Beyond the kidney: extra-renal manifestations of monogenic nephrolithiasis and their significance.

BACKGROUND: The objective of this study was to explore the frequency of occurrence of extra-renal manifestations associated with monogenic nephrolithiasis. METHODS: A literature review was conducted to identify genes that are monogenic causes of nephrolithiasis. The Online Mendelian Inheritance in Man (OMIM) database was used to identify associated diseases and their properties. Disease phenotypes were ascertained using OMIM clinical synopses and sorted into 24 different phenotype categories as classified in OMIM. Disease phenotypes caused by the same gene were merged into a phenotypic profile of a gene (PPG) such that one PPG encompasses all related disease phenotypes for a specific gene. The total number of PPGs involving each phenotype category was measured, and the median phenotype category was determined. Phenotype categories were classified as overrepresented or underrepresented if the number of PPGs involving them was higher or lower than the median, respectively. Chi-square test was conducted to determine whether the number of PPGs affecting a given category significantly deviated from the median. RESULTS: Fifty-five genes were identified as monogenic causes of nephrolithiasis. A total of six significantly overrepresented and three significantly underrepresented phenotype categories were identified (p < 0.05). Four phenotypic categories (growth, neurological, skeletal, and abdomen/gastrointestinal) are significantly overrepresented after Bonferroni correction for multiple comparisons (p < 0.002). Among all phenotypes, impaired growth is the most common manifestation. CONCLUSION: Recognizing the extra-renal manifestations associated with monogenic causes of kidney stones is critical for earlier diagnosis and optimal care in patients.

Incidence of Kidney Stones in the United States: The Continuous National Health and Nutrition Examination Survey.

PURPOSE: The incidence of kidney stones in the United States is currently unknown. Here, we assessed the incidence of kidney stones using recent, nationally representative data. MATERIALS AND METHODS: We used the National Health and Nutrition Examination Survey (NHANES) from 2015 to 2018. During this time participants were asked, "Have you ever had a kidney stone?" and "In the past 12 months, have you passed a kidney stone?" Demographics analyzed include age, race, gender, body mass index, history of smoking, diabetes, hypertension, hypercholesterolemia and gout. Multivariable models were used to assess the independent impact of subject characteristics on kidney stone prevalence and incidence. RESULTS: Data were available on 10,521 participants older than age 20. The prevalence of kidney stones was 11.0% (95% CI 10.1-12.0). The 12-month incidence of kidney stones was 2.1% (95% CI 1.5-2.7), or 2,054 stones per 100,000 adults. We identified significant relationships between stone incidence and subject age, body mass index, race and history of hypertension. CONCLUSIONS: Here we find a substantially higher 12-month incidence of kidney stones than previous reports. We also validate known risk factors for stone prevalence as associated with incidence. The remarkable incidence and prevalence of stones is concerning and has implications for disease prevention and allocation of medical resources.

Psychosocial mechanisms of a behavioral treatment for urinary incontinence of prostate cancer survivors.

Purpose: We examined underlying psychosocial processes of a behavioral treatment for urinary incontinence (UI) of prostate cancer survivors.Design: Secondary analysis of data collected from a clinical trial.Sample: Two hundred forty-four prostate cancer survivors who participated in a clinical trial of behavioral intervention to UI as intervention or control subjects.Methods: The participants had a 3-month behavioral intervention or usual care and were followed up for an additional 3 months. They were assessed at baseline, 3, and 6 months. Latent growth curve models were performed to examine trajectories of each study variable and relationships among the variables.Findings: Increasing self-efficacy and social support were significantly and independently associated with more reduction of urinary leakage frequency over time.Implications for psychosocial oncology: Providing problem-solving skills and social support, including peer support, are essential for empowering patients to reduce UI.

Green tea-induced epigenetic reactivation of tissue inhibitor of matrix metalloproteinase-3 suppresses prostate cancer progression through histone-modifying enzymes.

Green tea polyphenols (GTPs) and their major constituent, epigallocatechin-3-gallate (EGCG), have been reported to demonstrate many interesting biological activities, including anticancer properties. Recent studies on prostate cancer provide strong evidence that epigenetic mechanisms are major players in the regulation of matrix metalloproteinases (MMPs) and their binding partner tissue inhibitor of MMPs (TIMPs) involved in prostate cancer progression. Here we demonstrate that GTP/EGCG mediate epigenetic reactivation of TIMP-3 that plays a key role in suppressing invasiveness and cancer progression. Treatment of human prostate cancer DUPRO and LNCaP cells with 10 µg/mL GTP and 20 µM EGCG induced TIMP-3 mRNA and protein expression. This transcriptional activation of TIMP-3 was associated with the decrease in the expression of both enhancers of zeste homolog 2 (EZH2) and its catalytic product trimethylation of histone H3 at lysine 27 (H3K27me3) repressive marks at the TIMP-3 promoter with an accompanying increase in histone H3K9/18 acetylation. In addition, GTP/EGCG treatment significantly reduced class I histone deacetylase (HDAC) activity/expression and EZH2 and H3K27me3 levels in prostate cancer cells. EGCG/GTP exposure also reduced MMP-2/MMP-9 gelatinolytic activity and abrogated invasion and migration capabilities in these cells. Silencing of EZH2 and class I HDACs strikingly increased the expression of TIMP-3 independent of DNA methylation. Furthermore, clinical trials performed on patients undergoing prostatectomy consuming 800 mg EGCG (Polyphenon E) up to 6 weeks and grade-matched controls demonstrate an increase in plasma TIMP-3 levels. A marked reduction in class I HDACs activity/expression and EZH2 and H3K27me3 levels were noted in GTP-supplemented prostate tissue. Our findings highlight that TIMP-3 induction, as a key epigenetic event modulated by green tea in restoring the MMP:TIMP balance suppresses prostate cancer progression.

Mood outcomes of a behavioral treatment for urinary incontinence in prostate cancer survivors.

PURPOSE: This study aimed to assess whether prostate cancer survivors who received a behavioral intervention to urinary incontinence had experienced a significant mood improvement. METHODS: One hundred fifty-three prostate cancer survivors with persistent incontinence were included in this secondary data analysis. They were randomly assigned to usual care or interventions that provided pelvic floor muscle exercises and self-management skills. All subjects had measures of anxiety, depression, and anger at baseline, 3 months (post-intervention), and 6 months (follow-up). Negative binomial regression analysis was performed to examine the group status, daily leakage frequency at 3 months, and their interactions at 3 months as predictors for mood outcomes at 6 months, controlling for demographic and medical variables. RESULTS: The main effect of daily leakage frequency at 3 months significantly predicted anxiety at 6 months (p < .01). The group main effect on any mood outcomes at 6 months was not statistically significant. The interaction between the group and 3-month leakage had a significant effect on anxiety; intervention subjects achieving a significant leakage reduction at 3 months exhibited significantly less anxiety at 6 months than other subjects (p = .04). Age, employment status, and receiving surgery at baseline were significantly associated with less anxiety, depression, and anger at 6 months. CONCLUSIONS: Reduced urinary incontinence significantly predicted less anxiety, especially among the intervention subjects. The findings suggest a significant association between a behavioral therapy of urinary incontinence and anxiety reduction in prostate cancer survivors.

Effects of Patient Centered Interventions on Persistent Urinary Incontinence after Prostate Cancer Treatment: A Randomized, Controlled Trial.

PURPOSE: We examined whether an intervention combining pelvic floor muscle exercise and symptom self-management would improve urinary continence and quality of life in patients with prostate cancer. MATERIALS AND METHODS: In a randomized, controlled, longitudinal clinical trial 279 patients with prostate cancer with persistent urinary incontinence were randomized to 1 of 3 groups, including biofeedback pelvic floor muscle exercise plus a support group, the biofeedback exercise plus telephone contact and usual care without intervention. The biofeedback plus support and plus telephone groups received 1 session of biofeedback assisted exercise and 6 biweekly sessions of problem solving therapy. This delivered symptom management skills through a peer support group or telephone contacts for 3 months. All subjects were assessed in blinded fashion at baseline, and 3 and 6 months for urinary leakage frequency, leakage amount and disease specific quality of life. RESULTS: A total of 244 subjects completed the study. The biofeedback plus support and biofeedback plus telephone groups had a lower frequency of daily urinary leakage than the group with usual care without intervention at 3 months (p=0.019 and p≤0.001, respectively) but not at 6 months. The biofeedback plus support group but not the biofeedback plus telephone group had 13.3 gm lower leakage at 6 months than the usual care group (p=0.003). Overall the biofeedback plus support and plus telephone groups reported less symptom severity (p≤0.001) and fewer incontinence problems (p≤0.01) than the usual care group at 6 months. CONCLUSIONS: Study findings show that pelvic floor muscle exercise practice plus symptom self-management in a peer support setting can significantly improve urinary continence and quality of life in patients with prostate cancer.

Favorable Safety Outcomes of Delayed Primary Closure of Large Fournier's Gangrene Skin Defects.

OBJECTIVE: To assess the feasibility and safety of delayed primary closure (DPC) in Fournier's gangrene (FG) patients with large genital defects. METHODS: A single institution retrospective review was performed from October 2020 to December 2022 of adult males that underwent DPC for FG. All patients underwent standard medical management and were assessed for DPC eligibility by the urology service. Clinical data on patient factors and outcomes were collected, and descriptive statistics were assessed. RESULTS: Of 16 patients that underwent DPC, the average age was 61.1years and body mass index was 34.6 kg/m2. Median Charlson Comorbidity Index was 3.5 (IQR 2-5.3) and Fournier's Gangrene Severity Index was 6.5 (IQR 4.8-8). Median number of debridements was 2.5 (IQR 2-3), with a time to closure of 6.5days (IQR 3-11) and length of stay of 13days (IQR 9-16.3). Mean genital defect size was 119 cm2 (range 44-346 cm2). Eight patients (50%) were closed using scrotal flaps alone while other patients had advancement flaps using the inner thigh, lower abdomen, and perineum. The majority of patients were discharged home directly (63%). There were four Clavien-Dindo III complications: two partial flap necrosis, one wound dehiscence, and one instance of bleeding. Of patients with follow-up, 6/15 (40.0%) had no known complications. CONCLUSION: DPC is safe and effective for a range of patients presenting with FG. Patients with large defects may benefit from less complex wound management and direct discharge home.

Vascularized cadaveric fibula flap for treatment of erectile dysfunction following failure of penile implants.

INTRODUCTION: Postpriapism erectile dysfunction in patients with sickle cell disease is a particularly devastating condition. Where penile implants have failed, there is no good surgical alternative at present. Free tissue transfer is fraught with risks in patients with sickle cell disease and are not the best option for treatment. AIM: To describe a new surgical technique involving prefabrication of a bone flap for treatment of erectile dysfunction in a patient with sickle cell disease. METHODS: The descending branch of the lateral circumflex femoral artery was isolated and implanted within a cadaveric bone segment. The prefabricated flap was then transferred 2 months later as a neophallus for penile autoaugmentation. RESULTS: Bone scan showed viability of the bone flap after transfer. The patient was able to have vaginal intercourse and successfully achieve orgasm 2 months after the second stage surgery. CONCLUSIONS: Prefabrication of a cadaveric bone flap and subsequent transfer is a novel and effective technique for treatment of erectile dysfunction refractory to medical management. This technique may be particularly useful for "implant cripples," who have no other surgical option.

Il-1 beta-induced post-transition effect of NF-kappaB provides time-dependent wave of signals for initial phase of intrapostatic inflammation.

OBJECTIVE: Our previous findings have shown that systemic administration of interleukin (IL)-1 beta induces up-regulation of nuclear factor-kappa B (NF-kappaB) in mouse prostate tissue that may be responsible for leukocyte extravasation into prostate stroma. It has been hypothesized that NF-kappaB plays a role in the development of prostatitis, and that NF-kappaB activation might provide chemoattractive signals for leukocyte extravasation in the prostate. METHODS: IL-1 beta was administrated intravenously, alone or with dexamethasone (Dex), to separate groups of C57BL/6J mice. Expression of NF-kappaB, chemoattractant receptors, and IL-17F in the prostates of the two groups of mice at various time periods following treatment was evaluated and compared. RESULTS: IL-1 beta administration up-regulated NF-kappaB/p65 activity in the mouse prostate. IL-1 beta administration promoted extravasation and accumulation of CD45+ mononuclear cells but not neutrophils in the mouse prostate stroma. IL-1 beta administration provided earlier (4 hr) CXCR1/IL-8RA receptor expression in mouse prostate as a first signal, inducing capillary homing, adhesion, and initial extravasation of mononuclear cells into the prostate tissue. IL-1 beta administration also induced relatively late (24 hr) up-regulation of VCAM1 in the endothelial cells of microvessels and of IL-17F in prostate epithelium and in stromal infiltrating leukocytes. Concomitant administration of Dex, a known NF-kappaB inhibitor, resulted in significantly down-regulated IL-1 beta-induced NF-kappaB/p65 activity, as well as reduced expression of chemokine receptors and IL-17F in mouse prostate tissue. CONCLUSION: Systemic IL-1 beta administration induces NF-kappaB-responsive genes to promote aberrant NF-kappaB/p65 activity, which may be critical in the development of prostatitis through its role in the production of chemoattractant signals that promote extravasation and stromal accumulation of mononuclear cells (mainly by CXCR1/IL-8RA), and initiation of a new wave of pro-inflammatory signals favorable to chronic inflammation (mainly by IL-17F).

Measurement of sexual functioning after spinal cord injury: preferred instruments.

BACKGROUND/OBJECTIVE: To determine the utility of certain instruments to assess sexuality and fertility after SCI, an expert panel identified key areas to study and evaluated available instruments. These were rated according to certain predefined criteria. METHODS: The authors divided sexual issues into male and female sexual function, male reproductive function, and female reproductive function. The instruments that have been used most frequently to measure these aspects of sexual function over the past 5 years were identified by expert consensus. Finally, these instruments were subjected to a critical review. RESULTS: The Female Sexual Function Index (FSFI), measurement of vaginal pulse amplitude (VPA), the International Index of Erectile Function (IIEF), and the measurement of ejaculatory function and semen quality were considered appropriate measures to assess sexual responses and reproductive function after SCI. There were no measures identified to assess female reproductive function. CONCLUSIONS: For clinical trials aiming to improve sexual function after SCI, the FSFI or the IIEF is currently preferred. Although VPA is an appropriate means to assess female sexual responses, it is only useful for laboratory studies and is too invasive for use in clinical trials. For assessment of male fertility potential, assessment of ejaculatory capacity and semen analysis are recommended.

Evaluating the impact of the genitourinary multidisciplinary tumour board: Should every cancer patient be discussed as standard of care?

INTRODUCTION: We sought to prospectively evaluate the effectiveness of the multidisciplinary tumour board (MTB) on altering treatment plans for genitourinary (GU) cancer patients. METHODS: All GU cancer patients seen at our tertiary care hospital are discussed at MTB. We prospectively collected data on adult patients discussed over a continuous, 20-month period. Physicians completed a survey prior to MTB to document their opinion on the likelihood of change in their patient's treatment plan. Logistic regression was used to asses for factors associated with a change by the MTB, including patient age or sex, malignancy type, the predicted treatment plan, and the provider's years of experience or fellowship training. RESULTS: A total of 321 cancer patients were included. Patients were primarily male (84.4%) with a median age of 67 (range 20-92) years old. Prostate (38.9%), bladder (31.8%), and kidney cancer (19.6%) were the most common malignancies discussed. A change in management plan following MTB was observed in 57 (17.8%) patients. The physician predicted a likely change in six (10.5%) of these patients. Multivariate logistic regression did not determine physician prediction to be associated with treatment plan change, and the only significant variable identified was a plan to discuss multiple treatment options with a patient (odds ratio 2.46; 95% confidence interval 1.09-9.54). CONCLUSIONS: Routine discussion of all urologic oncology cases at MTB led to a change in treatment plan in 17.8% of patients. Physicians cannot reliably predict which patients have their treatment plan altered. Selectively choosing patients to be presented likely undervalues the impact of a multidisciplinary approach to care.