Репозиторий Университета

© 2018 by the authors; licensee Modestum Ltd., UK. Objective: The first interferon-free regimen became available in Russia in 2015. It brought hope to HCV Gt1 patients with cirrhosis for whom interferon-based schemes found to be non-effective or contraindicated. 3D therapy was the only available etiotropic option for them. New safety data published after the start of our study significantly limited usage of this regimen among patients with non-compensated cirrhosis. The aim of this study was to evaluate efficacy and safety of the 3D interferon-free regimen among HCV Gt1b patients with non-compensated cirrhosis. Method: 66 patients (26 males and 40 females) with HCV Gt1b and non-compensated cirrhosis were enrolled. All of them were treated with ombitasvir/paritaprevir/ritonavir, dasabuvir and ribavirin for 12 weeks. Ribavirin was discontinued after 4 weeks of therapy due to onset of new data on the efficacy of 3D regimen without ribavirin in Turquoise III study published in September 2015 before the change of package insert. Child-Pugh score was assessed before the start of antiviral therapy as follows: 21 patients (31,8%) – 9 points, 11 patients (16,7%) – 8 points, 34 patients (51,5%) – 7 points. The key method used to evaluate study results was modified intent-to-treat (mITT) analysis because number of analyzed patients within treatment period changed after withdrawal caused by safety reasons but followed by assessment of efficacy among patients who discontinued treatment. Per protocol (PP) method was also used in addition to mITT. Results: Aviremia after 14 days of treatment was reached among 35 out of 65 patients (53,8%), rapid virologic response – among 79,7% patients (51/64). Each patient who received full 12-week course of treatment (n=60) including those who discontinued due to safety reasons (n=3) between 14th and 30th days of therapy reached SVR12 and SVR24. Assessment of Child-Pugh score in 6 months after EOT demonstrated decrease by 3-4 points among 21 patients (33,9%) and by 1-2 points among 35 patients. 66,1% patients reached clinical improvement in MELD score. Treatment discontinuation was caused by progression of hepatic encephalopathy and/or jaundice (4 cases). Those adverse events regressed among majority of patients after discontinuation of therapy. 3 deaths were reported (bacterial endocarditis, progression of hepatic encephalopathy and bleeding from gastric ulcers) during treatment period and 1 death in follow-up period due to progression of hepatocellular carcinoma. Conclusion: 3D therapy was effective in 100% patients (mITT) with HCV GT1b and non-compensated cirrhosis both among those who completed full therapy course and those who discontinued the therapy due to safety reasons. Safety analysis demonstrated that the rate of severe adverse events was comparable with natural course of HCV-infection in patients on non-compensated cirrhotic stage without antiviral treatment.

© 2018 by the authors; licensee Modestum Ltd., UK. Objective: Prolongation of the QT interval in patients with coronary heart disease (CAD) is a risk factor of polymorphic ventricular tachycardia (PVT) and as consequence, the sudden death. Drug-drug interactions (DDI) on metabolic rate involving cytochrome P-450 (CYP) is the one of the major cause of Long QT Syndrome (LQTS). The aim of the present study was to improve the safety of combined pharmacotherapy when using drugs that affect the QT interval. Method and Results: Medication occurrence of potential dangerous combination of medicines that are affected on QT interval duration in patients with CAD are researched (outpatient medical records (patient history) analysis). Clinical relevance of DDI, which are associated with changes in CYP enzyme activity, categorized by drugs.com Medication Guide. Finding potential dangerous combination of medicines that are affected on QT interval duration were administered to patients with CAD in 3.6% cases in outpatient clinical practice. The most often prescribed combination of drugs is amiodarone and torasemide (13.3% evidence of all concomitant administration that are leading to QT prolongation). The potential mechanism of Amiodarone and Torasemide interaction on metabolic rate that are leading to QT prolongation are competitive substrates CYP 2C8 and a result of inhibited CYP 2C9 by amiodarone. Conclusion: Ability to predict the prolongation of the QT interval caused by DDI on metabolic rate make possible to improve the safety concomitant administration to patients with CAD.

© 2018 Interregional public organization Association of infectious disease specialists of Saint-Petersburg and Leningrad region (IPO AIDSSPbR). All rights reserved. The development of mesenteric lymphadenitis is typical for patients with HIV infection at the stage of secondary diseases. The purpose of our study is to decipher the etiology of lymphadenitis in patients with HIV infection at the stage of secondary diseases. The analysis of disease histories of 113 HIV infection patients at the stage of secondary diseases with the use of statistical processing was carried out. The article presents examples that characterize the polymorphism of clinical variants of the development of mesadenitis in HIV-infected patients with stage 4B, which has developed as a result of the influence of various etiological factors.

Problem of internal carotid artery disease diagnosis appears to be crucial today. Complications of this pathology are strokes and transient ischemic attacks. There is no technology for their prediction or at least stratifying risks. Some recent researches are devoted to a new diagnostic method. This new technology is called Contrast Enhanced Ultrasonography (CEUS) and followed by outstanding results in studying the morphological peculiarities of internal carotid artery plaques and predicting the probability of complications. CEUS is a new way for atherosclerotic process analysis because it is able to detect intraplaque neovascularization and vascular wall inflammation.

© 2018. Conjugates of Streptococcus pneumoniae type 9N capsular polysaccharide with tetanus toxoid have been prepared. Their interactions with specific antibodies to tetanus toxoid and polysaccharide 9N were assessed, which permitted to select a conjugate with the optimal ratio of the polysaccharide and carrier protein (3:4). The parameters of the efficient adsorption of tetanus toxoid and polysaccharide on aluminum hydroxide for the following in vivo experiments were determined using the quantitative ELISA; in particular, the optimum ratio of the conjugate and adjuvant was proved be ≤ 1:1 (w/w). The repetitive immunization with the selected conjugate adsorbed on aluminum hydroxide increased the anti-PS antibody titers up to 70400 (p < 0,001) which is 140-fold higher as compared to the antigen unconjugated form. The investigation of the antibody protection from Streptococcus pneumoniae 9N after the intranasal challenge of wild-type mice revealed that the titer of the bacterial contamination in the immunized mouse lung tissue was 10-fold lower than that in non-immune mice 72 h after the contamination (p > 0,05).

© 2018 Media Sphera Publishing Group.All Rights Reserved. Purpose of the study. To examine the frequency and risk factors for the development of diastolic dysfunction (DD) of the left ventricle (LV) of the heart in patients with chronic kidney disease (CKD). Materials and methods. The study included 225 patients with stage I-CKD of non-diabetic etiology (median age 47.0 years, 50.2% of women). Depending on the degree of decrease in the glomerular filtration rate (GFR), all patients were divided into 3 groups. Group 1 (n=70) consisted of patients with GFR 89-45 ml / min / 1.73 m2, group 2 (n=120) - patients with GFR 44-15 ml / min / 1.73 m2, group 3 (n=35) - patients with GFR <15 mL / min / 1.73 m2. The control group includes persons without CKD. All patients underwent general clinical examination and transthoracic echocardiography; in 86 patients the level of cystatin C in the blood serum was determined. Results. Hypertrophy of the left ventricle (LVH) of the heart was detected in 87 (38.7%) of 225 patients with CKD. Hypertrophic type (type I) of myocardial DD is diagnosed in 90 (41.4%) of 225 patients with CKD. The incidence of myocardial left ventricular dysfunction of the 1st type increased with a decrease in GFR, amounting to 30, 40 and 60% in groups 1, 2 and 3, respectively. The systolic function of the left ventricular myocardium was preserved. Patients with DD were older, they had a higher body mass index (BMI), a more pronounced decrease in GFR, a higher level of fibrinogen. They were more likely to have LVH. The level of cystatin C as the kidney function worsened, but when comparing the mean levels of cystatin C in patients with the presence / absence of DD in the groups isolated depending on the stage of CKD, no statistically significant differences were found. According to the multivariate analysis, the independent predictor of DD was the age (odds ratio 1.106, 95% confidence interval 1.051-1.157, p=0.00001). The conclusion. DD of the myocardium of the LV is detected on average in 40% of patients with CKD, the frequency of its development increases with the progression of renal dysfunction. The development of DD is influenced by traditional factors of cardiovascular risk (age, BMI), as well as the decline in GFR and closely related structural remodeling of LV myocardium.

© 2018 Media Sphera Publishing Group.All Rights Reserved. Vitamin D deficiency is widespread worldwide and present in about 30-50% of population. In most cases, this problem is associated with musculoskeletal system pathology: Rickets in children, and osteomalacia or osteoporosis in adults. However, in recent years, convincing data was obtained on the links between Vitamin D deficiency and cardiovascular pathology. Low Vitamin D levels in humans are associated with the unfavorable cardiovascular risk factors, such as arterial hypertension (AH), diabetes mellitus, and dyslipidemia, which are the predictors of the severe cardiovascular diseases, including strokes and infarctions. It has been demonstrated that Vitamin D has a strong vasoptotective effect via endothelial dysfunction improvement, prevents blood vessels and myocardium remodeling, improves blood pressure parameters, reduces the risk of development of left ventricular hypertrophy, slows down fibrosis, reduces the risk of atherosclerosis, reduces insulin resistance, and also affects inflammation and immunity. This article provides data of Russian and foreign studies demonstrating the effect of Vitamin D deficiency on the development of atherosclerosis, AH, heart rhythm disorder and progression of chronic heart failure.

Cases of dental needle fracture during mandibular block were studied in the last 10 years. Despite dental anesthesia development, the cases of needle fracture occur regularly in the world practice. Some of these complications has iatrogenic nature while others may be attributed to independent reasons like patients' sharp movement and needle manufacturing defect. In most of the cases the needle migrates to surrounding anatomical spaces making operative removing a challenging task. Subsequent surgical removing of a foreign body has severe consequences to patient in the form of a large operating injury, long-term disability and functional limitations. The article presents an algorithm for prevention and emergency care for a patient with dental needle fracture during mandibular block.

© 2018, Dynasty Publishing House. All rights reserved. The objective. To offer a clinical and laboratory characteristic of coronavirus infection in hospitalised children. Patients and methods. The group of study included 50 children, who were diagnosed with coronavirus infection by polymerase chain reaction (PCR). Mono-coronavirus infection was found in 40 children (80%), mixed virus infection conditioned by a combination of two or three viruses - in 10 children (20%). Results. In all examined children with coronavirus infection disease had an acute onset and took a mild or moderate course. In general, the clinical picture of disease was manifested by cough, signs of rhinitis (stuffy nose, mucus discharge from the nose), febrile fever (in 52.5% of patients with mono-infection and in 80% of children with mixed infection), laryngotracheitis with laryngeal stenosis grade 1 (in 52.5% with mono-infection and in 80% with mixed infection). In 10% of children with monoinfection and in 50% of children with mixed infection gastrointestinal dysfunction was noted in the form of repeated vomiting to 2-6 times, diarrhoea to 1-4 times daily without pathological admixtures. Haematological parameters did not show any characteristic specificities in any child in both mono-infection and mixed infection. Cclusionon. Catarrhal inflammation is the leading clinical syndrome in mono- and mixed coronavirus infection; disease was manifested by cough, often - elevated body temperature, signs of stenosing laryngitis; part of children developed gastrointestinal dysfunction.

Pathological lesions associated with multiple causes (infections, physical, chemical and thermal agents) of oral mucosa are equally widespread in all spheres of dental practice. The actual importance of pharmaceutical therapy of lesions of oral mucosa is associated with the lack of reliable traditional topical drugs - ointments, gels, pastes, lacquers, discs - caused by their little efficiency associated with poor maintaining of permanent concentration, short contact period, discomfort and long-term treatment. All the mentioned facts caused the development of various pharmaceutical forms with prolonged activity with improved adhesion to oral mucosa, prolonged saving of useful properties and protecting the lesion from oral infection and external influences and reducing the intensity of painful sensations during mastication and mimics. These drugs form the group of barrier drugs and drugs with prolonged release of medicine of the wide specter. During all the time of existence this group of drugs has undergone and is still undergoing several changes targeted on improvement of adhesion and maintaining of constant concentration of medicine in the lesion and extension of indications for use. The development of new pharmaceutical forms is still continuing.

AIM: To develop new criteria of radical surgery for hilar cholangiocarcinoma (HCC). MATERIAL AND METHODS: There were 165 HCC patients who underwent surgery in 1986-2016 at the Vishnevsky Institute of Surgery. TNM stage distribution: stage I - 4 (2.4%), II - 45 (27.3%) (29 of them are referred to the 1st period of work), IIIA - 23 (13.9%), IIIB - 41 (24.8%), IVA - 35 (21.2%), IVB - 17 (10.3%). 80 (48%) patients underwent hemihepatectomy, 17 (10%) - advanced hemihepatectomy, 16 (10%) - minor liver resection with common bile duct repair, 52 (32%) - common bile duct repair resection. Kaplan-Meier survival analysis was performed. Cox proportional hazard model was applied to access relationship between survival and prognostic factors. Log-rank test was used to compare both survival curves. RESULTS: R0-resection as followed by 5-year survival rate near 32%. Microvascular invasion was observed in 42.9%, lymphovascular invasion - in 88.2%, positive resection margin - in 59.2%, perineural invasion - in 83.3%, cells in surrounding fatty tissue were revealed in 92.3%. Resection may be considered radical (R0) if all variables are absent, 5-7 negative factors are followed by conditionally radical procedure (R+number of positive factors). Long-term outcomes and significance of new criteria were accessed (p=0.004). CONCLUSION: New criteria of radical procedure are presented. The last reflects the concept of dependence of 'pure' surgical edge from not only presence or absence of tumor cells in cut-off plane but also from important morphological features of tumor.

© Bionika Media Ltd. The literature data on the study of the microbiota of female genital organs and assess the clinical and microbiological characteristics of the probiotic strain LCR35, used in the treatment and prevention of vaginal infections were analyzed. Biotherapeutic aspects of treatment and prevention of dysbiotic conditions of vaginal microbiota have been analyzed. A comparative evaluation of the characteristics and requirements of lactobacillicontaining preparations with probiotic activity in obstetric-gynecological practice was carried out. The clinical and microbiological advantages of the original probiotic strain Lactobacillus casei rhamnosus Doderleini (LCR35) in the formulation Lactogynal in the treatment and prevention of vaginal infections were noted. The literary review of data the medical use of the culture of Lactobacillus casei rhamnosus Doderleini (LCR35) testifies to the expediency and validity of its use in the mode of two-stage therapy of the dysbiotic conditions of the vagina. Organization and conduct of additional post-registration clinical studies of medicinal product for medical use Lactogynal will strengthen the position of targeted probiotics in the complex treatment and prevention of bacterial and fungal infections of female genital organs.

© Bionika Media Ltd. A systems analysis of the data available in the literature on the problem of choosing the optimal folate formulation in order to correct folate status in obstetric and gynecologic practice was carried out. There is plenty of evidence that increasing the folate status reduces the risk of neonatal neural tube defects. Higher folate intake through supplementation with folic acid (FA) or 5-methyltetrahydrofolate (L-methyl-THF) is recommended during pregravid preparation and early pregnancy. L-5-methyl-THF has a number of advantages over FA, since it is a physiological compound and has greater bioavailability. 5-methyl-THF is also available as a crystalline form of calcium salt (metafolin) that has the stability required for use as a supplement. When correcting the folate status in obstetric and gynecological practice, it is recommended that a choice should be made in favor of a formulation that has the best bioavailability, as seen in metafolin.

MATERIAL AND METHODS: 154 patients with acute left-side colonic obstruction were enrolled. Patients were divided into 4 groups. In groups 1-3 (n=120) patients underwent surgery at the moment of colonic obstruction, in 34 patients obstruction was managed with transtumoral decompression followed by radical surgery. Self-expanding metallic stents (SEMS) were used in these patients. Radical and palliative procedures at the moment of colonic obstruction are associated with high rate of postoperative complications and mortality.RESULTS: Transtumoral decompression in malignant colonic obstruction resolves the main objectives of complicated colonic cancer management: absence of surgical trauma, endotracheal narcosis, reduced risk of abdominal infection, possible multidisciplinary assessment of patient's status and preparation for radical surgery.AIM: To prove an effectiveness of transtumoral decompression in patients with acute malignant left-sided colonic obstruction.

© 2018 Paediatrician Publishers, LLC. All rights reserved. Background. Planning the management for medical care delivery for children with cancer, as well as analysis of the effectiveness of medical care delivery is based on the statistical indicators analysis. Objective. Our aim was to analyze the main indicators characterizing medical care delivery for children with cancer in the Central Federal District. Methods. The operative reports for 2017 provided by the executive health protection authorities of 18 subjects of the Russian Federation that are part of the Central Federal District have been analyzed. Results. The study enrolled the following data: number of children was 6 824 049 (0–17 years), pediatric oncological departments — 9, pediatric oncological beds — 464, days of berth employment per year — 319.3. The number of practitioners providing medical care to children with cancer was 91, 64 (70.3%) of them had a certificate of training as a pediatric oncologist. In 11 subjects, the department of pediatric oncology was not available; one of the districts did not provide any pediatric oncological beds. The number of primary patients with malignant neoplasms was 821. The number of deceased patients was 156 including 66 identified in 2017. The incidence of malignant tumors was 12 (per 100 000 for the 0–17 age group), the mortality rate was 2.3 (per 100 thousand for the age group 0–17 years), one-year mortality rate — 8%. We failed to reveal the average time from diagnosis establishing till its validation before the treatment onset since the reports did not provide precise information on the point. 12 (1.5%) primary patients left for treatment abroad. Conclusion. Most reports included indicators which lack congruity with one another. The incidence rates were significantly lower than those in countries with high statistical reliability. The percentage of patients identified actively remained extremely low. To improve the revealed defects a single database of children with oncological diseases should be implemented in the Russian Federation.

© 2018 Vserossiiskoe Obshchestvo Kardiologov. All rights reserved. Aim. To evaluate the changes of endothelial function in arterial hypertension (AH) patients with paroxysmal atrial fibrillation (AF) in treatment with propafenone (Propanorm, PRO.MED.CS Praha a.s.) in comparison with bisoprolol. Material and methods. To the study, 62 AH patients included with paroxysmal AH, age 45-63 y.o. (mean age 54,5±3,7 y.o.). Patients were randomized to 2 groups: 32 of group 1 (main) for rhythm-control were taking propafenone (Propanorm, PRO.MED.CS Praha a. s.) 450 mg daily, and 30 of group 2 (comparison) were taking bisoprolol for rate control. The groups were comparable by gender, age, severity of AH and duration of arrhythmia. Changes in endothelium vascular motion function and biochemical markers of endothelial dysfunction were assessed at inclusion and in 12 months of therapy. Results. Sinus rhythm retention in propafenone group facilitated the improvement of vascular motion function of endothelium - endothelium dependent vasodilatation of brachial artery showed tendency to rise significantly from 5,4±0,3% to 6,9±0,1% (р=0,01). In patients taking bisoprolol for pulse reduction during 12 months, there was negative tendency from 4,8±0,2% to 3,6±0,1% (р=0,003), that points on worsening of endothelial function with persistent AF. Repeat measurement of biochemical markers of endothelial dysfunction revealed that in 12 months there is raise of endothelin concentration in both groups. Value of the collagen-binding activeness of von Willebrand factor in 12 months significantly reduced from 131±12 to 118±6 U/dL (р<0,05) in those retaining sinus rhythm with propafenone, and increased from 135±11 U/dL to 147±12 U/dL in those with rate control by bisoprolol. Conclusion. In AH patients with paroxysmal AF retention of sinus rhythm with propafenone facilitated the improvement of vascular motion function of endothelium and decrease of collagen binding activeness of von Willebrand factor.

© 2018 Russian Transplant Society. All rights reserved. Aim. To establish the ability of the total RNA extracted from the body’s bone marrow cells (BMCs), in which liver tissue was damaged, to serve as a carrier of targeted regenerative signals to this organ. Materials and methods. By method of adoptive transfer in rats (n = 37) the mitotic and proliferative activity of liver and kidney cells were studied in intact recipients after intraperitoneal injection: the mononuclear BMCs – 2,5×106; 5,0×106; 3,5×107 cells – group 1 and the total RNA of the same BMCs (30μg/100g of weight) – group 2 from donors in 12 hours after 70–75% of hepatectomy; in group 3 (control), a saline solution was injected. RNA from BMCs was extracted by the method developed by the «Evrogen» firm (Russia) with the reagent Extract RNA. Results. In group 2 in 48 and 72 h. there was the increasing of mitotic and proliferative cell activity in the liver, but not in the kidneys (control of the specificity of regenerative signals); in group 1 there was no transfer of regenerative signals to these organs. Conclusion. The authors believe that the total RNA from BMCs, activated by hepatectomy, accumulates targeted (hepatospecific) regeneration signals, but they are perceived only when RNA has been obtained by the damaged tissue.

© 2018 Russian Transplant Society. All rights reserved. Heart transplantation is the «gold standard» of treatment severe heart failure. Patient survival after heart transplantation has improved dramatically since the availability of calcineurin inhibitor (CNIs). However, nephrotoxicity of CNIs has been largely responsible for the progressive development of renal dysfunction and reduces long-term patient survival. Use mTOR inhibitor in immunosuppressive therapy may improve renal function when everolimus is administered associated with a progressive reduction of CNIs. The purpose of our report is to demonstrate the successful case of conversion of the recipient after heart transplantation to everolimus and to evaluate the effectiveness of this drug during the observation year after heart transplantation.

© 2018 Russian Transplant Society. All rights reserved. Chronic HCV infection is the leading cause of liver transplantation in adults in developed countries. Unfortunately, the reinfection of the graft inevitably occurs in all patients with persistent replication of the virus. Against the background of the necessary immunosuppressive therapy, the progression of the disease accelerates, leading to rapid decompensation of the liver. Antiviral therapy significantly improves the results of transplantation, but the use of standard interferon-based regimens is associated with low efficacy (no more than 30% for the most common 1 genotype of the virus) and poor tolerance. The article describes new interferon-free oral regimens used to treat the recurrence of HCV infection of 1 genotype.

© 2018 Izdatel'stvo Meditsina. All Rights Reserved. In the review article are considered the recent data that emphasize the role of cortical disturbances in the pathogenesis of vestibular disorders. The vestibular system not only provides a link between motor and sensory processes, its functions are much more extensive. The experiments conducted in recent years on primates, as well as the data obtained by neuroimaging methods, have significantly advanced our understanding of the functioning of the vestibular system, especially its central parts. The vestibular cortex can be considered as a network of connections between all cortical areas receiving sensory input from the vestibular system, including cerebral zones in which vestibular information affects the analysis of other sensory (i.e. somatosensory and visual) and motor activity. The pathogenesis of vertigo and tinnitus is especially analyzed.