Development and evaluation of a patient education programme for children, adolescents, and young adults with differences of sex development (DSD) and their parents: study protocol of Empower-DSD.

BACKGROUND: Differences in sexual development (DSD) are rare diseases, which affect the chromosomal, anatomical or gonadal sex differentiation. Although patient education is recommended as essential in a holistic care approach, standardised programmes are still lacking. The present protocol describes the aims, study design and methods of the Empower-DSD project, which developed an age-adapted multidisciplinary education programme to improve the diagnosis-specific knowledge, skills and empowerment of patients and their parents. METHODS: The new patient education programme was developed for children, adolescents and young adults with congenital adrenal hyperplasia, Turner syndrome, Klinefelter syndrome or XX-/or XY-DSD and their parents. The quantitative and qualitative evaluation methods include standardised questionnaires, semi-structured interviews, and participatory observation. The main outcomes (assessed three and six months after the end of the programme) are health-related quality of life, disease burden, coping, and diagnosis-specific knowledge. The qualitative evaluation examines individual expectations and perceptions of the programme. The results of the quantitative and qualitative evaluation will be triangulated. DISCUSSION: The study Empower-DSD was designed to reduce knowledge gaps regarding the feasibility, acceptance and effects of standardised patient education programmes for children and youth with DSD and their parents. A modular structured patient education programme with four generic and three diagnosis-specific modules based on the ModuS concept previously established for other chronic diseases was developed. The topics, learning objectives and recommended teaching methods are summarised in the structured curricula, one for each diagnosis and age group. At five study centres, 56 trainers were qualified for the implementation of the training programmes. A total of 336 subjects have been already enrolled in the study. The recruitment will go on until August 2022, the last follow-up survey is scheduled for February 2023. The results will help improve multidisciplinary and integrated care for children and youth with DSD and their families. TRIAL REGISTRATION: German Clinical Trials Register, DRKS00023096 . Registered 8 October 2020 - Retrospectively registered.

Phenotype profiling of primary testicular diffuse large B-cell lymphomas.

Primary testicular diffuse large B-cell lymphomas (tDLBCL) are rare neoplasms with few comprehensive studies conducted so far. We aimed to systematically characterize the phenotype of tDLBCL. Forty-five patients from three Swiss hospitals diagnosed with tDLBCL between 1972 and 2009 were reviewed and included in this study. A tissue microarray was assembled, and the protein expression profiles were assessed by immunohistochemistry and fluorescence in situ hybridization for the C-MYC locus. All tDLBCL expressed CD79a, followed by CD20 (98% of cases) and CD19 (93%). One case expressed the germ cell marker OCT4 and showed a rearrangement of C-MYC. Eighty-two per cent of cases showed active STAT signalling by expression of either pSTAT1 or pSTAT3 or both, but not pSTAT5. The p53 was overexpressed in 10% of cases, but p21 staining (∆p21/p53) did not suggest the presence of TP53 mutations. tDLBCL had a median MIB1 labelling index of 40%, and only 6% of cases appeared to have C-MYC rearrangements. Most cases were of the non-germinal centre type (77%), and showed as expected for this cell of origin B-cell lymphoma 2 (BCL2) rearrangements only in 4% and amplifications in 15% of cases, whereas BCL6 was rearranged in 48% of cases. CXCR4 was expressed in 52% of cases, and high CXCR4 expression was of prognostic significance for progression-free survival (p = 0.003). Because 84% of cases expressed nuclear p50, the canonical NF-κB signalling pathway seems to be active. Multimarker phenotyping is important for lineage determination of tDLBCL. Occasionally, tDLBCL can express germ cell markers like OCT4, and they have active STAT signalling mediated through pSTAT1 and pSTAT3 and active canonical NF-κB signalling. tDLBCL are of non-germinal centre/post-germinal centre cell origin and not hyperproliferative. TP53 mutations are unlikely, and C-MYC as well as BCL2 rearrangements are rare, whereas BCL6 is commonly rearranged. CXCR4 might prove to be the first protein-based prognostic marker for tDLBCL, inciting studies in larger cohorts corroborating these findings.

Harmonization of rat fetal external and visceral terminology and classification. Report of the Fourth Workshop on the Terminology in Developmental Toxicology, Berlin, 18-20 April 2002.

This article is a report on the Fourth Berlin Workshop on Terminology in Developmental Toxicology, which was held in April 2002. The workshop is part of an international project in the field of harmonization of terminology in developmental toxicology supported by IPCS. The goal of the Harmonization Project is to ensure better chemical risk assessment. The aim of this Fourth Workshop was to discuss the results of a previously conducted survey on classification of external and visceral anomalies, which are listed in the international glossary, developed under the auspices of IFTS (1997 glossary). The discussions among experts from research institutions, regulatory agencies, and industries were mainly focussed on terms for which there was disagreement and/or uncertainties and the possible reasons. For the illustration of "gray-zone" anomalies, pictures were provided by the participants, which constituted the basis for detailed discussions. There was high agreement that most of the external anomalies (>66%) should be classified as malformations. The few external anomalies for which there was low agreement to classify as a malformation were discussed in detail. None of the external findings, which had in the survey a high agreement, were categorized as a variation.A high agreement regarding the classification of approximately one-third of visceral anomalies was achieved with 34 and 2% being described as malformation and variation, respectively. Most of the visceral findings had low agreement indices and there appeared to be several reasons for this. Thus, the response, 'Not known/not used in the laboratory' (N) was often given. A couple of reasons for difficulties in the classification of an anomaly were that it is only rarely seen upon fetal examination or tends to be species specific. Furthermore, the classification of some anomalies as malformation or variation will remain vague as the decision must be made on a case-by-case basis. Factors affecting the decision include: the availability of appropriate historical control data, description of the grading and severity, whether the anomaly occurs in isolation or whether there is a relationship with an abnormal process, and finally, if the change represents an irreversible one, affecting human and/or animal health. It was concluded that a severity grading, supported by pictures of the anomaly, would be especially helpful to classify certain changes as malformation or as variation. Several of the soft tissue changes were considered likely to be the consequence of functional disorders and thus not strictly developmental anomalies. The possibility to describe a finding as 'Not Malformation' (Unclassified) was agreed upon. As a general conclusion it was emphasized that the observation of a permanent structural change should be considered to be a warning of possible consequences to humans, even when there is no apparent adverse effect on health and survival in adult animals of the species under investigation. Therefore, research is needed to further investigate postnatal consequences. Future collaboration in the field of reproductive and developmental toxicology should aim to further develop and implement a harmonized approach to the interpretation of study data. Therefore, this terminology work will continue in close cooperation with the IPCS Harmonization Project. A Steering Group should be established to facilitate the implementation of harmonized terminology into daily scientific work and its regulatory application.