Circulating markers of oxidative stress and liver fibrosis in Sudanese subjects at risk of schistosomiasis and hepatitis

Epidemiological studies in the developing world are frequently biased by the simultaneous presence of several infectious pathogens. In the present study, we examined the usefulness of circulating markers of oxidative stress and liver fibrosis to investigate the distinct forms of chronic liver inflammations associated with schistosomiasis and viral hepatitis, respectively. The study was performed in a Sudanese population exposed to Schistosoma. Circulating hyaluronic acid (HA) was used as a marker of liver fibrosis; the severity of schistosomiasis was determined by ultrasonic examination; viral hepatitis infection was ascertained by circulating anti-hepatitis antibodies. Serum markers were examined also in Sudanese subjects not exposed to Schistosoma infection and in French control subjects. We found a drastic decrease of lycopene levels in the subjects exposed to schistosomiasis in comparison with non-exposed Sudanese and French control subjects. Retinol, alpha-tocopherol and five carotenoids were unchanged. Lycopene depletion was unlikely to be due to variations of nutritional origin, since the lycopene/beta-carotene ratio was five-fold lower in the population at risk of schistosomiasis than in the other groups. We found that high HA serum levels were associated with severe periportal fibrosis but not with viral infection. Conversely, levels of the oxidized lipid malondialdehyde (MDA) were associated with viral infection but not with the severity of schistosomiasis, even though the two infections had additive effects. We concluded that serum markers are valuable tools for investigating the complex effects of co-existing factors of chronic liver inflammation.     

Delirium symptoms and low dietary intake in older inpatients are independent predictors of institutionalization: a 1-year prospective population-based study

OBJECTIVE: To assess the effects of delirium on the institutionalization rate, taking into account geriatric syndromes and nutritional status. METHODS: This population-based study took place in an acute care unit and included participants older than 75 years, arriving from home and later discharged. Confusion Assessment Method (CAM) symptoms were recorded by the nurses within 24 hours after admission and every 3 days. Delirium was defined using the CAM algorithm, and subsyndromal delirium responded to symptoms not fulfilling the CAM algorithm. These delirium categories were either present at admission (prevalent) or occurred during the hospital stay (incident). Participants were classified as having a low dietary intake when energy intake was at any time lower than 600 kcal/d. Age, sex, known cognitive impairment, weight, functional dependency, and laboratory testing as well as diagnoses were also recorded. Step-by-step backward logistic regression was used to identify predictors of institutionalization. RESULTS: Among 427 patients, 310 (72.6%) were discharged and were compared with 117 (27.4%) participants admitted to an institution. Female sex (odds ratio [OR]: OR 2.15, 95% confidence interval [CI]: CI 1.22-3.78), prevalent delirium (OR 3.19, 95% CI 1.33-7.64), subsyndromal delirium (OR 2.72, 95% CI 1.48-5.01), incident subsyndromal delirium (OR 4.27, 95% CI 2.17-8.39), low dietary intake (OR 2.50, 95% CI 1.35-4.63), and a fall (OR 2.16, 95% CI 1.22-3.84) or a diagnosis of stroke (OR 2.03, 95% CI 1.04-3.94) were independent predictors of institutionalization. CONCLUSIONS: Symptoms of delirium and severe nutritional impairment led patients to geriatric institutions. Therefore, these institutions need to implement policies that address both of these issues.     

Missing links in multiple sclerosis etiology. A working connecting hypothesis

The etiology of multiple sclerosis is still elusive despite an extended patchwork of mechanistic events has been accumulated. In this article, are tentatively identified from scattered literature sources new factors that may link well known characteristic of MS such as the central alteration of BBR selectivity, its association with EBV status and its biased distribution of the globe more comprehensively. The hypothesis proposes that the concomitant important rise in some heterophilic antibodies (anti Neu5Gc) which activate BBB endothelial cells and in the frequency of anti EBV committed T cells and of memory B infected cells with EBV contemporary to EBV infection play a major role in MS etiology. In addition, the hypothesis proposes new possible explanations for the elevated risk of MS in specific geographical area.     

CpG-ODN-induced sustained expression of BTLA mediating selective inhibition of human B cells

BTLA (B- and T-lymphocyte attenuator) is a prominent co-receptor that is structurally and functionally related to CTLA-4 and PD-1. In T cells, BTLA inhibits TCR-mediated activation. In B cells, roles and functions of BTLA are still poorly understood and have never been studied in the context of B cells activated by CpG via TLR9. In this study, we evaluated the expression of BTLA depending on activation and differentiation of human B cell subsets in peripheral blood and lymph nodes. Stimulation with CpG upregulated BTLA, but not its ligand: herpes virus entry mediator (HVEM), on B cells in vitro and sustained its expression in vivo in melanoma patients after vaccination. Upon ligation with HVEM, BTLA inhibited CpG-mediated B cell functions (proliferation, cytokine production, and upregulation of co-stimulatory molecules), which was reversed by blocking BTLA/HVEM interactions. Interestingly, chemokine secretion (IL-8 and MIP1β) was not affected by BTLA/HVEM ligation, suggesting that BTLA-mediated inhibition is selective for some but not all B cell functions. We conclude that BTLA is an important immune checkpoint for B cells, as similarly known for T cells.     

Antibiotic prescribing in patients with COVID-19: rapid review and meta-analysis

BackgroundThe proportion of patients infected with SARS-CoV-2 that are prescribed antibiotics is uncertain, and may contribute to patient harm and global antibiotic resistance.ObjectiveThe aim was to estimate the prevalence and associated factors of antibiotic prescribing in patients with COVID-19.Data SourcesWe searched MEDLINE, OVID Epub and EMBASE for published literature on human subjects in English up to June 9 2020.Study Eligibility CriteriaWe included randomized controlled trials; cohort studies; case series with ≥10 patients; and experimental or observational design that evaluated antibiotic prescribing.ParticipantsThe study participants were patients with laboratory-confirmed SARS-CoV-2 infection, across all healthcare settings (hospital and community) and age groups (paediatric and adult).MethodsThe main outcome of interest was proportion of COVID-19 patients prescribed an antibiotic, stratified by geographical region, severity of illness and age. We pooled proportion data using random effects meta-analysis.ResultsWe screened 7469 studies, from which 154 were included in the final analysis. Antibiotic data were available from 30 623 patients. The prevalence of antibiotic prescribing was 74.6% (95% CI 68.3–80.0%). On univariable meta-regression, antibiotic prescribing was lower in children (prescribing prevalence odds ratio (OR) 0.10, 95% CI 0.03–0.33) compared with adults. Antibiotic prescribing was higher with increasing patient age (OR 1.45 per 10 year increase, 95% CI 1.18–1.77) and higher with increasing proportion of patients requiring mechanical ventilation (OR 1.33 per 10% increase, 95% CI 1.15–1.54). Estimated bacterial co-infection was 8.6% (95% CI 4.7–15.2%) from 31 studies.ConclusionsThree-quarters of patients with COVID-19 receive antibiotics, prescribing is significantly higher than the estimated prevalence of bacterial co-infection. Unnecessary antibiotic use is likely to be high in patients with COVID-19.