Differential Gene Expression in Post-Finasteride Syndrome Patients.

BACKGROUND: An organic etiology underpinning post-finasteride syndrome, a constellation of persistent sexual, neuropsychiatric, and somatic symptoms reported by men exposed to 5-alpha-reductase inhibitors (5ARIs), is debated. Persistent changes in neurosteroid levels or androgen receptor expression have been implicated. AIM: To determine whether differences in gene expression, especially in relevant biologic pathways, exist between patients reporting post-finasteride syndrome symptoms and healthy controls. METHODS: This was a single center, prospective case-control study taking place between March 2013 and September 2018. Men 18 years and older being evaluated for sexual dysfunction (study) or circumcision (control) were eligible for inclusion. Twenty-six men with a history of 5ARI use reporting symptoms consistent with post-finasteride syndrome were included in the patient group. Twenty-six men consented to inclusion in the control group. OUTCOMES: The primary outcome measure is gene expression data for genes affecting neurosteroid levels and androgen receptor activity from penile skin cells. RESULTS: Gene expression of cells from penile skin samples from twenty-six men of median age 38 years (IQR, 33-42) in the study group was compared with that from twenty-six men of median age 41 years (IQR, 35-62) in the control group (P = .13), with 1,446 genes significantly over-expressed and 2,318 genes significantly under-expressed in study patients. Androgen receptor expression was significantly higher in study patients compared to controls (9.961 vs 9.494, adjusted P value = .01). Serum levels of androgen receptor activity markers 5α-androstanediol (0.950 ng/mL [0.749-1.587] vs 0.949 [0.817-1.337], P = .34) or 3α-androstanedione (3.1 ng/mL [1.925-5.475] vs 6.7 [3.375-11.4], P = .31) revealed no significant differences. No significant differences were found between the number of trinucleotide repeats (21.5 [20-23.75], 22 [19-25], P = .94). CLINICAL IMPLICATIONS: In this study we present evidence of gene expression correlating with observed biologic differences in patients with post-finasteride syndrome; providers who prescribe 5ARIs should be aware and advise their patients accordingly. STRENGTHS & LIMITATIONS: Strengths of this study include the evaluation of multiple proposed etiologies for post-finasteride syndrome. The study is also strengthened by the fact that not all data matched the initial hypotheses, qualifying the argument for the existence of PFS. Limitations include potential selection bias arising from more severe phenotypes seeking care; lack of gene expression data prior to 5ARI exposure; lack of non-penile tissue samples supposedly involved; and a lack of mechanistic data to imply causality. CONCLUSION: This study is the first to consider and demonstrate gene expression differences in patients with PFS as a potential etiology of sexual dysfunction. Howell S, Song W, Pastuszak A, et al. Differential Gene Expression in Post-Finasteride Syndrome Patients. J Sex Med 2021;18:1479-1490.

The Effect of Lipoaspirate Processing Technique on Complications in Autologous Fat Grafting for Breast Reconstruction: A Propensity Score Analysis Study.

BACKGROUND: The use of autologous fat grafting (AFG) is becoming increasingly common as an adjunct to breast reconstruction. However, there is a paucity of data comparing the varying processing devices. OBJECTIVES: The goal of this study was to compare the outcomes of 2 commercially available AFG processing devices. METHODS: A retrospective review was conducted of patients who underwent AFG with dual-filter (Puregraft) or single-filter (Revolve) processing systems between 2016 and 2019. Propensity score matching was utilized to adjust for confounding. A total of 38 breasts from the Puregraft group were matched with 38 breasts from the Revolve group. RESULTS: Matching was successful in achieving a similar distribution of baseline characteristics between the 2 groups. The mean number of AFG sessions was comparable between the 2 groups (P = 0.37) with a similar median total volume (Puregraft, 159 mL vs Revolve, 130 mL; P = 0.23). Complication rates were similar between the 2 devices (Puregraft, 26%; Revolve, 18%; P = 0.47). Patients with at least 1 complication had higher overall AFG volume (median, 200 mL vs 130 mL; P = 0.03) and number of sessions (mean, 2.4 vs 1.8, P = 0.009) compared with those without any postoperative complication. CONCLUSIONS: Overall complication rates were comparable between 2 commonly used, commercially available AFG processing systems, and therefore the choice of which to use should be based on surgeon preference. Future studies are underway to decipher whether either system offers superior graft retention, cosmetic, or patient-reported outcomes.

Altmetrics in Plastic Surgery Journals: Does It Correlate With Citation Count?

BACKGROUND: Altmetrics (alternative metrics) have become one of the most commonly utilized metrics to track the impact of research articles across electronic and social media platforms. OBJECTIVES: The goal of this study was to identify whether the Altmetric Attention Score (AAS) is a good proxy for citation counts and whether it can be employed as an accurate measure to complement the current gold standard. METHODS: The authors conducted a citation analysis of all articles published in 6 plastic surgery journals during the 2016 calendar year. Citation counts and AAS were abstracted and analyzed. RESULTS: A total of 1420 articles were identified. The mean AAS was 11 and the median AAS was 1. The journal with the highest mean AAS was Aesthetic Surgery Journal (31), followed by Plastic and Reconstructive Surgery (19). A weak positive correlation was identified (r = 0.33, P < .0001) between AAS and citations. Articles in the top 1% in terms of citation counts showed strong positive correlation between AAS and citation counts (r = 0.64, P = .01). On the contrary, articles in the top 1% of AAS had no significant correlation with citation counts (r = -0.31, P = .29). CONCLUSIONS: Overall correlation between citations and AAS was weak, and therefor AAS may not be an accurate early predictor of future citations. The 2 metrics seem to measure different aspects of the impact of scholarly work and should be utilized in tandem for determining the reach of a scientific article.

Manipulation of Extracellular Matrix Remodeling and Neurite Extension by Mouse Embryonic Stem Cells Using IKVAV and LRE Peptide Tethering in Hyaluronic Acid Matrices.

Cellular remodeling of the matrix has recently emerged as a key factor in promoting neural differentiation. Most strategies to manipulate matrix remodeling focus on proteolytically cleavable cross-linkers, leading to changes in tethered biochemical signaling and matrix properties. Using peptides that are not the direct target of enzymatic degradation will likely reduce changes in the matrix and improve control of biological behavior. In this study, laminin-derived peptides, IKVAV and LRE, tethered to independent sites in hyaluronic acid matrices using Michael addition and strain-promoted azide-alkyne cycloaddition are sufficient to manipulate hyaluronic acid degradation, gelatinase expression, and protease expression, while promoting neurite extension through matrix metalloprotease-dependent mechanisms in mouse embryonic stem cells encapsulated in hyaluronic acid matrices using an oxidation-reduction reaction initiated gelation. This study provides the foundation for a new strategy to stimulate matrix remodeling that is not dependent on enzymatic cleavage targets.

Comparison of satisfaction with penile prosthesis implantation in patients with prostate cancer radiation therapy versus radical prostatectomy.

Background: Penile prosthesis surgery (PPS) is a commonly used treatment for erectile dysfunction (ED), either as first-line therapy or in cases refractory to other treatment options. In patients with a urologic malignancy such as prostate cancer, surgical interventions like radical prostatectomy (RP) as well as non-surgical treatments such as radiation therapy can all induce ED. PPS as a treatment for ED has high satisfaction rates in the general population. Our aim was to compare sexual satisfaction in patients with prosthesis implantation for ED following RP versus ED following radiation therapy for prostate cancer. Methods: A retrospective chart review from our institutional database was conducted to identify patients who underwent PPS at our institution from 2011 to 2021. Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) questionnaire data at least 6 months from implant operative date available was required for inclusion. Eligible patients were placed in one of two groups depending on etiology of ED-following RP or prostate cancer radiation therapy. To prevent crossover confounding; patients with history of pelvic radiation were excluded from the RP group and patients with history of RP were excluded from the radiation group. Data were obtained from 51 patients in the RP group and 32 patients in the radiation therapy group. Mean EDITS scores and additional survey questions were compared between the radiation and RP groups. Results: There was a significant difference in mean survey responses for 8 of the 11 questions in the EDITS questionnaire between the RP group and the radiation group. Additional survey questions administered also found RP patients reported significantly higher rate of satisfaction with size of penis post-operatively versus the radiation group. Conclusions: These preliminary findings, while requiring large-scale follow-up, suggest that there is greater sexual satisfaction and penile prosthesis device satisfaction in patients undergoing IPP placement following RP versus radiation therapy for prostate cancer. Use of validated questionnaires should continue to be utilized in quantifying device and sexual satisfaction following PPS.

Does knowing pre-operative penile length influence patient satisfaction post penile prosthesis implantation?

Patients who undergo penile prosthesis implantation as treatment for erectile dysfunction commonly complain of penile shortening after implantation. We conducted a study to determine whether knowledge of pre-operative stretched penile length measurement influences patient satisfaction. This prospective study consisted of 149 patients undergoing inflatable penile prosthesis (IPP) implantation from August 2017 to December 2019. Study group participants underwent pre-operative stretched penile length measurement in clinic while the control group did not. Six months post-operatively, patients completed a modified 14-item Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) questionnaire to assess overall satisfaction and penile length satisfaction. A total of 102 patients were eligible for final analysis (49 in study group, 53 in control). Mean scores for overall treatment satisfaction were 3.57 and 3.53 (scale from 0 to 4) in the study versus control group, respectively (p = 0.483). Mean scores for satisfaction with penile length were 4.08 and 4.11 (scale from 1 to 5) in the study vs. control group (p = 0.645). The study suggests that knowledge of pre-operative stretched penile length does not influence post-operative satisfaction after penile prosthesis implantation. Therefore, performing pre-operative measurements in clinic solely for informing the patient may be unnecessary. Current interventions aimed at conserving penile length may be effective at maintaining satisfaction with penile length.Trial Registration- This trial is registered and approved by the IRB committee at our institution, ID: HSC-MS-19-0320.

Comparison of Satisfaction With Penile Prosthesis Implantation in Patients With Radical Prostatectomy or Radical Cystoprostatectomy to the General Population.

INTRODUCTION: Penile prosthesis implantation is a widely used treatment option for erectile dysfunction. Data is limited with regard to patient satisfaction with a penile prosthesis following radical prostatectomy/cystoprostatectomy vs patients with erectile dysfunction of other etiologies. AIM: To examine patient satisfaction with penile prosthesis implantation and determine if a difference in satisfaction exists in post-prostatectomy/cystoprostatectomy patients vs patients with erectile dysfunction of other etiologies. We hypothesize that etiology does not affect satisfaction. METHODS: A total of 164 patients underwent penile prosthesis implantation at our institution between August 2017 and December 2019, with 102 patients completing a validated 14 item questionnaire, Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS), at 6 months postoperation. Demographics, surgical characteristics, and erectile dysfunction etiology were recorded. Patients were assigned to one of 2 groups: postprostatectomy/postcystoprostatectomy erectile dysfunction or other etiologies. The study group was further analyzed between radical prostatectomy or radical cystoprostatectomy. MAIN OUTCOME MEASURES: Satisfaction based on key EDITS questions with postradical prostatectomy/cystoprostatectomy vs patients with erectile dysfunction of other etiologies. RESULTS: Responses to 3 questions were analyzed: overall satisfaction, expectations met in the past 4 weeks, and confidence in the ability to participate in sexual activity. Chi-square analysis was performed to determine the difference in responses. No difference was seen in overall satisfaction (P = .96), expectations (P = .78), or confidence (P = .78) between groups. On subgroup analysis, there was no difference in reported overall satisfaction (P = .47) or confidence (P = .080) between postprostatectomy and postcystoprostatectomy patients. Postprostatectomy and postcystoprostatectomy patients differed in whether the penile prosthesis implantation met expectations (P = .033). Postprostatectomy patients reported a mean score of 3.5/4 compared to postcystoprostatectomy patients, who reported a mean of 3.0/4. CONCLUSIONS: Our analysis suggests that key erectile function scores are not significantly different between postprostatectomy/postcystoprostatectomy patients compared to other etiologies. The difference in measures between postprostatectomy and postcystoprostatectomy patients is not significant or of unclear significance. Registration # of clinical trial: HSC-MS-19-0320 Howell S, Palasi S, Green T, et al. Comparison of Satisfaction With Penile Prosthesis Implantation in Patients With Radical Prostatectomy or Radical Cystoprostatectomy to the General Population. Sex Med 2021;9:100300.

Combination of IKVAV, LRE, and GPQGIWGQ Bioactive Signaling Peptides Increases Human Induced Pluripotent Stem Cell Derived Neural Stem Cells Extracellular Matrix Remodeling and Neurite Extension.

Extracellular matrix (ECM) remodeling is emerging as a modulator of neural maturation and axon extension. Most studies have used rodent cells to develop matrices capable of manipulating extracellular matrix remodeling for regenerative applications. However, clinically relevant human induced pluripotent stem cell derived neural stem cells (hNSC) do not always behave in a similar manner as rodent cells. In this study, hNSC response to a hyaluronic acid matrix with laminin derived IKVAV and LRE peptide signaling that has previously shown to promote ECM remodeling and neurite extension by mouse embryonic stem cells is examined. The addition of enzymatically degradable cross linker GPQGIWGQ to the IKVAV and LRE containing hyaluronic acid matrix is necessary to promote neurite extension, hyaluronic acid degradation, and gelatinase expression over hyaluronic acid matrices containing GPQGIWGQ, IKVAV and LRE, or no peptides. Changes in peptide content alters a number of matrix properties that can contribute to the cellular response, but increases in mesh size are not observed with cross linker cleavage in this study. Overall, these data imply a complex interaction between IKVAV, LRE, and GPQGIWGQ to modulate hNSC behavior.