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Background and objectives: We previously found a substantial familial aggregation of healthy aging phenotypes, including exceptional memory (EM) in long-lived persons. In the current study, we aim to assess whether long-lived families with EM and without EM (non-EM) differ in systemic inflammation status and trajectory. Methods: The current study included 4333 participants of the multi-center Long Life Family Study (LLFS). LLFS families were classified as EM (556 individuals from 28 families) or non-EM (3777 individuals from 416 families), with 2 or more offspring exhibiting exceptional memory performance (i.e. having baseline composite z-score representing immediate and delayed story memory being 1.5 SD above the mean in the nondemented offspring sample) considered as EM. Blood samples from baseline were used to measure inflammatory biomarkers including total white blood cell (WBC) and its subtypes (neutrophils, lymphocytes, monocytes) count, platelet count, high sensitivity C-reactive protein, and interleukin-6. Generalized linear models were used to examine cross-sectional differences in inflammatory biomarkers at baseline. In a sub-sample of 2227 participants (338 subjects from 24 EM families and 1889 from 328 non-EM families) with repeated measures of immune cell counts, we examined whether the rate of biomarker change differed between EM and non-EM families. All models were adjusted for family size, relatedness, age, sex, education, field center, APOE genotype, and body mass index. Results: LLFS participants from EM families had a marginally higher monocyte count at baseline (b = 0.028, SE = 0.0110, p = 0.010) after adjusting for age, sex, education, and field site, particularly in men (p < 0.0001) but not in women (p = 0.493) (p-interaction = 0.003). Over time, monocyte counts increased (p < 0.0001) in both EM and non-EM families, while lymphocytes and platelet counts decreased over time in the non-EM families (p < 0.0001) but not in the EM families. After adjusting for multiple variables, there was no significant difference in biomarker change over time between the EM and non-EM families. Discussion: Compared with non-EM families, EM families had significantly higher monocyte count at baseline but had similar change over time. Our study suggests that differences in monocyte counts may be a pathway through which EM emerges in some long-lived families, especially among men.
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BACKGROUND: Celiac disease (CD) has been associated with gastrointestinal malignancies. However, the magnitude of the risk of pancreatic cancer (PC) associated with CD is much less clear, and risks have not been estimated from large populations. AIM: To assess the risk of PC in CD patients. METHODS: We conducted a population-based, multicenter, propensity score-matched cohort study with consecutive patients diagnosed with CD using the TriNeTx research network platform. We examined the incidence of PC in patients with CD compared with a matched cohort of patients without CD (non-CD, controls). Each patient in the main group (CD) was matched to a patient in the control group using 1:1 propensity score matching to reduce confounding effects. The incidence of PC was estimated using a Cox proportional hazards model with a hazard ratio (HR) and 95% confidence interval (CI). RESULTS: A total of 389980 patients were included in this study. Among them, 155877 patients had a diagnosis of CD, and the remaining 234103 individuals without CD were considered a control cohort. The mean duration of follow-up for patients in the CD and control cohorts was 5.8 ± 1.8 and 5.9 ± 1.1 years, respectively. During the follow-up, 309 patients with CD developed PC, whereas 240 patients developed PC in the control group (HR = 1.29; 95%CI: 1.09-1.53). In the secondary analyses in the first year after diagnosis of CD, patients with CD were at a significant increase in risk for PC; 151 patients with CD had an incidence of PC compared with 96 incidences of PC among the patients in the non-CD control group (HR = 1.56; 95%CI: 1.20-2.01) and sensitivity analysis showed similar magnitude to the one generated in the primary and secondary analysis. CONCLUSION: Patients with CD are at increased risk of PC. Risk elevation persists beyond the first year after diagnosis to reference individuals without CD from the general population.
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BACKGROUND: Patients with autoimmune hepatitis (AIH) require life-long immunosuppressive agents that may increase the risk of poor coronavirus disease 2019 (COVID-19) outcomes. There is a paucity of large data at the population level to assess whether patients with AIH have an increased risk of severe diseases. AIM: To evaluate the impact of pre-existing AIH on the clinical outcomes of patients with COVID-19. METHODS: We conducted a population-based, multicenter, propensity score-matched cohort study with consecutive adult patients (≥ 18 years) diagnosed with COVID-19 using the TriNeTx research network platform. The outcomes of patients with AIH (main group) were compared to a propensity score-matched cohort of patients: (1) Without chronic liver disease (CLD); and (2) Patients with CLD except AIH (non-AIH CLD) control groups. Each patient in the main group was matched to a patient in the control group using 1:1 propensity score matching to reduce confounding effects. The primary outcome was all-cause mortality, and secondary outcomes were hospitalization rate, need for critical care, severe disease, mechanical ventilation, and acute kidney injury (AKI). For each outcome, the risk ratio (RR) and confidence intervals (CI) were calculated to compare the association of AIH with the outcome. RESULTS: We identified 375 patients with AIH, 1647915 patients with non-CLD, and 15790 patients with non-AIH CLD with COVID-19 infection. Compared to non-CLD patients, the AIH cohort had an increased risk of all-cause mortality (RR = 2.22; 95%CI: 1.07-4.61), hospitalization rate (RR = 1.78; 95%CI: 1.17-2.69), and severe disease (RR = 1.98; 95%CI: 1.19-3.26). The AIH cohort had a lower risk of hospitalization rate (RR = 0.72; 95%CI: 0.56-0.92), critical care (RR = 0.50; 95%CI: 0.32-0.79), and AKI (RR = 0.56; 95%CI: 0.35-0.88) compared to the non-AIH CLD patients. CONCLUSION: Patients with AIH are associated with increased hospitalization risk, severe disease, and all-cause mortality compared to patients without pre-existing CLD from the diagnosis of COVID-19. However, patients with AIH were not at risk for worse outcomes with COVID-19 than other causes of CLD.
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INTRODUCTION: African-Americans (AAs) are 64% more likely to be diagnosed with AD than non-Hispanic Whites. AAs with elevated AD biomarkers exhibit greater neurodegeneration in AD signature regions compared to non-Hispanic Whites with elevated AD biomarkers. This pilot trial examined whether normal or elevated plasma levels of interleukin (IL)-10 are associated with changes in executive function and short-term memory in AA women at risk for developing AD due to parental history. METHOD: Observational study comparing groups with elevated and normal plasma IL-10 levels. Study included 31 AA women (age=58.9±8 years) with parental history of AD. Measures included inflammatory blood biomarkers, executive function and visuospatial short-term memory tests. Multivariate linear regression with adjustment for comorbidities, and Bonferroni corrections for multiple comparisons were used to compare groups. Effect sizes (Cohen's d) were generated. Using endpoints with moderate-large effects between groups, Pearson correlations determined associations between biomarker levels and cognitive performance. RESULTS: The elevated IL-10 group performed worse on the Trail-Making Test proportional score ((B-A)/A) (effect size (d =-0.87 (-1.6, -.1)). Moderate effects with large confident intervals were noted in inhibition, set-switching, and body position spatial memory. Significant differences between groups in levels of other inflammatory markers were noted, including IL-7 (p=0.002) and interferon γ (p=0.02). IL-7 remained significant after Bonferroni correction. Correlation matrices revealed moderate-large, significant correlations (yet with wide confidence intervals) between levels of IL-10 and IL-9 with BPST total correct trials, and between interferon γ and delayed recall. CONCLUSIONS: Interleukins may incite inflammation, leading to impaired aspects of executive function and short-term memory in this sample of African American women at risk for developing AD. This research provides effect sizes that will be used to power future research that will further investigate the relationship between inflammation, AD biomarkers, and cognitive function in an understudied population.
