Benign prostatic hyperplasia nodules in patients treated with celecoxib and/or finasteride have reduced levels of NADH dehydrogenase [ubiquinone] iron-sulfur protein 3, a mitochondrial protein essential for efficient function of the electron transport chain.

BACKGROUND: Benign prostatic hyperplasia (BPH) is a condition generally associated with advanced age in men that can be accompanied by bothersome lower urinary tract symptoms (LUTS) including intermittency, weak stream, straining, urgency, frequency, and incomplete bladder voiding. Pharmacotherapies for LUTS/BPH include alpha-blockers, which relax prostatic and urethral smooth muscle and 5ɑ-reductase inhibitors such as finasteride, which can block conversion of testosterone to dihydrotestosterone thereby reducing prostate volume. Celecoxib is a cyclooxygenase-2 inhibitor that reduces inflammation and has shown some promise in reducing prostatic inflammation and alleviating LUTS for some men with histological BPH. However, finasteride and celecoxib can reduce mitochondrial function in some contexts, potentially impacting their efficacy for alleviating BPH-associated LUTS. METHODS: To determine the impact of these pharmacotherapies on mitochondrial function in prostate tissues, we performed immunostaining of mitochondrial Complex I (CI) protein NADH dehydrogenase [ubiquinone] iron-sulfur protein 3 (NDUFS3) and inflammatory cells on BPH specimens from patients naïve to treatment, or who were treated with celecoxib and/or finasteride for 28 days, as well as prostate tissues from male mice treated with celecoxib or vehicle control for 28 days. Quantification and statistical correlation analyses of immunostaining were performed. RESULTS: NDUFS3 immunostaining was decreased in BPH compared to normal adjacent prostate. Patients treated with celecoxib and/or finasteride had significantly decreased NDUFS3 in both BPH and normal tissues, and no change in inflammatory cell infiltration compared to untreated patients. Mice treated with celecoxib also displayed a significant decrease in NDUFS3 immunostaining and no change in inflammatory cell infiltration. CONCLUSIONS: These findings suggest that celecoxib and/or finasteride are associated with an overall decrease in NDUFS3 levels in prostate tissues but do not impact the presence of inflammatory cells, suggesting a decline in mitochondrial CI function in the absence of enhanced inflammation. Given that BPH has recently been associated with increased prostatic mitochondrial dysfunction, celecoxib and/or finasteride may exacerbate existing mitochondrial dysfunction in some BPH patients thereby potentially limiting their overall efficacy in providing metabolic stability and symptom relief.

A Brief Intervention on Alcohol Use Disorder Is Associated With Treatment Access for Inpatients With Alcohol-Associated Liver Disease.

BACKGROUND: Alcohol-associated liver disease (ALD) is the most common indication for liver transplantation in the United States. Alcohol use disorder (AUD) treatment is recommended in all patients with ALD and AUD, but it remains underutilized. AIMS: To identify predictors of AUD treatment and to assess 30-day readmission, return to drinking, and 1-year transplant-free survival. METHODS: Retrospective single-center cohort study of consecutive patients hospitalized with ALD and AUD between 2018 and 2020. Patients who died or were lost to follow-up at 90 days after hospitalization were excluded. AUD treatment was defined as receiving medication or participating in residential, outpatient, or support groups within 90 days of discharge. RESULTS: One hundred nine patients were included. Mean age was 51.7 years, and 63% were male. Fifty-six (51%) patients received AUD treatment, and 23 (21%) patients received more than one treatment. Predictors of AUD treatment were younger age (OR, 1.07 [95% CI, 1.04-1.12]; P < 0.001), gastroenterology/hepatology consult (AOR, 8.54 [95% CI, 2.55-39.50]; P = 0.0002), addiction psychiatry consult (AOR, 2.77 [95% CI, 1.16-6.84]; P = 0.02), and a brief AUD intervention (AOR, 18.19 [95% CI, 3.36-339.07]; P = 0.0001). Cirrhosis decompensation, MELD-Na score, and insurance status were not associated with treatment. Thirty-one patients (28.4%) were readmitted, and 29 (26.6%) remained abstinent 30 days from discharge. Patients who received treatment had improved transplant-free survival (HR, 0.44, P = 0.04). CONCLUSION: A brief intervention on AUD had the strongest association with receiving AUD treatment in our cohort. Further efforts to incorporate brief interventions when offering AUD treatment to patients with ALD may be beneficial.