Axonics® system for treatment of overactive bladder syndrome and urinary urgency incontinence.

Introduction: Overactive bladder and urge urinary incontinence affect millions of women and men and results in billions of dollars in health-care expenses. First- and second-line therapy includes behavioral modifications and/or pharmacotherapies however, many patients' symptoms remain or progress on these treatments. There has been concern regarding the detrimental side effects of the most widely prescribed medications for these bladder symptom management.Areas covered: As a result, there has been increased interest in continuous sacral neuromodulation, an FDA approved therapy for refractory urinary urgency and urge urinary incontinence. In this article, we specifically review current research on the efficacy and patient/provider satisfaction and safety profile of the Axonics® System. In addition, we address the current state of sacral neuromodulation and potential future direction and applicability.Expert opinion: The Axonics® system is a safe effective device for the treatment of overactive bladder and urinary urge incontinence. Additionally, it affords patient's the convenience of a rechargeable, compact, MRI safe system. It should be noted that the rechargeable system, while allowing for approximately 15 years of battery and lead life, may have its challenges in terms of charge burden. Furthermore, this system is easily adapted for experienced implanters of sacral neuromodulating devices.

Inflammation appears as high Prostate Imaging-Reporting and Data System scores on prostate magnetic resonance imaging (MRI) leading to false positive MRI fusion biopsy.

Purpose: To investigate if inflammation as a potential cause of false-positive lesions from recent UroNav magnetic resonance imaging (MRI) fusion prostate biopsy patients. Materials and Methods: We retrospectively identified 43 men with 61 MRI lesions noted on prostate MRI before MRI ultrasound-guided fusion prostate biopsy. Men underwent MRI with 3T Siemens TIM Trio MRI system (Siemens AG, Germany), and lesions were identified and marked in DynaCAD system (Invivo Corporation, USA) with subsequent biopsy with MRI fusion with UroNav. We obtained targeted and standard 12-core needle biopsies. We retrospectively reviewed pathology reports for inflammation. Results: We noted a total of 43 (70.5%) false-positive lesions with 28 having no cancer on any cores, and 15 lesions with cancer noted on systematic biopsy but not in the target region. Of the men with cancer, 6 of the false positive lesions had inflammation in the location of the targeted region of interest (40.0%, 6/15). However, when we examine the 21/28 lesions with an identified lesion on MRI with no cancer in all cores, 54.5% had inflammation on prostate biopsy pathology (12/22, p=0.024). We noted the highest proportion of inflammation. Conclusions: Inflammation can confound the interpretation of MRI by mimicking prostate cancer. We suggested focused efforts to differentiate inflammation and cancer on prostate MRI.

Microbiome diversity in carriers of fluoroquinolone resistant Escherichia coli.

Purpose: Fluoroquinolone-resistant (FQR) Escherichia coli causes transrectal prostate biopsy infections. In order to reduce colonization of these bacteria in carriers, we would like to understand the surrounding microbiome to determine targets for decolonization. Materials and Methods: We perform an observational study to investigate the microbiome differences in men with and without FQR organisms found on rectal culture. A rectal swab with two culturettes was performed on men before an upcoming prostate biopsy procedure as standard of care to perform "targeted prophylaxis." Detection of FQR was performed by the standard microbiology lab inoculates the swab onto MacConkey agar containing ciprofloxacin. The extra swab was sent for 16S rRNA amplicon sequencing (MiSeq paired-end) using the V1V2 primer. Alpha and beta-diversity analysis were performed using QIIME. We used PERMANOVA to evaluate the statistical significance of beta-diversity distances within and between groups of interest. Results: We collected 116 rectal swab samples before biopsy for 16S rRNA amplicon sequencing. We identified 18 isolates (15.5%, 18/116) that were positive and had relative reduced diversity profiles (p<0.05). Enterobacteriaceae were significantly over-represented in the FQR subjects (adjusted p=0.03). Conclusions: Microbiome analysis determined that men colonized with FQR bacteria have less diverse bacterial communities (dysbiosis), higher levels of Enterobacteriaceae and reduced levels of Prevotella disiens. These results may have implications in pre/probiotic intervention studies.

Local Antibiogram Predicts Appropriate Antibiotic Selection for Prostate Biopsy Prophylaxis.

INTRODUCTION: We evaluated our local antibiogram to determine the accuracy of its use in antibiotic augmentation before transrectal prostate biopsy. METHODS: We analyzed pre-transrectal prostate biopsy rectal swabs from January 2016 to September 2017 at the South Texas Veterans Health Care System (STVHCS). A query was run on pre-procedure rectal swabs positive for fluoroquinolone resistance in men undergoing transrectal prostate biopsy during this time. Culture results and antibiotic resistance profiles were recorded and compared to the proportion of antibiotic resistance in the STVHCS 2016 antibiogram. RESULTS: We identified 611 patients who underwent rectal culture before transrectal prostate biopsy, of which 98 were ciprofloxacin resistant Escherichia coli isolates. Our cohort demonstrated 80% sensitivity to ciprofloxacin compared to the STVHCS antibiogram sensitivity of 65% (p <0.001). Gentamicin demonstrated similar sensitivities between the antibiogram and cohort (90% and 88%, respectively). There were no statistically significant differences between the STVHCS antibiogram and the sensitivity profiles of our rectal swab cohort except for ampicillin/sulbactam, which was 57% in the antibiogram and 32% in our cohort (p=0.019). Of the ciprofloxacin resistant E. coli identified 4% (4 of 98) were considered extended spectrum beta-lactamase producers. CONCLUSIONS: Overall, resistance patterns in ciprofloxacin resistant E. coli isolates from our study population are consistent with the STVHCS antibiogram. Therefore, a local antibiogram may be used in an implementation strategy for targeted antibiotics or augmentation of fluoroquinolone prophylaxis for transrectal prostate biopsy.

Metabolic Biosynthesis Pathways Identified from Fecal Microbiome Associated with Prostate Cancer.

BACKGROUND: The fecal microbiome is associated with prostate cancer risk factors (obesity, inflammation) and can metabolize and produce various products that may influence cancer but have yet to be defined in prostate cancer. OBJECTIVE: To investigate gut bacterial diversity, identify specific metabolic pathways associated with disease, and develop a microbiome risk profile for prostate cancer. DESIGN, SETTING, AND PARTICIPANTS: After prospective collection of 133 rectal swab samples 2 wk before the transrectal prostate biopsy, we perform 16S rRNA amplicon sequencing on 105 samples (64 with cancer, 41 without cancer). Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) was applied to infer functional categories associated with taxonomic composition. The p values were adjusted using the false discovery rate. The α- and ß-diversity analyses were performed using QIIME. The Mann-Whitney U test was employed to evaluate the statistical significance of ß-diversity distances within and between groups of interest, and least absolute shrinkage and selection operator (LASSO) regression analysis was used to determine pathway significance. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The detection of prostate cancer on transrectal prostate needle biopsy and 16s microbiome profile. RESULTS AND LIMITATIONS: We identified significant associations between total community composition and cancer/non-cancer status (Bray-Curtis distance metric, p<0.01). We identified significant differences in enrichments of Bacteroides and Streptococcus species in cancer (all p<0.04). Folate (LDA 3.8) and arginine (LDA 4.1) were the most significantly altered pathways. We formed a novel microbiome-derived risk factor for prostate cancer based on 10 aberrant metabolic pathways (area under curve=0.64, p=0.02). CONCLUSIONS: Microbiome analyses on men undergoing prostate biopsy noted mostly similar bacterial species diversity among men diagnosed with and without prostate cancer. The microbiome may have subtle influences on prostate cancer but are likely patient-specific and would require paired analysis and precise manipulation, such as improvement of natural bacterial folate production. PATIENT SUMMARY: Microbiome evaluation may provide patients with personalized data regarding the presence or absence of particular bacteria that have metabolic functions and implications regarding prostate cancer risk. The study provides a basis to investigate the manipulation of aberrant microbiomes to reduce prostate cancer risk.

Large intra-abdominal seminoma in a left undescended testicle complicated by torsion.

A 39-year-old man presented with a 2-day history of worsening constant, dull diffuse lower abdominal pain with associated constipation and known history of left undescended testicle. He was evaluated at an outside hospital where a non-contrasted CT scan revealed a 20 cm well-circumscribed soft tissue mass within the pelvis.He was referred and further imaging revealed a 12 cm heterogeneous mass with foci of air that appeared to be contiguous with the left spermatic cord. This constellation of findings could represent torsion of undescended left testicle with infarction or underlying malignancy. Tumour markers were only significant for elevated lactate dehydrogenase of 1445. A subsequent ultrasound-guided biopsy of the mass demonstrated seminoma.Surgical resection revealed a large intra-abdominal mass emanating from the left spermatic cord with 270° of torsion. There appeared to be a left atrophic remnant testicle at the base of the mass with final pathology confirming the diagnosis of classic seminoma.

Monitoring metabolic side effects of atypical antipsychotics in people with an intellectual disability.

This audit was undertaken prospectively to examine the compliance of a group of psychiatrists against guidelines they developed for monitoring the onset of metabolic syndrome, a potential side effect of antipsychotic medication, especially second generation or atypical ones. Phase 1 of the audit was to set standards by a questionnaire survey of participating psychiatrists against Consensus Guidelines on monitoring (American Diabetic Association, 2004), which they favoured. The results led to modifying these guidelines to develop minimum acceptable standards against which their practice was audited in Phase 2. Although in Phase 1, 77% of the psychiatrists felt that they did some baseline recording, Phase 2 finding did not corroborate this--only 53.8% of the notes recorded the assessment of risk factors in personal history; 37.5% risk factors in family history; 31.7% baseline weight and 26.4% baseline blood sugar/lipid levels. In Phase 1, 85% of the psychiatrists thought that they carried out some of the recommended monitoring; our audit found the records of weight monitoring in 69.7% of the notes and blood sugar and lipids monitoring in 44.2%. People with intellectual disability have a shorter life expectancy and increased risk of early death when compared with the general population. Obesity is already a health issue for people with intellectual disability. We discuss the challenges faced by psychiatrists in implementing their own minimum acceptable standards and suggest measures to reduce the metabolic risk associated with antipsychotic medication through increasing awareness--use of information leaflets in accessible format, health promotion and use of side effect checklists and improving access--by working collaboratively with general practitioners utilising the forum of annual health checks.

Hodgkin lymphoma risk: role of genetic polymorphisms and gene-gene interactions in DNA repair pathways.

DNA repair variants may play a potentially important role in an individual's susceptibility to developing cancer. Numerous studies have reported the association between genetic single nucleotide polymorphisms (SNPs) in DNA repair genes and different types of hematologic cancers. However, to date, the effects of such SNPs on modulating Hodgkin lymphoma (HL) risk have not yet been investigated. We hypothesized that gene-gene interaction between candidate genes in direct reversal, nucleotide excision repair (NER), base excision repair (BER) and double strand break (DSB) pathways may contribute to susceptibility to HL. To test this hypothesis, we conducted a study on 200 HL cases and 220 controls to assess associations between HL risk and 21 functional SNPs in DNA repair genes. We evaluated potential gene-gene interactions and the association of multiple polymorphisms in a chromosome region using a multi-analytic strategy combining logistic regression, multi-factor dimensionality reduction and classification and regression tree approaches. We observed that, in combination, allelic variants in the XPC Ala499Val, NBN Glu185Gln, XRCC3 Thr241Me, XRCC1 Arg194Trp, and XRCC1 399Gln polymorphisms modify the risk for developing HL. Moreover, the cumulative genetic risk score revealed a significant trend where the risk for developing HL increases as the number of adverse alleles in BER and DSB genes increase. These findings suggest that DNA repair variants in BER and DSB pathways may play an important role in the development of HL.

Modulation of Radiation-Induced Genetic Damage by HCMV in Peripheral Blood Lymphocytes from a Brain Tumor Case-Control Study.

Human cytomegalovirus (HCMV) infection occurs early in life and viral persistence remains through life. An association between HCMV infection and malignant gliomas has been reported, suggesting that HCMV may play a role in glioma pathogenesis and could facilitate an accrual of genotoxic damage in the presence of g-radiation; an established risk factor for gliomas. We tested the hypothesis that HCMV infection modifies the sensitivity of cells to γ-radiation-induced genetic damage. We used peripheral blood lymphocytes (PBLs) from 110 glioma patients and 100 controls to measure the level of chromosome damage and cell death. We evaluated baseline, HCMV-, γ-radiation and HCMV + γ-radiation induced genetic instability with the comprehensive Cytokinesis-Blocked Micronucleus Cytome (CBMN-CYT). HCMV, similar to radiation, induced a significant increase in aberration frequency among cases and controls. PBLs infected with HCMV prior to challenge with γ-radiation led to a significant increase in aberrations as compared to baseline, γ-radiation and HCMV alone. With regards to apoptosis, glioma cases showed a lower percentage of induction following in vitro exposure to γ-radiation and HCMV infection as compared to controls. This strongly suggests that, HCMV infection enhances the sensitivity of PBLs to γ-radiation-induced genetic damage possibly through an increase in chromosome damage and decrease in apoptosis.

Reactive sulphur species: an in vitro investigation of the oxidation properties of disulphide S-oxides.

We have recently proposed that disulphide S-monoxides (thiosulphinates) and disulphide S-dioxides (thiosulphonates) are formed from their parent disulphides and 'reactive oxygen species' during oxidative stress. These 'reactive sulphur species' are themselves strong oxidizing agents that preferably attack the thiol functionality. We now show that under conditions where disulphides show little effect, disulphide S-oxides rapidly modify metallothionein, alcohol and glyceraldehyde 3-phosphate dehydrogenases and a zinc finger-protein fragment in vitro. The known antioxidants ascorbate, NADH, trolox and melatonin are unable to inhibit this oxidation pathway and only an excess of the cellular redox-buffer glutathione quenches the disulphide S-oxide activity. These results suggest that, under conditions of oxidative stress, despite the presence of high concentrations of antioxidants, reactive sulphur species formation may occur and inhibit the function of thiol-dependent proteins. Such a characterization of the disulphide S-oxide-oxidation pathway might also account for some previously observed anomalies in protein oxidation.