Transarterial Embolization of Liver Cancer in a Transgenic Pig Model.

PURPOSE: To develop and characterize a porcine model of liver cancer that could be used to test new locoregional therapies. MATERIALS AND METHODS: Liver tumors were induced in 18 Oncopigs (transgenic pigs with Cre-inducible TP53R167H and KRASG12D mutations) by using an adenoviral vector encoding the Cre-recombinase gene. The resulting 60 tumors were characterized on multiphase contrast-enhanced CT, angiography, perfusion, micro-CT, and necropsy. Transarterial embolization was performed using 40-120 µm (4 pigs) or 100-300 µm (4 pigs) Embosphere microspheres. Response to embolization was evaluated on imaging. Complications were determined based on daily clinical evaluation, laboratory results, imaging, and necropsy. RESULTS: Liver tumors developed at 60/70 (86%) inoculated sites. Mean tumor size was 2.1 cm (range, 0.3-4 cm) at 1 week. Microscopically, all animals developed poorly differentiated to undifferentiated carcinomas accompanied by a major inflammatory component, which resembled undifferentiated carcinomas of the human pancreatobiliary tract. Cytokeratin and vimentin expression confirmed epithelioid and mesenchymal differentiation, respectively. Lymph node, lung, and peritoneal metastases were seen in some cases. On multiphase CT, all tumors had a hypovascular center, and 17/60 (28%) had a hypervascular rim. After transarterial embolization, noncontrast CT showed retained contrast medium in the tumors. Follow-up contrast-enhanced scan showed reduced size of tumors after embolization using either 40-120 µm or 100-300 µm Embosphere microspheres, while untreated tumors showed continued growth. CONCLUSIONS: Liver tumors can be induced in a transgenic pig and can be successfully treated using bland embolization.

Superior Rectal Artery Embolization with Tris-Acryl Gelatin Microspheres: A Randomized Comparison of Particle Size.

PURPOSE: To evaluate the safety and efficacy of superior rectal artery embolization (SRAE) with different-sized tris-acryl gelatin microspheres in symptomatic hemorrhoidal disease (HD). MATERIALS AND METHODS: Forty-two patients (male, 30; female, 12; median age, 45 years) with symptomatic HD (2 grade I, 8 grade II, 17 grade III, and 15 grade IV) were divided into 3 experimental arms (500-700 µm, 700-900 µm, and 900-1,200 µm groups; each had 14 patients) in a prospective randomized style to perform SRAE. Follow-up was performed by rectoscopy, clinical examination, and questionnaires. The primary outcome measure was the clinical success rate at 12 months. Secondary outcome measures were technical success rate, recurrence rate, procedure-related mortality, procedure-related complications, and any outcome changes between particle sizes. RESULTS: No procedure-related deaths or major morbidities were observed. There was a 54% minor complication rate (n = 23/42) in the treated zone: 45% sustained small superficial ulcerations (n = 19/42), 7% small rectosigmoid junction ulcerations (n = 3/42), and 2% small fibrotic scar tissue (n = 1/42). The clinical success rate was 93%. Of the groups, the best French bleeding score decrease was obtained in the 900-1,200 µm group. There were improvements in the quality of life score and visual analogue scale score after the SRAE procedure, although not in the Goligher score. No recurrent disease was observed. CONCLUSIONS: SRAE with tris-acryl gelatin microspheres for symptomatic HD is a safe and efficient treatment, with results favoring the use of larger microspheres.

Safety and Efficacy of Arterially Directed Liver Therapies in the Treatment of Hepatic Metastatic Ovarian Cancer: A Retrospective Single-Institution Study.

PURPOSE: To evaluate the safety and efficacy of 2 locoregional therapies (LRTs) including hepatic artery embolization (HAE) and transarterial radioembolization (TARE) in the treatment of patients with metastatic ovarian cancer to the liver. MATERIAL AND METHODS: From October 2010 to May 2019, the data of 15 consecutive patients (median age, 54 years ± 9.8; range, 35-78 years) with hepatic metastatic ovarian cancer who were treated with either HAE (n = 6; 40%) or TARE (n = 9; 60%) were reviewed. The most common histopathologic type was epithelial ovarian carcinoma (80%). The most common chemotherapy regimens used prior to embolization included carboplatin, paclitaxel, cisplatin, and bevacizumab. Patients received a mean of 4 lines ± 3 (range, 1-9) of chemotherapy. All patients with serous carcinoma were resistant to platinum at the time of embolization. Indications for embolization were progression of disease to the liver while receiving chemotherapy in 14 (93.3%) patients and palliative pain control in 1 patient. RESULTS: The overall response rates at 1, 3, and 6 months were 92.4%, 85.6%, and 70%, respectively. Median overall survival from the time of LRT was 9 (95% confidence interval [CI], 4-14) months. Median local tumor progression was 6.4 months ± 5.03 (95% CI, 3.3-9.5). No grade 3-5 adverse events were detected in either group. CONCLUSIONS: HAE and TARE were well tolerated in patients with metastatic ovarian cancer to the liver and possibly ensured prolonged disease control in heavily treated, predominantly in patients resistant to platinum. Larger numbers are needed to verify these data.

Intravesical Prostatic Protrusion Does Not Influence the Efficacy of Prostatic Artery Embolization.

PURPOSE: To compare the outcomes of prostatic artery embolization (PAE) in patients with different intravesical prostatic protrusion (IPP) grades. MATERIALS AND METHODS: This retrospective single-center study included 128 patients (aged 50-86 years) who underwent PAE from 2013 to 2017. IPP grades were classified as follows: grade I (<10 mm), grade II (10-19 mm), and grade III (≥20 mm). Nineteen patients (14.8%) had grade I [mean IPP 7.8 mm, prostatic volume (PV) 64.1 cm3], 77 (60.2%) had grade II (mean IPP 14.9 mm, PV 87.0 cm3), and 32 (25%) had grade III (mean IPP 26.2 mm, PV 132.6 cm3), P < .01. The outcomes, including PV, international prostate symptom score (IPSS), and quality of life (QoL), were compared between the IPP grades at the 12-month follow-up. Clinical failure was defined as IPSS >7 or QoL >2. RESULTS: IPP decreased (I: -8.2%, II: -27.3%, and III: -38.7%, P = .01), and all other endpoints improved (P < .01). Adjusted covariance analysis, considering baseline PV as a confounding factor, showed no correlation between the 12-month outcomes and baseline IPP. Clinical failure was observed in 17/128 patients (13.3%) and was similar in prevalence among the IPP groups (P = .20). Minor complications occurred in 43 patients (33.6%) and major in 3 (2.3%). There were statistical differences in the complications between IPP grades II and III (P < .01). CONCLUSIONS: PAE was similarly effective in all the IPP grades at the 12-month follow-up, and there was no difference in the clinical failure between the groups. Complications in IPP grade III were more frequent than those in IPP grade II.

Topical microbicides for preventing sexually transmitted infections.

BACKGROUND: This is a updated version of our Cochrane Review published in Issue 6, 2012. Sexually-transmitted infections (STIs) continue to rise worldwide, imposing an enormous morbidity and mortality burden. Effective prevention strategies, including microbicides, are needed to achieve the goals of the World Heath Organization (WHO) global strategy for the prevention and control of these infections. OBJECTIVES: To determine the effectiveness and safety of topical microbicides for preventing acquisition of STIs, including HIV. SEARCH METHODS: We undertook a comprehensive search of the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, LILACS, CLIB, Web of Science, ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, and reference lists of relevant articles up to August 2020. In addition, we contacted relevant organisations and experts. SELECTION CRITERIA: We included randomised controlled trials of vaginal microbicides compared to placebo (except for nonoxynol-9 because it is covered in related Cochrane Reviews). Eligible participants were sexually-active non-pregnant, WSM and MSM, who had no laboratory confirmed STIs. DATA COLLECTION AND ANALYSIS: Two review authors independently screened and selected studies, extracted data, and assessed risks of bias in duplicate, resolving differences by consensus. We conducted a fixed-effect meta-analysis, stratified by type of microbicide, and assessed the certainty of the evidence using the GRADE approach. MAIN RESULTS: We included eight trials from the earlier version of the review and four new trials, i.e. a total of 12 trials with 32,464 participants (all WSM). We did not find any eligible study that enrolled MSM or reported fungal STI as an outcome. We have no study awaiting assessment. All 12 trials were conducted in sub-Saharan Africa, with one having a study site in the USA, and another having a site in India. Vaginal microbicides tested were BufferGel and PRO 2000 (1 trial, 3101 women), Carraguard (1 trial, 6202 women), cellulose sulphate (2 trials, 3069 women), dapivirine (2 trials, 4588 women), PRO 2000 (1 trial, 9385 women), C31G (SAVVY) (2 trials, 4295 women), and tenofovir (3 trials, 4958 women). All microbicides were compared to placebo and all trials had low risk of bias. Dapivirine probably reduces the risk of acquiring HIV infection: risk ratio (RR) 0.71, (95% confidence interval (CI) 0.57 to 0.89, I2 = 0%, 2 trials, 4588 women; moderate-certainty evidence). The other microbicides may result in little to no difference in the risk of acquiring HIV (low-certainty evidence); including tenofovir (RR 0.83, 95% CI 0.68 to 1.02, cellulose sulphate (RR 1.20, 95% CI 0.74 to 1.95, BufferGel (RR 1.05, 95% CI 0.73 to 1.52), Carraguard (RR 0.89, 95% CI 0.71 to 1.11), PRO 2000 (RR 0.93, 95% CI 0.77 to 1.14), and SAVVY (RR 1.38, 95% CI 0.79 to 2.41). Existing evidence suggests that cellulose sulphate (RR 0.99, 95% CI 0.37 to 2.62, 1 trial, 1425 women), and PRO 2000 (RR 0.95, 95% CI 0.73 to 1.23) may result in little to no difference in the risk of getting herpes simplex virus type 2 infection (low-certainty evidence). Two studies reported data on tenofovir's effect on this virus. One suggested that tenofovir may reduce the risk (RR 0.55, 95% CI 0.36 to 0.82; 224 participants) while the other did not find evidence of an effect (RR 0.94, 95% CI 0.85 to 1.03; 1003 participants). We have not reported the pooled result because of substantial heterogeneity of effect between the two studies (l2 = 85%). The evidence also suggests that dapivirine (RR 1.70, 95% CI 0.63 to 4.59), tenofovir (RR 1.27, 95% CI 0.58 to 2.78), cellulose sulphate (RR 0.69, 95% CI 0.26 to 1.81), and (Carraguard (RR 1.07, 95% CI 0.75 to 1.52) may have little or no effect on the risk of acquiring syphilis (low-certainty evidence). In addition, dapivirine (RR 0.97, 95% CI 0.89 to 1.07), tenofovir (RR 0.90, 95% CI 0.71 to 1.13), cellulose sulphate (RR 0.70, 95% CI 0.49 to 0.99), BufferGel (RR 0.97, 95% CI 0.65 to 1.45), Carraguard (RR 0.96, 95% CI 0.83 to 1.12), and PRO 2000 (RR 1.01, 95% CI 0.84 to 1.22) may result in little to no difference in the risk of acquiring chlamydia infection (low-certainty evidence). The evidence also suggests that current topical microbicides may not have an effect on the risk of acquiring gonorrhoea, condyloma acuminatum, trichomoniasis, or human papillomavirus infection (low-certainty evidence). Microbicide use in the 12 trials, compared to placebo, did not lead to any difference in adverse event rates. No study reported on acceptability of the intervention.  AUTHORS' CONCLUSIONS: Current evidence shows that vaginal dapivirine microbicide probably reduces HIV acquisition in women who have sex with men. Other types of vaginal microbicides have not shown evidence of an effect on acquisition of STIs, including HIV. Further research should continue on the development and testing of new microbicides.

Chitosan-bovine serum albumin-Carbopol 940 nanogels for mupirocin dermal delivery: ex-vivo permeation and evaluation of cellular binding capacity via radiolabeling.

The goal of this study was to develop and examine the nanogel-based topical delivery system of mupirocin. Nanogels were prepared with chitosan and bovine serum albumin by ionic gelation and Carbopol 940 was added to improve the gelling/adhesive properties. Detailed characterization studies were performed and the cellular binding capacity of radiolabeled nanogels was investigated on CCD-1070Sk cell lines. Results indicate the successful formation of nanogels with particle size and zeta potential ranged between 341.920-603.320 nm and 13.120-24.300 mV, respectively. The mechanical and rheological studies proved pseudoplastic and strong elastic gel behavior (G' > G''). Mupirocin was successfully entrapped into nanogels with a ratio of more than 95% and the loaded drug was slowly released up to 93.89 ± 3.07% within 24 h. The ex vivo penetration and permeation percentages of mupirocin were very low (1.172 ± 0.202% and 0.161 ± 0.136%) indicating the suitability of nanogels for dermal use against superficial skin infections. The microbiological studies pointed out the effectiveness of nanogels against Staphylococcus aureus strains. Nanogels did not show toxicity signs and the cell binding capacity of radiolabeled formulations was found to be higher than [99mTc]NaTcO4 to CCD-1070Sk cell line. Overall, mupirocin nanogels might be considered as a potential and safe topical treatment option for bacterial skin infections.

Polyvinyl Alcohol/Chitosan Single-Layered and Polyvinyl Alcohol/Chitosan/Eudragit RL100 Multi-layered Electrospun Nanofibers as an Ocular Matrix for the Controlled Release of Ofloxacin: an In Vitro and In Vivo Evaluation.

A novel nanofiber insert was prepared with a modified electrospinning method to enhance the ocular residence time of ofloxacin (OFX) and to provide a sustained release pattern by covering hydrophilic polymers, chitosan/polyvinyl alcohol (CS/PVA) nanofibers, with a hydrophobic polymer, Eudragit RL100 in layers, and by glutaraldehyde (GA) cross-linking of CS-PVA nanofibers for the treatment of infectious conjunctivitis. The morphology of the prepared nanofibers was studied using scanning electron microscopy (SEM). The average fiber diameter was found to be 123 ± 23 nm for the single electrospun nanofiber with no cross-linking (OFX-O). The single nanofibers, cross-linked for 10 h with GA (OFX-OG), had an average fiber diameter of 159 ± 30 nm. The amount of OFX released from the nanofibers was measured in vitro and in vivo using UV spectroscopy and microbial assay methods against Staphylococcus aureus, respectively. The antimicrobial efficiency of OFX formulated in cross-linked and non-cross-linked nanofibers was affirmed by observing the inhibition zones of Staphylococcus aureus and Escherichia coli. In vivo studies using the OFX nanofibrous inserts on a rabbit eye confirmed a sustained release pattern for up to 96 h. It was found that the cross-linking of the nanofibers by GA vapor could reduce the burst release of OFX from OFX-loaded CS/PVA in one layer and multi-layered nanofibers. In vivo results showed that the AUC0-96 for the nanofibers was 9-20-folds higher compared to the OFX solution. This study thus demonstrates the potential of the nanofiber technology is being utilized to sustained drug release in ocular drug delivery systems.

Tension-Free Vaginal Tape Surgery versus Polyacrylamide Hydrogel Injection for Primary Stress Urinary Incontinence: A Randomized Clinical Trial.

PURPOSE: We evaluated whether polyacrylamide hydrogel is noninferior to tension-free vaginal tape to treat women with primary stress urinary incontinence. MATERIALS AND METHODS: In this controlled noninferiority clinical trial patients with primary stress urinary incontinence were randomized to tension-free vaginal tape or polyacrylamide hydrogel treatment. The primary outcome was patient satisfaction and secondary outcomes were effectiveness in reducing urinary leakage and complications at 1-year followup. For statistical power significance was considered at 5%, power was set at 80% and the noninferiority limit was 20% with a 10% expected dropout rate. RESULTS: A total of 224 women with primary stress urinary incontinence entered the study between September 28, 2015 and March 1, 2017. Of the women 111 were randomized to tension-free vaginal tape and 113 were randomized to polyacrylamide hydrogel. At 1 year a satisfaction score of 80 or greater on a visual analogue scale of 0 to 100 was reached in 95.0% and 59.8% of patients treated with tension-free vaginal tape and polyacrylamide hydrogel, respectively. Thus, polyacrylamide hydrogel did not meet the noninferiority criteria set in our study. As secondary outcomes, the cough stress test was negative in 95.0% of tension-free vaginal tape cases vs 66.4% of polyacrylamide hydrogel cases (difference 28.6%, 95% CI 18.4-38.5). However, most perioperative complications, including those in 19 tension-free vaginal tape cases vs 3 polyacrylamide hydrogel cases (difference 16.0%, 95% CI 7.8-24.9), and all 6 reoperations due to complications (difference 5.9%, 95% CI 1.2-12.4) were associated with tension-free vaginal tape. CONCLUSIONS: Mid urethral tension-free vaginal tape slings were associated with better satisfaction and cure rates than polyacrylamide hydrogel in women with primary stress urinary incontinence. However, complications were mainly associated with tension-free vaginal tape. Thus, tension-free vaginal tape should be offered as first line treatment in women who expect to be completely cured by the initial treatment and are willing to accept the complication risks. Since polyacrylamide hydrogel treatment also provides high satisfaction and cure rates, women with primary stress urinary incontinence can be offered polyacrylamide hydrogel as an alternative treatment.

Three-Dimensional Augmented Reality Visualization Informs Locoregional Therapy in a Translational Model of Hepatocellular Carcinoma.

PURPOSE: To evaluate the utility of visualizing preprocedural MR images in 3-dimensional (3D) space using augmented reality (AR) before transarterial embolization of hepatocellular carcinoma (HCC) in a preclinical model. MATERIALS AND METHODS: A total of 28 rats with diethylnitrosamine-induced HCCs > 5 mm treated with embolization were included in a prospective study. In 12 rats, 3D AR visualization of preprocedural MR images was performed before embolization. Procedural metrics including catheterization time and radiation exposure were compared vs a prospective cohort of 16 rats in which embolization was performed without AR. An additional cohort of 15 retrospective cases was identified and combined with the prospective control cohort (n = 31) to improve statistical power. RESULTS: A 37% reduction in fluoroscopy time, from 11.7 min to 7.4 minutes, was observed with AR when compared prospectively, which did not reach statistical significance (P = .12); however, when compared with combined prospective and retrospective controls, the reduction in fluoroscopy time from 14.1 min to 7.4 minutes (48%) was significant (P = .01). A 27% reduction in total catheterization time, from 42.7 minutes to 31.0 minutes, was also observed with AR when compared prospectively, which did not reach statistical significance (P = .11). No significant differences were seen in dose-area product or air kerma prospectively. CONCLUSIONS: Three-dimensional AR visualization of preprocedural imaging may aid in the reduction of procedural metrics in a preclinical model of transarterial embolization. These data support the need for further studies to evaluate the potential of AR in endovascular oncologic interventions.

Prostatic Artery Embolization Using 100-300-µm Trisacryl Gelatin Microspheres to Treat Lower Urinary Tract Symptoms Attributable to Benign Prostatic Hyperplasia: A Single-Center Outcomes Analysis with Medium-Term Follow-up.

PURPOSE: To report medium-term outcomes of prostatic artery embolization (PAE) using 100-300-µm trisacryl gelatin microspheres to treat lower urinary tract symptoms (LUTS) from benign prostatic hyperplasia (BPH) and to evaluate how cone-beam computed tomography-measured prostate gland volume (PGV), median lobe enlargement (MLE), age, and Charlson Comorbidity Index (CCI) affect these results. MATERIALS AND METHODS: Seventy-four consecutive patients who underwent PAE from April 2014 through August 2018 were retrospectively reviewed. Patients had International Prostate Symptom Score (IPSS) >12, Quality of Life (QoL) score >2, prostate gland volume (PGV) >40 mL, age older than 45 years, and medical therapy failure. Twelve patients were excluded for bladder pathology or prostate cancer. Patients (n = 62, age = 71.8 ± 9.3 years, CCI = 3.5 ± 1.7, PGV = 174 ± 110 mL) had pre-procedure IPSS = 22.4 ± 5.6, QoL score = 4.4 ± 0.9, and post-void residual (PVR) = 172 ± 144 mL. Post-procedure values were compared to baseline at 1, 3, 6, 12, and 24 months. Associations between outcomes and PGV, MLE, age, and CCI were evaluated. Adverse event recording used Clavien-Dindo classification. RESULTS: One month after PAE (n = 37), IPSS improved to 7.6 ± 5.2 (P < .0001) and QoL score improved to 1.7 ± 1.4 (P < .0001). At 3 months (n = 32), improvements continued, with IPSS = 6.4 ± 5.1 (P < .0001), QoL score = 1.2 ± 1.2 (P < .0001), PVR = 53 ± 41 mL (P < .001), and PGV = 73 ± 38 mL (P < .0001). Results were sustained at 6 months (n = 35): IPSS = 6.4 ± 4.1 (P < .0001), QoL score = 1.2 ± 1.2 (P < .0001), PVR = 68 ± 80 mL (P < .0001), PGV = 60 ± 19 mL (P < .001). At 12 months, patients (n = 26) had IPSS = 7.3 ± 5.5 (P < .0001), QoL score = 1.2 ± 0.8 (P <.0001), PVR = 89 ± 117 mL (P < .0001), PGV = 60 ± 48 mL (P < .01). At 24 months, patients (n = 8) had IPSS = 8.0 ± 5.4 (P < .0001), QoL score = 0.7 ± 0.5 (P < .0001), PVR = 91 ± 99mL (P = 0.17), and PGV = 30 ± 5mL (P = .11). Improvements were independent of PGV, MLE, age, and CCI. Two grade II urinary infections occurred. CONCLUSIONS: PAE with 100-300-µm microspheres produced sustained substantial improvements in LUTS, PGV, and PVR, which were independent of baseline PGV, MLE, age, or CCI.

Intra-Arterial Lidocaine Administration for Anesthesia after Uterine Artery Embolization with Trisacryl Gelatin Microspheres for Leiomyoma.

PURPOSE: To evaluate whether administration of lidocaine into the uterine artery for anesthesia immediately after uterine artery embolization (UAE) with trisacryl gelatin microspheres (TAGM) for leiomyoma is safe and effective. MATERIALS AND METHODS: In a single-institution retrospective study, 100 patients underwent UAE using TAGM with a pruned tree endpoint between June 2014 and April 2019. The first 50 patients (control group) underwent UAE without lidocaine; in the second 50 patients (study group), lidocaine was administered into the uterine artery immediately after UAE. Baseline characteristics and technical and periprocedural outcomes were compared. Visual analog scale (VAS) scores 0, 3, 6, 9, 12, and 18 hours after UAE were compared between the groups with repeated measures analysis of variance. Each multivariate-adjusted VAS score < 24 hours was compared with analysis of covariance. RESULTS: No significant differences were observed in baseline characteristics or technical and periprocedural outcomes, including the volume of morphine used (P = .415), between the groups. No significant differences were found in crude or multivariate-adjusted VAS scores at each time point < 24 hours. Only the multivariate-adjusted VAS score 3 hours after UAE was 0.7 lower in the study group (mean ± SE, 2.2 ± 0.3 vs 2.9 ± 0.3); however, no significant difference was noted (P = .070). No adverse events associated with lidocaine were detected. CONCLUSIONS: Intra-arterial lidocaine administration immediately after UAE with TAGM for leiomyoma was safe, but did not contribute to significant reductions in pain or volume of narcotic agent administered.

The relationship of embolic particle size to patient outcomes in prostate artery embolisation for benign prostatic hyperplasia: a systematic review and meta-regression.

AIM: To explore the relationship of embolic particle size used in prostate artery embolisation (PAE) to patient outcomes. MATERIALS AND METHODS: A systematic review of PubMed, EMBASE, and the Cochrane database was undertaken to identify all existing studies using PAE for benign prostatic hyperplasia (BPH). Inclusion criteria included prospective studies reporting baseline and 12-month International Prostate Symptom Score (IPSS) and particle size. Exclusion criteria were overlapping studies, commentaries, abstracts, and letters. Data extraction from eligible studies included the size of embolic particle, particle material, and baseline and 12-month values for the following patient outcomes: IPSS, IPSS quality of life, urinary flow rate (Q-max), prostate volume, prostate specific antigen, and post-void residual volume. A meta-regression analysis was then undertaken to examine the relationship of particle size to patient outcome measures. RESULTS: Six studies with a total of 687 patients were identified. Meta-regression analysis demonstrated particle size as a statistically significant (p<0.001) moderator of 12-month IPSS change following PAE. No statistically significant relationships were identified with other patient outcome measures. CONCLUSION: Smaller embolic particle size is associated with a greater reduction in IPSS following PAE.

Oxiconazole nitrate solid lipid nanoparticles: formulation, in-vitro characterization and clinical assessment of an analogous loaded carbopol gel.

The aim of the present work was to develop a promising drug delivery system of oxiconazole nitrate-loaded solid lipid nanoparticles (SLNs) topical gel to enhance the drug effectiveness for the treatment of Tinea infection. SLNs were prepared by emulsification-solvent evaporation method. Particle size and entrapment efficiency of the prepared SLNs were investigated. An appropriate formulation was selected and examined for morphology and physicochemical characterization adopting Scanning electron microscope and Differential scanning colorimetry. In-vitro drug release was also investigated. The selected SLNs were loaded into 1% Carbopol 934 gel that was investigated for homogeneity, pH, grittiness, spreadability, viscosity and in vitro drug release. Clinical study for the developed gel system compared to the corresponding marketed product was conducted on 28 patients. The results revealed that the prepared oxiconazole nitrate SLNs had drug entrapment efficiency ranging from 41.34% to 75.07% and zeta potential lying between -13 and -50. Physicochemical characterization revealed a decrease in the drug crystallinity in the prepared SLNs. The gel formulation showed appropriate physical characteristics and sustained in-vitro drug release. Clinical study for the prepared oxiconazole nitrate SLNs gel showed significantly less side effects, better patient satisfaction and superior clinical improvement compared with the corresponding marketed product.

Patient Characteristics that May Influence the Effect of Urethral Injection Therapy for Female Stress Urinary Incontinence.

PURPOSE: Urethral injection therapy is a well-known treatment of female stress urinary incontinence but to our knowledge the optimal group of recipients has not been established. In this study we examined which patient characteristics are associated with success after urethral injection therapy. MATERIALS AND METHODS: This study is a post hoc analysis of a previously published, randomized, 33-center study of the hydrogel bulking agent Bulkamid® vs the collagen gel Contigen®. Regardless of the treatment women were considered cured if there were no stress incontinence episodes in the bladder diary and no stress incontinence symptoms on the ICIQ-UI-SF (International Consultation on Incontinence Questionnaire-Urinary Incontinence-Short Form), improved if there was a 50% or greater reduction in stress incontinence episodes and no effect if there was less than a 50% reduction in stress incontinence episodes 1 year after treatment. RESULTS: Of the 345 women who were initially randomized 291 were included in this study. A total of 191 women received hydrogel and 100 received collagen. At 1 year 74 women (25%) were cured, 164 (56%) were improved and 53 (18%) showed no effect. On multivariate logistic regression analysis age 60 years or greater and fewer than 2.5 daily stress incontinence episodes were associated with cure. In this group 90% of women experienced a treatment effect and 38% were cured compared with a 13% cure rate in those younger than 60 years with 2.5 or more daily stress incontinence episodes. CONCLUSIONS: Urethral injection therapy was more effective to treat stress urinary incontinence in women 60 years old or older with fewer than 2.5 daily stress incontinence episodes. It had a 90% success rate in these women.

Prostatic Artery Embolization for Benign Prostatic Hyperplasia: Prospective Randomized Trial of 100-300 µm versus 300-500 µm versus 100- to 300-µm + 300- to 500-µm Embospheres.

PURPOSE: This study compared the safety and efficacy of prostatic arterial embolization (PAE) with that of trisacryl gelatin microspheres of different sizes for treatment of benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: This study consisted of a single-center, randomized controlled clinical trial in 138 patients who underwent PAE for BPH between July 2015 and December 2016. Patients were randomized to PAE using microspheres of different sizes: group A patients were treated with microspheres 100-300 µm, group B with 300-500 µm, and group C with 100-300 µm followed by 300-500 µm. All patients were evaluated before and at 1, 3, 6, 12, and 18 months after PAE. Baseline data were comparable across the 3 groups, using the following mean International Prostate Symptom Score/quality of life (IPSS/QoL); prostate volume (PV) scores, respectively: 23.0/4.14; 87.9 cm3 (group A); 23.0/4.09; 89.0 cm3 (group B); and 24.2/4.29; 81.0 cm3 (group C) (P > 0.05). RESULTS: Mean IPSS/QoL scores; PV after PAE were: 9.98/2.49; 65.1 cm3 (group A); 8.24/2.26; 63.1 cm3 (group B); and 10.1/2.69; 53.1 cm3 (group C) (P = 0.23; P = 0.39; P = 0.24). There were 26 clinical failures. The cumulative probabilities of clinical success at 18 months were 76.7% in group A, 82.6% in group B, and 83.3% in group C (P = 0.68). Nontarget embolization was prevented in 6 patients by coil embolization. All adverse events were mild and self-limited with rates of 86.0% in group A (37 of 43); 41.3% in group B (19 of 46); and 58.3% in group C (28 of 48) (P < 0.001). Dysuria was the most frequent adverse event (28 of 137 [20.4%]). CONCLUSIONS: PAE outcomes were not significantly different among microspheres of different sizes. The use of 100- to 300-µm microspheres was associated with an increased risk of minor adverse events.

Randomized Clinical Trial of Balloon Occlusion versus Conventional Microcatheter Prostatic Artery Embolization for Benign Prostatic Hyperplasia.

PURPOSE: To compare balloon occlusion prostatic artery embolization (bPAE) with conventional microcatheter PAE (cPAE). MATERIALS AND METHODS: In this single-center trial, between November 2017 and November 2018, 89 patients with symptomatic benign prostatic hyperplasia were randomly assigned to cPAE (n = 43) or bPAE (n = 46). All patients received embolization with 300-500 µm Embosphere microspheres and were evaluated before and 1 and 6 months after PAE. Primary outcome measure was change from baseline in International Prostate Symptom Score (IPSS). Student t test was used for between-group comparisons of change from baseline, and paired t test was used for within-group comparisons. RESULTS: At baseline, groups were identical (P > .05). Unilateral PAE was performed in 4 patients receiving cPAE and 3 patients receiving bPAE (9.30% and 6.52%, P = .708). Procedural and fluoroscopy times, dose area product, air kerma, embolic volume, and mean prostate-specific antigen (PSA) 24 hours after PAE did not differ between groups (P > .05). Coils were used in 6 patients receiving cPAE and 4 patients receiving bPAE (14.0% and 8.70%, P = .51). Assessments at 6 months after PAE showed mean IPSS reduction was 7.58 ± 6.88 after cPAE and 8.30 ± 8.12 after bPAE (P = .65); mean prostate volume reduction was 21.9 cm3 ± 51.6 (18.2%) after cPAE and 6.15 cm3 ± 14.6 (7.3%) after bPAE (P = .05); mean PSA reduction was 0.9 ng/mL ± 2.22 after cPAE and 0.22 ng/mL ± 1.65 after bPAE (P = .10). Penile skin lesions (n = 3) and rectal bleeding (n = 2) were documented only in patients receiving cPAE (11.9%, P = .01). No major adverse events occurred. CONCLUSIONS: bPAE is as effective as cPAE in treating benign prostatic hyperplasia with a potential to reduce nontarget embolization.

Insufficient Leiomyoma Infarction in Uterine Artery Embolization: Relationship with Tumor Location.

PURPOSE: To evaluate which leiomyoma location in the uterus predicts insufficient tumor infarction after uterine artery embolization (UAE). MATERIALS AND METHODS: In this single-institution retrospective study, 45 patients (mean age, 43.4 y ± 4.1) underwent UAE for leiomyomas using trisacryl gelatin microspheres alone with "pruned-tree" endpoint performed by qualified interventional radiologists between October 2015 and July 2017. Technical outcomes and complications were assessed. All patients underwent unenhanced and enhanced MR imaging before and after UAE. A total of 476 tumors of ≥ 1 cm observed in all patients were evaluated. Multivariate generalized linear mixed model analysis was performed to investigate relationships between insufficient tumor infarction (< 90%) on contrast-enhanced MR imaging after UAE and baseline factors, including tumor location in the long-axis, front-back, and inner-outer directions and tumor size. RESULTS: All patients successfully underwent UAE with no major complications. Multivariate analysis revealed that there was a higher likelihood of insufficient infarction of tumors at the cervix (odds ratio [OR] 80.45; 95% confidence interval [CI] 9.97, 649.09; P < .001) and lower body (OR 4.31; 95% CI 2.52, 7.38; P < .001) than at the upper body and of tumors at the front than at the back wall (OR 2.20; 95% CI 1.32, 3.67; P = .002). Tumor size (OR 0.71; 95% CI 0.61, 0.82; P < .001) was a significant factor, whereas tumor location in the inner-outer direction was not. CONCLUSIONS: Insufficient leiomyoma infarction after UAE was more likely to involve tumors at the cervix, lower body, or front wall of the uterus or smaller tumors.

The Role of Non-Contrast Cone Beam CT in Identifying Incomplete Treatment during Uterine Artery Embolization.

PURPOSE: To describe the utility of post-procedure noncontrast cone-beam computed tomography (CT) in identifying cases of incomplete treatment and the need to search for additional vascular supply during uterine artery embolization (UAE). MATERIALS AND METHODS: From June 2013 to June 2018, 427 patients (age, 45 ± 5 years) underwent 430 consecutive UAEs with post-embolization noncontrast cone-beam CT. If noncontrast cone-beam CT showed an area of the uterus lacking contrast retention, aortography was performed to search for collateral supply. Procedures were characterized as suspected complete bilateral UAEs or suspected incomplete UAEs, such as in cases of a unilateral uterine artery or diminutive uterine arteries. Rates of inadequate contrast retention on noncontrast cone-beam CT and discovered collateral artery supply were calculated. In 10 consecutive cases in which both noncontrast cone-beam CT and aortography were performed, dose-area product radiation exposure from noncontrast cone-beam CT and aortography was compared using a 2-sided paired-sample t-test. RESULTS: Of the 411 suspected complete bilateral UAEs, noncontrast cone-beam CT showed an area of the uterus lacking contrast retention in 38 (9.2%) cases. Of the 19 suspected incomplete UAEs, noncontrast cone-beam CT demonstrated incomplete treatment in 6 (31.6%) patients. Aortography was performed in 40 of the 44 cases of incomplete treatment on noncontrast cone-beam CT, and collateral supply was found in 28 (70.0%) cases. In 22 of these cases (5.2% of the 427 patients studied), noncontrast cone-beam CT led to the discovery of significant collateral supply requiring further embolization. Dose-area product radiation exposure from noncontrast cone-beam CT was less than from aortography (P = .007). CONCLUSIONS: Post-UAE noncontrast cone-beam CT can be used to select a subset of patients with a higher likelihood of collateral supply who may benefit from post-embolization aortography.

Thickness-to-Height Ratio of Intravesical Prostatic Protrusion Predicts the Clinical Outcome and Morbidity of Prostatic Artery Embolization for Benign Prostatic Hyperplasia.

PURPOSE: To evaluate the presence of intravesical prostatic protrusion (IPP) and its thickness-to-height (T/H) ratio as a predictor for the clinical outcome and morbidity of prostatic artery embolization (PAE) for benign prostatic hyperplasia. MATERIALS AND METHODS: This was a prospective, single-center, institutional review board-approved study from June 2015 to December 2018 of 82 consecutive patients (age, 53-79 years; median, 66 years) with International Prostate Symptom Score (IPSS) ≥15 and quality-of-life (QOL) score ≥3. The presence of IPP and its T/H ratio were assessed on baseline magnetic resonance imaging for their correlation with the clinical outcomes of suboptimal IPSS (IPSS ≥10) and suboptimal QOL (QOL ≥3) up to 12 months after PAE and the occurrence of post-procedure complications (≤30 days), which caused a certain degree of urinary outflow obstruction. The chi-squared test was used for analysis. RESULTS: IPP was present in 57 of 82 patients (69.5%). The presence of IPP correlated with the occurrence of post-procedure complications (P = .009) but not with suboptimal IPSS at 12 months (P = .758). IPP with a T/H ratio ≤1.3 correlated with suboptimal IPSS at 12 months (P = .025) and suboptimal QOL at 6 months (P = .025) and 12 months (P = .008), as well as with the occurrence of post-procedure complications (P = .009). CONCLUSIONS: IPP with a T/H ratio ≤1.3 predicted the occurrence of post-procedure complications with urinary obstruction. A T/H ratio ≤1.3 but not the presence of IPP alone predicted the clinical outcome up to 12 months after PAE.

Mucoadhesive Polymeric Films to Enhance Barbaloin Penetration Into Buccal Mucosa: a Novel Approach to Chemoprevention.

Nowadays, chemoprevention by administering natural supplements is considered an attractive strategy to reverse, suppress, or prevent the evolution of premalignant oral lesions. In particular, Barbaloin exhibits anti-proliferative, anti-inflammatory, and anti-cancer properties, and it results useful in multi-therapy with classic chemotherapeutics. Therefore, in this work, mucoadhesive buccal films, as locoregional drug delivery system able to provide a targeted and efficient therapeutic delivery of Barbaloin, are proposed. Thus, Aloin extract-loaded Eudragit® RL100 or Eudragit® RS100-based buccal films were designed in order to obtain an easily self-administrable formulation capable of promoting Barbaloin penetration into buccal mucosa and assuring high patient compliance. Large amounts of extract (44%) were loaded into the polymer matrix and six formulations were prepared varying polymers and plasticizers ratios. For all formulations, physical form (thermogravimetric analysis-differential scanning calorimetry, TGA-DSC), swelling degree, mucoadhesiveness, drug release, and ability to promote drug penetration in mucosa have been investigated. After a sequential selection process, Eudragit RS 100-based film, with low PVP and high plasticizers amounts, emerged as the most promising. It results appropriately flexible, uniform in terms of weight, thickness and drug content, as well as characterized by suitable surface pH, good mucoadhesiveness, and low swelling degree. It displays a Higuchian drug release behavior up to 89% of Barbaloin released, thus demonstrating that diffusion through the matrix is the main release mechanism. Remarkable penetration enhancer properties of film were demonstrated by evidence of Barbaloin accumulation into buccal mucosa up to 10-fold higher than those obtained following administration of Aloin solution.