HES V2.0 outperforms GALAD for detection of HCC: A phase 3 biomarker study in the United States.

BACKGROUND AND AIMS: The original hepatocellular carcinoma early detection screening (HES) score, which combines alpha-fetoprotein (AFP) with age, alanine aminotransferase, and platelets, has better performance than AFP alone for early HCC detection. We have developed HES V2.0 by adding AFP-L3 and des-gamma-carboxy prothrombin to the score and compared its performance to GALAD and ASAP scores among patients with cirrhosis. APPROACH AND RESULTS: We conducted a prospective-specimen collection, retrospective-blinded-evaluation phase 3 biomarker cohort study in patients with cirrhosis enrolled in imaging and AFP surveillance. True-positive rate (TPR)/sensitivity and false-positive rate for any or early HCC were calculated for GALAD, ASAP, and HES V2.0 scores within 6, 12, and 24 months of HCC diagnosis. We calculated the AUROC curve and estimated TPR based on an optimal threshold at a fixed false-positive rate of 10%. We analyzed 2331 patients, of whom 125 developed HCC (71% in the early stages). For any HCC, HES V2.0 had higher TPR than GALAD overall (+7.2%), at 6 months (+3.6%), at 12 months (+7.2%), and 24 months (+13.0%) before HCC diagnosis. HES V2.0 had higher TPR than ASAP for all time points (+5.9% to +12.0%). For early HCC, HES V2.0 had higher sensitivity/TPR than GALAD overall (+6.7%), at 12 months (+6.3%), and 24 months (+14.6%) but not at 6 months (+0.0%) and higher than ASAP for all time points (+13.4% to +18.0%). CONCLUSIONS: In a prospective cohort study, HES V2.0 had a significantly higher performance for identifying new HCC, including early stage, than GALAD or ASAP.

Serum biomarker signature is predictive of the risk of hepatocellular cancer in patients with cirrhosis.

BACKGROUND: Inflammatory and metabolic biomarkers have been associated with hepatocellular cancer (HCC) risk in phases I and II biomarker studies. We developed and internally validated a robust metabolic biomarker panel predictive of HCC in a longitudinal phase III study. METHODS: We used data and banked serum from a prospective cohort of 2266 adult patients with cirrhosis who were followed until the development of HCC (n=126). We custom designed a FirePlex immunoassay to measure baseline serum levels of 39 biomarkers and established a set of biomarkers with the highest discriminatory ability for HCC. We performed bootstrapping to evaluate the predictive performance using C-index and time-dependent area under the receiver operating characteristic curve (AUROC). We quantified the incremental predictive value of the biomarker panel when added to previously validated clinical models. RESULTS: We identified a nine-biomarker panel (P9) with a C-index of 0.67 (95% CI 0.66 to 0.67), including insulin growth factor-1, interleukin-10, transforming growth factor ß1, adipsin, fetuin-A, interleukin-1 ß, macrophage stimulating protein α chain, serum amyloid A and TNF-α. Adding P9 to our clinical model with 10 factors including AFP improved AUROC at 1 and 2 years by 4.8% and 2.7%, respectively. Adding P9 to aMAP score improved AUROC at 1 and 2 years by 14.2% and 7.6%, respectively. Adding AFP L-3 or DCP did not change the predictive ability of the P9 model. CONCLUSIONS: We identified a panel of nine serum biomarkers that is independently associated with developing HCC in cirrhosis and that improved the predictive ability of risk stratification models containing clinical factors.

Role of Tamsulosin Therapy after Extracorporeal Shockwave Lithotripsy for Renal Stones: Randomized Controlled Trial.

INTRODUCTION: To evaluate the efficacy of adjunctive tamsulosin therapy after extracorporeal shockwave lithotripsy (SWL) for renal stones. MATERIALS AND METHODS: This prospective study was conducted on patients who underwent single-session SWL for solitary renal stone less than 20 mm. Post-SWL, patients were randomly divided into 2 groups; the tamsulosin group (TG), received a daily dose of tamsulosin 0.4 mg, for a maximum of 12 weeks, with post-SWL traditional analgesia and control group (CG), received the traditional analgesia alone. RESULTS: The study enrolled 271 patients and eventually only 249 (123 in TG and 126 in CG) completed the study. The overall stone free rate was 73.5%: 78.0% in TG and 69.0% in CG (p = 0.108). In TG, 8.1% of patients experienced at least one episode of acute renal/ureteral colic compared with 19.8% of controls (p = 0.008). The mean cumulative analgesia dosage per subject was 313 mg in TG and 346 mg in CG (p < 0.001). Overall, 14 patients developed steinstrasse and 6 of them (all in CG) needed urgent intervention (p = 0.031). CONCLUSIONS: Daily tamsulosin therapy does not enhance the clearance of stone fragments but decreases the pain episodes, analgesia dosage and need for adjuvant intervention after SWL for renal stones.

Differences in Prediagnostic Serum Metabolomic and Lipidomic Profiles Between Cirrhosis Patients with and without Incident Hepatocellular Carcinoma.

Background: Early detection of hepatocellular carcinoma (HCC) is crucial for improving patient outcomes, but we lack robust clinical biomarkers. This study aimed to identify a metabolite and/or lipid panel for early HCC detection. Methods: We developed a high-resolution liquid chromatography mass spectrometry (LC-MS)-based profiling platform and evaluated differences in the global metabolome and lipidome between 28 pre-diagnostic serum samples from patients with cirrhosis who subsequently developed HCC (cases) and 30 samples from patients with cirrhosis and no HCC (controls). We linked differentially expressed metabolites and lipids to their associated genes, proteins, and transcriptomic signatures in publicly available datasets. We used machine learning models to identify a minimal panel to distinguish between cases and controls. Results: Among cases compared with controls, 124 metabolites and 246 lipids were upregulated, while 208 metabolites and 73 lipids were downregulated. The top upregulated metabolites were glycoursodeoxycholic acid, 5-methyltetrahydrofolic acid, octanoyl-coenzyme A, and glycocholic acid. Elevated lipids comprised glycerol lipids, cardiolipin, and phosphatidylethanolamine, whereas suppressed lipids included oxidized phosphatidylcholine and lysophospholipids. There was an overlap between differentially expressed metabolites and lipids and previously published transcriptomic signatures, illustrating an association with liver disease severity. A panel of 12 metabolites that distinguished between cases and controls with an area under the receiver operating curve of 0.98 for the support vector machine (interquartile range, 0.9-1). Conclusion: Using prediagnostic serum samples, we identified a promising metabolites panel that accurately identifies patients with cirrhosis who progressed to HCC. Further validation of this panel is required.

Isolated pump erosion of an inflatable penile prosthesis through the scrotum in a diabetic patient.

Isolated pump erosion is a rare complication in patients with inflatable penile prosthesis. We describe a case of a diabetic patient who underwent inflatable penile prosthesis implantation with subsequent isolated pump erosion. Repeated attempts of conservative repair of the erosion failed. Finally, the inflatable penile prosthesis was replaced with a malleable one to avoid new pump erosion. In case of isolated pump erosion, replacement of the inflatable penile prosthesis with a malleable one looks to be a good alternative salvage treatment for the patient.

Ameliorative effect of selenium nanoparticles on testicular toxicity induced by cisplatin in adult male rats.

Cisplatin (Cis) is a treatment for testicular germ-cell tumors (TGCTs). Unfortunately, it causes testicular toxicity due to releasing reactive oxygen species (ROS) causing damage to testicular cells and chromosomes. The current study aimed to investigate the ameliorative effect of selenium nanoparticles (SeNPs) against cisplatin testicular toxicity in male rats by assessment of body weight, testis weight, oxidative stress markers in testis homogenates as (malondialdehyde (MDA), Superoxide dismutase (SOD), Glutathione reduced (GSH), Glutathione peroxidase (GSH âˆ¼ PX) and Catalase (CAT)), gene expression, testosterone concentration (T), sperm characteristics (count, motility and abnormality) and testicular histopathology. Methods: Thirty adult male rats divided equally into four groups; a single dose intraperitoneally injection of cisplatin (10 mg/kg) and selenium nanoparticles (2 mg/kg/day) were administrated alone or in combination. Cis group showed a decrease in body weight, testis weight, antioxidant activities (SOD, GSH, GSH âˆ¼ PX and CAT), T concentration and steroidogenetic expression, the data recorded an increase in MDA levels and sperm abnormality, meanwhile histopathology of testis sections showed degenerative changes in the seminiferous tubules. The co-administration of selenium nanoparticles ameliorated the harmful effects of cisplatin. In conclusion; SeNPs through its antioxidant potential may be useful to prevent the testicular toxicity induced by cisplatin to the rat testis by reducing oxidative stress.

A Comparative Analysis Between Ketamine Versus Combination of Midazolam and Haloperidol for Rapid Safe Control of Agitated Patients in Emergency Department: A Systematic Review.

We aim to discuss the efficacy and adverse effects of using ketamine in agitated patients in the emergency department (ED) compared with the combination therapy of haloperidol with benzodiazepine. This systematic review followed Preferred Reporting Items for Systematic Review and Meta-analyses (PRISMA) guidelines. An electronic search from PubMed/Medline, Cochrane library, and Google Scholar was conducted from their inception to 30th April 2022. We included agitated patients in ED who were given infusion with ketamine only. Our comparative group was patients infused with combined therapy of haloperidol and benzodiazepine. We did not include letters, case reports, abstracts, conference papers, appraisals, reviews, and studies where full text was unavailable. We did not put any language restrictions. Three studies were selected in our manuscript (one cohort and two randomized controlled trials). All three studies showed that ketamine was used to achieve sedation in less time than the other group. However, two studies reported significantly more adverse effects in ketamine-infused groups. We concluded that ketamine use is superior when its primary focus is to sedate the patient as quickly as possible, but it carries some side effects that should be considered. However, we still need more studies assessing the efficacy of ketamine in agitated patients presenting in the ED.

An Integrative Comparative Study Between Digoxin and Amiodarone as an Emergency Treatment for Patients With Atrial Fibrillation With Evidence of Heart Failure: A Systematic Review and Meta-Analysis.

The emergency treatment of atrial fibrillation (AF) involves utilizing two strategies. The first strategy normally involves permitting the atrial fibrillation to persevere as the ventricular rate is controlled. The other method involves utilizing anti-arrhythmic drugs in cardioversion and attempting to maintain sinus rhythm. Different pharmacological treatments, including digoxin and amiodarone, have been used to manage AF. A literature review on amiodarone and digoxin in the treatment of AF among patients with heart failure (HF) has shown that both drugs have potential risks. Therefore, we are conducting this systematic review and meta-analysis to compare the effectiveness of amiodarone and digoxin in the treatment of AF among patients with evidence of HF. A literature search of relevant articles was conducted on six electronic databases (PubMed, Web of Science, Medline, ScienceDirect, Cochrane Library, and Google Scholar) from 2000 to 2022. The search yielded seven studies that had met the inclusion criteria. Our meta-analysis of four studies showed that there was no significant difference in the reduction of heart rate after treatment with either amiodarone or digoxin (mean difference (MD): -5.44; 95% confidence interval (CI): -9.53 to -1.34; I2 = 25%; p = 0.26). On the other hand, the statistical analysis showed that amiodarone had a better effect on the conversion to sinus rhythm than digoxin (63% versus 35%, respectively). Based on evidence from our meta-analysis, the clinical effect of amiodarone and digoxin in the emergency treatment of AF on heart rate control was unclear. However, amiodarone has a significant impact on the restoration of sinus rhythm compared with digoxin and can be considered the first-line drug regimen in conversion to sinus rhythm for AF patients with evidence of heart failure. However, the use of amiodarone and digoxin is complicated by adverse events and all-cause mortality.

An Analytical Comparison Between Ketamine Alone and a Combination of Ketamine and Propofol (Ketofol) for Procedural Sedation and Analgesia From an Emergency Perspective: A Systematic Review and Meta-Analysis.

Procedural sedation and analgesia (PSA) is a treatment approach involving treating patients with agents with dissociative, sedative, or analgesic properties to suppress their consciousness to variable levels. Ketamine and propofol have been used historically for PSA. Because they each have their demerits, it was postulated that combining both drugs (ketofol) would result in a mixture with additive properties and lessen or eliminate the demerits attributed to each drug. The primary objective of this systematic review and meta-analysis is to compare ketamine alone and a combination of ketamine and propofol (ketofol) for procedural sedation and analgesia from an emergency perspective. A systematic search was conducted on published studies from the databases of Scopus, ScienceDirect, PubMed, Google Scholar, APA PsycInfo, and the Cochrane Central Register of Controlled Trial (CENTRAL) until July 2022. The articles that were published on the online databases were authored between January 2007 and 2018. The selected papers were scanned and examined to check whether they met the eligibility criteria for the study. The search produced six articles that were included in the systematic review and meta-analysis. All six articles that passed the eligibility criteria were viable for the analysis. All the trials focused on the effectiveness of ketofol versus ketamine for PSA from an emergency perspective. Ketofol was found to be safe and more effective in comparison to ketamine for PTA.

Bladder preservation multimodality therapy as an alternative to radical cystectomy for treatment of muscle invasive bladder cancer.

OBJECTIVE: • To evaluate the efficacy of a bladder preservation multimodality protocol for patients with operable carcinoma invading bladder muscle. MATERIALS AND METHODS: • In this prospective study, we included 33 patients with transitional cell carcinoma (TCC) (T2 and T3, Nx, M0) who were amenable to complete transurethral resection. • These patients refused radical cystectomy as their first treatment option. After maximum transurethral resection of bladder tumour (TURBT), all patients received three cycles of adjuvant chemotherapy in the form of methotrexate, vinblastin, adriamycin and cisplatin (MVAC) followed by radical radiotherapy. • Four weeks later, all cases had radiological and cystoscopical re-evaluation. • Complete responders were considered to be those patients who had no evidence of residual tumour. All patients were subjected to a regular follow-up by cystoscopy and tumour site biopsy conducted every 3 months. Abdomino-pelvic computed tomography and chest X-ray were conducted every 6 months. • The study endpoint was the response to treatment after completion of the first year of follow-up after therapy. RESULTS: • Out of 33 eligible patients, a total of 28 patients completed the study treatment protocol. Their mean ± SD age was 56.7 ± 6 years. Trimodal therapy was well tolerated in most of cases, with no severe acute toxicities. After 12 months of follow-up, a complete response was achieved in 39.3% and a partial response in 7.1%, with an overall response rate of 46.4%. • By the end of the first year, disease-free survival was reported in 39.3%, whereas 25% were still alive with their disease, giving an overall survival of 64.3% for all patients who maintained their intact, well functioning bladders. • Tumour stage and completeness of transurethral resection of bladder tumour were the most important predictors of response and survival. T2 lesions had complete and partial response rates of 69.2% and 23%, respectively, whereas T3 lesions had rates of 40% and 13.3%, respectively (P = 0.001). • The response rate in patients who had complete TURBT was 82.6% vs 20% in those with cystoscopic biopsy only (P = 0.001). In addition, disease-free survival was 72.7% in T2 patients and 27.3% in T3 patients (P = 0.001). CONCLUSION: • In the present study, bladder preservation protocol with MVAC and radical radiotherapy achieved suboptimal response rates at 1 year in patients with localized TCC invading bladder muscle. Patients with solitary T2 lesions that are amenable to complete TURBT achieved the best response rates. Longer follow-up is needed to verify these results. Patients with localized disease should be encouraged for radical cystectomy, which achieved better results.

Anti-infection dip suggestions for the Coloplast Titan Inflatable Penile Prosthesis in the era of the infection retardant coated implant.

INTRODUCTION: Infection is the worst complication seen with inflatable penile prosthesis (IPP). Both the American Medical Systems (AMS) and Coloplast IPP have infection retardant coatings. AMS is coated at the factory with rifampicin and minocycline (InhibiZone). The Coloplast IPP has a hydrophilic coating covalently bonded to its components that will absorb any aqueous solution before implantation and provides increased surface lubricity to decrease bacterial adherence. AIM: We tested several antibiotic dips comparing zones of inhibition (ZOI) against five commonly infecting bacteria with coated Coloplast implants. Results were compared with those ZOI created with strips of an AMS IPP precoated with InhibiZone. METHODS: Pieces of sterile Coloplast Titan IPP were dipped in (i) trimethoprim/polymixin B ophthalmic solution; (ii) trimethoprim/sulfamethoxazole infusion solution; (iii) bacitracin; (iv) rifampicin/minocycline; and (v) rifampin/trimehtoprim/sulfamethoxazole. ZOI for the Titan strips and for AMS InhibiZone coated strips were tested against Staphylococcus epidermidis, Staphylococcus lugdunensis, Staphylococcus aureus, Pseudomonas, and Enterococcus. MAIN OUTCOME MEASURE: ZOIs of the Coloplast Titan for each of the medicated solutions were compared with ZOI created by undipped strips of a sterile InhibiZone coated IPP placed on plates of the identical bacteria. RESULTS: All dips except bacitracin showed ZOI≥InhibiZone (P≥0.005) for most organisms. Because of broad-spectrum effectiveness, ease of handling, and cost, infusion vial of trimehtoprim/sulfamethoxazole seemed optimal at this time. If trimehtoprim/sulfamethoxazole is unavailable; the ZOI with Polytrim ophthalmic solution zones were almost as good. CONCLUSIONS: The Coloplast strips when dipped in several solutions showed equal or significantly larger ZOI against commonly infecting organisms than the InhibiZone coated strips. At the present time using off the shelf trimethoprim sulfamethoxazole infusion solution seems optimum. The flexibility of choosing the drug eluting from the Coloplast device seems promising in the changing bacterial environment.

Renoprotective effect of grape seed extract against oxidative stress induced by gentamicin and hypercholesterolemia in rats.

RATIONALE: Kidneys are dynamic organs and represent one of the major systems maintaining the body homeostasis; they are affected by many chemicals and drugs. Grape seed extract (GSE) has been targeted to prevent drug-induced renal toxicity. OBJECTIVES: This study investigates the possible renoprotective effect of GSE against oxidative stress, renal impairment, and hypercholesterolemia (HC) induced by gentamicin (GM) and cholesterol-enriched diet. Seventy adult male Wistar rats (160 ± 10 g) were divided into seven groups: (1) served as control, (2) GSE, (3) GM, (4) GSE + GM, (5) hypercholesterolemic (HC) group, (6) GM + HC group, and (7) GM + HC + GSE. Kidney functions, inflammatory mediators, cytokines, lipid profile, nitric oxide (NO), cyclic guanosine monophosphate (cGMP), and oxidative and antioxidative stress parameters were assessed in all groups. MAIN FINDINGS: GM induced renal dysfunction, which was exacerbated by the presence of HC as confirmed by laboratory determinations. Administration of GSE attenuated the renal toxicity evidenced in significant reduction in elevated kidney function, inflammatory cytokines as well as lipid profile, NO, cGMP, enzymatic, and nonenzymatic antioxidants. CONCLUSION: Administration of GSE simultaneously with GM attenuated oxidative stress, diminished renal toxicity, and improved lipid profile induced by GM and HC.

Management of ischemic priapism by penile prosthesis insertion: prevention of distal erosion.

PURPOSE: Refractory ischemic priapism results in cavernous smooth muscle necrosis, fibrosis and eventual penile shortening. Immediate penile implant insertion for acute ischemic priapism is done to avoid consequent fibrosis and shortening but ineffective shunt surgery trials may lead to potential weakness and erosion at the corporeal tip. We evaluate nonabsorbable sling sutures to fix the implant cylinder in place and prevent protrusion through the weak corporeal tip. MATERIALS AND METHODS: We prospectively evaluated 12 men who presented with prolonged refractory ischemic priapism a median of 120 hours (range 60 to 168) in duration. All patients were unresponsive to conventional treatment and 11 had undergone unsuccessful shunt surgery. Early malleable penile prosthesis implantation had been done in all cases. To avoid possible distal protrusion a nonabsorbable sling suture was taken through the cylinder and the edges of the opened tunicae albuginea to fix the cylinder to the corporotomy edges. RESULTS: Penile implants were successfully inserted in all patients. No intraoperative or early postoperative complications were noted except in 1 with sickle cell priapism, in whom dilation led to unilateral corporeal perforation, which was managed intraoperatively. All patients were satisfied with the surgical results. No distal erosion was noted through the weak corporeal tip. No postoperative infection was reported at a median followup of 15 months (range 6 to 36). All patients successfully achieved sexual intercourse. CONCLUSIONS: Early penile prosthesis insertion for acute ischemic priapism is simple and successful. Distal cylinder protrusion through the defective corpora due to previous shunt surgery remains to confound surgical success. Nonabsorbable sling suture of the cylinder to the tunica albuginea is effective, simple and safe treatment for this formidable complication.

New enhancements of the scrotal one-incision technique for placement of artificial urinary sphincter allow proximal cuff placement.

INTRODUCTION: Urinary incontinence impairs sexual functioning and sexual satisfaction. Traditional artificial urinary sphincter (AUS) implantation requires perineal incision for cuff placement and a second inguinal incision for reservoir and pump placement. We believed AUS could be placed easier and quicker through one scrotal incision. Aim. In an effort to effect more proximal placement of the cuff while keeping the advantages of the one scrotal incision technique, we report enhancements to the original surgical technique. METHODS: Thirty patients have been operated upon using the enhanced technique. A modification of the SKW retractor system (AMS) facilitates deep bulbar exposure. Twenty patients were first time implantations and 10 were revisions with five of the revisions having had the original AUS placed by traditional two-incision technique. Two of the first time AUS patients received an inflatable penile prosthesis through the same incision. MAIN OUTCOME MEASURES: We evaluated site of cuff placement, sizes of cuffs used, postoperative continence status. RESULTS: All of the virgin AUS required dissection of the bulbocavernosus muscle prior to cuff placement. In scrotally placed revisions, replacement cuffs were situated considerably proximal (4.5-7.5 cm) to the original cuff site. The perineal placed revisions were accomplished through a scrotal incision with replacement of two cuffs in the same site and the three other patients immediately distal. No intraoperative complications were seen. One patient developed scrotal hematoma requiring drainage. Only 15 patients are available for follow-up and all are socially continent (one pad or less). CONCLUSIONS: Transscrotal approach is used safely and efficiently for penile implants and AUS implantation. The new enhancements to the one-scrotal incision technique allow more proximal cuff placement as evidenced by the bulbocavernosus muscle dissection and use of larger cuffs. Continence rate is similar to rates achieved with perineal placement of cuff found in the literature.

Amelioration of gentamicin nephrotoxicity by green tea extract in uninephrectomized rats as a model of progressive renal failure.

RATIONALE: Gentamicin (GM) is an effective antibiotic against severe infection but has limitations related to nephrotoxicity. This study investigates whether green tea extract (GTE), an antioxidant, could ameliorate the nephrotoxic effect of GM in uninephrectomized rats. OBJECTIVES: The right kidneys of 40 rats were surgically removed and 1 week later the animals were divided into four groups (n = 10). Group 1 served as control, Group 2 as GTE group, Group 3 as GM group, and Group 4 as GM+GTE group. Kidney function, inflammatory cytokine TNF-α, oxidant and antioxidant parameters of renal tissue, as well as histopathological studies were assessed. MAIN FINDINGS: Injecting uninephrectomized rats with GM induced renal dysfunction as shown by significant elevations in serum creatinine and urea. Serum TNF-α and oxidative stress parameters (superoxide anion and lipid peroxides) were also significantly increased. On the contrary, antioxidative parameters [superoxide dismutase (SOD), catalase (CAT), and reduced glutathione (GSH)] were significantly decreased. Histopathological examination of renal tissue illustrated features of degeneration, marked cellular infiltration, tubular dilatation, and varying degrees of necrosis. GTE given to GM rats reduced these nephrotoxicity parameters. Serum creatinine, urea, and TNF-α were almost normalized in the GM+GTE group. The oxidative stress parameters were significantly decreased and the antioxidative parameters were significantly increased. CONCLUSION: GTE ameliorates GM-induced nephrotoxicity and oxidative damage by improving antioxidant defense and tissue integrity. Further human studies are necessary to demonstrate the antioxidant effects of GTE on renal diseases. Nevertheless, green tea (GT) may offer an inexpensive, nontoxic, and effective intervention strategy in subjects with a risk for GM-induced nephrotoxicity.

Protective effect of trapidil and l-arginine against renal and hepatic toxicity induced by cyclosporine in rats.

RATIONALE: Cyclosporine A (CsA) leads to renal and liver injury, production of free radicals and nitric oxide (NO) deficiency. This study investigates the possible protective effects of trapidil and L-arginine against CsA-induced tissue injury. OBJECTIVES: Forty adult male Wistar rats (180 +/- 20 g) were divided into five groups, eight animals in each. The first group served as control, second group served as CsA group, third group served as CsA + trapidil group, fourth group served as CsA + L-arginine group, and fifth group served as CsA + trapidil + L-arginine group. Kidney and liver functions, inflammatory mediators, cytokines, oxidant and antioxidant parameters as well as histopathological studies of renal and liver tissue were assessed in all groups. MAIN FINDINGS: CsA induced renal and hepatic dysfunction, which was confirmed by laboratory and histopathological examination. Administration of trapidil diminished the renal and liver injury and significantly attenuated the levels of serum creatinine, urea, aspartate aminotransferase (AST), alanine aminotransferase (ALT), interleukin-1beta (IL-1beta), tumor necrosis factor alpha (TNF-alpha), monocyte chemoattractant protein-1 (MCP-1), and oxidative stress, while it significantly elevated the level of serum nitric oxide and the activity of antioxidative stress. L-Arginine gave the same trend as trapidil, but trapidil effect was more pronounced. Coadministration of trapidil + L-arginine significantly ameliorated the toxic effect of CsA, but did not differ significantly from the effect of trapidil alone. CONCLUSIONS: Treatment with trapidil or L-arginine diminished the renal and hepatic CsA-induced toxicity. However, the effect of trapidil was more pronounced. Therefore, treatment with trapidil alone may be the most economic and effective as a potential therapeutic agent in CsA injury.

Mechanical reliability of AMS 700 CX improved by parylene coating.

INTRODUCTION: Parylene coating was added to the silicone layers of the American Medical Systems (AMS) 700 controlled expansion (CX) penile prosthesis cylinders in January 2001. The coating was placed on non-tissue contacting silicone surfaces to increase lubricity, reduce friction, and silicone wear AIM: We compared mechanical reliability of the original and Parylene-enhanced AMS 700 CX in a large single surgical group series. METHODS: Seven hundred seventy-five consecutive patients receiving the AMS 700CX prosthesis (596 first time [virgin] and 179 revisions) were followed for 3 years. Four hundred fourteen received the non-coated model and 361 received the Parylene-coated device. Revision-free survival was estimated using the Kaplan-Meier product limit method and compared using the log-rank test. MAIN OUTCOME MEASURES: We calculated overall survival from revision for any reason and survival from mechanical problems such as fluid leakage, cylinder, connector or tubing breakage, pump or reservoir defects. RESULTS: For the entire series (virgin + revised) the 3-year revision free survival for any cause improved from 78.6% for non-coated to 87.4% for the Parylene-coated implants. Freedom from mechanical breakage showed similar improvement from 89.2% for the non-coated to 97.5% for enhanced models. CONCLUSIONS: This study documents that short-term mechanical reliability and survival from revision for any cause is significantly increased with Parylene-coated AMS 700CX cylinders compared with the earlier AMS 700CX model with non-coated cylinders.

Modified 16-Dot plication technique for correction of penile curvature: prevention of knot-related complications.

Penile curvature is a common urological disease. Tunical plication for correction of penile curvature has been much popularized being simpler, adjustable to avoid overcorrection, less bleeding, and less postoperative erectile dysfunction. This study aims to assess the results of modified 16-dot plication technique for correction of congenital and acquired penile curvature and avoidance of knot-associated complications. Eighteen patients underwent correction of their penile curvature using the modified 16-dot plication technique between January 2014 and October 2015. Patients' pre and postoperative data were analyzed. The mean age of patients is 44 years old. Of the patients 15 who were available for follow-up, 8 patients had congenital penile curvature (CPC) and 7 had Peyronie's disease (PD). The angle of deviation ranged from 30° to 90°. Erectile function (EF) was assessed preoperative by IIEF score and duplex ultrasound. Postoperative follow-up at 3 and 6 months revealed straight erect penis in all patients. Longer follow-up at 1 to 2 years, 2 patients complained from slight recurrence of curve (<20°) and 2 patients complained of worsening of their erectile function. Penile shortening was noted by 6 patients. None of our patients stated any knot complication or bothersome, nor do hematomas, numbness, or painful erections. The modified 16-dot plication technique for correction if penile curvature is a safe and effective method. This modification allowed the knots to be tucked in the plicate tunical tissue avoiding knot-associated complications. More investigation on a large scale of patients or multicenter studies is recommended.

Sildenafil citrate in combination with tamsulosin versus tamsulosin monotherapy for management of male lower urinary tract symptoms due to benign prostatic hyperplasia: A randomised, double-blind, placebo-controlled trial.

OBJECTIVE: To assess the additive effect of sildenafil citrate to tamsulosin in the treatment of lower urinary tract symptoms due to benign prostatic hyperplasia (LUTS/BPH) in men with or without erectile dysfunction (ED). PATIENTS AND METHODS: In all, 150 men with untreated LUTS/BPH with or without ED were randomised to receive sildenafil 25 mg once daily (OD) or placebo OD (night time) combined with tamsulosin 0.4 mg OD (day time) for 6 months. Changes from pre-treatment scores in International Prostate Symptom Score (IPSS), IPSS-quality of life (QoL) score, maximum urinary flow rate (Qmax), and the five-item version of the International Index of Erectile Function questionnaire (IIEF-5) were assessed at 3 and 6 months. Safety profiles were assessed by physical examination and monitoring clinical adverse events. RESULTS: Group A comprised of men who received tamsulosin and sildenafil (75 men), whilst those in Group B received tamsulosin and placebo (75). The IPSS was significantly improved in Group A compared to Group B, at -29.3% vs -13.7% (P = 0.039) at 3 months and -37% vs -19.6% (P = 0.043) at 6 months after treatment. Qmax significantly improved in both groups compared with before treatment (P < 0.001). The IIEF-5 scores improved more in Group A than in Group B, at 58.7% vs 11.7% at 3 months and 62.4% vs 12.4% at 6 months after treatment (both P < 0.001). CONCLUSION: Sildenafil citrate combined with tamsulosin improved LUTS, erectile function, and patient QoL more than tamsulosin monotherapy with the merit of a comparable safety profile in patients with LUTS/BPH.