Relationship between autoantibodies to erythropoietin receptor and renal outcome in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis.

Purpose: We examined the relationship between autoantibodies to erythropoietin receptor (EPOR) and renal outcome in patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV).Materials and methods: Sixty-three Japanese patients with AAV were enrolled and followed for a median of 31.4 months. Patients were screened for serum anti-EPOR antibodies using an enzyme-linked immunosorbent assay. Associations of anti-EPOR antibodies with clinical parameters were analyzed using logistic-regression models.Results: Anti-EPOR antibodies were detected in 7 (11%) of the 63 patients, and levels of the antibodies decreased with immunosuppressive therapy. The presence of anti-EPOR antibodies was associated with a higher Birmingham vasculitis activity score. In addition, anti-EPOR antibodies were more frequently observed in patients with renal outcomes, which was defined as a sustained 50% reduction in the estimated glomerular filtration rate from baseline, than in those without. Multiple logistic regression analysis revealed that presence of anti-EPOR antibodies, as well as age at disease onset, were as risk factors for the renal outcome.Conclusion: Anti-EPOR antibodies were associated with the progression of renal dysfunction in patients with AAV.

A preliminary retrospective evaluation of screening and diagnosis of ornithine transcarbamylase deficiency in high-risk patients at a referral center in Vietnam.

Introduction: To date, newborn screening (NBS) for proximal urea cycle disorders, including Ornithine transcarbamylase deficiency (OTCD), was not recommended due to the lack of appropriate tests and insufficient evidence of the benefits. This study aimed to investigate the potential of tandem mass spectrometry (MS/MS) for OTCD screening and its value in guiding further investigation to obtain a final diagnosis in high-risk patients. Methods: The study included patients with OTCD referred to the National Children's Hospital between April 2020 and November 2023. A retrospective evaluation of amino acid concentrations measured by MS/MS and their ratios in patients with early-onset and late-onset OTCD was conducted. Results: While all ten early-onset cases had glutamine concentrations above the upper limit, only five of them had citrulline concentrations below the lower limit of the reference interval. Only two late-onset cases had elevated glutamine levels, while all had citrulline within reference intervals. The Cit/Phe ratio was decreased, and the Gln/Cit and Met/Cit ratios were increased in all early-onset OTCD cases, while they were abnormal in only one late-onset case. Conclusions: The preliminary results suggest that hyperglutaminemia, in combination with low or normal citrulline concentrations and specific ratios (Gln/Cit, Met/Cit, and Cit/Phe), can serve as reliable markers for screening early-onset OTCD in high-risk patients. However, these markers proved less sensitive for detecting the late-onset form, even in symptomatic patients.

Changes in the Proportion of Gastrointestinal Emergency Endoscopy and Peptic Ulcer Disease During the COVID-19 Pandemic: A Local Retrospective Observational Study From Vietnam.

OBJECTIVES: The coronavirus disease 2019 (COVID-19) pandemic has disrupted the practice of gastrointestinal (GI) endoscopy units and may increase the risk of digestive disorders. We described the situational changes in GI endoscopy and peptic ulcer disease (PUD) proportion during COVID-19 in Vietnam and examined the associated factors. METHODS: A retrospective ecological study was conducted on data of Hanoi Medical University Hospital, Vietnam. The number of upper GI endoscopy and the proportion of GI emergency endoscopy and PUD were compared between 2019 and 2020 by month (January to June). Log-binomial regression was used to explore associated factors of GI emergency endoscopy and PUD. RESULTS: The number of endoscopies decreased remarkably during the nationwide social distancing in April 2020. Compared to April 2019, the proportion in April 2020 of both GI emergency endoscopy [4.1 vs. 9.8%, proportion ratio (PR) 2.39, 95% CI 2, 2.87], and PUD [13.9 vs. 15.8%; PR, 1.14; 95% CI, 1.01, 1.29] was significantly higher. In log-binomial models, the proportion of GI emergency endoscopy was higher in April 2020 compared to April 2019 (adjusted PR, 2.41; 95% CI, 2.01, 2.88). Male sex and age of ≥50 years were associated with an increased PUD and GI emergency conditions. CONCLUSION: The proportion of both GI emergency endoscopy and PUD was significantly higher during the time of the state of emergency due to the ongoing COVID-19 pandemic in 2020 when compared to 2019 at the same health facility in Vietnam. The findings suggest that healthcare delivery reforms during the era of an emerging pandemic are required to reduce digestive disorders, in particular, and chronic diseases in general.

Clinical and Pathological Significance of Autoantibodies to Erythropoietin Receptor in Type 2 Diabetic Patients With CKD.

INTRODUCTION: We examined the impact of autoantibodies on the erythropoietin receptor (EPOR) in type 2 diabetic patients with chronic kidney disease (CKD). METHODS: A total of 112 Japanese patients with type 2 diabetes who had CKD were enrolled in this study and followed for a mean of 45 months. Sera from these patients were screened for anti-EPOR antibodies using enzyme-linked immunosorbent assays. RESULTS: Anti-EPOR antibodies were detected in 26 patients (23%). Anti-EPOR antibodies were associated with low hemoglobin concentrations and decreased renal function. In patients with biopsy-proven diabetic nephropathy, anti-EPOR antibodies were associated with increased levels of interstitial inflammation. A decrease in renal function was observed more frequently in patients with antibodies than in those without antibodies, and the presence of the antibodies together with well-known clinical parameters, including proteinuria and low glomerular filtration rate, was a significant risk factor for end-stage renal disease. In human tubular epithelial HK-2 cells, IgG fractions containing anti-EPOR antibodies upregulated the expression of monocyte chemoattractant protein-1 mRNA under a high concentration of glucose. CONCLUSION: Anti-EPOR antibodies might be involved in the progression of renal lesions and in the impaired erythropoiesis in type 2 diabetic patients with CKD. Furthermore, the presence of anti-EPOR antibodies may be an additional predictor for end-stage renal disease in type 2 diabetes.

Development of a new biochemical test to diagnose and monitor neuroblastoma in Vietnam: homovanillic and vanillylmandelic acid by gas chromatography-mass spectrometry.

OBJECTIVES: The aim of this study was to develop an accurate robust testing method to simultaneously measure urine levels of HVA and VMA using gas chromatography mass spectrometry (GCMS) and to establish age-specific reference intervals of HVA and VMA in random urines for Vietnamese children. DESIGN AND METHODS: The assay for urinary HVA and VMA was developed based on a classical urinary organic acid profiling method. Briefly, this incorporated 3-phenyl butyric acid as the internal standard and liquid-liquid extraction with ethyl acetate followed by derivatization with BSTFA. The Agilent 7890A GC and 5975C Mass Selective Detector in single ion monitoring mode was used for analysis. Reference intervals were developed from random urine samples collected from 634 disease free Vietnamese children and compared to 50 known neuroblastoma patient samples. Results were reported relative to creatinine concentration. Age related 95% reference intervals for urinary HVA and VMA were estimated from sample quantiles. The analytes (expressed as analyte/creatinine ratios) diagnostic values were determined by calculating the related sensitivity, specificity and likelihood ratios. RESULTS: HVA and VMA were linear to at least 193 and 221µmol/L, respectively. The limit of quantitation for both analytes was 0.9µmol/L. Using the bi-level control (n=15), the within-batch coefficients of variations (CVs) were less than 3% for both analytes across the assay range. The between-batch CVs (n=20 over three months), were 3.6% at 11µmol/L and 2.1% at 88µmol/L for HVA, 6.6% at 18.2µmol/L and 2.6% at 90.6µmol/L for VMA. Vietnamese age related reference intervals were established for urinary HVA and VMA per creatinine. HVA for children <6months (n=91) was 5.3-37.0µmol/mmol; 6months to <1year (n=141) was 2.7-27.7µmol/mmol; 1 to 5years (n=139) was 3.4-17.9µmol/mmol; 6 to 10years (n=136) was 2.7-8.8µmol/mmol; and 11 to 15years (n=127) was 1.1-9.4µmol/mmol. VMA for children <6months was 1.8-12.2µmol/mmol; 6months to <1year was 1.5-9.3µmol/mmol; 1 to 5years was 1.9-7.8µmol/mmol; 6 to 10years was 1.6-5.1µmol/mmol; and 11 to 15years was <0.9-6.3µmol/mmol. CONCLUSIONS: A robust testing method for simultaneous quantitation of urinary HVA and VMA by GCMS was developed. This method is accurate, precise and fit for its clinical purpose and suitable for developing countries. Age-related reference intervals of urinary HVA and VMA were established for Vietnamese children and the intervals declined progressively with increasing age for each analyte.