Prospective assessment of INTERGROWTH-21st and World Health Organization estimated fetal weight reference curves.

OBJECTIVES: To assess the suitability of the new INTERGROWTH-21st and World Health Organization (WHO) estimated fetal weight (EFW) references in a Southern Chinese population. A secondary aim was to determine the accuracy of EFW by assessing the difference between EFW and actual birth weight. METHODS: This was a prospective cross-sectional cohort study. Viable singleton pregnancies at 11-13 weeks' gestation were recruited to undergo a single standardized fetal biometric scan after 20 weeks. The gestational age at which the scan was performed was allocated randomly at the time of recruitment. EFW was predicted using both the Hadlock and INTERGROWTH-21st weight estimation model formulae. Population-specific EFW references were constructed. Z-scores were used to compare these references against the INTERGROWTH-21st and WHO international size references. Gestational-age-adjusted projection was used to assess the difference between EFW on the day of delivery and birth weight for fetuses having biometry scans ≥ 34 weeks. RESULTS: Fetuses of 970 participants had biometry scans. The median number of scans per gestational week was 48 (interquartile range, 43-53). Z-score comparison indicated that the WHO 10th , 50th and 90th centiles of the EFW reference were consistently higher than the corresponding local centiles, whilst the INTERGROWTH-21st 10th centile was lower. Fewer than 2% of fetuses scanned at or after 34 weeks would be considered as potentially large-for-gestational age, irrespective of which model was used to predict weight. Adopting the WHO international reference would result in approximately one in six fetuses being regarded as potentially small-for-gestational age, 50% more than the number determined using a population-specific reference. Systematic errors of extrapolated EFW were similar, ranging from 5.5% to 7.4%. CONCLUSIONS: Centers seeking to use new references, such as the INTERGROWTH-21st and/or WHO international references, as a means of determining whether a fetus is small- or large-for-gestational age, would be advised to assess the suitability of these references within their own population using standardized methodology. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Surgical outcome of daytime and out-of-hours surgery for elderly patients with hip fracture.

INTRODUCTION: Surgery for hip fracture may be performed out-of-hours to avoid surgical delay. There is, however, a perception that this may constitute less-than-ideal conditions and result in a poorer outcome. The aim of this study was to evaluate the surgical outcome of elderly patients with hip fracture who underwent daytime versus out-of-hours surgery in Hong Kong. This will help make decisions about whether to operate out-of-hours or to delay surgery until the following day. METHODS: This retrospective study included all elderly patients with hip fracture who were operated on and discharged from the Prince of Wales Hospital in 2014. Patients were divided into groups according to the time of surgical incision. Records were examined for 30-day mortality and postoperative surgical complications, and their potential associations with surgeon characteristics. RESULTS: Overall, 367 patients were selected in this study with 242 patients in the daytime group and 125 in the out-of-hours group. Demographic characteristics were comparable between the two groups. The overall 30-day mortality rate was 2.0% and the surgical complication rate was 24.2%. Compared with the daytime group, there was no increase in 30-day mortality or surgical complications for out-of- hours group. Fewer surgeons were involved in out-of-hours surgery but the number of surgeons and their qualifications did not affect the outcomes. CONCLUSIONS: The two groups were homogeneous in terms of demographic characteristics. Outcomes for 30-day mortality and postoperative surgical complications were comparable between the two groups. Surgeons' qualifications and number of surgeons involved were also not associated with the outcomes. Out-of-hours surgery remains a viable option in order to facilitate early surgery.

Identification of fragile X pre-mutation carriers in the Chinese obstetric population using a robust FMR1 polymerase chain reaction assay: implications for screening and prenatal diagnosis.

INTRODUCTION: There is significant morbidity associated with fragile X syndrome. Unfortunately, most maternal carriers are clinically silent during their reproductive years. Because of this, many experts have put forward the notion of preconception or prenatal fragile X carrier screening for females. This study aimed to determine the prevalence of fragile X syndrome pre-mutation and asymptomatic full-mutation carriers in a Chinese pregnant population, and the distribution of cytosine-guanine-guanine (CGG) repeat numbers using a robust fragile X mental retardation 1 (FMR1) polymerase chain reaction assay. METHODS: This was a cross-sectional survey in prospectively recruited pregnant women from a university hospital in Hong Kong. Chinese pregnant women without a family history of fragile X syndrome were recruited between April 2013 and May 2015. A specific FMR1 polymerase chain reaction assay was performed on peripheral blood to determine the CGG repeat number of the FMR1 gene. Prenatal counselling was offered to full-mutation and pre-mutation carriers. RESULTS: In 2650 Chinese pregnant women, two individuals with pre-mutation alleles (0.08%, one in 1325) and one asymptomatic woman with full-mutation (0.04%, one in 2650) alleles were identified. The overall prevalence of pre-mutation and full-mutation alleles was 0.11% (1 in 883). Furthermore, 30 (1.1%) individuals with intermediate alleles were detected. In the 2617 women with normal CGG repeats, the most common CGG repeat allele was 30. CONCLUSIONS: The overall prevalence of pre-mutation and asymptomatic full-mutation carriers in the Chinese pregnant population was one in 883, detected by a new FMR1 polymerase chain reaction assay.

Impact of replacing Chinese ethnicity-specific fetal biometry charts with the INTERGROWTH-21(st) standard.

OBJECTIVE: To assess the impact of adopting the INTERGROWTH-21(st) biometry standards in a Chinese population. DESIGN: Retrospective cohort study. SETTING: A teaching hospital in Hong Kong. POPULATION: A total of 10 527 Chinese women with a singleton pregnancy having a second- or third-trimester fetal anomaly or growth scan between January 2009 and June 2014. METHODS: Z-scores were derived for fetal abdominal circumference (AC), head circumference (HC), and femur length (FL) using the INTERGROWTH-21(st) and Chinese biometry standards. Pregnancies with aneuploidy, structural or skeletal abnormalities, or that developed pre-eclampsia were excluded. Z-scores were stratified as <2.5th, <5th, <10th, >90th, >95th, or >97.5th percentile. Birthweight centile, adjusted for gestation and gender, was categorised as ≤3rd, 3rd to ≤5th, 5th to ≤10th, and >10th. Pairwise comparison and the McNemar test were performed to assess biometry Z-score differences and concordance between the INTERGROWTH-21(st) and Chinese standards. MAIN OUTCOME MEASURES: The sensitivity of both the local and INTERGROWTH-21(st) AC standards to identify pregnancies that were small-for-gestational-age (SGA) was assessed. RESULTS: INTERGROWTH-21(st) AC, HC, and FL Z-scores were significantly lower than those obtained using our local reference for AC, HC, and FL (P < 0.0001 for all). The proportion of fetuses with biometry in the <2.5th, <5th, <10th, >90th, >95th, or >97.5th percentiles was statistically significant (P < 0.01 for all). A total of 1224 (15.5%) of the scans at 18-22 weeks of gestation had AC, HC, or FL below the 3rd percentile of the INTERGROWTH-21(st) standard. CONCLUSIONS: Adopting the INTERGROWTH-21(st) standard would lead to a significant number of fetuses being at risk of misdiagnosis for small fetal size, particularly when using HC and FL measures. TWEETABLE ABSTRACT: INTERGROWTH-21(st) biometry assessment in Chinese leads to fetuses being at risk of misdiagnosis of small fetal size.

The effect of dietary intake changes on nutritional status in acute leukaemia patients after first induction chemotherapy.

This study aimed to evaluate how changes in dietary intake among acute lymphoblastic and acute myeloid leukaemia (ALL and AML) patients affect nutritional status after the first induction chemotherapy. Dietary intake was assessed using 24-h recall and a 136-item food frequency questionnaire. Nutritional status was assessed by Patients Subjective Global Assessment questionnaire before starting induction therapy and again after 1 month. All newly diagnosed acute leukaemia patients aged 15 years old and older who attended three referral hospitals for initiation of their induction chemotherapy were included in the sample selection provided that they gave informed consent. A total of 30 AML and 33 ALL patients participated in the study. Dietary intake and nutritional status worsened after the chemotherapy treatment. Dietary intake in terms of macronutrients, micronutrients, food variety and diet diversity score changed significantly after the induction chemotherapy. No significant relationship was found between the changes in dietary indices and nutritional status. Chemotherapy-related side effects as an additional factor to cancer itself could affect dietary intake of leukaemia patients. The effectiveness of an early assessment of nutritional status and dietary intake should be further investigated in order to deter further deterioration.

The Functional Living Index-Cancer is a reliable and valid instrument in Chinese cancer patients.

PURPOSE: To evaluate the linguistic and psychometric properties of the Functional Living Index-Cancer (FLIC) in assessing the quality of life of Chinese cancer patients. METHODS: The English FLIC was translated into Traditional Chinese by the standard forward-backward procedure. After cognitive debriefing, a Traditional Chinese FLIC was administered to 500 cancer patients in a major public hospital in Hong Kong. Of which, 200 were invited to complete the questionnaire in 2 weeks. To identify a scale structure appropriate to Chinese, exploratory and confirmatory factor analyses were performed on two randomly split halves of the sample. RESULTS: We identified five scales of the Traditional Chinese FLIC which assess the physical, psychological, hardship, nausea and social aspects. These five scales and the overall scale demonstrated satisfactory fit and had the alpha coefficient ranged from 0.68 to 0.92. The intra-class correlation coefficient ranged from 0.67 to 0.88. In addition, all FLIC scales were negatively associated with the Eastern Cooperative Oncology Group performance status and, also except for the psychological scale, had lower scores in patients who were treated by chemotherapy. CONCLUSIONS: The Traditional Chinese FLIC is an appropriate health indicator for Chinese cancer patients.

Nutritional status and quality of life in patients with acute leukaemia prior to and after induction chemotherapy in three hospitals in Tehran, Iran: a prospective study.

BACKGROUND: The primary objective of the present study was to assess changes in the nutritional status and quality of life in acute leukaemia patients, aged ≥15 years, who had undergone induction chemotherapy. METHODS: A preliminary and post-induction chemotherapy assessment of patients' nutritional status, quality of life, sociodemographic status and medical characteristics was conducted using the Patient Generated Subjective Global Assessment (PG-SGA) and the European Organization for Research and Treatment of Cancer quality of life (QOL-C30, version 3) questionnaires. The PG-SGA is a clinical nutrition assessment tool used to evaluate oncology patients. Patients with newly-diagnosed acute leukaemia, aged ≥15 years, at three hospitals in Tehran (from May 2009 to March 2010), were recruited for the present study. RESULTS: Sixty-three acute leukaemia patients [65% men and 35% women with a mean (SD) age of 33 (15.4) years] participated in the present study. A total of 19.4% were found to be malnourished prior to chemotherapy. After chemotherapy, 76.1% of patients were considered moderately malnourished, whereas 6.3% were severely malnourished. After induction chemotherapy, both the nutritional status and quality of life deteriorated in the majority of patients, as demonstrated by a paired t-test. CONCLUSIONS: A deteriorated nutritional status and quality of life was the result of the side effects posed by induction chemotherapy in the patients investigated in the present study. These findings highlight the need for an appropriate nutritional support programme to improve the nutritional status and quality of life in patients with leukaemia undergoing chemotherapy.

Effectiveness of medical nutrition treatment delivered by dietitians on glycaemic outcomes and lipid profiles of Arab, Omani patients with Type 2 diabetes.

AIMS: In this randomized controlled trial we evaluated the effectiveness of medical nutritional therapy on Arab patients with Type 2 diabetes in Oman delivered by a dietitian. METHODS: Patients with Type 2 diabetes (n = 170) were randomly assigned to a group receiving usual nutritional care (n = 85) or a group receiving practice guidelines nutritional care (n = 85). Anthropometric (weight, height, BMI and waist circumference) and biochemical (fasting blood glucose, HbA1c ) variables were measured at baseline and after each appointment. Patients were given 1-3 appointments with a dietitian over 6 months. RESULTS: Those in the group receiving practice guidelines nutritional care (n = 85) had significant changes in HbA(1c) (-0.8%, P = 0.001), fasting plasma glucose (-1.3 mmol\l, P = 0.003) and weight (-5.1 kg, P = 0.05), whereas the patients in the usual nutritional care group (n = 85) had no significant improvements in either HbA(1c) (-0.4%, P = 0.248) or fasting plasma glucose (-0.2 mmol/l, P = 0.638) during the same period. We also found a significant difference between the group receiving practice guidelines nutritional care and the usual nutritional care group, respectively, in waist circumference (96.9 ± 7.9 vs. 100.0 ± 8.7 cm, P = 0.019), triglycerides levels (1.42 ± 0.58 vs. 1.98 ± 0.96 mmol\l, P = 0.001), cholesterol levels (5.1 ± 1.0 vs. 5.5 ± 0.9 mmol/l, P = 0.009) and LDL cholesterol levels (3.58 ± 0.98 vs. 3.89 ± 0.98 mmol/l, P = 0.046). CONCLUSIONS: Medical nutrition therapy provided by dietitians to Arab patients with Type 2 diabetes in Oman resulted in significant improvements in anthropometric and biochemical outcomes in both the usual nutritional care group and the group receiving practice guidelines nutritional care. Subjects with Type 2 diabetes tended to do better with practice guidelines nutritional care than with usual nutritional care. Ongoing medical counselling in nutrition by a trained dietitian is important for better long-term metabolic control.

Decrease in hypothalamic Kiss1 and Kiss1r expression: a potential mechanism for fasting-induced suppression of the HPG axis in the adult male rhesus monkey (Macaca mulatta).

Fasting suppresses functioning of the hypothalamic-pituitary-gonadal (HPG) axis by mechanisms that are incompletely understood. In 2003, hypothalamic kisspeptin-Kiss1r signaling was discovered to play a significant role in regulating the HPG axis. We have recently shown that in adult male macaques, short-term fasting attenuates the response of the HPG axis to an exogenous kisspeptin challenge. In the present study, we explored the mechanism underlying this attenuated response by examining the modulation of the hypothalamic expression of KISS1 and KISS1R under short-term fasting and normal feeding conditions in the adult male macaques. Hypothalamic mRNA was extracted from normal fed (n=3) and 48-h fasted (n=3) monkeys. KISS1, KISS1R, and GNRH1 mRNA were quantified by reverse transcription followed by real-time polymerase chain reaction. In addition, blood samples were collected for measurement of plasma concentrations of glucose, cortisol, leptin, and testosterone. In contrast to fed animals, plasma glucose, leptin, and testosterone levels decreased and cortisol levels increased in fasted animals. The hypothalamic expression of KISS1 and KISS1R mRNA was significantly lower (p<0.05) in fasted monkeys compared to fed monkeys while hypothalamic GNRH1 mRNA expression was comparable between the 2 groups. Thus, our results demonstrate that expression of hypothalamic KISS1 and KISS1R decrease after a short-term fasting in monkeys. This decrease may contribute to the suppression of the HPG axis during fasting conditions in primates. In addition, our finding of lower expression of KISS1R in fasted monkeys provides an explanation for the attenuation in the HPG axis response to peripheral kisspeptin challenge during short-term fasting.

Cracks in the foundation: keratin filaments and genetic disease.

In the past three years, defects in the genes that encode intermediate filament (IF) proteins have been found to be responsible for some inherited skin diseases, and others have been implicated in certain motor neuron diseases and cardiomyopathies. This article reviews how knowledge of IF structure led to the discovery of genetic disorders of IFs, and how the clinical manifestations of these diseases have confirmed the notion that IFs provide the mechanical strength of cells.

Deletions in epidermal keratins leading to alterations in filament organization in vivo and in intermediate filament assembly in vitro.

To investigate the sequences important for assembly of keratins into 10-nm filaments, we used a combined approach of (a) transfection of mutant keratin cDNAs into epithelial cells in vivo, and (b) in vitro assembly of mutant and wild-type keratins. Keratin K14 mutants missing the nonhelical carboxy- and amino-terminal domains not only integrated without perturbation into endogenous keratin filament networks in vivo, but they also formed 10-nm filaments with K5 in vitro. Surprisingly, keratin mutants missing the highly conserved L L E G E sequence, common to all intermediate filament proteins and found at the carboxy end of the alpha-helical rod domain, also assembled into filaments with only a somewhat reduced efficiency. Even a carboxy K14 mutant missing approximately 10% of the rod assembled into filaments, although in this case filaments aggregated significantly. Despite the ability of these mutants to form filaments in vitro, they often perturbed keratin filament organization in vivo. In contrast, small truncations in the amino-terminal end of the rod domain more severely disrupted the filament assembly process in vitro as well as in vivo, and in particular restricted elongation. For both carboxy and amino rod deletions, the more extensive the deletion, the more severe the phenotype. Surprisingly, while elongation could be almost quantitatively blocked with large mutations, tetramer formation and higher ordered lateral interactions still occurred. Collectively, our in vitro data (a) provide a molecular basis for the dominance of our mutants in vivo, (b) offer new insights as to why different mutants may generate different phenotypes in vivo, and (c) delineate the limit sequences necessary for K14 to both incorporate properly into a preexisting keratin filament network in vivo and assemble efficiently into 10-nm keratin filaments in vitro.

Molecular organization of sarcoglycan complex in mouse myotubes in culture.

The sarcoglycans are a complex of four transmembrane proteins (alpha, beta, gamma, and delta) which are primarily expressed in skeletal muscle and are closely associated with dystrophin and the dystroglycans in the muscle membrane. Mutations in the sarcoglycans are responsible for four autosomal recessive forms of muscular dystrophy. The function and the organization of the sarcoglycan complex are unknown. We have used coimmunoprecipitation and in vivo cross-linking techniques to analyze the sarcoglycan complex in cultured mouse myotubes. We demonstrate that the interaction between beta- and delta-sarcoglycan is resistant to high concentrations of SDS and alpha-sarcoglycan is less tightly associated with other members of the complex. Cross-linking experiments show that beta-, gamma-, and delta-sarcoglycan are in close proximity to one another and that delta-sarcoglycan can be cross-linked to the dystroglycan complex. In addition, three of the sarcoglycans (beta, gamma, and delta) are shown to form intramolecular disulfide bonds. These studies further our knowledge of the structure of the sarcoglycan complex. Our proposed model of their interactions helps to explain some of the emerging data on the consequences of mutations in the individual sarcoglycans, their effect on the complex, and potentially the clinical course of muscular dystrophies.

Filamin 2 (FLN2): A muscle-specific sarcoglycan interacting protein.

Mutations in genes encoding for the sarcoglycans, a subset of proteins within the dystrophin-glycoprotein complex, produce a limb-girdle muscular dystrophy phenotype; however, the precise role of this group of proteins in the skeletal muscle is not known. To understand the role of the sarcoglycan complex, we looked for sarcoglycan interacting proteins with the hope of finding novel members of the dystrophin-glycoprotein complex. Using the yeast two-hybrid method, we have identified a skeletal muscle-specific form of filamin, which we term filamin 2 (FLN2), as a gamma- and delta-sarcoglycan interacting protein. In addition, we demonstrate that FLN2 protein localization in limb-girdle muscular dystrophy and Duchenne muscular dystrophy patients and mice is altered when compared with unaffected individuals. Previous studies of filamin family members have determined that these proteins are involved in actin reorganization and signal transduction cascades associated with cell migration, adhesion, differentiation, force transduction, and survival. Specifically, filamin proteins have been found essential in maintaining membrane integrity during force application. The finding that FLN2 interacts with the sarcoglycans introduces new implications for the pathogenesis of muscular dystrophy.

A survey of prenatal first-trimester aneuploidy screening among Hong Kong specialist obstetricians.

OBJECTIVES: To determine the background, qualifications, and certification status of specialists currently performing first trimester screening in Hong Kong, the extent of their participation (and the laboratories they use) in quality assurance programmes, and their willingness to provide follow-up data for auditing purposes. DESIGN: Questionnaire survey. SETTING: Hong Kong. PARTICIPANTS: A survey was mailed to all registered Hong Kong specialist obstetricians. Results were reported using descriptive statistics. RESULTS: The response rate was 32% (106/331). Overall, 73% offered universal screening to all pregnant women. The majority (72%) most commonly performed first trimester screening for their patients. Sixty-six (62%) of the respondents performed nuchal translucency scanning; only 30 (45%) were accredited by a recognised body to perform such scans. Only 33% of the relevant laboratories used by specialists participated in external quality assurance programmes specific to Down's syndrome screening undertaken by a third party organisation. CONCLUSIONS: According to our data, first trimester screening has become one of the most common screening strategies for Down's syndrome in Hong Kong, but there is a need to assess the quality of such prenatal screening for aneuploidy to ensure its efficacy.

Parent perceptions of psychosocial care for children with differences of sex development.

SHORT INTRODUCTION/BACKGROUND: Children affected by differences/disorders of sex development (DSDs) and their families are vulnerable to significant risks across developmental stages that threaten quality of life and psychosocial functioning. Accordingly, both experts in DSD treatment and patient advocacy groups have endorsed the incorporation of psychosocial care into interdisciplinary management of DSD conditions. OBJECTIVE: This study assessed psychosocial needs and received services reported by parents of children with DSD treated at two large US academic medical centers. Specifically, differences in parents' perceptions of psychosocial service needs were compared between those who received or did not receive interdisciplinary care that included psychology/social work professionals. STUDY DESIGN: In a cross-sectional study, sixty-four parents of children with DSD aged 0-19 years attending two major academic centers with interdisciplinary teams completed a questionnaire about their receipt and perception of 12 individual psychosocial services throughout their child's DSD treatment. RESULTS: Receipt of individual psychosocial services ranged from 27 to 81%. Most commonly, parents reported having a psychosocial provider explain medical terms and answer questions after talking with a doctor (81%), assist with words and terms to describe the condition and treatment (69%), and help navigate the hospital system (63%). Families positively endorsed psychosocial services, with 91-100% of services received rated as helpful. Parents of children who received care as part of an interdisciplinary team were significantly more likely to receive psychosocial services than those treated by single providers (e.g., urologists). Specific gaps in psychosocial care were noted in regard to access to mental health providers familiar with DSD, fertility counseling, and support with community advocacy (e.g., arranging for accommodations at the school or advocating on patient's behalf with the insurance company). Among families who had not received them, services most desired were assistance with words and terms to describe condition or treatment; explanation of medical terms and answering questions after meeting with a doctor; connection to resources such as books, pamphlets, websites, and support groups; and a central care coordinator for the medical team. DISCUSSION AND CONCLUSION: Families value psychosocial services but are far less likely to receive services if they are not seen in an interdisciplinary clinic visit that includes a psychosocial provider. Families desire but often lack mental health, advocacy, and fertility-related support. This study highlights the need for sustained psychosocial follow-up across development, even in the absence of pressing medical concerns, to provide support and anticipatory guidance as needs and issues evolve.

Preliminary report: Surgical outcomes following genitoplasty in children with moderate to severe genital atypia.

INTRODUCTION: Prior studies of outcomes following genitoplasty have reported high rates of surgical complications among children with atypical genitalia. Few studies have prospectively assessed outcomes after contemporary surgical approaches. OBJECTIVE: The current study reported the occurrence of early postoperative complications and of cosmetic outcomes (as rated by surgeons and parents) at 12 months following contemporary genitoplasty procedures in children born with atypical genitalia. STUDY DESIGN: This 11-site, prospective study included children aged ≤2 years, with Prader 3-5 or Quigley 3-6 external genitalia, with no prior genitoplasty and non-urogenital malformations at the time of enrollment. Genital appearance was rated on a 4-point Likert scale. Paired t-tests evaluated differences in cosmesis ratings. RESULTS: Out of 27 children, 10 were 46,XY patients with the following diagnoses: gonadal dysgenesis, PAIS or testosterone biosynthetic defect, severe hypospadias and microphallus, who were reared male. Sixteen 46,XX congenital adrenal hyperplasia patients were reared female and one child with sex chromosome mosaicism was reared male. Eleven children had masculinizing genitoplasty for penoscrotal or perineal hypospadias (one-stage, three; two-stage, eight). Among one-stage surgeries, one child had meatal stenosis (minor) and one developed both urinary retention (minor) and urethrocutaneous fistula (major) (Summary Figure). Among two-stage surgeries, three children developed a major complication: penoscrotal fistula, glans dehiscence or urethral dehiscence. Among 16 children who had feminizing genitoplasty, vaginoplasty was performed in all, clitoroplasty in nine, external genitoplasty in 13, urethroplasty in four, perineoplasty in five, and total urogenital sinus mobilization in two. Two children had minor complications: one had a UTI, and one had both a mucosal skin tag and vaginal mucosal polyp. Two additional children developed a major complication: vaginal stenosis. Cosmesis scores revealed sustained improvements from 6 months post-genitoplasty, as previously reported, with all scores reported as good or satisfied. DISCUSSION: In these preliminary data from a multi-site, observational study, parents and surgeons were equally satisfied with the cosmetic outcomes 12 months after genitoplasty. A small number of patients had major complications in both feminizing and masculinizing surgeries; two-stage hypospadias repair had the most major complications. Long-term follow-up of patients at post-puberty will provide a better assessment of outcomes in this population. CONCLUSION: In this cohort of children with moderate to severe atypical genitalia, preliminary data on both surgical and cosmetic outcomes were presented. Findings from this study, and from following these children in long-term studies, will help guide practitioners in their discussions with families about surgical management.

Variation in the clinical and genetic evaluation of undervirilized boys with bifid scrotum and hypospadias.

BACKGROUND: Bifid scrotum and hypospadias can be signs of undervirilization, yet boys presenting with these findings often do not undergo genetic evaluation. In some cases, identifying an underlying genetic diagnosis can help to optimize clinical care and improve guidance given to patients and families. OBJECTIVES: The aim of this study was to characterize current practice for genetic evaluation of patients with bifid scrotum, and to identify approaches with a good diagnostic yield. METHODS: A retrospective study of the Boston Children's Hospital electronic medical records (1993-2015) was conducted using the search term "bifid scrotum" and clinical data were extracted. Data were abstracted into a REDCap database for analysis. Statistical analysis was performed using SPSS, SAS, and Excel software. RESULTS: The search identified 110 subjects evaluated in the Urology and/or Endocrinology clinics for bifid scrotum. Genetic testing (including karyotype, microarray, or targeted testing) was performed on 64% of the subjects with bifid scrotum; of those tested, 23% (15% of the total cohort of 110 subjects) received a confirmed genetic diagnosis. Karyotype analysis, when performed, led to a diagnosis in 17% of patients. Of the ten instances when androgen receptor gene sequencing was performed, a pathogenic mutation was identified 20% of the time. CONCLUSION: This study demonstrated that the majority of individuals with moderate undervirilization resulting in bifid scrotum do not receive a genetic diagnosis. Over a third of the analyzed subjects did not have any genetic testing, even though karyotype analysis and androgen receptor (AR) sequencing were both relatively high yield for identifying a genetic etiology. Increased utilization of traditional genetic approaches could significantly improve the ability to find a genetic diagnosis.

Prospective assessment of cosmesis before and after genital surgery.

INTRODUCTION: Little data exist about the surgical interventions taking place for children with disorders of sex development (DSD). Most studies that have evaluated cosmetic outcomes after genitoplasty have included retrospective ratings by a physician at a single center. OBJECTIVE: The present study aimed to: 1) describe frequency of sex assignment, and types of surgery performed in a cohort of patients with moderate-to-severe genital ambiguity; and 2) prospectively determine cosmesis ratings by parents and surgeons before and after genital surgery. STUDY DESIGN: This prospective, observational study included children aged <2 years of age, with no prior genitoplasty at the time of enrollment, moderate-to-severe genital atypia, and being treated at one of 11 children's hospitals in the United States of America (USA). Clinical information was collected, including type of surgery performed. Parents and the local pediatric urologist rated the cosmetic appearance of the child's genitalia prior to and 6 months after genitoplasty. RESULTS: Of the 37 children meeting eligibility criteria, 20 (54%) had a 46,XX karyotype, 15 (40%) had a 46,XY karyotype, and two (5%) had sex chromosome mosaicism. The most common diagnosis overall was congenital adrenal hyperplasia (54%). Thirty-five children had surgery; 21 received feminizing genitoplasty, and 14 had masculinizing genitoplasty. Two families decided against surgery. At baseline, 22 mothers (63%), 14 fathers (48%), and 35 surgeons (100%) stated that they were dissatisfied or very dissatisfied with the appearance of the child's genitalia. Surgeons rated the appearance of the genitalia significantly worse than mothers (P < 0.001) and fathers (P ≤ 0.001) at baseline. At the 6-month postoperative visit, cosmesis ratings improved significantly for all groups (P < 0.001 for all groups). Thirty-two mothers (94%), 26 fathers (92%), and 31 surgeons (88%) reported either a good outcome, or they were satisfied (see Summary Figure); there were no significant between-group differences in ratings. DISCUSSION: This multicenter, observational study showed surgical interventions being performed at DSD centers in the USA. While parent and surgeon ratings were discordant pre-operatively, they were generally concordant postoperatively. Satisfaction with postoperative cosmesis does not necessarily equate with satisfaction with the functional outcome later in life. CONCLUSION: In this cohort of children with genital atypia, the majority had surgery. Parents and surgeons all rated the appearance of the genitalia unfavorably before surgery, with surgeons giving worse ratings than parents. Cosmesis ratings improved significantly after surgery, with no between-group differences.