bluuebunny/crossref_metadata_2025_split huggingface dataset:
(074) Association of Androgen Receptor Signaling in Human Corpus Cavernosum with Serum Testosterone Levels
Authors: Khodamoradi K , Dullea A , Golan R , Ory J , Bidhan J , Arora H , Ramasamy R 
Published: May 2023

Abstract

Introduction
Testosterone (T) plays an important role in properly developing and maintaining male reproductive tissues. The normal serum testosterone levels can vary between 300 to 1000 ng/dL or 10.4 to 34.7 nmol/L. However, it is unclear whether androgen receptor signaling can vary based on serum T levels or the half-life of testosterone therapy. What remains unknown is whether there is a uniform serum T level above which androgen receptor signaling within the tissue remains similar (saturation hypothesis).

Objective
We first evaluated whether varying serum levels of T alter androgen receptor (AR) signaling in human penile tissue. Then, we evaluated and compared AR signaling in corpus cavernosum tissue of men treated with short-acting vs. long-acting testosterone. We hypothesized that we would find similar AR signaling in the penile tissue of both eugonadal and hypogonadal men as well as those men receiving short and long-acting testosterone.

Methods
We obtained human corpus cavernosum (hCC) tissue biopsies during penile surgery (for erectile dysfunction) from 14 men. We recorded their serum T levels on week prior to surgery before 10AM. We used western blot to evaluate adrenergic receptor (AR) and VEGF protein levels. Men without erectile dysfunction undergoing penile surgery for Peyronie's disease were used as controls.

Results
The median age of participants was 61 (IQR 12) and the median T level was 325ng/dL (IQR 201.45). The results of western blot showed expression of similar levels of VEGF in hCC samples from men with T &gt;200ng/dL. However, men with serum T levels lower than 200 ng/dL had decreased expression of VEGF and AR.

Conclusions
This finding is significant because it demonstrates that serum testosterone beyond a certain threshold may have a minimal impact on erectile function. If a serum testosterone threshold is identified, this threshold could be a valuable target for future studies on the effects of testosterone on ED. It may alter the treatment threshold for men who have ED as their primary symptom of hypogonadism. This data also suggests the saturation value for penile androgen receptors.

Disclosure
Any of the authors act as a consultant, employee or shareholder of an industry for: Acerus Pharmaceuticals, Boston Scientific, Coloplast, Endo Pharmaceuticals, Empower Pharmacy, Nestle Health, Olympus, Hims, Inc
(075) Exposing the Unsung Cycle: A Proposed Study to Examine the Connection Between Allopregnanolone and Adverse Mood Effects of Hormonal Contraception
Authors: Schuppe K , Abbe C , Hall B , Prager S 
Published: May 2023

Abstract

Introduction
Allopregnanolone is a GABAnergic neurosteroid. Reduced concentration of allopregnanolone in the cerebrospinal fluid (CSF) and serum are closely associated with several neuropsychiatric conditions, including Alzheimer’s disease, anxiety disorders, premenstrual dysphoric disorder, and postpartum depression. Allopregnanolone is a progesterone metabolite predominantly synthesized in women in the ovaries and prior literature shows the menstrual cycle directly affects serum and CSF allopregnanolone concentrations. We hypothesize that allopregnanolone’s biosynthesis is similarly affected by exogenous hormonal contraceptives. In the United States, 65% of reproductive-aged women use hormonal contraceptives and their discontinuation is commonly attributed to adverse changes in mood; yet, little is understood when it comes to what and how specific components of hormonal contraceptives affect mood and how to manage such effects.

Objective
We aim to review current literature and propose a study to understand the connection between allopregnanolone and the adverse mood effects of hormonal contraceptives in order to improve women’s health.

Methods
We conducted a semi-systematic literature search, using PubMed Central and other databases, compiling peer-reviewed material using keywords including allopregnanolone AND hormonal contraceptives; combined oral contraceptive; progestin; suppression; levonorgestrel, ethinyl estradiol, medroxyprogesterone. All languages of publication were included where reliable translations were available. Studies were excluded if they did not include serum and/or CSF measurements of allopregnanolone.

Results
Rodent studies demonstrated that exogenous hormonal contraceptives reduce both the serum and CSF concentration of allopregnanolone. Human studies analyzing only serum allopregnanolone concentrations showed the same results, but no human studies analyzing CSF allopregnanolone concentrations were identified. Only two human studies have examined serum allopregnanolone levels and mood, and no studies have done so in the context of exogenous hormonal contraceptive use.

Conclusions
While exogenous sex hormones, namely progestins, affect allopregnanolone levels in rodents, their impact on both allopregnanolone levels and mood remains inconclusive and under-researched in humans. We propose a large multi-arm study on humans analyzing CSF and serum allopregnanolone and mood effects following administration of hormonal contraceptives to assess how contraceptives affect allopregnanolone metabolism in connection to adverse mood effects. This research will allow clinicians to better tailor contraceptive selection.

Disclosure
No
(084) Analysis of BMP4 and GREMLIN as targets of SHH signaling and regulators of the collagen axis in the penis.
Authors: Martn S , Deng J , Searl T , Ohlander S , Harrington D , Stupp S , Mcvary K , Podlasek C 
Published: May 2023

Abstract

Introduction
Increased collagen deposition occurs in erectile dysfunction (ED) patients and animal models, and the underlying causes of these fibrotic changes have not been well defined. The Sonic hedgehog (SHH) pathway is critical for the response of the penis to denervation. Decreased SHH in the penis due to cavernous nerve (CN) injury, causes smooth muscle apoptosis and ED. As smooth muscle is lost, increased collagen occurs by a largely unknown mechanism. We have shown that collagen abundance is responsive to SHH signaling in the penis. Microarray analysis identified increased GREMLIN (BMP4 antagonist) in corpora cavernosa of ED patients, and SHH is a regulator of GREMLIN in the limb bud.

Objective
We hypothesize that SHH regulation of collagen occurs through a BMP4/GREMLIN dependent mechanism and will examine BMP4 and GREMLIN signalling in corpora cavernosa of ED patients and a rat prostatectomy model. Study of how collagen induction occurs after prostatectomy would be useful to determine the underlying mechanism of penile remodeling.

Methods
Corpora cavernosal tissue (n=36) from prostatectomy, diabetic and Peyronie’s (control) patients were examined by immunohistochemical and western analysis for BMP-4 and GREMLIN proteins. Localization was determined by dual staining with ACTA2 and CD31. Collagen was quantified by hydroxyproline assay and trichrome stain with Image J analysis. Primary cultures of patient corpora cavernosa were established and treated with BMP4 and GREMLIN proteins, and smooth muscle cell growth was quantified. Sprague dawley rat penis was treated in vivo with SHH protein by peptide amphiphile, 5E1 SHH inhibitor, BMP4 and GREMLIN via Affi-Gel beads. Collagen was quantified.

Results
BMP-4 and GREMLIN were identified in smooth muscle of Peyronie’s, prostatectomy and diabetic ED patients. Western analysis identified increased BMP4 and GREMLIN proteins in prostatectomy and diabetic patients where collagen is increased. Primary culture of corpora cavernosal smooth muscle cells showed an increase in growth with BMP4 and decreased growth with GREMLIN treatment. This trend was more pronounced in cells from hypertension and cardiovascular disease patients. BMP4 and GREMLIN proteins increased 1-2 days after CN injury in a rat prostatectomy model that showed decreasing SHH in the penis. SHH inhibition in the penis increases BMP4, GREMLIN and collagen. SHH treatment of the penis after CN injury in the rat decreases collagen, BMP4 and GREMLIN.

Conclusions
SHH is decreased in corpora cavernosa of prostatectomy and diabetic ED patients while BMP4 and GREMLIN are increased. Decreased SHH increases BMP4 protein and collagen, suggesting a possible mechanism for fibrotic penile remodelling after CN injury. This study is the first step in understanding the mechanism of how SHH regulates collagen abundance in the penis, which is important for clinical translation.

Disclosure
No
(097) A Novel Therapeutic Strategy for Recovery from Cavernous Veno-Occlusive Dysfunction through Chronic Administration of Hepatocyte Growth Factor and a JNK Inhibitor in a Rat Model of Cavernous Nerve Injury
Authors: Lee J , Cho M C , Choi H , Son H , Kim S W 
Published: May 2023

Abstract

Introduction
Structural alterations of penis including cavernosal apoptosis and fibrosis induce venous leakage in the corpus cavernosum or cavernosal veno-occlusive dysfunction, a key pathophysiology of erectile dysfunction (ED) after radical prostatectomy.

Objective
We aimed to determine if JNK inhibition in combination with intracavernosal administration of hepatocyte growth factor (HGF) would completely restore cavernosal veno-occlusive function (CVOF) in a rat model of ED induced by bilateral CN crush injury (CNCI).

Methods
A total of forty-two male Sprague-Dawley rats were randomly assigned to sham control (S), CNCI (I) and CNCI treated with combination of JNK inhibitors and HGF (J+H) for 5 weeks after surgery. All rats in each group were evaluated by dynamic infusion cavernosometry (DIC), caspase-3 activity assay, Masson’s trichrome staining, immunohistochemical staining of α-smooth muscle actin (α-SMA) and immunoblotting at 5 weeks after surgery.

Results
Regarding CVOF, Group I showed a decreased papaverine response, an increased maintenance and drop rates compared to Group S. Group J+H showed significant improvements in the three DIC parameters compared to Group I. There were no differences in papaverine response and drop rate between Group J+H and Group S. Regarding the structural integrity of corpus cavernosum, Group I had an increased caspase-3 activity, decreased SM/collagen ratio, decreased content of SM, decreased protein expression of PECAM-1, and decreased phosphorylation of c-Jun and c-Met. Group J+H had significant alleviation in the histological and molecular derangement compared to Group I. There were no differences in caspase-3 activity, SM content, PECAM-1 protein expression, c-Jun phosphorylation and c-Met phosphorylation between Group J+H and Group S.

Conclusions
Our data indicate that chronic administration of JNK inhibitors and HGF may restore CVOF to the level comparable to sham control level through preservation of structural integrity of the corpus cavernosum. Combination of JNK inhibition and HGF might be a potential therapeutic option for recovering from CVOD.

Disclosure
No
(101) Ultrasonography and Magnetic Resonance Imaging are Accurate for Suspected Penile Fracture
Authors: Lee W G , Von Stempel C , Cayetano A , Mount C , Ralph D 
Published: May 2023

Abstract

Introduction
Penile fracture (PF) is a rare but potentially catastrophic injury due to the risk of erectile dysfunction (ED) and penile curvature in young, sexually active men. The diagnosis is commonly made by clinical examination only but may be inaccurate in 15% of men. Despite this, penile ultrasound (US) and magnetic resonance imaging (MRI) remains poorly utilised.

Objective
This study aims to correlate for the first time imaging suggestive of PF with intraoperative findings as the gold standard comparator in order to calculate the sensitivity and specificity as accurately as possible.

Methods
Retrospective analysis (electronic and paper records) of all men referred for imaging querying penile fracture over ten years at a single centre (January 2010 - December 2020). All men with suspected PF on US and/or MRI were included. Same day MRI was performed in equivocal cases or to further define the extent of injury. Imaging findings were correlated with intraoperative findings.

Results
114 men underwent surgical exploration for PF over 10 years with a median age of 39 years (range 16-74). Pre-existing ED was reported in 9 men and 6 men reported pre-existing Peyronie’s disease. Most men had a pre-operative doppler US (92.6%, n=112) with subsequent MRI in 13 men (11.6%). Two men were surgically explored after MRI only. Table 1 summarises the strong correlation between imaging and intraoperative findings. PF was not identified on US in 8 men (7.1%). MRI upgraded equivocal US findings to PF or showed a greater extent of injury in 76.5% (n=13). All PF were identified on MRI but there was a single false positive where PF was not found on exploration. MRI may have been confounded by Peyronie’s plaque calcification. Urethral injury was identified in 24 men intraoperatively but US only identified 10 with a further 4 identified on subsequent MRI.

Conclusions
Penile US has a high sensitivity and PPV for PF when compared to the gold standard of intraoperative findings. MRI has excellent specificity for both PF and urethral injury and should be considered in equivocal cases. The combination of US and MRI is useful to avoid unnecessary surgery and can characterise complex/atypical injuries to guide choice of incision and surgical planning. Imaging should be routinely offered to all men prior to surgical exploration.

Disclosure
No
(102) Complications of the Penuma Penile Implant for Genital Enhancement
Authors: Barham D , Barnard J , Gelman J 
Published: May 2023

Abstract

Introduction
The Penuma penile implant (PPI) is a subcutaneous silicone implant intended to increase penile length and girth. Only one case report and one case series of four patients have been published on the complications of PPIs.

Objective
To report a single center experience treating complications of the PPI both prior to and after implant removal.

Methods
Patients with a prior history of PPI surgery treated at our center were identified between 2012 and 2022. Demographic data, implant date, complications leading to explant, postoperative course, and functional outcomes were recorded. Our protocol is to wait 6 months after explant prior to scar excision (SE)/revision should disabling capsular contraction develop.

Results
A total of 13 patients were evaluated at our institution. Median age at time of implant was 36 (26-54) years. The median duration of implant was 3 months (range 3 days-33 months). Mean follow-up was 21.6 months. The most common complication leading to explant was distal lateral protrusion of the implant at the coronal margin causing patient and partner discomfort which occurred in 8 patients. Other reasons for explant were skin erosion, infection, decreased sensation, ventral curvature, and penile shortening each occurring in 1 patient. Adverse sensation changes occurred in 2 patients after implant. Following explant 9 (69%) patients developed disabling dorsal curvature, 8 (62%) patients had penile shortening, 3 (23%) had infections, 2 (15%) had de novo sensation changes, 2 (15%) had erectile dysfunction, and 1 (8%) had right lateral curvature. Curvature occurred because of capsule contraction following explant. Of those with disabling curvature, 6 (67%) underwent scar excision (SE), 1 is awaiting scar maturation for SE, 1 more is considering SE for disabling curvature, and 1 has elected not to undergo further surgery. In patients who underwent SE, severe scarring was noted superficial to the neurovascular bundles. All patients who have undergone SE had improvement in curvature and were able to have functional erections.

Conclusions
PPI for cosmetic penile enhancement can be associated with a variety of complications leading to device removal. Subsequent to explant, capsular contraction can result in disabling curvature and penile shortening which can be managed successfully with SE.

Disclosure
No
(103) 3-Piece Inflatable Penile Implant Pump Malfunction: Management using Pump Replacement Alone
Authors: Taniguchi H , Sullivan J , Flores J , Salter C , Bernie H , Jenkins L , Mulhall J 
Published: May 2023

Abstract

Introduction
Expert opinion is that when an implant malfunctions after 2 years it should be replaced in its entirety, despite the fact that reservoir removal is associated with serious potential complications. Furthermore, modern reservoir construction is such that material fracture and leak is rare.

Objective
In this time we reviewed our experience with replacing only the reservoir in patients with malfunctioning 3-piece inflatable implants resulting from pump breakdown.

Methods
The study population consisted of (i) men who had had 3-piece inflatable penile implant surgery (ii) with device malfunction (iii) resulting from pump malfunction (iv) who had all other components functional (v) who underwent pump replacement alone and (vi) had ≥5 years follow-up after device repair (clinic visit, telephone call, letter). Only patients who had undergone a single prior implant operation were included. At the time of the repair, the pump was removed and replaced with a new pump, making sure that both cylinders and reservoir were filled fully intraoperatively and retained all fluid that was instilled. At the postoperative appointment, all patients were retrained in the correct means of device inflation, specially focused on avoidance of pump torqueing.

Results
88 patients had pump tubing blow-out upon delivery of the pump at a mean duration post-primary implant of 9 ± 11 (2-16) years. Mean age 62 ±14 years. All patients had either a Mentor Alpha-1 or a Coloplast Titan devices placed. Tubing disruption was present ≤1cm from pump itself in 66 (75%) or &gt;1cm from the pump in 22 (20%) patients. 25% had a blow out of the pump-reservoir tubing, while 66 (75%) had a tear in the pump-cylinder tubing (46 frayed tubing, 20 compete transection), evenly distributed between right and left-sided tubing. With a mean follow-up of 7±2.5 years, none of the devices had failed again.

Conclusions
In patients with a malfunctioning penile implant with proven pump-only failure, replacing the pump is a viable repair option, thus, circumventing the need for reservoir placement.

Disclosure
No
(106) Concept of Enhanced Recovery Implant Care (ERIC) in Inflatable Penile Prosthesis Surgery: A Double-blind, Randomized, Controlled Trial on Clinical Outcomes and Patient Satisfaction Rate
Authors: Chung E 
Published: May 2023

Abstract

Introduction
ERAS (Enhanced Recovery After Surgery) is considered a standard of care intended to achieve earlier recovery and reduce stress response following surgery. While inflatable penile prosthesis (IPP) surgery is a safe and effective treatment for males with erectile dysfunction, complications such as significant postoperative pain and scrotal hematoma are not uncommon and can result in delayed IPP cycling and lower patient satisfaction rate

Objective
To evaluate the concept of ERIC (Enhanced Recovery Implant Care) on clinical outcomes and patient satisfaction rate following IPP surgery.

Methods
This prospective double-blind, randomised, controlled clinical trial received internal ethics approval and 60 males were randomised to receive “normal care” (NC) vs ERIC pathway which consisted of a strict perioperative regime of intra-operative regional nerve block and device analgesia elution, meticulous haemostatic corporotomy closure and multi-layered scrotal closure as well as postoperative 7 days of fitted scrotal support following IPP surgery. An independent third-party survey with objective measurement of pain score (visual analogue scale, VAS), analgesic requirement (conversion to opioid dose equivalence), time to IPP cycling and overall patient satisfaction rates (on a 5-point scale) were collected and compared on Day 1, 7, 14, 28 and 42 postoperatively.

Results
There was no significant difference in patient demographics between the 2 groups. No intraoperative complication was documented. Males in the ERIC group reported lower VAS scores (p&lt;0.05), less analgesic requirement (p&lt;0.05) and shorter time to IPP cycling (p=0.08). Twelve (40%) patients in NC had a scrotal hematoma (Clavien-Dindo grade 1) compared to 2 (7%) patients in the ERIC group on days 1 and 7 postoperative. The overall patient satisfaction rate (rated 4 or 5) was higher in the ERIC compared to NC groups (93% vs. 70%; p&lt;0.05).

Conclusions
The ERIC pathway appears to improve clinical outcomes and postoperative recovery following IPP surgery in terms of pain score, the analgesic requirement, and time to IPP cycling, as well as the overall patient satisfaction rate.

Disclosure
No
(107) Delayed Closed-Suction Drain Removal Following Inflatable Penile Prosthesis: A Multi-Institutional Experience
Authors: Shumaker L , Zulia N , Kennedy E , Ortiz N , Beilan J , Baumgarten A 
Published: May 2023

Abstract

Introduction
There is a paucity of outcome data for prolonged (&gt;48 hours) closed-suction drains following inflatable penile prosthesis (IPP) placement. Tissue dissection and corporal dilation make scrotal hematomas a potential complication within the first 72 hours following surgery. Maintaining a closed-suction drain represents a method to reduce scrotal hematoma formation and prevent sequela such as infection. However, maintaining a percutaneous tract also represents a feasible pathway for bacterial seeding of a new prosthesis. Given the severe consequences of prosthetic infection, establishing comparable outcomes for delayed drain removal is necessary.

Objective
To evaluate rates of infection, hematoma and device explantation in a multi-institutional cohort of patients undergoing IPP placement with delayed closed-suction drain removal (48-hour duration or greater) and compare observed outcomes to published outcomes in modern IPP cohorts.

Methods
Data was collected retrospectively for 209 patients undergoing virgin IPP placement with delayed closed-suction drain removal. Cases were performed by three surgeons at three high-volume centers between 01/01/2020 and 3/31/2022. R for Statistical Computing was used to generate descriptive statistics (Figure 1) and categorical data visualization (Figure 2). No quantitative statistical analysis was performed regarding infection outcomes as the low observed rate would not accommodate robust quantitative analysis.

Results
Mean drain duration was 66 hours (48 – 312, SD 23). There were 3 device infections (1.4%). Mean patient age was 64.5 years. 84 (40.2%) patients were diabetic, with a mean hemoglobin A1c of 7.2 in these patients. Both penoscrotal and infrapubic approaches were performed (95 versus 114). Reservoir location was either space of Retzius (SOR) or high submuscular (HSM) with the former being more common (164 versus 45). There were 7 (3.3%) post-operative hematomas and 6 patients (2.9%) required device revision for non-infectious causes. Mean follow up interval postoperatively was 170 days (10 – 421 days, SD 78).

Conclusions
Delayed removal of closed-suction drains after virgin IPP is safe. The outcomes for this study cohort are similar to outcomes reported in other modern virgin IPP series where closed-suction drains were not routinely employed. Prospective studies to further characterize how closed-suction drain placement influences hematoma formation, infection rates, and postoperative pain are necessary to definitively establish the role of delayed drain removal following IPP implantation.

Disclosure
No