Vol 73, No 2 (2018)

INTERNAL DISEASES: CURRENT ISSUES
EFFICACY OF SELECTIVE PDE-4 INHIBITOR IN PATIENTS WITH PSORIASIS: CLINICAL OBSERVATIONS
Kubanov A.A., Karamova A.Е., Artamonova O.G.

Abstract

Objective: We aim to present preliminary on about the efficacy of a new drug for plaque psoriasis and psoriatic arthritis treatment - an oral selective PDE-4 inhibitor (apremilast) in 3 psoriasis patients and evaluate apremilast efficacy and safety.

Materials and methods: The study enrolled patients with moderate-to-severe plaque psoriasis and psoriatic arthritis who demonstrated lack of efficacy, negative side effects or intolerance to systemic therapy with methotrexate, acitretin, and phototherapy in anamnesis. Patients were administered with apremilast according to the prescription (start 10 mg daily, stepwise increase to 30 mg taken orally twice a day). The severity was estimated by PASI, BSA, sPGA, ptPGA; the patient’s quality of life was determined by DLQI. The efficacy was evaluated at week 14.

Results: All patients reached significant clinical improvement (two patients reached ΔPASI50, one patient ΔPASI75, improvement of the nail plate state).

Conclusion: According to our observations, apremilast is safe and effective for the treatment of moderate-to-severe plaque psoriasis, scalp and nail psoriasis, and psoriatic arthritis.

Annals of the Russian academy of medical sciences. 2018;73(2):81-87
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NEUROLOGY AND NEUROSURGERY: CURRENT ISSUES
LONG-TERM RESULTS OF SURGICAL TREATMENT IN PATIENTS WITH INTRADURAL SPINAL TUMORS
Byvaltsev V.A., Stepanov I.A., Belykh E.G., Aliyev M.A.

Abstract

Background: Intradural spinal cord tumors include extramedullary and intramedullary tumors. The search for literature sources in the Pubmed, Medline, and E-Library databases detected a little number of researches on the long-term results of the surgical treatment of intradural spinal cord tumors. These clinical series include a small number of patients and do not consider the factors influencing clinical outcomes of surgical treatment.

Aim: To evaluate the long-term results of surgical treatment in patients with intradural spinal cord tumors, to identify the main factors influencing the clinical and neurological outcomes of surgical interventions in this group of patients.

Materials and methods: The study included 277 medical records of 244 patients with intradural extramedullary and 33 patients with intradural intramedullary tumors of the spinal cord. Clinical-neurological outcomes of surgical treatment in patients with intradural spinal cord tumors and factors influencing the outcomes were analyzed.

Results: When comparing the degree of neurologic deficit in patients with intradural extramedullary tumors prior to surgery, no significant differences were found (p=0.241) both in the early postoperative period and 6 months after the surgery. Nevertheless, when comparing these indicators in a period of 12, 24, 36, 48, and 60 months after the surgery, statistically significant differences were revealed (p<0.001). There was no statistically significant difference (p=0.437) between the scores in patients with intramedullary tumors on the modified McCormick Scale preoperatively, at the 6-month and one-year follow-up; however, comparison of the clinical and neurological indicators at 24, 26, 48, and 60 months revealed a significant difference (p<0.001). The surgery outcomes in considered groups of patients were significantly influenced by the following indicators: the ASA risk level (odds ratio (OS) 2.138; 95% confidence interval (95% CI) 3.346–12.145) and intraoperative neurophysiological monitoring (OR 2.84; 95% CI 1.67–9.56).

Conclusion: The study registered good and excellent long-term outcomes in most cases of intradural spinal cord tumors when the maximum possible tumor excision was performed. Analysis of the influence of various factors on the clinical and neurological outcomes in the study group of patients showed that the use of intraoperative neurophysiological monitoring and the degree of operational and anesthetic risk according to the ASA scale have a significant effect.
Annals of the Russian academy of medical sciences. 2018;73(2):88-95
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ONCOLOGY: CURRENT ISSUES
THE USE OF SYNTHETIC IMAGES FOR SOLVING THE CLASSIFICATION PROBLEM BY THE EXAMPLE OF LUNG CANCER DIAGNOSIS
Gundyrev I.A., Bel'skaya L.V., Kosenok V.K., Sarf E.A.

Abstract

Background: From a mathematical point of view, the problems of medical diagnostics are the tasks of data classification. It is important to understand how significant distortions can contribute to the result of classification errors in the collection of primary diagnostic information, in particular, the results of biochemical tests.

Aims: Determination of the dependence of the prediction result on the variability of the primary diagnostic information on the example of the model classifier.

Materials and methods: The case-control study enrolled patients who were divided into 2 groups: the main (diagnosed with lung cancer, n=200) and the control group (conditionally healthy, n=500). Questioning and biochemical saliva study was performed in all participants. Patients of the main group and the comparison group were hospitalized for surgical treatment, after which carried out the histological verification of the diagnosis. The biochemical composition of saliva is determined spectrophotometrically. Based on the data obtained, a model classifier for the diagnosis of lung cancer (a random forest) has been constructed. In each parameter underlying the classifier, deviations were made in the specified range (±1–5%, ±5–10%, ±10–15%), creating synthetic images. Then, the results of the classification were evaluated by the cross-validation method.

Results: The basic diagnostic characteristics of the model classifier are determined (sensitivity ― 72.5%, specificity ― 86.0%). As the deviations of synthetic images from the baseline increase, diagnostic characteristics deteriorate with the general classification. However, the result of a confident classification, on the contrary, gives higher values (sensitivity ― 81.8%, specificity ― 93.1%). In case of a confident classification, similar images that fall into different classes according to the classification results are deleted, whereas in the case of a general classification, they are taken into account. The difference between methods of classification is associated with the presence of images on which the classifier gives the result of belonging to the class in the range of 0.45–0.55. Therefore, it is necessary to introduce a third class into the classifier, the so-called gray zone (0.4–0.6), since the probability of making an erroneous diagnosis in this area is significantly increased.

Conclusions: The obtained results allow to conclude that the measurement error in the range (±1–15%) does not significantly affect the quality of the classification.

Annals of the Russian academy of medical sciences. 2018;73(2):96-104
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HEALTH CARE MANAGEMENT: CURRENT ISSUES
THE PROBLEM OF KNOWLEDGE TRANSLATION IN HEALTHCARE: TOOLS FOR ITS SOLUTION IN THE AREA OF PATIENT SAFETY
Kleymenova E.B., Nazarenko G.I., Payushchik S.A., Yashina L.P.

Abstract

Adherence to evidence-based clinical guidelines enhances patient safety, but the level of knowledge implementation into routine practice remains unsatisfactory. The concept of knowledge translation (KT) was proposed as a «process that includes the synthesis, dissemination, exchange, and ethically sound application of knowledge» to define the framework of knowledge transfer from research to practical activities aimed at improving the quality and safety of healthcare. Although Russian authors pay much attention to translational medicine, the problem of implementation research is poorly discussed. Modern information technologies including clinical decision support systems (CDSS) play a crucial role in KT, but the evidence of their effectiveness is poor. The authors describe a systematic approach to the practical implementation of knowledge imbedded in clinical guidelines based on the use of CDSS. CDSS implementation was accompanied by organizational measures that ensured the overall success: creation of standard operating protocols and quality register, clinical audit with feedback, and staff training. The effectiveness of this approach in reducing the risk of inhospital complications in Moscow general hospital is illustrated by the example of hospital-acquired venous thromboembolism (HA-VTE) prevention. Implementation of a comprehensive program for HA-VTE prevention in 2014−2016 helped to increase the coverage with VTE and bleeding risk assessment from 15% to 80% (p<0.0001), to reduce the frequency of pharmacological prophylaxis defects from 50.6% to 23% (p=0.01), to increase the compliance with anticoagulant use from 50% to 76% (p=0.0005), without increasing the rate of hemorrhagic complications. The HA-VTE rates decreased from 10 to 4.25 cases per 1000 overall hospital admissions (p=0.001), from 8 to 1.27 cases per 1000 operations in surgical patients (p=0.001) and from 12 to 6.38 cases per 1000 hospitalizations in therapeutic patients (p=0.06; with a statistically significant downward linear trend for HA-VTE rate, p=0.038).

Annals of the Russian academy of medical sciences. 2018;73(2):105-114
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ENDOCRINOLOGY: CURRENT ISSUES
Wnt10b and Wnt3a AS BIOMARKERS OF CHANGES IN THE REGULATION OF BONE METABOLISM IN PATIENTS WITH CUSHING’S DISEASE
Grebennikova T.A., Belaya Z.E., Solodovnikov A.G., Ilyin A.V., Nikankina L.V., Melnichenko G.A.

Abstract

Background: Endogenous hypercortisolism due to Cushing’s disease (CD) is complicated by low-traumatic fractures in 50% of cases. Modern technologies allow to study pathogenetic changes in the regulation of bone remodeling in hypercortisolism and to offer new serum biomarkers.

Aims: To evaluate levels of Wnt proteins related to bone remodeling regulation in serum samples from patients with CD.

Materials and methods: Fasting serum samples were taken and stored in aliquot at ≤-80 °C from 42 consecutive subjects with clinically evident and biochemically confirmed active CD and 42 healthy volunteers matched by age, sex and body mass index (BMI). Evaluation of the levels of Wnt proteins (Wnt3a, Wnt10b) was measured by immunochemiluminescence assay using the WNT3a SEL818Hu (USCN) and the WNT10b SEP553Hu (USCN). Twenty-four hours urine free cortisol (24hUFC) (60−413 nmol/24h) and bone turnover markers was measured by electrochemiluminescence assay on a Cobas 6000 Module e601 (Roche). At the time of enrollment all participants were questioned regarding any low traumatic fractures for the period of the disease. Patients underwent standard spinal radiographs in anterior-posterior and lateral positions of the vertebrae Th4−L4 (Axiom Icons R200 Siemens).

Results: The median (Ме Q25; Q75) age of patients with CD was 33 (21; 43) years with no difference among the groups, p=0.936; BMI ― 29 (23; 34) kg/m2, p=0.094 and without differences by sex, p=0.254. The median 24hUFC in subjects with CD ― 825 (301; 2077) nmol/24h was significantly higher as compared to the control group (p<0.001). We report increased levels of Wnt3a and Wnt10b in patients with CD: Wnt3а 0.15 (0.04; 0.23) ng/ml in patients with CD vs 0,04 (0.01; 0.13) ng/ml in control group (p=0.017) and Wnt10b 2621 (2226; 3688) pg/ml vs 1917 (1721; 2549) pg/ml (p=0.008).

Conclusions: The serum level of Wnt3a and Wnt10b reflects the intensity of Wnt-signaling dysregulation, and therefore they may be considered as biomarkers of bone remodeling deterioration in hypercortisolism.

Annals of the Russian academy of medical sciences. 2018;73(2):115-121
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РATHOPHYSIOLOGY: CURRENT ISSUES
PROSPECTIVE RESEARCH OF HEMOSTASIS DISORDERS IN THE I PHASE OF SERIOUS ACUTE PANCREATITIS
Vinnik Y.S., Dunaevskaya S.S., Antufrieva D.A.

Abstract

Background: Acute pancreatitis is one of the most common surgical abdominal diseases. The development of trypsin autoaggression which provokes hemostasis disorders play significant role for pathogenesis of severe acute pancreatitis. The study of biochemical hemostasis-related markers and general homocysteine as a marker of endothelium damage at acute pancreatitis and their influence on development of heavy complications of the I phase of a disease is actual and relevant task. These complications are the reason for about 40% of lethal outcomes.

Aims: To study hemostasis disorders and homocysteine as marker of damage of endothelial cells in patients with acute pancreatitis during the initial period of a disease depending on disease severity, the volume of injury of a pancreas, and development of complications.

Materials and methods: 127 patients who were divided into two groups: with severe AP and not severe AP. We investigated variables and indicators of hemostasis system: activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time (TT), international normalized ratio (INR) fibrinogen, and homocysteine.

Results: The most expressed hemostasis disorders and level of the general homocysteine were registered on 3rd day from the disease onset. On the 7th day, the tendency to decrease in indexes of a coagulative link of a hemostasis and decrease in level of the general homocysteine was registered in patients with severe acute pancreatitis. There were correlative communications of high and average degree between the volume of a pancreatonecrosis and violation of a hemostasis on 3rd day from the disease onset, and the level of the general homocysteine rS=0.94 (p1=0.001). In patients with severe pancreatitis, systemic complications of different degree of expressiveness were observed in 69.57% of cases. There were average and high correlations between violation of system of a hemostasis on the 3rd day and systemic complications development, as well as high direct correlation between increase in level of the general homocysteine and systemic complications development rS=0.77, p1=0.001.

Conclusions: Hemostasis disorders and the level of general homocysteine correlated with volume of pancreas and retroperitoneal cellular tissue affection and system complications development at the 1-th phase of severe acute pancreatitis.

Annals of the Russian academy of medical sciences. 2018;73(2):122-129
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PHARMACOLOGY: CURRENT ISSUES
APPLICATION OF INDOMETHACIN IN MEDICINE AND PHARMACY
Krasnuk I.I., Kosheleva T.M., Belyatskaya A.V., Krasnuk I.I., Stepanova O.I., Skovpen' Y., Vorobiev A.N., Grikh V.V., Ovsyannikova L.V.

Abstract

Indomethacin, a non-steroid anti-inflammatory drug (NSAID), has been used in different spheres of medicine since the 1960s. It is successfully administered as an anti-inflammatory and pain-relieving medication in rheumatoid and other diseases. According to recent research, indomethacin may become a promising drug enhancing endogenous remyelination in patients with multiple sclerosis. Also, indomethacin affects cell proliferation and invasion, thus it is used to manage pancreatic cancer in patients with hyperglycemia. In addition, indomethacin can inhibit protein synthesis in colorectal carcinoma and other types of cancer cells. The article reviews modern indomethacin medications and the different dosage forms on the Russian pharmaceutical market. Indomethacin poor water solubility is one of the reasons for decreasing its biopharmaceutical characteristics. According to the conducted research, a prospective way to improve indomethacin solubility and bioavailability is the Solid Dispersion (SD) method. SDs are bi- or multicomponent systems consisting of the drug and the carrier. They are a highly dispersed solid phase of the drug or molecular-dispersed solid solutions with a partial formation of a variable composition complex and a carrier. The article provides a brief overview on different aspects of obtaining, investigating, and applying indomethacin SDs with various polymers.

Annals of the Russian academy of medical sciences. 2018;73(2):130-134
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HISTORY OF MEDICINE
TO THE 100TH ANNIVERSARY OF THE NN BURDENKO VORONEZH STATE MEDICAL UNIVERSITY. THE HISTORY OF THE DEPARTMENT OF THE PROPAEDEUTIC OF INTERNAL DISEASES
Esaulenko I.E., Nikitin A.V., Vasilieva L.V., Gosteva E.V., Starodubtseva I.A., Karpuhina E.P., Malukov D.А.

Abstract

The article concerns the 100th anniversary of the Department of Propaedeutics of Internal Diseases at the NN Burdenko Voronezh State Medical University. There are several important stages in the formation of the department. The history of the development of the department of propaedeutics of internal diseases is inextricably linked with the formation of the Voronezh Medical University from the day of its foundation. During the last century, the department was headed by famous scientists-clinicians: Philosophov P.I., Kurshakov N.A., Gerke A.A., Ravich-Shcherbo V.A., and others. The national medicine owes to their work in the field of diagnosis and treatment of tuberculosis diseases of the lungs and pleura, the clinical course of adhesive pericarditis. During the postwar periods, the department was headed by professors Tumanovsky M.N., Kobyzev A.S., Safonov Yu.D. Their contribution to the development of medical science is difficult to overestimate. The doctrine of Professor Safonov Yu.D. on the bio-hydraulic mechanism of origin of heart sounds found resonance all over the world. Since 1987 to the present time the department of propaedeutics of internal diseases is headed by Professor Nikitin A.V. known as the founder of a new scientific direction in the field of non-drug treatment methods for diseases of internal organs. For his scientific contribution, Anatoly Vladimirovich was awarded the USSR Council of Ministers Prize, and was given an Honorary title «Honored Worker of the Higher School of the Russian Federation». Professor Nikitin A.V. is a famous scientist, a clinician, and a teacher who advised on 50 candidate and 5 doctoral dissertations defended afterward.

Annals of the Russian academy of medical sciences. 2018;73(2):135-140
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ЮБИЛЕИ
LEONID ANDREEVICH IL'IN
 

Abstract

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Annals of the Russian academy of medical sciences. 2018;73(2):141-142
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