Integrated approach to radiodiagnosis of follicular thyroid neoplasia: a retrospective cohort trial

Background. An evidence-based diagnostic tactics for follicular thyroid gland neoplasia is lacking to date. First-line priority are radiography diagnostic techniques, which vary in capacities and therefore must be regulated in use.Objectives. An efficacy evaluation of multiparametric ultrasound (US), sonoelastography (SEG) and radionuclide scintigraphy (RS) in diagnosis of follicular thyroid neoplasms (FTN).Methods. Preoperative examination was interpreted in 222 FTN patients (86 with follicular thyroid adenoma, FTA, and 136 with follicular thyroid cancer, FTC) with subsequent surgery. A retrospective statistical data analysis was performed for B-mode US, colour Doppler imaging (CDI), power Doppler imaging (PDI), sonoelastography and Tc-99m pertechnetate scintigraphy.Results. Novel FTN descriptive evidence has been obtained. Particularly, an FTA vs. FTC trait comparison showed no reliable US marker of a node assignment to FTA or FTC. Trials of the national-manufactured TI-RADS system showed its good diagnostic potential: FTN sensitivity 89.55, specificity 77.58 and accuracy 83.52%. A SEG picture of FTN was typically motley-colour and mosaic. Young’s modulus in FTA was 27.5 ± 7.1 kPa, a higher stiffness (62.1 ± 12.1 kPa) in FTC indicated a higher likelihood of malignancy. Scintigraphy exhibited a modest capacity for FTN diagnosis (sensitivity 86.67, specificity 48.08 and accuracy 56.72%). AUC values (0.617) indicate its limited use for differential FTN diagnosis, mainly in hyperfunctioning nodules. Our experience elaborated an original algorithm for radiographic techniques application in FTN diagnosis.Conclusion. Several radiographic methods are warranted in suspected FTN. First-line is multiparametric US B-mode imaging to detect FTN priority markers and US symptom complexes. Sonoelastography is second-line in ambiguous cases to further clarify structure (stiffness) of the thyroid nodule examined. Unlike SEG, scintigraphy assesses the functional traits of thyroid nodule and so has limited indications, an important factor to consider in FTN

EVALUATION OF VIBRIO CHOLERAE 569B INABA PROTECTIVE ANTIGENES, DERIVED ON INDUSTRIAL AND DEVELOPED BIOREACTORS AS WELL AS BY IMPROVED TECHNOLOGY

We evaluated immunochemical, physical and biochemical properties of Vibrio cholerae 569B INABA protective antigenes, derived on industrial and own-developed bioreactors as well as by technology of its concentration by tangential ultrafiltration. We detected, protease, twinase and. lysophospholipase in all samples. Also, dotimmunoanalysis showed equal concentration, of cholerogen-anatoxine and. O-antigen in all samples too. Using chromatography and. electrophoresis, we found their properties as similar. Thus, we suppose to be possible using developed bioreactor as well as technology of Vibrio cholerae 569B INABA protective antigens concentration by tangential concentration during a process of synthetic oral cholera vaccine production

MEASUREMENT OF PROCALCITONIN IN THE CEREBROSPINAL FLUID FOR DIFFERENTIAL DIAGNOSTICS IN CHILDREN WITH MENINGITIS

Background: High production of pro-inflammatory cytokines associated with procalcitonin synthesis  and  its increased  blood  levels play an important role in the pathophysiology of systemic inflammation  in generalized  bacterial  infections. Aim: To assess diagnostic  value of procalcitonin measurement as a marker of bacterial  inflammation in cerebrospinal  fluid for differential diagnostics of bacterial  and  viral meningitis. Materials and methods: Procalcitonin  levels in blood  and cerebrospinal  fluid were measured by immunoenzyme analysis in 88 children aged from 3 months to 14 years who had been admitted to the hospital. Forty five percent  (45.4%) of them had acute bacterial meningitis, 27.3%, viral meningitis and 27.3% had the meningitis-like syndrome (control group). Results:  There  was a high  procalcitonin  level in   cerebrospinal  fluid in patients with bacterial purulent meningitis  (0,14 [0.0; 0.34] ng/mL (р < 0.006), with  the  normal  range  in the  control  group  of 0.07 [0.0; 0.07] ng/mL. This parameter correlated with blood procalcitonin level (9.8 [2.05; 13.19] ng/mL)  and  severity  of  meningitis.  In  patients with viral meningitis, the procalcitonin levels were below the normal range  (0.02 [0.01; 0.07] ng/mL). Conclusion: Measurement of procalcitonin  levels in cerebrospinal  fluid could be recommended for inclusion into the differential diagnostic algorithm of meningitis of various etiologies in children

Development and Validation of Valganciclovir and its Active Metabolite Ganciclovir Determination in Human Plasma by HPLC-UV Method

Introduction. Viral infections are a serious problem that occurs during the use of immunosuppressants in preparation for organ transplantation and in the postoperative period. Cytomegalovirus (CMV) infection is one of the main causes of diseases in people with weakened immune systems. It has a direct impact on one’s body and makes it more likely to reject a transplanted organ. Antiviral drugs are used to treat and prevent this infectious disease. Valganciclovir is a prodrug whose active metabolite is ganciclovir. Valganciclovir is the drug of choice in the treatment of CMV infections. Currently, there are no researches on the matter of simultaneous determination of both valganciclovir and ganciclovir in human blood plasma by means of high-performance liquid chromatography (HPLC) with ultraviolet detection. This research delivers a thorough description of development and validation of a particular method for simultaneous determination of valganciclovir and ganciclovir in the plasma after sample preparation by the method of protein precipitation.Aim. The aim of this study is to develop method for the quantitative determination of valganciclovir and its active metabolite ganciclovir in human plasma by HPLC-UV for pharmacokinetic studies.Materials and methods. Quantitative determination of tadalafil in plasma by HPLC-UV. A sample was prepared using protein precipitation.Results and discussion. This method was validated by next validation parameters: selectivity, matrix effect, calibration curve, accuracy, precision, lower limit of quantification, carry-over and stability.Conclusion. The method of the quantitative determination of valganciclovir and its active metabolite ganciclovir in human plasma was developed and validated by HPLC-UV. The analytical range of the was 5,0–1000,0 ng/ml for valganciclovir and 100,0–10000,0 ng/ml for ganciclovir in plasma. Method could be applied to determination of valganciclovir and ganciclovir in plasma for PK and BE studies

Development and Validation of Atazanavir and Ritonavir Determination in Human Plasma by HPLC-MS Method

Introduction. HIV infection is one of the most relevant diseases from a medical, epidemiological and social point of view. Timely diagnosis, detection and control of the disease, adequate prescription of antiretroviral therapy can sufficiently reduce the viral load on the patient's body, reduce the risk of transmission of infection. Currently, combinations of various antiretroviral drugs are increasingly being prescribed as therapy. One of the most important is combination of atazanavir and ritonavir. The most important stage for the study of pharmacokinetics, studies of comparative pharmacokinetics and bioequivalence is the development of an analytical method that allows you to determine the investigated substances in human plasma. There are currently no published methods for the determination of atazanavir and ritonavir in human plasma using high performance liquid chromatography with mass selective detection using a single quadrupole mass detector. In this article presents the development and validation of a method for the determination of atazanavir and ritonavir in blood plasma after sample preparation by the method of protein precipitation.Aim. The aim of the study is to develop a method for the quantitative determination of atazanavir and ritonavir in human plasma by HPLC with mass spectrometric detection for performing the analytical part of pharmacokinetic studies.Materials and methods. Determination of atazanavir and ritonavir in human plasma by HPLC with mass spectrometric detection. A sample was prepared using protein deposition.Results and discussion. The method was validated of selectivity, matrix effect, calibration curve, accuracy, precision, limit of quantification, carry-over effect and sample stability.Conclusion. The method of the determination of atazanavir and ritonavir in human plasma was developed and validated by HPLC-MS. The analytical range of the was 50.0–10000.0 ng/mL in plasma for atazanavir and 10.0–2500.0 ng/mL in plasma for ritonavir. Method could be applied to determination of atazanavir and ritonavir in plasma for PK and BE studies

Development and Validation of Pomalidomide Determination in Human Plasma by HPLC-MS/MS Method

Introduction. B-cell malignancies of the plasma cell leads to the second most spread hematological malignancy disease, called multiple myeloma. Pomalidomide is used in case of previous multiple myeloma ineffective treatment. Pomalidomide is a thalidomide synthetic derived, approved as immunomodulatory drug by the Food and Drug Administration (FDA). Nowadays, detection of pomalidomide in blood plasma by high performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) is not spread. Moreover, the detection and the experimental setting accumulated data are varying greatly. This investigation provides development and validation of pomalidomide aiming to determine human blood plasma by HPLC-MS/MS method. The samples were processed by methanol protein precipitation.Aim. The aim of this study is to develop a method for the pomalidomide in human plasma by HPLC-MS/MS for pharmacokinetic studies.Materials and methods. Determination of pomalidomide in plasma by HPLC-MS/MS. The samples were processed by methanol protein precipitation.Results and discussion. This method was validated by next parameters: selectivity, matrix effect, calibration curve, accuracy, precision, spike recovery, lower limit of quantification, detection limit, carry-over and stability.Conclusion. The method of the determination of pomalidomide in human plasma was developed and validated by HPLC-MS/MS. The linearity in plasma sample was achieved in the concentration range of 1,00 – 500,00 ng/ml. Method could be applied to pomalidomide determination in plasma for PK and BE studies

THE DEVELOPMENT OF DIAGNOSTICS AND ALIMENTARY PREVENTION SYSTEM OF NON-COMMUNICABLE DISEASES

Background: Violation of dietary intake structure leads to changes in nutritional status. This contributes to the development of non-communicable diseases, which account for more than half of causes of death inRussia. Materials and methods: In a consultative and diagnostic center "Healthy Nutrition" of theInstituteofNutritionthe nutritional status of 3580 patients (mean age 48.4±0.3  years) has been examined, including genomic and post-translational analysis. 30.0% of patients were overweight and 34.1% were obese.Results: Analysis of actual dietary intake showed an increase in energy intake due to excess intake of total (44.2%  energy) and saturated fat (13.6%). Serum biochemistry analyses revealed increased cholesterol levels in 68.7%  of patients, increased low-density lipoprotein cholesterol in 63.9%, increased triglycerides in 22.5%, and increased blood glucose in 29.4%. The frequencies of risk alleles of genes associated with development of obesity and type 2 diabetes mellitus were as follows: 47.8% for the polymorphism rs9939609 (FTO gene), 8.3% for the polymorphism rs4994 (gene ADRB3), 60.2% for the polymorphism rs659366 (gene UCP2), 36.6% for the rs5219  polymorphism in the gene of ATPdependent potassium channel.Conclusion: These results can be used for development of a personalized diet based on assessment of a patient's nutritional status

ДИФФЕРЕНЦИАЛЬНОДИАГНОСТИЧЕСКОЕ ЗНАЧЕНИЕ ОПРЕДЕЛЕНИЯ ПРОКАЛЬЦИТОНИНА В ЦЕРЕБРОСПИНАЛЬНОЙ ЖИДКОСТИ ПРИ МЕНИНГИТАХ У ДЕТЕЙ

Background: High production of pro-inflammatory cytokines associated with procalcitonin synthesis  and  its increased  blood  levels play an important role in the pathophysiology of systemic inflammation  in generalized  bacterial  infections. Aim: To assess diagnostic  value of procalcitonin measurement as a marker of bacterial  inflammation in cerebrospinal  fluid for differential diagnostics of bacterial  and  viral meningitis. Materials and methods: Procalcitonin  levels in blood  and cerebrospinal  fluid were measured by immunoenzyme analysis in 88 children aged from 3 months to 14 years who had been admitted to the hospital. Forty five percent  (45.4%) of them had acute bacterial meningitis, 27.3%, viral meningitis and 27.3% had the meningitis-like syndrome (control group). Results:  There  was a high  procalcitonin  level in   cerebrospinal  fluid in patients with bacterial purulent meningitis  (0,14 [0.0; 0.34] ng/mL (р < 0.006), with  the  normal  range  in the  control  group  of 0.07 [0.0; 0.07] ng/mL. This parameter correlated with blood procalcitonin level (9.8 [2.05; 13.19] ng/mL)  and  severity  of  meningitis.  In  patients with viral meningitis, the procalcitonin levels were below the normal range  (0.02 [0.01; 0.07] ng/mL). Conclusion: Measurement of procalcitonin  levels in cerebrospinal  fluid could be recommended for inclusion into the differential diagnostic algorithm of meningitis of various etiologies in children.Актуальность. В патогенезе системных воспалительных процессов  при генерализованных бактериальных  инфекциях важное  значение  имеет активация образования провоспалительных  цитокинов, сопровождающаяся синтезом прокальцитонина  и повышением  его уровня  в   крови. Цель – оценить информативность  определения уровня  прокальцитонина как биомаркера бактериального  воспаления  в цереброспинальной жидкости при  дифференциальной диагностике менингита  бактериальной и  вирусной  этиологии. Материал и методы.  У 88 детей в возрасте от 3 месяцев  до  14 лет,  госпитализированных в стационар, определяли уровень прокальцитонина  в крови  и цереброспинальной жидкости методом  иммуноферментного  анализа.  У  45,4% из них был диагностирован  острый бактериальный  менингит, у 27,3% – вирусный  менингит и  у 27,3% –  синдром  менингизма  (группа контроля).   Результаты.   Установлен   высокий   уровень прокальцитонина в цереброспинальной жидкости у пациентов с бактериальным гнойным  менингитом  –  0,14  (0,0; 0,34)  нг/мл (р < 0,006) при норме (группа контроля) 0,07 (0,0; 0,07) нг/мл, коррелирующий  с повышением прокальцитонина  в  крови   –  9,8  (2,05; 13,19) нг/мл и тяжестью менингита. При вирусных менингитах уровень прокальцитонина определялся   ниже  контрольных   значений   –  0,02 (0,01; 0,07)  нг/мл.  Заключение.   Определение уровня прокальцитонина в крови и цереброспинальной  жидкости  может  быть рекомендовано к включению в алгоритм дифференциальной  диагностики  менингита  разной  этиологии у детей

Frontal cephalometric landmarking: humans vs artificial neural networks

Frontal cephalometric radiography (frontal ceph) is one of the important diagnostic methods in orthodontics and maxillofacial surgery. It allows one to determine occlusion anomalies in the transverse and vertical planes and to evaluate the symmetry of the facial skeleton relative to the median plane, including analysis of the position of the jawbone. Aim: The aim of this study was to develop an artificial neural network (ANN) for placing cephalometric points (CPs) on frontal cephs and to compare the accuracy of its performance against humans. Materials and methods: The study included 330 depersonalized frontal cephs: 300 cephs for training ANNs and 30 for research. Each image was imported into the ViSurgery software (Skolkovo, Russia) and the 45 CPs were arranged. The CPs were divided into three groups: 1) precise anatomical landmarks; 2) complex anatomical landmarks; and 3) indistinct anatomical landmarks. Two ANNs were used to improve the accuracy of CP placement. The first ANN solved the problem of multiclass image segmentation, and the second regression ANN was used to correct the predictions of the first ANN. The accuracy of CP placement was compared between the ANN and three groups of doctors: expert, regular, and inexperienced. Then, using the Wilcoxon t test, the hypothesis that an ANN makes fewer or as many errors as doctors in the three groups of points was tested. Results: The deviation was estimated by the mean absolute error (MAE). The MAE for the points placed by the ANN, as compared with the control, was close to the average result for the regular doctor group: 2.87 mm (ANN) and 2.85 mm (regular group); 2.47 mm (expert group), and 3.61 mm (inexperienced group). The results for individual groups of points are presented. On average, the ANN places CPs no less accurately than the regular doctor group in each group of points. However, calculating all points in total, this hypothesis was rejected because the P value was 0.0056. A different result was observed among the inexperienced doctor group. Points from groups 2 and 3, as well as all points in total, were placed more accurately by the ANN (P = 0.9998, 0.2628, and 0.9982, respectively). The exception was group 1, where the points were more accurately placed by the inexperienced doctors (P = 0.0006). Conclusion: The results of the present study show that ANNs can achieve accuracy comparable to humans in placing CPs, and in some cases surpass the accuracy of inexperienced doctors (students, residents, graduate students)