Medications for blood pressure, blood glucose, lipids, and anti-thrombotic medications: relationship with cardiovascular disease and death in adults from 21 high-, middle-, and low-income countries with an elevated body mass index.

AIMS: Elevated body mass index (BMI) is an important cause of cardiovascular disease (CVD). The population-level impact of pharmacologic strategies to mitigate the risk of CVD conferred by the metabolic consequences of an elevated BMI is not well described. METHODS AND RESULTS: We conducted an analysis of 145 986 participants (mean age 50 years, 58% women) from 21 high-, middle-, and low-income countries in the Prospective Urban and Rural Epidemiology study who had no history of cancer, ischaemic heart disease, heart failure, or stroke. We evaluated whether the hazards of CVD (myocardial infarction, stroke, heart failure, or cardiovascular death) differed among those taking a cardiovascular medication (n = 29 174; including blood pressure-lowering, blood glucose-lowering, cholesterol-lowering, or anti-thrombotic medications) vs. those not taking a cardiovascular medication (n = 116 812) during 10.2 years of follow-up. Cox proportional hazard models with the community as a shared frailty were constructed by adjusting age, sex, education, geographic region, physical activity, tobacco, and alcohol use. We observed 7928 (5.4%) CVD events and 9863 (6.8%) deaths. Cardiovascular medication use was associated with different hazards of CVD (interaction P < 0.0001) and death (interaction P = 0.0020) as compared with no cardiovascular medication use. Among those not taking a cardiovascular medication, as compared with those with BMI 20 to <25 kg/m2, the hazard ratio (HR) [95% confidence interval (95% CI)] for CVD were, respectively, 1.14 (1.06-1.23); 1.45 (1.30-1.61); and 1.53 (1.28-1.82) among those with BMI 25 to <30 kg/m2; 30 to <35 kg/m2; and ≥35 kg/m2. However, among those taking a cardiovascular medication, the HR (95% CI) for CVD were, respectively, 0.79 (0.72-0.87); 0.90 (0.79-1.01); and 1.14 (0.98-1.33). Among those not taking a cardiovascular medication, the respective HR (95% CI) for death were 0.93 (0.87-1.00); 1.03 (0.93-1.15); and 1.44 (1.24-1.67) among those with BMI 25 to <30 kg/m2; 30 to <35 kg/m2; and ≥35 kg/m2. However, among those taking a cardiovascular medication, the respective HR (95% CI) for death were 0.77 (0.69-0.84); 0.88 (0.78-0.99); and 1.12 (0.96-1.30). Blood pressure-lowering medications accounted for the largest population attributable benefit of cardiovascular medications. CONCLUSION: To the extent that CVD risk among those with an elevated BMI is related to hypertension, diabetes, and an elevated thrombotic milieu, targeting these pathways pharmacologically may represent an important complementary means of reducing the CVD burden caused by an elevated BMI.

Application of antifungal agents in special populations / 中华皮肤科杂志

Antifungal agents have shown good efficacy and tolerability in the general population. However, the antifungal treatment remains a great challenge in some special populations due to their special conditions, such as children, the elderly, pregnant women and patients with hepatic insufficiency. This review summarizes recommendations for the use of common antifungal agents in the above special populations.

Retrospective analysis of 201 clinical isolates of Aspergillus fumigatus from a hospital in Nanjing: clinical characteristics of infected patients and azole resistance / 中华皮肤科杂志

Objective:To summarize clinical characteristics of patients with Aspergillus fumigatus infection in a hospital in Nanjing, to preliminarily assess azole resistance in clinical isolates of Aspergillus fumigatus, and to investigate risk factors for the emergence of azole-resistant Aspergillus fumigatus. Methods:Clinical isolates of Aspergillus fumigatus were collected from inpatients in Department of Laboratory, Nanjing Drum Tower Hospital from March 2017 to February 2021. Clinical data on these infected patients were analyzed, azole sensitivity testing and mutation analysis of the cyp51A gene and its promoter region were performed for these Aspergillus fumigatus isolates. Results:A total of 201 strains of Aspergillus fumigatus were collected, and mainly isolated from sputum specimens. Among the infected patients, there were 131 males and 70 females, and their age were 64.2 ± 15.8 years. The patients were mainly collected from department of respiratory medicine (79 cases), department of intensive medicine (34 cases), department of rheumatology (19 cases), etc. Among these patients, common underlying diseases included interstitial pneumonia (32 cases), malignant tumors (18 cases), pneumonia (13 cases), trauma (12 cases), systemic lupus erythematosus (8 cases), etc. Drug susceptibility testing showed that 6 (2.99%) strains of Aspergillus fumigatus were resistant to itraconazole and posaconazole, and 3 patients infected with azole-resistant Aspergillus fumigatus had used antifungal drugs before testing. Sequencing was performed on the cyp51A gene and its promoter region in the 6 strains of azole-resistant Aspergillus fumigatus, and showed TR34/L98H/S297T/F495I mutation in 5 strains and TR34/L98H mutation in 1 strain. Conclusion:Compared with previously published data about azole resistance in China during 2010 -2015, the resistance of Aspergillus fumigatus to azoles in Nanjing Drum Tower Hospital did not increase from 2017 to 2021, and the mechanism of azole resistance was mostly associated with TR34/L98H/S297T/F495I mutation in the cyp51A gene and its promoter region.

Comparison of drug susceptibility of and drug resistance mutations in fluconazole-resistant Candida albicans strains from superficial and deep infections / 中华皮肤科杂志

Objective:To compare the in vitro susceptibility of fluconazole-resistant Candida albicans strains from superficial and deep infections to 8 antifungal drugs, and to compare drug resistance mutations in these strains. Methods:According to the Clinical and Laboratory Standards Institute (CLSI) protocol M27-A4, 26 deep infection-derived and 33 superficial infection-derived drug-resistant Candida albicans strains were tested for in vitro susceptibility to 8 antifungal drugs (fluconazole, voriconazole, itraconazole, posaconazole, amphotericin B, fluorocytosine, terbinafine, and micafungin) alone or in combination. DNA was extracted from all drug-resistant strains, and mutations in 3 drug resistance genes, including ERG3, ERG11 and FUR1, were detected by PCR. Normally distributed measurement data with homogeneous variance were compared between two groups by using two-independent-sample t test, non-normally distributed measurement data with non-homogeneous variance were compared using Mann-Whitney U test, and enumeration data were compared using chi-square test. Results:The minimum inhibitory concentrations (MICs) of fluconazole, itraconazole, voriconazole, posaconazole and fluorocytosine all significantly differed between the superficial infection group and deep infection group (all P < 0.05) , while there was no significant difference in the MIC of amphotericin B or micafungin between the two groups (both P > 0.05) . The MIC of terbinafine was >64 μg/ml in 96.6% of the above strains, so could not be compared between groups. As combination drug susceptibility testing revealed, the combination of terbinafine with azoles (fluconazole, voriconazole, itraconazole or posaconazole) showed synergistic inhibitory effects against 15 Candida albicans strains (7 strains from deep infections, 8 strains from superficial infections) , with fractional inhibitory concentration (FIC) indices being 0.033 to 0.187; no marked synergistic effect was observed in the combinations between fluorocytosine and azoles, between fluorocytosine and amphotericin B, or between amphotericin B and fluconazole, with the FIC indices being 0.56 to 1.125. The missense mutation V351A in the ERG3 gene was identified in all the 33 (100%) superficial infection-derived strains, as well as in 13 (50%) deep infection-derived strains, and the mutation A353T in the ERG3 gene was identified in 4 (15%) deep infection-derived strains; as for the ERG11 gene, missense mutations identified in the superficial infection-derived strains included I437V (32 strains, 97%) , Y132H (23 strains, 70%) , T123I (16 strains, 48%) , K128T (6 strains, 18%) , D116E (5 strains, 15%) , A114S (4 strains, 12%) , E266D (2 strains, 6%) , G448E (2 strains, 6%) , and G465S (2 strains, 6%) , while missense mutations identified in the deep infection-derived strains included I437V (23 strains, 88%) , E266D (13 strains, 50%) , E260G (5 strains, 19%) , and V488I (4 strains, 15%) ; the missense mutation R101C in the FUR1 gene was identified in 11 (33%) superficial infection-derived strains, but not identified in deep infection-derived strains. Conclusion:The drug susceptibility and drug resistance mutations differed to some extent between superficial infection- and deep infection-derived fluconazole-resistant Candida albicans strains.

Psychosocial Risk Factors and Cardiovascular Disease and Death in a Population-Based Cohort From 21 Low-, Middle-, and High-Income Countries.

Importance: Stress may increase the risk of cardiovascular disease (CVD). Most studies on stress and CVD have been conducted in high-income Western countries, but whether stress is associated with CVD in other settings has been less well studied. Objective: To investigate the association of a composite measure of psychosocial stress and the development of CVD events and mortality in a large prospective study involving populations from 21 high-, middle-, and low-income countries across 5 continents. Design, Setting, and Participants: This population-based cohort study used data from the Prospective Urban Rural Epidemiology study, collected between January 2003 and March 2021. Participants included individuals aged 35 to 70 years living in 21 low-, middle-, and high-income countries. Data were analyzed from April 8 to June 15, 2021. Exposures: All participants were assessed on a composite measure of psychosocial stress assessed at study entry using brief questionnaires concerning stress at work and home, major life events, and financial stress. Main Outcomes and Measures: The outcomes of interest were stroke, major coronary heart disease (CHD), CVD, and all-cause mortality. Results: A total of 118 706 participants (mean [SD] age 50.4 [9.6] years; 69 842 [58.8%] women and 48 864 [41.2%] men) without prior CVD and with complete baseline and follow-up data were included. Of these, 8699 participants (7.3%) reported high stress, 21 797 participants (18.4%) reported moderate stress, 34 958 participants (29.4%) reported low stress, and 53 252 participants (44.8%) reported no stress. High stress, compared with no stress, was more likely with younger age (mean [SD] age, 48.9 [8.9] years vs 51.1 [9.8] years), abdominal obesity (2981 participants [34.3%] vs 10 599 participants [19.9%]), current smoking (2319 participants [26.7%] vs 10 477 participants [19.7%]) and former smoking (1571 participants [18.1%] vs 3978 participants [7.5%]), alcohol use (4222 participants [48.5%] vs 13 222 participants [24.8%]), and family history of CVD (5435 participants [62.5%] vs 20 255 participants [38.0%]). During a median (IQR) follow-up of 10.2 (8.6-11.9) years, a total of 7248 deaths occurred. During the course of follow-up, there were 5934 CVD events, 4107 CHD events, and 2880 stroke events. Compared with no stress and after adjustment for age, sex, education, marital status, location, abdominal obesity, hypertension, smoking, diabetes, and family history of CVD, as the level of stress increased, there were increases in risk of death (low stress: hazard ratio [HR], 1.09 [95% CI, 1.03-1.16]; high stress: 1.17 [95% CI, 1.06-1.29]) and CHD (low stress: HR, 1.09 [95% CI, 1.01-1.18]; high stress: HR, 1.24 [95% CI, 1.08-1.42]). High stress, but not low or moderate stress, was associated with CVD (HR, 1.22 [95% CI, 1.08-1.37]) and stroke (HR, 1.30 [95% CI, 1.09-1.56]) after adjustment. Conclusions and Relevance: This cohort study found that higher psychosocial stress, measured as a composite score of self-perceived stress, life events, and financial stress, was significantly associated with mortality as well as with CVD, CHD, and stroke events.

Association of ultra-processed food intake with risk of inflammatory bowel disease: prospective cohort study.

OBJECTIVE: To evaluate the relation between intake of ultra-processed food and risk of inflammatory bowel disease (IBD). DESIGN: Prospective cohort study. SETTING: 21 low, middle, and high income countries across seven geographical regions (Europe and North America, South America, Africa, Middle East, south Asia, South East Asia, and China). PARTICIPANTS: 116 087 adults aged 35-70 years with at least one cycle of follow-up and complete baseline food frequency questionnaire (FFQ) data (country specific validated FFQs were used to document baseline dietary intake). Participants were followed prospectively at least every three years. MAIN OUTCOME MEASURES: The main outcome was development of IBD, including Crohn's disease or ulcerative colitis. Associations between ultra-processed food intake and risk of IBD were assessed using Cox proportional hazard multivariable models. Results are presented as hazard ratios with 95% confidence intervals. RESULTS: Participants were enrolled in the study between 2003 and 2016. During the median follow-up of 9.7 years (interquartile range 8.9-11.2 years), 467 participants developed incident IBD (90 with Crohn's disease and 377 with ulcerative colitis). After adjustment for potential confounding factors, higher intake of ultra-processed food was associated with a higher risk of incident IBD (hazard ratio 1.82, 95% confidence interval 1.22 to 2.72 for ≥5 servings/day and 1.67, 1.18 to 2.37 for 1-4 servings/day compared with <1 serving/day, P=0.006 for trend). Different subgroups of ultra-processed food, including soft drinks, refined sweetened foods, salty snacks, and processed meat, each were associated with higher hazard ratios for IBD. Results were consistent for Crohn's disease and ulcerative colitis with low heterogeneity. Intakes of white meat, red meat, dairy, starch, and fruit, vegetables, and legumes were not associated with incident IBD. CONCLUSIONS: Higher intake of ultra-processed food was positively associated with risk of IBD. Further studies are needed to identify the contributory factors within ultra-processed foods. STUDY REGISTRATION: ClinicalTrials.gov NCT03225586.

Clinical diagnosis and treatment of tinea of vellus hair / 中华皮肤科杂志

Tinea of vellus hair is caused by dermatophyte infection of vellus hairs, and commonly affects children. It usually occurs on the face, and clinically manifests as annular or semi-annular erythema gradually spreading to the surrounding area, with central clearing and a slightly elevating border covered with papules and papulovesicles. Intense inflammation, which may manifest as pustules, erosions, exudation, scales and crusts, can be observed in patients with severe tinea of vellus hair. Direct microscopy of fungi showed abundant hyphae and/or spores on vellus hairs. Topical antifungal therapy is usually ineffective, and systemic antifungal therapy should be considered. In order to reduce the high rate of missed diagnosis and misdiagnosis, and to improve clinicians′ understanding of this disease, this review summarizes the incidence, clinical manifestations, diagnosis and treatment of tinea of vellus hair.

Research progress in antifungal resistance mechanisms in Candida auris / 中华微生物学和免疫学杂志

Candida auris ( C. auris) is a recently emerged multidrug-resistant fungal pathogen, featured by difficulty in identification, high mortality and easy spread in hospital environments. Furthermore, C. auris is resistant to various frontline antifungals. However, the mechanisms governing drug resistance remain unclear. This review summarized the mechanisms of triazole resistance in C. auris, including ERG11 missense mutations or overexpression, the activity of efflux pumps, missense mutations in TAC1 B, the gain of an extra copy of chromosomeⅤ, the role of Hsp90 and biofilm formation. In addition, the factors associated with the resistance to other drugs including echinocandins, polyenes, nucleoside analogues and acrylamide were also reviewed.

Progress in mechanisms and immunological treatment of chronic mucocutaneous candidiasis associat-ed with congenital IL-17 pathway deficiency / 中华微生物学和免疫学杂志

Chronic mucocutaneous candidiasis (CMC) is a rare, persistent and recurrent infection affecting skin, nails, and oral and genital mucosae. It is mainly caused by Candida albicans and hard to be cured with routine antifungal therapy. Usually, CMC is a primary immunodeficiency disease and can be di-vided into two categories. The most common one is CMC disease ( CMCD) , which defined as Candida infec-tion confined to the surface of the skin and mucous membranes and not complicated by systemic Candida al-bicans infection or other clinical symptoms. The other category is systemic CMC ( SCMC) complicated by in-fections caused by other pathogens, systemic invasive fungal infections, or other clinical symptoms apart from the symptoms of CMCD. It is currently believed that both CMCD and SCMC are related to immunodeficiency caused by gene mutations related to IL-17 signal pathway. The inhibited Th17 proliferation, decreased secre-tion of IL-17 or IL-22 cytokine, or increased IL-17 or IL-22 neutralizing antibody induced by the mutations promoted the susceptibility to Candida or other pathogens. In the treatment of CMC, in addition to the tradi-tional antifungal drugs such as azoles, polyenes and echinocandins, biological agents and target gene therapy offer potential new therapeutic strategies. This article reviewed the association between congenital immunode-ficiency in the IL-17 signaling pathway and CMC, and the possible immunological therapeutic approaches and new therapeutic targets.

Progress in mechanisms and immunological treatment of chronic mucocutaneous candidiasis associated with congenital IL-17 pathway deficiency / 中华微生物学和免疫学杂志

Chronic mucocutaneous candidiasis (CMC) is a rare, persistent and recurrent infection affecting skin, nails, and oral and genital mucosae. It is mainly caused by Candida albicans and hard to be cured with routine antifungal therapy. Usually, CMC is a primary immunodeficiency disease and can be divided into two categories. The most common one is CMC disease (CMCD), which defined as Candida infection confined to the surface of the skin and mucous membranes and not complicated by systemic Candida albicans infection or other clinical symptoms. The other category is systemic CMC (SCMC) complicated by infections caused by other pathogens, systemic invasive fungal infections, or other clinical symptoms apart from the symptoms of CMCD. It is currently believed that both CMCD and SCMC are related to immunodeficiency caused by gene mutations related to IL-17 signal pathway. The inhibited Th17 proliferation, decreased secretion of IL-17 or IL-22 cytokine, or increased IL-17 or IL-22 neutralizing antibody induced by the mutations promoted the susceptibility to Candida or other pathogens. In the treatment of CMC, in addition to the traditional antifungal drugs such as azoles, polyenes and echinocandins, biological agents and target gene therapy offer potential new therapeutic strategies. This article reviewed the association between congenital immunodeficiency in the IL-17 signaling pathway and CMC, and the possible immunological therapeutic approaches and new therapeutic targets.