A prospective evaluation of the diagnostic potential of EBV-DNA in plasma and whole blood.

BACKGROUND: Quantitative polymerase chain reaction (qPCR) for Epstein-Barr virus (EBV)-DNA is an important diagnostic tool for EBV-associated disease, but interpretation of its clinical significance is challenging. OBJECTIVES: We assessed the diagnostic and clinical performance of WHO-standardised qPCR for EBV-DNA (WHO EBV-qPCR) in plasma and whole blood (WB) for proven EBV disease in a prospectively accrued patient cohort. STUDY DESIGN: Central Denmark Region patients, tested with WHO EBV-qPCR from November 2017 to March 2019, were screened for EBV disease. Incidence (IR) was estimated by Poisson regression. Sensitivity, specificity, positive and negative predictive values (PPV, NPV) were calculated for EBV-qPCR in plasma and WB. Risk of diagnostic latency was compared between patients with EBV-positive and EBV-negative lymphomas. RESULTS: EBV disease was diagnosed in 95 of 1484 participants (IR: 16.3 per 1000 patientyears 95%CI; 13.3-19.9). Sensitivity and specificity of WHO EBV-qPCR in plasma was 82.4% (95% CI; 74.2-90.7%) and 87.8% (95% CI; 85.6-90%), yielding a PPV of 32.2% (95% CI; 24.9-39.5%) and NPV of 98.6% (95% CI; 97.7-99.5%) for proven EBV disease. Sensitivity and NPV were comparable in WB, while specificity and PPV decreased to 66.9% (95% CI; 60.6-73.1%) and 18.1% (95% CI; 7.5-28.7%). Risk of diagnostic latency was 2.3-fold (95% CI 1.4-4.1) higher for patients with EBV-positive compared with EBV-negative lymphomas. CONCLUSIONS: WHO EBV-qPCR in plasma and WB have a low PPV but a high NPV for proven EBV disease. Implementation of WHO EBV-qPCR could improve interpretation and facilitate EBV-positive lymphoma diagnosis.

Infective endocarditis in patients receiving chronic hemodialysis: A 21-year observational cohort study in Denmark.

BACKGROUND: Chronic hemodialysis is a risk factor for invasive bacterial infections. We conducted a nationwide study of risk and mortality of infective endocarditis (IE) among patients undergoing chronic hemodialysis. METHODS: In this observational cohort study, patients with end-stage renal disease who initiated hemodialysis in Denmark during 1990 to 2010 were matched on age, gender, and municipality with up to 19 population controls. We extracted information on first admissions with IE, comorbidity, and arteriovenous fistula surgery from medical administrative databases. Incidence rates (IRs) of IE were compared between patients undergoing hemodialysis and population controls using Poisson regression. Risk factors for IE were assessed by Cox regression. RESULTS: IE was diagnosed in 150 of 9392 patients undergoing hemodialysis (IR: 6.83 per 1000 person-years, 95% confidence interval [CI]; 5.82-8.01) and 250 of 176,369 population controls (IR: 0.18 per 1000 person-years, 95% CI; 0.16-0.20) yielding an incidence rate-ratio of 38.1 (95% CI; 31.2-46.7). Among patients undergoing hemodialysis, absence of arteriovenous fistula surgery was associated with increased risk of IE (hazard ratio [HR] = 1.57; 95% CI; 1.09-2.27) after adjusting for age, sex, valvular disease, diabetes and period of first hemodialysis. Age ≥70 years was associated with a lower risk of IE (HR = 0.59; 95% CI 0.37-0.93). The 90-day all-cause mortality following diagnose of IE was 27% (95% CI; 20-35) for patients undergoing hemodialysis and 23% (95% CI; 18-29) for controls. CONCLUSIONS: Patients undergoing hemodialysis have markedly elevated risk of IE compared to the general population. Future challenges will be to develop strategies to prevent IE, to reduce IE-related morbidity and mortality in this vulnerable population.

[Oral ulcer as primary manifestation of HIV infection in an 80-year-old man].

Oral lesions such as candidiasis, Kaposi's sarcoma, hairy leukoplakia, herpes simplex infection, and ulcerative periodontitis are associated with HIV infection and may be the primary presentation in persons with undiagnosed HIV. We report a clinical case in which an 80-year-old man presented with an oral ulcer with morphological signs of immuno-suppression. The patient was perceived to be at low risk of HIV infection and thus, diagnostic HIV testing was delayed until subsequent development of Kaposi's sarcoma on the skin.