Child ; Humans ; Infertility, Male/therapy* ; Male ; Sperm Count ; Varicocele/therapy* ; Young Adult

We aimed to evaluate ten-year outcomes of penile prosthesis (PP) implantation for the treatment of erectile dysfunction and to assess predictors of early prosthetic infection (EPI). We identified 549 men who underwent 576 PP placements between 2008 and 2018. Univariate and multivariate analyses were used to identify potential predictors of EPI. An EPI predictive nomogram was developed. Thirty-five (6.1%) cases of EPI were recorded with an explant rate of 3.1%. In terms of satisfaction, 82.0% of the patients defined themselves as "satisfied," while partner's satisfaction was 88.3%. Diabetes (P = 0.012), longer operative time (P = 0.032), and reinterventions (P = 0.048) were associated with EPI risk, while postoperative ciprofloxacin was inversely associated with EPI (P = 0.014). Rifampin/gentamicin-coated 3-piece inflatable PP (r/g-c 3IPP) showed a higher EPI risk (P = 0.019). Multivariate analyses showed a two-fold higher risk of EPI in diabetic patients, redo surgeries, or when a r/g-c 3IPP was used (all P < 0.03). We showed that diabetes, longer operative time, and secondary surgeries were the risk factors for EPI. Postoperative ciprofloxacin was associated with a reduced risk of EPI, while r/g-c 3IPP had higher EPI rates without an increased risk of PP explant. After further validation, the proposed nomogram could be a useful tool for the preoperative counseling of PP implantation.
Erectile Dysfunction/surgery* ; Humans ; Male ; Patient Satisfaction ; Penile Implantation ; Penile Prosthesis ; Penis/surgery* ; Tertiary Care Centers

Drug optimization, which improves drug potency/specificity by structure‒activity relationship (SAR) and drug-like properties, is rigorously performed to select drug candidates for clinical trials. However, the current drug optimization may overlook the structure‒tissue exposure/selectivity-relationship (STR) in disease-targeted tissues vs. normal tissues, which may mislead the drug candidate selection and impact the balance of clinical efficacy/toxicity. In this study, we investigated the STR in correlation with observed clinical efficacy/toxicity using seven selective estrogen receptor modulators (SERMs) that have similar structures, same molecular target, and similar/different pharmacokinetics. The results showed that drug's plasma exposure was not correlated with drug's exposures in the target tissues (tumor, fat pad, bone, uterus), while tissue exposure/selectivity of SERMs was correlated with clinical efficacy/safety. Slight structure modifications of four SERMs did not change drug's plasma exposure but altered drug's tissue exposure/selectivity. Seven SERMs with high protein binding showed higher accumulation in tumors compared to surrounding normal tissues, which is likely due to tumor EPR effect of protein-bound drugs. These suggest that STR alters drug's tissue exposure/selectivity in disease-targeted tissues vs. normal tissues impacting clinical efficacy/toxicity. Drug optimization needs to balance the SAR and STR in selecting drug candidate for clinical trial to improve success of clinical drug development.