Dengue NS1 antibodies are associated with clearance of viral NS1.

BACKGROUND: Dengue vascular permeability syndrome is the primary cause of death in severe dengue infections. The protective versus potentially pathogenic role of dengue NS1 antibodies are not well understood. The main goal of this analysis was to characterize the relationship between free NS1 concentration and NS1 antibody titers in primary and secondary dengue infection in order to better understand the presence and duration of NS1 antibody complexes in clinical dengue infections. METHODS: Hospitalized participants with acute dengue infection were recruited from Northern Colombia between 2018 to 2020. Symptom assessment including dengue signs and symptoms, chart review and blood collection was performed. Primary versus secondary Dengue was assessed serologically. NS1 titers and anti-NS1 antibodies were measured daily. RESULTS: Patients with secondary infection have higher antibody titers than those in primary infection, and we find a negative correlation between anti-NS1 antibody titer and NS1 protein. We demonstrate that in a subset of secondary infection, there are indeed NS1 antibody-antigen complexes at the admission day during the febrile phase that are not detectable by the recovery phase. Furthermore, dengue infection status is associated with higher circulating sialidases. DISCUSSION: The negative correlation between antibody and protein suggests that antibodies may play a role in clearing this viral protein.

International time trends and differences in topical actinic keratosis therapy utilization.

Background: Actinic Keratoses (AK) are precancerous lesions that can lead to Squamous Cell Carcinoma. International differences in the utilization of topical medications to treat AK are not well described. Objectives: To describe international differences in topical AK medication utilization, including associations of countries' economic status with AK medication utilization. Methods: We used IQVIA MIDAS pharmaceutical sales data for 65 countries (42 high-income, 24 middle-income) from April 2011 to December 2021. We calculated each country's quarterly utilization of medications in grams per 1000 population. We used univariable linear regression to assess the association between country economic status and AK medication utilization. Results: High-income countries used 15.37 more grams per 1000 population of 5-fluorouracil (95% CI: 9.68, 21.05), 4.64 more grams per 1000 population of imiquimod (95% CI: 3.45, 5.83), and 0.32 more grams per 1000 population of ingenol mebutate (95% CI: 0.05, 0.60). Limitations: Missing medication utilization data for some countries. Conclusion: High-income countries use more topical AK therapies than middle-income countries.

Association of Countries' Atopic Dermatitis Burden and Sociodemographic Index with Topical Calcineurin Inhibitor Utilization.

Background: There is limited knowledge on international trends in topical calcineurin inhibitor (TCI) utilization. Objective: To describe international TCI utilization trends from 2012 to 2019 and evaluate the relationship of country-level economic status, geographic location, and atopic dermatitis (AD) disease burden with drug utilization. Methods: We used IQVIA MIDAS® pharmaceutical quarterly sales data to attain country-level purchasing of TCIs in grams from 2012 to 2019. A multivariable linear regression estimated the association between countries' sociodemographic index (SDI), AD disability-adjusted life year (DALY) rates, and geographic location with TCI utilization. Results: A total of 68 countries were included in our analysis. From 2012 to 2019, overall TCI utilization increased by 66% but remained 11.2 times higher in high-sociodemographic compared with low-middle/low-sociodemographic countries. SDI and geographic location were associated with greater TCI utilization in multivariable analyses, whereas AD DALY rates were not. High-SDI countries used 21,476 grams (95% confidence interval [CI]: 11,915 to 31,036) and high-middle SDI countries used 9,403 grams (95% CI: -393 to 19,200) more TCIs per 100,000 people compared with low-middle/low-SDI countries, respectively. Northern hemisphere countries used 8,588 grams more TCIs per 100,000 people (95% CI: 612 to 16,564). Conclusions: We demonstrated greater TCI utilization among high-SDI compared with lower SDI countries.

Novel Insights into the Cardioprotective Effects of the Peptides of the Counter-Regulatory Renin-Angiotensin System.

Currently, cardiovascular diseases are a major contributor to morbidity and mortality worldwide, having a significant negative impact on both the economy and public health. The renin-angiotensin system contributes to a high spectrum of cardiovascular disorders and is essential for maintaining normal cardiovascular homeostasis. Overactivation of the classical renin-angiotensin system is one of the most important pathophysiological mechanisms in the progression of cardiovascular diseases. The counter-regulatory renin-angiotensin system is an alternate pathway which favors the synthesis of different peptides, including Angiotensin-(1-7), Angiotensin-(1-9), and Alamandine. These peptides, via the angiotensin type 2 receptor (AT2R), MasR, and MrgD, initiate multiple downstream signaling pathways that culminate in the activation of various cardioprotective mechanisms, such as decreased cardiac fibrosis, decreased myocardial hypertrophy, vasodilation, decreased blood pressure, natriuresis, and nitric oxide synthesis. These cardioprotective effects position them as therapeutic alternatives for reducing the progression of cardiovascular diseases. This review aims to show the latest findings on the cardioprotective effects of the main peptides of the counter-regulatory renin-angiotensin system.

Inpatient Management of Hidradenitis Suppurativa: A Delphi Consensus Study.

Inpatient hospitalization of individuals with hidradenitis suppurativa (HS) has increased. Inpatient services may not be familiar enough with this disease to understand how to manage severe HS and/or HS flares. It would be beneficial to the inpatient medical community to establish consensus recommendations on holistic inpatient care of patients with HS. A survey study was developed and distributed by Wake Forest University School of Medicine (Winston-Salem, North Carolina). A total of 26 dermatologists participated in the Delphi process, and the process was conducted in 2 rounds. Participants voted on proposal statements using a 9-point scale (1=very inappropriate; 9=very appropriate). Statements were developed using current published guidelines for management of HS and supportive care guidelines for other severe inpatient dermatologic diseases. A total of 50 statements were reviewed and voted on between the 2 rounds. Consensus was determined using the RAND/UCLA Appropriateness Method. Twenty-six dermatologists completed the first-round survey, and 24 completed the second-round survey. The 40 consensus recommendations generated through these surveys can serve as a resource for providers caring for inpatients with HS.

Cytokine and T cell responses in post-chikungunya viral arthritis: A cross-sectional study.

OBJECTIVE: To define the relationship between chronic chikungunya post-viral arthritis disease severity, cytokine response and T cell subsets in order to identify potential targets for therapy. METHODS: Participants with chikungunya arthritis were recruited from Colombia from 2019-2021. Arthritis disease severity was quantified using the Disease Activity Score-28 and an Arthritis-Flare Questionnaire adapted for chikungunya arthritis. Plasma cytokine concentrations (interleukin (IL)-1ß, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, interferon-γ and tumor necrosis factor (TNF)) were measured using a Meso Scale Diagnostics assay. Peripheral blood T cell subsets were measured using flow cytometry. RESULTS: Among participants with chikungunya arthritis (N = 158), IL-2 levels and frequency of regulatory T cells (Tregs) were low. Increased arthritis disease activity was associated with higher levels of inflammatory cytokines (IL-6, TNF and CRP) and immunoregulatory cytokine IL-10 (p<0.05). Increased arthritis flare activity was associated with higher Treg frequencies (p<0.05) without affecting T effector (Teff) frequencies, Treg/Teff ratios and Treg subsets. Finally, elevated levels of IL-2 were correlated with increased Treg frequency, percent Tregs out of CD4+ T cells, and Treg subsets expressing immunosuppressive markers, while also correlating with an increased percent Teff out of live lymphocytes (p<0.05). CONCLUSION: Chikungunya arthritis is characterized by increased inflammatory cytokines and deficient IL-2 and Treg responses. Greater levels of IL-2 were associated with improved Treg numbers and immunosuppressive markers. Future research may consider targeting these pathways for therapy.