Epstein-Barr virus-associated gastric carcinoma among patients with pernicious anemia.

Approximately 9% of gastric carcinomas worldwide are associated with Epstein-Barr virus (EBV), making it the most frequent EBV-associated malignancy. Pernicious anemia, a condition with chronic gastritis and achlorhydria, is strongly associated with gastric carcinoma. Both chronic inflammation and the lack of stomach acid may influence the likelihood of EBV infection of the neoplastic gastric epithelium, but the prevalence of EBV-associated gastric carcinoma among patients with pernicious anemia is unknown. Therefore, we conducted a Danish nationwide case-control study comparing gastric carcinoma patients with pernicious anemia (PA-GC) with those without pernicious anemia (nonPA-GC), frequency matched 1:2. Tumor tissues were reclassified by expert histopathologists blinded to pernicious anemia and EBV status. In total, 186 samples (55 PA-GC and 131 nonPA-GC) were identified. EBV-associated gastric carcinoma (EBV-GC) was more common among PA-GC compared with nonPA-GC, adjusted odds ratio (OR) = 2.53 (CI: 0.88; 7.14), p = 0.08, with further adjustment for lymphocytic infiltrate OR = 2.94 (0.99-8.67), p = 0.05. Gastric carcinomas with signet-ring cell morphology were significantly less common in patients with PA-GC compared with nonPA-GC (OR = 0.05, CI 0.01; 0.24). Although these conditions are rare, we found suggestive evidence that EBV-associated gastric carcinomas are more common among gastric carcinoma patients with pernicious anemia compared with those without.

Familial aggregation and heritability of pyloric stenosis.

CONTEXT: Pyloric stenosis is the most common condition requiring surgery in the first months of life. Case reports have suggested familial aggregation, but to what extent this is caused by common environment or inheritance is unknown. OBJECTIVES: To investigate familial aggregation of pyloric stenosis from monozygotic twins to fourth-generation relatives according to sex and maternal and paternal contributions and to estimate disease heritability. DESIGN, SETTING, AND PATIENTS: Population-based cohort study of 1,999,738 children born in Denmark between 1977 and 2008 and followed up for the first year of life, during which 3362 children had surgery for pyloric stenosis. MAIN OUTCOME MEASURE: Familial aggregation of pyloric stenosis, evaluated by rate ratios. RESULTS: The incidence rate (per 1000 person-years) of pyloric stenosis in the first year of life was 1.8 for singletons and 3.1 for twins. The rate ratios of pyloric stenosis were 182 (95% confidence interval [CI], 70.7-467) for monozygotic twins, 29.4 (95% CI, 9.45-91.5) for dizygotic twins, 18.5 (95% CI, 13.7-25.1) for siblings, 4.99 (95% CI, 2.59-9.65) for half-siblings, 3.06 (95% CI, 2.10-4.44) for cousins, and 1.60 (95% CI, 0.51-4.99) for half-cousins. We found no difference in rate ratios for maternal and paternal relatives of children with pyloric stenosis and no difference according to sex of cohort member or sex of relative. The heritability of pyloric stenosis was 87%. CONCLUSION: Pyloric stenosis in Danish children shows strong familial aggregation and heritability.

Recurrent Intracerebral Hemorrhage: Associations with Comorbidities and Medicine with Antithrombotic Effects.

BACKGROUND: Intracerebral hemorrhage (ICH) is a disease with high mortality and a substantial risk of recurrence. However, the recurrence risk is poorly documented and the knowledge of potential predictors for recurrence among co-morbidities and medicine with antithrombotic effect is limited. OBJECTIVES: 1) To estimate the short- and long-term cumulative risks of recurrent intracerebral hemorrhage (ICH). 2) To investigate associations between typical comorbid diseases, surgical treatment, use of medicine with antithrombotic effects, including antithrombotic treatment (ATT), selective serotonin reuptake inhibitors (SSRI's), and nonsteroidal anti-inflammatory drugs (NSAID's) with recurrent ICH. METHODS: The cohort consisted of all individuals diagnosed with a primary ICH in Denmark 1996-2011. Information on comorbidities, surgical treatment for the primary ICH, and the use of ATT, SSRI's and NSAID's was retrieved from the Danish national health registers. The cumulative recurrence risk of ICH was estimated using the Aalen-Johansen estimator, thus taking into account the competing risk of death. Associations with potential predictors of recurrent ICH were estimated as rate ratios (RR's) using Poisson regression. Propensity score matching was used for the analyses of medicine with antithrombotic effects. RESULTS: Among 15,270 individuals diagnosed with a primary ICH, 2,053 recurrences were recorded, resulting in cumulative recurrence risk of 8.9% after one year and 13.7% after five years. Surgical treatment and renal insufficiency were associated with increased recurrence risks (RR 1.64, 95% CI 1.39-1.93 and RR 1.72, 95% CI 1.34-2.17, respectively), whereas anti-hypertensive treatment was associated with a reduced risk (RR 0.82, 95% CI 0.74-0.91). We observed non-significant associations between the use of any of the investigated medicines with antithrombotic effect (ATT, SSRI's, NSAID's) and recurrent ICH. CONCLUSIONS: The substantial short-and long-term recurrence risks warrant aggressive management of hypertension following a primary ICH, particularly in patients treated surgically for the primary ICH, and patients with renal insufficiency.