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Background Liver tumours observed in rats exposed to micafungin led to a black box warning upon approval in Europe in 2008. Micafungin’s risk for liver carcinogenicity in humans has not been investigated. We sought to describe the risk of fatal hepatocellular carcinoma (HCC) among persons who received micafungin and other parenteral antifungals (PAFs) with up to 12 years of follow-up. Methods We assembled a US multicentre cohort of hospitalized patients who received micafungin or other PAFs between 2005 and 2012. We used propensity score (PS) matching on patient characteristics from electronic medical records to compare rates of HCC mortality identified through the National Death Index though to the end of December 2016. We computed HRs and 95% CIs. Results A total of 40110 patients who received a PAF were identified; 6903 micafungin recipients (87% of those identified) were successfully matched to 16317 comparator PAF users. Ten incident HCC deaths, one in the micafungin-exposed group and nine among comparator PAF users, occurred in 71285 person-years of follow-up. The HCC mortality rate was 0.05 per 1000 person-years in micafungin patients and 0.17 per 1000 person-years in comparator PAF patients. The PS-matched HR for micafungin versus comparator PAF was 0.29 (95% CI 0.04–2.24). Conclusions Both micafungin and comparator PAFs were associated with HCC mortality rates of

BACKGROUND: Clostridium difficile infection (CDI) is a leading cause of infectious complications in allogeneic hematopoietic cell transplant recipients (alloHCT). We sought to evaluate whether prophylactic oral vancomycin reduces the incidence of CDI in alloHCT recipients. METHODS: We conducted a retrospective cohort study to examine the effectiveness of CDI prophylaxis with oral vancomycin, as compared to no prophylaxis, in 145 consecutive adult alloHCT recipients at the University of Pennsylvania between April 2015 and November 2016. Patients received oral vancomycin 125 mg twice daily, starting on admission and continuing until discharge. The primary outcome of interest was the association between oral vancomycin prophylaxis and CDI diagnosis. Secondary outcomes included graft-versus-host disease (GVHD) and relapse. RESULTS: There were no cases of CDI in patients that received prophylaxis (0/90, 0%), whereas 11/55 (20%) patients who did not receive prophylaxis developed CDI (P < .001). Oral vancomycin prophylaxis was not associated with a higher risk of acute, grades 2–4 GVHD (subhazard ratio [sHR] 1.59; 95% confidence interval [CI] 0.88–2.89; P = .12), acute, grades 3–4 GVHD (sHR 0.65; 95% CI 0.25–1.66; P = .36), or acute, grades 2–4 gastrointestinal GVHD (sHR 1.95; 95% CI 0.93–4.07; P = .08) at day 180 post-transplant. No associations between oral vancomycin and relapse or survival were observed. CONCLUSIONS: Prophylaxis with oral vancomycin is highly effective in preventing CDI in alloHCT recipients without increasing the risk of graft-versus-host disease or disease relapse. Further evaluation via a prospective study is warranted.

Invasive fungal infections (IFI) are a significant source of morbidity and mortality for patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). Given the heterogeneity of the population receiving hypomethylating agents (HMA), it is difficult for clinicians to accurately assess their patients' risk of infection. Literature on the incidence of IFI following HMA is limited to several studies of azacitidine. The primary objective of this retrospective study was to establish the incidence of IFI in HMA treated AML/MDS patients at a large U.S. comprehensive cancer center. Secondary objectives included comparing incidence of IFI among pre-specified subgroups to identify potential risk factors for IFI. Two hundred three patients with AML, intermediate to very high risk MDS or chronic myelomonocytic leukemia who received at least two cycles of HMA were included. The incidence of IFI, as defined by the European Organization for Research and Treatment of Cancer / Invasive Fungal Infections Cooperative Group criteria, was 9.6%, with 20 IFI diagnosed following HMA (three proven, four probable, 13 possible). Among the proven cases of IFI, molds included Scedosporium and Fusarium spp. Eleven patients who developed IFIs were neutropenic upon initiating HMA. The majority (17/20) of infections occurred during the first four cycles. Given this incidence, mold-active prophylaxis can be considered in patients who are neutropenic at the start of therapy.

BACKGROUND: Most studies of post-transplant CMV infection have focused on either solid organ or hematopoietic cell transplant (HCT) recipients. A large prospective cohort study involving both lung and HCT recipients provided an opportunity to compare the epidemiology and outcomes of CMV infections in these two groups. METHODS: Patients were followed for 30 months in a 6-center prospective cohort study. Data on demographics, CMV infections, tissue-invasive disease, recurrences, rejection, and immunosuppression were recorded. RESULTS: The overall incidence of CMV infection was 83/293 (28.3%) in the lung transplant group and 154/444 (34.7%) in the HCT group (p = 0.0706). Tissue-invasive CMV disease occurred in 8/83 (9.6%) of lung and 6/154 (3.9 %) of HCT recipients with CMV infection, respectively (p=0.087). Median time to CMV infection was longer in the lung transplant group (236 vs. 40 days, p < 0.0001), likely reflecting the effects of prophylaxis vs. pre-emptive therapy. Total IgG levels of < 350 mg/dl in lung recipients and graft versus host disease (GvHD) in HCT recipients were associated with increased CMV risk. HCT recipients had a higher mean number of CMV episodes (p=0.008), although duration of viremia was not significantly different between the two groups. CMV infection was not associated with reduced overall survival in either group. CONCLUSIONS: Current CMV prevention strategies have resulted in a low incidence of tissue-invasive disease in both lung transplant and HCT, although CMV viremia is still relatively common. Differences between the lung and HCT groups in terms of time to CMV and recurrences of CMV viremia likely reflect differences in underlying host immunobiology and in CMV prevention strategies in the modern era.

To assess clinical safety (primary) and efficacy (secondary) of histotripsy for treatment of symptomatic benign prostatic enlargement in a first-in human study.Twenty-five male subjects with moderate to severe lower urinary tract symptoms, prostate size between 30 and 80 g, and no evidence of prostate cancer were enrolled at 2 sites in a prospective, single-arm study. Treatment consisted of acoustic energy delivery through the perineum with integrated real-time transrectal ultrasound monitoring using the Vortx RTwenty-five men underwent histotripsy treatment with no serious intraoperative adverse events. Postoperatively, 3 cases of transient urinary retention (3 days), 1 case of urinary retention (8 days in duration, defined as serious), a minor anal abrasion, and microscopic hematuria were considered device-related adverse events. Debulking of targeted prostate tissue was not observed with transrectal ultrasound imaging or with endoscopic visualization, and clinically meaningful improvement in uroflow or postvoid residual urine (PVR) did not occur. However, International Prostate Symptom Score improvement at 1 month was 12.5 (52.4%) ± 6.6 points (n = 25), at 3 months was 11.9 (50.8%) ± 7.6 points (n = 24), and at 6 months was 10.4 (44.0%) ± 7.6 points (n = 24) (P .001).Prostate histotripsy was safe and well tolerated in this pilot human trial with improvement in lower urinary tract symptoms.

Background Invasive fungal infections are a major cause of morbidity and mortality among solid organ transplant (SOT) and hematopoietic cell transplant (HCT) recipients, but few data have been reported on the epidemiology of endemic fungal infections in these populations. Methods Fifteen institutions belonging to the Transplant-Associated Infection Surveillance Network prospectively enrolled SOT and HCT recipients with histoplasmosis, blastomycosis, or coccidioidomycosis occurring between March 2001 and March 2006. Results A total of 70 patients (64 SOT recipients and 6 HCT recipients) had infection with an endemic mycosis, including 52 with histoplasmosis, 9 with blastomycosis, and 9 with coccidioidomycosis. The 12-month cumulative incidence rate among SOT recipients for histoplasmosis was 0.102%. Occurrence of infection was bimodal; 28 (40%) infections occurred in the first 6 months post transplantation, and 24 (34%) occurred between 2 and 11 years post transplantation. Three patients were documented to have acquired infection from the donor organ. Seven SOT recipients with histoplasmosis and 3 with coccidioidomycosis died (16%); no HCT recipient died. Conclusions This 5-year multicenter prospective surveillance study found that endemic mycoses occur uncommonly in SOT and HCT recipients, and that the period at risk extends for years after transplantation.

Background Invasive candidiasis is the third most common bloodstream infection in the intensive care unit (ICU) and is associated with morbidity and mortality. Prophylaxis and preemptive therapy are attractive strategies for this setting. Methods We conducted a multicenter, randomized, double-blind, placebo-controlled trial of caspofungin as antifungal prophylaxis in 222 adults who were in the ICU for at least 3 days, were ventilated, received antibiotics, had a central line, and had 1 additional risk factor (parenteral nutrition, dialysis, surgery, pancreatitis, systemic steroids, or other immunosuppressants). Subjects' (1,3)-β-d-glucan levels were monitored twice weekly. The primary endpoint was the incidence of proven or probable invasive candidiasis by EORTC/MSG criteria in patients who did not have disease at baseline. Patients who had invasive candidiasis were allowed to break the blind and receive preemptive therapy with caspofungin. The preemptive approach analysis included patients all patients who received study drug, including those positive at baseline. Results The incidence of proven/probable invasive candidiasis in the placebo and caspofungin arms was 16.7% (14/84) and 9.8% (10/102), respectively, for prophylaxis (P = .14), and 30.4% (31/102) and 18.8% (22/117), respectively, for the preemptive approach (P = .04); however, this analysis included patients with baseline disease. There were no significant differences in the secondary endpoints of mortality, antifungal use, or length of stay. There were no safety differences. Conclusions Caspofungin was safe and tended to reduce the incidence of invasive candidiasis when used for prophylaxis, but the difference was not statistically significant. A preemptive therapy approach deserves further study. Clinical trials registration NCT00520234.

Summary Objectives To investigate the risk factors and outcomes associated with Candida krusei bloodstream. Methods We performed a case control study of patients with C. krusei bloodstream infection at the University of Pennsylvania from 1982 to 2010. Controls were without candidemia, and matched to cases on duration of hospitalization and underlying disease. Results We enrolled 34 cases and 114 matched controls. Most subjects (62%) had hematologic malignancies. In the multivariate model, including a priori the duration of fluconazole use (OR 1.06; 95% CI 1.00, 1.11) and days of neutropenia (OR 1.01; 95% CI 0.98, 1.13), risk factors associated with C. krusei bloodstream infection were splenectomy (OR 11.66; 95% CI 1.04, 130.64), and exposure to antimicrobials with anaerobic activity (OR 5.74; 95% CI 1.76, 18.67). Outcomes of infected patients were poor. Only 32% of case patients survived to hospital discharge, compared to 89% of controls. For 48% death was attributed to C. krusei infection. Conclusions C. krusei bloodstream infection occurs most commonly in neutropenic patients with hematologic malignancy. The association with prior fluconazole exposure is less marked than previously described. Splenectomy and the receipt of antimicrobials with anaerobic activity are significant risk factors. The outcome of infected patients remains poor, despite appropriate antifungal therapy.

The impact of antifungal therapy on economic outcomes in patients with invasive aspergillosis (IA) needs further exploration. The purpose of this study was to describe antifungal therapy and factors associated with hospital length of stay (LOS) in transplant patients with IA. Patients were enrolled from March 2001 to October 2005 and IA cases identified through March 2006 from a sub-group of patients in the Transplant Associated Infection Surveillance Network (TRANSNET). Factors associated with hospital LOS were determined by logistic regression analysis. Of 361 patients, the mean age was 49 years, 60.7% were male, and 63% were hematopoietic stem cell transplantation (HSCT) recipients. Primary monotherapy was used in 233 (64.5%) patients, of which voriconazole (93/233, 39.9%) was most commonly used antifungal. Primary combination therapy was used in 128 (35.4%) of 361 patients, with voriconazole plus caspofungin (81/361, 22.4%) the most frequently employed. Mean duration of therapy was 115 days (HSCT 109.7; solid organ transplant [SOT] 125.3). Mean hospital LOS was 35.3 days (HSCT 38.7; SOT 29.7). Regression analysis identified disseminated IA, neutropenia, malnutrition and length of ICU stay as factors associated with increased hospital LOS. Initial voriconazole use was associated with decreased LOS. Further investigation on impact of antifungal therapy on economic outcomes is needed.

Recent reports describe increasing incidence of non-Aspergillus mold infections in hematopoietic cell transplant (HCT) and solid organ transplant (SOT) recipients. To investigate the epidemiology of infections with Mucorales, Fusarium spp., and Scedosporium spp. molds, we analyzed data from the Transplant-Associated Infection Surveillance Network, 23 transplant centers that conducted prospective surveillance for invasive fungal infections during 2001–2006. We identified 169 infections (105 Mucorales, 37 Fusarium spp., and 27 Scedosporium spp.) in 169 patients; 124 (73.4%) were in HCT recipients, and 45 (26.6%) were in SOT recipients. The crude 90-day mortality rate was 56.6%. The 12-month mucormycosis cumulative incidence was 0.29% for HCT and 0.07% for SOT. Mucormycosis incidence among HCT recipients varied widely, from 0.08% to 0.69%, with higher incidence in cohorts receiving transplants during 2003 and 2004. Non-Aspergillus mold infections continue to be associated with high mortality rates. The incidence of mucormycosis in HCT recipients increased substantially during the surveillance period.

We describe findings from a Urological Surgery Quality Collaborative project focused on improving the use of radiographic staging in men with newly diagnosed prostate cancer.From May 2009 through September 2010 Urological Surgery Quality Collaborative surgeons collected uniform data for men with newly diagnosed prostate cancer. During this period we implemented 3 phases of data collection. Unlike the baseline phase, the second and third rounds were preceded by collaborative quality improvement interventions, including comparative performance feedback, and review and dissemination of clinical guidelines. We evaluated the use of bone scans and computerized tomography across prostate cancer risk strata, Urological Surgery Quality Collaborative practice locations, and before and after quality improvement interventions.We collected data for 858 men with prostate cancer. Based on the D'Amico classification 44%, 39% and 17% of the men had low, intermediate and high risk cancer, respectively. Overall 25% and 22% of patients underwent staging with a bone scan or computerized tomography, respectively, ordered by a Urological Surgery Quality Collaborative urologist. Urological Surgery Quality Collaborative practices differed significantly in their baseline use of bone scans and computerized tomography for men with low and intermediate risk cancer (p0.01). Compared with baseline practice patterns (31% bone scans, 28% computerized tomography), urologists in Urological Surgery Quality Collaborative practices ordered fewer bone and computerized tomography scans in post-intervention phases 2 (23%, 21%) and 3 (16%, 13%) of data collection (p0.01), including a significant reduction in the use of these studies in patients with low and intermediate risk cancer (p0.05).Following collaborative feedback on baseline use and review of clinical guidelines, urologists in Urological Surgery Quality Collaborative practices dramatically reduced variations in practice patterns and improved adherence with recommended staging practices.

Background The incidence and epidemiology of invasive fungal infections (IFIs), a leading cause of death among hematopoeitic stem cell transplant (HSCT) recipients, are derived mainly from single-institution retrospective studies. Methods The Transplant Associated Infections Surveillance Network, a network of 23 US transplant centers, prospectively enrolled HSCT recipients with proven and probable IFIs occurring between March 2001 and March 2006. We collected denominator data on all HSCTs preformed at each site and clinical, diagnostic, and outcome information for each IFI case. To estimate trends in IFI, we calculated the 12-month cumulative incidence among 9 sequential subcohorts. Results We identified 983 IFIs among 875 HSCT recipients. The median age of the patients was 49 years; 60% were male. Invasive aspergillosis (43%), invasive candidiasis (28%), and zygomycosis (8%) were the most common IFIs. Fifty-nine percent and 61% of IFIs were recognized within 60 days of neutropenia and graft-versus-host disease, respectively. Median onset of candidiasis and aspergillosis after HSCT was 61 days and 99 days, respectively. Within a cohort of 16,200 HSCT recipients who received their first transplants between March 2001 and September 2005 and were followed up through March 2006, we identified 718 IFIs in 639 persons. Twelve-month cumulative incidences, based on the first IFI, were 7.7 cases per 100 transplants for matched unrelated allogeneic, 8.1 cases per 100 transplants for mismatched-related allogeneic, 5.8 cases per 100 transplants for matched-related allogeneic, and 1.2 cases per 100 transplants for autologous HSCT. Conclusions In this national prospective surveillance study of IFIs in HSCT recipients, the cumulative incidence was highest for aspergillosis, followed by candidiasis. Understanding the epidemiologic trends and burden of IFIs may lead to improved management strategies and study design.

Background Clostridium difficile infection (CDI) is a common complication of lung and allogeneic hematopoietic cell (HCT) transplant, but the epidemiology and outcomes of CDI after transplant are poorly described. Methods We performed a prospective, multicenter study of CDI within 365 days post-allogeneic HCT or lung transplantation. Data were collected via patient interviews and medical chart review. Participants were followed weekly in the 12 weeks post-transplant and while hospitalized and contacted monthly up to 18 months post-transplantation. Results Six sites participated in the study with 614 total participants; 4 enrolled allogeneic HCT (385 participants) and 5 enrolled lung transplant recipients (229 participants). One hundred and fifty CDI cases occurred within 1 year of transplantation; the incidence among lung transplant recipients was 13.1% and among allogeneic HCTs was 31.2%. Median time to CDI was significantly shorter among allogeneic HCT than lung transplant recipients (27 days vs 90 days; P = .037). CDI was associated with significantly higher mortality from 31 to 180 days post-index date among the allogeneic HCT recipients (Hazard ratio [HR] = 1.80; P = .007). There was a trend towards increased mortality among lung transplant recipients from 120 to 180 days post-index date (HR = 4.7, P = .09). Conclusions The epidemiology and outcomes of CDI vary by transplant population; surveillance for CDI should continue beyond the immediate post-transplant period.

The motility of testicular derived spermatozoa reflects viability and predicts success during intracytoplasmic sperm injection. Although improvements in sperm motility are seen after incubation for extended periods, no guidelines suggest duration or media use for optimal improvement in motility.Between July 1999 and February 2005 testicular aspirations were performed on 95 men with azoospermia, including 51 with obstructive azoospermia and 44 with nonobstructive azoospermia. Sperm motility was determined at initial collection and following incubation for 24 or 48 hours in processing media or Ham's F10 + protein. A mixed regression model controlling for testis side, media and baseline motility was created to analyze the change in motility between 24 and 48 hours.Mean motility improved from 3% to 20% at 24 hours and 25% at 48 hours for OA cases and from 0% to 5% at 24 hours and 11% at 48 hours for nonobstructive azoospermia cases. The improvement in motility from 24 to 48 hours was significant for obstructive azoospermia cases (p = 0.001). While media was a nonsignificant factor in regression models, when patients were grouped into categories of motility change there was a significantly better response to F10 compared to processing media (p = 0.03).Incubation in processing media or Ham's F10 + albumin media improves sperm motility with significant improvement noted between 24 and 48 hours for obstructive azoospermia cases. Ham's F10 + albumin media may provide extra benefit for cases of nonobstructive azoospermia or nerve injury. These results suggest the ideal timing of oocyte retrieval for intracytoplasmic sperm injection correlates with 48-hour sperm incubation for obstructive azoospermia cases, and 24 hours for nonobstructive azoospermia and nerve injury cases.

OBJECTIVES Urinary retention after urethral catheter removal is a well-established complication of radical prostatectomy (RP). Its effect on subsequent urethral stricture formation has not been established. The objective of this study was to evaluate the association between post-RP early urinary retention (EUR) and subsequent symptomatic urethral stricture formation. METHODS A total of 1289 patients who underwent RP from January 1998 to November 2004 at our tertiary medical center were included in a prospective database project. EUR was defined as that which occurred 7 days or earlier after urethral catheter removal and was identified by retrospective chart review. Multivariate logistic regression models were constructed to evaluate the association between EUR and symptomatic urethral stricture formation. RESULTS Of the 1289 patients, 44 (3.4%) experienced EUR, and 16 of these patients (36.4%) developed symptomatic urethral strictures. The stricture rate for patients without EUR was 9.0% (112 of 1245). Compared with the patients without EUR, the patients with EUR had a greater rate of bladder neck contracture (94% versus 68%, P = 0.04) and exhibited a significantly decreased time to stricture formation (1.6 months versus 3.0 months, P = 0.002). After adjusting for patient age, clinical stage, surgeon, and Gleason score, the odds of developing a symptomatic urethral stricture were 4.7 times greater in the patients with EUR (95% confidence interval 2.3 to 9.6). CONCLUSIONS The results of this study have shown that patients with EUR after RP are at a significantly greater risk of developing symptomatic urethral strictures, tend to form bladder neck contractures instead of more distal strictures, and to form strictures sooner after surgery. EUR might be a previously unrecognized risk factor for the development of post-RP urethral stricture.

Infection is a major complication of hematopoietic cell transplantation. Prolonged neutropenia and graft-versus-host disease are the 2 major complications with an associated risk for infection, and these complications differ according to the graft source. A phase 3, multicenter, randomized trial (Blood and Marrow Transplant Clinical Trials Network [BMT CTN] 0201) of transplantation of bone marrow (BM) versus peripheral blood stem cells (PBSC) from unrelated donors showed no significant differences in 2-year survival between these graft sources. In an effort to provide data regarding whether BM or PBSC could be used as a preferential graft source for transplantation, we report a detailed analysis of the infectious complications for 2 years after transplantation from the BMT CTN 0201 trial. A total of 499 patients in this study had full audits of infection data. A total of 1347 infection episodes of moderate or greater severity were documented in 384 (77%) patients; 201 of 249 (81%) of the evaluable patients had received a BM graft and 183 of 250 (73%) had received a PBSC graft. Of 1347 infection episodes, 373 were severe and 123 were life-threatening and/or fatal; 710 (53%) of these episodes occurred on the BM arm and 637 (47%) on the PBSC arm, resulting in a 2-year cumulative incidence 84.7% (95% confidence interval [CI], 79.6 to 89.8) for BM versus 79.7% (95% CI, 73.9 to 85.5) for PBSC, P = .013. The majority of these episodes, 810 (60%), were due to bacteria, with a 2-year cumulative incidence of 72.1% and 62.9% in BM versus PBSC recipients, respectively (P = .003). The cumulative incidence of bloodstream bacterial infections during the first 100 days was 44.8% (95% CI, 38.5 to 51.1) for BM versus 35.0% (95% CI, 28.9 to 41.1) for PBSC (P = .027). The total infection density (number of infection events/100 patient days at risk) was .67 for BM and .60 for PBSC. The overall infection density for bacterial infections was .4 in both arms; for viral infections, it was .2 in both arms; and for fungal/parasitic infections, it was .04 and .05 for BM and PBSC, respectively. The cumulative incidence of infection before engraftment was 47.9% (95% CI, 41.5 to 53.9) for BM versus 32.8% (95% CI, 27.1 to 38.7) for PBSC (P = .002), possibly related to quicker neutrophil engraftment using PBSC. Infections remain frequent after unrelated donor hematopoietic cell transplantation, particularly after BM grafts.

Transplant recipients are at a high risk for developing invasive fungal infections. The agents of phaeohyphomycosis are environmental molds found worldwide, and they cause a broad spectrum of disease including skin and subcutaneous lesions, pneumonia, central nervous system disease, fungemia, and disseminated disease. Using data from the Transplant Associated Infection Surveillance Network (TRANSNET), we evaluated patients with proven and probable phaeohyphomycosis. Centers collected data on demographics, co-morbid conditions, clinical features, treatment, and three-month mortality. Fifty-six patients with phaeohyphomycosis were identified from 15 centers, comprising 26 stem cell transplant (SCT) and 30 solid organ transplant (SOT) recipients. Median time to diagnosis post-transplant was 358 days (SCT 100 days; SOT 685 days; P =

A randomized, blinded, multicenter trial was conducted to compare fluconazole (800 mg per day) plus placebo with fluconazole plus amphotericin B (AmB) deoxycholate (0.7 mg/kg per day, with the placebo/AmB component given only for the first 5-6 days) as therapy for candidemia due to species other than Candida krusei in adults without neutropenia. A total of 219 patients met criteria for a modified intent-to-treat analysis. The groups were similar except that those who were treated with fluconazole plus placebo had a higher mean (+/- standard error) Acute Physiology and Chronic Health Evaluation II score (16.8+/-0.6 vs. 15.0+/-0.7; P=.039). Success rates on study day 30 by Kaplan-Meier time-to-failure analysis were 57% for fluconazole plus placebo and 69% for fluconazole plus AmB (P=.08). Overall success rates were 56% (60 of 107 patients) and 69% (77 of 112 patients; P=.043), respectively; the bloodstream infection failed to clear in 17% and 6% of subjects, respectively (P=.02). In nonneutropenic subjects, the combination of fluconazole plus AmB was not antagonistic compared with fluconazole alone, and the combination trended toward improved success and more-rapid clearance from the bloodstream.

BACKGROUND With the availability of ICSI, men with severe oligozoospermia (

Objectives To review our perioperative experience with patients presenting with high-risk bladder cancer who had undergone prior therapy for prostate cancer. With the increase in diagnosis and subsequent treatment of prostate cancer, more patients presenting with high-risk bladder cancer have undergone prior therapy for prostate cancer. Radical cystectomy in these patients can be technically challenging and may be associated with added morbidity. Methods A retrospective review of 458 patients treated with radical cystectomy between January 1993 and January 2002 revealed 29 patients (mean age 72 years) who had received definitive treatment for prostate cancer prior to cystectomy for bladder carcinoma. The initial treatment in this cohort was radical prostatectomy or external beam radiotherapy in 12 (41%) and 17 (59%) men, respectively. Cystectomy was performed for transitional cell carcinoma in 25 (86%), small cell carcinoma in 2 (6%), and sarcoma in 2 (6%) patients. Results At the time of cystectomy, the mean blood loss was 1175 mL (range 275 to 3500), and the median length of hospitalization was 8 days (range 4 to 23). No intraoperative or perioperative deaths occurred in this cohort. Twenty-seven early complications were identified in 16 (55%) of 29 patients; no rectal injuries occurred. Patients with prior radiotherapy had a higher rate of extravesical bladder carcinoma (60%) than those patients treated with prior prostatectomy (33%). An orthotopic neobladder diversion was created in 5 patients (17%). Conclusions Patients with bladder cancer previously treated for prostate cancer with external beam radiotherapy or radical prostatectomy have an increased risk of perioperative complications compared with patients undergoing cystectomy without prior therapy. This risk is not prohibitive, and radical cystectomy should remain the treatment of choice for high-risk bladder cancer in this population. Furthermore, orthotopic urinary diversion may be a reasonable option and should be considered in select patients.

A microfluidic device was designed with two parallel laminar flow channels where non-motile spermatozoa and debris would flow along their initial streamlines and exit one outlet, whereas motile spermatozoa had an opportunity to swim into a parallel stream and exit a separate outlet. Motile sperm samples were prepared with density gradient separation (n = 5). Sperm motility was assessed the following day after exposing aliquots to polydimethylsiloxane (PDMS) used to construct the device. There was no difference in sperm motility when compared with unexposed aliquots (P > 0.05). Unprocessed semen samples (n = 10) were placed in wider channels and sperm motility and strict morphology were assessed from sorted outlets. Sperm motility increased from 44 +/- 4.5% to 98 +/- 0.4% (P < 0.05) and morphology increased from 10 +/- 1.05% to 22 +/- 3.3% (P < 0.05) following processing. Finally, density gradient prepared samples (n = 6) containing 5 x 10(6) motile spermatozoa/ml and 50 x 10(6) round immature germ cells/ml were sorted and assessed in a similar fashion. The ratio of motile spermatozoa to round immature germ cells in the wide inlet (1:10) was significantly improved in the thin outlet (33:1) (P < 0.05). This microfluidic device provides a novel method for isolating motile, morphologically normal spermatozoa from semen samples without centrifugation. This technology may prove useful in isolating motile spermatozoa from oligozoospermic samples, even with high amounts of non-motile gamete and/or non-gamete cell contamination. A movie sequence showing streaming and sorting of spermatozoa may be purchased for viewing on the internet at www.rbmonline.com/Article/847 (free to web subscribers).

Nonmyeloablative allogeneic transplantation is an emerging therapy for hematologic and solid malignancies and potentially offers patients reduced transplant-related toxicity. Data regarding infectious complications of these protocols are limited, but early studies have demonstrated little infectious morbidity, particularly low rates of invasive fungal infections (IFIs). In the present study, 31 consecutive cases of nonmyeloablative transplantation were reviewed over a 2.5-year period, with a specific focus on infectious complications. Twenty-six patients (84%) had at least 1 significant infection during the year after transplantation, and infection-related mortality was 37%. Cytomegalovirus end-organ disease was diagnosed in 3 patients (10%). Ten patients (32%) were given the diagnosis of IFI; 7 (23%) met criteria for proven IFI. Fungal-related mortality was 80% within the group of patients with IFI and accounted for a significant portion of the overall mortality in the study. Severe graft-versus-host disease, high-dose corticosteroid use, recurrent neutropenia, and relapsed or refractory disease were factors associated with development of IFI.

Human infection with Mycoplasma species other than M. pneumoniae are infrequent, but may be encountered in patients with immunodeficiencies. We report a patient with combined variable immunodeficiency that developed multiple abscesses and destructive bone disease caused by M. orale, an organism generally considered to be non-pathogenic. Molecular laboratory methods, 16S rRNA sequence analysis, were used to detect the organism directly in the surgical specimen and confirmed following isolating of the organism. This case demonstrates the importance of molecular technology in the diagnosis of difficult infectious disease problems.

Ureteroscopy for treating urolithiasis in prepubertal children has become more common with the advent of smaller instruments. We reviewed our experience with ureteroscopy for urolithiasis in this cohort of patients as well as the literature using this treatment modality in children.Between 1994 and 2000 we performed 27 ureteroscopic stone extractions in 25 children. Ureteroscopy was done in a manner similar to that in adults. Ureteral dilation was performed when necessary to access the ureter. A stent was placed postoperatively if there was significant ureteral trauma.Of the 25 children 13 were male and 12 were female. Average age was 9.2 years (range 3 to 14). Stones were 2 to 12 mm. in greatest diameter (average 6). Of the 27 procedures the ureteral orifice was dilated before stone treatment in 15 (56%), while in 19 (70%) a stent was placed afterward. No intraoperative and 2 postoperative complications were identified. Overall 92% of the children were rendered stone-free after 1 procedure and 100% were stone-free after 2.Ureteroscopy for urolithiasis in prepubertal children is safe and effective. Routine ureteral dilation and ureteral stent placement are not always necessary in these patients.

Invasive Fusarium infections occur in immunosuppressed patients, especially those with haematological malignancies. We conducted a descriptive analysis of data from patients with invasive fusariosis identified in the Prospective Antifungal Therapy Alliance registry, which collected data on invasive fungal infections in the United States and Canada from 2004 to 2008. In this series of 65 patients with proven (83.1%) and probable (16.9%) invasive fusariosis, the most common underlying condition was haematological malignancy, in which neutropenia and corticosteroid usage frequently occurred. Seven patients with invasive Fusarium infections had cross-reactive galactomannan assay results. The survival rate for all patients at 90 days was 44%, which was an improvement compared with historical data. Disseminated disease occurred frequently (35.4%), and patients with and without disseminated disease had survival rates of 33% and 50%, respectively. Posaconazole and voriconazole were the most frequently employed therapies and may be linked to the improved survival rate observed in this patient series. In summary, patients with invasive Fusarium infections continue to have high fatality rates, especially those with disseminated disease. Fusarium infections should be strongly considered in the absence of Aspergillus isolation in patients at high risk of mould infections with positive galactomannan assay test results.

There are no recognized orally administered treatments for any of the leishmaniases. The 8-aminoquin- oline WR6026 is an orally administered analog of primaquine that cured 50% of patients with kala-azar in Kenya at a dose of 1 mg/kg/day for 28 days. A further phase 2, open-label, dose-escalating safety and efficacy study was performed for kala-azar in Brazil. Cure rates for Brazilian patients treated for 28 days were as follows: 1 mg/kg/day: 0 of 4 (0%); 1.5 mg/kg/day: 1 of 6 (17%); 2.0 mg/kg/day: 4 of 6 (67%); 2.5 mg/kg/day: 1 of 5 (20%); and 3.25 mg/ kg/day: 0 of 1 (0%). Nephrotoxicity that was not anticipated from preclinical animal studies or from phase 1 studies was seen at 2.5 mg/kg/day in 2 patients and in the single patient administered 3.25 mg/kg/day. WR6026 demonstrated the unusual clinical features of lack of increased efficacy against Brazilian kala-azar with increased dosing above 2 mg/kg/day and toxicity that was not present in previous investigations.

Objectives. To compare the safety and efficacy of ureteroscopy performed for proximal and distal ureteral calculi in a contemporary cohort. Ureteroscopy has been used most often for distal ureteral calculi. However, advances in endoscopic equipment have facilitated access to the proximal urinary tract and have broadened the indications for ureteroscopy. Methods. One hundred ninety-one patients underwent rigid and/or flexible ureteroscopy for ureteral calculi at the University of Michigan between January 1, 1997 and September 30, 1999. Only 7 patients with either bilateral calculi or steinstrasse were excluded. The final cohort consisted of 184 patients who underwent ureteroscopy for distal stones (n = 103) or middle/upper ureteral stones (n = 81). Results. Bivariate analyses of pretreatment and perioperative characteristics were used to assess the sample population. The initial success rate for the distal and proximal ureteral calculi was 96% and 78%, respectively ( P = 0.0008). After a “second-look” procedure in 4 and 7 patients with distal and proximal calculi, respectively, the success rate improved to 99% and 88%, respectively ( P = 0.004). No differences were noted between groups regarding the intraoperative ( P = 0.51) or postoperative ( P = 0.85) complication rates. Multivariate logistic regression analysis confirmed that larger stone size (odds ratio 1.2, P = 0.0006) and proximal ureteral location (odds ratio 4.8, P = 0.01) are independent predictors of treatment failure. Conclusions. Ureteroscopic management of proximal and distal ureteral calculi is highly successful, and the difference in success rates has narrowed substantially. Currently, no greater risk is conferred to the patient for endoscopy of more proximal ureteral calculi.

WR 238605 is an 8-aminoquinoline developed for the radical cure of Plasmodium vivax. Forty-four P. vivax-infected patients were randomly assigned to 1 of 4 treatment regimens: 3 groups received a blood schizonticidal dose of chloroquine followed by WR 238605: group A (n=15) received 300 mg daily for 7 days; group B (n=11), 500 mg daily for 3 days, repeated 1 week after the initial dose; group C (n=9), 1 dose of 500 mg. A fourth group (D; n=9) received chloroquine only. Among patients who completed 2-6 months of follow-up (n=23), there was 1 relapse in group B (day 120) and 1 in group C (day 112). Among patients treated with chloroquine only, there were 4 relapses (days 40, 43, 49, and 84). WR 238605 was safe, well tolerated, and effective in preventing P. vivax relapse.

Objectives With the increased use of prostate-specific antigen screening, younger men are being diagnosed with prostate cancer. A subset of these men is still interested in potentially having children after cancer treatment. To our knowledge, the topic of future fertility in patients with newly diagnosed prostate cancer has not previously been reported. Methods The charts of 8 patients with prostate cancer who were interested in future fertility before treatment were retrospectively reviewed. Preceding definitive treatment, the men underwent fertility counseling and were counseled to preserve semen before treatment. Results All 8 patients decided to have their semen stored using cryopreservation before their operation. After undergoing radical prostatectomy, one of the patients and his wife underwent successful intrauterine insemination and bore a child. Conclusions A subset of men, regardless of age, diagnosed with prostate cancer will be interested in preserving their fertility for the future. Fertility options and potential counseling should be part of the routine pretreatment appointments in men undergoing treatment of prostate cancer.

The incidence of bacteremia due to vancomycin-resistant Enterococcus (VRE) has increased markedly in recent years. We investigated the role of chloramphenicol in its treatment. All cases of VRE bacteremia occurring at our facility during a 45-month period were analyzed. The response to chloramphenicol, its effect on mortality, and the incidence of adverse effects were assessed. Fifty-one patients (65.4%) received chloramphenicol. Among patients in whom a response could be assessed, 22 (61.1%) of 36 demonstrated a clinical response, while 34 (79.1%) of 43 showed a microbiological response. Forty-two patients (53.8%) died as a result of the bacteremia. Although the mortality rate was lower for patients treated with chloramphenicol, the difference was not significant (odds ratio = 0.72; 95% confidence interval, 0.28-1.85; P = .49), nor was there an association between earlier initiation of therapy and reduced mortality (P = .45). In cases with central line-related bacteremia, there was no difference in mortality among patients treated with chloramphenicol, line removal, or both (P = .36). Although 16 patients (31.4%) had adverse effects, none could be definitely attributed to chloramphenicol. Although chloramphenicol was well-tolerated, no significant effect of its use on mortality could be demonstrated.

WR 238605 is an 8-aminoquinoline drug currently under development for prophylaxis and treatment of malaria. Preclinical studies have demonstrated that it has greater efficacy and less toxicity compared with primaquine. In this first-time-in-human randomized, double-blind, placebo-controlled study designed to evaluate the safety, tolerance and pharmacokinetics, WR 238605 was administered to 48 men in single oral doses ranging from four to 600 mg (base). It was well tolerated, with gastrointestinal disturbances as possible side effects. Linear kinetics were demonstrated at these doses. WR 238605 has a long absorption phase and is slowly metabolized, with a tmax of 12 hr and an elimination half-life of 14 days. These safety, efficacy and pharmacokinetic properties make this drug an excellent candidate for further testing as a prophylactic, radical curative, and terminal eradication drug.

This study was conducted to determine the pharmacokinetics and pharmacodynamics of pyridostigmine given as 30 mg of pyridostigmine bromide every 8 hours in healthy subjects. Plasma pyridostigmine concentration and red blood cell acetylcholinesterase activity were measured in blood samples collected during a 3-week period. Population analysis was performed using standard pharmacokinetic and pharmacodynamic models with the nonlinear mixed-effect modeling software (NONMEM). The pharmacokinetic model that best fit the pyridostigmine plasma levels was a two-compartment open model with first-order absorption, a lag time, and first-order elimination from the central compartment. The pharmacodynamic model that best fit red blood cell acetylcholinesterase activity was an inhibitory E max model with an effect compartment linked to the central compartment. The results showed that the pharmacokinetics of pyridostigmine bromide are both gender and weight dependent. The pharmacodynamic effect does not lag significantly from the plasma concentration and returns to near normal within 8 hours. With the present dosage regimen of 30 mg every 8 hours, 30% of individuals may not have red blood cell acetylcholinesterase inhibition >10% at the time of the trough.

The correlation of P. falciparum lactate dehydrogenase (pLDH) activities and patent infections was evaluated for monitoring therapeutic responses and drug resistance in 70 patients with microscopically confirmed P. falciparum malaria in Nigeria. Each patient was treated with standard dosages of artemether (53 patients), chloroquine (7 patients), sulfadoxine-pyrimethamine (6 patients), or halofantrine (4 patients). Response of infection to treatment was monitored by microscopic examination of thick and thin blood smears, clinical symptoms, and levels of pLDH activities in blood products. pLDH activity was determined using an antibody capture technique and 3-acetyl pyridine adenine dinucleotide developed to enhance sensitivity of the enzyme detection. All patients treated with artemether were cured while 5 patients treated with chloroquine, 1 treated with sulfadoxine-pyrimethamine, and 2 treated with halofantrine suffered recrudescent infections after treatment. pLDH activity was detected in blood products obtained from patients with patent or recrudescent infections determined by microscopy and clinical symptoms. Levels of pLDH activities in whole blood and packed cells from the patients correlated with qualitative detection of parasites in blood smears and in patients with high gametocyte counts. Gametocyte counts in the patients after treatment ranged from 40 gametocytes/microliter of blood to 4923 gametocytes/microliter of blood. There is a consistent relationship between patent infection and pLDH activities that could easily be determined in whole blood and packed cells from the patients. Further development of the procedure will enhance its valuable application in clinical management of drug-resistant malaria in the endemic areas.

Candida osteomyelitis is associated with significant morbidity; however, data on the management of Candida osteomyelitis are limited. The Prospective Antifungal Therapy (PATH) Alliance® registry is a comprehensive, multicenter, prospective, observational registry that collected data on patients with invasive fungal infections between 2004 and 2008. The aim of this descriptive analysis was to evaluate the clinical characteristics, treatment, and outcomes of patients with Candida osteomyelitis. Using the PATH Alliance® registry, we performed a review of all patients with a proven diagnosis of Candida osteomyelitis who received a minimum of 14 days of antifungal treatment and/or a therapeutic surgical intervention (n = 53). The epidemiology, diagnosis, treatment, and outcomes of these patients were assessed at 12 weeks. C. albicans (56.6 %) was the most commonly identified organism, followed by C. parapsilosis (18.9 %), C. glabrata (9.4 %), and C. tropicalis (9.4 %). The mean treatment duration was 54.9 days. Multiple different treatment regimens were administered to patients. These included fluconazole (56.0 %), echinocandins (29.3 %), amphotericin B formulations (10.7 %), and voriconazole (4.0 %). Twenty-eight patients (52.8 %) also had a therapeutic surgical intervention. Clinical response was improved in 38 (71.7 %) patients (43.4 % complete and 28.3 % partial response), stable in 11 (20.8 %), and worse in one (1.9 %); three (5.7 %) patients had unknown response. The 12-week survival rate was 93.8 %. In summary, C. albicans was the predominant pathogen, and fluconazole was the most commonly administered agent. However, treatment patterns vary and remain non-standardized. Concurrent candidemia was infrequent, and 12-week survival was notably good in this series of 53 patients with Candida osteomyelitis.

Many studies have examined the etiology of fever complicating neutropenia. Little is known about the etiology of fever occurring immediately following recovery from myelosuppression. We reviewed 165 episodes of fever in patients who were admitted to the University of Pennsylvania Medical Center (Philadelphia) between 1 August 1992 and 15 August 1994 for the treatment of acute leukemia. We included patients who had episodes of fever (temperature of > or = 38 degrees C) for > or = 48 hours within 10 days after an absolute neutrophil count of < or = 500 cells/mm3 was determined. Twenty-nine (20%) of 145 episodes met these criteria. In 5 (17%) of 29 episodes the cause of fever was a bacterial infection, in 6 (21%) of 29 episodes the cause of fever was noninfectious, and in 12 (41%) of 29 episodes the cause of fever was unknown. Six (21%) of 29 episodes were due to documented or suspected fungal infection, four were due to suspected pulmonary aspergillosis, and two were due to systemic candidal infections. Fever following recovery from chemotherapy-induced neutropenia is common. Fungal infections occur frequently after recovery from myelosuppression despite widespread use of empirical and prophylactic antifungal therapy. Improved strategies for diagnosing and preventing fungal infections in patients who have fever following recovery from myelosuppression are clearly needed.

We wanted to determine whether a saline flush during vasectomy would reduce the time needed to reach azoospermia.During vasectomy men were randomly assigned to flush the prostatic end of the vas deferens with 10 mL of normal saline (intervention group, n = 50), while the remaining men (n = 56) served as controls. Sperm counts were performed on the immediate postprocedure urine specimen and on semen samples at 1, 6, and 12 weeks after vasectomy.The postprocedure urine specimens from the intervention and control groups contained 29.2 x 106 and 0.004 x 106 sperm, respectively (P.001). Total sperm counts in the ejaculate for intervention and control groups at 1, 6, and 12 weeks were (in millions of sperm): 14.1 and 13.8, 0.4 and 8.0, and 0.0 and 0.011, respectively (P.05 at all time points). There was no difference in the rate at which the men in the 2 groups achieved azoospermia.Vasal perfusion with saline during vasectomy was effective in removing sperm from the distal vas; however, perfusion did not increase the rate at which men achieve azoospermia.

Objective To describe the clinical and radiographic presentation, risk factors, response to therapy and outcome of 16 patients with HIV infection and pulmonary infections caused by Pseudomonas aeruginosa. Design Retrospective review of medical records. Setting An academic tertiary-care hospital. Patients Sixteen patients who met the case definition were included for retrospective review. Results P. aeruginosa pneumonia was community-acquired in 15 patients (94%). The majority of patients (94%) had a diagnosis of AIDS with a mean CD4 cell count of 27 x 10(6)/l cells. Traditional risk factors for the development of P. aeruginosa were missing in most patients. Cavitary infiltrates were present on admission chest radiograph in eight patients (50%). An additional three patients (19%) presented with pulmonary infiltrates that cavitated subsequently. Clinical course was extremely varied with an in-hospital mortality of only 19%, but with an additional 25% of patients developing chronic or recurrent disease. Conclusions Community-acquired pneumonia caused by P. aeruginosa occurs in patients with end-stage HIV infection. The presence of cavitary pulmonary infiltrates on chest radiograph in a patient with a low CD4 count should raise suspicion of P. aeruginosa infection. Obvious risk factors for P. aeruginosa infection may be absent. While the initial mortality rate is lower than that observed in other immunocompromised hosts, the potential for chronic or recurrent infection should be recognized and patients should be followed closely.

Artemisinin (qinghaosu) and several derivatives have been developed and are in use as antimalarial drugs but scant information is available regarding animal or human toxicity. Following a eight-day, multiple-dose, pharmacokinetic study of arteether (AE) (10 mg/kg/day [n = 6] and 20 mg/kg/day [n = 6]) in dogs, all high-dose animals displayed a progressive syndrome of clinical neurologic defects with progressive cardiorespiratory collapse and death in five of six animals. Neurologic findings included gait disturbances, loss of spinal and pain response reflexes, and prominent loss of brain stem and eye reflexes. Animals had prolongation of QT interval corrected for rate (QTc) on electrocardiograms (ECGs) with bizarre ST-T segment changes. Prominent neuropathic lesions were noted to be primarily limited to the pons and medulla. Similar lesions with dose-related severity were noted in eight other dogs studied in a second study with intramuscular (IM) administration of AE in sesame oil during a 28-day, dose-ranging study using 5, 10, 15, and 20 mg/kg/day. Injury, graded by a pathologist blinded to the dose group, showed a dose-related, region-specific injury in all animals that was most pronounced in the pons. Further studies in Sprague-Dawley rats using IM administration of AE and artemether (AM) at a dose of 12.5-50 mg/kg/day for 28 days confirmed the onset of a clinical neurologic syndrome with dose-related changes in body weight, activity, and seizure-like activity, stereotypic movement disorders, and ECG changes.(ABSTRACT TRUNCATED AT 250 WORDS)

New treatments for malaria are urgently needed in areas such as Thailand where highly drug-resistant strains of Plasmodium falciparum are prevalent. Mefloquine is rapidly losing efficacy and conventional doses of halofantrine are ineffective. We therefore used pharmacokinetic simulation to design an extended-dose halofantrine regimen and tested it in 26 soldiers stationed along the Thai-Cambodian border. Halofantrine was given after meals as three doses of 500 mg each at 4-hr intervals on the first day, followed by 500 mg a day for six days (total dose 4.5 g). Twenty-six soldiers treated with quinine-tetracycline for seven days (Q(7)T(7)) served as controls. There were no significant differences in efficacy between halofantrine and Q(7)T(7) (P > 0.1) as assessed by cure rate (92% versus 85%), mean parasite clearance time (82 hr versus 81 hr), or mean fever clearance time (93 hr versus 99 hr). Halofantrine was better tolerated than Q(7)T(7). The side effects score was lower (2 versus 11; P < 0.001), there were less days on which side effects occurred (2.0 days versus 5.5 days; P < 0.001), and fewer patients had adverse effects on every treatment day (4% versus 42%; P < 0.01). High-dose halofantrine is as effective and better tolerated than quinine-tetracycline for multidrug-resistant falciparum malaria.

Although overall and major complication rates of 10% to 20% and 0% to 6%, respectively, have been observed in large series of ureteroscopy, to our knowledge no systemic analysis to determine factors predictive of these complications has been reported.We retrospectively reviewed all ureteroscopies performed at our institution for calculous disease from January 1997 through September 1999. A total of 322 procedures were performed by 5 attending surgeons. Intraoperative and immediate postoperative complications were identified. Bivariate and multivariate analysis was performed to identify associated factors with ureteral perforation and postoperative complications as the dependent variables.Bivariate analysis showed a significant association of ureteral perforation with increased operative time (p = 0.0001). In addition, we noted a significant association of postoperative complications with stones in the kidney (p = 0.0004), operative time (p = 0.05) and decreased surgeon experience (p = 0.0035) as well as a trend toward significance for the type of ureteroscope used (p = 0.0609). In multivariate logistic regression models ureteral perforation remained highly associated with operative time (p = 0.0005) when controlling for the other factors. Similarly decreased surgeon experience and a stone in the kidney were predictive of postoperative complications when controlling for the other factors (p = 0.004).Longer duration of the ureteroscopic procedure is strongly associated with ureteral perforation. The likelihood of immediate postoperative complications is greater when renal calculi are treated and less when the surgeon is more experienced.

Invasive aspergillosis (IA) is an important cause of morbidity and mortality in hematopoietic stem cell transplant (HSCT) and solid organ transplant (SOT) recipients. The purpose of this study was to evaluate factors associated with mortality in transplant patients with IA.Transplant patients from 23 US centers were enrolled from March 2001 to October 2005 as part of the Transplant Associated Infection Surveillance Network. IA cases were identified prospectively in this cohort through March 2006, and data were collected. Factors associated with 12-week all-cause mortality were determined by logistic regression analysis and Cox proportional hazards regression.Six-hundred forty-two cases of proven or probable IA were evaluated, of which 317 (49.4%) died by the study endpoint. All-cause mortality was greater in HSCT patients (239 [57.5%] of 415) than in SOT patients (78 [34.4%] of 227; P.001). Independent poor prognostic factors in HSCT patients were neutropenia, renal insufficiency, hepatic insufficiency, early-onset IA, proven IA, and methylprednisolone use. In contrast, white race was associated with decreased risk of death. Among SOT patients, hepatic insufficiency, malnutrition, and central nervous system disease were poor prognostic indicators, whereas prednisone use was associated with decreased risk of death. Among HSCT or SOT patients who received antifungal therapy, use of an amphotericin B preparation as part of initial therapy was associated with increased risk of death.There are multiple variables associated with survival in transplant patients with IA. Understanding these prognostic factors may assist in the development of treatment algorithms and clinical trials.

Invasive fungal infections (IFIs) are a major cause of morbidity and mortality among organ transplant recipients. Multicenter prospective surveillance data to determine disease burden and secular trends are lacking.The Transplant-Associated Infection Surveillance Network (TRANSNET) is a consortium of 23 US transplant centers, including 15 that contributed to the organ transplant recipient dataset. We prospectively identified IFIs among organ transplant recipients from March, 2001 through March, 2006 at these sites. To explore trends, we calculated the 12-month cumulative incidence among 9 sequential cohorts.During the surveillance period, 1208 IFIs were identified among 1063 organ transplant recipients. The most common IFIs were invasive candidiasis (53%), invasive aspergillosis (19%), cryptococcosis (8%), non-Aspergillus molds (8%), endemic fungi (5%), and zygomycosis (2%). Median time to onset of candidiasis, aspergillosis, and cryptococcosis was 103, 184, and 575 days, respectively. Among a cohort of 16,808 patients who underwent transplantation between March 2001 and September 2005 and were followed through March 2006, a total of 729 IFIs were reported among 633 persons. One-year cumulative incidences of the first IFI were 11.6%, 8.6%, 4.7%, 4.0%, 3.4%, and 1.3% for small bowel, lung, liver, heart, pancreas, and kidney transplant recipients, respectively. One-year incidence was highest for invasive candidiasis (1.95%) and aspergillosis (0.65%). Trend analysis showed a slight increase in cumulative incidence from 2002 to 2005.We detected a slight increase in IFIs during the surveillance period. These data provide important insights into the timing and incidence of IFIs among organ transplant recipients, which can help to focus effective prevention and treatment strategies.

Background Invasive infection with Candida species is an important cause of morbidity and mortality in intensive care unit (ICU) patients. Optimal preventive strategies have not been clearly defined. Objective To see whether empirical fluconazole improves clinical outcomes more than placebo in adult ICU patients at high risk for invasive candidiasis. Design Double-blind, placebo-controlled, randomized trial conducted from 1995 to 2000. Setting 26 ICUs in the United States. Patients 270 adult ICU patients with fever despite administration of broad-spectrum antibiotics. All had central venous catheters and an Acute Physiology and Chronic Health Evaluation II score greater than 16. Intervention Patients were randomly assigned to either intravenous fluconazole, 800 mg daily, or placebo for 2 weeks and were followed for 4 weeks thereafter. Two hundred forty-nine participants were available for outcome assessment. Measurements A composite primary outcome that defined success as all 4 of the following: resolution of fever; absence of invasive fungal infection; no discontinuation because of toxicity; and no need for a nonstudy, systemic antifungal medication (as assessed by a blinded oversight committee). Results Only 44 of 122 (36%) fluconazole recipients and 48 of 127 (38%) placebo recipients had a successful outcome (relative risk, 0.95 [95% CI, 0.69 to 1.32; P = 0.78]). The main reason for failure was lack of resolution of fever (51% for fluconazole and 57% for placebo). Documented invasive candidiasis occurred in 5% of fluconazole recipients and 9% of placebo recipients (relative risk, 0.57 [CI, 0.22 to 1.49]). Seven (5%) fluconazole recipients and 10 (7%) placebo recipients had adverse events resulting in discontinuation of the study drug. Discontinuation because of abnormal liver test results occurred in 3 (2%) fluconazole recipients and 5 (4%) placebo recipients. Limitations Twenty-one randomly assigned patients were not included in the analysis because they either did not meet entry criteria or did not have postbaseline assessments. Fewer fungal infections than anticipated occurred in the control group. Confidence bounds were wide and did not exclude potentially important differences in outcomes between groups. Conclusion In critically ill adults with risk factors for invasive candidiasis, empirical fluconazole did not clearly improve a composite outcome more than placebo.

Objective To investigate optimal test vial (TV) volume, utility and reliability of TVs, intermediate temperature exposure (−88°C to −93°C) before cryostorage, cryostorage in nitrogen vapor (VN 2 ) and liquid nitrogen (LN 2 ), and long-term stability of VN 2 cryostorage of human semen. Design Prospective clinical laboratory study. Setting University assisted reproductive technology (ART) laboratory. Patient(s) A total of 594 patients undergoing semen analysis and cryopreservation. Intervention(s) Semen analysis, cryopreservation with different intermediate steps and in different volumes (50–1,000 μL), and long-term storage in LN 2 or VN 2 . Main Outcome Measure(s) Optimal TV volume, prediction of cryosurvival (CS) in ART procedure vials (ARTVs) with pre-freeze semen parameters and TV CS, post-thaw motility after two- or three-step semen cryopreservation and cryostorage in VN 2 and LN 2 . Result(s) Test vial volume of 50 μL yielded lower CS than other volumes tested. Cryosurvival of 100 μL was similar to that of larger volumes tested. An intermediate temperature exposure (−88°C to −93°C for 20 minutes) during cryopreservation did not affect post-thaw motility. Cryosurvival of TVs and ARTVs from the same ejaculate were similar. Cryosurvival of the first TV in a series of cryopreserved ejaculates was similar to and correlated with that of TVs from different ejaculates within the same patient. Cryosurvival of the first TV was correlated with subsequent ARTVs. Long-term cryostorage in VN 2 did not affect CS. Conclusion(s) This study provides experimental evidence for use of a single 100 μL TV per patient to predict CS when freezing multiple ejaculates over a short period of time ( 2 provides a stable and safe environment over time.

Objectives Epididymectomy is an option for the relief of epididymal pain related to postoperative obstruction, epididymal cysts, or epididymitis. We performed 66 epididymectomies on 52 patients from 1996 to 2006 at our institution for localized epididymal pain. We evaluated the long-term symptomatic relief after epididymectomy. Methods All 52 epididymectomy patients were mailed questionnaires regarding their current pain level and satisfaction. Patients who did not return the questionnaires were interviewed by telephone for follow-up. Results Of the 52 patients, 34 returned 44 completed questionnaires (the patients with bilateral procedures were mailed a questionnaire for each side). The average age at epididymectomy was 44.2 years (range 25.0 to 67.9). The average follow-up was 45.8 months (range 4.2 to 119.3). Of the 34 procedures, 17 were left sided, 7 right sided, and 10 were bilateral; 25 had been performed for postvasectomy pain and 5 for obstruction related to hernia repair. Of the 44 cases, 31 (70%) reported no pain. Of the 13 still with pain, 8 (62%) reported less pain. Also, 90% were very satisfied or satisfied with their choice to undergo epididymectomy. Conclusions We found excellent results after epididymectomy, especially for the indication of postvasectomy pain.

The aim of this study was to determine if, following vasectomy, epididymal obstruction resulted in changes in vasal stump fluid using a rat vasectomy model. One hundred and twenty-two mature male rats underwent bilateral surgical vasectomy and subsequent unilateral epididymal obstruction. Animals were randomly assigned to one of the five cohorts, which determined the time to kill and vasal fluid assessment. Numbers of whole sperm and sperm heads were compared between the obstructed and non-obstructed sides. Parametric analysis of microscopic vasal fluid findings was performed using a paired t-test. Whole sperm and sperm heads were detected bilaterally among the initial five cohorts. On the obstructed epididymis side, percentage of whole sperm dropped from 36.9% to less than 1% and sperm heads increased from 63.2 to 99.7% at 12 weeks post-obstruction (p < 0.05 at each time interval). On the unobstructed side, percentage of whole sperm rose from 66.3 to 89.5% and sperm heads dropped from 33.7 to 10.5% (p < 0.05 at each time interval). At 12 weeks, the difference between the obstructed and non-obstructed sides for both percentage and quantity of whole sperm and heads was significant with a p value of

Premature ejaculation is a common entity that can have a significant impact on an individual's sexual satisfaction and quality of life. Both behavioral and pharmacological options are available and effective for men presenting with this condition.

Prevention of invasive fungal infections (IFIs) in orthotopic liver transplant (OLT) recipients utilizing postoperative systemic antifungal prophylaxis, typically with fluconazole, is justified among those at high risk for IFI. Use of postoperative antifungal prophylaxis for low-risk OLT recipients is widely practiced but not universally accepted nor supported by data. We conducted a prospective observational study among 200 OLT recipients who were at low risk for IFI and did not receive postoperative antifungal prophylaxis. Patients were considered low risk if they had ≤1 of the following conditions: choledochojejunostomy anastomosis; retransplantation; intra-operative administration of ≥units of 40 blood products or return to the operating room for intra-abdominal bleeding; return to the operating room for anastomotic leak or vascular insufficiency; preoperative serum creatinine of ≥2 mg/dL; and perioperative Candida colonization. Patients were followed 100 d post-transplantation for evidence of IFI. Of 193 eligible patients, 7 (4%) developed an IFI. Three (2%) IFIs were due to Candida spp. and potentially preventable by standard fluconazole prophylaxis. Three patients developed invasive aspergillosis; one developed late onset disseminated cryptococcosis. Liver transplant recipients at low risk for IFI can be identified utilizing pre-determined criteria, and post-transplantation antifungal prophylaxis can be routinely withheld in these patients.

Aspergillus endocarditis is very difficult to cure, even with aggressive surgical debridement and antifungal therapy. Patients with embolic involvement of the central nervous system have an extremely poor prognosis. We describe a patient with prosthetic valve endocarditis due to Aspergillus fumigatus who developed emboli in the brain, eye, and lower extremities. With aggressive surgical debridement of involved sites, aortic valve and root replacement, and long-term therapy with oral voriconazole, he remains without any evidence of infection 2 years later.