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Purpose: Antibodies to select Epstein-Barr virus proteins can diagnose early-stage nasopharyngeal carcinoma (NPC). We have previously shown that IgA against Epstein-Barr virus nuclear antigen 1 (EBNA1) can predict incident NPC in high- and intermediate-risk cohorts 4 years before diagnosis. Here, we tested EBNA1 variants, with mutants, to define the sequence requirements for an NPC risk assay., Experimental Design: Mammalian-expressed constructs were developed to represent EBNA1 variants 487V and 487A, which can differ by ≥15 amino acids in the N- and C-termini. Denatured lysates were evaluated by a refined IgA and IgG immunoblot assay in a case-control study using prediagnostic NPC sera from two independent cohorts in Singapore and Shanghai, the People's Republic of China., Results: At 95% sensitivity, 487V yielded a 94.9% specificity compared with 86.1% for 487A. EBNA1 deleted for the conserved glycine-alanine repeats (GAr) reduced false positives by 22.8%. NPC sera reacted more strongly to the C-terminus than healthy controls, but the C-terminal construct (a.a. 390-641) showed lower specificity (84.8%) than the EBNA1 GAr-deleted construct (92.4%) at 95% sensitivity., Conclusions: Although EBNA1 IgA was present in healthy sera, most epitopes localized to the immunodominant GAr. We conclude that a refined EBNA1 antigen deleted for the GAr, but with residues consistently detected in Southeast Asian NPC tumors, is optimized for risk prediction with an extended sojourn time of 7.5 years. Furthermore, distinct EBNA1 serologic profiles enhanced the utility of the EBNA1 IgA assay for risk stratification. This illustrates the importance of serologically relevant EBNA1 sequences for NPC risk prediction and early detection., (©2024 American Association for Cancer Research.)

Introduction: To improve the nutritional care and resource allocation of critically ill patients with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), we described their characteristics, treatment modalities and clinical outcomes, and compared their nutrition interventions against the American Society for Parenteral and Enteral Nutrition (ASPEN) recommendations., Methods: This was a retrospective observational study conducted in 5 tertiary hospitals in Singapore. Characteristics, treatment modalities, clinical outcomes and nutrition interventions of critically ill patients with SARS-CoV-2 who received enteral and parenteral nutrition were collected between January and May 2020., Results: Among the 83 critically ill patients with SARS-CoV-2, 22 (28%) were obese, 45 (54%) had hypertension, and 21 (25%) had diabetes. Neuromuscular blockade, prone therapy and dialysis were applied in 70% (58), 47% (39) and 35% (29) of the patients, respectively. Refeeding hypophosphataemia and hospital mortality occurred respectively in 6% (5) and 18% (15) of the critically ill patients with SARS-CoV-2. Late enteral nutrition and cardiovascular comorbidities were associated with higher hospital mortality (adjusted relative risk 9.00, 95% confidence interval [CI] 2.25-35.99; 6.30, 95% CI 1.15-34.40, respectively). Prone therapy was not associated with a higher incidence of high gastric residual volume (≥250mL). The minimum caloric (15kcal/kg) and protein (1.2g/kg) recommendations of ASPEN were achieved in 54% (39) and 0% of the patients, respectively., Conclusion: The high obesity prevalence and frequent usage of neuromuscular blockade, prone therapy, and dialysis had considerable implications for the nutritional care of critically ill patients with SARS-CoV-2. They also did not receive adequate calories and protein. More audits should be conducted to refine nutritional interventions and guidelines for this ever-evolving disease.