ABO-adjusted cPRA metric for kidney allocation in an Asian-predominant population.

Recent studies showed that ABO-adjusted calculated panel reactive antibody (ABO-cPRA) may better reflect the histocompatibility level in a multi-ethnic population, but such data in Asians is not available. We developed an ABO-adjusted cPRA metric on a cohort of waitlist kidney transplant patients (n = 647, 99% Chinese) in Hong Kong, based on HLA alleles and ABO frequencies of local donors. The concordance between the web-based ABO-cPRA calculator and the impact on kidney allocation were evaluated. The blood group distribution for A, B, O and AB among waitlist kidney candidates were 26.2%, 27.5%, 40.1%, and 6.1%, and their chances of encountering incompatible blood group donors were 32.6%, 32.4%, 57.6%, and 0%, respectively. There is poor agreement between web-based ABO-cPRA calculator and our locally developed metrics. Over 90% of patients showed an increase in cPRA after ABO adjustment, most notably in those with cPRA between 70% and 79%. Blood group O patients had a much greater increase in cPRA scores after adjustment while patients of blood group A and B had similar increment. 10.6% of non-AB blood group waitlist patients had ABO-cPRA elevated to ≥80%. A local ABO-adjusted cPRA metric is required for Asian populations and may improve equity in kidney distribution for patients with disadvantageous blood groups. The result from the current study potentially helps other countries/localities in establishing their own unified ABO-cPRA metrics and predict the impact on kidney allocation.

The characterization of CD8+ T-cell responses in COVID-19.

This review gives an overview of the protective role of CD8+ T cells in SARS-CoV-2 infection. The cross-reactive responses intermediated by CD8+ T cells in unexposed cohorts are described. Additionally, the relevance of resident CD8+ T cells in the upper and lower airway during infection and CD8+ T-cell responses following vaccination are discussed, including recent worrisome breakthrough infections and variants of concerns (VOCs). Lastly, we explain the correlation between CD8+ T cells and COVID-19 severity. This review aids in a deeper comprehension of the association between CD8+ T cells and SARS-CoV-2 and broadens a vision for future exploration.

Safety and tolerability of tedizolid as oral treatment for bone and joint infections.

Bone and joint infections (BJIs) are common infections increasingly managed with oral therapy. However, there are limited safe oral options for many Gram-positive pathogens. In animal studies and short-term human use, tedizolid lacks the hematologic and neurologic toxicity of the other available oxazolidinone, linezolid. However, there are limited prospective safety data. We conducted an open-label, non-comparative trial of oral tedizolid for BJI treatment. Primary outcomes were safety and cure rate. Eligible patients had a BJI caused by documented or suspected Gram-positive pathogen, required 4-12 weeks of therapy, and did not have myelosuppression or peripheral/optic neuropathy. Subjects underwent weekly evaluation for cytopenias and neuropathy. We enrolled 44 subjects; five were lost to follow-up. Two subjects did not complete planned treatment because of rash (n = 1) and urgent surgery (n = 1). Of 37 patients with evaluable outcomes, 17 (46%) had hardware-associated infection, 13 (35%) had osteomyelitis, 5 (14%) had prosthetic joint infection, and 2 (5%) had other BJIs. Median (mean, range) treatment duration was 12 (10.1, 4-12) weeks. There were no cases of cytopenias or peripheral or optic neuropathy. Treatment cure occurred in 13 (35%); 19 (51%) required antibiotic continuation after 12 weeks of tedizolid related to retained hardware at the BJI site, and failure occurred in four (11%), two unlikely, one possibly, and one probably due to tedizolid. We found that oral tedizolid was well tolerated for prolonged BJI treatment without significant toxicity. Clinical failure rate was similar to that of other published BJI investigations. (This study has been registered at Clinicaltrials.gov under identifier NCT03009045.) IMPORTANCE Bone and joint infections are common infections with limited effective and safe oral options for Gram-positive infections. The largest prospective clinical trial of tedizolid therapy for bone and joint infections enrolled 44 patients and tested each in person weekly with detailed safety monitoring including tests for leukopenia, anemia, thrombocytopenia, peripheral neuropathy, and optic neuropathy for up to 12 weeks. Findings demonstrated tedizolid was generally well tolerated and there were no incident cases of cytopenias or neuropathy. Cure rates were similar to that in other bone and joint infection studies. In summary, oral tedizolid appears to be a well-tolerated oral option for Gram-positive bone and joint infections.

Endobronchial mucosal nodules and actinomycosis in a child with activated phosphatidylinositol 3-kinase delta syndrome (APDS).

In this report, we describe a case of a 5-year-old girl with poor growth and unresolving pneumonia. Bronchoscopy showed numerous endobronchial mucosal nodules, consisting of dense lymphoid infiltrates. Bacterial culture of the nodule biopsy suggested endobronchial actinomycosis. Genetic test confirmed the diagnosis of APDS.

Multiple liver abscesses secondary to Listeria monocytogenes complicated by hepatic artery mycotic aneurysm.

A woman in her 50s presented to the emergency department with 5 days of abdominal pain, nausea and vomiting. CT imaging of her liver demonstrated three enhancing, cystic lesions in her hepatic parenchyma and a large enhancing lesion in her porta hepatis concerning for a hepatic artery aneurysm. Radiographic-guided drainage was performed on two accessible liver abscesses, and cultures from this drainage grew Listeria monocytogenes Serial imaging of the aneurysm demonstrated that the aneurysm spontaneously thrombosed and did not require further intervention. She was subsequently discharged on intravenous ampicillin with a plan to continue until radiographic resolution of the abscesses.

Risk and Factors associated with disease manifestations in systemic lupus erythematosus - lupus nephritis (RIFLE-LN): a ten-year risk prediction strategy derived from a cohort of 1652 patients.

Objectives: Lupus nephritis (LN) remains one of the most severe manifestations in patients with systemic lupus erythematosus (SLE). Onset and overall LN risk among SLE patients remains considerably difficult to predict. Utilizing a territory-wide longitudinal cohort of over 10 years serial follow-up data, we developed and validated a risk stratification strategy to predict LN risk among Chinese SLE patients - Risk and Factors associated with disease manifestations in systemic Lupus Erythematosus - Lupus Nephritis (RIFLE-LN). Methods: Demographic and longitudinal data including autoantibody profiles, clinical manifestations, major organ involvement, LN biopsy results and outcomes were documented. Association analysis was performed to identify factors associated with LN. Regression modelling was used to develop a prediction model for 10-year risk of LN and thereafter validated. Results: A total of 1652 patients were recruited: 1382 patients were assigned for training and validation of the RIFLE-LN model; while 270 were assigned for testing. The median follow-up duration was 21 years. In the training and validation cohort, 845 (61%) of SLE patients developed LN. Cox regression and log rank test showed significant positive association between male sex, age of SLE onset and anti-dsDNA positivity. These factors were thereafter used to develop RIFLE-LN. The algorithm was tested in 270 independent patients and showed good performance (AUC = 0·70). Conclusion: By using male sex, anti-dsDNA positivity, age of SLE onset and SLE duration; RIFLE-LN can predict LN among Chinese SLE patients with good performance. We advocate its potential utility in guiding clinical management and disease monitoring. Further validation studies in independent cohorts are required.

Real-World Implementation of a COVID-19 Monoclonal Antibody Treatment Program in a Los Angeles County Safety Net Ambulatory Healthcare System - Barriers to Treatment and Lessons Learned.

Throughout the COVID-19 pandemic, low-income, minority, and otherwise vulnerable populations have repeatedly been shown to receive unequal access to novel therapies. Addressing this inequity requires specific awareness of the barriers experienced by vulnerable patients, and systemic efforts to address these barriers to provide equitable health care. We designed and implemented an ambulatory COVID-19 treatment program expressly aimed at increasing COVID-19 treatment uptake in a safety-net healthcare system. We describe systemic and human obstacles encountered as well as strategies used to increase use of COVID-19 treatments. Thanks to these strategies, we observed an increase in monoclonal antibody acceptance rate from 29 to 69% over the course of 10 months. We found that interventions such as engaging primary care providers, creating clear-language scripts for outreach calls, assisting with logistic barriers such as transportation, and addressing medical mistrust and hesitancy among both staff and patients were critical to increasing treatment uptake among our safety-net patient population.

Prognostic prediction by 18F-FDG-PET/CT parameters in patients with neuroblastoma: a systematic review and meta-analysis.

Purpose: Neuroblastoma is a solid malignant tumor with high malignancy and high risk for metastasis. The prognosis of neuroblastoma ranges from spontaneous regression to insensitivity to therapies and widespread metastasis. There is a non-invasive, panoramic imaging technique called 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography-computed tomography (PET/CT), which can provide both complete anatomical information via CT and extent of FDG uptake value in tumors via positron emission detection. PET/CT is a powerful approach to estimating tumoral metabolic activities, and PET/CT parameters have been demonstrated to be associated with the prognosis of various tumors. However, the predictive performance of PET/CT for the prognosis of neuroblastoma remains unclear. This meta-analysis aims to assess the predictive values of maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) for progression-free survival (PFS), event-free survival (EFS), and overall survival (OS) in neuroblastoma patients. Methods: Literature in PubMed, Embase, Cochrane Library, and Web of Science from January 1985 to June 2023 was searched for studies evaluating predictive values of PET/CT parameters for the prognosis of neuroblastoma. Search items mainly included "Positron Emission Tomography Computed Tomography" and "Neuroblastoma". Hazard ratio (HR) was used as a pooled statistic to assess the association of SUVmax, MTV, and TLG with PFS, EFS, and OS in neuroblastoma patients. Heterogeneity test and sensitivity analysis were performed. Results: There were eight studies included, with 325 participants. Meta-analysis showed that higher SUVmax was associated with shorter OS [HR = 1.27, 95% CI (1.11, 1.45), p = 0.001], while no association with PFS [HR = 1.03, 95% CI (0.99, 1.07), p = 0.222] and EFS [HR = 2.58, 95% CI (0.37, 18.24), p = 0.341] was presented. MTV showed no association with OS [HR = 2.46, 95% CI (0.34, 18.06), p = 0.376] and PFS [HR = 2.60, 95% CI (0.68, 9.88), p = 0.161]. There was a statistically significant association between TLG and OS [HR = 1.00, 95% CI (1.00, 1.00), p = 0.00], while the HR was 1, so the association could not be concluded, and TLG showed no association with PFS [HR = 1.00, 95% CI (0.99, 1.00), p = 0.974]. Conclusion: High SUVmax indicates poor OS in patients with neuroblastoma. The MTV and TLG are potential prognostic predictors that need to be further validated by more well-designed studies. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier 340729.

The role of regulatory T cells and follicular T helper cells in HBV infection.

Hepatitis B has become one of the major global health threats, especially in developing countries and regions. Hepatitis B virus infection greatly increases the risk for liver diseases such as cirrhosis and cancer. However, treatment for hepatitis B is limited when considering the huge base of infected people. The immune response against hepatitis B is mediated mainly by CD8+ T cells, which are key to fighting invading viruses, while regulatory T cells prevent overreaction of the immune response process. Additionally, follicular T helper cells play a key role in B-cell activation, proliferation, differentiation, and formation of germinal centers. The pathogenic process of hepatitis B virus is generally the result of a disorder or dysfunction of the immune system. Therefore, we present in this review the critical functions and related biological processes of regulatory T cells and follicular T helper cells during HBV infection.

The role of Raptor in lymphocytes differentiation and function.

Raptor, a key component of mTORC1, is required for recruiting substrates to mTORC1 and contributing to its subcellular localization. Raptor has a highly conserved N-terminus domain and seven WD40 repeats, which interact with mTOR and other mTORC1-related proteins. mTORC1 participates in various cellular events and mediates differentiation and metabolism. Directly or indirectly, many factors mediate the differentiation and function of lymphocytes that is essential for immunity. In this review, we summarize the role of Raptor in lymphocytes differentiation and function, whereby Raptor mediates the secretion of cytokines to induce early lymphocyte metabolism, development, proliferation and migration. Additionally, Raptor regulates the function of lymphocytes by regulating their steady-state maintenance and activation.

Towards a global partnership model in interprofessional education for cross-sector problem-solving.

OBJECTIVES: A partnership model in interprofessional education (IPE) is important in promoting a sense of global citizenship while preparing students for cross-sector problem-solving. However, the literature remains scant in providing useful guidance for the development of an IPE programme co-implemented by external partners. In this pioneering study, we describe the processes of forging global partnerships in co-implementing IPE and evaluate the programme in light of the preliminary data available. METHODS: This study is generally quantitative. We collected data from a total of 747 health and social care students from four higher education institutions. We utilized a descriptive narrative format and a quantitative design to present our experiences of running IPE with external partners and performed independent t-tests and analysis of variance to examine pretest and posttest mean differences in students' data. RESULTS: We identified factors in establishing a cross-institutional IPE programme. These factors include complementarity of expertise, mutual benefits, internet connectivity, interactivity of design, and time difference. We found significant pretest-posttest differences in students' readiness for interprofessional learning (teamwork and collaboration, positive professional identity, roles, and responsibilities). We also found a significant decrease in students' social interaction anxiety after the IPE simulation. CONCLUSIONS: The narrative of our experiences described in this manuscript could be considered by higher education institutions seeking to forge meaningful external partnerships in their effort to establish interprofessional global health education.

The first successful bone marrow transplantation in Vietnam for a young Vietnamese boy with chronic granulomatous disease: a case report.

Background: Chronic granulomatous disease (CGD) is an inborn error of immunity (IEI) disorder that results from defects in the respiratory burst activity in phagocytes, leading to the inability to kill bacterial and fungal microorganisms. CGD patients usually have a high incidence of morbidity such as infections and autoinflammatory diseases and a high mortality rate. Allogeneic bone marrow transplantation (BMT) is the only definitive cure for patients who suffer from CGD. Case presentation: We report the first transplant case of chronic granulomatous disease in Vietnam. A 25-month-old boy with X-linked CGD underwent bone marrow transplantation from his 5-year-old, full-matched human leukocyte antigen (HLA)-carrier sibling after myeloablative conditioning regimen with busulfan 5.1 mg/kg/day for 4 days, fludarabine 30 mg/m2/day for 5 days, and rATG (Grafalon-Fresenius) 10 mg/kg/day for 4 days. Neutrophil was engrafted on day 13 posttransplant, donor chimerism was 100% on day 30 with the dihydrorhodamine-1,2,3 (DHR 123) flow cytometric assay test that reached 38% of the normal 45 days posttransplant. Five months after transplant, the patient was free of infection with stable DHR 123 assay at 37%, and donor chimerism remained 100%. No sign of a graft-versus-host disease had been observed posttransplant. Conclusion: We suggest that bone marrow transplantation is a safe and effectual cure for CGD patients, especially for patients with HLA-identical siblings.

Haploidentical Transplant Achieves Long-Term Remission in Relapsed Refractory Leukemia With Fludarabine-Induced Neurotoxicity Complication.

Hematopoietic stem cell transplant is potentially curative for relapsed/refractory leukemia. However, neurotoxicity is common and has been reported in 11% to 59% of children following hematopoietic stem cell transplant. Most pediatric studies of the neurological effects of hematopoietic stem cell transplant have focused on acute neurotoxicity. Limited information is available for long-term neurotoxicity, particularly those cases that are severe and permanent and caused by conditioning chemotherapy. Here, we report 2 cases of relapsed acute lymphoblastic leukemia that achieved long-term remission by haploidentical hematopoietic stem cell transplant but remained complicated with severe and persistent fludarabine-induced neurotoxicity.

Safety and immunogenicity of 3 doses of BNT162b2 and CoronaVac in children and adults with inborn errors of immunity.

Our study (NCT04800133) aimed to determine the safety and immunogenicity in patients with IEIs receiving a 3-dose primary series of mRNA vaccine BNT162b2 (age 12+) or inactivated whole-virion vaccine CoronaVac (age 3+) in Hong Kong, including Omicron BA.1 neutralization, in a nonrandomized manner. Intradermal vaccination was also studied. Thirty-nine patients were vaccinated, including 16 with homologous intramuscular 0.3ml BNT162b2 and 17 with homologous intramuscular 0.5ml CoronaVac. Two patients received 3 doses of intradermal 0.5ml CoronaVac, and 4 patients received 2 doses of intramuscular BNT162b2 and the third dose with intradermal BNT162b2. No safety concerns were identified. Inadequate S-RBD IgG and surrogate virus neutralization responses were found after 2 doses in patients with humoral immunodeficiencies and especially so against BA.1. Dose 3 of either vaccine increased S-RBD IgG response. T cell responses against SARS-CoV-2 antigens were detected in vaccinated IEI patients by intracellular cytokine staining on flow cytometry. Intradermal third dose vaccine led to high antibody response in 4 patients. The primary vaccination series of BNT162b2 and CoronaVac in adults and children with IEIs should include 3 doses for optimal immunogenicity.

B cell-T cell interplay in immune regulation: A focus on follicular regulatory T and regulatory B cell functions.

B cells are the core components of humoral immunity. A mature B cell can serve in multiple capacities, including antibody production, antigen presentation, and regulatory functions. Forkhead box P3 (FoxP3)-expressing regulatory T cells (Tregs) are key players in sustaining immune tolerance and keeping inflammation in check. Mounting evidence suggests complex communications between B cells and Tregs. In this review, we summarize the yin-yang regulatory relationships between B cells and Tregs mainly from the perspectives of T follicular regulatory (Tfr) cells and regulatory B cells (Bregs). We discuss the regulatory effects of Tfr cells on B cell proliferation and the germinal center response. Additionally, we review the indispensable role of B cells in ensuring homeostatic Treg survival and describe the function of Bregs in promoting Treg responses. Finally, we introduce a new subset of Tregs, termed Treg-of-B cells, which are induced by B cells, lake the expression of FoxP3 but still own immunomodulatory effects. In this article, we also enumerate a sequence of research from clinical patients and experimental models to clarify the role of Tfr cells in germinal centers and the role of convention B cells and Bregs to Tregs in the context of different diseases. This review offers an updated overview of immunoregulatory networks and unveils potential targets for therapeutic interventions against cancer, autoimmune diseases and allograft rejection.

Epidemiology and outcomes of pediatric transplant-associated thrombotic microangiopathy in Hong Kong.

BACKGROUND: Transplant-associated thrombotic microangiopathy (TA-TMA) is an under-recognized yet potentially devastating complication of hematopoietic stem cell transplantation (HSCT) which had increased awareness in recent years. This report summarizes the demographics and outcomes of pediatric TA-TMA in Hong Kong. METHODS: All patients aged below 18 years who underwent HSCT in the Hong Kong Children's Hospital and were diagnosed to have TA-TMA during the 2-year period from April 1, 2019 to March 31, 2021 were included. RESULTS: A total of 73 transplants (51 allogeneic and 22 autologous) in 63 patients had been performed. Six patients (four males and two females) developed TA-TMA at a median duration of 2.5 months post-HSCT. The incidence rate was 9.52%. Of the six TA-TMA patients, five underwent allogenic one underwent autologous HSCT, respectively. Three of them were histologically proven. All four patients with cyclosporine had stopped the drug once TA-TMA was suspected. Median six doses of eculizumab were administered to five out of six patients. Three patients died (two due to fungal infection and one due to acute-on-chronic renal failure) within 3 months upon diagnosis of TA-TMA. Among three survivors, two stabilized with mild stage 2 chronic kidney disease (CKD) while the other suffered from stage 5 end-stage CKD requiring lifelong dialysis. CONCLUSION: In conclusion, recognition and diagnosis of TA-TMA are challenging. Early recognition and prompt administration of complement blockage with eculizumab may be beneficial in selected cases. Further prospective research studies are recommended to improve the management and outcomes of TA-TMA.