Summary Background and objectives Onychomycosis (OM) and tinea pedis (TP) are common fungal infections. Currently, diagnosis is based on direct microscopy and culture that have a low to moderate sensitivity and/or require up to 3–4 weeks until results are obtained. PCR techniques have emerged for the diagnosis of fungal infections, but little is known about their sensitivity and specificity in diagnosing. Here, we compared the diagnostic value of a DNA‐chip technology, that detects 56 fungal pathogens, in a single‐center prospective diagnostic study with microscopy and culture in suspected OM/TP. Patients and methods Microscopy, culture and DNA microarray assays were performed on scraping material from patients with suspected OM (n = 67) or TP (n = 73). To test whether swabs can be used as an alternative for scraping, PCR yields were compared in a further 13 patients with OM and 11 patients with TP. Results DNA microarrays had the highest sensitivity. Combination of DNA‐chip technology with microscopy further increased the sensitivity, and results from this combined laboratory diagnosis can be obtained within 24 hours. Comparison of sampling techniques (scraping, dry or wet swab) for DNA‐chip assays showed similar results in suspected OM or TP. Conclusions DNA‐chip technology shows high sensitivity for OM and TP diagnosis, especially when combined with microscopy.

Onychomycosis (OM) is a common fungal nail infection. Based on the rich mycobial diversity in healthy toenails, we speculated that this is lost in OM due to the predominance of a single pathogen. We used next generation sequencing to obtain insights into the biodiversity of fungal communities in both healthy individuals and OM patients. By sequencing, a total of 338 operational-taxonomic units were found in OM patients and healthy controls. Interestingly, a classifier distinguished three distinct subsets: healthy controls and two groups within OM patients with either a low or high abundance of Trichophyton . Diversity per sample was decreased in controls compared to cases with low Trichophyton abundance (LTA), while cases with a high Trichophyton abundance (HTA) showed a lower diversity. Variation of mycobial communities between the samples showed shifts in the community structure between cases and controls—mainly driven by HTA cases. Indeed, LTA cases had a fungal β-diversity undistinguishable from that of healthy controls. Collectively, our data provides an in-depth characterization of fungal diversity in health and OM. Our findings also suggest that onychomycosis develops either through pathogen-driven mechanisms, i.e., in HTA cases, or through host and/or environmental factors, i.e., in cases with a low Trichophyton abundance.

Background: Many people with diabetes have permanently elevated blood sugar concentrations and a high level of diabetes-related psychological stress. also called "diabetes distress." In clinical practice, diabetes distress is often an impediment to successful self-management. psy-PAD is a psychodynamically oriented short-term therapy program whose goal is to reduce diabetes distress and improve glycemic control. Methods: A randomized controlled trial was conducted with 143 patients with either type 1 or type 2 diabetes who were being treated in eleven specialized diabetological practices. psy-PAD in the intervention group (eight sessions) was compared with optimized standard care as the control condition. The inclusion criteria were HbA1c >= 7.5% combined with diabetes distress (PAID >35, or doctor's determination). The primary endpoint was the HbA1c at six months (t(1)). Diabetes-related distress (PAID), depressive symptoms (HADS-D, PHQ-9), anxiety symptoms (HADS-A), health-related quality of life (SF-36), panic (short form of the PHQ-D), body mass index (BMI), and triglyceride levels were secondary endpoints. Follow-ups were conducted at six (t(1)) and 12 months (t(2)) (trial registration: DRKS00003247). Results: The intergroup comparison at t 1 revealed a significant, clinically relevant reduction of HbA1c by -0.53 percentage points (95% confidence interval [-0.89; -0.16], p = 0.005). The secondary analyses revealed relevant differences in the point estimators for diabetes distress at t(1) and t(2), depressive symptoms at t(2) and BMI at t(1). Conclusion: For people with diabetes and diabetes distress who do not achieve satisfactory glycemic control despite intensive treatment in specialized diabetological practices. integrated psychosomatic-psychotherapeutic treatment can lower blood sugar levels over the intermediate term and also reduce diabetes distress and depressive symptoms over a one-year period.

ZusammenfassungHintergrund und ZieleOnychomykose (OM) und Tinea pedis (TP) sind häufige Pilzinfektionen der Haut. Aktuell basiert die Diagnose vornehmlich auf mikroskopischem Direktnachweis und/oder Kultur. Beide Methoden haben jedoch eine geringe bis mäßige Sensitivität und benötigen teilweise mehrere Wochen, bis endgültige Laborergebnisse vorliegen. Um die Diagnose kutaner Pilzinfektionen zu verbessern, wurden PCR‐basierte Methoden entwickelt. Hier haben wir hier die Sensitivität und Spezifität einer Chip‐basierten Multiplex‐PCR mit mikroskopischen Direktnachweis und verglichen.Patienten und MethodikIn einer monozentrischen, prospektiven Studie wurden bei Patienten mit Verdacht auf OM (n = 67) oder TP (n = 73) Schuppenpräparate entnommen und mittels mikroskopischem Direktnachweis, Kultur und DNA‐Chip‐Technologie der Erregernachweis durchgeführt. In einem weiteren Ansatz wurde überprüft, ob Abstriche als Alternative zur Entnahme eines Schuppenpräparates verwendet werden können. Hierfür wurden 24 weitere OM/TP‐Patienten rekrutiert und die Ergebnisse der DNA‐Chip‐Technologie aus Abstrichen mit denen aus den Schuppenpräparaten verglichen.ErgebnisseIm Vergleich aller Methoden hatte die DNA‐Chip‐Technologie die höchste Sensitivität, eine Kombination von DNA‐Chip‐Technologie mit mikroskopischem Direktnachweis erhöhte dies weiter. Ergebnisse dieser kombinierten Labordiagnostik sind innerhalb von 24 Stunden verfügbar. Der Vergleich der Probenentnahmetechniken (Abstrich beziehungsweise Schuppenpräparat) zeigte vergleichbare Ergebnisse.SchlussfolgerungenDie molekulare Diagnostik (mittels DNA‐Chip‐Technologie) hat eine hohe Sensitivität für die OM‐ und TP‐Diagnostik, insbesondere in Kombination mit dem mikroskopischen Direktnachweis.

In this article international trends in surgical practice in girls with congenital adrenal hyperplasia (CAH) are evaluated. All cases that had been classified in the I-CAH/I-DSD registry as 46,XX CAH and who were born prior to 2017 were identified. Centers were approached to obtain information on surgical decision making. Of the 330 included participants, 208 (63.0%) presented within the first month of life, and 326 (98.8%) cases were assigned female. Genital surgery had been performed in 250 (75.8%). A total of 64.3, 89.2, and 96.8% of cases residing in Europe, South America and Asia, respectively, had at least one surgery. In a logistic regression model for the probability of surgery before the second birthday (early surgery) over time an increase of probability for early vaginal surgery could be identified, but not for clitoral surgery or both surgeries combined. Genitoplasty in girls with CAH remains controversial. This large international study provides a snapshot of current practice and reveals geographical and temporal differences. Fewer surgeries were reported for Europe, and there seems to be a significant trend towards aiming for vaginal surgery within the first 2 years of life.

Over a decade ago, the participants at the International Consensus Conference on Intersex proposed Disorders of Sex Development (DSD) as an umbrella term for "congenital conditions in which the development of chromosomal, gonadal, or anatomical sex is atypical". The Group recommended the terminology be sensitive to concerns of individuals having these conditions. Yet, controversy rages over the term DSD. This multicentre clinical evaluation study was initiated as part of the European research group dsd-LIFE to evaluate patient-reported outcome. In total, 1,040 individuals with conditions labeled as Disorders of Sex Development were recruited in Poland, Sweden, Germany, France, United Kingdom and the Netherlands. All participants were asked to rate the terms describing their conditions. Overall, a large majority of participants (69%) reported that the term Disorders of Sex Development applied to their condition or that they felt neutral about it. Most participants preferred terms that were specific to their somatic condition. Overall, our data do not support the view that, in general, the term Disorders of Sex Development is insensitive to concerns of affected persons and that it should therefore be abandoned. However, in the clinical encounter, we recommend that clinicians evaluate each patient's preferences.

OBJECTIVE:The aim of the study was to evaluate psychiatric symptoms among 1022 persons with various disorders of sex development (DSDs). METHODS:The study was a European multicenter cross-sectional clinical evaluation in six countries. The mean (SD) age of participants was 32.1 (13.4) years. The cohort consisted of 325 individuals with Turner syndrome, 219 individuals with Klinefelter syndrome (KS), female individuals with various XY-DSD conditions (107 with and 67 without androgenization), 87 male individuals with XY-DSD conditions, and 221 female individuals with congenital adrenal hyperplasia. The Hospital Anxiety and Depression Scale, the Short Autism Spectrum Quotient, the Adult Attention-Deficit/Hyperactivity Disorder Self-Report Scale, and self-reported mental health history were used to assess psychiatric symptoms. RESULTS:Across the six DSD diagnostic groups, clinical cutoff symptom scores were reached in 19.5% of participants for anxiety, in 7.1% for depression, in 4.1% for attention-deficit/hyperactivity disorder, and in 9.1% for autism. The mean depression and anxiety scores were higher compared with population norms in men with KS and men with XY-DSD. Compared with participants with other DSD conditions, men with KS reported significantly more mental health symptoms. Self-esteem, satisfaction with care, body dissatisfaction, and experiences of shame were associated with psychiatric symptoms in many DSD conditions. CONCLUSIONS:A substantial minority of adults with DSD, with KS in particular, experience psychiatric morbidity. Across DSD conditions, adults may share feelings of shame. Developing a positive self-esteem and body image may be challenging. Multidisciplinary DSD care that involves specialized mental health support can be of important value. TRIAL REGISTRATION:German Clinical Trials Register DRKS00006072.

For various reasons, sexuality of individuals with differences/disorders of sex development (DSD) may be affected. The aim of the study was to describe sexual activity, satisfaction with sex life, satisfaction with genital function, and sexual problems in people with different DSD conditions. Data were collected from 1,040 participants in Europe. Many people with a variety of DSD conditions do not appear to be satisfied with their sex life, experience a variety of sexual problems, and are less sexually active than the general population; therefore sexuality should be explicitly addressed in the care of people with DSD.

Variation in karyotype may be associated with the phenotype of patients with Turner syndrome (TS). Our objective was to identify these associations between karyotype and phenotype in TS patients. This study was part of the European multicentre dsd-LIFE study. We evaluated the associations between different karyotypes of TS patients and age at diagnosis, Turner stigmata, cardiac/renal involvement and gonadal function. Information was available for 328 TS patients. Participants had a monosomy 45,X (46%), mosaicism 45,X/46,XX (10%), karyotype with isochromosome (18%), or other karyotype (26%). The clinical signs of TS were the most severe in patients with monosomy 45,X and the least severe in patients with mosaicism 45,X/46,XX. Patients with isochromosome and y-material showed an intermediate phenotype. Despite the more severe features in patients with monosomy 45,X, the median age at diagnosis was only slightly lower compared to patients with other karyotypes, which suggests opportunities for improvement of knowledge and diagnostics.

Previous studies have reported a shift in the timing of sleep during adolescence toward a later time. To date, it is unclear whether hormonal changes during puberty might contribute to this change in sleeping behavior. We systematically assessed pubertal development and sleep timing in a cross-sectional case-control study in girls with precocious (n = 42) and boys with delayed pubertal development (n = 19). We used the Munich ChronoType Questionnaire and the Children's ChronoType Questionnaire to assess sleep timing in patients and age- and sex-matched controls (n = 309) and used the midpoint of sleep on free days, corrected for potential sleep debt accumulated during the school week, as a marker for sleep timing. Compared to the controls, girls with central precocious puberty showed a delay in sleep timing of 54 min, and girls with premature pubarche slept on average 30 min later. Male adolescents with delayed pubertal development showed an average sleep midpoint that was 40 min earlier compared to the control group. The results of this pilot study suggest an association between pubertal onset and shifts in sleep timing, which is a novel finding in human sleep behavior. Prospective studies in larger cohorts will be needed to examine the robustness and generalizability of the findings.

The treatment and care of individuals who have a difference of sex development (DSD) have been revised over the past two decades and new guidelines have been published. In order to study the impact of treatments and new forms of management in these rare and heterogeneous conditions, standardised assessment procedures across centres are needed. Diagnostic work-up and detailed genital phenotyping are crucial at first assessment. DSDs may affect general health, have associated features or lead to comorbidities which may only be observed through lifelong follow-up. The impact of medical treatments and surgical (non-) interventions warrants special attention in the context of critical review of current and future care. It is equally important to explore gender development early and refer to specialised services if needed. DSDs and the medical, psychological, cultural and familial ways of dealing with it may affect self-perception, self-esteem, and psychosexual function. Therefore, psychosocial support has become one of the cornerstones in the multidisciplinary management of DSD, but its impact remains to be assessed. Careful clinical evaluation and pooled data reporting in a global DSD registry will allow linking genetic, metabolomic, phenotypic and psychological data. For this purpose, our group of clinical experts and patient and parent representatives designed a template for structured longitudinal follow-up. In this paper, we explain the rationale behind the selection of the dataset. This tool provides guidance to professionals caring for individuals with a DSD and their families. At the same time, it collects the data needed for answering unsolved questions of patients, clinicians, and researchers. Ultimately, outcomes for defined subgroups of rare DSD conditions should be studied through large collaborative endeavours using a common protocol.

STUDY QUESTION: What are the levels of breast development and satisfaction in women with a Disorder/Difference of Sex Development (DSD)? SUMMARY ANSWER: Compared with normative data, women with DSD reached lower Tanner stages and reported less breast satisfaction. WHAT IS KNOWN ALREADY: Women with DSD may have chromosomal and hormonal variations that can impact typical breast development. While much emphasis is placed on genital development in this group, little is known about breast development, satisfaction and their association. STUDY DESIGN, SIZE, DURATION: Data collection was part of the cross-sectional European multicenter dsd-LIFE study. Fourteen recruiting sites included 1040 participants between February 2014 and September 2015. PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 695 female-identifying participants were included (Turner n = 332, 46,XY DSD n = 141 and congenital adrenal hyperplasia n = 222), with a median age of 28 years. Clinical (i.e. history of hormone and surgical treatments, Tanner breast examination) and patient-reported (i.e. breast satisfaction, relationship status, sexual satisfaction and experienced femininity) data was collected by independent trained research staff. The relationship between breast development, satisfaction and femininity was assessed. Control data on breast development and satisfaction in women without DSD was retrieved from the literature. MAIN RESULTS AND THE ROLE OF CHANCE: Of the 695 participants, 61% had received estrogen replacement and 51% puberty induction therapy, whereas 2% had received breast augmentation surgery. Approximately 65% of participants had reached Tanner breast stage 5, which is substantially less than the general population (90%). Breast satisfaction was lower than normative data as well (P<0.001, Cohen's d = 0.45). Breast size and breast satisfaction were associated with feelings of femininity. LIMITATIONS, REASONS FOR CAUTION: Limitations include the sample representativeness (e.g. regarding the clinical heterogeneity) and the limited in-depth knowledge on (prior) hormonal regimens. Furthermore, no (matched) control data was collected as part of this study. WIDER IMPLICATIONS OF THE FINDINGS: In order to support the psychosexual well-being of women with DSD, enhancing breast development by sufficient hormone replacement and possible augmentation surgery is advocated. The scope of DSD management should be beyond genital development only and consider breasts as well.

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

OBJECTIVE:Changes of sex hormone levels in disorders of sex development (DSD) can affect the body, including the vocal folds, during and after foetal development. The voice is a gender characteristic that may also be affected. There is a lack of knowledge on voice alteration in DSD. To explore this in different forms of DSD, we describe the prevalence of voice alterations and investigate patient satisfaction with voice.DESIGN:The study is part of dsd-LIFE, a multicentre cross-sectional clinical evaluation project assessing the long-term outcomes of surgical, hormonal and psychological interventions in individuals with DSD.PATIENTS:The study included 1040 individuals with different forms of DSD, that is Turner and Klinefelter syndromes, different degrees of gonadal dysgenesis and 46 XY DSD. Participants were recruited through patient advocacy groups and health care.MEASUREMENTS:Satisfaction with voice, Adam's apple, if patient's self-identified gender was mistaken on the phone leading to distress.RESULTS:A vast majority of the participants with DSD (between 58.3% to 82% in various groups) were not satisfied with their voice, and approximately 15% (n = 147) were mistaken on the phone in accordance with self-identified gender. For 102 participants, this caused distress.CONCLUSIONS:We have identified that voice problems are a cause of distress in all forms of DSD. This result needs to be confirmed and compared with controls. We recommend that evaluation of the voice should be included in future international guidelines for management of DSD.

Previous studies in quality of life (QOL) in individuals with disorders/differences of sex development (DSD) have been restricted to subpopulations of the condition. We describe QOL in adult persons with DSD compared to country specific references and assess the impact of diagnosis.