Yield of modern genetic evaluation for patients with proximal hypospadias and descended gonads.

INTRODUCTION AND BACKGROUND: Although the pediatric urologic community has embraced a multidisciplinary genetic and endocrine evaluation for newborns with ambiguous genitalia, this approach has been reserved for the most severe cases of undervirilized 46,XY individuals despite growing evidence that genetic differences are found even in patients whose only genitourinary anomaly appears to be proximal hypospadias. Identifying these genetic differences is vital for counseling patients as they move through puberty to parenthood as well as parents on future pregnancies. OBJECTIVE: The primary objective was to evaluate genetic diagnosis in patients with proximal hypospadias. The authors hypothesized the more sensitive genetic evaluation available in the modern era will reveal a high rate of patients with proximal hypospadias and descended testicles who are found to have a genetic difference, supporting a thorough genetic evaluation in these patients. STUDY DESIGN: A retrospective review was performed of all patients who underwent surgical correction for proximal hypospadias at a single institution from January 1, 2010, to December 31, 2016. Those with midshaft hypospadias were excluded as were patients whose primary surgery was performed at an outside institution. Patient characteristics, including demographics, clinical presentation, genetic evaluation, and referral to a multidisciplinary difference of sex development (DSD) clinic, were collected. The chi-squared test and t-test were used for analysis. RESULTS: There were 112 patients with proximal hypospadias who met the inclusion criteria. Of these, 91 had bilaterally descended testicles, whereas 21 had one or more undescended testicles. Thirty-three percent of patients with isolated proximal hypospadias received genetic testing of some kind, with 24% seen in the multidisciplinary DSD clinic. Four patients had an associated genetic syndrome identified, and 5 had a genetic difference of unknown clinical significance. Overall, 10% of patients with proximal hypospadias and descended testicles had an identifiable genetic difference vs 33% with associated cryptorchidism. Of these, one patient with proximal hypospadias and descended testicles had a genetic difference of known clinical significance that was likely to have been missed in the absence of an evaluation by a geneticist. DISCUSSION AND CONCLUSION: There was a high rate of identifiable genetic differences in patients whose only genitourinary abnormality was proximal hypospadias, especially with the 1% risk of a likely missed diagnosis. These findings support the discussion of a genetic evaluation for all patients with proximal hypospadias, regardless of the testicular location.

A Societies for Pediatric Urology survey of opioid prescribing practices after ambulatory pediatric urology procedures.

INTRODUCTION: Opioid dependence and abuse has been declared a national public health emergency, and overprescribing of opioids after surgery has been identified as a driving factor. To date, opioid prescribing after pediatric urology ambulatory surgery has not been well-described. OBJECTIVE: The study's objective was to assess pediatric urologists' practices in prescribing opioids for routine ambulatory procedures. STUDY DESIGN: A 23-question survey was created, including eight case vignettes describing routine procedures (orchiopexy, hydrocele repair, circumcision) across three age groups (8 months, 3 years, 13 years). Multiple choice questions asked about typical opioid type and duration for each case. Respondent attitudes and practice types were also evaluated. The survey was administered through the Societies for Pediatric Urology. RESULTS: Of the 102 respondents, 48% reported prescribing postoperative opioids for all cases described (Figure 1). Fourteen percent reported prescribing no opioids for all cases. Longer prescription duration was associated with older age (p = 0.003). Acetaminophen-hydrocodone was prescribed most commonly, while a few respondents reported prescribing acetaminophen-codeine. North Central and Southeastern respondents were more likely to prescribe opioids for all cases described (p = 0.003). The majority of respondents work in academic settings and had >10 years in practice. Only 16% believe that their patients take the majority of opioids prescribed, while only 35% provide education to their patients on proper disposal. DISCUSSION: There is significant variability in reported opioid prescribing practices after ambulatory procedures amongst pediatric urologists. Only 16% of respondents believe that patients take the majority of opioids prescribed, and only 14% reported never prescribing opioids for these procedures. There is an opportunity for guidelines and standardization of care for postoperative analgesia in this patient population. Given that overprescribing can lead to abuse and misuse, further work needs to be done to establish postoperative analgesia needs and to educate providers and families on proper prescribing and disposal. CONCLUSION: Pediatric urologists report prescribing opioids frequently after routine ambulatory procedures in infants, children, and adolescents despite believing that patients do not take the majority of the prescribed medication.

Early versus delayed closure of bladder exstrophy: A National Surgical Quality Improvement Program Pediatric analysis.

INTRODUCTION: Delayed closure of bladder exstrophy has become more popular; however, there is limited the evidence of its success. Existing literature focuses on intermediate and long-term outcomes, and short-term postoperative outcomes are limited by the small number of cases and varying follow-up methods. OBJECTIVE: The objectives of the current study were to: 1) compare 30-day complications after early and delayed closure of bladder exstrophy, and 2) evaluate practice patterns of bladder exstrophy closure. STUDY DESIGN: The National Surgical Quality Improvement Program Pediatric (NSQIPP) database from 2012 to 2015 was reviewed for all cases of bladder exstrophy closure. Early closure was defined as surgery at age 0-3 days, and delayed closure was defined as age 4-120 days at time of surgery. Demographic, clinical, and peri-operative characteristics were collected, as were postoperative complications, readmissions, and re-operations up to 30 days. Descriptive statistics were performed, and multivariate linear and logistic regression analyses were performed for salient complications. RESULTS: Of 128 patients undergoing bladder exstrophy closure, 62 were included for analysis, with 44 (71%) undergoing delayed closure. Mean anesthesia and operative times were greater in the delayed closure group, and were associated with more concurrent procedures, including inguinal hernia repairs and osteotomies. The delayed closure group had a higher proportion of 30-day complications, due to a high rate of blood transfusion (57% vs 11%). Wound dehiscence occurred in 6/44 (14%) delayed closures, as compared with 0/18 (0%) early closures. When compared with prior published reports of national data from 1999 to 2010, delayed closure was performed more frequently in this cohort (71% vs 27%). DISCUSSION: The NSQIPP provides standardized reporting of peri-operative characteristics and 30-day complications, allowing a comparison of early to delayed closure of bladder exstrophy across multiple institutions. Assessing short-term risks in conjunction with long-term follow-up is crucial for determining optimal management of this rare but complex condition. CONCLUSION: Delayed closure of bladder exstrophy is performed frequently, yet it carries a high rate of 30-day complications worthy of further investigation. This can be useful in counseling patients and families, and to understand practice patterns across the country.

Estimating retrospective exposure of household humidifier disinfectants.

UNLABELLED: We conducted a comprehensive humidifier disinfectant exposure characterization for 374 subjects with lung disease who presumed their disease was related to humidifier disinfectant use (patient group) and for 303 of their family members (family group) for an ongoing epidemiological study. We visited the homes of the registered patients to investigate disinfectant use characteristics. Probability of exposure to disinfectants was determined from the questionnaire and supporting evidence from photographs demonstrating the use of humidifier disinfectant, disinfectant purchase receipts, any residual disinfectant, and the consistency of their statements. Exposure duration was estimated as cumulative disinfectant use hours from the questionnaire. Airborne disinfectant exposure intensity (µg/m(3)) was estimated based on the disinfectant volume (ml) and frequency added to the humidifier per day, disinfectant bulk level (µg/ml), the volume of the room (m(3)) with humidifier disinfectant, and the degree of ventilation. Overall, the distribution patterns of the intensity, duration, and cumulative exposure to humidifier disinfectants for the patient group were higher than those of the family group, especially for pregnant women and patients ≤6 years old. Further study is underway to evaluate the association between the disinfectant exposures estimated here with clinically diagnosed lung disease. PRACTICAL IMPLICATIONS: Retrospective exposure to household humidifier disinfectant as estimated here can be used to evaluate associations with clinically diagnosed lung disease due to the use of humidifier disinfectant in Korea. The framework, with modifications to account for dispersion and use patterns, can also be potentially adapted to assessment of other household chemical exposures.

A comparative study of hair shafts in scalp psoriasis and seborrheic dermatitis using atomic force microscopy.

BACKGROUND: As the inflammatory scalp conditions share similar clinical manifestations of scaling, inflammation, and pruritus, the differential diagnosis of these lesions; especially between scalp psoriasis (SP) and seborrheic dermatitis (SD) is sometimes difficult. OBJECTIVES: The aim of this study was to investigate the differences on the hair surface in SP and SD for a clinical diagnosis, using atomic force microscopy (AFM). METHODS: The hair shafts of 14 patients and 28 patients with SP and SD respectively, were taken from the lesional region. Hairs from healthy adults not having any hair diseases were also examined in the same way for the controls. Surface characteristics of SP and SD-affected hair shafts such as, pitting, scale thickness, and roughness, were observed on the AFM images. RESULTS: One hundred percentage and four percentage of the patients with SP and SD respectively had macropits on their hair shafts. In both the SP and SD-affected hairs, the scale thickness was more than 4-fold than that in the control hairs. The surface of SP-affected hairs was rougher than that of SD-affected and control hairs. CONCLUSION: The differences in hair shafts between SP and SD were investigated noninvasively using AFM. The presence of macropits could be helpful in the differentiation between SP and SD.

Investigation of the hair of patients with scalp psoriasis using atomic force microscopy.

BACKGROUND: Psoriasis affects not only the soft keratin of the skin, but also hard keratin, such as nails and hair. However, few studies have described the changes induced in the hair of patients with psoriasis. AIM: Using atomic force microscopy (AFM), we investigated the morphological property of hair samples taken from the scalp of patients with psoriasis. METHODS: Lesional and nonlesional hairs taken from 15 patients with scalp psoriasis were investigated. Hairs from 15 healthy adults were also examined as controls. Using AFM, surface images were taken of an area of 20 × 20 µm(2), with 512 × 512 pixels and a scan speed of 0.8 lines/s. results: Pits were frequently seen in the hair shafts of patients with psoriasis, similar to those seen in their nail plates. Macropit number, scale thickness and surface roughness were all significantly increased in lesional hairs compared with both nonlesional and control hairs, and macropits and scale thickness were also increased in nonlesional hairs compared with control hairs. CONCLUSIONS: The hair shafts of patients with scalp psoriasis exhibited the same macropits seen in their nails. Both lesional and nonlesional hairs had similar changes in morphological structure compared with controls. This supports the generalized nature of psoriasis, with changes in hair structure being analogous to the changes seen in skin and nails.

A national survey on the practice and outcomes of mechanical ventilation in Korean intensive care units.

A study was undertaken to describe the practice and outcomes of mechanical ventilation throughout Korea. This prospective cohort study was conducted over a three-month period enrolling patients (n = 519) who received mechanical ventilation for more than 72 hours in 21 university hospital intensive care units throughout Korea. The most common indication for mechanical ventilation was acute respiratory failure. The most common cause of acute-on-chronic respiratory failure was tuberculous lung disease. The most common initial mode for ventilation was volume-controlled ventilation. The mean tidal volume of acute respiratory distress syndrome patients was 7.6 ml/kg of the predicted body weight and the mean positive end-expiratory pressure was 9.4 cmH20. The weaning success rate at 28 days was 50.3%. Pressure support and the T-piece were most commonly used as initial and final weaning modes respectively. Preventive measures against deep vein thrombosis during mechanical ventilation were performed more frequently in intensive care units with full-time critical care physicians than those without such physicians. Multivariate analysis showed that the APACHE II score, indication for mechanical ventilation, respiratory rate at 72 hours, enteral feeding and prophylaxis of deep vein thrombosis were prognostic factors for survival. In Korean intensive care units, tuberculous lung disease remains an important cause for mechanical ventilation. The practice of mechanical ventilation in Korean intensive care units in general appeared to comply with the current international recommendations with regard to lung protection and weaning. However, intensive care units lacking critical care physicians seemed to be adopting fewer ancillary measures, such as deep vein thrombosis prophylaxis.

Mullerian adenosarcoma with sarcomatous overgrowth of the cervix presenting as cervical polyp: a case report and review of the literature.

An aggressive variant of adenosarcoma, mullerian adenosarcoma with sarcomatous overgrowth (MASO) in the cervix is extremely rare. This variant contains obvious, high-grade sarcoma in addition to a low-grade form. In this report, we describe a case of MASO of the uterine cervix and review the clinical and pathological features of these tumors. The patient was a 37-year-old woman with a cervical polypoid mass, which was morphologically considered as a benign endocervical polyp. Microscopically, polypoid cervical mass showed diffuse and dense malignant spindle cell proliferation around the benign endocervical glands and also an area of markedly anaplastic and pleomorphic spindle cell proliferation, so called, sarcomatous overgrowth. Total abdominal hysterectomy and bilateral salpingo-oophorectomy with pelvic lymph node dissection were performed. The patient has been followed-up and neither chemotherapy nor other adjuvant therapies have been administered. At present, she has been clinically free of disease for 9 months since she received surgery. It is extremely rare that MASO of the uterine cervix is presented in premenopausal woman. Gynecologists and pathologists should be aware of the difficulties associated with a delay in the diagnosis of MASO when the tumor is present as a benign looking cervical polyp.

Interleukin-1beta regulates urokinase plasminogen activator (u-PA), u-PA receptor, soluble u-PA receptor, and plasminogen activator inhibitor-1 messenger ribonucleic acid expression in cultured human endometrial stromal cells.

The interleukin-1 (IL-1) system plays an integral role in local intercellular interactions during implantation. In addition, the plasminogen activator system, especially urokinase plasminogen activator (u-PA), plasminogen activator inhibitor (PAI-1), and u-PA receptor (u-PAR), are crucial during embryo implantation. Decidualization and implantation are complex processes dependent upon several proteases, including u-PA, and IL-1 is known to affect PA activity in several cell types. We investigated the role of IL-1beta in regulating u-PA, PAI-1, u-PAR, and soluble u-PAR messenger ribonucleic acid (mRNA) expression in cultured human endometrial stromal cells using quantitative competitive PCR. For confirmation of the mRNA data, we measured PAI-1 and u-PAR protein by enzyme-linked immunosorbent assay. Confluent stromal cell cultures treated with progesterone and estradiol for 9 days were stimulated with IL-1beta, and IL-1beta plus IL-1beta antibody for an additional 24 h. Total RNA was extracted, reverse transcribed, and coamplified using quantitative and competitive PCR with internal standards. IL-1beta increased PAI-1, u-PAR, and soluble u-PAR expression in a dose-dependent manner, and this result was reversed by anti-IL-1beta antibody treatment. u-PA mRNA expression was not dependent on IL-1beta. These results suggest that IL-1 may be important in regulating PAI-1 and u-PAR during stromal cell decidualization before implantation.

Concentration of vascular endothelial growth factor (VEGF) and transforming growth factor-beta1 (TGF-beta1) in the serum of patients with cervical cancer: prediction of response.

The aim of this study was to determine the value of the measurement of serum VEGF and TGF-beta1 levels in the diagnosis of cervical cancer and to see whether these levels decrease after treatment for cervical cancer. We measured serum VEGF and TGF-beta1 levels through EIA in patients with CIN (n = 35), and cervical squamous cell cancer (n = 48). We also measured serum VEGF, TGF-beta1, and SCC antigen levels before and after radiotherapy in 13 cervical squamous cell cancer patients. The sizes of the tumors in those patients were measured by a computer tomography scan or magnetic resonance imaging. The serum VEGF levels were different between CIN and cervical cancer groups (P < 0.1), and the serum TGF-beta 1 levels in the cervical cancer group were lower than those in the other groups (P < 0.05). The serum VEGF levels were significantly related to the serum TGF-beta 1 levels in the cervical cancer patients (P < 0.01). In the cervical cancer patients, the decrease in the circulating VEGF levels after receiving radiotherapy was related to the decrease in tumor size (P < 0.01). While the measurement of serum VEGF level is adjuvant in diagnosing cervical cancers, serial serum VEGF level measurements may find a clinical use in the follow-up of women treated for cervical cancer.

The effect of cytokine mediators on prostaglandin inhibition by human decidual cells.

OBJECTIVE: The purpose of this study was to determine the inhibitory effects of anti-interleukin-1beta and transforming growth factor-beta2 on the production of interleukin-1beta and prostaglandin E2 by human decidual cells. STUDY DESIGN: Decidual membranes were obtained from 30 patients between 37 and 40 weeks' gestation. Decidual cells were isolated and grown in culture. Incubations were conducted with lipopolysaccharide as a control, lipopolysaccharide plus anti-interleukin-1beta, and lipopolysaccharide plus transforming growth factor-beta2, respectively. Interleukin-1beta and prostaglandin E2 were measured by enzyme-linked immunosorbent assay and radioimmunoassay. RESULTS: At the end of a 24-hour culture with lipopolysaccharide plus anti-interleukin-1beta, anti-interleukin-1beta decreased the lipopolysaccharide-induced prostaglandin E2 production significantly at the concentrations of 50 ng/mL, 100 ng/mL, and 500 ng/mL (P < .05) and also decreased the lipopolysaccharide-induced interleukin-1beta production significantly at the concentrations of 10 ng/mL, 50 ng/mL, and 100 ng/mL (P < .05). In the medium containing lipopolysaccharide plus transforming growth factor-beta2, transforming growth factor-beta2 also decreased the lipopolysaccharide-induced prostaglandin E2 production significantly at the concentrations of 1 ng/mL and 10 ng/mL (P < .05) but increased the lipopolysaccharide-induced interleukin-1beta production significantly at the concentration of 1 ng/mL (P < .05). CONCLUSIONS: Lipopolysaccharide-induced prostaglandin E2 production by human decidual cells in vitro may be prevented by anti-interleukin-1beta and transforming growth factor-beta2, and interleukin-1beta production may be prevented by anti-interleukin-1beta.