Citations

Abstract Asparagine‐linked glycosylation 13 homolog ( ALG13 ) encodes a nonredundant, highly conserved, X‐linked uridine diphosphate (UDP)‐ N ‐acetylglucosaminyltransferase required for the synthesis of lipid linked oligosaccharide precursor and proper N‐linked glycosylation. De novo variants in ALG13 underlie a form of early infantile epileptic encephalopathy known as EIEE36, but given its essential role in glycosylation, it is also considered a congenital disorder of glycosylation (CDG), ALG13‐CDG. Twenty‐four previously reported ALG13‐CDG cases had de novo variants, but surprisingly, unlike most forms of CDG, ALG13‐CDG did not show the anticipated glycosylation defects, typically detected by altered transferrin glycosylation. Structural homology modeling of two recurrent de novo variants, p.A81T and p.N107S, suggests both are likely to impact the function of ALG13. Using a corresponding ALG13‐deficient yeast strain, we show that expressing yeast ALG13 with either of the highly conserved hotspot variants rescues the observed growth defect, but not its glycosylation abnormality. We present molecular and clinical data on 29 previously unreported individuals with de novo variants in ALG13 . This more than doubles the number of known cases. A key finding is that a vast majority of the individuals presents with West syndrome, a feature shared with other CDG types. Among these, the initial epileptic spasms best responded to adrenocorticotropic hormone or prednisolone, while clobazam and felbamate showed promise for continued epilepsy treatment. A ketogenic diet seems to play an important role in the treatment of these individuals.

Abstract Introduction Infection remains a persistent complication of penile prosthesis (PP) surgery. Despite popularity of Mulcahy’s PP washout protocol, Betadine has known tissue toxicity. Aim We evaluated PP infection rate based on the type of intraoperative irrigation used, ½ strength Betadine vs vancomycin/gentamicin. Methods We reviewed a prospective database of men undergoing primary, revision, and salvage PPs. No other changes to operative or perioperative techniques occurred after the change in irrigation solution. Univariate and logistic regression analyses were used to evaluate differences in infection rate with use of Betadine vs vancomycin/gentamicin irrigation. Potential confounders were reviewed. Main Outcome Measure The primary outcome was rate of PP infection before and after change of intraoperative irrigation. Results From 2014 to 2018, 217 patients underwent PP placement at our institution by a single surgeon; of whom, 21 (9.7%) experienced an infection (primary = 10 [7.1%], revision = 11 [17.19%], salvage = 0 [0%]). Overall, 152 (70%) received irrigation with Betadine and 65 (30%) with Vancomycin/Gentamicin. Univariate analysis demonstrated significantly increased infection rates with Betadine irrigation (odds ratio [OR]: 4.64, P = .006) and with revision surgery (OR: 2.68, P = .02). Significance of increased infection rate with Betadine was maintained (OR: 9.3; P = .025) after controlling for age, body mass index, Charlson comorbidity index, smoking, diabetes, primary vs revision/salvage, prior penile surgery, use of ectopic reservoir, and adjunctive glanulopexy. Conclusions Changing from intraoperative Betadine to vancomycin/gentamicin solution dramatically reduced infection rates among men undergoing PP placement in both primary and revision cases. We hypothesize that differences in infection rate may relate to the relative toxicity or non-sterile nature of Betadine. Manka MG, Yang D, Andrews J, et al. Intraoperative Use of Betadine Irrigation is Associated With a 9-Fold Increased Likelihood of Penile Prosthesis Infection: Results From a Retrospective Case-Control Study. Sex Med 2020;8:422–427.

Abstract Background Adjuvant maneuvers are often necessary to correct residual curvature during inflatable penile prosthesis (IPP) placement in patients with Peyronie's disease (PD). Aim We present our multicenter experience using collagen fleece as graft material for plaque incision and grafting (PIG) during IPP placement in patients with moderate to severe PD. Methods We retrospectively reviewed 51 patients with IPP from 3 sites who underwent PIG with Tachosil (Baxter, IL) collagen fleece. Coloplast (Minneapolis, MN) IPP devices were used. Factors associated with residual curvature, revision, and patient satisfaction were performed using chi-squared analysis. Outcomes We evaluated postoperative outcomes including factors associated with residual curvature, revision, and patient satisfaction. Results The mean compound curvature was 69.6°. The mean follow-up was 10.6 (range 1–38) months. All patients reported erections sufficient for penetrative intercourse at the last follow-up. Residual curvature <15° was noted in 6 of 51 (12%) patients. 3 patients required device revision. 2 patients experienced temporary glanular paresthesia, and no patients experienced device infection. Clinical Implications In our multicenter study, patients experienced substantial curve correction with minimal complications, and in the few patients who had persistent mild curvature, severe preoperative curvature (>60°) was found to be the only risk factor. Strengths & Limitations Our study represents the largest series of patients coming from multiple centers undergoing surgical correction of PD with IPP and collagen fleece grafting. Limitations of this study include the retrospective study design, lack of a comparison group, and modest follow-up. Conclusion PIG using collagen fleece is a safe and effective means of correcting residual curvature after IPP placement in patients with moderate to severe PD.

Candida species cause hundreds of thousands of invasive infections with high mortality each year. Developing novel antifungal agents is challenging due to the many similarities between fungal and human cells. Maintaining phosphate balance is essential for all organisms but is achieved completely differently by fungi and humans. A protein that imports phosphate into fungal cells, Pho84, is not present in humans and is required for normal cell wall stress resistance and cell wall integrity signaling in C. albicans . Nucleotide sugars, which are phosphate-containing building block molecules for construction of the cell wall, are diminished in cells lacking Pho84. Cell wall-constructing enzymes may be slowed by lack of these building blocks, in addition to being inhibited by drugs. Combined targeting of Pho84 and cell wall-constructing enzymes may provide a strategy for antifungal therapy by which two sequential steps of cell wall maintenance are blocked for greater potency.

Abstract Background Climacturia is an under-reported complication of definitive therapy for prostate cancer (PCa) - that is, radical prostatectomy (RP) and/or radiation therapy (RT). Aim We sought to identify the prevalence and predictors of climacturia and associated patient/partner bother in patients with and without prior PCa treatment. Methods We analyzed a database of patients who presented to our Men's Health clinic and filled out a questionnaire related to sexual function and pertinent medical histories. The prevalence of climacturia and associated patient/partner bother in patients with/without prior RP/RT was calculated. Univariable and multivariable logistic regressions were performed to identify predictors associated with climacturia and patient/partner bother. Outcomes The primary outcomes were the prevalence and predictors of climacturia and associated patient/partner bother in patients with/without history of definitive PCa treatment. Results Among 1,117 patients able to achieve orgasm, 192 patients (17%) had prior history of definitive therapy for PCa (RP alone = 139 [72%]; RT alone = 22 [11%]; RP + RT = 31 [16%]). Climacturia was reported by 39%, 14%, 52%, and 2.4% of patients with history of RP alone, RT alone, RP + RT, and neither RP nor RT, respectively (P < .05 between all groups). 33 to 45 percent of patients with climacturia noted significant patient/partner bother. Factors significantly associated with climacturia were prior RP, prior RT, history of other prostate surgery, and erectile dysfunction, although erectile dysfunction was not significant on multivariable analysis. Significant reduction in climacturia prevalence was noted for patients who were ≥1 year out from RP, compared with patients who were <1 year out. Among patients with prior RP/RT, stress urinary incontinence was associated with increased risk of climacturia, whereas diabetes was associated with decreased risk. No factors were associated with patient/partner bother. Among patients with prior RP, nerve-sparing technique did not predict presence of climacturia but was associated with reduced patient/partner bother. Clinical translation Given significant prevalence of climacturia and associated patient/partner bother, patients should be counseled on the risk of climacturia before undergoing RP/RT. Strengths and limitations Strengths include the large study population and the focus on both RP and RT. Limitations include the facts that this is a single-institution study that primarily relies on patients’ subjective reporting and that the study population may not represent the general population. Conclusions Climacturia affects a significant proportion of patients with history of RP/RT for PCa, and many patients and their partners find this bothersome.