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991.

Background

The MENSA trial assessed the efficacy and safety of mepolizumab in patients with severe eosinophilic asthma. This report describes the efficacy and safety of mepolizumab in Japanese patients from MENSA.

Methods

A post hoc analysis of the Japanese subgroup from the randomized, double-blind, placebo-controlled, double-dummy, Phase III MENSA trial (NCT01691521). Patients ≥12 years with severe eosinophilic asthma received mepolizumab 75 mg intravenously (IV), 100 mg subcutaneously (SC), or placebo, every 4 weeks for 32 weeks. The primary endpoint was the annualized rate of exacerbations. Secondary and other endpoints included annualized rate of exacerbations requiring emergency department (ED) visit/hospitalization, morning peak expiratory flow (PEF), St George's Respiratory Questionnaire (SGRQ) score and eosinophil counts. Adverse events (AEs) were monitored.

Results

In the Japanese subgroup (N = 50), the rate of clinically significant exacerbations was reduced by 90% (rate ratio [RR]: 0.10; 95% confidence interval [CI]: 0.02–0.57; P = 0.010) with mepolizumab IV and 62% (RR: 0.38; 95% CI: 0.12–1.18; P = 0.094) with mepolizumab SC, versus placebo. No exacerbations requiring ED visit/hospitalization were reported with mepolizumab IV; exacerbations were reduced by 73% (RR: 0.27; 95% CI: 0.06–1.29; P = 0.102) with mepolizumab SC versus placebo. Compared with placebo, mepolizumab IV and SC numerically increased morning PEF from baseline by 40 L/min and 13 L/min, improved quality of life by greater than the minimal clinically important difference (SGRQ: 9.5 [P = 0.083] and 7.9 [P = 0.171] points) and reduced eosinophil counts. AE incidence was similar between treatments. Results were broadly consistent with the overall population.

Conclusions

Mepolizumab was efficacious and well tolerated in Japanese patients with severe eosinophilic asthma, producing similar responses to the overall MENSA population.  相似文献   
992.

Background

Hepatitis E virus (HEV) infection in patients with pre-existing liver disease has shown high morbidity and lethality. The consequences of HEV superinfection in patients with chronic hepatitis C virus (HCV) infection are not fully understood. This study aimed to evaluate the association between the presence of anti-HEV antibodies, liver cirrhosis, and insulin resistance.

Methods

A total of 618 patients chronically infected with HCV were included from three reference centers for viral hepatitis in São Paulo, Brazil. Presence of anti-HEV IgG was assessed by enzyme-linked immunosorbent assay (WANTAI HEV-IgG ELISA).

Results

The seroprevalence of anti-HEV in patients with cirrhosis was significantly higher than in patients without cirrhosis (13.2% vs 8%, OR = 1.74, p = 0.04). Seropositivity for anti-HEV, adjusted for sex, age, and HCV genotype showed an association trend with hepatic cirrhosis (aOR = 1.75, p = 0.059). Presence of HEV antibodies, adjusted for age, body mass index and cirrhosis, was shown to be independently associated with insulin resistance (aOR: 4.39; p = 0.045).

Conclusion

Patients with chronic hepatitis C are under risk of hepatitis E virus superinfection in Brazil. The trend toward association between cirrhosis and previous HEV infection suggests that it may accelerate liver fibrosis in patients with chronic hepatitis C. In addition, previous infection by HEV is independently associated with insulin resistance in the studied population, which may be an extra-hepatic manifestation of hepatitis E that persists after resolution of the active infection, and may contribute to fibrosis progression.  相似文献   
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Population studies have demonstrated an association between sodium and potassium intake and blood pressure levels and lipids. The aim of this study was to describe the dietary intake and contribution of sodium and potassium to the Mexican diet, and to describe its association with nutrition status and clinical characteristics. We analyzed a national survey with 4219 participants. Dietary information was obtained with a 24-h recall. Foods and beverages were classified according to level of processing. The mean intake (mg/d) of Na was 1512 in preschool children, 2844 in school-age children, 3743 in adolescents, and 3132 in adults. The mean intake (mg/d) of K was 1616 in preschool children, 2256 in school-age children, 2967 in adolescents, and 3401 in adults. Processed and ultra-processed foods (UPF) contribute 49% of Na intake in preschool children, 50% in school-age children, 47% in adolescents, and 39% in adults. Adults with high Na intake had lower serum concentrations of cholesterol, HDL-c, and LDL-c. A significant proportion of the Mexican population has a high intake of Na (64–82%) and low K (58–73%). Strategies to reduce Na and increase K intake need to reduce the possibility of having high BP and serum lipid disturbances.  相似文献   
995.
Extracts (aqueous, methanol and dichloromethane) from Ambrosia tenuifolia, Aristolochia triangularis, Baccharis tucumanensis, Campyloneuron phyllitidis and Eupatorium christieanum were screened for antiinflammatory activity. On the croton oil induced mouse ear oedema test, the highest activities were exhibited by dichloromethane extracts assayed, especially those of Baccharis tucumanensis and Campyloneuron phyllitidis. On the carrageenan mouse paw oedema test, Baccharis tucumanensis and Campyloneuron phyllitidis showed the highest activity.  相似文献   
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997.
Small cell carcinoma (SCC) of the uterine cervix is a rare and aggressive form of neuroendocrine carcinoma, which resembles small cell lung cancer (SCLC) in its histology and poor survival rate. Here, we sought to define the genetic underpinning of SCCs of the uterine cervix and compare their mutational profiles with those of human papillomavirus (HPV)‐positive head and neck squamous cell carcinomas, HPV‐positive cervical carcinomas, and SCLCs using publicly available data. Using a combination of whole‐exome and targeted massively parallel sequencing, we found that the nine uterine cervix SCCs, which were HPV18‐positive (n = 8) or HPV16‐positive (n = 1), harbored a low mutation burden, few copy number alterations, and other than TP53 in two cases no recurrently mutated genes. The majority of mutations were likely passenger missense mutations, and only few affected previously described cancer‐related genes. Using RNA‐sequencing, we identified putative viral integration sites on 18q12.3 and on 8p22 in two SCCs of the uterine cervix. The overall nonsilent mutation rate of uterine cervix SCCs was significantly lower than that of SCLCs, HPV‐driven cervical adeno‐ and squamous cell carcinomas, or HPV‐positive head and neck squamous cell carcinomas. Unlike SCLCs, which are reported to harbor almost universal TP53 and RB1 mutations and a dominant tobacco smoke‐related signature 4, uterine cervix SCCs rarely harbored mutations affecting these genes (2/9, 22% TP53; 0% RB1) and displayed a dominant aging (67%) or APOBEC mutational signature (17%), akin to HPV‐driven cancers, including cervical adeno‐ and squamous cell carcinomas and head and neck squamous cell carcinomas. Taken together, in contrast to SCLCs, which are characterized by highly recurrent TP53 and RB1 alterations, uterine cervix SCCs were positive for HPV leading to inactivation of the suppressors p53 and RB, suggesting that these SCCs are convergent phenotypes.  相似文献   
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