Browsing by Author "Taylor, Stephanie"

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    Development of Alcohol-Associated Hepatitis Is Associated With Specific Changes in Gut-Modified Bile Acids
    (Wolters Kluwer, 2022) Muthiah, Mark D.; Smirnova, Ekaterina; Puri, Puneet; Chalasani, Naga; Shah, Vijay H.; Kiani, Calvin; Taylor, Stephanie; Mirshahi, Faridoddin; Sanyal, Arun J.; Medicine, School of Medicine
    The perturbations in bile acids (BAs) in alcohol-associated hepatitis (AH) and its relationship to disease severity is not well defined. The aims of this study were to define (1) the effects of heavy alcohol consumption on BAs and related microbiome, (2) the additional changes with AH, and (3) the relationship of these changes to disease severity. In this multicenter study, plasma and fecal BAs and related microbiome were interrogated in healthy individuals, heavy drinking controls (HDCs) without overt liver disease, and AH. Compared to healthy controls, HDCs had increased glycine-conjugated 7α and 27α primary BAs and increased secondary BA glycocholenic sulfate (multiple-comparison adjusted P < 0.05 for all). Plasma-conjugated cholic and chenodeoxycholic acid increased in AH along with the secondary BAs ursodeoxycholic and lithocholic acid (P < 0.001 for all), whereas deoxycholic acid decreased; however fecal concentrations of both deoxycholic acid and lithocholic acid were decreased. Glycocholenic acid further increased significantly from HDCs to AH. HDCs and AH had distinct plasma and fecal BA profiles (area under the curve, 0.99 and 0.93, respectively). Plasma taurochenodeoxycholic acid and tauroursodeoxycholic acid were directly related to disease severity, whereas fecal ursodeoxycholic acid was inversely related. The fecal abundance of multiple taxa involved in formation of secondary BAs, especially deoxycholic acid (Clostridium cluster XIVa) was decreased in AH. Multiple genera containing taxa expressing 3α, 3β, 7α, and 7β epimerases were decreased with concordant changes in fecal BAs that required these functions for formation. Conclusion: There are distinct changes in BA-transforming microbiota and corresponding BAs in AH that are related to disease severity.
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    Jarisch-Herxheimer Reaction After Benzathine Penicillin G Treatment in Adults With Early Syphilis: Secondary Analysis of a Randomized Clinical Trial
    (American Medical Association, 2025-02-03) Dionne, Jodie A.; Zhu, Chunming; Mejia-Galvis, Jorge; Workowski, Kimberly; Batteiger, Teresa A.; Dombrowski, Julia C.; Mayer, Kenneth H.; McNeil, Candice J.; Seña, Arlene C.; Taylor, Stephanie; Wiesenfeld, Harold C.; Hamill, Matthew M.; Perlowski, Charlotte; Hook, Edward W., III; Medicine, School of Medicine
    Importance: Syphilis rates have been increasing in the US for the past decade. The incidence of the Jarisch-Herxheimer reaction (JHR) after penicillin treatment for early syphilis is reported to range from 8% to 56%. Objectives: To prospectively assess the incidence of JHR signs and symptoms among adults with early syphilis treated with benzathine penicillin G and to document factors associated with JHR and benzathine penicillin G treatment response outcomes. Design, setting, and participants: The main study was designed as a phase 4 randomized clinical trial to compare the treatment efficacy of 1 vs 3 doses of benzathine penicillin G in adults with early syphilis, measured as serologic response at 6 months. A total of 249 adults with or without HIV were screened and enrolled between October 31, 2018, and March 3, 2020. Participants were screened and enrolled at 10 US study sites in the Sexually Transmitted Infections Clinical Trials Group. Statistical analysis for this secondary analysis took place between March 2023 and August 2024. Intervention: Participants received a first dose of benzathine penicillin G, 2.4 million units intramuscularly, at the enrollment visit. The JHR assessment window was day 1 to day 7 after the first dose of benzathine penicillin G. Main outcomes and measures: Primary outcomes in this study were the incidence of symptoms consistent with JHR within 7 days after benzathine penicillin G treatment. Unelicited and elicited symptoms were assessed by participant self-report using a standardized checklist during contact made by a study clinician. Factors associated with JHR were collected at baseline, and serologic treatment response was assessed at 6 months. Posttreatment incident JHR symptoms were captured as safety outcomes for this trial. Analysis was performed on an intention-to-treat basis. Results: Of 249 participants, the median age was 32 years (IQR, 27-41 years), 242 (97.2%) were men, and 153 (61.4%) were living with HIV. One or more JHR symptoms occurred in 59 participants (23.7%) treated for early syphilis, with a median symptom onset at 4.9 hours (IQR, 3.0-9.2 hours) and a median duration of 12.8 hours (IQR, 5.0-24.0 hours). Symptom onset was within 12 hours of treatment for 49 of 57 participants (86.0%). Among 59 symptomatic participants, myalgias (30 [50.8%]), chills (27 [45.8%]), weakness (23 [39.0%]), and feverishness (21 [35.6%]) were most common. In adjusted models, JHR was associated with secondary syphilis (adjusted odds ratio [AOR], 2.91 [95% CI, 1.51-5.61]) and the absence of HIV (AOR for living with HIV, 0.49 [95% CI, 0.26-0.94]). The proportion of participants with a serologic treatment response to benzathine penicillin G at 6 months was higher among participants with JHR (84.7% [50 of 59] vs 68.9% [131 of 190] without JHR). Conclusions and relevance: In this prespecified secondary analysis of a randomized clinical trial of early syphilis treatment wtih benzathine penicillin G in adults, approximately 1 in 4 participants experienced short-lived JHR symptoms, which were associated with secondary syphilis stage, lack of HIV, and successful treatment outcomes at 6 months. These messages could be used in patient counseling.