A Host Defense Mechanism Involving CFTR-Mediated Bicarbonate Secretion in Bacterial Prostatitis

BACKGROUND: Prostatitis is associated with a characteristic increase in prostatic fluid pH; however, the underlying mechanism and its physiological significance have not been elucidated. METHODOLOGY/PRINCIPAL FINDINGS: In this study a primary culture of rat prostatic epithelial cells and a rat prostatitis model were used. Here we reported the involvement of CFTR, a cAMP-activated anion channel conducting both Cl(-) and HCO(3)(-), in mediating prostate HCO(3)(-) secretion and its possible role in bacterial killing. Upon Escherichia coli (E. coli)-LPS challenge, the expression of CFTR and carbonic anhydrase II (CA II), along with several pro-inflammatory cytokines was up-regulated in the primary culture of rat prostate epithelial cells. Inhibiting CFTR function in vitro or in vivo resulted in reduced bacterial killing by prostate epithelial cells or the prostate. High HCO(3)(-) content (>50 mM), rather than alkaline pH, was found to be responsible for bacterial killing. The direct action of HCO(3)(-) on bacterial killing was confirmed by its ability to increase cAMP production and suppress bacterial initiation factors in E. coli. The relevance of the CFTR-mediated HCO(3)(-) secretion in humans was demonstrated by the upregulated expression of CFTR and CAII in human prostatitis tissues. CONCLUSIONS/SIGNIFICANCE: The CFTR and its mediated HCO(3)(-) secretion may be up-regulated in prostatitis as a host defense mechanism

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Biological and hormonal markers of chlamydia, human papillomavirus, and bacterial vaginosis among adolescents attending genitourinary medicine clinics

Objective: To assess maturity indices, menstrual patterns, hormonal factors, and risk of adolescent genital tract infections. Methods: Cross sectional study in three genitourinary medicine clinics. Females 17 years or less, within 5 years of menarche, or reporting oligo-amenorrhoea were screened for genital tract infections and menstrual cycle characteristics determined. The outcome measures were risk factors associated with chlamydia, human papillomavirus (HPV DNA) and bacterial vaginosis (BV), separately and pooled. Correlations between estrone-3-glucuronide (E3G) and pregnanediol-3α-glucuronide (P3G) hormone concentrations and chlamydia, HPV, and BV. Results: Among 127 adolescents, HPV was present in 64.4% (95% CI: 54.5 to 74.3), BV in 33.9% (19.1 to 34.5), and chlamydia in 26.8% (19.1 to 34.5). Breast maturity, oligomenorrhoea, and older gynaecological age were associated with lower risk of all infections. After adjustment for calendar age, race, and behavioural factors, gynaecological age remained significant (OR = 0.7, 0.6–0.9; p = 0.008). Behavioural risk factors differed by infection. Smoking was protective for HPV (OR = 0.1, 0.0 to 0.9; p = 0.007), and a recent new partner for chlamydia (OR = 0.3, 0.1 to 0.9; p = 0.024). Sex during menses was associated with increased BV risk (OR = 3.3, 1.5 to 7.2; p = 0.003). Chlamydia was higher among adolescents who used emergency contraception (2.5; 1.1 to 5.9, p = 0.029) and lower among those using condoms at last sex (OR = 0.3, 0.1 to 0.9; p = 0.015). Among 25 adolescents not using hormonal contraceptives, 15 had disturbed or anovulatory cycles. Chlamydia risk was inversely associated with P3G concentrations (Mann-Whitney; p = 0.05). Conclusions: Adolescents engaging in high risk behaviour at a young gynaecological age are susceptible to multiple infections. Adolescent clinical assessment should include gynaecological age

Factors affecting vaginal pH levels among female adolescents attending genitourinary medicine clinics

Objectives: Vaginal pH is related to hormonal status, and adolescents experience disturbed hormonal patterns following menarche. We assessed hormonal factors and risk of abnormal vaginal pH and bacterial vaginosis (BV) among adolescents attending genitourinary medicine (GUM) clinics. Methods: In a cross sectional study adolescents within 5 years of menarche, ⩽17 years, or with oligo-amenorrhoea were recruited. Vaginal pH and BV were assessed and among those not using hormonal contraceptives, estrone-3-glucuronide (E3G) and pregnanediol-3α-glucuronide (P3G) concentrations were measured. Results: Among 102 adolescents, 59.8% (61) had a high vaginal pH (>4.5), which was higher than the prevalence of BV, detected in 33% (34). No association was found between presence of sexually transmitted infections (STI) and vaginal pH. In logistic regression, after controlling for BV and condom use, vaginal pH was positively associated with cervical ectopy (OR = 2.5; 95% CI 1.0 to 6.6, p = 0.05) and STI treatment history (OR = 2.5; 95% CI 0.9 to 6.5, p = 0.07), and negatively associated with use of Depo-Provera (OR = 0.1; 95% CI 0.03 to 0.6, p = 0.003) and recent onset (<12 months) of sexual activity (OR = 0.2; 95% CI 0.1 to 0.7, p = 0.004). Among 23 adolescents not using hormonal contraceptives, a high pH occurred more often in abnormal compared to normal menstrual cycles (OR = 10.8; 95% CI 1.4 to 85.4; p = 0.026). E3G concentrations were inversely correlated with vaginal pH in the follicular phase (Spearman: r = 0.51; p = 0.024). Conclusions: Ectopy and abnormal menstrual cycles are common features of adolescence. Their presence is associated with increased risk of abnormal pH, and may also predispose to BV