The impact of the coronavirus disease 2019 pandemic on changes in antimicrobial prophylaxis and development of genito-urinary tract infections after urodynamic study: A retrospective comparative study of a single rehabilitation hospital in Japan.

AIMS: To investigate the changes in the proportion of antimicrobial prophylaxis (AP) during the urodynamic study (UDS) and the frequency of posttest genito-urinary tract infections (GUTI) before and after coronavirus disease 2019 (COVID-19) pandemic, and evaluate this associations. PATIENTS AND METHODS: Patients who underwent UDS between 2015 and 2021 were targeted, and they were allocated to pre-2020 as before the appearance of COVID-19 and post-2020 as after that, and propensity score matching was performed. The impact on AP was assessed by the administration rate, and that on the development of febrile GUTI after UDS was assessed for an equivalence by the GUTI-free rate at 7 days after testing. RESULTS: After matching, 384 cases of 192 cases each were included. The frequency of AP was 58.3% in pre-2020 and 77.1% in post-2020, an increase of about 19%, and the rate increased significantly in post-2020 (p < 0.001). However, the incidence of GUTI after UDS was 4.2% and 4.7%, respectively, with no significant difference. The ratio of GUTI-free rates was within the equivalence margin, confirming an equivalence before and after the appearance of COVID-19. CONCLUSIONS: Under the influence of COVID-19 pandemic, even though AP rate during UDS was increased by 19% from that brought by following the guideline-based administration methods, the frequency of GUTI after UDS was similar, so it is thought to be important to use AP during UDS appropriately for high-risk cases as recommended in the guidelines.

Retrospective Observational Study of Risk Factors for Febrile Infectious Complications after Urodynamic Studies in Patients with Suspected Neurogenic Lower Urinary Tract Disturbance.

INTRODUCTION: We retrospectively investigated the risk factors for post-urodynamic study (UDS) infectious complications in long-term hospitalized inpatients with suspected neurogenic lower urinary tract disturbance (NLUTD) in a monocenter study, to accurately assess post-UDS urinary tract infections (UTI). METHODS: We retrospectively analyzed data including background information, UDS-related data, and potential risk factors for infection from 489 NLUTD-suspected inpatients who underwent UDS from 2015 to 2019 and examined the risk factors for post-UDS infectious complications using univariate and multivariate statistical analyses. RESULTS: Symptomatic post-UDS UTI occurred in 20 out of 489 (4.1%) patients, including 3 (15%) with recurrent UTI. During follow-up prior to UDS for 1 year, 220 cases were investigated by urine culture revealing Escherichia coli (n = 77), Klebsiella pneumoniae (n = 29), Enterococcus faecalis (n = 18), extended-spectrum beta-lactamase-producing E. coli (n = 17), and Pseudomonas aeruginosa (n = 9). As risk factors for post-UDS infectious complications, American Spinal Injury Association impairment scale (AIS): AIS ≧ C (A or B or C) (hazard ratio: 4.29, p = 0.0076), management method of urination (hazard ratio: 4.30, p = 0.048), and age (hazard ratio: 1.04, p = 0.025) were significantly correlated with the occurrence of post-UDS infection. CONCLUSIONS: The significant risk factors for post-UDS UTI were AIS ≧ C, management method of urination, and age in the suspected NLUTD patient context. This study was originally started with the goal of reducing unnecessary antibiotics and may contribute to the proper use of antibiotics based on antimicrobial stewardship.

Risk factors for febrile genito-urinary infection in the catheterized patients by with spinal cord injury-associated chronic neurogenic lower urinary tract dysfunction evaluated by urodynamic study and cystography: a retrospective study.

INTRODUCTION: To investigate the risk factors for febrile genito-urinary tract infection (GUTI) in spinal cord injury-associated neurogenic lower urinary tract dysfunction (NLUTD) patients who perform routine clean intermittent catheterization (CIC) evaluated by urodynamic study (UDS) and cystography. PATIENTS AND METHODS: Over a 3-year period, we retrospectively assessed risk factors for febrile UTI in 141 spinal cord injury patients diagnosed as NLUTD and performing routine CIC, regarding gender, UDS findings such as bladder compliance, maximum cystometric capacity, and cystography. RESULTS: A total of 41 patients had febrile GUTI in the follow-up period as along with 32 cases of pyelonephritis, 10 cases of epididymitis, and 1 case of prostatitis, including patients with multiple infectious diseases. The causative bacteria were Escherichia coli (14 cases) followed by Pseudomonas aeruginosa (n = 5), Klebsiella pneumoniae (n = 4), and Klebsiella oxytoca (n = 4). Antibiotic-resistant E. coli were seen, with 36.4% instances of extended-spectrum beta-lactamase production in whole of E. coli. Male gender (p = 0.018), ASIA Impairment Scale (AIS) C or more severe (p = 0.031), the number of CIC (p = 0.034), use of quinolones (p < 0.001) and severe bladder deformity (DG 2 or more, p = 0.004) were significantly associated with febrile GUTI occurrence. CONCLUSIONS: Our data demonstrated that male gender, severe bladder deformity (DG 2 or more), AIS C or more, the number of CIC, and use of quinolones were significantly associated with febrile GUTI occurrence in NLUTD patients employing routine CIC. Further prospective studies are necessary to define the full spectrum of possible risk factors for febrile GUTI in these patients.

Use of oral third generation cephalosporins and quinolones and occurrence of antibiotic-resistant strains in the neurogenic bladder (NB) outpatient setting: a retrospective chart audit.

STUDY DESIGN: A retrospective chart audit. OBJECTIVES: Neurogenic bladder (NB), a risk factor for urinary tract infection, has not been comprehensively studied in terms of antimicrobial stewardship. In this study, we studied the relationship between the use of oral third generation cephalosporins and quinolones, and the occurrence of antibiotic-resistant strains. SETTING: Hyogo Prefectural Central Rehabilitation Hospital, Hyogo, Japan. METHODS: We retrospectively investigated antibiotic-resistant bacteria and the amount of antibiotics prescribed in outpatients with NB caused by spinal cord injury between 2012 and 2017. We intervened in urological departments whose physicians often prescribed third generation cephalosporins and fluoroquinolone, and analyzed the number of prescriptions and the amount of Cefdinir (CFDN) and Levofloxacin (LVFX), and studied changes of ratios in antibiotic-resistant strains such as extended-spectrum ß-lactamases (ESBLs) and quinolone-resistant Escherichia coli and Klebsiella pneumoniae. RESULTS: The number of CFDN prescriptions per year significantly decreased from 463 cases to 130 cases over 6 years (p = 0.012). The number of LVFX prescriptions per year decreased from 640 cases to 171 cases (p = 0.025). The incidence rate of ESBL-producing K. pneumoniae decreased from 25% to 7% of total K. pneumoniae (p < 0.001). The incidence of LVFX-resistant E. coli and K. pneumoniae significantly decreased in 2017 compared with 2012 (p = 0.03 and p = 0.016, respectively). CONCLUSIONS: Antimicrobial stewardship interventions decreased the use of CFDN and LVFX for outpatients with NB. Our findings suggested that the reduction in the use of third generation cephalosporins and quinolones correlates with observed decrease in the occurrence of antibiotic-resistant, ESBL-producing, and quinolone-resistant bacteria.

Factors associated with symptomatic urinary tract infection in persons with spinal cord lesions who perform clean intermittent catheterization with single-use catheters.

OBJECTIVES: To investigate factors associated with symptomatic urinary tract infection (sUTI) in persons with chronic spinal cord lesion (SCL) who were using single-use catheters for intermittent self-catheterization (ISC). METHODS: Among respondents to an internet survey on the burden of illness on persons with SCL who were considered to be able to perform ISC, 111 persons using single-use catheters were included to examine factors associated with self-reported sUTI by univariate as well as multivariable analysis. RESULTS: The incidence of sUTI was significantly higher in males than in females (56.9% vs. 31.6%, p = .011), persons with stocks of antibiotics than those without it (82.9% vs. 28.6%, p < .011), and persons with more frequent bleeding during catheterization than those with less frequent bleeding (100% vs. 46.5%, p = .036). The incidence did not significantly differ between respective groups when various variables were evaluated by other characteristics of the participants, adherence to ISC procedures, and complications. On multivariable analysis, male gender and stocks of antibiotics were significant independent factors for sUTI. CONCLUSIONS: Male gender and stocks of antibiotics were associated with sUTI in persons with SCL who were performing ISC with single-use catheters.

[DEVELOPMENT OF JAPANESE TRANSLATION OF THE NEUROGENIC BLADDER SYMPTOM SCORE].

(Objectives) To develop Japanese translations of the standard and short forms of the Neurogenic Bladder Symptom Score (Subjects and methods) The questionnaires were forward translated by a Japanese healthcare professional and non-medical professional and backward translated by two native English-speaking translators. Then, the products were harmonized by the participants involved in the translational processes. Finally, 15 persons with spinal cord lesions were interviewed to improve the provisional Japanese translations based on their suggestions. (Results) Throughout the forward and backward translations and their harmonization, no major translational problems were encountered, other than those attributable to differences in syntax between English and Japanese. The persons could complete the provisional Japanese translations of the standard and short forms in median 7.0 and 3.0 minutes, respectively. Although none of them reported difficulty in answering the questions, 6, 3, and 5 persons pointed out that the tenth question (the seventh question in the short form) and the answers to the nineteenth and twenty-second questions, respectively, were not easy to understand. Taking their suggestions into consideration, we finalized the Japanese translations with the help of a developer of the questionnaire as well as the back-translators. (Conclusions) After a multi-step review process, linguistically valid Japanese translations of the standard and short forms of the Neurogenic Bladder Symptom Score (Neurogenic Bladder Symptom Score Japanese version 1.0) were completed. We hope that these Japanese translations will facilitate future research on patient-reported outcomes in persons with neurogenic lower urinary tract dysfunction.

Cross-sectional internet survey exploring symptomatic urinary tract infection by type of urinary catheter in persons with spinal cord lesion in Japan.

STUDY DESIGN: Cross-sectional study by members of patient advocacy groups. OBJECTIVES: To evaluate the incidence and frequency of symptomatic urinary tract infection (sUTI) in persons with spinal cord lesion (SCL) using different types of catheters based on an internet survey in Japan. SETTING: An internet survey. METHODS: We conducted an Internet survey of persons with SCL who were considered to be able to perform intermittent self-catheterization (ISC). We evaluated the incidence and frequency of sUTI over the last year in persons performing ISC and those managed by indwelling catheterization (IDC). We also compared the same parameters between persons in the ISC group using reusable silicone catheters and single-use catheters and those with and without a concomitant use of intermittent balloon catheters (i-IDC). RESULTS: Two-hundred and eighty-two persons were analyzed. In the ISC and IDC groups, sUTI occurred in 52.2% and 31.4% of persons (p = 0.021), respectively, in the last year, and the frequencies were 2.8 and 3.5 times a year (p = 0.127), respectively. There were no significant differences in the incidence or frequency of sUTI between persons using reusable catheters and single-use catheters or those with and without the concomitant use of i-IDC. CONCLUSIONS: sUTI occurred in about 1 in 2 persons with SCL performing ISC, which was significantly higher than in the IDC group, and the frequency of sUTI in persons performing ISC was about 3 times a year. The different types of catheters used for ISC were not associated with the incidence or frequency of sUTI. Sponsorship Coloplast Japan Inc.

Hygiene management of intermittent self-catheterization using reusable silicone catheters in people with spinal cord lesions: A cross-sectional Internet survey in Japan.

OBJECTIVES: To investigate hygiene management and catheter maintenance of reusable silicone catheters for intermittent self-catheterization (ISC) in Japan and examine their relationship with symptomatic urinary tract infection (sUTI). METHODS: We conducted a cross-sectional Internet survey of people performing ISC using reusable silicone catheters owing to spinal cord lesions in Japan. Hygiene management and catheter maintenance of reusable silicone catheters and the incidence and frequency of sUTI were evaluated. We also examined the significant risk factors for sUTI. RESULTS: Of 136 respondents, 62 (46%), 41 (30%), and 58 (43%) washed hands with water, washed hands with soap, and cleaned or disinfected the urethral meatus every time or most of the time before ISC, respectively. No significant difference was observed in the incidence and frequency of sUTI between respondents who adhered to these procedures and those who did not. There were no significant differences in the incidence and frequency of sUTI in respondents who changed their catheters every month and in those who changed their preservation solution within 2 days compared with those who did not. In multivariate analysis, pain during ISC, inconvenience of indoor mobility, bowel management problems, and participants' feeling of never having received instruction on catheter replacement were significant risk factors for sUTI. CONCLUSIONS: There are individual differences in hygiene management and catheter maintenance of reusable silicone catheters, but the influence of these differences on the incidence and frequency of sUTI is not clear. Pain during ISC, bowel management problems, and inadequate instruction on catheter maintenance procedures are factors associated with sUTI.

Comparison between antimicrobial stewardship program and intervention by infection control team for managing antibiotic use in neurogenic bladder-related urinary tract infection patients: A retrospective chart audit.

BACKGROUND: Antimicrobial prescriptions are relatively common in urologic outpatients. Therefore, it is necessary to investigate the impact of antimicrobial stewardship program (ASP) interventions. METHODS: In urology outpatients, antimicrobial use density (AUD), antimicrobial agent costs, isolation of urinary tract infection (UTI)-causing organisms and their antimicrobial susceptibilities were compared between intervention by infection control team (ICT) era (pre-2014) and ASP era (post-2014) in 2739 patients with lower urinary tract symptoms, including neurogenic bladder patients with UTI or suspected UTI, from 2011 to 2020. RESULTS: In the ASP, overall AUD (P<.001), cefotiam (CTM) (P=.0013), 2nd-generation cephalosporins (P=.026), cefdinir (CFDN) (P<.001), levofloxacin (LVFX) (P<.001), sitafloxacin (STFX) (P=.0016), and tosufloxacin (TFLX) (P=.0044) showed a significant decrease, but cefaclor (P=.019) showed a significant increase. Regarding antimicrobial agent costs, overall (P=.016), CTM (P=.021), 2nd-generation cephalosporins (P=.033), CFDN (P=.016), LVFX (P=.016), STFX (P=.033), and TFLX (P=.033) showed a significant decrease in the ASP. UTI-causing antimicrobial susceptibilities, CTM (P=.035), LVFX (P=.026) and sulfamethoxazole/trimethoprim (P=.048) in E. coli, and minocycline (P=.026) in K. pneumoniae showed a significant improve in the ASP. CONCLUSION: ASP contributed to decrease AUD and antimicrobial agent costs, and to improve antimicrobial susceptibilities of E. coli and K. pneumoniae to several antibiotics, compared to ICT. Further prospective studies are necessary for definitive conclusions.

Validation of the Monitoring Efficacy of Neurogenic Bowel Treatment on Response (MENTOR) Tool in a Japanese Rehabilitation Setting.

STUDY DESIGN: Prospective observational study. OBJECTIVE: To validate the Monitoring Efficacy of NBD Treatment On Response (MENTOR) tool in individuals with a spinal cord injury (SCI) or spina bifida, suffering from neurogenic bowel dysfunction (NBD) in a rehabilitation center in Japan. METHODS: First, the MENTOR tool was translated from English to Japanese using a validated translation process. Second, the MENTOR tool was validated in a rehabilitation clinic in Japan. Participants completed the MENTOR tool prior to a consultation with an expert physician. According to the results of the tool, each participant was allocated to one of three categories regarding change in treatment: "adequately treated," "further discussion," and "recommended change." The results of the MENTOR tool were compared with the treatment decision made by an expert physician, who was blinded to the results of the MENTOR tool. RESULTS: A total of 60 participants completed the MENTOR tool. There was an acceptable concordance between individuals allocated as respectively, being adequately treated (100%) and recommended change in treatment (61%) and the physicians' decision on treatment. The concordance was lower for individuals allocated as requiring further discussion (48%). CONCLUSIONS: In this study the MENTOR tool was successfully validated in a Japanese rehab setting. The tool will help identify individuals with SCI that need further treatment of their NBD symptoms.

The 1-year continuation rate and discontinuation factors of vibegron and mirabegron: A retrospective comparative study in a rehabilitation hospital in Japan.

OBJECTIVES: To compare the 1-year continuation rate and discontinuation factors between vibegron and mirabegron in patients with neurogenic and nonneurogenic overactive bladder. METHODS: Continuation or discontinuation of the target drugs and reasons for discontinuation as well as patients' grounds and adverse effects were evaluated retrospectively from the medical records between September 2018 and December 2020. After selecting patients according to the inclusion and exclusion criteria, 180 cases taking mirabegron and 132 taking vibegron were adjusted for intergroup variability by propensity score matching. We performed Cox proportional hazards regression for the 1-year continuation rate and Fine-Gray proportional hazards regression for the 1-year cumulative incidence of discontinuation events. Subgroup analysis was also performed for the background factors related to the 1-year continuation rate. RESULTS: The 1-year continuation rate was 83.8% for vibegron and 58.2% for mirabegron, and the hazard ratio was 0.32 (95% CI: 0.18-0.57, P < .001) as for an incidence of discontinuation events of vibegron against mirabegron. The incidence of discontinuation due to an inadequate efficacy was 8.7% for vibegron and 29.1% for mirabegron, and similarly the hazard ratio was 0.26 (95% CI: 0.12-0.55, P < .001). The subgroup analysis indicated a similar tendency in each subgroup except for that of catheterization, and there was no significant interaction between the groups. CONCLUSIONS: It is suggested that vibegron is superior to mirabegron in the continuity of administration in neurogenic and nonneurogenic overactive bladder populations without catheterization with fewer discontinuations due to inadequate efficacy.

[SIMULATION ANALYSIS ON COST-EFFECTIVENESS OF SANITARY AND MEDICAL MATERIAL USAGE AT URINARY TRACT INFECTION OUTBREAK CAUSED BY ANTIBIOTIC-RESISTANT BACTERIA IN UROLOGICAL WARD].

(Purpose) The purpose of this study is to compare the costs of active surveillance culture (ASC) and of an environmental cleaner and disinfectant, with the medical costs for inhibiting hospitalized urinary tract infection (UTI) outbreaks in a urology ward over a 3 year 8 months period by simulation calculation. (Methods) We previously reported a UTI outbreak via antibiotic resistant bacteria transmission in 9 hospitalized patients, for which we initiated ASC and introduced a potassium peroxymonosulfate-based product (RUBYSTA® (RST)) as a disinfectant environmental cleaner, then prevented recurrence for 3 years and 8 months. This study compared the actual costs of ASC and RST use to the calculated medical expense for an outbreak leading to urosepsis on the same scale caused by transmission of antibiotic resistant bacteria. (Results) Based on our simulation calculation, ASC and disinfectant costs were about 770,000 Japanese yen lower than the medical expense of resolving an outbreak without recurrence for a period of 3 years and 8 months, based on our direct clinical experience. (Conclusion) Even though it is needless to say that education for medical stuffs, patients and their families is the most important as to the measures for prevention of infections, our simulation study suggests that ASC and RST use may reduce medical costs for resolving such outbreaks and preventing their recurrence for an extended period of time.

Modulation of the microenvironment by growth factors regulates the in vivo growth of skeletal myoblasts.

OBJECTIVE: To investigate the optimal microenvironment for efficient myoblast transplantation in vivo. MATERIALS AND METHODS: The effects of co-culture with growth factors, including basic fibroblast growth factor (bFGF), hepatocyte growth factor (HGF), insulin-like growth factor-I) and platelet-derived growth factor (PDGF), on in vitro growth, migration and proteolytic activity of mouse skeletal myoblasts were investigated. Myoblasts were co-injected with growth factors into the subcutis and bladder wall of nude mice, and its impact on the growth patterns of myoblasts in vivo assessed. RESULTS: There was dose-dependent stimulation of in vitro myoblast growth after treatment with each of the four growth factors, but bFGF induced the most marked increase in the growth of myoblasts. Treatment of myoblasts with all types of growth factors also resulted in a dose-dependent increase in the in vitro migration of myoblasts, and PDGF had the most prominent effect on myoblast migration. Increased secretion of matrix metalloproteinase-9 (MMP-9) in myoblasts induced by growth factors was proportional to their increased migration capacity, which was partly inhibited by SB-3CT, an inhibitor of MMP-9. The in vivo growth of myoblasts was significantly enhanced by co-injection with all types of growth factor into both the subcutis and bladder wall, but this effect was most marked 1 and 2 weeks after co-injection with bFGF and PDGF, respectively. Furthermore, there was synergistic in vivo growth of myoblasts by co-injection of both bFGF and PDGF compared with that achieved with either agent alone. CONCLUSIONS: These findings suggest that modulation of the microenvironment using growth factors, particularly bFGF and PDGF, could provide the optimum condition for effective myoblast transplantation in vivo.

Cost-Effectiveness Analysis of Transanal Irrigation for Managing Neurogenic Bowel Dysfunction in Japan.

BACKGROUND: Neurogenic bowel dysfunction (NBD) is a common sequela in Spinal Cord Injury (SCI) patients. Bowel dysfunction symptoms have a significant negative impact on quality of life (QOL) and are often socially disabling. Transanal irrigation (TAI) is a bowel management procedure that significantly mitigates NBD symptoms in patients refractory to standard bowel care (SBC) by reducing the incidence of fecal incontinence, ameliorating constipation, and improving QOL. TAI devices are used across many countries such as the United Kingdom, Germany, and France, and introduction of the devices is being considered in Japan. In this context, a cost-effectiveness analysis specific to Japanese settings is relevant. OBJECTIVES: To analyze the cost-effectiveness of TAI for bowel management of SCI patients with NBD in a Japanese clinical setting. METHODS: A modified version of a previously developed and published Markov model was used to evaluate the cost-effectiveness of TAI. In the model, SCI patients using TAI due to NBD were compared with SCI patients not responding to TAI and continuing with SBC. Quality-adjusted Life Years (QALYs) were used as the primary effectiveness measure, and the analysis was conducted from the payer's perspective. RESULTS: The model predicts a lifetime incremental cost of TAI to be 3 198 687 yen compared with SBC. TAI provided an additional 0.8 QALY, which leads to an incremental cost-effectiveness ratio (ICER) of TAI vs SBC of 4 016 287 yen/QALY. CONCLUSIONS: An ICER of 4 million yen falls within the range of reported willingness to pay (WTP) per QALY gain (5-6.7 million yen) in Japan, and TAI is therefore found to be a cost-effective treatment strategy compared to SBC. The result should be further corroborated in future Japanese trials of TAI.

Comparison of antibiotics use, urinary tract infection (UTI)-causative bacteria and their antibiotic susceptibilities among 4 hospitals with different backgrounds and regions in Japan.

In this study, we compared the antibiotic use, urinary tract infection-causative bacteria and their antibiotic susceptibilities among four hospitals with different backgrounds and regions in Japan in 2014. Frequency of antibiotic use (antibiotic use density: AUD/all AUD) were: ampicillin: 0.21-20.3 (median: 1.6) and cefazolin: 0.8-34.2 (2.5), representatively. The antibiotic resistant rates of Escherichia coli were ampicillin: 1.1-52.3% (median: 51.8%), piperacillin: 47.9-49.1% (48.0%), cefazolin: 23.2-34.1% (28.9%), levofloxacin: 36.6-43.8% (40.2%).We found that there were significant correlations (1) between antibiotic resistance of E. coli and annual total amount of antibiotic use (p = 0.017), annual number of days of antibiotic use (p = 0.002) and days of therapy (DOT, p = 0.002), and (2) between antibiotic resistance of extended-spectrum ß-lactamase-producing bacteria and annual number of days of antibiotic use (p = 0.004) and DOT (p = 0.004) in a rehabilitation hospital. These results suggested that more antibiotic uses could lead to antibiotic resistances. Further analyses with more number of data are being undertaken.

Infection Control Following an Outbreak of Extended-Spectrum Beta-Lactamase-Producing Klebsiella pneumoniae Isolated from Catheter-Associated Urinary Tract Infection.

We present our experience with controlling an outbreak of extended-spectrum beta-lactamase (ESBL)-producing bacteria in catheter-associated urinary tract infection and the measures taken to prevent future outbreaks. In June 2015, 9 out of 44 hospitalized patients in the same ward tested positive for antibiotic-resistant bacteria in urine cultures, including ESBL-producing Klebsiella pneumoniae. Since these bacteria belonged to the same cluster, we concluded this was a localized outbreak. Seven out of 10 environmental tests detected resistant strains at 1,000 colony forming units/cm2 or more. After an outbreak, we undertook periodic monitoring by active surveillance culture (ASC) every 2 months, along with environmental wipe testing. Cleaning regimen was performed through alcohol disinfection 5 or 7 times a day, then changed to complex-type chlorine-based disinfectant cleaner once a day that includes potassium peroxymonosulfate. ASC revealed only one positive case of antibiotic-resistant strain after incorporating new infection controls. Only a few environmental tests were positive for the bacteria after the new cleaning regimen, suggesting this cleaner might be effective for inhibiting outbreaks. Our control measures successfully prevented further outbreak and inhibited the recurrence.

[Individualized treatment of undescended testis].

Undescended testis is one of the most common congenital anomalies requiring surgery. The guideline for the treatment of undescended testis was published by Japanese Society of Pediatric Urology in 2005. However, the management of undescended testis has been still controversial, particularly in case of impalpable testis including abdominal testis. In this article, we review our experience and published reports of orchiopexy for undescended testis and emphasize that the anatomical condition of undescended testis should be applied to individualized surgical treatment.

Comparison of cost-effectiveness between the quantiFERON-TB Gold-In-Tube and T-Spot tests for screening health-care workers for latent tuberculosis infection.

OBJECTIVE/BACKGROUND: There are several methods used to screen for latent tuberculosis (TB) infection (LTBI) including the QuantiFERON-TB Gold-in-Tube (QFT-GIT) and T-SPOT-TB (T-SPOT) tests. Many studies have reported the equivalence of these two methods, but it is unclear which of them is more cost effective. We investigated the age and cost issues of these tests in screening for LTBI among health-care workers. MATERIALS AND METHODS: One hundred and forty new employees during 2008-2011 in our hospital were screened using the QFT-GIT test, and 140 new employees during 2011-2014 were screened with the T-SPOT test for LTBI. The results of both tests were classified as positive, undetermined (retesting required), or negative. RESULTS: There were six positive results (4.29%), eight undetermined results (5.71%), and 126 negative results (90.0%) with the QFT-GIT test. As for the T-SPOT test, there were eight positive results (5.71%), three undetermined results (2.14%), and 129 negative results (92.1%). Fourteen LTBI employees (6 in QFT-GIT and 8 in T-SPOT) were detected statistically equally using the two methods (P = 0.79). The total costs, including those incurred for retesting, were $7,711.86 (US dollar) and $6,525.42 for the QFT-GIT and T-SPOT tests (cost of one test is $55.08 for QFT-GIT and $46.61 for T-SPOT), respectively. CONCLUSION: T-SPOT is one of the options for screening for LTBI partly owing to the viewpoint of cost-effectiveness. Further prospective studies need to be considered for a definitive conclusion.

Endostatin inhibits the vascular endothelial growth factor-induced mobilization of endothelial progenitor cells.

Circulating endothelial cells (CECs) are present in peripheral blood and have been shown to contribute to normal and pathological neovascularization. Antiangiogenic molecules can inhibit neovascularization in tumors and other sites, but their effect on CECs has not yet been determined. We hypothesize that angiogenic factors will increase the number of CECs, and conversely, antiangiogenic treatment will reduce these numbers. Mice treated with high levels of vascular endothelial growth factor (VEGF) showed increased numbers of Flk-1-positive cells in peripheral blood and endothelial cell colonies compared with vehicle-treated controls. These changes were accompanied by increased bone marrow neovascularization. In contrast, mice that received VEGF and endostatin had significantly lower numbers of CECs and reduced bone marrow vascularization. Endostatin-induced apoptosis was probably responsible for the decreased number of CECs. Systemic delivery of a VEGF antagonist, soluble Flt-1, also inhibited the VEGF-induced increase in CECs. These results were further confirmed in a Tie2/LacZ mouse model, in which endostatin reduced the number of beta-galactosidase-expressing peripheral blood mononuclear cells. We propose that endothelial progenitor cells are a novel target for endostatin and suggest that the relative numbers of CECs can serve as a surrogate marker for the biological activity of antiangiogenic treatment.

Angiogenic gene-modified muscle cells for enhancement of tissue formation.

Engineering muscle tissue with inadequate vascularity may lead to fibrosis and loss of muscle function. In this study we combined the isolation and genetic engineering of myoblasts with tissue transplantation in an attempt to create well-vascularized muscle tissue. Myoblasts were obtained from a single explant of adult Lewis rat myofibers and transfected with a bicistronic plasmid encoding vascular endothelial growth factor (VEGF) and green fluorescent protein (GFP) or with a plasmid encoding a nonfunctional VEGF-alkaline phosphatase (AP) fusion protein. VEGF expression and GFP expression in vitro were, respectively, assessed by Western blot analysis ELISA and fluorescence microscopy, showing that the myoblasts were successfully expressing the recombinant proteins. The transfected cells were suspended in collagen type I and injected subcutaneously into nude mice. Analysis of the retrieved engineered muscle tissues by RT-PCR immunostaining and fluorescence showed expression of VEGF and GFP proteins. Immunohistochemical analysis of the muscle tissues 1, 3, and 4 weeks after implantation confirmed the muscle phenotype. Neovascularization and muscle tissue mass significantly increased with functional VEGF-transfected cells compared with nonfunctional VEGF-transfected cells. In conclusion, this study demonstrates that in vivo engineered muscle tissues improve their volumes when VEGF-expressing muscle cells are used.