👤 Tomasz Marek

Researchers reported on the pathogenic role of hypercholesterolemia in thyroid orbitopathy (TO) and the use of statins in its prevention and treatment. To confirm these observations, we conducted a prospective study of patients with Graves' and Basedow's disease (GBD) to evaluate the relationship between the presence of TO and levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglyceride (TG), and apolipoproteins A1 and B (Apo A1, Apo B), along with the impact of immunosuppressive treatment on the lipid profile. Forty-seven patients with GBD diagnosed within the past 12 months were eligible for the study. In the GBD group, 31 patients were diagnosed with active TO and qualified for immunosuppressive treatment, while 16 patients did not have TO. TC, TG, HDL-C, and LDL-C levels were measured in serum using enzymatic methods, and Apo A-1 and Apo B levels were determined by immunoturbidimetric methods. The mean TC concentration in patients with active TO who qualified for immunosuppressive treatment was 207.7 ± 42.7 mg/dL, significantly higher than the values in GBD patients without TO symptoms (191.5 ± 47.8 mg/dL). After completing immunosuppressive treatment, the mean TC concentration increased to 214.3 ± 49.8 mg/dL, remaining significantly higher than before treatment. The mean LDL-C concentration in patients with active TO was 131.6 ± 40.4 mg/dL and was higher, though not significantly, compared to the GBD group without TO symptoms (122.6 ± 49.0 mg/dL). After immunosuppressive treatment, the mean LDL-C levels increased to 142.1 ± 54.5 mg/dL and were also significantly higher than before treatment. Additionally, the mean Apo B concentration in patients with active TO was significantly higher than in patients without TO. After immunosuppressive treatment, the mean Apo B concentration increased and remained significantly higher than before treatment. There was no significant difference in HDL-C, Apo A1, and TG concentrations between the groups with and without TO, nor their levels after immunosuppressive treatment. The use of statins as adjunctive therapy in GBD patients with active TO qualified for immunosuppressive treatment is reasonable due to the increase in TC, LDL-C, and Apo B levels during treatment, as well as for their pleiotropic effects, including their anti-inflammatory effects. Show less

The Rare Gynecologic Sarcoma study involved 23 institutions from 10 countries focusing on myxoid leiomyosarcoma and non-smooth muscle uterine sarcomas. Here, we present the main results of the study, including the comparison between the original and final diagnosis, the frequency and type of molecular aberrations, and the clinicopathologic outcomes. A total of 379 cases were included, with available results for next-generation sequencing (NGS) RNA in 338 of 379 cases and NGS DNA in 335 of 379 cases. According to the original diagnoses, the study included 204 cases of low-grade endometrial stromal sarcoma (LG-ESS), 75 cases of high-grade endometrial stromal sarcoma (HG-ESS), 74 cases of undifferentiated uterine sarcoma (UUS), 17 cases of myxoid leiomyosarcoma, and 9 cases of unclassifiable sarcoma. The results of our second reading showed that 29% (110/379) of all the tumors had been originally misdiagnosed. After the reclassification, the final diagnoses were 147 cases of LG-ESS, 69 cases of HG-ESS, 58 cases of UUS, 3 cases of LG-ESS with high-grade transformation, 7 cases of perivascular epithelioid cell tumor, 9 cases of uterine tumor resembling ovarian sex cord tumor, 8 cases of tumors with a KAT6B/A::KANSL1 fusion, 2 cases of tumors with an NTRK fusion, 29 cases of undifferentiated carcinoma, and 47 tumors with smooth muscle differentiation. The molecular testing showed that LG-ESS harbor a recurrent fusion in 75.9% and HG-ESS in 43.7% of cases. The results of our study emphasize the diagnostic, prognostic, and predictive significance of molecular testing in mesenchymal uterine tumors. Show less

Gastric antral vascular ectasia (GAVE) is a rare vasculopathy that associates several diseases, most commonly liver cirrhosis. It usually presents as an occult gastrointestinal bleeding leading to profound iron deficiency anemia. We hypothesized that GAVE is local mucosal pathology dependent on genetic mechanisms, and the purpose of the study was to characterize miRNAs expression in gastric tissue of patients with cirrhosis and GAVE. Thirteen patients with GAVE and cirrhosis and 35 healthy subjects were recruited. Microarray analysis and comparative microRNA study was done by quantitative polymerase chain reaction (qPCR). The microarray scores were grouped with use of the hierarchical clusterization analysis and miRNA target prediction was done with TargetScan 6.2 algorithm and Gene Ontology analysis (DIANA-miRPath). Concentration of miR-3677 in GAVE-affected mucosa was higher by 72% in comparison with GAVE-free mucosa of patients with cirrhosis (33.7 vs. 35.6 PCR cycles; p < .001) and by 45% in comparison with normal mucosa (33.7 vs. 34.9 PCR cycles; p < .05). According to Gene Ontology analysis miR-3677 was related to angiopoietin-like protein 4 (ANGPTL4) gene. GAVE in liver cirrhosis is associated with increased expression of miR-3667 that may be linked with ANGPTL4 gene. Show less

Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and ∼ 2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 × 10⁻⁸), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation. Show less