Hepatitis C Virus Recurrence Occurs Earlier in Patients Receiving Donation After Circulatory Death Liver Transplant Grafts Compared With Those Receiving Donation After Brainstem Death Grafts.

INTRODUCTION: Hepatitis C virus (HCV)-related cirrhosis remains the commonest indication for liver transplantation worldwide, yet few studies have investigated the impact of donation after circulatory death (DCD) graft use on HCV recurrence and patient outcomes. DCD grafts have augmented the limited donor organ pool and reduced wait-list mortality, although concerns regarding graft longevity and patient outcome persist. METHODS: This was a single-center study of all HCV + adults who underwent DCD liver transplantation between 2004 and 2014. 44 HCV+ patients received DCD grafts, and were matched with 44 HCV+ recipients of donation after brainstem death (DBD) grafts, and their outcomes examined. RESULTS: The groups were matched for age, sex, and presence of hepatocellular carcinoma; no significant differences were found between the group's donor or recipient characteristics. Paired and unpaired analysis demonstrated that HCV recurrence was more rapid in recipients of DCD organs compared with DBD grafts (408 vs 657 days; P = .006). There were no significant differences in graft survival, patient survival, or rates of biliary complications between the cohorts despite DCD donors being 10 years older on average than those used in other published experience. CONCLUSIONS: In an era of highly effective direct acting antiviral therapy, rapid HCV recrudescence in grafts from DCD donors should not compromise long-term morbidity or mortality. In the context of rising wait-list mortality, it is prudent to use all available sources to expand the pool of donor organs, and our data support the practice of using extended-criteria DCD grafts based on donor age. Notwithstanding that, clinicians should be aware that HCV recrudescence is more rapid in DCD recipients, and early post-transplant anti-viral therapy is indicated to prevent graft injury.

Microwave thermotherapy for benign prostatic hyperplasia.

BACKGROUND: Transurethral resection of the prostate (TURP) has been the gold-standard treatment for alleviating urinary symptoms and improving urinary flow in men with symptomatic benign prostatic hyperplasia (BPH). However, the morbidity of TURP approaches 20%, and less invasive techniques have been developed for treating BPH. Preliminary data suggest that microwave thermotherapy, which delivers microwave energy to produce coagulation necrosis in prostatic tissue, is a safe, effective treatment for BPH. OBJECTIVES: To assess the therapeutic efficacy and safety of microwave thermotherapy techniques for treating men with symptomatic benign prostatic obstruction. SEARCH STRATEGY: Randomized controlled trials were identified from the Cochrane Collaboration Library, MEDLINE, EMBASE, bibliographies of retrieved articles and reviews, and by contacting expert relevant trialists and microwave manufacturers. SELECTION CRITERIA: All randomized controlled trials evaluating transurethral microwave thermotherapy (TUMT) for men with symptomatic BPH were eligible for this review. Comparison groups could include transurethral resection of the prostate, minimally invasive prostatectomy techniques, sham thermotherapy procedures, and medications. Outcome measures included urinary symptoms, urinary function, prostate volume, mortality, morbidity, and retreatment. Two reviewers independently identified potentially relevant abstracts and then assessed the full papers for inclusion. DATA COLLECTION AND ANALYSIS: Two reviewers independently abstracted study design, baseline characteristics and outcomes data and assessed methodological quality using a standard form. We attempted to obtain missing data from authors and/or sponsors. MAIN RESULTS: Fourteen studies involving 1493 patients met inclusion criteria, including six comparisons of microwave thermotherapy with TURP, seven comparisons with sham thermotherapy procedures, and one comparison with an alpha blocker. Study durations ranged from 3 to 60 months. The mean age of subjects was 66.8 years, and the baseline symptom scores and urinary flow rates, which did not differ across treatment groups, demonstrated moderately severe lower urinary tract symptoms. The pooled mean urinary symptom scores decreased by 65% with TUMT and by 77% with TURP. The weighted mean difference (WMD) (95% confidence interval) for the symptom score was -1.36 (-2.25 to -0.46), favoring TURP. The pooled mean peak urinary flow increased by 70% with TUMT and by 119% with TURP. The WMD for peak urinary flow was 5.08 (3.88 to 6.28) mL/s, favoring TURP. Compared to TURP, TUMT was associated with decreased risks for retrograde ejaculation, treatment for strictures, hematuria, blood transfusions, and the transurethral resection syndrome, but increased risks for dysuria, urinary retention, and retreatment for BPH symptoms. Microwave thermotherapy improved symptom scores (IPSS WMD -4.75, 95% CI -3.89 to -5.60) and peak urinary flow (WMD 1.67 mL/s, 95% CI 0.99 to 2.34) compared with sham procedures. Microwave thermotherapy also improved symptom scores (IPSS WMD -4.20, 95% CI -3.15 to -5.25) and peak urinary flow (WMD 2.30 mL/s, 95% CI 1.47 to 3.13) in the one comparison with alpha blockers. No studies evaluated the effects of symptom duration, patient characteristics, prostate-specific antigen levels, or prostate volume on treatment response. AUTHORS' CONCLUSIONS: Microwave thermotherapy techniques are effective alternatives to TURP and alpha-blockers for treating symptomatic BPH for men with no history of urinary retention or previous prostate procedures and prostate volumes between 30 to 100 mL. However, TURP provided greater symptom score and urinary flow improvements and reduced the need for subsequent BPH treatments compared to TUMT. Small sample sizes and differences in study design limit comparison between devices with different designs and energy levels. The effects of symptom duration, patient characteristics, or prostate volume on treatment response are unknown.

Botulinum toxin for treatment of urinary incontinence due to detrusor overactivity: a systematic review of effectiveness and adverse effects.

STUDY DESIGN: Systematic review. OBJECTIVE: To evaluate effectiveness and adverse effects of botulinum toxin (BTX) for treatment of urinary incontinence (UI) due to detrusor overactivity (DO). METHODS: Randomized controlled trials published in English before November 2006 were included if they enrolled subjects with UI caused by DO and reported incontinence outcomes. RESULTS: Three trials totaling 104 subjects with DO refractory to antimuscarinic treatment were included. Two BTX-A trials enrolled primarily patients with NDO secondary to spinal cord injury (SCI) (93%). BTX-A decreased daily UI episodes compared to placebo but the reductions were only significantly different at a few of the time intervals during 24 weeks of follow-up. BTX-A was superior in reducing daily UI episodes in SCI subjects compared to intravesical resiniferatoxin at 12 and 18 months after injections. A small crossover study found BTX-B significantly more effective than placebo in reducing weekly UI episodes in subjects with predominately idiopathic DO. Adverse events (AEs) in BTX-A-treated subjects included urinary tract infection, pain at the injection site, hematuria and autonomic dysreflexia. Four subjects treated with BTX-B reported autonomic AEs. CONCLUSIONS: BTX may improve UI for subjects with refractory DO. The preferred dose and type of BTX is not known. Long-term efficacy and safety remain unclear and require conduct of larger RCT using standardized and validated clinical outcomes measures.

An abnormal screening ultrasound: concordance with a tertiary obstetrical ultrasound unit.

OBJECTIVE: To determine concordance of ultrasound diagnosis in referrals to a tertiary obstetrical ultrasound unit (TOU) for suspected abnormalities. STUDY DESIGN: Consecutive referrals for "abnormal outside ultrasound" during a 6-month period were compared with the TOU ultrasound diagnosis. Concordance of diagnosis was compared on the basis of organ system involved and referral for single or multiple suspected abnormalities. Chi(2) analysis was used; p < 0.05 was considered significant. RESULTS: Of 104 consecutive referrals reviewed, 42 (40.4%) had no abnormality documented at the TOU. Of the 62 abnormal ultrasound scans at the TOU, 78.3% were concordant. Concordance based on organ system involvement was central nervous system, 30.3%; cardiothoracic, 66.7%; gastrointestinal, 63.6%; genitourinary, 50%. Referrals for a single suspected anomaly were statistically no more likely to have a normal TOU ultrasound scan (40.4%) than those referred for multiple suspected anomalies (36.4%, p > 0.05). CONCLUSIONS: Most referrals to a tertiary center for "abnormal outside ultrasound" will be diagnosed with an abnormality.

Extracorporeal shockwave therapy for peyronie disease.

While surgery is the mainstay of therapy for Peyronie disease requiring correction of angulation, interest has grown in the application of extracorporeal shockwave therapy (ESWT) as a minimally invasive approach. This article reviews the current literature reporting the use of ESWT for Peyronie disease.

Erectile dysfunction: current concepts and future directions.

Major advances in science and medicine have led to improved understanding of the pathophysiology of erectile dysfunction. The development of reliable pharmacological therapy for erectile dysfunction has led to heightened awareness in the public and medical communities. This article reviews recent clinical advances and future research directions.

Patient satisfaction with testosterone supplementation for the treatment of erectile dysfunction.

The long-term efficacy of testosterone supplementation for erectile dysfunction was evaluated using standardized questionnaires and differences between testosterone delivery systems analyzed. Forty-four patients receiving parenteral depo-testosterone, Testoderm scrotal patches, or Testoderm-TTS nonscrotal patches were evaluated with the Erectile Dysfunction Inventory of Treatment Satisfaction and International Index of Erectile Function questionnaires. Global questions regarding libido, energy, and improved erections demonstrated a significantly better response with depo-testosterone and Testoderm-TTS nonscrotal patches as compared to Testoderm scrotal patches. Testoderm-TTS nonscrotal patches and depo-testosterone resulted in significantly higher overall treatment satisfaction (p <.001), confidence in ability to engage in sexual activity (p <.001), and total Erectile Dysfunction Inventory of Treatment Satisfaction and International Index of Erectile Function scores (p <.001). Testoderm-TTS nonscrotal patches were significantly better than depo-testosterone with regard to satisfaction with sexual intercourse (International Index of Erectile Function question 5, p <.05). Testosterone replacement improved the quality of erections and level of libido in patients with erectile dysfunction. Treatment delivery systems appear to impact the success of therapy.

Oral therapy for Peyronie's disease.

Peyronie's disease (PD) remains a therapeutic dilemma for the urologist. Despite a myriad of medical therapies proposed for PD there have been limited advances in oral medical treatment. Several new approaches are presented which hold promise of success, although a definitive medical therapy for PD has yet to be established. Since early stage disease is reputed to respond better than well-established plaques, an early trial of inexpensive, safe and well-tolerated oral therapy is often initially recommended. This review discusses the historical aspects as well as contemporary oral medical therapy for PD. With advances in the molecular biology of inflammation and wound healing, the management and understanding of this frustrating disease will no doubt improve.

Developmental therapeutics program at the NCI: molecular target and drug discovery process.

As the drug discovery and developmental arm of the National Cancer Institute (NCI), the Developmental Therapeutics Program (DTP) plans, conducts and facilitates development of therapeutic agents for cancer and AIDS. DTP's goal is to turn 'molecules into medicine for the public health'. Areas of support by DTP are discovery, development and pathways to development for the intramural and the extramural community. The Developmental Therapeutics Program (DTP) operates a repository of synthetic and pure natural products, which are evaluated as potential anticancer agents. The repository derives from a historical database of greater than 600 000 compounds, which have been supplied to DTP from a variety of sources worldwide. The in vitro anti-cancer drug cell line screen established at DTP is unique in several respects. It has changed the NCI emphasis from a compound-oriented drug discovery effort to a disease-panel oriented exercise, emphasized human tumor cells derived from solid tumors, developed a high volume screening method that can adapt to processing of numerous chemical agents or natural source-derived extracts, that has minimized the use of animals, and saved on the amount of material required for the initial screening. The hollow fiber assay created at the DTP has demonstrated the ability to provide quantitative initial indices of in vivo drug efficacy, with minimum expenditures of time and materials and is currently being utilized as the initial in vivo experience for agents found to have reproducible activity in the in vitroanticancer drug screen. Drugs showing activity with unique mechanisms of actions are being further developed for treatment of hematopoietic neoplasms, prominent examples being flavopiridol, UCN-01 and depsipeptide among others.

Ureteral access for upper urinary tract disease: the access sheath.

Ureteral access with the flexible ureteroscope remains a challenge for the urologist. The routine use of a newly developed, site-specific ureteral access sheath facilitates entry into the ureter for fragmentation and basket extraction of ureteral and renal calculi. The step-by-step technique of ureteral access with the Access Sheath is described.

Urinary transforming growth factor-beta1 levels correlate with bladder outlet obstruction.

BACKGROUND: Urinary transforming growth factor-beta1 (TGF-beta1) levels have been shown to correlate with elevated intrapelvic pressure associated with ureteropelvic junction obstruction. Other studies have evaluated urinary TGF-beta1 levels in prostate cancer. This study tests the hypothesis that urinary TGF-beta1 levels might correlate with objective measures of bladder outlet obstruction (BOO). METHODS: Twenty-three men (age: 46-85 years) with lower urinary tract symptoms underwent urodynamic studies consisting of non-invasive uroflowmetry, cystometrogram and voiding pressure flow studies. Patients were classified as obstructed (n = 17) or not obstructed (n = 6) based on Abrams-Griffith nomograms. Urinary TGF-beta1 was extracted from an aliquot of urine obtained at the time of bladder catheterization for urodynamic studies. Urinary TGF-beta1 levels were then determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: There was a strong correlation between urinary TGF-beta1 levels and the presence of obstruction by Abrams-Griffith nomogram criteria (P = 0.025). Urinary TGF-beta1 levels were significantly higher in men with obstruction (0.039 +/- 0.011 pg/mL) than in men without obstruction (0.029 +/- 0.009 pg/mL; P = 0.036). CONCLUSION: Urinary TGF-beta1 levels correlate with objective measures of BOO. Further study is needed to test the utility of urinary TGF-beta1 as a non-invasive diagnostic tool for BOO.

Ureteral stenting after ureteroscopy for distal ureteral calculi: a multi-institutional prospective randomized controlled study assessing pain, outcomes and complications.

PURPOSE: We compare postoperative pain, stone-free rates and complications after ureteroscopic treatment of distal ureteral calculi with or without the use of ureteral stents. MATERIALS AND METHODS: A total of 113 patients with distal ureteral calculi amenable to ureteroscopic treatment were prospectively randomized into stented (53) and unstented (60) groups. Stones were managed with semirigid ureteroscopes with or without distal ureteral dilation and/or intracorporeal lithotripsy. Preoperative and postoperative pain questionnaires were obtained from each patient. Patients with stents had them removed 3 to 10 days postoperatively. Radiographic followup was performed postoperatively to assess stone-free rates and evidence of obstruction. RESULTS: Six patients randomized to the unstented group were withdrawn from the study after significant intraoperative ureteral trauma was recognized, including 3 ureteral perforations, that required ureteral stent placement, leaving 53 with stents and 54 without for analysis. Patients with stents had statistically significantly more postoperative flank pain (p = 0.005), bladder pain (p <0.001), urinary symptoms (p = 0.002), overall pain (p <0.001) and total narcotic use (p <0.001) compared to the unstented group. Intraoperative ureteral dilation or intracorporeal lithotripsy did not statistically significantly affect postoperative pain or narcotic use in either group (p >0.05 in all cases). Overall mean stone size in our study was 6.6 mm. There were 4 (7.4%) patients without stents who required postoperative readmission to the hospital secondary to flank pain. All patients (85%) who underwent imaging postoperatively were without evidence of obstruction or ureteral stricture on followup imaging (mean followup plus or minus standard deviation 1.8 +/- 1.5 months), and the stone-free rate was 99.1%. CONCLUSIONS: Uncomplicated ureteroscopy for distal ureteral calculi with or without intraoperative ureteral dilation can safely be performed without placement of a ureteral stent. Patients without stents had significantly less pain, fewer urinary symptoms and decreased narcotic use postoperatively.

Characterization of ultrastructural and metabolic abnormalities in semen from men with spinal cord injury.

BACKGROUND: In men with spinal cord injury (SCI), fertility is impaired because of a combination of ejaculatory dysfunction and poor semen quality. We hypothesized that ultrastructural and metabolic abnormalities of sperm could be an underlying factor in infertility in these men. METHODS: To investigate mechanisms contributing to the abnormal sperm parameters, we analyzed seminal constituents and sperm ultrastructure in ejaculates from 7 men with SCI and compared them with 5 control subjects. Sperm adenosine triphosphate (ATP) content was measured using a firefly luciferase bioluminescent assay kit, and ultrastructure was evaluated by electron microscopy. Seminal oxidative stress (8-iso-prostaglandin F-2alpha [8-iso-PGF2alpha]) and transforming growth factor-beta1 (TGF-beta1) levels were measured by specific enzyme-linked immunoabsorbent assay kits. RESULTS: Semen samples from men with SCI showed azoospermia (3) and severe asthenospermia (2; motility 0-5%). A majority (65%) of sperm from asthenospermic samples showed degenerative changes and significant axonemal defects. Incubation of normal sperm with SCI seminal plasma induced a concentration-dependent decrease in sperm motility (43%) accompanied by a significant drop in intracellular ATP content (33%). Semen samples from men with SCI exhibited levels of 8-iso-PGF2alpha 3.5-fold higher than those from controls and levels of TGF-beta1 that were 10% higher than those from controls. CONCLUSION: Our results suggest that seminal constituents of men with SCI are detrimental to sperm movement and that ultrastructural degenerative changes may contribute to the impaired sperm motility and viability seen in these patients. These preliminary results must be confirmed in larger patient populations and longitudinal studies.

Intravesical ethanol as quantitative measure of bladder hyperpermeability.

BACKGROUND AND PURPOSE: Bladder surface hyperpermeability may be a factor in the etiology of interstitial cystitis (IC). We evaluated the intravesical instillation of ethanol as a quantitative measure of bladder hyperpermeability in an experimental model in male New Zealand White rabbits. MATERIALS AND METHODS: In two study groups (N = 4 each), the glycosaminoglycan (GAG) layer on the bladder surface was disrupted via a 10-minute exposure to 10% protamine sulfate (PS). The study groups then underwent bladder instillation of 10% (group 1) and 20% (group 2) ethanol. The control groups underwent bladder instillation of either 10% (N = 2) or 20% ethanol (N = 2) without exposure to PS. Ten minutes after ethanol instillation, venous blood was sampled, and the ethanol concentration was determined by mass spectrometry. Study group animals were sacrificed after blood sampling. Control animals were sacrificed at 2 weeks and 4 weeks for histologic examination of the bladder. RESULTS: The blood alcohol concentration was 0 in the control animals exposed to 10% or 20% ethanol, 14.5+/-2.2 ng/dL in the 10% ethanol study group, and 25.6+/-3.6 ng/dL in the 20% ethanol study group. Histologic examination of bladder tissue revealed no ethanol-induced abnormalities in the control animals. CONCLUSION: Intravesical instillation of 10% and 20% ethanol is a safe and reliable quantitative measure of bladder hyperpermeability in an animal model. Clinical trials are ongoing to evaluate the utility of the intravesical ethanol test for diagnosing IC and monitoring the response to therapy.

Seizure disorders in pregnancy.

Epilepsy is the presence of two or more seizures in the absence of an identifiable cause for the seizures; that is, no intracranial or metabolic abnormality. Epilepsy affects approximately 1% of the US population, which represents an estimated 1.1 million women of reproductive age. The management of women with epilepsy during pregnancy is the focus of this article.

Correlation of external and internal monitoring of uterine activity in a cohort of term patients.

External tocodynamometry (ET) and intrauterine pressure monitoring (IUPC) are commonly used to assess uterine contractile activity. It is believed that ET does not accurately document contraction amplitude. However, no direct comparison of ET and IUPC has been published in term patients. Our objective was to determine the correlation between frequency, duration, and amplitude as measured by ET and IUPC. Twenty patients between 36 and 41 weeks' gestation were enrolled during active spontaneous labor. Uterine contractions were recorded simultaneously by ET and IUPC for 2 hours. ET and IUPC data were compared using the Spearman correlation coefficient and the Wilcoxon signed-rank test. The median body mass index (BMI) of the patient population was 31.8 kg/m2 (range 22.2 to 42.3). There was good correlation of contraction frequency measured by ET and IUPC (r = 0.75, p = 0.001), but poor correlation of both contraction amplitude (r = 0.26) and duration (r = 0.27). ET and IUPC assessment of uterine contractile activity, specifically contraction amplitude and duration, do not appear to correlate in a population of moderately obese patients. This suggests that ET should not exclusively be relied upon in this population to assess uterine contractile activity during labor.

Betamethasone alteration of the one-hour glucose challenge test in pregnancy.

OBJECTIVE: To determine if betamethasone administration alters the one-hour (50-g) glucose challenge test (GCT) and, if so, to determine the duration of this effect. STUDY DESIGN: Pregnant women with singleton gestations eligible to receive antenatal betamethasone (24-34 weeks) with no evidence of infection, diabetes mellitus, hepatic or pancreatic disease, betamimetic therapy or prolonged steroid use were invited to participate. Betamethasone (12 mg) was administered intramuscularly upon admission and repeated in 24 hours. After an 8-hour fast, a 50-g GCT was administered 24 hours (day 1) and 72 hours (day 3) after the second betamethasone injection. Plasma glucose samples were drawn one hour after the glucose challenge. Statistical analysis utilized the McNemar exact test. RESULTS: Seven patients, all with normal GCTs 7-10 days outside the study period, were enrolled. Six had abnormal GCT results on day 1 (P = .03). Three had abnormal results on day 3. CONCLUSION: Betamethasone administration results in abnormal one-hour GCTs in pregnant women.

Third year medical student attitudes toward learning urology.

PURPOSE: We studied certain research questions, including the learning environments in which third year medical students perceive that they acquire urological knowledge and skills, and whether medical students interested in urology as a career have different perceived learning needs than those interested in other specialties. MATERIALS AND METHODS: A survey instrument was pilot tested and revised. The instrument elicited student perceptions of how they best learned urological diagnosis and skills. Student attitudes toward the third year urology rotation and career motivation toward urology were assessed. Consecutive students were surveyed after completing the third year urology rotation. RESULTS: Most students perceived that they learned to manage most urological problems by seeing patients in outpatient clinics and they learned to perform physical examination and urinalysis interpretation by seeing patients. The overall usefulness of various learning environments was highest for seeing patients in clinic, followed by resident teaching, following inpatients, independent reading, watching open surgery, formal conferences, watching endoscopic surgery and routine menial work. Students interested in urology as a career choice were equally motivated by seeing patients in clinic, the subject matter and seeing surgery. CONCLUSIONS: Third year medical students perceive that the most important urological learning environment is outpatient evaluation of patients. The urological learning needs of third year medical students are not different in those interested and not interested in urology as a career.