Prediction of the transsphenoidal endoscopic adenomectomy results in patients with cushing’s disease

Introduction. Transsphenoidal adenomectomy (TSA) is the method of choice in the treatment of Cushing’s disease (CD), but remission of hypercorticism cannot be achieved in all patients. The search for predictors of CD remission after TSA remains to be an important challenge in the endocrinology today.Aim. To study the preoperative and postoperative data of patients with CD to identify the predictors of hypercorticism remission after TSA.Materials and methods. 101 patients with confirmed CD after TSA were included. One year after operation all patients were examined for the presence of hypercorticism remission and divided into two groups: with CD remission and its absence. In both groups’ preoperative pituitary magnetic resonance imaging (MRI) data, the results of preoperative high dose dexamethasone suppression test (HDDST) and the results of serum cortisol collected in the morning 2–3 days after surgery were compared.Results. One year after TSA, CD remission was confirmed in 63 patients (62.4%), whereas in 38 patients (37.6%) hypercortisolism persisted. Favorable predictors of CD remission were: the adenoma size > 3 mm without the invasive growth according to pituitary MRI (specificity 82.4%, sensitivity 82.8%), serum cortisol suppression ≥ 74% in preoperative HDDST (specificity 81.5%, sensitivity 86.3%), morning serum cortisol level in 2–3 days after surgery ≤ 388 nmol/l (specificity 79.3%, sensitivity 97.4%).Conclusions. Pituitary MRI data, the results of preoperative HDDST and morning serum cortisol in the 2–3 days after surgery can be used as predictors of CD remission

Фармакотерапия инсомнии в детском возрасте

Insomnia is the most common form of sleep disturbance in childhood. Sleep disorders and a decrease in its duration and quality lead to the development of cognitive disorders, change emotional and behavioral functions of the developing organism, and negatively affect medical and psychological aspects that require medical correction. The article provides an overview of current literature data on pharmacological approaches to insomnia therapy in childhood. The general principles of treatment and the use of various pharmacological groups of drugs are discussed. It is shown that pharmacotherapy of childhood insomnia should be carried out based on knowledge about the age characteristics of patients, efficacy, safety, analysis of pharmacodynamic and pharmacokinetic parameters of the drugs used. Drug therapy should be combined with cognitive behavioral techniques, including adherence to sleep patterns and hygiene.Инсомния является наиболее распространенной формой нарушения сна в детском возрасте. Дисфункции сна, уменьшение его продолжительности и качества приводят к развитию когнитивных нарушений, изменяют эмоционально-поведенческие функции развивающегося организма, негативно влияют на медико-психологические аспекты, которые требуют медикаментозной коррекции. В статье представлен обзор современных литературных данных о фармакологических подходах к терапии инсомнии в детском возрасте. Рассматриваются общие принципы лечения и применение различных фармакологических групп препаратов. Показано, что фармакотерапия инсомнии в детском возрасте должна основываться на знаниях о возрастных особенностях пациентов, а также на анализе эффективности, безопасности, фармакодинамических и фармакокинетических параметров применяемых препаратов. Медикаментозную терапию необходимо сочетать с когнитивно-поведенческими методиками, включая соблюдение режима сна и гигиены

Влияние фазового состава и локальной кристаллической структуры на транспортные свойства твердых растворов ZrO2—Y2O3 и ZrO2—Gd2O3

Abstract. The results of investigation of crystal structure, ion conductivity and local structure of solid solutions (ZrO2)1−x(Gd2O3)x and (ZrO2)1−x(Y2O3)x (x = 0.04, 0.08, 0.10, 0.12, 0.14). The crystals were grown by directional crystallization of the melt in a cold container. The phase composition of the crystals was studied by X−ray diffractometry and transmission electron microscopy. Transport characteristics were studied by impedance spectroscopy in the temperature range 400—900 °C. The local crystal structure was studied by optical spectroscopy. Eu3+ ions were used as a spectroscopic probe. The results of the study of the local structure of solid solutions of ZrO2—Y2O3 and ZrO2—Gd2O3 systems revealed the peculiarities of the formation of optical centers, which reflect the nature of the localization of oxygen vacancies in the crystal lattice depending on the stabilizing oxide concentration. It is established that the local crystal environment of Eu3+ Ions in solid solutions (ZrO2)1−x(Y2O3)x and (ZrO2)1−x(Gd2O3)x is determined by the stabilizing oxide concentration and practically does not depend on the type of stabilizing oxide (Y2O3 or Gd2O3). The maximum conductivity at 900 °C was observed in crystals containing 10 mol.% Gd2O3 and 8 mol.% Y2O3. These compositions correspond to the t′′−phase and are close to the boundary between the regions of the cubic and tetragonal phases. It was found that in the system ZrO2—Y2O3 stabilization of the highly symmetric phase occurs at a lower stabilizing oxide concentration than in the system ZrO2—Gd2O3. Analysis of the data obtained allows us to conclude that in this range of compositions the main influence on the concentration dependence of the ion conductivity has a phase composition, rather than the nature of the localization of oxygen vacancies in the crystal lattice.Аннотация. Приведены результаты исследования кристаллической структуры, ионной проводимости и локальной структуры твердых растворов (ZrO2)1−х(Gd2O3)х и (ZrO2)1−х(Y2O3)х при (x = 0,04, 0,08, 0,10, 0,12, 0,14). Кристаллы выращивали методом направленной кристаллизации расплава в холодном контейнере. Исследования фазового состава кристаллов проводили методом рентгеновской дифрактометрии и просвечивающей электронной микроскопии. Транспортные характеристики изучали методом импедансной спектроскопии в температурном диапазоне 400—900 °С. Исследование локальной структуры кристаллов выполняли методом оптической спектроскопии. В качестве спектроскопического зонда использовали ионы Eu3+. В результате исследования локальной структуры твердых растворов систем ZrO2—Y2O3 и ZrO2—Gd2O3 выявлены особенности формирования оптических центров, которые отражают характер локализации кислородных вакансий в кристаллической решетке в зависимости от концентрации стабилизирующего оксида. Установлено, что локальное кристаллическое окружение ионов Eu3+ в твердых растворах (ZrO2)1−х(Y2O3)х и (ZrO2)1−х(Gd2O3)х определяется концентрацией стабилизирующего оксида и практически не зависит в рассмотренном случае от вида стабилизирующего оксида (Y2O3 или Gd2O3). Максимальная проводимость при температуре 900 °С выявлена в кристаллах, содержащих 10 % (мол.) Gd2O3 и 8 % (мол.) Y2O3. Эти составы соответствуют t′′−фазе и близки к границе между областями кубической и тетрагональной фаз. Установлено, что в системе ZrO2—Y2O3 стабилизация высокосимметричной фазы происходит при меньшей концентрации стабилизирующего оксида, чем в системе ZrO2—Gd2O3. Анализ полученных данных позволяет сделать вывод о том, что в этом диапазоне составов основное влияние на концентрационную зависимость ионной проводимости оказывает фазовый состав, а не характер локализации кислородных вакансий в кристаллической решетке

Prognosis criteria for remission of hypercorticism after transsphenoidal endoscopic adenomectomy in patients with Cushing’s disease

The aim of the study. To assess the role of early postoperative examination in the prognosis of cd remission 1 year after TSS.Patients and methods. 101 Patients (12 men, 89 women, mean age 41,2 years (15-72) with confirmed cd were included. Midnight and morning serum cortisol and plasma ACTH, late night salivary cortisol, 24-h urinary free cortisol (ufc) excretion were performed at the days 2-3 and 12-14 after the TSS. Hypercortisolism remission status was estimated one year after surgery. The optimal threshold values of ACTH and cortisol parameters at 2-3 and 12-14 days after surgery to prediction of cd remission after TSS were calculated by roc-analysis.Results. One year after surgery cd remission was confirmed in 63 patients, whereas in 38 patients hypercortisolism persisted. Postoperative parameters of cortisol and ACTH secretion had comparable high specificity and sensitivity at 2-3 and 12-14 days after surgery for prediction cd remission.Conclusion. According to our data, morning serum cortisol ≤388 nmol/l and plasma ACTH ≤20 pg/ml at 2-3 d after TSS may be used as a prognostic criterion for cd remission 1 year after surgery with sensitivity and specificity 94,9%, 75,9% and 83,3%, 95,8%, respectively

A Comprehensive Approach to Predicting the Outcomes of Transsphenoidal Endoscopic Adenomectomy in Patients with Cushing’s Disease

Persistent and recurrent hypercortisolism after transsphenoidal endoscopic surgery (TSS) is considered to be an urgent issue prompting the search for Cushing’s disease (CD) remission predictors. The goal was to find a combination of predictors that can forecast the remission of CD after TSS. A total of 101 patients with CD who had undergone TSS were included. One year after surgery, CD remission status was evaluated. Preoperative pituitary magnetic resonance imaging (MRI) data, preoperative results of a high-dose dexamethasone suppression test (HDDST) and morning serum cortisol level collected 24 h after TSS (24 h MSeC) were compared in patients with and without remission of hypercortisolism. Remission one year after TSS was confirmed in 63 patients. CD remission predictors one year after TSS were: adenoma size ≥ 3 mm in the absence of invasive growth and the suppression of serum cortisol ≥ 74% in the HDDST, 24 h MSeC ≤ 388 nmol/L. A total of 38 patients had three favorable values of detected predictors; all of them had CD remission one year after TSS. With long-term follow-up, 36 of them remained in remission. Patients who had no one favorable predictor had no remission of hypercortisolism one year after TSS. Our data confirmed the prospects of using a combination of selected predictors to forecast CD remission after TSS

PATHOGENETIC MECHANISMS OF EPITHELIALIZATION AND FORMATION OF PERSISTENT ULCERS OF THE GRAFT IN PATIENTS WITH DESTRUCTIVE CORNEAL PROCESSES AFTER PENETRATING KERATOPLASTY

Keratoplasty in patients with recurrent destructive processes in the cornea nowadays remains one of the most serious problems in ophthalmic surgery.Purpose. The analysis of results of penetrating keratoplasty (PK) in patients with destructive processes of the cornea or the corneal graft depending on the initial level of GDNF and the activity of the MAP kinase cascade of the signaling pathways.Material  and  methods.  The  analysis  of  the  results  of  PK  was performed in 23 patients (34 eyes) with acute destructive processes of cornea or the corneal graft in different etiologies. The follow-up period was from 6 months to 2 years. The analysis of the results of treatment was carried out depending on the condition of the corneal graft at various times after PK.The  immunohistochemical  examination  of  the  biological  material (corneal disks of the recipient) was performed using antibodies to GDNF, phospho-ERK1 / 2, phospho-JNK1 / 2, Ki67, GAP43, Bcl2 and Bax.Results.  The  time  of  epithelialization  of  the  graft  after  PK  in destructive processes of the cornea was increased in 79% of cases. When the epithelialization of the corneal graft was completed more than 6 and 10 days after PK in the postoperative period persistent erosions of the graft (PEG) with ulceration were formed in 22% and 89% of cases, respectively.The intensity of immunohistochemical reactions with antibodies to GDNF, phospho-ERK1 / 2, phospho-JNK1 / 2 in corneal disks at the epithelialization time of up to 5, 10 days and more eythan 10 days after PK was reduced from moderately positive to weakly positive and negative, respectively.When the time of epithelialization was completed in 6-10 days and there was not PECG, the intensity of reactions with antibodies to GDNF remains moderately positive, phospho-ERK1 / 2, phospho-JNK1 / 2 was lightly positive; when there was PEG the intensity of all reactions was weakly positive.Conclusion. The severity of the destructive pathological process in the cornea and postoperative complications after PK in patients with destructive corneal processes depend on the degree of GDNF deficiency, the decrease in the activity of the MAP kinase cascade of signaling pathways; the density of nerve plexuses in the own corneal tissue or corneal graft, and the activity of apoptosis processes