Preliminary Outcomes of the Male Urethral "Mini-Sling": A Modified Approach to the Andrianne Mini-Jupette Procedure With Penile Prosthesis Placement for Climacturia and Mild Stress Urinary Incontinence.

INTRODUCTION: Previous worked showed that the Andrianne Mini-Jupette (AMJ) procedure with inflatable penile prosthesis (IPP) significantly improves climacturia or stress urinary incontinence (SUI) that may accompany erectile dysfunction (ED) after radical prostatectomy. However, with the AMJ procedure, the graft is incorporated into the medial aspect of the corporotomy, thereby requiring a more complex closure. Moreover, in the original report, multiple graft materials were used. AIM: To describe our technique for "male urethral mini-sling" (MUMS) with a Virtue sling mesh, which is a modified approach to the AMJ, and to assess early postoperative outcomes. METHODS: A retrospective chart review was performed for men who underwent IPP and MUMS placement with a modified Virtue mesh by 2 high-volume prosthetic urologic surgeons using the same technique. After proximal urethral exposure, the MUMS is sutured to the latera corpora over the bulbar urethra, proximal to and separate from the planned corporotomy, with care taken to avoid excessive urethral tension. The IPP is then placed in standard fashion. Changes in patient-reported climacturia and pads per day for SUI were assessed before and after surgery. RESULTS: 36 men underwent both IPP and MUMS placement between January 2016-October 2018. Mean patient age was 68 years. Etiology for ED and urinary symptoms was prostatectomy alone in 30 of 36 (83%) and prostatectomy plus radiation in 6 of 36 (17%). Preoperative urinary symptoms included climacturia in 30 of 36 (83%) and SUI in 27 of 36 (75%). Mean (SD) follow-up was 5.9 (3.7) months. Climacturia resolved in 28 of 30 (93%), and SUI improved in 23 of 27 (85%). The mean (SD) number of pads per day for those patients with SUI decreased significantly from 1.4 (1.1) before surgery to 0.4 (0.6) after surgery (P = .02). 1 patient required MUMS explantation for urethral erosion after prolonged postoperative catheterization. CLINICAL IMPLICATIONS: The MUMS with modified Virtue mesh at the time of IPP placement can be used to treat ED with climacturia or mild SUI after radical prostatectomy. STRENGTHS & LIMITATIONS: Strengths include the use of a consistent operative technique with a single graft material by 2 experienced prosthetic urologic surgeons. Limitations include the retrospective study design, use of subjective postoperative outcomes, lack of comparison group, and relatively moderate follow-up duration. CONCLUSIONS: Our early results suggest that the MUMS significantly improves bothersome climacturia and mild SUI in addition to treating ED, with little added morbidity. Although further study, including longer-term follow-up, is needed, this approach may be considered in the appropriately counseled patient. Valenzuela RJ, Ziegelmann MJ, Hillelsohn JH, et al. Preliminary Outcomes of the Male Urethral "Mini-Sling": A Modified Approach to the Andrianne Mini-Jupette Procedure With Penile Prosthesis Placement for Climacturia and Mild Stress Urinary Incontinence. J Sex Med 2019;16:1310-1317.

A Single-Surgeon Retrospective and Preliminary Evaluation of the Safety and Effectiveness of the Penuma Silicone Sleeve Implant for Elective Cosmetic Correction of the Flaccid Penis.

BACKGROUND: Silicone blocks and sleeves are simple devices used in cosmetic surgery. They are generally viewed as safe and effective; however, there is little information on their use in the penis. AIM: This study evaluates a large single-surgeon series using a novel silicone sleeve penile implant (Penuma) to cosmetically correct the flaccid penis. METHODS: 526 patients underwent elective cosmetic penile surgery using a silicone sleeve penile implant between 2009 and 2014. Institutional Review Board approval was obtained for a retrospective analysis, and study consent was obtained from 400 patients. Penile circumference was measured before surgery, immediately after surgery, and 30-90 days after the implant surgery. Using the nonvalidated Augmentation Phalloplasty Patient Selection and Satisfaction Inventory (APPSSI), changes in self-confidence, self-esteem, and satisfaction scores were assayed 6-8 weeks postoperatively. Scores were again assayed 2-6 years postoperatively in 77% of patients. The questionnaires rated patient self-confidence, self-esteem, and satisfaction as very low, low, medium, high, or very high. MAIN OUTCOME MEASURE: Outcomes include changes in penile measurements; changes in APPSSI satisfaction, self-confidence, and self-esteem scores; and incidences of adverse events. RESULTS: In the 400 patients, the implantation of the Penuma silicone implant increased midshaft circumference from an average of 8.5 ± 1.2 cm to 13.4 ± 1.9 cm (56.7% increase; P < .001). A 2-category improvement in self-confidence and self-esteem was noted in 83% of patients 6-8 weeks postoperatively. On long-term follow-up (2-6 years; mean 4 years), 72% patients remained improved (2-category improvement in APPSSI scoring), and 81% of subjects reported "high" or "very high" levels of satisfaction. The most frequently reported postoperative complications were seroma (4.8%), scar formation (4.5%), and infection (3.3%). No patients reported any changes in sexual function, erections, or ejaculation. 3% experienced adverse events necessitating device removal. CLINICAL IMPLICATIONS: The Penuma silicone implant can help patients cosmetically correct the penis with increased flaccid penile girth and achieve enhanced self-confidence and self-esteem over the short- and long term. STRENGTHS AND LIMITATIONS: Strengths include the large number of subjects (400 men) and the long-term follow-up period (2-6 years). Limitations include the retrospective and single-surgeon (inventor) nature of the study; the presence of 126 non-consenting subjects, potentially impacting the complication rate; and the APPSSI's lack of validation. CONCLUSION: Retrospective analysis of 400 men electing to have penile cosmetic correction with the Penuma device demonstrates improvements in girth (56.7% increase) and high and sustained patient satisfaction, self-confidence, and self-esteem with minimal and manageable adverse events. Elist JJ, Valenzuela R, Hillelsohn J, et al. A Single-Surgeon, Retrospective, and Preliminary Evaluation of the Safety and Effectiveness of the Penuma Silicone Sleeve Implant for Elective Cosmetic Correction of the Flaccid Penis. J Sex Med 2018;15:1216-1223.

Andrianne Mini-Jupette Graft at the Time of Inflatable Penile Prosthesis Placement for the Management of Post-Prostatectomy Climacturia and Minimal Urinary Incontinence.

BACKGROUND: After radical prostatectomy (RP), erectile dysfunction, often necessitating the need for inflatable penile prosthesis (IPP) insertion, and urinary incontinence and climacturia can ensue. AIM: To assess the efficacy and safety of the mini-jupette, a mesh used to approximate the medial aspects of the 2 corporotomies at the time of IPP insertion, for the management of climacturia and urine leakage in patients with minimal incontinence. METHODS: We conducted a pilot multicenter study of patients with post-RP erectile dysfunction and climacturia and/or mild urinary incontinence (≤2 pads/day [ppd]) undergoing IPP insertion with concomitant placement of a mini-jupette graft. OUTCOMES: Pre- and postoperative erectile function, continence and climacturia, and overall surgical outcomes were assessed. RESULTS: 38 patients underwent the mini-jupette procedure. The mean age of the population was 65.3 years (SD = 7.7). 30 had post-RP climacturia and 32 patients had post-RP incontinence (mean = 1.3 ppd, SD = 0.8). 31 patients received Coloplast Titan, 4 received AMS 700 LGX, and 3 received AMS 700 CX IPPs. Mean corporotomy size was 2.9 cm (SD = 1.0). Mean graft measurements were 3.2 cm (SD = 0.9) for width, 3.3 cm (SD = 1.3) for length, and 11.0 cm2 (SD = 5.1) for surface area. At a mean follow-up of 5.1 months (SD = 6.9), there were 5 postoperative complications (13.2%) of which 4 required explantation. Climacturia and incontinence were subjectively improved in 92.8% and 85.7%, respectively. Mean ppd decreased by 1.3 postoperatively. CLINICAL IMPLICATIONS: The Andrianne mini-jupette is a feasible adjunct to IPP placement that can be used for subsets of patients with post-RP climacturia and/or minimal incontinence. STRENGTHS AND LIMITATIONS: Strengths of this study include the novel nature of this intervention, the multi-institutional nature of the study, and the promising results demonstrated. Limitations include the retrospective nature of the study and the heterogeneity of the techniques and grafts used by different surgeons involved. CONCLUSION: Longer follow-up and larger patient cohorts are needed to confirm the long-term safety and benefits of this intervention. Yafi FA, Andrianne R, Alzweri L, et al. Andrianne Mini-Jupette Graft at the Time of Inflatable Penile Prosthesis Placement for the Management of Post-Prostatectomy Climacturia and Minimal Urinary Incontinence. J Sex Med 2018;15:789-796.

Sub-Coronal Inflatable Penile Prosthesis Placement With Modified No-Touch Technique: A Step-by-Step Approach With Outcomes.

INTRODUCTION: The surgical treatment of disorders of male sexual function requires specific exposure to correct the underlying problem safely and efficiently. Currently, sub-coronal exposure is used for treatment of phimosis, Peyronie's disease plaque (PDP), and semirigid penile prosthesis insertion. Infra-pubic and scrotal incisions are used for inflatable penile prosthesis (IPP) placement. However, men who present with several disorders might require multiple procedures and surgical incisions. AIM: To report a prospective review of our surgical experience and outcomes with a single sub-coronal incision for IPP placement with a modified no-touch technique. This approach allows for access to the entire corporal body for multiple reconstructive procedures. METHODS: Two hundred men had IPPs placed through a sub-coronal incision using our modified no-touch technique. The penis was degloved to the level of the penoscrotal junction and the dartos muscle was everted and secured to the drapes. This allowed exclusion of the scrotal and penile skin from the operative field. After artificial erection, the patient's corpora were inspected for PDP and other abnormalities. Penoscrotal IPP models were placed in all cases with insertion proximal to the penoscrotal junction. After placement of the IPP, the abnormalities were repaired. MAIN OUTCOME MEASURES: Feasibility of the procedure, operative times, complication rate, utilization of accessory, reconstructive procedures, and post-operative penile length. RESULTS: Of the 200 men who had IPP placement, 92 had PDP that was treated, 106 (53%) consented to circumcision, 24 (12%) had their reservoir placed ectopically, and 31 (16%) had a prosthesis exchanged through the sub-coronal technique. Mean operative time was 73 minutes (39-161 minutes). CONCLUSION: Specialists in the surgical treatment of disorders of male sexual function can perform multiple procedures safely and easily through a modified no-touch single sub-coronal incision. This approach allows access to the entire corporal body, providing excellent visibility and allowing the surgeon to perform multiple penile reconstructive surgeries through a single incision.

Age of onset of myopia predicts risk of high myopia in later childhood in myopic Singapore children.

PURPOSE: To investigate the effect of age of myopia onset on the severity of myopia later in life among myopic children. METHODS: In this prospective study, school children aged 7-9 years from the Singapore Cohort Of the Risk factors for Myopia (SCORM) were followed up till 11 years (n = 928). Age of myopia onset was defined either through questionnaire at baseline (age 7-9 years) or subsequent annual follow-up visits. Age of onset of myopia was a surrogate indicator of duration of myopia progression till age 11 years. Cycloplegic refraction and axial length were measured at every annual eye examination. High myopia was defined as spherical equivalent of ≤-5.0 D. A questionnaire determined the other risk factors. RESULTS: In multivariable regression models, younger age of myopia onset (per year decrease) or longer duration of myopia progression was associated with high myopia (odds ratio (OR) = 2.86; 95% CI: 2.39 to 3.43), more myopic spherical equivalent (regression coefficient (ß) = -0.86 D; 95% CI: -0.93 to -0.80) and longer axial length (ß = 0.28 mm; 95% CI: 0.24 to 0.32) at aged 11 years, after adjusting for gender, race, school, books per week and parental myopia. In Receiver Operating Curve (ROC) analyses, age of myopia onset alone predicted high myopia by 85% (area under the curve = 0.85), while the addition of other factors including gender, race, school, books per week and parental myopia only marginally improved this prediction (area under the curve = 0.87). CONCLUSIONS: Age of myopia onset or duration of myopia progression was the most important predictor of high myopia in later childhood in myopic children. Future trials to retard the progression of myopia to high myopia could focus on children with younger age of myopia onset or with longer duration of myopia progression.

Genetic analysis of SNPs in CACNA1C and ANK3 gene with schizophrenia: A comprehensive meta-analysis.

Recently, genome-wide association studies (GWAS), meta-analyses, and replication studies focusing on bipolar disorder (BD) have implicated the α-1C subunit of the L-type voltage-dependent calcium channel (CACNA1C) and ankyrin 3 (ANK3) genes in BD. Based on the hypothesis that both schizophrenia (SZ) and BD may share some common genetic risk factors, we investigated the association of CACNA1C and ANK3 with SZ using meta-analytic techniques, combining all published data up to April 2015. Nine teams, including four European decent samples and five Asian samples, contributed 14,141 cases and 30,679 controls for the analysis of CACNA1C rs1006737 and SZ. A significant difference was identified between patients and controls for the A-allele of rs1006737 in combined studies (Z = 6.02, P = 1.74E-09), in European studies (Z = 4.08, P = 4.50E-05), and in Asian studies (Z = 4.60, P = 4.22E-06). Meanwhile, for the T-allele of ANK3 rs10761482 (1,794 cases versus 1,395 controls), a significant association was observed in combined samples (Z = 2.06, P = 0.04) and in Asian samples (Z = 3.10, P = 0.002). In summary, our study provides further evidence for the positive association of CACNA1C and ANK3 with SZ. These results support the hypothesis that both SZ and BD share common genetic risk factors. Further research is needed to examine the functions of CACNA1C and ANK3, and their interacting partners in the molecular, developmental, and pathophysiological processes in SZ.

Himplant® subcutaneous penile implant improves penile appearance and erectile dysfunction after radical prostatectomy: a case series.

Erectile dysfunction is a major postoperative complication following radical prostatectomy. Various treatments for post- radical prostatectomy erectile dysfunction including nonsurgical phosphodiesterase-5 inhibitors, intraurethral alprostadil, intracavernosal injections and penile implant prosthesis, often yield suboptimal results. In this prospective single-center case series, we examine the efficacy and outcomes of Himplant®, a subcutaneous silicone penile implant, placement in four patients with post-radical prostatectomy erectile dysfunction who experienced limited benefits with phosphodiesterase-5 inhibitors. Patient data including demographics, prostate cancer diagnoses, erectile dysfunction characteristics, previous treatments, and outcomes were collected. Himplant® placement was performed in a standardized manner through a high scrotal incision in all cases. Follow-up evaluations were conducted to assess the effectiveness of the procedure and any associated complications. Patients were contacted and asked 15 questions regarding satisfaction and erectile function with the responses recorded. This study presents findings of high patient satisfaction, increases in flaccid penile length and girth, no incidence of adverse events, and improved erectile function following Himplant® placement post-radical prostatectomy. Accordingly, we suggest Himplant® placement in patients who are frustrated by their penile appearance and suffering from erectile dysfunction after radical prostatectomy. Further multicenter studies are warranted to validate these findings and assess long-term outcomes and patient-reported satisfaction.

A multi-institutional update on surgical outcomes after penile silicone sleeve implantation.

Background: The increasing popularity of the silicone sleeve penile implant has been accompanied by concerns over potential risks and adverse events. Objectives: To provide multi-institutional data on safety outcomes in patients undergoing silicone sleeve penile implant surgery across high-volume implant surgeons. In addition, we discuss preventative techniques to minimize postoperative complications and the management of these events. Design and methods: We performed a retrospective analysis of men undergoing penile silicone sleeve implants between November 2020 and November 2022 with four surgeons, each from a separate institution. Perioperative and postoperative adverse events, including unsatisfactory cosmetic outcomes requiring revision, were determined by physician follow-up. Flaccid penile length and girth were measured preoperatively and postoperatively. Results: A total of 299 male patients underwent silicone sleeve implant surgery, with an average age of 42.5 ± 10.5 years and an average body mass index of 28.5 ± 4.0. The patient cohort exhibited minimal comorbidities, with 5% having hyperlipidemia, 2% being smokers, 2% having cardiovascular disease, and 1% having diabetes. Patients experienced an average increase of 4.1 ± 1.5 cm in their flaccid penile length (a 50% increase) and an average increase of 3.4 ± 1.5 cm in their flaccid girth (a 37% increase) (p < 0.01). Complication rates included new-onset postoperative erectile dysfunction (0%), infection (1.3%), seroma (2.0%), and erosion (5.0%). The average follow-up time was 11.6 months. Notably, our rates of infection and seroma were lower than those reported in a previous single-center review, while erosion rates were higher. Conclusion: This is the largest study to characterize the safety of the penile silicone sleeve implant across multiple institutions. In men who desire cosmetic size augmentation, silicone sleeve implant surgery is associated with significantly increased flaccid penile length and girth. Complications are mainly cosmetic and may be corrected; however, patients should be appropriately counseled on the risk of erosion, which appears to be higher than previously reported.

Outcomes for penile silicone sleeve surgery This is the largest study to characterize the safety of the penile silicone sleeve implant across multiple institutions. In men who desire cosmetic penile size improvement, the silicone sleeve implant surgery is associated with significantly increased flaccid penile length and girth. Complications are mainly cosmetic and may be corrected, however, patients should be appropriately counseled on the risk of erosion, which appears to be higher than previously reported.

Schizophrenia-Like Deficits and Impaired Glutamate/Gamma-aminobutyric acid Homeostasis in Zfp804a Conditional Knockout Mice.

BACKGROUND AND HYPOTHESIS: Zinc finger protein 804A (ZNF804A) was the first genome-wide associated susceptibility gene for schizophrenia (SCZ) and played an essential role in the pathophysiology of SCZ by influencing neurodevelopment regulation, neurite outgrowth, synaptic plasticity, and RNA translational control; however, the exact molecular mechanism remains unclear. STUDY DESIGN: A nervous-system-specific Zfp804a (ZNF804A murine gene) conditional knockout (cKO) mouse model was generated using clustered regularly interspaced short palindromic repeat/Cas9 technology and the Cre/loxP method. RESULTS: Multiple and complex SCZ-like behaviors, such as anxiety, depression, and impaired cognition, were observed in Zfp804a cKO mice. Molecular biological methods and targeted metabolomics assay validated that Zfp804a cKO mice displayed altered SATB2 (a cortical superficial neuron marker) expression in the cortex; aberrant NeuN, cleaved caspase 3, and DLG4 (markers of mature neurons, apoptosis, and postsynapse, respectively) expressions in the hippocampus and a loss of glutamate (Glu)/γ-aminobutyric acid (GABA) homeostasis with abnormal GAD67 (Gad1) expression in the hippocampus. Clozapine partly ameliorated some SCZ-like behaviors, reversed the disequilibrium of the Glu/GABA ratio, and recovered the expression of GAD67 in cKO mice. CONCLUSIONS: Zfp804a cKO mice reproducing SCZ-like pathological and behavioral phenotypes were successfully developed. A novel mechanism was determined in which Zfp804a caused Glu/GABA imbalance and reduced GAD67 expression, which was partly recovered by clozapine treatment. These findings underscore the role of altered gene expression in understanding the pathogenesis of SCZ and provide a reliable SCZ model for future therapeutic interventions and biomarker discovery.

Mutation identification of the DSPP in a Chinese family with DGI-II and an up-to-date bioinformatic analysis.

In this study, through linkage analysis of a four-generation Chinese family with multiple members afflicted with DGI (type II), we identified a novel missense mutation in DSPP. The mutation was located in exon 2 at the second nucleotide position of the last codon and resulted in a substitution of a proline with a leucine residue (c.50C>T, p.P17L, g.50C>T). To assess the potential effects of this novel mutation, we utilized various bioinformatics analysis programs. The results indicate that the mutation likely affects protein cleavage/trafficking. We also analyzed previously reported mutations of DSPP. In summary, our finding supports that the genomic sequence that corresponds to the P17 residue of DSPP is a mutational hotspot and P17 may be critical for the function of DSPP.

Outcomes of a Single Center's Initial Experience With the Penuma® Penile Implant.

OBJECTIVE: To provide new data, techniques, and safety and efficacy outcomes in patients undergoing Penuma penile implant surgery at a large tertiary care center. METHODS: We performed a retrospective analysis of men undergoing Penuma implants between November 2020 and January 2022 with a single surgeon at a tertiary hospital. Measurements of penile length were made both pre- and postoperatively. Adverse events including infection and unsatisfactory cosmetic outcomes requiring revision were recorded. We also provide detailed technique descriptions of Penuma implantation and revision. Outcomes include measurements of incidents of peri and post-operative adverse events and penile length and girth pre- and post-operatively. RESULTS: 49 male patients underwent Penuma implant surgery. Mean age was 40.2 ± 8.9 years. Mean BMI was 28.2 ± 4.5. All but 2 patients were nonsmokers and only 2 had comorbidities (diabetes). Preoperative mean flaccid length was 8.1 ± 1.9 cm. Postoperative mean length was 12.3 ± 1.9 cm. Patients added an average of 4.9 ± 2.9 cm to their penile length, a 52% increase (P < .01). Average follow up time was 6 months. Among the complications were 1 case of infection and 2 cases of erosion. There were 4 cases of persistent flaring of the Penuma; 3 required revision surgery, all with a good cosmetic outcome. CONCLUSION: The Penuma implant can be used to safely enhance flaccid penile length and girth in patients with retractile penis or other cosmetic deformities. Should complications occur, they are mainly cosmetic and can be easily corrected with low risk.

Assessing ChatGPT's ability to answer questions pertaining to erectile dysfunction: can our patients trust it?

Erectile dysfunction (ED) is a disorder that can cause distress and shame for men suffering from it. Men with ED will often turn to online support and chat groups to ask intimate questions about their health. ChatGPT is an artificial intelligence (AI)-based software that has been trained to engage in conversation with human input. We sought to assess the accuracy, readability, and reproducibility of ChatGPT's responses to frequently asked questions regarding the diagnosis, management, and care of patients with ED. Questions pertaining to ED were derived from clinic encounters with patients as well as online chat forums. These were entered into the free ChatGPT version 3.5 during the month of August 2023. Questions were asked on two separate days from unique accounts and computers to prevent the software from memorizing responses linked to a specific user. A total of 35 questions were asked. Outcomes measured were accuracy using grading from board certified urologists, readability with the Gunning Fog Index, and reproducibility by comparing responses between days. For epidemiology of disease, the percentage of responses that were graded as "comprehensive" or "correct but inadequate" was 100% across both days. There was fair reproducibility and median readability of 15.9 (IQR 2.5). For treatment and prevention, the percentage of responses that were graded as "comprehensive" or "correct but inadequate" was 78.9%. There was poor reproducibility of responses with a median readability of 14.5 (IQR 4.0). Risks of treatment and counseling both had 100% of questions graded as "comprehensive" or "correct but inadequate." The readability score for risks of treatment was median 13.9 (IQR 1.1) and for counseling median 13.8 (IQR 0.5), with good reproducibility for both question domains. ChatGPT provides accurate answers to common patient questions pertaining to ED, although its understanding of treatment options is incomplete and responses are at a reading level too advanced for the average patient.

Gene signatures associated with prognosis and chemotherapy resistance in glioblastoma treated with temozolomide.

Background: Glioblastoma (GBM) prognosis remains extremely poor despite standard treatment that includes temozolomide (TMZ) chemotherapy. To discover new GBM drug targets and biomarkers, genes signatures associated with survival and TMZ resistance in GBM patients treated with TMZ were identified. Methods: GBM cases in The Cancer Genome Atlas who received TMZ (n = 221) were stratified into subgroups that differed by median overall survival (mOS) using network-based stratification to cluster patients whose somatic mutations affected genes in similar modules of a gene interaction network. Gene signatures formed from differentially mutated genes in the subgroup with the longest mOS were used to confirm their association with survival and TMZ resistance in independent datasets. Somatic mutations in these genes also were assessed for an association with OS in an independent group of 37 GBM cases. Results: Among the four subgroups identified, subgroup four (n = 71 subjects) exhibited the longest mOS at 18.3 months (95% confidence interval: 16.2, 34.1; p = 0.0324). Subsets of the 86 genes that were differentially mutated in this subgroup formed 20-gene and 8-gene signatures that predicted OS in two independent datasets (Spearman's rho of 0.64 and 0.58 between actual and predicted OS; p < 0.001). Patients with mutations in five of the 86 genes had longer OS in a small, independent sample of 37 GBM cases, but this association did not reach statistical significance (p = 0.07). Thirty-one of the 86 genes formed signatures that distinguished TMZ-resistant GBM samples from controls in three independent datasets (area under the curve ≥ 0.75). The prognostic and TMZ-resistance signatures had eight genes in common (ANG, BACH1, CDKN2C, HMGA1, IFI16, PADI4, SDF4, and TP53INP1). The latter three genes have not been associated with GBM previously. Conclusion: PADI4, SDF4, and TP53INP1 are novel therapy and biomarker candidates for GBM. Further investigation of their oncologic functions may provide new insight into GBM treatment resistance mechanisms.

Three piece penile prosthesis salvage with chlorhexidine gluconate and length preservation: our technique and outcomes.

OBJECTIVE: Since the advent of the Mulcahy technique of three-piece inflatable penile prosthesis (IPP) salvage, there have been multiple iterations of salvage prosthesis procedures reported in the literature. All of these techniques employ traditional antibiotic irrigation with or without rechanneling. We present our technique of salvage IPP using 0.05% chlorhexidine gluconate (Irrisept®) with corporal rechanneling for length preservation. MATERIALS AND METHODS: Our technique of IPP salvage begins with access via a 5 cm vertical midline scrotal incision. Dissection down to the corpora is performed with a combination of blunt dissection and dissection with fine tipped Metzenbaum scissors. Each component of the prior IPP is sequentially removed starting with the cylinders, followed by the pump, and finally the reservoir. Irrisept® is used to copiously irrigate out both cavernosal bodies as well as the scrotal compartment and prior reservoir location. A two minute dwell time of the Irrisept® is employed after mechanical irrigation. A penrose drain is placed from the space of Retzius through a separate stab incision in the scrotum. Corporotomies are closed, followed by Dartos fascia and scrotal skin. A complete change in gown and gloves of all members of the surgical team and a new set of drapes and instruments is performed. Through a separate subcoronal incision, two new corporotomies are made and separate channels created using nine inch Metzenbaum scissors. These channels are irrigated with Irrisept®. A 9 mm malleable penile prosthesis (MPP) is inserted and corporotomies and skin incision are closed. RESULTS: A total of four men with prior penoscrotal IPP placement underwent salvage IPP with MPP from January 2022 to October 2022. Median operative time was 165 minutes. Median preoperative cylinder size was 23.5 cm. Median postoperative malleable cylinder size was 23 cm. Median length of follow up was 4.8 months. There were no cases of MPP erosion or infection. Two patients elected to undergo repeat IPP insertion after 6 months with same cylinder size. CONCLUSION: IPP salvage with chlorhexidine irrigation and soak as well as separate corporal channeling in a noninfected field for MPP insertion is a viable strategy for infected prostheses given the ease of performance, low risk of repeat infection of the malleable device, and maintenance of corporal length of any subsequent prostheses.

Genetic risk score in multiple sclerosis is associated with unique gut microbiome.

Multiple sclerosis (MS) is a complex autoimmune disease in which both the roles of genetic susceptibility and environmental/microbial factors have been investigated. More than 200 genetic susceptibility variants have been identified along with the dysbiosis of gut microbiota, both independently have been shown to be associated with MS. We hypothesize that MS patients harboring genetic susceptibility variants along with gut microbiome dysbiosis are at a greater risk of exhibiting the disease. We investigated the genetic risk score for MS in conjunction with gut microbiota in the same cohort of 117 relapsing remitting MS (RRMS) and 26 healthy controls. DNA samples were genotyped using Illumina's Infinium Immuno array-24 v2 chip followed by calculating genetic risk score and the microbiota was determined by sequencing the V4 hypervariable region of the 16S rRNA gene. We identified two clusters of MS patients, Cluster A and B, both having a higher genetic risk score than the control group. However, the MS cases in cluster B not only had a higher genetic risk score but also showed a distinct gut microbiome than that of cluster A. Interestingly, cluster A which included both healthy control and MS cases had similar gut microbiome composition. This could be due to (i) the non-active state of the disease in that group of MS patients at the time of fecal sample collection and/or (ii) the restoration of the gut microbiome post disease modifying therapy to treat the MS. Our study showed that there seems to be an association between genetic risk score and gut microbiome dysbiosis in triggering the disease in a small cohort of MS patients. The MS Cluster A who have a higher genetic risk score but microbiome profile similar to that of healthy controls could be due to the remitting phase of the disease or due to the effect of disease modifying therapies.

Scrotal approach for tunica expansion procedure (TEP) for penile girth and length restoration during penile prosthesis implantation in patients with penile angulation due to Peyronie's disease and erectile dysfunction: technique and outcomes.

Peyronie's disease is often comorbid with erectile dysfunction and can cause significant penile shortening. We describe our modified tunica expansion procedure (TEP) technique of penile length preservation and girth enhancement with correction of penile angulation in patients with mild Peyronie's disease (<30 degree angulation, or hourglass deformity, no hinging) and erectile dysfunction presenting for inflatable penile prosthesis (IPP) surgery. A retrospective review of IPP placement from one high volume surgeon was performed. A total of 474 patients' charts from June 2017 to June 2021 were reviewed and those charts of patients undergoing modified TEP in the setting of Peyronie's disease were analyzed. Average increase in length and girth were measured and means with standard deviations calculated. The modified TEP is performed through a scrotal approach and involves complete eversion of the penis with dissection of Buck's fascia off the underlying tunica. Subsequently, staggered scorings of the underlying tunica are performed allowing for circumferential girth enhancement and length preservation. In men with Peyronie's disease, these scorings are preferentially concentrated on the side of the plaque to allow straightening without loss of length. A total of 32 patients with Peyronie's disease from the larger cohort underwent the modified TEP. Mean increase in length of distal corpora was 2.8 ± 0.8 cm (range 2.0-3.4 cm) (measured using Furlow before and after penile eversion with TEP), while mean increase in girth (measured at midphallus prior to prosthesis insertion and after IPP inflation) was 1.6 ± 0.4 cm (range 1.2-2.2 cm). There were no reported complications. A scrotal approach to TEP is an easy to perform technique that can be used to restore length and enhance girth in men with Peyronie's disease undergoing insertion of IPP. Additionally, it is a customizable approach that can also be used to correct mild penile angulation.

Midline submuscular penile prosthesis reservoir placement for patients with bilateral inaccessible inguinal rings: technique and outcomes.

Introduction: One of the most challenging aspects of inflatable penile prosthesis (IPP) surgery is reservoir placement. The traditional space of Retzius (SOR) is not suitable for all patients. For example, radical cystectomy or prostatectomy may alter the anatomical SOR. Hence, traditional placement of the reservoir in this space increases the risk of bowel or vascular injury. Also, patients with bilateral inguinal hernias repaired with mesh, or those with previous reservoirs that have been retained, are not eligible for a Retzius reservoir. Our study reports on the use of midline sub-rectus muscle placement of a penile prosthesis reservoir in these patients as an alternative to high submuscular placement commonly used. Methods: A retrospective chart review of male patients who underwent IPP surgery between June 2017 and 2021 was conducted. Patients were divided into two groups based on the location of the reservoir: SOR versus Midline Submuscular Reservoir (MSMR). Complication rates were compared, including herniated reservoirs, infections, bowel injuries, and vascular injuries. Results: Our cohort included 461 patients who underwent IPP surgery between June 2017 and 2021 in one tertiary center. SOR was used in 89% of patients and MSMR in 11% of patients (n = 413 and 48, respectively). Median follow-up for all patients was 28 months. The mean age was 67 ± 8 years. There was no statistically significant difference between the two groups regarding age or comorbidities (BMI, diabetes mellitus, hypertension, hyperlipidemia, and coronary artery disease). The complication rate was low in both the SOR and MSMR groups, with device malfunction being the most common (2% versus 4%, respectively; p = 0.32). The infection rate was 0.5% in the SOR group with no infections in the MSMR group (NS). There was only one case of herniation requiring surgical revision in the SOR group and no cases of bowel or vascular injury. Conclusion: Placement of a penile prosthesis reservoir within a midline rectus submuscular space is a safe and effective technique when the SOR is compromised by previous surgery or bilateral inguinal canals are not accessible.

Identifying susceptibility genes for essential hypertension by transcriptome-wide association study.

Hypertension is a leading risk factor of cardiovascular disease and mortality in the population worldwide. Recently, hundreds of genomic loci were reported for hypertension by GWAS, however, the most SNPs are located in intergenic regions of genome, where a functional cause is difficult to determine. In the current study, a TWAS of hypertension was conducted using 452,264 individuals including 84,640 patients. KEGG and GO enrichment analyses were performed for the hypertension-related genes identified via TWAS. PPI network analysis based on the STRING database was also performed to detect TWAS-identified genes in hypertension. We have identified 18,420 genes from the GWAS summary data, and of those 1010 non-overlapping genes expression were significantly associated with hypertension after FDR correction (PFDR <0.05) in four tissues (left heart ventricle, aorta, whole blood, and peripheral blood). The KEGG and GO terms were mostly related to autoimmune mechanisms, and the autoimmune-related pathways have also been enriched using GO analysis for PPI genes. We further performed Mendelian randomization analysis, and the results supported a significant association between autoimmunity and hypertension. Moreover, 15 novel hypertension-susceptible genes were identified in all tissues, and five of the genes (RBM6, HLA-DRB5, UHRF1BP1, LYZ, and TMEM116) were associated with autoimmune system, which provide further evidence supporting an autoimmune mechanism in hypertension. In summary, our study supports that an autoimmune mechanism plays an important role in the development of hypertension, and these findings will provide new biological insights that will assist in deciphering the molecular etiology of hypertension.

Medium-Term Real-World Outcomes of Minimally Invasive Surgical Therapies for Benign Prostatic Hyperplasia: Water Vapor Thermal Therapy (Rezum) vs Prostatic Urethral Lift (UroLift) in a High-Volume Urban Academic Center.

Purpose: Water vapor thermal therapy (WVTT, i.e., Rezum®) and prostatic urethral lift (PUL, i.e., Urolift®) are minimally invasive surgical therapy (MIST) options for benign prostatic hyperplasia (BPH). Few studies have directly compared the two procedures. We examined the clinical characteristics and postoperative outcomes of patients undergoing WVTT and PUL at our high-volume urban academic center. Methods: We reviewed our institutional MIST database to identify patients with prostate sizes ≥30 and ≤80 cc who underwent WVTT or PUL for treatment of BPH between January 2017 and September 2021. Pre- and postoperative outcomes, including retreatment rates, American Urological Association symptom score (AUA-SS), maximum flow (Qmax), postvoid residual (PVR), medication usage, trial of void success rates, catheterization requirements, and postoperative complications within 90 days were extracted and compared between procedures. Results: Three hundred seven patients received WVTT and 110 patients received PUL with average follow-up times of 11.3 and 12.8 months, respectively. WVTT patients showed significant improvements in AUA-SS, Qmax, and PVR, whereas PUL patients showed improvements in only AUA-SS and Qmax. Both WVTT and PUL patients with longitudinal follow-up demonstrated improvements in AUA-SS, Qmax, and PVR. Postoperatively, alpha-blocker utilization was significantly decreased following both WVTT and PUL (WVTT: 73.9%-46.6%, PUL: 76.4%-38.2%, both p < 0.001). Compared to patients receiving PUL, WVTT patients more frequently reported postoperative dysuria (22.8% vs 8.3%, p = 0.001) and nonclot-related retention (18.9% vs 7.3%, p = 0.005); PUL patients more frequently experienced postoperative clot retention (7.3% vs 2.6%, p = 0.027). There were no differences in rates of postoperative bladder spasm, trial of void success, urinary tract infections, or emergency department visits. Postoperative erectile dysfunction and retrograde ejaculation were rare and occurred at similar rates. Conclusion: In the real-world setting, WVTT and PUL have similar medium-term efficacy in improving symptoms and decreasing medication utilization for patients with BPH. Differences in postoperative complication profiles should inform patient counseling.

A novel replicated association between FXYD6 gene and schizophrenia.

FXYD6 gene is located in chromosome region 11q22-q24 where previous studies have shown an association with schizophrenia. However, the subsequent studies failed to replicate this finding. To investigate the relationship between FXYD6 locus and schizophrenia in Chinese population, we genotyped six single-nucleotide polymorphisms (SNPs) in this region of FXYD6 in 1142 Han Chinese subjects (576 cases and 566 controls), and performed an association analysis. Significant associations with schizophrenia and the marker rs11544201 (P=0.0028) and the haplotype rs10790212-rs11544201 (global P=0.005) were found. Our results support that FXYD6 is a susceptibility gene of schizophrenia. Replication of larger samples and functional analysis of FXYD6 are needed.