Mortality rates in transplant recipients and transplantation candidates in a high prevalence COVID-19 environment

Background: The risk of COVID-19 infection in transplant recipients (TRs) is unknown. Patients on dialysis may be exposed to greater risk of infection due to an inability to isolate. Consideration of these competing risks is important before restarting suspended transplant programs. This study compared outcomes in kidney and kidney/pancreas TRs with those on the waiting list, following admission with COVID-19 in a high-prevalence region. Methods: Audit data from all 6 London transplant centers were amalgamated. Demographic and laboratory data were collected and outcomes included mortality, intensive care (ITU) admission, and ventilation. Adult patients who had undergone a kidney or kidney/pancreas transplant, and those active on the transplant waiting list at the start of the pandemic were included. Results: One hundred twenty-one TRs and 52 waiting list patients (WL) were admitted to hospital with COVID-19. Thirty-six TR died (30%), while 14 WL patients died (27% P = 0.71). There was no difference in rates of admission to ITU or ventilation. Twenty-four percent of TR required renal replacement therapy, and 12% lost their grafts. Lymphocyte nadir and D-dimer peak showed no difference in those who did and did not die. No other comorbidities or demographic factors were associated with mortality, except for age (odds ratio of 4.3 [95% CI 1.8-10.2] for mortality if aged over 60 y) in TR. Conclusions: TRs and waiting list patients have similar mortality rates after hospital admission with COVID-19. Mortality was higher in older TRs. These data should inform decisions about transplantation in the COVID era

Subregional DXA-derived vertebral bone mineral measures are stronger predictors of failure load in specimens with lower areal bone mineral density, compared to those with higher areal bone mineral density

Measurement of areal bone mineral density (aBMD) in intravertebral subregions may increase the diagnostic sensitivity of dual-energy X-ray absorptiometry (DXA)-derived parameters for vertebral fragility. This study investigated whether DXA-derived bone parameters in vertebral subregions were better predictors of vertebral bone strength in specimens with low aBMD, compared to those with higher aBMD. Twenty-five lumbar vertebrae (15 embalmed and 10 fresh-frozen) were scanned with posteroanterior- (PA) and lateral-projection DXA, and then mechanically tested in compression to ultimate failure. Whole-vertebral aBMD and bone mineral content (BMC) were measured from the PA- and lateral-projection scans and within 6 intravertebral subregions. Multivariate regression was used to predict ultimate failure load by BMC, adjusted for vertebral size and specimen fixation status across the whole specimen set, and when subgrouped into specimens with low aBMD and high aBMD. Adjusted BMC explained a substantial proportion of variance in ultimate vertebral load, when measured over the whole vertebral area in lateral projection (adjusted R2 0.84) and across the six subregions (ROIs 2–7) (adjusted R2 range 0.58–0.78). The association between adjusted BMC, either measured subregionally or across the whole vertebral area, and vertebral failure load, was increased for the subgroup of specimens with identified ‘low aBMD’, compared to those with ‘high aBMD’, particularly in the anterior subregion where the adjusted R2 differed by 0.44. The relative contribution of BMC measured in vertebral subregions to ultimate failure load is greater among specimens with lower aBMD, compared to those with higher aBMD, particularly in the anterior subregion of the vertebral body

Clinical and biomarker changes in premanifest Huntington disease show trial feasibility: A decade of the PREDICT-HD study

There is growing consensus that intervention and treatment of Huntington disease (HD) should occur at the earliest stage possible. Various early-intervention methods for this fatal neurodegenerative disease have been identified, but preventive clinical trials for HD are limited by a lack of knowledge of the natural history of the disease and a dearth of appropriate outcome measures. Objectives of the current study are to document the natural history of premanifest HD progression in the largest cohort ever studied and to develop a battery of imaging and clinical markers of premanifest HD progression that can be used as outcome measures in preventive clinical trials. Neurobiological predictors of Huntington’s disease is a 32-site, international, observational study of premanifest HD, with annual examination of 1013 participants with premanifest HD and 301 gene-expansion negative controls between 2001 and 2012. Findings document 39 variables representing imaging, motor, cognitive, functional, and psychiatric domains, showing different rates of decline between premanifest HD and controls. Required sample size and models of premanifest HD are presented to inform future design of clinical and preclinical research. Preventive clinical trials in premanifest HD with participants who have a medium or high probability of motor onset are calculated to be as resource-effective as those conducted in diagnosed HD and could interrupt disease 7–12years earlier. Methods and measures for preventive clinical trials in premanifest HD more than a dozen years from motor onset are also feasible. These findings represent the most thorough documentation of a clinical battery for experimental therapeutics in stages of premanifest HD, the time period for which effective intervention may provide the most positive possible outcome for patients and their families affected by this devastating disease

In vitro measures of membrane changes reveal differences between red blood cells stored in saline-adenine-glucose-mannitol and AS-1 additive solutions: a paired study

BACKGROUND: Saline-Adenine-Glucose-Mannitol (SAGM) and a variant solution, AS-1 have been used for over 30 years to preserve red blood cells (RBCs). Reputedly these RBC components have similar quality, although no paired study has been reported. To determine whether differences exist, a paired study of SAGM-RBCs and AS-1-RBCs was conducted to identify membrane changes, including microparticle (MP) quantitation and in vitro RBC-endothelial cell (EC) interaction. STUDY DESIGN AND METHODS: Two whole blood packs were pooled-and-split and RBCs prepared (n=6 pairs). One pack was suspended in SAGM and one in AS-1. Samples were collected during 42 days of refrigerated storage. RBC shape/size, glycophorin A (GPA)(+) and phosphatidylserine (PS)(+) MPs were measured by flow cytometry. RBC adhesion to ECs was determined by an in vitro flow perfusion assay. Routine parameters (pH, hemolysis) were also measured. RESULTS: Compared to SAGM-RBCs, AS-1-RBCs had lower hemolysis (p<0.04), lower GPA(+) MPs (p<0.03) and lower PS(+) MPs (p<0.03) from day 14 onwards. AS-1-RBCs had higher (p<0.02) side scatter from day 28 onwards, compared to SAGM-RBCs. SAGM-RBCs were more adherent to ECs at day 28 of storage compared to AS-1 RBCs (p=0.04), but reversed at day 42 (p=0.02). No significant differences in forward scatter or pH were found. CONCLUSION: SAGM-RBCs lose more membrane during storage. SAGM-RBCs had increased adherence to ECs at day 28 of storage, while AS-1-RBCs were more adherent at day 42. The effect of these differences on the function and survival of SAGM-RBCs and AS-1-RBCs following transfusion remains to be determined

Structural diversity and photo-physical and magnetic properties of dimeric to 1D polymeric coordination polymers of lighter lanthanide(III) dinitrobenzoates

International audienc

Structural and magnetic investigations of a binuclear coordination compound of dysprosium(iii) dinitrobenzoate

International audienc