Incidence and presentation of new-onset type 1 diabetes in children and adolescents from Germany during the COVID-19 pandemic 2020 and 2021: Current data from the DPV Registry.

AIMS: To determine whether the incidence of type 1 diabetes mellitus (T1D), autoantibody-negative diabetes, and diabetic ketoacidosis (DKA) at diabetes onset in 2020 and 2021 changed when compared to long-standing trends. METHODS: Our study is based on diabetes manifestation data of the 0.5-<18-year-old children/adolescents from the German multicenter Diabetes Prospective Follow-up Registry. Based on long-term pre-pandemic trends from 2011 to 2019, we estimated adjusted incidence rate ratios (IRR) for T1D and DKA, and prevalence rate ratios (PRR) regarding autoantibody status with 95 % confidence intervals (CI) for the years 2020 and 2021 (observed versus predicted rates), using multivariable negative binomial or beta-binomial regression, respectively. RESULTS: We analyzed data of 30,840 children and adolescents with new-onset T1D. The observed incidences were significantly higher than the predicted incidences (IRR2020 1.13 [1.08-1.19]; IRR2021 1.20 [1.15-1.26]). The prevalence of autoantibody-negative diabetes did not change (PRR2020 0.91 [0.75-1.10]; PRR2021 1.03 [0.86-1.24]). The incidence of DKA during the pandemic was higher than predicted (IRR2020 1.34 [1.23-1.46]; IRR2021 1.37 [1.26-1.49]). CONCLUSIONS: An increase in the incidences of T1D and DKA, but not of autoantibody-negative diabetes was observed during both pandemic years. Further monitoring and efforts for DKA prevention at onset are necessary.

Gonadoblastoma Y locus genes expressed in germ cells of individuals with dysgenetic gonads and a Y chromosome in their karyotypes include DDX3Y and TSPY.

STUDY QUESTION: Which Y genes mapped to the 'Gonadoblastoma Y (GBY)' locus on human Y chromosome are expressed in germ cells of individuals with some Differences of Sexual Development (DSD) and a Y chromosome in their karyotype (DSD-XY groups)? SUMMARY ANSWER: The GBY candidate genes DDX3Y and TSPY are expressed in the germ cells of DSD-XY patients from distinct etiologies: patients with mixed gonadal dysgenesis (MGD) and sex chromosome mosaics (45,X0/46,XY; 46,XX/46,XY); patients with complete androgen insensitivity (CAIS), patients with complete gonadal dysgenesis (CGD; e.g. Swyer syndrome). WHAT IS KNOWN ALREADY: A GBY locus was proposed to be present on the human Y chromosome because only DSD patients with a Y chromosome in their karyotype have a high-although variable-risk (up to 55%) for germ cell tumour development. GBY was mapped to the proximal part of the short and long Y arm. TSPY located in the proximal part of the short Y arm (Yp11.1) was found to be a strong GBY candidate gene. It is expressed in the germ cells of DSD-XY patients with distinct etiologies but also in foetal and pre-meiotic male spermatogonia. However, the GBY region extends to proximal Yq11 and therefore includes probably more than one candidate gene. STUDY DESIGN, SIZE, DURATION: Protein expression of the putative GBY candidate gene in proximal Yq11, DDX3Y, is compared with that of TSPY in serial gonadal tissue sections of 40 DSD-XY individuals from the three DSD patient groups (MGD, Complete Androgen Insensitivity Syndrome [CAIS], CGD) with and without displaying malignancy. Expression of OCT3/4 in the same tissue samples marks the rate of pluripotent germ cells. PARTICIPANTS/MATERIALS, SETTING, METHOD: A total of 145 DSD individuals were analysed for the Y chromosome to select the DSD-XY subgroup. PCR multiplex assays with Y gene specific marker set score for putative microdeletions in GBY Locus. Immunohistochemical experiments with specific antisera mark expression of the GBY candidate proteins, DDX3Y, TSPY, in serial sections of the gonadal tissue samples; OCT3/4 expression analyses in parallel reveal the pluripotent germ cell fraction. MAIN RESULTS AND THE ROLE OF CHANCE: Similar DDX3Y and TSPY protein expression patterns were found in the germ cells of DSD-XY patients from each subgroup, independent of age. In CAIS patients OCT3/4 expression was often found only in a fraction of these germ cells. This suggest that GBY candidate proteins are also expressed in the non-malignant germ cells of DSD-XY individuals like in male spermatogonia. LIMITATIONS, REASONS FOR CAUTION: Variation of the expression profiles of GBY candidate genes in the germ cells of some DSD-XY individuals suggests distinct transcriptional and translational control mechanisms which are functioning during expression of these Y genes in the DSD-XY germ cells. Their proposed GBY tumour susceptibility function to transform these germ cells to pre-malignant GB/Germ Cell Neoplasia in Situ (GB/GCNIS) cells seems therefore to be limited and depending on their state of pluripotency. WIDER IMPLICATIONS OF THE FINDINGS: These experimental findings are of general importance for each individual identified in the clinic with DSD and a Y chromosome in the karyotype. To judge their risk of germ cell tumour development, OCT3/4 expression analyses on their gonadal tissue section is mandatory to reveal the fraction of germ cells still being pluripotent. Comparative expression analysis of the GBY candidate genes can be helpful to reveal the fraction of germ cells with genetically still activated Y chromosomes contributing to further development of malignancy if at high expression level. STUDY FUNDING/COMPETING INTEREST(S): This research project was supported by a grant (01GM0627) from the BMBF (Bundesministerium für Bildung und Forschung), Germany to P.H.V. and B.B. The authors have no competing interests.

Analyses of Gonadoblastoma Y (GBY)-locus and of Y centromere in Turner syndrome patients.

BACKGROUND: Mosaicism with cytogenetically visible Y chromosome is found in 5-6% of Turner Syndrome (TS) patients. Additionally, occult Y-chromosome derived material is increasingly found in patients with monosomy X when using more sensitive molecular techniques. These TS patients are at risk of developing gonadoblastomas when the Y genes presumed to be involved in gonadoblastoma development (Gonadoblastoma-Y-locus; GBY) are present. AIM: To find occult Y-chromosome material in TS patients and to correlate the patient's phenotype to Y-chromosome material. METHODS: We studied 60 TS-patients for presence of the Y chromosome with focus on the Gonadoblastoma Y-locus and its extension in Yp and Yq using sensitive Y centromere and Y gene deletion PCR assays. In addition, we evaluated their individual clinical and auxological characteristics. RESULTS: We identified presence of the GBY-locus in 7 patients (11.7%) including 4 patients without evidence for a Y chromosome in their preceding standard karyotype analyses. Clinical and auxological characteristics were similar in GBY-positive and GBY-negative patients. CONCLUSIONS: Presence of the GBY locus in Turner patients with no indication of the Y chromosome in standard cytogenetic chromosome analysis can be revealed by sensitive molecular PCR assays screening for presence of the Y centromere and the GBY-candidate-genes in proximal Yp11 and Yq11, respectively.

Lipid-laden macrophages in bronchoalveolar lavage fluid as a marker for pulmonary aspiration.

An increased lipid content in alveolar macrophages of bronchoalveolar lavage (BAL) fluid is thought to be a useful indicator for recurrent pulmonary aspiration. To assess whether pulmonary diseases unrelated to aspiration can raise the lipid content in alveolar macrophages, we evaluated Oil-Red-O-stained smears of BAL fluid in 18 children aged 3-15 years undergoing elective surgery for nonpulmonary illnesses under general anesthesia and in 18 children aged 1-16 years who had pulmonary diseases without clinical evidence of aspiration (pneumonia, exogenous allergic alveolitis, or cystic fibrosis). A semiquantitative lipid-laden macrophage (LLM) index was determined for each patient. LLM indices in children without pulmonary disease were higher than those published for healthy adults. In children with pulmonary diseases but without evidence of aspiration, a significantly higher LLM index was observed compared to controls. The LLM indices of children with pulmonary diseases were similar to those published by other authors for children with pulmonary aspiration. We conclude that an elevated LLM index in alveolar macrophages of BAL can be found in a variety of pulmonary diseases in which there is no clinical evidence of aspiration and is therefore unlikely to be a specific parameter for silent pulmonary aspiration.

Tuberculoma of the pons.

A case of a pontine tuberculoma in a 12-year-old male from Somalia is presented. Cranial magnetic resonance imaging, performed in Abu Dhabi 1 month before admission in Germany revealed a tumorous lesion in the pons with surrounding edema; a presumptive diagnosis of a pontine glioma was made. Chest radiograph disclosed a pulmonary infiltrate with cavitation, as well as hilar and left mediastinal lymphadenopathy, suggestive of active tuberculosis. Tuberculostatic therapy led to an improvement of the patient's clinical status and a significant reduction in the size of the pontine tuberculoma. Intracranial tuberculomas rarely are seen in industrialized countries. They should, however, be considered as an important part of the differential diagnosis of intracranial space-occupying lesions. In most cases, as in this patient, conservative therapy provides good or excellent results.

[Mastoiditis in childhood]. / Mastoiditis im Kindesalter.

BACKGROUND: Despite new antibiotics mastoiditis in children still is a serious infection confronting the pediatrician and otolaryngologist with diagnostic and therapeutic problems. PATIENTS AND METHODS: In a retrospective study we reviewed the charts of 48 children who had a mastoidectomy from 1990 to 1995 in the Department of Oto-Rhino-Laryngology at the University of Essen. RESULTS: 60% of the patients presented with a retroauricular swelling, and a pathologic tympanic membrane was found in 89%. The erythrocyte sedimentation rate as the most valuable laboratory parameter was increased in 95% of cases. Larger osteodestructive lesions as a complication of mastoiditis could be predicted in three of ten cases by plain x-ray of the temporal bone. The most common bacteria to be isolated were Staphylococcus aureus, Streptococcus pneumoniae and Pseudomonas aeruginosa. CONCLUSION: Because of potential endocranial complications (10% in our patients) as well as difficult radiologic diagnosis of osteodestructive lesions by plain x-ray, we advocate mastoidectomy instead of a mere pharmacological therapy in the treatment of mastoiditis.