Efficacy and safety of oral ibrexafungerp in Chinese patients with vulvovaginal candidiasis: a phase III, randomized, double-blind study.

PURPOSE: To evaluate the efficacy and safety of oral ibrexafungerp (HS-10366) versus placebo in Chinese patients with vulvovaginal candidiasis (VVC). METHODS: A double-blind, placebo-controlled, randomized, multicenter phase III study was conducted in symptomatic VVC patients. Patients received (2:1) twice-daily oral ibrexafungerp 300 mg or matching placebo for 1 day. The primary endpoint was clinical cure (vulvovaginal signs and symptoms [VSS] score = 0) at test-of-cure (TOC) on day 11 ± 3. The secondary endpoints included mycological eradication, overall response, and clinical improvement (VSS score ≤ 1) at TOC, and vulvovaginal symptom resolution at follow-up on day 25 ± 4. RESULTS: In total, 360 patients were included in the modified intention-to-treat set (defined as positive Candida cultured and receiving at least one study drug; 239 for ibrexafungerp, 121 for placebo). Compared with placebo, patients receiving ibrexafungerp had a significantly higher proportion of clinical cure (51.0% vs. 25.6%), mycological eradication (55.6% vs. 18.2%), overall response (33.9%, vs. 8.3%) at TOC and complete symptom resolution (74.5% vs. 39.7%, all P < 0.001) at follow-up. Subgroup analysis of clinical cure indicated that patients with C. albicans could benefit from ibrexafungerp over placebo. A similar benefit trend was also observed in those with non-albicans Candida by post-hoc analysis. Further analyses revealed similar efficacy of ibrexafungerp between patients with fluconazole non-susceptible C. albicans and fluconazole susceptible C. albicans regarding clinical cure and mycological eradication. Ibrexafungerp was generally well tolerated. Adverse events were primarily gastrointestinal and were mainly mild in severity. CONCLUSIONS: As a first-in-class antifungal agent, ibrexafungerp demonstrated promising efficacy and favorable safety for VVC treatment in Chinese patients. CHINADRUGTRIALS.ORG. CN REGISTRY NUMBER: CTR20220918.

Characterization of the Microbiome and Host's Metabolites of the Lower Respiratory Tract During Acute Community-Acquired Pneumonia Identifies Potential Novel Markers.

Purpose: Community-acquired pneumonia (CAP) is one of the most frequently encountered infectious diseases worldwide. Few studies have explored the microbial composition of the lower respiratory tract (LRT) and host metabolites of CAP. We analyzed the microbial composition of the LRT and levels of host metabolites to explore new biomarkers for CAP. Patients and Methods: Bronchoalveolar lavage fluid (BALF) was collected from 28 CAP patients and 20 healthy individuals. Following centrifugation, BALF pellets were used for amplicon sequencing of a variable region of the bacterial 16S rDNA gene to characterize the microbial composition. Non-targeted metabolomics was used to detect host's metabolites in the supernatant. Results: Compared with healthy individuals, the bacterial alpha diversity in the LRT of CAP patients was significantly lower in CAP patients (p<0.05). On the bacterial genus level, over 20 genera were detected with lower relative abundance (p<0.05), while the relative abundance of Ruminiclostridium-6 was significantly higher in CAP patients. The levels of the host metabolites dimethyldisulfide, choline, pyrimidine, oleic acid and N-acetyl-neuraminic acid were all increased in BALF of CAP patients (p<0.05), while concentrations of lysophosphatidylcholines (LPC (12:0/0:0)) and phosphatidic acid (PA (20:4/2:0)) were decreased (p<0.05). Furthermore, the relative abundance of Parvimonas, Treponema-2, Moraxella, Aggregatibacter, Filifactor, Fusobacterium, Lautropia and Neisseria negatively correlated with concentrations of oleic acid (p<0.05). A negative correlation between the relative abundance of Treponema-2, Moraxella, Filifactor, Fusobacterium and dimethyldisulfide concentrations was also observed (p<0.05). In contrast, the relative abundance of Treponema-2, Moraxella, Filifactor, and Fusobacterium was found to be positively associated with concentrations of LPC (12:0/0:0) and PA (20:4/2:0) (p<0.05). Conclusion: The composition of the LRT microbiome differed between healthy individuals and CAP patients. We propose that some respiratory microbial components and host metabolites are potentially novel diagnostic markers of CAP.

Is There an Association Between Contraception and Sexual Dysfunction in Women? A Systematic Review and Meta-analysis Based on Female Sexual Function Index.

BACKGROUND: A growing body of research investigates the sexual functioning status in women with contraceptives use; however, the evidence is still inconclusive. AIM: To examine whether contraceptives use is associated with a higher risk of female sexual dysfunction (FSD). METHODS: The electronic databases MEDLINE, Embase, Cochrane Library databases, and PsychINFO were systematically screened for eligible studies before December 2019. We only included those studies assessing women's sexual functioning by the Female Sexual Function Index (FSFI). This study was registered on the PROSPERO (ID: CRD42020167723, http://www.crd.york.ac.uk/PROSPERO). OUTCOMES: The strength of the association between contraceptives use and risk of FSD was presented by calculating the standard mean dierences (SMDs) and the relative risk (RR) with a 95% confidence interval (CI). The pooled results were calculated using a random-effects model. RESULTS: A total of 12 studies (7 cross-sectional studies, 3 cohorts, and 1 case-control study) involving 9,427 participants were included. The mean age in the contraceptive users ranged from 22.5 ± 2.4 years to 38.2 ± 4.6 years, while the mean age in the nonusers was 22.5 ± 2.4 years to 36.0 ± 1.0 years. Pooled results showed that no significant difference in the total FSFI scores was observed between contraceptives use and noncontraception (SMD = -1.03, 95% CI: -2.08 to 0.01, P = .053; heterogeneity: I2 = 98.2%, P < .001). In line with this finding, the pooled RR also yielded no association between contraception use and the risk of FSD (RR = 1.29, 95% CI: 0.72-2.28, P = .392; heterogeneity: I2 = 76.0%, P = .0015). However, the subscale sexual desire showed a significant reduction in women who received contraceptives than those did not use contraception (SMD = -1.17, 95% CI: -2.09 to -0.24, P = .014; heterogeneity: I2 = 97.7%, P < .001), while no significant differences were found in sexual arousal, lubrication, orgasm, satisfaction, and pain domain. CLINICAL IMPLICATIONS: Though evidence from this meta-analysis did not support an association between contraceptives use and the risk of FSD, the sexual desire could be significantly impaired by contraceptives use. STRENGTHS & LIMITATIONS: This is the first meta-analysis quantifying the relationship between contraceptives use and the risks of FSD. However, substantial heterogeneities were presented across the included studies. CONCLUSION: No direct association between contraceptives use and the risk of FSD was found. Nevertheless, declining sexual desire was significantly associated with contraceptives use. Additional double-blind, randomized, placebo-controlled trials are still warranted. Huang M, Li G, Liu J, et al. Is There an Association Between Contraception and Sexual Dysfunction in Women? A Systematic Review and Meta-analysis Based on Female Sexual Function Index. J Sex Med 2020;17:1942-1955.

[A comparative research on the conventional transbronchial needle aspiration and endobronchial ultrasound-guided transbronchial needle aspiration for the diagnosis of mediastinum lesions].

OBJECTIVE: To compare the diagnostical yields and complication of conventional transbronchial needle aspiration (TBNA) and endobronchial ultrasound guided transbronchial needle aspiration (EBUS-TBNA) for the mediastinum lesions under the same condition. METHOD: Ninety-five patients with mediastinal lesions on chest CT were included. Bronchoscopy was performed under the local anesthesia, TBNA, EBUS-TBNA performed sequentially as a single combined procedure. RESULTS: Of the 71 patients confirmed to be malignant, the positive rate of TBNA was 92% (65/71), and 96% (68/71) by EBUS-TBNA. There was no difference in malignant and benign lesions between conventional TBNA and EBUS-TBNA, but the success rate for obtaining adequate samples was higher by EBUS-TBNA (39/95) as compared to TBNA (22/95). Accidental injury of the blood vessels occurred in 7 cases by TBNA as compared to 3 cases by EBUS-TBNA, but the difference was not significant. CONCLUSION: Satisfactory diagnostic yields can be obtained by either conventional TBNA or EBUS-TBNA in skilled hands.