Advances in the Understanding and Treatment of Male Urethritis.

Neisseria gonorrhoeae and Chlamydia trachomatis are well-documented urethral pathogens, and the literature supporting Mycoplasma genitalium as an etiology of urethritis is growing. Trichomonas vaginalis and viral pathogens (herpes simplex virus types 1 and 2 and adenovirus) can cause urethritis, particularly in specific subpopulations. New data are emerging regarding the potential role of bacterial vaginosis-associated bacteria in urethritis, although results are inconsistent regarding the pathogenic role of Ureaplasma urealyticum in men. Mycoplasma hominis and Ureaplasma parvum do not appear to be pathogens. Men with suspected urethritis should undergo evaluation to confirm urethral inflammation and etiologic cause. Although nucleic acid amplification testing would detect N. gonorrhoeae and C. trachomatis (or T. vaginalis if utilized), there is no US Food and Drug Administration-approved clinical test for M. genitalium available in the United States at this time. The varied etiologies of urethritis and lack of diagnostic options for some organisms present treatment challenges in the clinical setting.

Lifestyle and Risk of Chronic Prostatitis/Chronic Pelvic Pain Syndrome in a Cohort of United States Male Health Professionals.

PURPOSE: Although chronic prostatitis/chronic pelvic pain syndrome is a prevalent urological disorder among men of all ages, its etiology remains unknown. Only a few previous studies have examined associations between lifestyle factors and chronic prostatitis/chronic pelvic pain syndrome, of which most were limited by the cross-sectional study design and lack of control for possible confounders. To address these limitations we performed a cohort study of major lifestyle factors (obesity, smoking and hypertension) and chronic prostatitis/chronic pelvic pain syndrome risk in the HPFS (Health Professionals Follow-up Study), a large ongoing cohort of United States based male health professionals. MATERIALS AND METHODS: The HPFS includes 51,529 men who were 40 to 75 years old at baseline in 1986. At enrollment and every 2 years thereafter participants have completed questionnaires on lifestyle and health conditions. In 2008 participants completed an additional set of questions on recent chronic prostatitis/chronic pelvic pain syndrome pain symptoms modified from the NIH (National Institutes of Health)-CPSI (Chronic Prostatitis Symptom Index) as well as questions on approximate date of symptom onset. The 653 participants with NIH-CPSI pain scores 8 or greater who first experienced symptoms after 1986 were considered incident chronic prostatitis/chronic pelvic pain syndrome cases and the 19,138 who completed chronic prostatitis/chronic pelvic pain syndrome questions but did not report chronic prostatitis/chronic pelvic pain syndrome related pain were considered noncases. RESULTS: No associations were observed for baseline body mass index, waist circumference, waist-to-hip ratio, cigarette smoking and hypertension with chronic prostatitis/chronic pelvic pain syndrome risk (each OR ≤1.34). CONCLUSIONS: In this large cohort study none of the lifestyle factors examined was associated with chronic prostatitis/chronic pelvic pain syndrome risk. As the etiology of chronic prostatitis/chronic pelvic pain syndrome remains unknown, additional prospective studies are needed to elucidate modifiable risk factors for this common condition.

Ca(2+)/calmodulin-dependent protein kinase II is associated with pelvic pain of neurogenic cystitis.

Interstitial cystitis/painful bladder syndrome is a chronic bladder inflammatory disease of unknown etiology that is often regarded as a neurogenic cystitis. Interstitial cystitis is associated with urothelial lesions, voiding dysfunction, and pain in the pelvic/perineal area. In this study, we used a murine neurogenic cystitis model to identify genes participating in the development of pelvic pain. Neurogenic cystitis was induced by the injection of Bartha's strain of pseudorabies virus (PRV) into the abductor caudalis dorsalis (tail base) muscle of female C57BL/6J mice. Mice infected with PRV developed progressive pelvic pain. The sacral spinal cord was harvested on postinfection days (PID) 2 and 4, and gene expression was analyzed by microarrays and confirmed by quantitative RT-PCR. On PID 2, the overall expression profile was similar to that of uninfected sacral spinal cord; by PID 4, there were substantial differences in expression of multiple functional classes of genes, especially inflammation. Analysis of pain-signaling pathways at the dorsal horn suggested that Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) contributes to neurogenic cystitis pelvic pain. Consistent with this, CaMKIIδ expression exhibited a mast cell-dependent increase in the sacral spinal cord at the mRNA level, and phospho-CaMKII immunoreactivity in the dorsal horn was increased on postinfection day (PID) 4 during PRV infection. Finally, intrathecal injection of the CaMKII inhibitor KN-93 attenuated the PRV pain response. These data suggest that CaMKII plays a functional role in pelvic pain due to neurogenic cystitis.

Minimum data elements for research reports on CFS.

Chronic fatigue syndrome (CFS) is a debilitating condition that has received increasing attention from researchers in the past decade. However, it has become difficult to compare data collected in different laboratories due to the variability in basic information regarding descriptions of sampling methods, patient characteristics, and clinical assessments. The issue of variability in CFS research was recently highlighted at the NIH's 2011 State of the Knowledge of CFS meeting prompting researchers to consider the critical information that should be included in CFS research reports. To address this problem, we present our consensus on the minimum data elements that should be included in all CFS research reports, along with additional elements that are currently being evaluated in specific research studies that show promise as important patient descriptors for subgrouping of CFS. These recommendations are intended to improve the consistency of reported methods and the interpretability of reported results. Adherence to minimum standards and increased reporting consistency will allow for better comparisons among published CFS articles, provide guidance for future research and foster the generation of knowledge that can directly benefit the patient.

The role of phenotyping in chronic prostatitis/chronic pelvic pain syndrome.

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a chronic pain syndrome identified by the presence of noninfectious pelvic or perineal pain lasting longer than 3 months. Current diagnoses and treatments for the syndrome solely depend on and target symptoms, respectively. Thus far, the mechanistic disturbances responsible for the pathogenesis of CP/CPPS have remained largely elusive and treatments, and therefore, continue to be ineffective. To move toward successful management and treatment of CP/CPPS, it is necessary to elicit the underlying biological mechanisms responsible for the syndrome. Therefore, a phenotyping system that is able to bridge the gap between current symptom-based diagnosis and future mechanistic approaches to diagnosis and treatment is needed. In this article, we examine current CP/CPPS phenotyping systems, analyze their utility, and make suggestions for changes in clinical approaches to the syndrome that would both promulgate a mechanistic understanding and advance treatment approaches.

Alkaline Phosphatase Kinetics Predict Metastasis among Prostate Cancer Patients Who Experience Relapse following Radical Prostatectomy.

INTRODUCTION: Metastasis prostate cancer (CaP) occurs in a small fraction of patients. Improved prognostication of disease progression is a critical challenge. This study examined alkaline phosphatase velocity (APV) in predicting distant metastasis-free survival (DMFS). MATERIALS AND METHODS: This retrospective cohort study examined CaP patients enrolled in the Center for Prostate Disease Research (CPDR) multicenter national database who underwent RP and experienced BCR (n=1783). BCR was defined as a PSA ≥ 0.2 ng/mL at ≥ 8 weeks post-RP, followed by at least one confirmatory PSA ≥ 0.2 ng/mL or initiation of salvage therapy. APV was computed as the slope of the linear regression line of all alkaline phosphatase (AP) values after BCR and prior to distant metastasis. APV values in the uppermost quartile were defined as "rapid" and compared to the lower three quartiles combined ("slower"). Unadjusted Kaplan Meier (KM) estimation curves and multivariable Cox proportional hazards analysis were used to examine predictors of DMFS. RESULTS: Of the 1783 eligible patients who experienced post-RP BCR, 701 (39.3%) had necessary AP data for APV calculation. PSA doubling time (PSADT) and APV were strongly associated (p=0.008). No differences in APV were observed across race. In KM analysis, significantly poorer DMFS was observed among the rapid versus slower APV group (Log-rank p=0.003). In multivariable analysis, a rapid APV was predictive of a twofold increased probability of DMFS (HR = 2.2; 95% CI = 1.2, 3.9; p = 0.008), controlling for key study covariates. CONCLUSIONS: Building on previous work, this study found that rapid APV was a strong predictor of DMFS for a broader group of CaP patients, those who undergo post-RP BCR who were enrolled in a longitudinal cohort with long-term follow-up and equal health care access. APV is worth considering as a complementary clinical factor for predicting DMFS.

Physical activity and chronic prostatitis/chronic pelvic pain syndrome.

PURPOSE: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a prevalent urologic disorder among men, but its etiology is still poorly understood. Our objective was to examine the relation between physical activity and incidence of CP/CPPS in a large cohort of male health professionals. METHODS: We conducted a prospective cohort study among men in the Health Professionals Follow-up Study followed from 1986 to 2008. The study population included 20,918 men who completed all CP/CPPS questions on the 2008 questionnaire. Leisure-time physical activity, including type and intensity of activity, was measured by questionnaire in 1986. A National Institute of Health Chronic Prostatitis Symptom Index pain score was calculated on the basis of the responses on the 2008 questionnaire. Participants with pain scores ≥8 were considered CP/CPPS cases (n = 689). RESULTS: Higher leisure-time physical activity was associated with lower risk of CP/CPPS. The multivariable-adjusted odds ratio comparing >35.0 to ≤3.5 MET·h·wk of physical activity was 0.72 (95% confidence interval, 0.56-0.92; P for trend <0.001). Observed inverse associations between physical activity and CP/CPPS were similar for both moderate- and vigorous-intensity activities. Sedentary behavior, measured as time spent watching television, was not associated with risk of CP/CPPS (P for trend = 0.64). CONCLUSIONS: Findings from this study, the first large scale and most comprehensive study to date on this association, suggest that higher levels of leisure-time physical activity may lower risk of CP/CPPS in middle-age and older men.

Chronic Fatigue Syndrome: The Current Status and Future Potentials of Emerging Biomarkers.

Chronic fatigue syndrome (CFS) remains an incompletely characterized illness, in part due to controversy regarding its definition, biological basis and diagnosis. Biomarkers are objective measures that may lead to improvements in our understanding of CFS by providing a more coherent and consistent approach to study, diagnosis and treatment of the illness. Such metrics may allow us to distinguish between CFS subtypes - each defined by characteristic biomarkers - currently conflated under the single, heterogeneous condition of CFS. These delineations, in turn, may guide more granular, focused, and targeted treatment strategies based on more precise characterizations of the illness. Here, we review potential CFS biomarkers related to neurological and immunological components of the illness, and discuss how these biomarkers may be used to move the field of CFS forward, emphasizing clinical utility and potential routes of future research.

Mycoplasma genitalium and preterm delivery at an urban community health center.

OBJECTIVE: To determine the prepartum prevalence of cervical Mycoplasma genitalium colonization and evaluate prospectively whether colonization is associated with preterm delivery among women from a racial/ethnic minority background with a high risk of delivering a low birth weight newborn and a high prevalence of sexually transmitted infections. METHODS: In a prospective cohort study at an urban community health center in Roxbury, MA, USA, 100 women receiving routine prenatal care for singleton pregnancies were enrolled between August 2010 and December 2011. Endocervical samples were tested for M. genitalium, and delivery data were collected. RESULTS: The prevalence of M. genitalium colonization at the first prenatal visit was 8.4%. The incidence of low birth weight was 16.7%. The incidence of preterm delivery among women who were known to have a live birth was 16.7%. The incidence of preterm delivery did not differ with respect to M. genitalium colonization. The crude odds ratio for preterm delivery among women with M. genitalium colonization versus those without was 1.27 (95% confidence interval, 0.02-14.78). CONCLUSION: M. genitalium colonization was not associated with preterm delivery among women with a high incidence of low birth weight newborns and preterm delivery, and a high prevalence of sexually transmitted infections.

Novel PI3Kγ mutation in a 44-year-old man with chronic infections and chronic pelvic pain.

A 44-year-old man is presented here with 14 years of chronic purulent sinusitis, a chronic fungal rash of the scrotum, and chronic pelvic pain. Treatment with antifungal therapy resulted in symptom improvement, however he was unable to establish an effective long-term treatment regimen, resulting in debilitating symptoms. He had undergone extensive work-up without identifying a clear underlying etiology, although Candida species were cultured from the prostatic fluid. 100 genes involved in the cellular immune response were sequenced and a missense mutation was identified in the Ras-binding domain of PI3Kγ. PI3Kγ is a crucial signaling element in leukotaxis and other leukocyte functions. We hypothesize that his mutation led to his chronic infections and pelvic pain.