Sree Harsha Mandava

Infection Retardant Coated Inflatable Penile Prostheses Decrease the Incidence of Infection: A Systematic Review and Meta-Analysis

PURPOSE This systematic review was done to compare the effectiveness of infection retardant coated inflatable penile prostheses vs noncoated devices. MATERIALS AND METHODS We systematically reviewed PubMed® and Galileo® to identify all relevant case studies. The postoperative infection incidence rate was compared for coated and noncoated inflatable penile prostheses to determine whether coating the implant affects the rate of surgical implant infection. RESULTS Included in analysis were 14 clinical case studies in a total of 9,910 patients with a first time implant, including 5,214 inflatable penile prostheses without an infection retardant coating and 4,696 coated inflatable penile prostheses impregnated with minocycline/rifampin (3,158), rifampin/gentamycin immersion (181), vancomycin/gentamycin immersion (181) and a hydrophilic coating only (1,176). For noncoated vs coated prostheses the infection rate was 2.32% vs 0.89% (p <0.01), including 0.63%, 0.55%, 4.42% and 1.11% for minocycline/rifampin, rifampin/gentamycin immersion, vancomycin/gentamycin immersion and hydrophilic coatings, respectively. CONCLUSIONS This analysis documents a significant advantage of using coated compared to noncoated inflatable penile prostheses to prevent postoperative device infection. Infection retardant coatings that allow antibiotics to elute off the device components decrease the incidence of device infection by approximately 50%. Future studies must address novel techniques, such as preventing bacterial adhesion, to further decrease infectious etiologies.

PDE5 inhibitors: considerations for preference and long‐term adherence

Introduction:  Erectile dysfunction (ED) is a highly prevalent condition affecting nearly one in five men worldwide. The advent of phosphodiesterase type 5 inhibitors (PDE5i) has revolutionised the ED treatment landscape and provided effective, minimally invasive therapies to restore male sexual function.

In Vitro/In Vivo Toxicity Evaluation and Quantification of Iron Oxide Nanoparticles.

Increasing biomedical applications of iron oxide nanoparticles (IONPs) in academic and commercial settings have alarmed the scientific community about the safety and assessment of toxicity profiles of IONPs. The great amount of diversity found in the cytotoxic measurements of IONPs points toward the necessity of careful characterization and quantification of IONPs. The present document discusses the major developments related to in vitro and in vivo toxicity assessment of IONPs and its relationship with the physicochemical parameters of IONPs. Major discussion is included on the current spectrophotometric and imaging based techniques used for quantifying, and studying the clearance and biodistribution of IONPs. Several invasive and non-invasive quantification techniques along with the pitfalls are discussed in detail. Finally, critical guidelines are provided to optimize the design of IONPs to minimize the toxicity.

Long‐Term Revision Rate due to Infection in Hydrophilic‐Coated Inflatable Penile Prostheses: 11‐Year Follow‐up

INTRODUCTION Penile implant surgery continues to be an important option for men with erectile dysfunction. Advancements in technology of implants have contributed to improved survival from mechanical breakdown. Prosthesis infection remains a serious adverse event. For the last 8 years, the Titan implant (Coloplast Corporation, Minneapolis, MN, USA) has been available with an infection-retardant polyvinylpyrrolidone coating. AIM To compare the infection rates between coated three-piece inflatable penile prostheses (IPPs) with the previous non-coated model. MAIN OUTCOME MEASURES Infection-related revisions reported in the physician-generated, manufacturer-tabulated patient information forms (PIFs). METHODS PIFs reported into the voluntary, post-market registry of Coloplast Corporation from July 14, 2000 to September 30, 2011 were retrospectively reviewed. Infection-related revisions entered into the product evaluation database for coated and non-coated IPPs were compared. Data were analyzed using Pearsons chi-squared test. RESULTS The database included 36,391 PIFs related to primary IPP implantation. At 11 years of follow-up, 4.6% (7,031) of non-coated IPPs were removed or replaced due to infections, whereas 1.4% (29,360) of hydrophilic-coated implants reported replacements due to device infections. The hydrophilic coating of the IPP components makes the device slippery and prevents bacterial attachment. The hydrophilic coating allows rapid absorption of antibiotics in an aqueous solution and allows these water-soluble antibiotics to elute off the device into the implant spaces. Unfortunately, information pertaining to what agents were used in the studies patients was not tabulated. The rate of revision due to device infection was reduced 69.56% in patients with hydrophilic-coated IPPs (P<0.001). CONCLUSION To the best of our knowledge, this is the longest post-marketing registry report related to IPP infections. At 8 years of follow-up, the hydrophilic-coated IPPs demonstrated a significant reduction in revision rates due to infection when compared with the 11-year follow-up of non-coated implants. Since there was no information or uniformity of antibiotics used in the soaking solution, it is uncertain which antibiotic selection provided the best results. In vitro testing against known infectious agents may further benefit IPP patients by reducing the prosthesis infection rate.

Comparison of sorafenib-loaded poly (lactic/glycolic) acid and DPPC liposome nanoparticles in the in vitro treatment of renal cell carcinoma.

The objective of this study is to develop and compare several Sorafenib-loaded biocompatible nanoparticle models in order to optimize drug delivery and tumor cellular kill thereby improving the quality of Sorafenib-regimented chemotherapy. Sorafenib-loaded poly (lactic-co-glycolic) acid (PLGA), 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) liposomes, and hydrophobically modified chitosan (HMC)-coated DPPC liposomes were evaluated for several characteristics including zeta potential, drug loading, and release profile. Cytotoxicity and uptake trials were also studied using cell line RCC 786-0, a human metastatic clear cell histology renal cell carcinoma cell line. Sorafenib-loaded PLGA particles and HMC-coated DPPC liposomes exhibited significantly improved cell kill compared to Sorafenib alone at lower concentrations, namely 10-15 and 5-15 μM from 24 to 96 h, respectively. At maximum dosage and time (15 μM and 96 h), Sorafenib-loaded PLGA and HMC-coated liposomes killed 88.3 ± 1.8% and 98 ± 1.1% of all tumor cells, significant values compared with Sorafenib 81.8 ± 1.7% (p < 0.01). Likewise, HMC coating substantially improved cell kill for liposome model for all concentrations (5-15 μM) and at time points (24-96 h) (p < 0.01). PLGA and HMC-coated liposomes are promising platforms for drug delivery of Sorafenib. Because of different particle characteristics of PLGA and liposomes, each model can be further developed for unique clinical modalities.

Robotic Partial Nephrectomy for Clinical Stage T1b Tumors: Intermediate Oncologic and Functional Outcomes

OBJECTIVE The objective of this study was to examine our intermediate oncologic and functional outcomes of robotic partial nephrectomy for clinical T1b tumors. Partial nephrectomy has become the gold standard of treatment for small renal masses. Recently, indications for minimally invasive partial nephrectomy have extended to larger and more complicated renal masses in some centers. MATERIALS AND METHODS Between July 2008 and September 2013, 241 robotic partial nephrectomies were performed at our institution, including 46 for clinical ≥ T1b tumors. We reviewed the intermediate-term functional and oncologic outcomes of this cohort of patients. RESULTS Of the 46 patients, the median age was 55.5 years (interquartile range [IQR], 51-68 years) with a median body mass index of 31.6 (IQR, 27.4-38.9), tumor diameter of 5.0 cm (IQR, 4.1-5.2 cm), and RENAL nephrometry score of 7.1 (range, 5-11). Renal cell carcinoma was confirmed in 35 patients, and 11 patients had benign pathology. There was 1 patient with an established positive margin and 2 patients had a focal positive margin. At a median follow-up of 24.3 months (range, 2.3-61.1 months), the overall, recurrence-free and cancer-specific survival was 97.1%, 97.1%, and 100%, respectively. No patient progressed to dialysis postoperatively and there was no significant difference between preoperative and postoperative serum creatinine or estimated glomerular filtration rate using the Modification of Diet in Renal Disease equation. CONCLUSION Because of the many adverse medical effects of chronic renal insufficiency, the indications for partial nephrectomy are expanding at many institutions. We demonstrated that robotic partial nephrectomy is a safe and efficacious procedure for the treatment of T1b renal tumors with excellent intermediate oncologic and functional outcomes.

Transforming Growth Factor-β1 Induced Urethral Fibrosis in a Rat Model

PURPOSE We sought to develop a reproducible TGF-β1 injection technique to induce urethral fibrosis in the rat urethra. MATERIALS AND METHODS A total of 32 male Sprague Dawley® rats weighing 300 to 350 gm were anesthetized with ketamine/xylazine intraperitoneally. Using a 5 mm penoscrotal incision the rat urethra was exposed. In the experimental group varying doses of TGF-β1 (5, 10 and 25 μg) were injected in each side of the urethral wall. Normal saline infiltration was used in the sham treated group. Rats were sacrificed 2 and 4 weeks following TGF-β1 injection. Urethral specimens were stained with hematoxylin and eosin, and Masson trichrome, and Western blot evaluations were performed. Normal and strictured urethral tissues from patients were collected and evaluated in the same fashion. RESULTS There was no evidence of urethral wall thickening or fibrosis in the sham treated group. Varied histological evidence of fibrosis was noted in all experimental groups. There was a significant increase in collagen type I expression 2 weeks after injection of 5, 10 and 25 μg TGF-β1. Collagen type III expression was significantly increased 2 weeks after injecting 10 and 25 μg of TGF-β1, which persisted to 28 days after injection. CONCLUSIONS TGF-β1 injection can successfully generate a reproducible rat model of urethral spongiofibrosis. This technique is simple, inexpensive and reproducible. Our series is a proof of concept study. Additional studies in larger animals are needed to further confirm our findings.

Effect of Botulinum-A Toxin Injection into Bulbospongiosus Muscle on Ejaculation Latency in Male Rats

INTRODUCTION Premature ejaculation (PE) is the most common male sexual dysfunction. A variety of pharmacotherapeutic strategies have been employed to treat men suffering with lifelong PE. However, there are currently no pharmaceuticals approved by the U.S. Food and Drug Administration specifically designed for PE treatment. AIM Given that the bulbospongiosus muscle is involved in the ejaculatory reflex in both humans and rodents and that local administration of botulinum-A can abolish muscle contractions, the current study examined the effect of injection of botulinum-A toxin into the bulbospongiosus muscle on the ejaculatory latency of male rats. METHODS After screening for normal sexual activity with sexually receptive female rats, 33 sexually experienced male Long-Evans rats (Harlan Laboratories, Indianapolis, IN, USA) underwent an additional four pretreatment sexual exposures over the course of the following week, during which all components of sexual behavior were video recorded by trained observers. On the day after their fourth experience, rats were anesthetized and received a single injection of either 0.5 unit (n = 11) or 1 unit (n = 11) of botulinum-A toxin or saline vehicle (n = 11). Botulinum-A toxin was dissolved in 0.1 mL of saline vehicle and injected bilaterally into the bulbospongiosus muscle by the percutaneous route. Beginning 2 days after treatment, sexual behaviors were reexamined over the course of the following week on four separate occasions. MAIN OUTCOME MEASURES The latency to achieve ejaculation, and the frequencies and latencies of mounts and intromissions were video recorded by trained observers in a blinded fashion. RESULTS Relative to pretreatment measurements, bilateral injection of saline vehicle into the bulbospongiosus muscle did not affect ejaculation latencies. However, rats treated with either 0.5 or 1 unit of botulinum-A toxin exhibited significantly longer latencies to achieve ejaculation relative to pretreatment performance. Of note, botulinum-A toxin did not affect the ability to achieve mounts, intromissions, or ejaculation. CONCLUSIONS These results demonstrate that botulinum-A toxin injection into the bulbospongiosus muscle is a safe and effective treatment that extends ejaculatory latency in rats without affecting the ability to engage in sexual activity or achieve ejaculation. Further studies are required to evaluate this therapeutic concept in PE patients.

Chronic escitalopram treatment induces erectile dysfunction by decreasing nitric oxide bioavailability mediated by increased nicotinamide adenine dinucleotide phosphate oxidase activity and reactive oxygen species production.

OBJECTIVE To investigate the effects of escitalopram, a selective serotonin reuptake inhibitor, on erectile and penile vascular function in the rat. METHODS The effect of chronic treatment with escitalopram (0.286 mg/kg/day) on change in intracavernosal pressure, maximum intracavernosal pressure/mean arterial pressure, and area under the intracavernosal pressure curve in response to cavernosal nerve stimulation was measured. The effect of chronic escitalopram treatment on endothelial-dependent relaxant responses was investigated in isolated mesenteric and internal pudendal resistance arteries. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity and nitric oxide synthase levels were determined with enzymatic assay and Western blot, respectively. RESULTS Chronic treatment with escitalopram resulted in a significant reduction in the erectile response to cavernosal nerve stimulation without an effect on the response to intracavernosal injection of the nitric oxide donor sodium nitroprusside. The decrease in erectile function was associated with marked increases in NADPH oxidase activity in the corpora cavernosa. Treatment with escitalopram also caused a significant reduction in the relaxant response to acetylcholine in isolated internal pudendal and mesenteric resistance arteries without altering the response to sodium nitroprusside. The decreased response to acetylcholine in the isolated vascular segments was associated with a marked increase in NADPH oxidase activity that was corrected by treatment with the NAPDH oxidase inhibitor apocynin. CONCLUSION The inhibitory effects of escitalopram on erectile and vascular function were not accompanied by a change in endothelial nitric oxide synthase, neuronal nitric oxide synthase, inducible nitric oxide synthase expression, or endothelial nitric oxide synthase activity, suggesting that the inhibitory effect is caused by a decrease in nitric oxide bioavailability mediated by increased NADPH oxidase and reactive oxygen species production.

Gigapixel surface imaging of radical prostatectomy specimens for comprehensive detection of cancer-positive surgical margins using structured illumination microscopy.

Achieving cancer-free surgical margins in oncologic surgery is critical to reduce the need for additional adjuvant treatments and minimize tumor recurrence; however, there is a delicate balance between completeness of tumor removal and preservation of adjacent tissues critical for normal post-operative function. We sought to establish the feasibility of video-rate structured illumination microscopy (VR-SIM) of the intact removed tumor surface as a practical and non-destructive alternative to intra-operative frozen section pathology, using prostate cancer as an initial target. We present the first images of the intact human prostate surface obtained with pathologically-relevant contrast and subcellular detail, obtained in 24 radical prostatectomy specimens immediately after excision. We demonstrate that it is feasible to routinely image the full prostate circumference, generating gigapixel panorama images of the surface that are readily interpreted by pathologists. VR-SIM confirmed detection of positive surgical margins in 3 out of 4 prostates with pathology-confirmed adenocarcinoma at the circumferential surgical margin, and furthermore detected extensive residual cancer at the circumferential margin in a case post-operatively classified by histopathology as having negative surgical margins. Our results suggest that the increased surface coverage of VR-SIM could also provide added value for detection and characterization of positive surgical margins over traditional histopathology.