Explore the vast range of titles available.

Abstract Context Standardized description of external genitalia is needed in the assessment of children with atypical genitalia. Objectives To validate the External Genitalia Score (EGS), to present reference values for preterm and term babies up to 24 months and correlate obtained scores with anogenital distances (AGDs). Design, Setting A European multicenter (n = 8) validation study was conducted from July 2016 to July 2018. Patients and Methods EGS is based on the external masculinization score but uses a gradual scale from female to male (range, 0–12) and terminology appropriate for both sexes. The reliability of EGS and AGDs was determined by the interclass correlation coefficient (ICC). Cross-sectional data were obtained in 686 term babies (0–24 months) and 181 preterm babies, and 111 babies with atypical genitalia. Results The ICC of EGS in typical and atypical genitalia is excellent and good, respectively. Median EGS (10th to 90th centile) in males < 28 weeks gestation is 10 (8.6–11.5); in males 28–32 weeks 11.5 (9.2–12); in males 33–36 weeks 11.5 (10.5–12) and in full-term males 12 (10.5–12). In all female babies, EGS is 0 (0-0). The mean (SD) lower/upper AGD ratio (AGDl/u) is 0.45 (0.1), with significant difference between AGDl/u in males 0.49 (0.1) and females 0.39 (0.1) and intermediate values in differences of sex development (DSDs) 0.43 (0.1). The AGDl/u correlates with EGS in males with typical genitalia and in atypical genitalia. Conclusions EGS is a reliable and valid tool to describe external genitalia in premature and term babies up to 24 months. EGS correlates with AGDl/u in males. It facilitates standardized assessment, clinical decision-making and multicenter research.

The FRAS1-related extracellular matrix 1 (FREM1) gene encodes an extracellular matrix protein that plays a critical role in the development of multiple organ systems. In humans, recessive mutations in FREM1 cause eye defects, congenital diaphragmatic hernia, renal anomalies and anorectal malformations including anteriorly placed anus. A similar constellation of findings-microphthalmia, cryptophthalmos, congenital diaphragmatic hernia, renal agenesis and rectal prolapse-have been described in FREM1-deficient mice. In this paper, we identify a homozygous Frem1 missense mutation (c.1687A>T, p.Ile563Phe) in an N-ethyl-N-nitrosourea (ENU)-derived mouse strain, crf11, with microphthalmia, cryptophthalmos, renal agenesis and rectal prolapse. This mutation affects a highly conserved residue in FREM1's third CSPG domain. The p.Ile563Phe change is predicted to be deleterious and to cause decreased FREM1 protein stability. The crf11 allele also fails to complement the previously described eyes2 allele of Frem1 (p.Lys826*) providing further evidence that the crf11 phenotype is due to changes affecting Frem1 function. We then use mice bearing the crf11 and eyes2 alleles to identify lung lobulation defects and decreased anogenital distance in males as novel phenotypes associated with FREM1 deficiency in mice. Due to phenotypic overlaps between FREM1-deficient mice and mice that are deficient for the retinoic acid-responsive transcription factor GATA4 and the extracellular matrix protein SLIT3, we also perform experiments to look for in vivo genetic interactions between the genes that encode these proteins. These experiments reveal that Frem1 interacts genetically with Gata4 in the development of lung lobulation defects and with Slit3 in the development of renal agenesis. These results demonstrate that FREM1-deficient mice faithfully recapitulate many of the phenotypes seen in individuals with FREM1 deficiency and that variations in GATA4 and SLIT3 expression modulate some FREM1-related phenotypes in mice.

Background Several studies have assessed the epidemiology of HPV infection among MSM, but no qualitative studies have specifically assessed how HPV and genital warts (GW) affect South American men who have sex with men (MSM) and male-to-female transgendered women (TG). This study explored the knowledge, attitudes and experiences of Peruvian MSM and TG regarding HPV and GW. Methods We performed a qualitative study consisting of fifteen in-depth interviews and three focus groups carried out in Lima, Peru with diverse MSM and TG groups, including sex workers. Resulting data were analyzed by applying a systematic comparative and descriptive content analysis. Results While knowledge of HPV was limited, awareness of GW was common, particularly among TG persons and sex workers. Still, few participants recognized that GW are sexually transmitted, and many had problems differentiating between GW and other STI/anogenital conditions. Stigmatizing experiences were common during sexual encounters with people who had visible GW. Shame, emotional and physical troubles, and embarrassing sexual experiences were reported by individuals with GW. Search for treatment was mediated by peers, but stigma and apparent health services' inability to deal with GW limited the access to effective medical care. Conclusions In Peru, public health interventions should strengthen services for HPV/GW management and increase accurate knowledge of the transmission, treatment, and sequelae of HPV/GW in MSM and TG populations.

Abstract Context The anogenital distance (AGD) is considered a postnatal readout of early fetal androgen action. Little is known of prenatal AGD and how it correlates with AGD postnatally. Objective We present longitudinal measurements of fetal and infant AGD. We evaluate the impact of testosterone and dihydrotestosterone at minipuberty on AGD and penile size. Methods We performed secondary analyses of an observational, prospective pregnancy and birth cohort, COPANA (2020-2022), at Copenhagen University Hospital—Rigshospitalet, enrolling 685 healthy, singleton pregnant women, of whom 657 attended third trimester ultrasound and 589 infants completed follow-up. Fetal AGD was measured at third semester ultrasound (gestational week 29-34), and infant AGD, penile width, stretched penile length, and circulating testosterone and dihydrotestosterone (LC-MS/MS) were assessed at the minipuberty clinical examination (approximately 3.5 months postpartum): Results AGD was available in 650/657 fetuses (310 boys) and 588/589 infants (287 boys). Boys had longer fetal and infant AGD than girls; fetal AGDas: mean (SD) 21.4 mm (±3.5), fetal AGDaf: 12.8 mm (±2.3), P < .001, infant AGDas: 32.0 mm (±5.6) and infant AGDaf: 15.8 (±3.3), P < .001. Fetal AGD correlated with infant AGD in boys and girls (Spearman r = .275, P < .001 and r = .189, P = .001 respectively), but not with circulating testosterone or dihydrotestosterone at minipuberty. Penile size correlated positively with circulating androgen levels at minipuberty: stretched penile length vs testosterone: r = .235, P < .001. Conclusion AGD is sexually dimorphic already in the third trimester. Fetal and infant AGD correlate. AGD is associated with body size but not circulating androgen levels at minipuberty. These findings suggest that fetal and infant AGD reflect androgen action during early fetal development.

Background There is currently a lack of information on full anogenital evaluation of women with a previous history of anogenital neoplasia. Methods Retrospective analysis of the Homerton Anogenital Neoplasia Service records from January 2012 to March 2017, to identify all new referrals of women with previous anogenital neoplasia, who had had at least one complete examination of all anogenital sites. Multizonal anogenital disease (MZD) was defined as the presence of high-grade squamous intraepithelial lesions (HSIL)/carcinoma concurrently at two or more of the following sites/zones: perianus, anal canal, vulva, vagina or cervix. Results 253 women were included, mean age was 47 (SD=15) years and median duration of follow-up was 12 (IQR=21) months. Fifty-six women (22%) were diagnosed with MZD at first assessment and/or during follow-up. Current smokers (RR=1.84, 95% CI 1.21–2.79, p=0.004) and women on immunodulators/immunosuppressive drugs (RR=2.57, 95% CI 1.72-3.86, p<0.001) had an increased risk for MZD. The risk was lower for women without a previous history of anogenital high-grade lesions/cancer compared to those with this history (RR=0.06, 95% CI 0.01-0.45, p =0.006). Conclusions Multizonal assessment was important to diagnose occult areas of disease and should be especially considered in current smokers, pharmacologically immunocompromised and those with a previous history of anogenital HSIL/cancer.

Male reproductive development is intricately dependent on fetal androgen action. Consequently, disrupted androgen action during fetal life can interfere with the development of the reproductive system resulting in adverse effects on reproductive function later in life. One biomarker used to evaluate fetal androgen action is the anogenital distance (AGD), the distance between the anus and the external genitalia. A short male AGD is strongly associated with genital malformations at birth and reproductive disorders in adulthood. AGD is therefore used as an effect readout in rodent toxicity studies aimed at testing compounds for endocrine activity and anti-androgenic properties, and in human epidemiological studies to correlate fetal exposure to endocrine disrupting chemicals to feminization of new-born boys. In this review, we have synthesized current data related to intrauterine exposure to xenobiotics and AGD measurements. We discuss the utility of AGD as a retrospective marker of in utero anti-androgenicity and as a predictive marker for male reproductive disorders, both with respect to human health and rodent toxicity studies. Finally, we highlight four areas that need addressing to fully evaluate AGD as a biomarker in both a regulatory and clinical setting.

: Women carry two-thirds of the global anal cancer burden. Persistent genital (vulval, vaginal and cervical) high-risk Human Papillomavirus (hrHPV) infection and the resultant genital high-grade squamous intraepithelial lesions (HSILs) and genital cancers are now acknowledged as independent risk factor for anal dysplasia in women. Patients with both genital and anal hrHPV-related diseases, however, are poorly researched. : National Cancer Registration and Analysis Service (NCRAS) data was requested via the NHS Digital data access request service (DARS). Women in England over the age of 25 years diagnosed with anal HSIL/cancer between 2001 and 2020 who also had a vulval and/or vaginal and/or cervical cancer HSIL/cancer diagnosis within the 20-year period before or 1-year period after their anal cancer/HSIL were studied. The burden of genital disease in women with anal cancer, their sociodemographic risk factors and timelines between acquisition of genital and anal pathology were assessed. : A total of 8% ( = 1297/16,301) of all women with anal HSIL/cancer also had metachronous or synchronous genital HSIL/cancer diagnoses. Women who were first diagnosed with cervical HSIL had a lower burden of recurrent anogenital lesions over time ( = 0.04) but a significantly higher risk of presenting with late-stage anal cancer than women first presenting with vulval pathology ( = 0.02). Women who had disease in more than one anatomical site developed disease features 10-20 years earlier compared to other published datasets on women with single site disease. : These findings support the current IANS screening recommendation guidelines and suggest that the current anal cancer risk for women with cervical dysplasia may be underestimated.

Before April 2022, monkeypox virus infection in humans was seldom reported outside African regions where it is endemic. Currently, cases are occurring worldwide. Transmission, risk factors, clinical presentation, and outcomes of infection are poorly defined. We formed an international collaborative group of clinicians who contributed to an international case series to describe the presentation, clinical course, and outcomes of polymerase-chain-reaction-confirmed monkeypox virus infections. We report 528 infections diagnosed between April 27 and June 24, 2022, at 43 sites in 16 countries. Overall, 98% of the persons with infection were gay or bisexual men, 75% were White, and 41% had human immunodeficiency virus infection; the median age was 38 years. Transmission was suspected to have occurred through sexual activity in 95% of the persons with infection. In this case series, 95% of the persons presented with a rash (with 64% having ≤10 lesions), 73% had anogenital lesions, and 41% had mucosal lesions (with 54 having a single genital lesion). Common systemic features preceding the rash included fever (62%), lethargy (41%), myalgia (31%), and headache (27%); lymphadenopathy was also common (reported in 56%). Concomitant sexually transmitted infections were reported in 109 of 377 persons (29%) who were tested. Among the 23 persons with a clear exposure history, the median incubation period was 7 days (range, 3 to 20). Monkeypox virus DNA was detected in 29 of the 32 persons in whom seminal fluid was analyzed. Antiviral treatment was given to 5% of the persons overall, and 70 (13%) were hospitalized; the reasons for hospitalization were pain management, mostly for severe anorectal pain (21 persons); soft-tissue superinfection (18); pharyngitis limiting oral intake (5); eye lesions (2); acute kidney injury (2); myocarditis (2); and infection-control purposes (13). No deaths were reported. In this case series, monkeypox manifested with a variety of dermatologic and systemic clinical findings. The simultaneous identification of cases outside areas where monkeypox has traditionally been endemic highlights the need for rapid identification and diagnosis of cases to contain further community spread.

Historically, human monkeypox virus cases in the UK have been limited to imported infections from west Africa. Currently, the UK and several other countries are reporting a rapid increase in monkeypox cases among individuals attending sexual health clinics, with no apparent epidemiological links to endemic areas. We describe demographic and clinical characteristics of patients diagnosed with human monkeypox virus attending a sexual health centre. In this observational analysis, we considered patients with confirmed monkeypox virus infection via PCR detection attending open-access sexual health clinics in London, UK, between May 14 and May 25, 2022. We report hospital admissions and concurrent sexually transmitted infection (STI) proportions, and describe our local response within the first 2 weeks of the outbreak. Monkeypox virus infection was confirmed in 54 individuals, all identifying as men who have sex with men (MSM), with a median age of 41 years (IQR 34–45). 38 (70%) of 54 individuals were White, 26 (48%) were born in the UK, and 13 (24%) were living with HIV. 36 (67%) of 54 individuals reported fatigue or lethargy, 31 (57%) reported fever, and ten (18%) had no prodromal symptoms. All patients presented with skin lesions, of which 51 (94%) were anogenital. 37 (89%) of 54 individuals had skin lesions affecting more than one anatomical site and four (7%) had oropharyngeal lesions. 30 (55%) of 54 individuals had lymphadenopathy. One in four patients had a concurrent STI. Five (9%) of 54 individuals required admission to hospital, mainly due to pain or localised bacterial cellulitis requiring antibiotic intervention or analgesia. We recorded no fatal outcomes. Autochthonous community monkeypox virus transmission is currently observed among MSM in the UK. We found a high proportion of concomitant STIs and frequent anogenital symptoms, suggesting transmissibility through local inoculation during close skin-to-skin or mucosal contact, during sexual activity. Additional resources are required to support sexual health and other specialist services in managing this condition. A review of the case definition and better understanding of viral transmission routes are needed to shape infection control policies, education and prevention strategies, and contact tracing. None.

In 2009, Norway initiated routine quadrivalent HPV (qHPV) vaccination for girls at 12–13 years of age to protect against virus types causing cervical cancer, HPV16/18, and HPV6/11 which cause anogenital warts (AGW). We wanted to investigate qHPV vaccine effectiveness (VE) against AGW in females before and after first AGW episode and to assess the impact of female vaccination in males. QHPV vaccination and AGW episodes were collected for the time period 2006–2016 for birth cohorts 1975–2003. Cox models were applied to age at first, as well as at second AGW episode. Finally, we estimated the impact of the female vaccination program on unvaccinated males. The VE against the first episode of AGW was strongly dependent on vaccination age, with hazard ratios (HRs) compared to unvaccinated individuals of 0.2, 0.2, 0.3, 0.5, 1.0, 1.3, and 2.7, for age groups of ⩽13, 14–15, 16–17, 18–19, 20–24, 25–29, and 30+ years at first vaccination, respectively. Among women who had suffered a first episode of AGW, subsequent qHPV vaccination did not protect against a second episode, with HRs of 0.8, 1.0, and 1.4, for age groups of ⩽17, 18–24, and 25+ years at first vaccination. A gradually decreasing AGW risk was seen in unvaccinated male cohorts neighboring the first routinely vaccinated female 1997 cohort. When administered before 14 years of age, qHPV vaccination reduced the probability of AGW about fivefold. The effect decreased sharply with vaccination age, and was not significant among women vaccinated after age 20 years. QHPV administered after the first AGW episode did not protect against a second AGW episode. Herd effects were indicated in unvaccinated males, as we observed a gradual decrease in AGW rates from the 1993 male birth cohort and onwards.