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Background Despite concerns about worsening pregnancy outcomes resulting from healthcare restrictions, economic difficulties and increased stress during the COVID-19 pandemic, preterm birth (PTB) rates declined in some countries in 2020, while stillbirth rates appeared stable. Like other shocks, the pandemic may have exacerbated existing socioeconomic disparities in pregnancy, but this remains to be established. Our objective was to investigate changes in PTB and stillbirth by socioeconomic status (SES) in European countries. Methods The Euro-Peristat network implemented this study within the Population Health Information Research Infrastructure (PHIRI) project. A common data model was developed to collect aggregated tables from routine birth data for 2015–2020. SES was based on mother's educational level or area-level deprivation/maternal occupation if education was unavailable and harmonized into low, medium and high SES. Country-specific relative risks (RRs) of PTB and stillbirth for March to December 2020, adjusted for linear trends from 2015 to 2019, by SES group were pooled using random effects meta-analysis. Results Twenty-one countries provided data on perinatal outcomes by SES. PTB declined by an average 4% in 2020 {pooled RR: 0.96 [95% confidence intervals (CIs): 0.94–0.97]} with similar estimates across all SES groups. Stillbirths rose by 5% [RR: 1.05 (95% CI: 0.99–1.10)], with increases of between 3 and 6% across the three SES groups, with overlapping confidence limits. Conclusions PTB decreases were similar regardless of SES group, while stillbirth rates rose without marked differences between groups. [ABSTRACT FROM AUTHOR]

Aims: In somatotroph pituitary neuroendocrine tumours (adenomas), a pattern of cytokeratin (CK) 18 expression is used for tumour subclassification, with possible clinical implications. Rare somatotroph tumours do not express CK 18. We aimed to characterise this subset clinically and histologically. Methods and results: Clinical and pathological data for the study were derived from a previously published data set of a cohort of 110 patients with acromegaly. Data included serum levels of insulin‐like growth factor 1 (IGF1), growth hormone (GH), prolactin and thyroid‐stimulating hormone (TSH), tumour diameter, tumour invasion defined by Knosp grade and immunohistochemical data concerning the expression of Ki67, p53, E‐cadherin, somatostatin receptor (SSTR)1, SSTR2A, SSTR3, SSTR5 and D2 dopamine receptor. Additional immunohistochemical analysis (AE1/3, CK 8/18, vimentin, neurofilament light chain, internexin‐α) was performed. CK 18 was negative in 10 of 110 (9.1%) tumours. One of these tumours was immunoreactive with CK 8/18 antibody, while the remainder expressed only internexin‐α intermediate filament in patterns similar to CK 18 (perinuclear fibrous bodies). CK‐negative tumours showed no significant differences with respect to biochemical, radiological or pathological features. They showed significantly higher expression of SSTR2A compared to the sparsely granulated subtype and significantly lower expression of E‐cadherin compared to the non‐sparsely granulated subtypes of tumours. The tumours showed divergent morphology and hormonal expression: two corresponded to densely granulated tumours and three showed co‐expression of prolactin and morphology of either mammosomatotroph or somatotroph–lactotroph tumours. Four tumours showed morphology and immunoprofile compatible with plurihormonal Pit1‐positive tumours. Conclusions: CK‐negative somatotroph tumours do not represent a distinct subtype of somatotroph tumours, and can be further subdivided according to their morphology and immunoprofile. [ABSTRACT FROM AUTHOR]

In somatotroph pituitary tumours, somatostatin analogue (SSA) therapy outcomes vary throughout the studies. We performed an analysis of cohort of patients with acromegaly from the Czech registry to identify new prognostic and predictive factors. Clinical data of patients were collected, and complex immunohistochemical assessment of tumour samples was performed (SSTR1‐5, dopamine D2 receptor, E‐cadherin, AIP). The study included 110 patients. In 31, SSA treatment outcome was evaluated. Sparsely granulated tumours (SGST) differed from the other subtypes in expression of SSTR2A, SSTR3, SSTR5 and E‐cadherin and occurred more often in young. No other clinical differences were observed. Trouillas grading system showed association with age, tumour size and SSTR2A expression. Factors significantly associated with SSA treatment outcome included age, IGF1 levels, tumour size and expression of E‐cadherin and SSTR2A. In the group of SGST, poor SSA response was observed in younger patients with larger tumours, lower levels of SSTR2A and higher Ki67. We observed no relationship with expression of other proteins including AIP. No predictive value of E‐cadherin was observed when tumour subtype was considered. Multiple additional factors apart from SSTR2A expression can predict treatment outcome in patients with acromegaly. [ABSTRACT FROM AUTHOR]

Background: Females with Turner syndrome (TS) are prone to develop autoimmune diseases (AIDs). The X chromosome contains several immune-related genes. Growth hormone (GH) and estrogens modulate the immune system. We aimed to clarify whether the loss of a specific X chromosome gene locus and the administration of GH and estradiol facilitate the development of AIDs in TS females. Methods: Retrospective data on clinical course, AIDs, karyotype and treatment were analyzed from a cohort of 286 Czech females with TS (current age 2.8–43.3 years; median age 18.7 years). The karyotypes were sorted using two different classification systems: a mosaicism-focused and an isochromosome (isoXq)-focused approach. Karyotype subgroups with a significantly higher prevalence of AIDs were further evaluated. Data of common therapies were correlated with the prevalence of AIDs. Results: The most frequent AIDs were autoimmune thyroid disease (AITD; 37.4%; n = 107) and celiac disease (CD; 8.7%; n = 25). All karyotype subgroups were prone to develop AIDs. Females with an isolated Xp deletion had a significantly higher prevalence of AITD and CD compared to all other individuals with TS (AITD: 66.0% vs. 31.5%, p < 0.0001; CD: 17.4% vs. 7.2%; p = 0.04, respectively). We observed no link between the mean age at initiation as well as the duration of GH and/or estrogen administration and the occurrence of AIDs. Conclusions: Isolated Xp deletion contributes to the development of AIDs in TS patients. The haploinsufficiency of genes located in Xpter-p11.2 may explain this observation. Common therapies used in TS do not modify the risk of AIDs. [ABSTRACT FROM AUTHOR]

Aims. Pituitary adenomas (PA) are non-invasive benign tumors with a high autopsy prevalence. They are classified according to the type of hormone secreted (prolactin, growth hormone, adrenocorticotropin, thyrotropin, folitropin, or luteinizing hormone). Clinically non-functioning adenomas (CNFA) lacking the typical hypersecretion of hormones make up a significant portion of PA. The aim of the study was to determine the complete expression profiles of somatostatin receptors (SSTR1-SSTR5), dopamine receptors type 2 (D2R), and estrogen receptors (ER1) in various types of PA. Methods. Adenoma specimens were obtained from 206 patients during transsphenoidal resection. For quantitative analysis, reverse transcription and consequent real-time PCR with synthetic multilocus calibrators (SMC) were used. The obtained data were normalized to the number of transcripts of the beta-glucuronidase gene. Results. The use of SMC enabled the alignment of individual calibration functions for all the receptors. No relationships between the expression of the receptors and the tumor size, site of extension, gender or age at diagnosis were significant. In growth hormone-secreting adenomas, D2R and SSTR2 transcripts were extensively expressed, followed by ER1, SSTR5, SSTR3, and SSTR1. In patients with macroprolactinomas, transsphenoidal resection was indicated because dopamine agonists did not normalize prolactin levels. D2R, ER1 and SSTR1 transcripts were significantly transcribed. Corticotroph adenomas showed high levels of D2R and ER1 transcripts and lower amounts of SSTR2 and SSTR1 transcripts. SSTR5 transcripts were very low. Subjects with CNFA dominantly expressed D2R and ER1, followed by SSTR2 and SSTR3 mRNA. Conclusion. We evaluated SSTR1-SSTR5, D2R, and ER1 expressions in a large group of pituitary adenomas and we found that determining their individual expression profiles could help when choosing the optimal postoperative treatment. [ABSTRACT FROM AUTHOR]

The increasing global competition within today's manufacturing industries is confronting organizations with interdisciplinary challenges that require intellectual expertise and innovative technological solutions in various knowledge areas. Research organizations and manufacturing companies can improve their overall performance by bundling expertise in collaborative innovation networks. For this purpose a systematic Benchmarking approach has been developed by Fraunhofer IPK to match the competencies and capacities within a pool of organizations in order to facilitate a sustainable cooperation in terms of resources, customers and R&D topics. Furthermore, a KPI-based identification of best performing network-partners allows an initiation of Best-Practice transfers to gain sustainable competitive advantages for the whole network. Based on a methodological approach, the identification of collaboration potentials and Best-Practices is supported by software tools that visualize the results in an understandable and applicable way. [ABSTRACT FROM AUTHOR]

The aim of the study was to investigate the mechanism of action of somatostatin analogues (SSA), ionizing radiation, and their combination on pituitary adenoma cells with special emphasis on proliferative and apoptotic activity. In the 14 GH-secreting adenomas pretreated with SSA before surgery, more prominent regressive changes were found accompanied by compensatory increase in perivascular fibrosis than in the reference group of 17 unpretreated adenomas. The proliferative Ki-67 labeling index was significantly lower in the treated group (median 1.6 per 1000) than in the untreated patients (median 5.0 per 1000). Apoptosis was detected in only 2 of the 14 pretreated adenomas, and it was more frequent (9/17) and more prominent in the untreated group. In cell lines, the SSA had minimal antiproliferative effect, and they were unable to induce apoptosis. Ionizing radiation at doses of 5-20 Gy induced apoptosis in the corticotroph cell line AtT20 with no cell-cycle block. In the somatotroph GH3 cell line the early (premitotic) apoptosis was detectable using only a high dose of 200 Gy; after irradiation with doses of 20-50 Gy, apoptosis appeared with the latency of 48-72 hours, and was preceded by cell-cycle arrest in the G2/M phase. The treatment with somatostatin-14 during irradiation increased the percentage of apoptotic cells in culture 10 days after irradiation (11% versus 3% using 20 Gy). [ABSTRACT FROM AUTHOR]

Focuses on the risk of thyroid carcinoma for patients with Graves disease. Frequency of thyroid nodules found in patients with Graves disease; Result of the pathological examination of patients who underwent thyroidectomy for Graves disease; Use of fine needle aspiration to examine the presence of thyroid nodules.

Introduction: The relationship between Hashimoto's thyroiditis (HT) and thyroid cancer (TC) is controversial. While most surgical studies report a high incidence of malignancy among patients with HT, cytological studies do not. The role of autoantibodies in the incidence of malignancy is unclear., Material and Methods: A single-centre retrospective observational study was conducted in patients evaluated for thyroid nodules by US-guided fine-needle aspiration cytology (FNAC) and, if indicated, by surgery. The levels of thyroid-stimulating hormone (TSH) and anti-thyroid antibodies were measured at the time of FNAC., Results: Of 4947 patients, 599 (12.1%) were diagnosed with HT. A malignant/suspicious cytological result was found in 14.2% of the patients with HT and in 15.2% of the others. The odds ratio (OR) for malignancy in HT was 0.921 (0.716-1.183, p = 0.51). Of 1603 patients who underwent surgery, differentiated thyroid carcinoma was found in 29.5% of the HT patients and in 15.2% of the others (OR 2.33, 95% confidence interval CI, 1.403-3.854, p < 0,001). Low TSH (< 0.4 mIU/L) decreased the malignancy rate in the entire patient population, both when considering the cytological results and the surgical results. This was not confirmed in the subgroup diagnosed with HT. No relationship was observed between autoantibodies against thyroid peroxidase (ATP) or thyroglobulin (ATG) and malignancy rate., Conclusions: No association between HT and thyroid cancer was observed cytologically; a positive relationship in histological series was caused by selection bias. Low TSH levels decreased the risk of TC in patients with nodular goitre, but this has not been proven in patients with HT.

Objective: To evaluate the efficacy and safety of coadministered lanreotide Autogel (LA; 120  mg/month) and pegvisomant (40-120  mg/week) in acromegaly., Design: This is a 28-week, multicenter, open-label, single-arm sequential study., Methods: Patients (n=92) biochemically uncontrolled, on somatostatin analogs (SSAs) or using pegvisomant monotherapy entered a 4-month run-in taking LA (120  mg/month). Patients uncontrolled after the run-in period (n=57) entered a 28-week coadministration period, receiving LA 120  mg/month plus pegvisomant (60  mg once weekly, adapted every 8 weeks based on IGF1 levels to 40-80  mg once weekly or 40 or 60  mg twice weekly)., Results: In total, 33 (57.9%) patients had normalized IGF1 following coadministration (P<0.0001 versus 30% minimum clinically relevant); median pegvisomant dose in normalized patients was 60  mg/week. IGF1 normalized at any time during coadministration in 45 (78.9%) patients (P<0.0001) with median pegvisomant dose at 60  mg/week. Being nondiabetic (odds ratio (OR): 4.65) and older (OR, upper versus lower quartile: 3.40) showed increased likelihood of normalization. Symptom reduction was greatest for arthralgia (-0.6 ± 1.6) and soft tissue swelling (-0.6 ± 1.8). Five patients reported treatment-emergent adverse events causing treatment withdrawal: three serious (treatment related - thrombocytopenia, urticaria; not treatment related - abdominal pain/vomiting) and two nonserious (hepatotoxicity and cytolytic hepatitis, both elevating alanine aminotransferase to >5 × upper limit of normal with normalization after withdrawal)., Conclusions: In patients partially controlled by SSAs, LA (120  mg/month) plus pegvisomant normalized IGF1 in 57.9% of patients after 7 months, at a median effective pegvisomant dose of 60  mg/week, and 78.9% at any time. In these patients, results suggest a pegvisomant-sparing effect versus daily pegvisomant monotherapy.

Objective: In primary aldosteronism, adrenal venous sampling (AVS) is essential for subtype differentiation as it evaluates aldosterone secretion from both adrenals. Selectivity of adrenal sampling is assessed by the ratio of cortisol concentrations in adrenal venous blood and inferior vena cava blood (C(adrenal)/C(ivc)). Since the criteria for selective adrenal sampling differ among the reported literature, we performed a study to evaluate the influence of different selectivity criteria on AVS results., Design and Methods: Reports of AVS were screened retrospectively. All AVS were performed with cosyntrophin infusion. Reports containing samples with C(adrenal)/C(ivc)>or=10 taken from both adrenals and at least one other adrenal sample characterised by C(adrenal)/C(ivc)>or=1.1 were enrolled. For each individual, we chose reference samples that were defined by the highest C(adrenal)/C(ivc) achieved from each adrenal. The significance of the remaining samples with C(adrenal)/C(ivc)>or=1.1 was analysed in regard to their respective reference samples. We assessed the impact of analysed samples on identification of lateralisation of aldosterone secretion that is crucial for decisions concerning adrenalectomy., Results: AVS reports of 87 patients were enrolled. A total of 225 adrenal samples were analysed and divided into five groups according to C(adrenal)/C(ivc):1.1-1.99, 2-2.99, 3-4.99, 5-9.99 and >or=10. By comparing reference with analysed samples, a concordant assessment with respect to lateralisation of aldosterone secretion was observed in 39, 52, 72, 85 and 94% of the respective groups of analysed samples., Conclusion: AVS provides consistent information when adrenal samples with high cortisol concentrations are used.