Comprehensive immune profiling of SARS-CoV-2 infected kidney transplant patients.

Introduction: The immune responses of kidney transplant recipients against SARS-CoV-2 remains under studied.

Methods: In this prospective pilot study, we performed comprehensive immune profiling using cellular, proteomic, and serologic assays on a cohort of 9 kidney transplant recipients and 12 non-transplant individuals diagnosed with COVID-19.

Results: Our data show that in addition to having reduced SARS-CoV-2 specific antibody levels, kidney transplant recipients exhibited significant cellular differences including a decrease in naïve-but increase in effector T cells, a high number of CD28+ CD4 effector memory T cells, and increased CD8 T memory stem cells compared with non-transplant patients.

The John Charnley Award: The Impact of Human Leukocyte Antigen Genotype on Bacterial Infection Rates and Successful Eradication in Total Hip Arthroplasty.

Background: Genetics play an important role in several medical domains; however, the influence of human leukocyte antigen (HLA) genotype on the development of periprosthetic joint infection (PJI) in total hip arthroplasty (THA) remains unknown. The primary aim of this study was to determine if HLA genotype is associated with the development of bacterial PJI in THA. Secondarily, we evaluated the association between HLA genotype and PJI treatment success.

Development and evaluation of a personalised sleep care plan on child and adolescent in-patient mental health wards.

Aims And Method: The study evaluated a package of measures to improve sleep on psychiatric wards admitting patients from children and young people's services (CYPS). Sleep disturbance has significant impact on adolescent mental health, and in-patient wards can directly cause sleep disturbance, independent of the problem that led to admission. We developed a CYPS-specific package (TeenSleepWell) that promoted a better sleep environment, enhanced staff education about sleep, screened for sleep disorders, and raised awareness of benefits and side-effects of hypnotics.

Clinical relevance of HLA-DQ eplet mismatch and maintenance immunosuppression with risk of allosensitization after kidney transplant failure.

The optimal immunosuppression management in patients with a failed kidney transplant remains uncertain. This study analyzed the association of class II HLA eplet mismatches and maintenance immunosuppression with allosensitization after graft failure in a well characterized cohort of 21 patients who failed a first kidney transplant. A clinically meaningful increase in cPRA in this study was defined as the cPRA that resulted in 50% reduction in the compatible donor pool measured from the time of transplant failure until the time of repeat transplantation, death, or end of study.

Viral load kinetics and the clinical consequences of cytomegalovirus in kidney transplantation.

Background: Despite advances in clinical management, cytomegalovirus (CMV) infection remains a serious complication and an important cause of morbidity and mortality following kidney transplantation. Here, we explore the importance of viral load kinetics as predictors of risk and potential guides to therapy to reduce transplant failure in a large longitudinal Genome Canada Transplant Consortium (GCTC) kidney transplant cohort.

Methods: We examined the relationship between CMV infection rates and clinical characteristics, CMV viral load kinetics, and graft and patient outcomes in 2510 sequential kidney transplant recipients in the British Columbia Transplant Program.

NephroCAGE-German-Canadian Consortium on AI for Improved Kidney Transplantation Outcome: Protocol for an Algorithm Development and Validation Study.

Background: Recent advances in hardware and software enabled the use of artificial intelligence (AI) algorithms for analysis of complex data in a wide range of daily-life use cases. We aim to explore the benefits of applying AI to a specific use case in transplant nephrology: risk prediction for severe posttransplant events. For the first time, we combine multinational real-world transplant data, which require specific legal and technical protection measures.

Canadian Kidney Transplant Professionals' Perspectives on Precision Medicine and Molecular Matching in Kidney Allocation.

Background: Antibody-mediated rejection is an important cause of kidney transplant loss. A new strategy requiring application of precision medicine tools in transplantation considers molecular compatibility between donors and recipients and holds the promise of improved immunologic risk, preventing rejection and premature graft loss. The objective of this study was to gather Canadian transplant professionals' perspectives on molecular compatibility in kidney transplantation.

Are patients with primary glomerular disease at increased risk of malignancy?

Over the past decade, several observational studies and case series have provided evidence suggesting a connection between glomerular diseases and the development of malignancies, with an estimated risk ranging from 5 to 11%. These malignancies include solid organ tumours as well as haematologic malignancies such as lymphoma and leukaemia. However, these risk estimates are subject to several sources of bias, including unmeasured confounding from inadequate exploration of risk factors, inclusion of glomerular disease cases that were potentially secondary to an underlying malignancy, misclassification of glomerular disease type and ascertainment bias arising from an increased likelihood of physician encounters compared with the general population.

Validation of next-generation sequencing-based chimerism testing for accurate detection and monitoring of engraftment in hematopoietic stem cell transplantation.

Allogenic hematopoietic stem cell transplantation (allo-HSCT) is a life-saving treatment for various hematological disorders. The success of allo-HSCT depends on the engraftment of donor cells and the elimination of recipient cells monitored through chimerism testing. We aimed to validate a next-generation sequencing (NGS)-based chimerism assay for engraftment monitoring and to emphasize the importance of including the most prevalent cell subsets in proficiency testing (PT) programs.

Novel alleles in the era of next-generation sequencing-based HLA typing calls for standardization and policy.

Next-Generation Sequencing (NGS) has transformed clinical histocompatibility laboratories through its capacity to provide accurate, high-throughput, high-resolution typing of Human Leukocyte Antigen (HLA) genes, which is critical for transplant safety and success. As this technology becomes widely used for clinical genotyping, histocompatibility laboratories now have an increased capability to identify novel HLA alleles that previously would not be detected using traditional genotyping methods. Standard guidelines for the clinical verification and reporting of novelties in the era of NGS are greatly needed.

NOAA Open Data Dissemination: Petabyte-scale Earth system data in the cloud.

NOAA Open Data Dissemination (NODD) makes NOAA environmental data publicly and freely available on Amazon Web Services (AWS), Microsoft Azure (Azure), and Google Cloud Platform (GCP). These data can be accessed by anyone with an internet connection and span key datasets across the Earth system including satellite imagery, radar, weather models and observations, ocean databases, and climate data records. Since its inception, NODD has grown to provide public access to more than 24 PB of NOAA data and can support billions of requests and petabytes of access daily.

Regulatory T Cell Biomarkers Identify Patients at Risk of Developing Acute Cellular Rejection in the First Year Following Heart Transplantation.

Background: Acute cellular rejection (ACR), an alloimmune response involving CD4+ and CD8+ T cells, occurs in up to 20% of patients within the first year following heart transplantation. The balance between a conventional versus regulatory CD4+ T cell alloimmune response is believed to contribute to developing ACR. Therefore, tracking these cells may elucidate whether changes in these cell populations could signal ACR risk.

Adding epitope compatibility to deceased donor kidney allocation criteria: recommendations from a pan-Canadian online public deliberation.

Background: The widening supply-demand imbalance for kidneys necessitates finding ways to reduce rejection and improve transplant outcomes. Human leukocyte antigen (HLA) epitope compatibility between donor and recipient may minimize premature graft loss and prolong survival, but incorporating this strategy to deceased donor allocation criteria prioritizes transplant outcomes over wait times. An online public deliberation was held to identify acceptable trade-offs when implementing epitope compatibility to guide Canadian policymakers and health professionals in deciding how best to allocate kidneys fairly.

Public values and guiding principles for implementing epitope compatibility in kidney transplantation allocation criteria: results from a Canadian online public deliberation.

Background: Epitope compatibility in deceased donor kidney allocation is an emerging area of precision medicine (PM), seeking to improve compatibility between donor kidneys to transplant candidates in the hope of avoiding kidney rejection. Though the potential benefits of using epitope compatibility are promising, the implied modification of deceased organ allocation criteria requires consideration of significant clinical and ethical trade-offs. As a matter of public policy, these trade-offs should consider public values and preferences.

Clinical application of immune repertoire sequencing in solid organ transplant.

Background: Measurement of T cell receptor (TCR) or B cell receptor (BCR) gene utilization may be valuable in monitoring the dynamic changes in donor-reactive clonal populations following transplantation and enabling adjustment in therapy to avoid the consequences of excess immune suppression or to prevent rejection with contingent graft damage and to indicate the development of tolerance.

Objective: We performed a review of current literature to examine research in immune repertoire sequencing in organ transplantation and to assess the feasibility of this technology for clinical application in immune monitoring.

Methods: We searched MEDLINE and PubMed Central for English-language studies published between 2010 and 2021 that examined T cell/B cell repertoire dynamics upon immune activation.

Dissecting the impact of molecular T-cell HLA mismatches in kidney transplant failure: A retrospective cohort study.

Introduction: Kidney transplantation is the optimal treatment in end-stage kidney disease, but donor specific antibody development continues to negatively impact patients undergoing kidney transplantation. One of the recent advances in solid organ transplantation has been the definition of molecular mismatching between donors and recipients' Human Leukocyte Antigens (HLA). While not fully integrated in standard clinical care, cumulative molecular mismatch at the level of eplets (EMM) as well as the PIRCHE-II score have shown promise in predicting transplant outcomes.

Beyond medicines' barriers: exploring the true cost of multiple myeloma.

Aim: The goal of this research was to quantify and qualify all the costs associated with multiple myeloma (MM) from a healthcare and societal perspective and to highlight certain costs that are often underestimated.

Materials And Methods: The study used a mixed methods approach that consisted of three phases: a systemic literature review (SLR), a virtual roundtable discussion based on the results of the SLR, and an online survey.

Results: In total, 4321 records were identified by literature and snowball searches.

Systematic literature review of health economic models developed for multiple myeloma to support future analyses.

Aims: The goal of this study was to review the economic evaluations of health technologies in multiple myeloma (MM) and provide guidance and recommendations for future health economic analyses.

Materials And Methods: A systemic literature review (SLR) was conducted on original economic assessment studies and structured review papers focusing on the studies in MM. The search was limited to English language papers published from 1 January 2000 onwards.

A Systematic Review of Kidney Transplantation Decision Modelling Studies.

Background: Genome-based precision medicine strategies promise to minimize premature graft loss after renal transplantation, through precision approaches to immune compatibility matching between kidney donors and recipients. The potential adoption of this technology calls for important changes to clinical management processes and allocation policy. Such potential policy change decisions may be supported by decision models from health economics, comparative effectiveness research and operations management.

Patient and Caregiver Experience Decision Factors in Treatment Decision Making: Results of a Systematic Literature Review of Multiple Myeloma Decision Aids.

Objectives: Decision-aids (DAs) may facilitate shared decision-making for patients and caregivers, by providing evidence-based information to assist healthcare professionals, patients, and caregivers in making choices about aspects of care, and/or highlighting decision factors to discuss with the potential of altering the treatment decision. These decision factors may not be well integrated in DAs.

Methods: A systematic literature review was conducted in the field of multiple myeloma (MM) on peer-reviewed publications, extended with a gray literature search.

Genome Canada precision medicine strategy for structured national implementation of epitope matching in renal transplantation.

Advances in immunology support the understanding that precise structural epitopes on the antibody-accessible region of the HLA molecule determine antigenicity and challenge the need for identity across the full HLA molecule to minimize graft immunogenicity. Retrospective studies confirm that quantitative measurement of epitope-level mismatching between donor and recipient is an informative marker of graft rejection and survival and suggest that prospective allocation of donor organs based on this principle may improve graft survival. Here we describe the process for rigorous prospective evaluation of this hypothesis in a formal national proof-of-concept program for epitope-based matching.

The Penrose hypothesis in the second half of the 20th century: investigating the relationship between psychiatric bed numbers and the prison population in England between 1960 and 2018-2019.

Background: NHS Psychiatric beds comprise mental illness and intellectual disability beds. Penrose hypothesised that the number of psychiatric in-patients was inversely related to prison population size.

Aims: To ascertain whether the Penrose hypothesis held true in England between 1960 and 2018-2019.

Comprehensive Immune Profiling of a Kidney Transplant Recipient With Peri-Operative SARS-CoV-2 Infection: A Case Report.

To date there is limited data on the immune profile and outcomes of solid organ transplant recipients who encounter COVID-19 infection early post-transplant. Here we present a unique case where the kidney recipient's transplant surgery coincided with a positive SARS-CoV-2 test and the patient subsequently developed symptomatic COVID-19 perioperatively. We performed comprehensive immunological monitoring of cellular, proteomic, and serological changes during the first 4 critical months post-infection.

On Path to Informing Hierarchy of Eplet Mismatches as Determinants of Kidney Transplant Loss.

Introduction: To mitigate risks related to human leukocyte antigen (HLA) incompatibility, we assessed whether certain structurally defined HLA targets present in donors but absent from recipients, known as eplet mismatches (EMM), are associated with death-censored graft failure (DCGF).

Methods: We studied a cohort of 118,313 American 0% panel reactive antibodies (PRA) first kidney transplant recipients (2000 to 2015) from the Scientific Registry of Transplant Recipients. Imputed allele-level donor and recipient HLA-A, -B, -C, -DRB1, and -DQB1 genotypes were converted to the repertoire of EMM.