Type-specific whole blood still has a role in the era of low-titer O universal donor transfusion for severe trauma hemorrhage.

Whole blood can be ABO-type specific (type-specific whole blood (TSWB)) or low-titer O universal donor (low-titer O whole blood (LTOWB)). Having previously used LTOWB, the US Armed Forces Blood Program began using TSWB in 1965 as a method of increasing the donor pool. In contrast to military practice, the Association for the Advancement of Blood and Biotherapies formerly the American association of blood banks (AABB), from its first guidelines in 1958 until 2018, permitted only TSWB.

Novel WRN Helicase Inhibitors Selectively Target Microsatellite-Unstable Cancer Cells.

Microsatellite-unstable (MSI) cancers require WRN helicase to resolve replication stress due to expanded DNA (TA)n dinucleotide repeats. WRN is a promising synthetic lethal target for MSI tumors, and WRN inhibitors are in development. In this study, we used CRISPR-Cas9 base editing to map WRN residues critical for MSI cells, validating the helicase domain as the primary drug target.

Cannabis use disorders and outcome of admission to intensive care: A retrospective multi-centre cohort study.

Purpose: To identify factors associated with cannabinoid use among patients admitted to ICU and its impact on survival.

Methods: A cohort of adult patients admitted to four public Australian ICUs was assembled. Individuals with mental and behavioural disorders related to cannabinoids were identified using ICD10-AM codes.

Publication outcomes among intensive care trainees.

There is a paucity of literature describing the research productivity among trainees in intensive care medicine. We sought to examine the occurrence and determinants of successful publication outcomes associated with intensive care training. The study cohort consisted of all individuals admitted to fellowship of the College of Intensive Care Medicine of Australia and New Zealand (CICM) from 2012 to 2019.

Impact of allele-specific anti-human leukocyte antigen class I antibodies on organ allocation.

Technological advances in the field of histocompatibility have allowed us to define anti-human leukocyte antigen (HLA) antibody specificity at the allelic level. However, how allele-specific antibodies affect organ allocation is poorly studied. We examined allelic specificities of class I HLA antibodies in 6726 consecutive serum samples from 2953 transplant candidates and evaluated their impact on the corresponding crossmatch and organ allocation.

ABO Genotyping finds more A to B kidney transplant opportunities than lectin-based subtyping.

ABO compatibility is important for kidney transplantation, with longer waitlist times for blood group B kidney transplant candidates. However, kidneys from non-A (eg, A) subtype donors, which express less A antigen, can be safely transplanted into group B recipients. ABO subtyping is routinely performed using anti-A lectin, but DNA-based genotyping is also possible.

Fingolimod does not prevent syndecan-4 shedding from the endothelial glycocalyx in a cultured human umbilical vein endothelial cell model of vascular injury.

Background: Shedding of the endothelial glycocalyx (EG) is associated with poor outcomes in a range of conditions including sepsis. Fresh frozen plasma (FFP) restores the damaged EG to baseline thickness, however the mechanism for this effect is unknown, and some components of FFP have adverse effects unrelated to the EG. There is some limited evidence that sphingosine-1-phosphate (S1P) within FFP restores the EG by activating the endothelial cell S1P receptor 1 (S1PR).

Immune Regulatory 1 Cells: A Novel and Potent Subset of Human T Regulatory Cells.

A subset of T regulatory cells (Tregs), identified by TIRC7 (T cell immune response cDNA 7) expression is designated as Immune Regulatory 1 Cells (IR1 cells). TIRC7 is an immune checkpoint inhibitor, co-localized with the T- cell receptor, HLA-DR and CTLA-4 during T-cell activation, which delivers regulatory signals binding to its ligand, HLA-DR 2 domain. IR1 cells express FOXP3, and multiple other markers associated with immune suppression.

Recipient sex and estradiol levels affect transplant outcomes in an age-specific fashion.

Sex-specific influences have been shown for a variety of diseases. Whether donor or recipient sex and sex hormone levels impact alloimmune responses remains unclear. In unifactorial and multifactorial analyses of more than 400 000 SRTR listed kidney transplant patients, we found that younger female recipients had an inferior death-censored graft survival that was independent of donor sex.

Cultural competence of Australian dental students.

Background: Australia possesses a highly multicultural demographic, and thus dental practitioners are likely to regularly encounter culturally and linguistically diverse individuals. It is important for dental practitioners to be culturally competent, however, cultural competency education is highly variable in the curricula of dentistry and oral health courses in Australia, and research is largely limited to dentistry students. This study aims to investigate and compare perceived attitudes, beliefs and practices of cultural competence amongst first and final year Doctor of Dental Surgery (DDS) and Bachelor of Oral Health (BOH) students at the University of Melbourne Dental School.

Author Correction: STING and IRF3 in stromal fibroblasts enable sensing of genomic stress in cancer cells to undermine oncolytic viral therapy.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Peripheral host T cells survive hematopoietic stem cell transplantation and promote graft-versus-host disease.

Graft-versus-host disease (GVHD) is a major cause of morbidity and mortality in hematopoietic stem cell transplantation (HSCT). Donor T cells are key mediators in pathogenesis, but a contribution from host T cells has not been explored, as conditioning regimens are believed to deplete host T cells. To evaluate a potential role for host T cells in GVHD, the origin of skin and blood T cells was assessed prospectively in patients after HSCT in the absence of GVHD.

STING and IRF3 in stromal fibroblasts enable sensing of genomic stress in cancer cells to undermine oncolytic viral therapy.

Cancer-associated fibroblasts (CAFs) perform diverse roles and can modulate therapy responses. The inflammatory environment within tumours also influences responses to many therapies, including the efficacy of oncolytic viruses; however, the role of CAFs in this context remains unclear. Furthermore, little is known about the cell signalling triggered by heterotypic cancer cell-fibroblast contacts and about what activates fibroblasts to express inflammatory mediators.

Aging and Sex Effects on Mastication Performance in Healthy, Nondysphagic, Community-Dwelling Adults.

Purpose This study investigated the impact of age and sex on mastication performance in healthy, nondysphagic, community-dwelling adults as observed during videofluoroscopy. Method Videofluoroscopic swallowing study imaging and mastication performance metrics (cycles, duration) were used to evaluate 185 healthy individuals (102 women, 83 men) aged 21-89 years. Results A significant effect of age on mastication cycles was not observed; however, a significant but weak effect of age on mastication duration was found.

Development of a Calculated Panel Reactive Antibody Web Service with Local Frequencies for Platelet Transfusion Refractoriness Risk Stratification.

Background: Calculated panel reactive antibody (cPRA) scoring is used to assess whether platelet refractoriness is mediated by human leukocyte antigen (HLA) antibodies in the recipient. cPRA testing uses a national sample of US kidney donors to estimate the population frequency of HLA antigens, which may be different than HLA frequencies within local platelet inventories. We aimed to determine the impact on patient cPRA scores of using HLA frequencies derived from typing local platelet donations rather than national HLA frequencies.

Preformed Donor-specific Antibodies Against HLA Class II and Graft Outcomes in Deceased-donor Kidney Transplantation.

Background: Many kidney transplant centers in the United States report both HLA class I and II antibodies detected by sensitive solid-phase assays (SPAs) to United Network for Organ Sharing as unacceptable antigens, significantly reducing the compatible donor organ pool and prolonging waiting time for highly sensitized patients. However, the clinical relevance of all detected donor-specific antibodies (DSAs) by SPA is not unequivocal, because fluorescence intensity does not always accurately reflect antibody pathogenicity. Our center does not exclude patients from transplantation based on DSA class II.

Resuscitation Fluid Choices to Preserve the Endothelial Glycocalyx.

This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2019. Other selected articles can be found online at https://www.biomedcentral.

Sensitization in Transplantation: Assessment of Risk (STAR) 2017 Working Group Meeting Report.

The presence of preexisting (memory) or de novo donor-specific HLA antibodies (DSAs) is a known barrier to successful long-term organ transplantation. Yet, despite the fact that laboratory tools and our understanding of histocompatibility have advanced significantly in recent years, the criteria to define presence of a DSA and assign a level of risk for a given DSA vary markedly between centers. A collaborative effort between the American Society for Histocompatibility and Immunogenetics and the American Society of Transplantation provided the logistical support for generating a dedicated multidisciplinary working group, which included experts in histocompatibility as well as kidney, liver, heart, and lung transplantation.

Association of Cold Ischemia Time With Acute Renal Transplant Rejection.

Background: Kidney transplantation holds much promise as a treatment of choice for patients with end-stage kidney disease. The impact of cold ischemia time (CIT) on acute renal transplant rejection (ARTR) remains to be fully studied in a large cohort of renal transplant patients.

Methods: From the Organ Procurement and Transplantation Network database, we analyzed 63 798 deceased donor renal transplants performed between 2000 and 2010.

Detection and clinical impact of human leukocyte antigen antibodies in lung transplantation: A systematic review and meta-analysis.

There is significant variability in lung transplant centers' approach to HLA antibodies, creating heterogeneity regarding their clinical significance. Some institutions use beads coated with multiple HLA to screen candidate sera and then use single antigen bead (SAB) to determine antibody identity if the pre-screen is positive. Other centers do not pre-screen, using SAB alone, which may detect low-level antibodies of unknown significance.

A simple questionnaire to detect chronic kidney disease patients from Long An province screening data in Vietnam.

Background: The prevalence of chronic kidney disease (CKD) in rural Vietnam is unknown. We wished to determine the prevalence of CKD and determine whether a simple questionnaire was able to detect individuals at high risk of CKD before expensive confirmatory laboratory testing.

Methods: A cross sectional study was performed.

The Presence of Pretransplant HLA Antibodies Does Not Impact the Development of Chronic Lung Allograft Dysfunction or CLAD-Related Death.

Background: Development of donor-specific antibodies (DSA) after lung transplantation is associated with antibody mediated rejection, acute cellular rejection, and bronchiolitis obliterans syndrome; however, the significance of circulating antibodies before transplant remains unclear.

Methods: We performed a retrospective cohort study including recipients of primary lung transplants between 2008 and 2012. We assessed the impact of circulating HLA and noncytotoxic DSA detected before transplant on development of Chronic Lung Allograft Dysfunction (CLAD) or CLAD-related death.

Antibodies against HLA-DP recognize broadly expressed epitopes.

HLA matching and avoidance of pre-transplant donor-specific antibodies are important in selection of donors for solid organ transplant. Solid phase testing with single antigen beads allows resolution of antibody reactivity to the level of the allele. Single antigen bead testing results at a large transplant center were reviewed to identify selective reactivity patterns of anti-HLA antibodies.