Mathematical model for preoperative differential diagnosis for the parathyroid neoplasms.

Background and objective: Preoperative diagnosis of parathyroid carcinoma (PC) is critical for the determination of the scope of surgical intervention. Nowadays, specific diagnostic markers for differentiation of PC and benign tumors are unknown, and less than half of patients with PC undergo necessary en bloc surgery. The aim of this study was to develop the instrument for preoperative diagnosis of PC. Methods: A multi-center retrospective study included 242 patients with primary hyperparathyroidism: 50 patients with PC, 30 with аtypical adenoma (AA), and 162 with adenoma of the parathyroid glands. Results: Patients with PC and AA had higher levels of PTH, ionized and albumin-corrected calcium, ALP, volume and the largest diameter of neoplasm, and the higher frequency of GFR decrease less than 60 ml/min/1.73 m2 compared to patients with adenoma. The frequency of low-energy fractures was higher in the carcinoma group versus the adenoma group (32% vs 8%). Heterogeneous structure and indefinite contour of glands detected by US were more typical for PC than for AA and adenomas. The mathematical model was developed using CatBoost gradient boosting algorithm for the noninvasive preoperative differential diagnosis of PC, AA, and adenoma. Conclusions: Model can predict adenoma with PPV 100% and PC with PPV 81-92%. Using model clinicians could plan extended en bloc resection for PC and selective parathyroidectomy for adenoma. If AA is predicted, he has to make a decision on the choice of the necessary volume of PTE based on his experience, because AA are the zone of uncertainty.

[The rules for predicting remission in patients with Cushing disease after successful endoscopic transnasal adenomectomy].

BACKGROUND: The recurrence rate after successful transnasal adenomectomy in Cushing’s disease (CD) can reach 47%. We have previously shown that patients with ACTH levels less than 7 pg/ml recurred over 3 years 4.5 times less often than patients with higher levels of ACTH, patients with cortisol levels below 123 nmol/l — in 3.4 times less than at higher values of this hormone, however, these indicators are dissociated in 41% of cases, so it is not possible use them for prediction separately. AIM: To develop a method for managing patients after successful transnasal adenomectomy depending on prognosis. METHODS: A monocenter retrospective comparative study included 349 patients (52 men, 297 women) with a confirmed diagnosis of CD, who underwent effective endoscopic transsphenoidal adenomectomy in 2007−2014. Various combinations of postoperative morning levels of ACTH and cortisol were analyzed. RESULTS: Based on the developed forecasting methods and their best characteristics, the following rules were formulated. If postoperative morning ACTH is less than 7 pg/ml and/or postoperative morning cortisol is less than 123 nmol/l, then the patient will remain in remission for 1 year with probability of 99% (95% CI 97%–100%) and for 3 years with probability of 86% (95% CI 80%–91%). CONCLUSION: The rules for predicting remission for 1 and 3 years for patients after neurosurgical treatment for CD are proposed. These rules are based on combinations of ACTH and cortisol levels.

Prediction of recurrence and remission within 3 years in patients with Cushing disease after successful transnasal adenomectomy.

BACKGROUND: Some laboratory and clinical features are associated with a probability of recurrence after transnasal adenomectomy for Cushing disease (CD). However, there is no consensus on a set of predictors. Rules for prediction of recurrence were not proposed earlier. AIM: To develop prediction model of recurrence/remission after successful neurosurgical treatment for CD. METHODS: Retrospective single-site comparative study included 349 patients (52 men and 297 women) with a verified diagnosis of CD who underwent effective endoscopic transsphenoidal adenomectomy between 2007 and 2014. Clinical and laboratory parameters were evaluated. Laboratory tests were performed using immunochemiluminescent method. Time-to-event analysis and ROC-analysis were applied. Multivariate models were developed using logistic regression and artificial neural network (ANN). RESULTS: Postoperative cortisol and ACTH levels and their combinations cannot be used for prediction of recurrence. ANN for prediction of recurrence within 3 years after successful surgery was developed. Input variables are age, duration of the disease, MRI data on adenoma, morning postoperative levels of ACTH and cortisol, output variable is binary (recurrence/remission). Predictive value for remission is 93%, 95% CI [89%; 96%], and predictive value for recurrence is 85%, 95% CI [71%; 94%]. Web-calculator based on the model is developed and free for use. CONCLUSION: Effective method for prediction of recurrence and long-term remission within 3 years after successful endoscopic transsphenoidal adenomectomy is proposed.

TOR1A polymorphisms in a Russian cohort with primary focal/segmental dystonia.

PURPOSE/AIM OF THE STUDY: To analyze contribution of rs3842225 and rs1182 single nucleotide polymorphisms (SNP) in TOR1A gene, the causative gene for the DYT1 form of hereditary early-onset generalized dystonia, to the development of focal and segmental dystonia in Russian patients. MATERIALS AND METHODS: We analyzed associations between rs3842225 and rs1182 polymorphisms in TOR1A and focal/segmental dystonia in 254 patients from Russian population, including 218 Slavic patients and 36 patients of mixed ethnic background. RESULTS: Stratification of patients based on age at the disease onset (≤ 30 years and > 30 years) showed statistically significant prevalence of the del-allele at the rs3842225 locus in Slavic patients with earlier age of onset of dystonia (36.96% vs. 21.39% in patients with late age of onset, p = 0.002) and an overrepresentation of the T-allele at the rs1182 locus (36.96% vs. 21.69%, p = 0.003). In Slavs, we also observed an overrepresentation of the homozygous genotypes, T/T (general sample of dystonia, 9.17% and focal dystonia, 10.28%) or G/G (general sample of dystonia, 60.55% and focal dystonia, 58.86%), compared to controls (T/T, 4.27% and G/G, 55.49%). In non-Slavic patients, we revealed neither significant associations, nor statistical tendencies regarding any of the clinical features. CONCLUSIONS: Our data in an Eastern Slavic (Russian) population correspond well to results of other studies from different countries and confirm that certain TOR1A genotypes may be regarded as factors predisposing to focal and segmental dystonia.

Cytokine gene expression in the skin and peripheral blood of atopic dermatitis patients and healthy individuals.

OBJECTIVES: Atopic dermatitis (AD) is an increasingly common, chronic, relapsing, inflammatory skin disease characterized by impaired epidermal barrier function and cutaneous inflammation. The prevalence of AD has steadily increased during the past few decades. The aim of this study was to comparatively investigate cytokine gene expression in the skin and peripheral blood of atopic dermatitis patients and healthy individuals. RESULTS: In the skin of patients with AD, a significant increase of the level of gene expression was observed for interleukin (IL)-2r (p < 0.0023), IL-5 (p = 0.002), IL-6 (p < 0.0023), IL-8 (p = 0.01), IL-12B (p < 0.0023), IL-10 (p < 0.0023), IL-23 (p = 0.002), IL-29 (p < 0.0023), and transforming growth factor beta (tGFbeta) (p < 0.0023) as compared to healthy individuals. In contrast, no difference between AD patients and healthy donors was detected with respect to cytokine gene expression in the peripheral blood. METHODS: Samples of skin and peripheral blood from 48 severe AD patients (SCORAD = 78.5 [57;89], IGA = 4.2 [3,9;4,7]) at the age of 17 to 45 years and 20 healthy donors aged from 19 to 32 years were analyzed for gene expression of cytokines using real-time reverse transcription polymerase chain reaction (RT-PCR). CONCLUSIONS: Activity of markers of chronic inflammation and Th1 immune response in severe AD, namely IL-2r, IL-8, IL-12B, IL-23, IL-29 and TGFbeta, as well as activity of anti-inflammatory IL-5 were predominant in the skin but not in the blood of AD patients.

Logical and Statistical Approach for the Analysis of Immunological Parameters in Patients with Wilson's Disease.

The immunological tests were performed for blood samples from 30 patients with Wilson's disease and 37 healthy patients. The processed data included conventional statistical analysis and computer programs, consisting of new pattern recognition methods - method of statistically weighted syndromes and that of detecting the informative conjunctions. In Wilson's disease group the significant alterations of parameters were determined: the decrease of T lymphocytes amount and CD4/CD8 ratio; the increase of circulating immune complexes and IgM levels; and B lymphocytes and NK amount. The methods of pattern recognition allowed to generate the rule to discriminate the cases from Wilson's disease and control groups with 87% effectiveness. The most frequently observed combinations of the altered parameters' values were revealed, and then the subgroups of Wilson's disease cases were considered. They were characterised by activation of the humoral immunity and/or depression of the cellular one. The heterogeneity of the immunity modifications may be the reflection of both genetic polymorphism and stages of the immunity violation. Some essential features of the immune status of patients with Wilson's disease are discussed.