Impact of Acute Rejection on Kidney Allograft Outcomes in Recipients on Rapid Steroid Withdrawal

Background. Our aim was to study the impact of clinical acute rejection (CR) and subclinical rejection (SR) on outcomes in kidney transplant recipients treated with rapid steroid withdrawal (RSW). Methods. All patients who received a living or deceased donor kidney transplant and were treated with RSW were included. The primary outcome was death-censored graft survival. Biopsies with Banff borderline changes were included with the rejection groups. Results. 457 kidney transplant recipients treated with RSW were included; 46 (10%) experienced SR, and 36 (7.8%) had CR. Mean HLA mismatch was significantly higher in the CR group. The Banff grade of rejection was higher in the CR group. There was a larger proportion of patients in both rejection groups with the combination of IFTA and persistent inflammation on the follow-up protocol biopsy done at 1 year. The estimated 5-year death-censored graft survival was 81% in SR, 78% in CR, and 97% in the control group (P < .0001). Significant differences were observed in allograft survival between the CR and control group (HR 9.06, 95% CI 3.39–24.2) and between the SR and control group (HR 4.22, 95% CI 1.30–13.7). Conclusion. Both SR and CR are associated with an inferior graft survival in recipients on RSW

Trends in Outcomes for Neonates Born Very Preterm and Very Low Birth Weight in 11 High-Income Countries

Objective To evaluate outcome trends of neonates born very preterm in 11 high-income countries participating in the International Network for Evaluating Outcomes of neonates. Study design In a retrospective cohort study, we included 154 233 neonates admitted to 529 neonatal units between January 1, 2007, and December 31, 2015, at 24(0/7) to 31(6/7) weeks of gestational age and birth weight <1500 g. Composite outcomes were in-hospital mortality or any of severe neurologic injury, treated retinopathy of prematurity, and bronchopulmonary dysplasia (BPD); and same composite outcome excluding BPD. Secondary outcomes were mortality and individual morbidities. For each country, annual outcome trends and adjusted relative risks comparing epoch 2 (2012-2015) to epoch 1 (2007-2011) were analyzed. Results For composite outcome including BPD, the trend decreased in Canada and Israel but increased in Australia and New Zealand, Japan, Spain, Sweden, and the United Kingdom. For composite outcome excluding BPD, the trend decreased in all countries except Spain, Sweden, Tuscany, and the United Kingdom. The risk of composite outcome was lower in epoch 2 than epoch 1 in Canada (adjusted relative risks 0.78; 95% CI 0.74-0.82) only. The risk of composite outcome excluding BPD was significantly lower in epoch 2 compared with epoch 1 in Australia and New Zealand, Canada, Finland, Japan, and Switzerland. Mortality rates reduced in most countries in epoch 2. BPD rates increased significantly in all countries except Canada, Israel, Finland, and Tuscany. Conclusions In most countries, mortality decreased whereas BPD increased for neonates born very preterm

Pathogenicity and Impact of HLA Class I Alleles in Aplastic Anemia Patients of Different Ethnicities

Acquired aplastic anemia (AA) is caused by autoreactive T cell-mediated destruction of early hematopoietic cells. Somatic loss of human leukocyte antigen (HLA) class I alleles was identified as a mechanism of immune escape in surviving hematopoietic cells of some patients with AA. However, pathogenicity, structural characteristics, and clinical impact of specific HLA alleles in AA remain poorly understood. Here, we evaluated somatic HLA loss in 505 patients with AA from 2 multi-institutional cohorts. Using a combination of HLA mutation frequencies, peptide-binding structures, and association with AA in an independent cohort of 6,323 patients from the National Marrow Donor Program, we identified 19 AA risk alleles and 12 non-risk alleles and established a potentially novel AA HLA pathogenicity stratification. Our results define pathogenicity for the majority of common HLA-A/B alleles across diverse populations. Our study demonstrates that HLA alleles confer different risks of developing AA, but once AA develops, specific alleles are not associated with response to immunosuppression or transplant outcomes. However, higher pathogenicity alleles, particularly HLA-B*14:02, are associated with higher rates of clonal evolution in adult patients with AA. Our study provides insights into the immune pathogenesis of AA, opening the door to future autoantigen identification and improved understanding of clonal evolution in AA

The Role of Social Media in Improving Patient Recruitment for Research Studies on Persistent Post-Infectious Olfactory Dysfunction

Background and Objectives: Since the COVID-19 pandemic, the number of cases of post-infectious olfactory dysfunction (PIOD) has substantially increased. Despite a good recovery rate, olfactory dysfunction (OD) becomes persistent in up to 15% of cases and further research is needed to find new treatment modalities for those patients who have not improved on currently available treatments. Social media has emerged as a potential avenue for patient recruitment, but its role in recruiting patients with smell dysfunction remains unexplored. We conducted a survey using the AbScent Facebook page to evaluate the feasibility of using this platform for future studies on smell dysfunction. Materials and Methods: Between 26 October and 4 November 2021, we conducted an online survey to evaluate propensity of patients with PIOD who would be willing to participate in research studies on smell dysfunction. Results: Sixty-five subjects were surveyed with a response rate of 90.7%. The median visual analogue scale (VAS) for sense of smell was 0 at infection and 2 at survey completion. The median length of OD was 1.6 years, and the main cause of OD was SARS-CoV-2 (57.6%). Parosmia was reported in 41 subjects (69.5%) whilst phantosmia in 22 (37.3%). The median length of olfactory training (OT) was 6 months but subjectively effective in 15 subjects (25.4%). Twenty-seven subjects (45.8%) tried other medications to improve olfaction, but only 6 participants (22.2%) reported an improvement. All subjects expressed their propensity to participate in future studies with most of them (38; 64.4%) willing to be enrolled either in medical and surgical studies or to be part of a randomised study design (11; 18.6%). Conclusions: Using the AbScent Facebook platform we successfully selected a population of subjects with persistent and severe OD that have failed to improve on available treatments and are willing to participate in further clinical trials

Clinical Study Impact of Acute Rejection on Kidney Allograft Outcomes in Recipients on Rapid Steroid Withdrawal

Background. Our aim was to study the impact of clinical acute rejection (CR) and subclinical rejection (SR) on outcomes in kidney transplant recipients treated with rapid steroid withdrawal (RSW). Methods. All patients who received a living or deceased donor kidney transplant and were treated with RSW were included. The primary outcome was death-censored graft survival. Biopsies with Banff borderline changes were included with the rejection groups. Results. 457 kidney transplant recipients treated with RSW were included; 46 (10%) experienced SR, and 36 (7.8%) had CR. Mean HLA mismatch was significantly higher in the CR group. The Banff grade of rejection was higher in the CR group. There was a larger proportion of patients in both rejection groups with the combination of IFTA and persistent inflammation on the follow-up protocol biopsy done at 1 year. The estimated 5-year death-censored graft survival was 81% in SR, 78% in CR, and 97% in the control group (P &lt; .0001). Significant differences were observed in allograft survival between the CR and control group (HR 9.06, and between the SR and control group (HR 4.22, 95% CI 1.30-13.7). Conclusion. Both SR and CR are associated with an inferior graft survival in recipients on RSW