Diagnosis and treatment patterns of Peyronie's disease among different racial, ethnic, and regional groups in the Veterans Affairs healthcare system.

Peyronie's Disease, which is known to have racial/ethnic disparities in the general population, has never been studied in the veteran population. We compared the diagnosis and treatment rates for Peyronie's Disease among United States veterans of various racial-ethnic backgrounds at Veterans Affairs medical centers, which are equal-access systems. We queried the Veterans Affair Informatics and Computing Infrastructure to identify 17,647 Peyronie's Disease patients in the United States by ICD-9 or ICD-10 code between 2015-2020. We assessed demographic characteristics, clinical characteristics, Veterans Affairs facility information, and treatment patterns. Racial-ethnic demographics of veterans with Peyronie's Disease were 71.4% White, 15.4% Black, 5.8% Hispanic, 1.6% Native American, 0.3% Asian, and 5.4% unknown. Treatment rate was 13.6% overall, 13.6% of Whites (ref), 14.3% of Blacks (p = 0.2985), 13.5% of Hispanics (p = 0.9205), 9.1% of Asians (p = 0.3319), 16.7% of Native Americans (p = 0.1406), and 9.6% of unknown (p = 0.0041). White patients were more likely to receive injectional therapy and less likely to undergo surgery than Black patients. Peyronie's Disease patients at Veterans Affairs facilities are treated at the same rate, indicating that equal-access healthcare systems may mitigate racial-ethnic disparities. Further research is necessary to account for differences in disease severity and Veterans Affairs surgeon availability.

Whole-Genome Sequencing Identifies Novel Heterozygous Mutation in ALMS1 in Three Men With Both Peyronie's and Dupuytren's Disease.

Peyronie's Disease (PD) is estimated to occur in up to 13% of males and has been associated with Dupuytren's Disease (DD). We identified 3 men with PD/DD and hypothesized that there may be a genetic association between the 2 diseases. Blood samples were collected from the participants and sent for whole genome sequencing. A rare non-synonymous mutation in the ALMS1 gene was identified in 3 men. Interestingly, ALMS1 is associated with TGF-b, and aberrant fibrosis. This pilot study generates the hypothesis that mutations in ALMS1 may predispose patients to development of PD/DD.

Discordant erectile function assessment between validated questionnaire scores and penile Doppler ultrasound in Peyronie's disease.

Peyronie's disease results in curvature of the penis which may cause difficulty with penetrative intercourse. The diagnosis of Peyronie's disease is easily obtained through history and physical examination alone, but the severity of erectile dysfunction relies on patient history and use of validated questionnaires. However, erectile dysfunction questionnaires were not validated in the Peyronie's disease population and may not be a reliable assessment. Penile Doppler ultrasound is a noninvasive tool that assesses vascular function. We hypothesized that penile Doppler ultrasound will be discordant with International Index of Erectile Function (IIEF) results in men with Peyronie's disease and erectile dysfunction. In this cross-sectional study, we reviewed a prospectively collected database of men with Peyronie's disease. In total, 108 men had questionnaire and ultrasound data. Of them, 87 had erectile dysfunction based on IIEF-EF or IIEF-5 (SHIM). However, 48 (55%) of those men had normal vascular parameters. Interestingly, among a subgroup of 33 men with severe erectile dysfunction on IIEF-EF or IIEF-5, 20 (61%) had normal vascular parameters. Our study demonstrates significant discordance between questionnaires and penile Doppler ultrasound. Therefore, ultrasound may be a useful tool in the workup of men with Peyronie's disease and erectile dysfunction.

Whole Exome Sequencing Identifies a Rare Mutation in NACAD as a Possible Cause of COVID Orchitis in Brothers.

COVID orchitis (testicular pain) is reported in 10-15% of men with long COVID. We identified 2 siblings with COVID orchitis and hypothesized that genetic mutations are associated with susceptibility. Blood samples from 5 COVID-19 (+) men, three of whom had orchitis were evaluated by whole-exome-sequencing. A rare deletion on chromosome 7 was found in NACAD among the 3 men with orchitis. Interestingly, circulating ACE2 levels was decreased in men with COVID orchitis. This pilot study generated the hypothesis that men who develop COVID orchitis could have underlying genetic variants and altered levels in circulating ACE2 that may increase their risk.

The potential of platelet-rich plasma injections and stem cell therapy for penile rejuvenation.

Penile concerns include erectile dysfunction (ED) and Peyronie disease (PD). Restorative therapies including Stem Cell Therapy (SCT) and Platelet Rich Plasma (PRP) injections are proposed to treat these concerns. SCT encompasses the harvesting and injection of mesenchymal stem cells or stromal vascular fractions from various tissue sources. PRP is derived autologously from a patient's plasma and is then injected into the penile tissue. These therapies repair damaged penile tissue and promote both new cellular and vascular growth, as demonstrated in basic science studies. Human trials on SCT and PRP for both ED and PD and have yielded promising results with few side effects. While encouraging, small cohort size and lack of blinding or placebo control limit these studies' external validity. Recently, the first double-blinded randomized controlled trial on PRP for ED was published, providing significant evidence of efficacy. With the rapid commercial availability of SCT and PRP for ED and PD, it is imperative to perform more randomized and placebo-controlled trials with standardized procedures and preparations to evaluate efficacy and safety. This narrative review will summarize the available literature on these penile restorative therapies to date.

Adverse effects and potential benefits among selective androgen receptor modulators users: a cross-sectional survey.

Selective androgen receptor modulators (SARMs) are a class of androgen receptor ligands that bind androgen receptors and display tissue selective activation of androgenic signaling. SARMs have selective anabolic effects on muscle and bone, and were originally synthesized for treatment of muscle wasting conditions, osteoporosis, breast cancer. To date, no SARM has been clinically approved and little is known about the beneficial effects and other adverse effects on users. We examined the adverse effects and potential benefits of SARMs amongst users. We performed an internet survey assessing the demographics of users via a 32-question survey. Using reddit as a platform, we distributed the survey through various subreddits that included potential SARMs users. Out of the 520 responses, 343 participants admitted having used SARMs. Most were males (98.5%), between the ages of 18-29 (72.3%). More than 90% of users acquired SARMs via the internet and did not consult with a physician. More than half of SARMs users experienced side effects including mood swings, decreased testicular size, and acne. More than 90% of men reported increased muscle mass and were satisfied with their SARMs usage. Despite having seemingly positive effects, more than 50% of SARMs users report significant adverse effects. Chi square was the main method of statistical analysis. Future studies should focus on comprehensive reproductive evaluation of men using SARMs.

Novel methods to enhance surgical sperm retrieval: a systematic review.

Objectives: To explore the use of novel technologies in sperm retrieval in men with azoospermia due to a production defect. Methods: We performed a Preferred Reporting Items for Systemic Reviews and Meta-Analysis (PRISMA)-compliant systemic literature review for manuscripts focussed on novel sperm-retrieval methods. We identified 30 studies suitable for qualitative analysis. Results and Conclusions: We identified multiple new promising technologies, each with its own distinct set of benefits and limitations, to enhance chances of sperm retrieval; these include the use of multiphoton microscopy, Raman spectroscopy, and full-field optical coherence tomography during a microdissection-testicular sperm extraction procedure. ORBEYE and ultrasonography technologies can also serve to better visualise areas of sperm production. Finally, artificial intelligence technology can play a role in the identification of sperm and, perhaps, better-quality sperm for use with assisted reproduction. Abbreviations: AI: artificial intelligence; ANN: artificial neural network; ART: assisted reproductive technology; 3D: three-dimensional; DNN: deep neural networks; FFOCT: full-field optical coherence tomography; H&E: haematoxylin and eosin; ICSI: intracytoplasmic sperm injection; IVF: in vitro fertilisation; MESA: micro-epididymal sperm aspiration; MeSH: Medical Subject Heading; MPM: multiphoton microscopy; (N)OA: (non-)obstructive azoospermia; SCO: Sertoli cell-only syndrome; SRR: sperm retrieval rates; TESA: testicular sperm aspiration; (micro-)TESE: (microdissection-) testicular sperm extraction; (CE)US: (contrast-enhanced) ultrasonography.

Analysis of the growing public interest in selective androgen receptor modulators.

To characterise trends and interest in selective androgen receptor modulators (SARMs). SARMs are androgen receptor ligands that bind androgen receptors selectively. SARMs have anabolic effects on muscle and bone and were originally synthesised for treatment of muscle wasting conditions, osteoporosis and breast cancer. To date, no SARM has been clinically approved and little is known about their beneficial effects and other adverse effects on users. We examined Google Trend searches of SARMs. Using Google Trends, we analysed how interest in SARMs has evolved over the last 15 years and compared it to trends in testosterone. Comparing 'TRT', 'SARMs' and 'Low Testosterone' together, we see low search interest in SARMs compared to TRT until February 2018, when the interest in both SARMs and TRT terms appear to be the same. Since February 2018, search interest for SARMs has surpassed search interest for both 'TRT' and 'Low Testosterone'. Trends for SARMs demonstrate a continuous increase over the years which has to date surpassed interest for both 'TRT' and 'low testosterone'. The rising interest in SARMs is concerning as the adverse effects of its usage, including its potential effects on fertility, have not been explored. Further investigation is necessary.

Reversal of motor-skill transfer impairment by trihexyphenidyl and reduction of dorsolateral striatal cholinergic interneurons in Dyt1 ΔGAG knock-in mice.

DYT-TOR1A or DYT1 early-onset generalized dystonia is an inherited movement disorder characterized by sustained muscle contractions causing twisting, repetitive movements, or abnormal postures. The majority of the DYT1 dystonia patients have a trinucleotide GAG deletion in DYT1/TOR1A. Trihexyphenidyl (THP), an antagonist for excitatory muscarinic acetylcholine receptor M1, is commonly used to treat dystonia. Dyt1 heterozygous ΔGAG knock-in (KI) mice, which have the corresponding mutation, exhibit impaired motor-skill transfer. Here, the effect of THP injection during the treadmill training period on the motor-skill transfer to the accelerated rotarod performance was examined. THP treatment reversed the motor-skill transfer impairment in Dyt1 KI mice. Immunohistochemistry showed that Dyt1 KI mice had a significant reduction of the dorsolateral striatal cholinergic interneurons. In contrast, Western blot analysis showed no significant alteration in the expression levels of the striatal enzymes and transporters involved in the acetylcholine metabolism. The results suggest a functional alteration of the cholinergic system underlying the impairment of motor-skill transfer and the pathogenesis of DYT1 dystonia. Training with THP in a motor task may improve another motor skill performance in DYT1 dystonia.

Is Female Wellness Affected When Men Blame Them for Erectile Dysfunction?

INTRODUCTION: Several studies have investigated the association between erectile dysfunction (ED), its treatment, and female sexual dysfunction, but the impact of males blaming their female partners for their ED remains unknown. AIMS: To investigate whether women who are blamed by their male partners for their ED experience worse overall sexual function and satisfaction. METHODS: We performed a global, cross-sectional web-based survey to investigate female perceptions of ED. We distributed the 30-item survey via email, Reddit, Amazon Mechanical Turk, and Facebook. Women 18 years of age or older were eligible to participate and answered questions based on a 5-point Likert scale. Women were grouped by ages 18-29, 30-39, and 40 and older. MAIN OUTCOME MEASURES: The survey collected data that included general demographics and questions regarding experiencing male blame for ED and its relationship with each subject's sexual health and wellness. RESULTS: A total of 13,617 females participated in the survey. Of the women surveyed, 79% have experienced their partner losing their erection during sexual activity and approximately 1 out of 7 women (14.7%) had experienced being blamed by their partner for loss of their erection. Women who were blamed for their partner's ED were more likely to end the sexual encounter, were less sexually satisfied, and were more likely to end relationships due to their partner's ED. CONCLUSION: Approximately 1 out of 7 women have experienced male blame for their partner's ED which is associated with negative impacts on female mental health, sexual satisfaction and the success of the overall partnership. Because of its widespread impact on female wellness, male blame should be considered during evaluation of female sexual history and men must be educated on the significant impact their reactions during intimacy have on their female partners and their relationships as a whole. Dubin JM, Wyant WA, Balaji NC, et al. Is Female Wellness Affected When Men Blame Them for Erectile Dysfunction?. Sex Med 2021;9:100352.

Dorsal Hand Rejuvenation: A Systematic Review of the Literature.

BACKGROUND: Dorsal hand appearance undergoes changes with aging. Grading systems have been designed to provide numerical scores to dorsal hand appearance. Various modalities have been utilized to improve the aesthetic appearance and rejuvenate the dorsal hand. METHODS: The MEDLINE database was searched for articles investigating dorsal hand rejuvenation. Studies were grouped by method including fat grafting, injectable filler, laser/light-based treatments and miscellaneous treatments. Treatment protocols and outcomes were compiled along with patient information and complications. RESULTS: Forty-six articles were identified for inclusion. This included 9 studies of fat grafting procedures, 20 studies of injectable filler, 10 studies of laser/light-based treatments and 7 miscellaneous. Most studies showed overall good results with high patient satisfaction. Satisfaction rates were lower in laser/light-based treatments compared with the other modalities. The average patient age for included studies ranged from 41.5 to 69. Across all studies, 96.8% of patients were female and 3.2% male. CONCLUSIONS: Procedures for dorsal hand rejuvenation in the literature include procedures to address volume atrophy and superficial wrinkling. These procedures are overall safe with most studies reporting no complications or only mild adverse events. With high satisfaction rates and anecdotal reports of increasing patient interest, these procedures represent a developing area in aesthetic surgery likely to continue increasing in popularity. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Decreased number of striatal cholinergic interneurons and motor deficits in dopamine receptor 2-expressing-cell-specific Dyt1 conditional knockout mice.

DYT1 early-onset generalized torsion dystonia is a hereditary movement disorder characterized by abnormal postures and repeated movements. It is caused mainly by a heterozygous trinucleotide deletion in DYT1/TOR1A, coding for torsinA. The mutation may lead to a partial loss of torsinA function. Functional alterations of the basal ganglia circuits have been implicated in this disease. Striatal dopamine receptor 2 (D2R) levels are significantly decreased in DYT1 dystonia patients and in the animal models of DYT1 dystonia. D2R-expressing cells, such as the medium spiny neurons in the indirect pathway, striatal cholinergic interneurons, and dopaminergic neurons in the basal ganglia circuits, contribute to motor performance. However, the function of torsinA in these neurons and its contribution to the motor symptoms is not clear. Here, D2R-expressing-cell-specific Dyt1 conditional knockout (d2KO) mice were generated and in vivo effects of torsinA loss in the corresponding cells were examined. The Dyt1 d2KO mice showed significant reductions of striatal torsinA, acetylcholine metabolic enzymes, Tropomyosin receptor kinase A (TrkA), and cholinergic interneurons. The Dyt1 d2KO mice also showed significant reductions of striatal D2R dimers and tyrosine hydroxylase without significant alteration in striatal monoamine contents or the number of dopaminergic neurons in the substantia nigra. The Dyt1 d2KO male mice showed motor deficits in the accelerated rotarod and beam-walking tests without overt dystonic symptoms. Moreover, the Dyt1 d2KO male mice showed significant correlations between striatal monoamines and locomotion. The results suggest that torsinA in the D2R-expressing cells play a critical role in the development or survival of the striatal cholinergic interneurons, expression of striatal D2R mature form, and motor performance. Medical interventions to compensate for the loss of torsinA function in these neurons may affect the onset and symptoms of this disease.