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    RNA-Sequencing Gene Expression Profiling of Orbital Adipose-Derived Stem Cell Population Implicate HOX Genes and WNT Signaling Dysregulation in the Pathogenesis of Thyroid-Associated Orbitopathy. Tao Wensi,Ayala-Haedo Juan A,Field Matthew G,Pelaez Daniel,Wester Sara T Investigative ophthalmology & visual science Purpose:The purpose of this study was to characterize the intrinsic cellular properties of orbital adipose-derived stem cells (OASC) from patients with thyroid-associated orbitopathy (TAO) and healthy controls. Methods:Orbital adipose tissue was collected from a total of nine patients: four controls and five patients with TAO. Isolated OASC were characterized with mesenchymal stem cell-specific markers. Orbital adipose-derived stem cells were differentiated into three lineages: chondrocytes, osteocytes, and adipocytes. Reverse transcription PCR of genes involved in the adipogenesis, chondrogenesis, and osteogenesis pathways were selected to assay the differentiation capacities. RNA sequencing analysis (RNA-seq) was performed and results were compared to assess for differences in gene expression between TAO and controls. Selected top-ranked results were confirmed by RT-PCR. Results:Orbital adipose-derived stem cells isolated from orbital fat expressed high levels of mesenchymal stem cell markers, but low levels of the pluripotent stem cell markers. Orbital adipose-derived stem cells isolated from TAO patients exhibited an increase in adipogenesis, and a decrease in chondrogenesis and osteogenesis. RNA-seq disclosed 54 differentially expressed genes. In TAO OASC, expression of early neural crest progenitor marker (WNT signaling, ZIC genes and MSX2) was lost. Meanwhile, ectopic expression of HOXB2 and HOXB3 was found in the OASC from TAO. Conclusion:Our results suggest that there are intrinsic genetic and cellular differences in the OASC populations derived from TAO patients. The upregulation in adipogenesis in OASC of TAO may be is consistent with the clinical phenotype. Downregulation of early neural crest markers and ectopic expression of HOXB2 and HOXB3 in TAO OASC demonstrate dysregulation of developmental and tissue patterning pathways. 10.1167/iovs.17-22237
    Simple and practical parameters for differentiation between destruction-induced thyrotoxicosis and Graves' thyrotoxicosis. Izumi Yukiko,Hidaka Yoh,Tada Hisato,Takano Toru,Kashiwai Taku,Tatsumi Ke-ita,Ichihara Kiyoshi,Amino Nobuyuki Clinical endocrinology OBJECTIVE:Differentiation of destruction-induced thyrotoxicosis from Graves' thyrotoxicosis is important for selection of therapy. It is, however, often difficult to make this distinction without measurement of radioactive iodine uptake. We searched for simple and practical parameters that might allow differentiation between the two entities. PATIENTS:One hundred and eleven untreated patients with thyrotoxicosis (69 Graves' disease, 21 painless thyroiditis, 21 subacute thyroiditis) and 45 normal controls were examined. MEASUREMENTS:Serum levels of free T4 (FT4) and free T3 (FT3) were measured by radioimmunoassay, and anti-TSH receptor antibodies (TBII) were measured by radioreceptor assay. Peripheral leucocyte counts and the percentages of eosinophils and monocytes were measured using an automated leucocyte differential system. RESULTS:Peripheral eosinophils were significantly higher in Graves' disease (3.54 +/- 4.18%, P < 0.05) and lower in subacute thyroiditis (1.08 +/- 1.03%, P < 0.001) than in normal controls (2.26 +/- 1.33%). Peripheral monocytes were significantly higher in painless thyroiditis (6.87 +/- 2.85%, P < 0.01) than that in normal controls (4.63 +/- 2.14%). In comparison between groups, FT3 was higher with Graves' disease (20.55 +/- 10.29 pmol/l) than both painless thyroiditis (11.59 +/- 8.22 pmol/l, P < 0.001) and subacute thyroiditis (15.27 +/- 8.63 pmol/l, P < 0.05). The eosinophil to monocyte (Eo/Mo) ratio, FT3/FT4 ratio and Eo/Mo ratio multiplied by FT3 (pmol/ml) (Eo/Mo.FT3) were calculated and compared in these three disease groups. The Eo/Mo ratio, FT3/FT4 ratio and Eo/Mo.FT3 were significantly higher in patients with Graves' thyrotoxicosis (0.782 +/- 0.759, 0.399 +/- 0.089, 16.7 +/- 23.5 pmol/l, respectively) than in those with painless thyroiditis (0.259 +/- 0.157, 0.304 +/- 0.072, 2.43 +/- 1.49 pmol/l, respectively) and subacute thyroiditis (0.234 +/- 0.241, 0.335 +/- 0.057, 2.98 +/- 3.51 pmol/l, respectively). Twenty-two of 24 (91.7%) thyrotoxic patients with Eo/Mo < 0.2 had destruction-induced thyrotoxicosis (painless or subacute thyroiditis). Twenty-two of 28 (78.6%) thyrotoxic patients with FT3/FT4 < 0.3 had destruction-induced thyrotoxicosis. Thirty-six of 42 (85.7%) thyrotoxic patients with Eo/Mo.FT3 < 4.5 had destruction-induced thyrotoxicosis. The Eo/Mo ratio, FT3/FT4 ratio and Eo/Mo.FT3 were found to be similarly useful for differentiation between the two types of thyrotoxicosis. All thyrotoxic patients with TBII > or = 20% had Graves' disease and 76.4% of patients with TBII < 20% had destruction-induced thyrotoxicosis. CONCLUSION:The Eo/Mo ratio, FT3/FT4 ratio, and Eo/Mo.FT3 are simple, practical parameters and were as effective as TBII for differentiation of destruction-induced thyrotoxicosis (painless or subacute thyroiditis) from Graves' thyrotoxicosis. Eo/Mo < 0.2 and/or Eo/Mo.FT3 < 4.5 in untreated thyrotoxic patients are laboratory signals of destruction-induced thyrotoxicosis, and if these are determined, the radioactive iodine uptake test can be omitted for differential diagnosis of these two types of thyrotoxicosis.
    Neutrophil-to-lymphocyte ratio in thyroid ophthalmopathy. Celik T Bratislavske lekarske listy PURPOSE:To evaluate the neutrophil-to-lymphocyte ratio (NLR) levels to predict the severity of inflammation in thyroid ophthalmopathy (TO). METHODS:Fifty-six patients with TO and 40 healthy subjects were included in this study. TO patients were divided into two groups according to clinical activity score (CAS). Group 1 included 24 active TO patients and Group 2 included 32 inactive TO patients. The thyroid status, white blood cell (WBC), neutrophil, and lymphocyte counts were performed. NLR was calculated by dividing the neutrophil count by the lymphocyte count. RESULTS:The mean age was 53.6 ± 5.4 in active TO group, 54.2 ± 5.6 in inactive TO group, and 52.7 ± 5.2 in the control group. The WBC, neutrophil, lymphocyte and NLR levels were higher in patients with TO than in the control group (p < 0.05). A significant difference in NLR was found between the inactive and active TO groups (p < 0.05). CONCLUSION:NLR values were found to be higher in patients with TO than in controls. NLRvalues were also found higher in active TO patients than in inactive TO patients (Tab. 3, Ref. 26). 10.4149/BLL_2017_095
    Peripheral T and B lymphocytes do not correlate with Graves' orbitopathy. Ionni I,Rotondo Dottore G,Marinò M Journal of endocrinological investigation 10.1007/s40618-018-0950-9
    Evaluation of neutrophil-to-lymphocyte ratio and hematologic parameters in patients with Graves' disease. Turan E Bratislavske lekarske listy AIM:While the ratio of neutrophil-to-lymphocyte (NLR) increases with inflammation, its importance in Graves' disease is not clear. The aim of this study was to evaluate NLR, a marker of chronic inflammmation, in Graves' disease. METHODS:86 Graves' patients (37 before treatment,49 euthyroid patients after treatment) and 112 controls were enrolled. Hematologic parameters, thyroid function tests, age and gender were recorded. NLRs were calculated. Firstly, groups were composed as Graves' group (Group1) and participants without thyroid disorder as control group (Group2). Secondly, Graves' patients before treatment were considered as Group1a, euthyroid Graves' patients after antithyroid treatment were considered as Group1b. These groups were compared with each other in terms of descriptive data and hematological parameters. RESULTS:Lymphocyte, monocyte, platelet, free T3, and free T4 levels were significantly higher in Graves' group than the controls. TSH and NLR were significantly lower in Graves' group Graves' than the controls. Differences among group1a and group1b for monocyte (p = 0.013), for basophil (p= 0.002), for platelet (p = 0.029), and for NLR (p = 0.029) were statistically significant. CONCLUSION:Unlike other inflammatory diseases, in Graves' disease; hematological parameters may not give information about inflammatory state of the disease. Therefore, NLR should be evaluated with other serum inflammatory markers in Graves' disease (Tab. 2, Fig. 1, Ref. 26). 10.4149/BLL_2019_076
    Diagnosing brain tumours by routine blood tests using machine learning. Podnar Simon,Kukar Matjaž,Gunčar Gregor,Notar Mateja,Gošnjak Nina,Notar Marko Scientific reports Routine blood test results are assumed to contain much more information than is usually recognised even by the most experienced clinicians. Using routine blood tests from 15,176 neurological patients we built a machine learning predictive model for the diagnosis of brain tumours. We validated the model by retrospective analysis of 68 consecutive brain tumour and 215 control patients presenting to the neurological emergency service. Only patients with head imaging and routine blood test data were included in the validation sample. The sensitivity and specificity of the adapted tumour model in the validation group were 96% and 74%, respectively. Our data demonstrate the feasibility of brain tumour diagnosis from routine blood tests using machine learning. The reported diagnostic accuracy is comparable and possibly complementary to that of imaging studies. The presented machine learning approach opens a completely new avenue in the diagnosis of these grave neurological diseases and demonstrates the utility of valuable information obtained from routine blood tests. 10.1038/s41598-019-51147-3
    Neutrophil-to-lymphocyte ratio, monocyte-to-lymphocyte ratio, and platelet-tolymphocyte ratio in different etiological causes of thyrotoxicosis Taşkaldiran Işilay,Omma Tülay,Önder Çağatay Emir,Firat Sevde Nur,Koç Gönül,Kiliç Mustafa Kemal,Kuşkonmaz Şerife Mehlika,Çulha Cavit Turkish journal of medical sciences Background/aim:The most common causes of thyrotoxicosis include Graves’ disease (GD), toxic multinodular goiter (TMNG), toxic adenoma (TA), and subacute granulomatous thyroiditis (SAT). In our study, we aimed to see whether neutrophil‐to‐lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet‐to‐lymphocyte ratio (PLR), and mean platelet volume (MPV) may be helpful in the differential diagnosis of these diseases. Materials and methods:We retrospectively analyzed the hospital records of the Endocrinology Clinic of our hospital between 2016 and 2019. We included data from 66 GD, 37 TA, and 35 SAT patients. We compared the data with those of 35 healthy subjects as controls. Results:NLR, MLR, and PLR were found to be higher in the SAT group when compared to other groups. The post hoc analysis of comparison of NLR, MLR, and PLR in each group showed that NLR and PLR were significantly different in the SAT group whencompared to the GD, TA, and controls groups (P < 0.001, P = 0.003, and P < 0.001 for NLR respectively and P < 0.001 for PLR in all groups). MPV levels were different between groups (P = 0.007). However, the intergroup analysis (Tukey’s test) failed to show a statistically significant difference for any of the groups. In patients with SAT, PLR and NLR were significantly higher than in the GD, TA, and control groups. MLR was also higher in SAT when compared to other groups, but the difference was not statistically significant. Conclusion:High PLR and NLR may be helpful to differentiate SAT from GD and TA, the other common causes of thyrotoxicosis. 10.3906/sag-1901-116
    Neutrophil-to-Lymphocyte, Monocyte-to-Lymphocyte and Platelet-to-Lymphocyte Ratios in Relation to Clinical Parameters and Smoking Status in Patients with Graves' Orbitopathy-Novel Insight into Old Tests. Szydełko Joanna,Litwińczuk Michał,Szydełko Magdalena,Matyjaszek-Matuszek Beata Journal of clinical medicine Graves' orbitopathy (GO) is an autoimmune disease with a chronic inflammatory background. Smoking behavior is the main environmental factor responsible for the transition of this major extra thyroidal manifestation of Graves' disease (GD) from the subclinical to the overt form. Complete blood count-derived parameters are suggested to be novel inflammatory indices. The aim of this retrospective study was to investigate the association between neutrophil-to-lymphocyte (NLR), monocyte-to-lymphocyte (MLR), and platelet-to-lymphocyte ratios (PLR) with selected clinical parameters and smoking status in 406 GD patients with ( = 168) and without GO ( = 238). The control group consisted of 100 healthy individuals. The activity of GO was graded according to Clinical Activity Score. Significantly higher white blood cells (WBC), neutrophil, and NLR ( < 0.05) values were observed in GD patients with GO compared with those without GO. PLR values were significantly higher in GO patients than in the controls. WBC (6.81 ± 1.56 vs. 5.70 ± 1.23) and neutrophils (3.89 ± 1.06 vs. 3.15 ± 0.95) count was higher in active GO patients than in those with inactive GO. Positive correlation ( < 0.05) between CAS score and WBC, neutrophil and monocyte count, and NLR was found. Smoking was associated with higher WBC ( = 0.040), neutrophil ( = 0.049), PLR ( = 0.032) values. Multivariate analysis revealed that WBC, NLR may be risk factors for GO development. WBC, neutrophil, NLR and PLR values seem to be useful tools in the assessment of inflammation in GD. 10.3390/jcm9103111