Phase equilibria in the In-Pd-Sn system were investigated by a combination of key experiments and thermodynamic modeling. Partial isothermal sections at 500 °C and 800 °C of the In-Pd-Sn system for ...Pd contents above 66 at.% have been plotted experimentally using scanning electron microscopy with energy-dispersive X-ray spectroscopy (SEM/EDX) and X-ray diffraction (XRD). The solubility of the third component in binary compounds InPd
and Pd
Sn was determined. The new ternary compound τ
was found in Pd contents ranging from 20 to 25 at.% and at Sn contents varying from 5 to approximately 17 at.% Sn. This compound crystallizes in an Al
Ti-type tetragonal structure. Isostructural InPd
and Pd
Sn phases from the In-Pd and Pd-Sn binary compositions form a continuous phase field in the ternary system at both temperatures. The temperatures of the solidus, liquidus, and phase transitions of the alloys along the Pd-In50Sn50 line were measured using DTA/DSC. Thermodynamic calculation of the In-Pd-Sn ternary system is performed using the CALPHAD method using the Thermo-Calc
software. The thermodynamic properties of the disordered fcc and liquid phases were described by the Redlich-Kister-Muggianu model. To describe intermetallic phases, namely, InPd
, Pd
Sn, τ
and Pd
(In
Sn
), a two-sublattice models was used. Thermodynamic description of the In-Pd-Sn system obtained in this study is in good agreement both with our results and the published experimental data.
Abstract
Context
Autoimmune polyendocrine syndrome type 1 (APS-1) is a rare monogenic autoimmune disease caused by mutations in the autoimmune regulator (AIRE) gene and characterized by chronic ...mucocutaneous candidiasis, hypoparathyroidism, and primary adrenal insufficiency. Comprehensive characterizations of large patient cohorts are rare.
Objective
To perform an extensive clinical, immunological, and genetic characterization of a large nationwide Russian APS-1 cohort.
Subjects and Methods
Clinical components were mapped by systematic investigations, sera were screened for autoantibodies associated with APS-1, and AIRE mutations were characterized by Sanger sequencing.
Results
We identified 112 patients with APS-1, which is, to the best of our knowledge, the largest cohort described to date. Careful phenotyping revealed several additional and uncommon phenotypes such as cerebellar ataxia with pseudotumor, ptosis, and retinitis pigmentosa. Neutralizing autoantibodies to interferon-ω were found in all patients except for one. The major Finnish mutation c.769C>T (p.R257*) was the most frequent and was present in 72% of the alleles. Altogether, 19 different mutations were found, of which 9 were unknown: c.38T>C (p.L13P), c.173C>T (p.A58V), c.280C>T (p.Q94*), c.554C>G (p.S185*), c.661A>T (p.K221*), c.821del (p.Gly274Afs*104), c.1195G>C (p.A399P), c.1302C>A (p.C434*), and c.1497del (p.A500Pfs*21).
Conclusions
The spectrum of phenotypes and AIRE mutation in APS-1 has been expanded. The Finnish major mutation is the most common mutation in Russia and is almost as common as in Finland. Assay of interferon antibodies is a robust screening tool for APS-1.
Studying several typings of a Russian APS-1 cohort, we found wide clinical variation and what to our knowledge were novel components and nine novel mutations in AIRE, p.R257* being the most common.
Insulinomas are very rare in childhood with sparse knowledge on the clinical aspects and the presence of Multiple Endocrine Neoplasia type 1 (MEN1).
We conducted a retrospective review of patients ...diagnosed with insulinoma between 1995 and 2021, presenting to one referral centre in Russia. Clinical, biochemical, genetic, imaging and histological data were collected. In addition, follow-up and family data were obtained.
A total of twenty-two children aged 5 to 16 years were identified. The median (range) gap between the first hypoglycaemia symptoms and diagnosis was 10 (1-46) months. Twelve children (55%) were misdiagnosed to have epilepsy and were treated with anticonvulsants before hypoglycemia was revealed. Contrast enhanced MRI and/or CT were accurate to localize the lesion in 82% (n=18). Five patients (23%) had multiple pancreatic lesions. All children underwent surgical treatment. The median (range) diameter of removed tumors was 1.5 (0.3-6) cm. Histopathological studies confirmed the presence of insulinoma in all cases. Immunohistochemical studies revealed G2 differentiation grade in 10 out of 17 cases. Two patients were diagnosed with metastatic insulinoma. One of them had metastases at the time of insulinoma diagnosis, while the other was diagnosed with liver metastases eight years after the surgery. Eight children (36%) were found to carry
mutations, inherited n=5,
n=1, no data, n=2. Children with MEN1 had significantly higher number of pancreatic tumors compared to sporadic cases. All of them developed additional MEN1 symptoms during the following 2-13 years. In the five patients with inherited MEN1, seven family members had hitherto undiscovered MEN1 manifestations.
In this large cohort of children with rare pediatric insulinomas, MEN1 syndrome and G2 tumors were frequent, as well as hitherto undiscovered MEN1 manifestations in family members. Our data emphasize the need of genetic testing in all children with insulinoma and their relatives, even in the absence of any other features, as well as the importance of a prolonged follow-up observation.
Neuroendocrine tumors (NET) of the thymus are rare, usually aggressive, and prone to metastatic lesion. Ectopic adrenocorticotropic hormone (ACTH) secretion in thymic NET (TNEN) is associated with ...poor prognosis. Most of TNET express somatostatin receptors, it allows the use of somatostatin receptor scintigraphy (SRS) and SPECT/CT or PET/CT with 68Ga-labeled peptides for diagnosis and staging of the disease. Surgery (macroscopic-complete resection) is the mainstay treatment for TNET. Now, there are no unequivocal data in adjuvant therapy and its effectiveness. We present a case report of the pediatric patient with well differentiated atypical ACTH-producing thymic carcinoid. This localization was verified by whole body somatostatin receptor scintigraphy with 111In-DTPA-octreotide (Octreoscan). The patient proceeded with the surgical treatment followed by remission of hypercorticism without adjuvant chemotherapy. Tumor recurrence with redevelopment of ACTH-ectopic syndrome was detected after 67 months of observation.
Autoimmune polyglandular syndrome type 1 (APS-1) (OMIM 240300) is a rare autosomal recessive disorder associated with three major manifestations: chronic mucocutaneous candidiasis, ...hypoparathyroidism, and adrenal insufficiency. There are, however, multiple minor components of APS-1 that induce significant phenotype variability. Subsequently, the diagnosis of APS-1 during early stages is often challenging.
We aimed to provide clinical and mutational data for a large number of APS-1 patients in the Russian population.
We analyzed clinical variations and component prevalence in APS-1 patients. DNA screening for autoimmune regulator (AIRE) gene mutations was performed in established APS-1 patients and in patients with the single components of chronic mucocutaneous candidiasis, hypoparathyroidism, adrenal insufficiency, or alopecia.
We identified 46 patients from 42 families with APS-1. Eighteen different components were present in the patients, including very rare conditions - bone dysplasia and retinitis pigmentosa. We identified 10 different mutations, 3 of which were novel (M1T, E298K, c1053_1060del). The common Finnish mutation, R257X, was the most frequent in our population, present in 64/92 (70%) of the alleles.
We found that the R257X AIRE mutation is common in Russian APS-1 patients. The majority of children with hypoparathyroidism and chronic mucocutaneous candidiasis were carriers of the AIRE mutations.
A 26-year-old female with the classic major and minor components of autoimmune polyglandular syndrome type 1 was diagnosed as having pure red cell aplasia. Treatment with 1.5 g/d mycofenolate mofetil ...for 3 months failed to restore erythroid production. Treatment with cyclosporine A produced a good partial response but led to renal toxicity and was therefore substituted with cyclophosphamide, which had a good partial effect and lasted for 18 months. The relapse of anemia was not observed during the 6-month follow-up period after the cessation of treatment.
Background:
Hypothalamic obesity often develops after surgical treatment of craniopharyngioma and is characterized by rapid weight gain, high frequency of metabolic disorders, body composition ...specificity and resistance to standard lifestyle modification approaches and medication therapy of obesity. Recent studies show that one of the mechanisms, explaining weight gain in these children is decrease in resting energy expenditure (REE).
Aims:
To compare REE, body composition parameters, and the frequency of metabolic disorders in children with hypothalamic and simple obesity.
Materials and methods
: The study included 60 obese children aged 7 to 17 years, divided into two groups. The study group included 20 children with hypothalamic obesity, developed after craniopharyngioma treatment. The control group consisted of 40 children with simple obesity. Body composition, REE, and metabolic disorders were associated in all children.
Results:
Children with hypothalamic obesity showed a significant decrease of resting energy expenditure. The average decrease in REE was 13.1%, but in single patients it reached 33.4%. The percentage of fat mass in hypothalamic and simple obesity does not differ significantly (39.7% 36.2; 42.6 vs 38.8 % 35.9; 43.2; p=0.69). Screening for metabolic disorders revealed a high prevalence of metabolic disorders in hypothalamic obesity: impaired glucose tolerance - in 10%; dyslipidemia - 55%, insulin resistance-50%, non-alcoholic fatty liver disease - 60 %.
Conclusions:
Children with hypothalamic obesity showed a significant decrease of resting energy expenditure. When planning a diet in this group of patients it is preferable to use indirect calorimetry. Hypothalamic obesity even at an early age is associated with a high frequency of metabolic disturbance. Hypothalamic obesity in children is not associated with more pronounced hyperinsulinemia and insulin resistance compared to the simple obesity.
Patients with biallelic loss-of-function variants of AIRE suffer from autoimmune polyendocrine syndrome type-1 (APS-1) and produce a broad range of autoantibodies (auto-Abs), including circulating ...auto-Abs neutralizing most type I interferons (IFNs). These auto-Abs were recently reported to account for at least 10% of cases of life-threatening COVID-19 pneumonia in the general population. We report 22 APS-1 patients from 21 kindreds in seven countries, aged between 8 and 48 yr and infected with SARS-CoV-2 since February 2020. The 21 patients tested had auto-Abs neutralizing IFN-α subtypes and/or IFN-ω; one had anti-IFN-β and another anti-IFN-ε, but none had anti-IFN-κ. Strikingly, 19 patients (86%) were hospitalized for COVID-19 pneumonia, including 15 (68%) admitted to an intensive care unit, 11 (50%) who required mechanical ventilation, and four (18%) who died. Ambulatory disease in three patients (14%) was possibly accounted for by prior or early specific interventions. Preexisting auto-Abs neutralizing type I IFNs in APS-1 patients confer a very high risk of life-threatening COVID-19 pneumonia at any age.
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