV donor positive/recipient negative (D+/R-) mismatching among DDKT recipients with the explicit goal of deriving a mathematical mismatching penalty.MethodsWe conducted a retrospective, secondary analysis of the Scientific Registry of Transplant Recipients (SRTR) database using donor-matched DDKT recipient pairs (N=105,608) transplanted between 2011-2022. All-cause mortality and graft failure hazard ratios were calculated from one year to ten years post-DDKT. All-cause graft failure included death events. Survival curves were calculated using the Kaplan-Meier estimation at 10 years post-DDKT and extrapolated to 20 years to provide the average graft days lost (aGDL) and average patient days lost (aPDL) due to CMV D+/R- serostatus mismatching. We also performed an age-based stratification analysis to compare the relative risk of CMV D+ mismatching by age.ResultsAmong 31,518 CMV D+/R- recipients, at 1 year post-DDKT, the relative risk of death increased by 29% (p

On July 14, 2022, the Organ Procurement and Transplantation Network's (OPTN) Membership and Professional Standards Committee (MPSC) approved bylaws including two new post-transplant performance evaluation metrics, the 90-day (90D) and 1-year conditional on the 90-day (1YC90D) graft survival hazard ratio (HR). These metrics have replaced the previous 1-year (1Y) unconditional, post-transplant graft survival HR and are used to nationally rank and identify programs for MPSC review. The MPSC's policies have major implications for all transplant programs, providers, and patients across the United States. Herein we show two significant limitations with the new evaluation criteria, arbitrary censoring periods and interdependence in the new performance metrics. We have demonstrated a strong and consistent inverse correlation between the new evaluation metrics, thus proving a lack of independence. Moreover, these two evaluation criteria are interdependent even at nominal HRs. Thus, the 90D cohort can be used to accurately predict whether the 1YC90D is above or below a given HR threshold. This could alter practice behaviors and the timing of patient event reporting, which may result in many unintended consequences related to clinical practice. Here we provide the first evidence that this new evaluation system will lead to a significant increase in the number of programs flagged for MPSC review. When this occurs, the cost of operating a transplant program will increase without a clear demonstration of an increased accuracy in identifying problematic programs.

Summary: Background: The estimated long-term survival (EPTS) score is used for kidney allocation. A comparable prognostic tool to accurately quantify EPTS benefit in deceased donor liver transplant (DDLT) candidates is nonexistent. Methods: Using the Scientific Registry of Transplant Recipients (SRTR) database, we developed, calibrated, and validated a nonlinear regression equation to calculate liver-EPTS (L-EPTS) for 5- and 10-year outcomes in adult DDLT recipients. The population was randomly split (70:30) into two discovery (N = 26,372 and N = 46,329) and validation cohorts (N = 11,288 and N = 19,859) for 5- and 10-year post-transplant outcomes, respectively. Discovery cohorts were used for variable selection, Cox proportional hazard regression modeling, and nonlinear curve fitting. Eight clinical variables were selected to construct the L-EPTS formula, and a five-tiered ranking system was created. Findings: Tier thresholds were defined and the L-EPTS model was calibrated (R2 = 0.96 [5-year] and 0.99 [10-year]). Patients’ median survival probabilities in the discovery cohorts for 5- and 10-year outcomes ranged from 27.94% to 89.22% and 16.27% to 87.97%, respectively. The L-EPTS model was validated via calculation of receiver operating characteristic (ROC) curves using validation cohorts. Area under the ROC curve was 82.4% (5-year) and 86.5% (10-year). Interpretation: L-EPTS has high applicability and clinical utility because it uses easily obtained pre-transplant patients characteristics to accurately discriminate between those who are likely to receive a prolonged survival benefit and those who are not. It is important to evaluate medical urgency alongside survival benefit and placement efficiency when considering the allocation of a scarce resource. Funding: There are no funding sources related to this project.

Summary:. Because nearly all the vascularized composite allotransplants performed in the United States have been proposed and carried out as research, the ethical duty to report outcomes pertains. This duty is set forth in several international statements, including the World Health Organization’s Statement on Public Disclosure of Clinical Trial Results, the 2013 Helsinki Declaration, and the Singapore Statement on Research Integrity. These international statements call for the reporting of negative and inconclusive outcomes as well as positive outcomes, and for the reporting of results from previously unreported past research. In 2014, the Organ Procurement and Transplant Network vascularized composite allotransplant committee proposed mandatory data collection and submission requirements for transplants, but only for those which took place in September 2015 or later. Reporting of data for the allotransplants which took place before September 2015 was regarded as optional, even though the pre-September 2015 transplants represent the majority of vascularized composite allotransplants in the United States and all the long-term outcome data. We encourage the American Society of Reconstructive Transplantation and the Organ Procurement and Transplant Network committee to embrace the international ethical standards and to hold all vascularized composite allotransplant programs in the United States accountable for reporting data on outcomes of pre-September 2015 transplants.

Background: The One Health (OH) concept, formerly referred to as ‘One Medicine’ in the later part of the 20th century, has gained exceptional popularity in the early 21st century, and numerous academic and non-academic institutions have developed One Health programs. Objectives: To summarize One Health training, research, and outreach activities originating in North America. Methods: We used data from extensive electronic records maintained by the One Health Commission (OHC) (www.onehealthcommission.org/) and the One Health Initiative (www.onehealthinitiative.com/) and from web-based searches, combined with the corporate knowledge of the authors and their professional contacts. Finally, a call was released to members of the OHC's Global One Health Community listserv, asking that they populate a Google document with information on One Health training, research, and outreach activities in North American academic and non-academic institutions. Results: A current snapshot of North American One Health training, research, and outreach activities as of August 2016 has evolved. Conclusions: It is clear that the One Health concept has gained considerable recognition during the first decade of the 21st century, with numerous current training and research activities carried out among North American academic, non-academic, government, corporate, and non-profit entities.

BackgroundSignificant heterogeneity exists in practice patterns and algorithms used for cardiac screening before kidney transplant. Cardiorespiratory fitness, as measured by peak oxygen uptake (VO2peak), is an established validated predictor of future cardiovascular morbidity and mortality in both healthy and diseased populations. The literature supports its use among asymptomatic patients in abrogating the need for further cardiac testing. Methods and ResultsWe outlined a pre–renal transplant screening algorithm to incorporate VO2peak testing among a population of asymptomatic high‐risk patients (with diabetes mellitus and/or >50 years of age). Only those with VO2peak 90%) negative predictive value, indicating that VO2peak ≥17 mL/kg per minute is effective to rule out future cardiac events and all‐cause mortality. However, lower VO2peak had low positive predictive value and should not be used as a reliable metric to predict future cardiac events and/or mortality. In addition, a simple mathematical calculation documented a cost savings of ≈$272 600 in the cardiac screening among our study cohort of 637 patients undergoing evaluation for kidney and/or pancreas transplant. ConclusionsWe conclude that incorporating an objective measure of cardiorespiratory fitness with VO2peak is safe and allows for a cost savings in the cardiovascular screening protocol among higher‐risk phenotype (with diabetes mellitus and >50 years of age) being evaluated for kidney transplant.

Solubility of Tumorigenicity 2 (sST2) is a novel biomarker that better stratifies risk of cardiovascular events (CVE) compared to cardiac troponin T(cTnT) in heart failure. We assessed the association of sST2 with the composite outcome of CVE and/or mortality compared to cTnT in kidney transplant candidates.200 kidney transplant candidates between 2010 and 2013 were included. Elevated sST2 was defined as ≥30ng/ml, cTnT≥0.01 ng/ml.Median age 53 (interquartile range (IQR) 42-61) years, 59.7% male and 82.0% white. 33.5% had history of CVE, 42.5% left ventricular hypertrophy (LVH) and 15.6% positive cardiac stress test. Elevated sST2 correlated with male gender, history of prior-transplants, CVE, positive stress test, LVH, elevated cTnT, anemia, hyperphosphatemia, increased CRP and non-transplanted status. Male gender, history of CVE and LVH were independent determinants of sST2. During 28 months (IQR 25.3-30), 7.5% died, 13.0% developed CVE and 19.0% developed the composite outcome. Elevated sST2 was associated with the composite outcome (hazard ratio = 1.76, CI 1.06-2.73, p = 0.029) on univariate analysis but not after adjusting for age, diabetes and cTnT (p = 0.068). sST2 did not change the risk prediction model for composite outcome after including age, diabetes, prior history of CVE and elevated cTnT.Increased sST2 level is significantly associated with variables associated with CVE in kidney transplant candidates. sST2 was associated with increased risk of the composite outcome of CVE and/or death but not independent of cTnT. Larger studies are needed to confirm these findings and determine whether sST2 has added value in CV risk stratification in this cohort of patients.

The expression One Health refers to the unified human and veterinary approach to zoonoses, an approach that used to be identified with Medicine throughout the 20th Century. Zoonotic tuberculosis (TB), a disease due to bacteria of the Mycobacterium tuberculosis complex, is a recognized global public veterinary health problem. The significance of the health and economic threats posed by zoonotic TB has been recognized by several global health agencies, which have called for control and eradication programs for zoonotic TB. The interplay between humans, livestock, wildlife, and ecology in the epidemiology of zoonotic TB make arduous the control of the disease, as such zoonotic TB is the ideal target for the application of the One Health approach. This article argues that a successful One Health response to TB will consider the effects of disease on socio-economic well-being, and allow for addressing the social, cultural and economic conditions that facilitate spread and maintenance of this disease. The One Health approach will also enable the development of disease control programs involving both animal and human populations, fostering the participation of various stakeholders. One Health approach will also allow for expanding scientific knowledge, improve medical education and clinical care, and develop effective disease control programs for both human and animal populations.

INTRODUCTION:Decreased insulin sensitivity blunts the normal increase in gene expression from skeletal muscle after exercise. In addition, chronic inflammation decreases insulin sensitivity. Chronic kidney disease (CKD) is an inflammatory state. How CKD and, subsequently, kidney transplantation affects skeletal muscle gene expression after exercise are unknown. METHODS:Study cohort: non-diabetic male/female 4/1, age 52±2 years, with end-stage CKD who underwent successful kidney transplantation. The following were measured both pre-transplant and post-transplant and compared to normals: Inflammatory markers, euglycemic insulin clamp studies determine insulin sensitivity, and skeletal muscle biopsies performed before and within 30 minutes after an acute exercise protocol. Microarray analyses were performed on the skeletal muscle using the 4x44K Whole Human Genome Microarrays. Since nuclear factor of activated T cells (NFAT) plays an important role in T cell activation and calcineurin inhibitors are mainstay immunosuppression, calcineurin/NFAT pathway gene expression was compared at rest and after exercise. Log transformation was performed to prevent skewing of data and regression analyses comparing measures pre- and post-transplant performed. RESULT:Markers of inflammation significantly improved post-transplantation. Insulin infusion raised glucose disposal slightly lower post-transplant compared to pre-transplant, but not significantly, thus concluding differences in insulin sensitivity were similar. The overall pattern of gene expression in response to exercise was reduced both pre-and post-transplant compared to healthy volunteers. Although significant changes were observed among NFAT/Calcineurin gene at rest and after exercise in normal cohort, there were no significant differences comparing NFAT/calcineurin pathway gene expression pre- and post-transplant. CONCLUSIONS:Despite an improvement in serum inflammatory markers, no significant differences in glucose disposal were observed post-transplant. The reduced skeletal muscle gene expression, including NFAT/calcineurin gene expression, in response to a single bout of exercise was not improved post-transplant. This study suggests that the improvements in inflammatory mediators post-transplant are unrelated to changes of NFAT/calcineurin gene expression.

The transformation and implementation of the One Health concept into a broad-spectrum institutional approach for health, health care and environmental health for humans and animals in society will require a paradigm shift. This represents a worldwide strategic scientific revolution vis-à-vis the status quo of traditional science-based activities of past and current medical and health endeavours that are frequently limited to provincial ‘turf’-domains. It means expanding interdisciplinary collaborations and communications into an all inclusive utilisation of co-equal participation among physicians, veterinarians and a host of other health scientist professionals. The resulting synergism will ‘advance health care for the 21st century and beyond by accelerating biomedical research discoveries, enhancing public health efficacy, expeditiously expanding the scientific knowledge base, and improving medical education and clinical care’. Untold millions of lives will be protected and saved in this generation and in those of the future.

An eclectic collection of papers by physicians, veterinarians and other allied health medical scientists on the ‘One Medicine - One Health’ concept has been assembled in this monograph. The contributions include thirteen individual ‘One Health’ papers by fifty-three participants from twelve countries. The authors joined to confront various global health threats. In addition to the participating countries, individuals from twenty-six other nations have united as supporters of the ‘One Health initiative’. Biomedical research, scientific knowledge, environmental health, public health, individual health and clinical health care will all be enhanced by implementing the ‘One Medicine - One Health’ concept which promotes co-equal, cross-disciplinary communication and collaboration. The scientific coalition that evolves through this collaborative effort will significantly enhance human and animal health for future generations.

This series of short articles was published in 2007 and distributed to the Kahn-Kaplan-Monath ‘One Health’ email distribution list. The articles are further examples of historical achievements obtained across numerous scientific disciplines, including human and veterinary medicine. Each article was written and developed with assistance from the Kahn-Kaplan-Monath ‘One Health’ team.The expanding ‘One Health’ email distribution list now totals approximately 590 individuals in 38 countries including Argentina, Australia, Bangladesh, Bahrain, Belgium, Belize, Bosnia and Herzegovina, Brazil, Canada, China, Colombia, Costa Rica, Croatia, France, Germany, Grenada, India, Indonesia, Israel, Japan, Malta, The Netherlands, Nepal, New Zealand, Nigeria, Norway, Portugal, Puerto Rico, Senegal, South Africa, Sri Lanka, Sweden, Switzerland, Thailand, Turkey, United Kingdom, United States and Uruguay.The list of supporters currently totals 417. If these lists are still being actively maintained by the publication date of this ‘One Medicine -One Health’ monograph, any allied health scientist, physician, osteopath or veterinarian may be added to one and/or both lists by contacting us at bkapdvm@verizon.net. Please include your curriculum vitae or brief biography, title, degree(s), affiliation and address consistent with those currently acknowledged as ‘One Health - One Medicine’ supporters. There are no obligations attached to joining this group and you may have your name removed at any time upon request.Those who have prepared this message and the two lists act independently of any other entity or organisation. However, where feasible, we attempt to augment and support those organisations' efforts to recognise, promote and implement this initiative, such as the American Veterinary Medical Association, American Medical Association, Society for Tropical Veterinary Medicine, Croatian Society for Infectious Diseases, American Society of Tropical Medicine and Hygiene, World Association of Veterinary Laboratory Diagnosticians, Delta Society, American Association of Veterinary Laboratory Diagnosticians, American Phytopathological Society, Association of American Veterinary Medical Colleges, Association of Schools of Public Health, American Society for Microbiology, National Association of State Public Health Veterinarians, Council of State and Territorial Epidemiologists, Association of Academic Health Centers, Association of American Medical Colleges and Immuno Valley Consortium in The Netherlands.This autonomous endeavour has been maintained pro bono due to our firm conviction regarding the enormous value of the ‘One Medicine - One Health’ concept.

In essence, the One Health concept represents a visionary paradigm shift for health and health care (for humans and animals) by promoting interdisciplinary communications and by co-equal and respectful collaborations for more expeditious public health (infectious diseases) and comparative biomedical investigations, research and discoveries. This is intended to be all-inclusive among the scientific disciplines of human medicine, veterinary medicine and all other related scientific health disciplines. This reprinted Opinion piece, ‘One Health…or some health?’ highlights a potentially serious disconnect within the One Health movement viz. the trend towards excluding the One Health comparative medicine research and clinical advances resulting from the utilisation of One Health principles. The view that including this critical aspect of One Health endeavours may unduly detract from international public health considerations is short-sighted and deleterious to the promotion of health in its broadest sense.

Antibody-mediated rejection (AMR) is a major cause of late kidney transplant failure. It is important to have an understanding of human-leukocyte antigen (HLA) typing including well-designed studies to determine anti-MHC-class-I-related chain A (MICA) and antibody rejection pathogenesis. This can allow for more specific diagnosis and treatment which may improve long-term graft function. HLA-specific antibody detection prior to transplantation allows one to help determine the risk for AMR while detection of DSA along with a biopsy confirms it. It is now appreciated that biopsy for AMR does not have to include diffuse C4d, but does require a closer look at peritubular capillary microvasculature. Although plasmapheresis (PP) is effective in removing alloantibodies (DSAs) from the circulation, rebound synthesis of alloantibodies can occur. Splenectomy is used in desensitization protocols for ABO incompatible transplants as well as being found to treat AMR refractory to conventional treatment. Also used are agents targeted for plasma cells, B cells, and the complement cascade which are bortezomib rituximab and eculizumab, respectively.

The national program to report hospital-level outcomes for transplantation has been in place since 1991, yet it has not been addressed in the existing literature on hospital report cards. We study the impact of reported outcomes on demand at kidney transplant centers. Using a negative binomial regression with hospital fixed effects, we estimate the number of patients choosing each center as a function of reported outcomes. Parameters are identified by the within-hospital variation in outcomes over five successive report cards. We find some evidence that report cards influence younger and college-educated patients, but, overall, report cards do not affect demand.

Dr Janis H. Audin (MSc Illinois 1975, DVM Illinois 1979), a champion of progressive veterinary medical journalism and ‘One Health’ died on 22 April 2009 following a long, courageous and difficult battle with pancreatic cancer. The world has lost a truly significant One Health leader and advocate. Under her guidance, the Journal of the American Veterinary Medical Association (JAVMA) implemented a ‘one-health wonders’ column that recognised and highlighted prominent One Health individuals among the medical and veterinary medical professions in the United States. The American Veterinary Medical Association (AVMA) has lost a dedicated and gifted editor-in-chief.Dr Audin joined the editorial staff of the AVMA in 1985, as an assistant editor and was promoted to associate editor in 1989 and editor in 1994. She became the editor-in-chief of both the JAVMA and the American Journal of Veterinary Research in 1995. Prior to that, Dr Audin practised as an associate veterinarian in Calumet City, Illinois, for four years.During her tenure, Dr Audin was noted for implementing procedural and technological changes in the journal to reduce costs, improve timeliness of publications and promote readership interest and awareness. New features in the News section introduced under her leadership have made the journals more practical and public health-relevant. For instance, Dr Audin fostered the United States Department of Agriculture’s Food Safety and Inspection Service (USDA-FSIS) ‘Inspection Insights’ - a public health-oriented food safety monthly column related to meat, poultry and egg products - from 1996 through 1998. She also increased international manuscript submissions.On 23 March 2009 AVMA Executive Vice President Dr W. Ron DeHaven named Dr Audin as editor-in-chief emeritus of the Publications Division. Wisely, it also meant that Dr Audin could continue contributing to the staff effort to ensure the high quality of the AVMA scientific journals while the Association began a comprehensive search for her successor.Having observed the JAVMA editors-in-chief for 50 years, I consider her one of the best, if not the best of a most distinguished list. Janis was a special personal friend and my soul mate with respect to dealing with life-threatening cancer. I deeply mourn her loss and will miss her.Dr Bruce Kaplan is gratefully acknowledged for authorising the reproduction of this text which was first published on the One Health Initiative website (www.onehealthinitiative.com) on Thursday, 23 April 2009Please also see the AVMA and JAVMA News articles at www.avma.org/aa/audin_janis_090423.asp and www.avma.org/onlnews/javma/may09/090515ff.asp

It is with tremendous sadness that we report the passing, on 6 November 2008, of Ronald M. Davis, MD, past President of the American Medical Association (AMA) and a major supporter of the One Health Initiative. Indeed, the AMA wouldn't have passed its historic One Health Resolution without Ron's leadership. As the first preventive medicine physician to be president of the AMA, he recognised the need for collaboration between veterinarians and physicians. As he said, ‘I was primed for the issue of One Health’.Roger Mahr, who was President of the AVMA at the same time, contacted Ron to discuss bringing animal and human medicine together. They met and had dinner together. After Roger educated Ron about the issues, Ron told him that he would be happy to help. Ron not only advocated One Health principles within AMA, but he personally represented AMA on the AVMA One Health Initiative Task Force and contributed materially to the development of the Task Force recommendations (www.avma.org/onehealth/).This was a case where the right people were in the right place at the right time. In our subsequent One Health collaborations regarding drafting the AMA One Health Resolution and other related issues, Ron always graciously and expeditiously supported and guided our efforts with much wisdom.Tragically, not long after the AMA passed the One Health Resolution in June 2007, Ron was diagnosed with stage 4 pancreatic cancer.He fought the disease with grace and dignity. The New York Times reported on his battle. (www.nytimes.com/2008/09/23/health/23voic.html?partner=rssnyt&emc=rss).On 14 June 2008, at the AMA Annual Meeting of the House of Delegates, Ron gave a very moving speech entitled Legacies in the circle of life. The transcript can be read at www.ama-assn.org/ama/no-index/news-events/18670.shtml and the video can be watched at www.webguild.com/TeamRon/.The world has lost a great man and we have lost an esteemed colleague, friend, and One Health champion.This tribute was written by Laura Kahn, Bruce Kaplan and Tom Monath and was published on the ‘One Health Initiative’ website (www.onehealthinitiative.com) on 8 November 2008.