[Experience with dupilumab in the treatment of chronic rhinosinusitis with nasal polyps]. / Opyt primeneniya dupilumaba v lechenii khronicheskogo rinosinusita s polipami.

Chronic rhinosinusitis (CRS) with nasal polyps is the most severe form of inflammatory diseases of the paranasal sinuses, especially in combination with comorbid asthma. A new avenue for the personalized treatment of severe forms of eosinophilic inflammation are biologics based on humanized monoclonal antibodies. OBJECTIVE: To study the effectiveness of targeted therapy in patients with CRS with nasal polyps and comorbid asthma. MATERIAL AND METHODS: 19 patients selected for biological therapy according to international criteria were studied. The patients were randomly divided into 2 groups. The first group included 10 patients treated with dupilumab. Dupilumab was administered subcutaneously 300 mg every 2 weeks for 24 weeks. Group 2 included 9 patients treated with reslizumab for severe eosinophilic asthma with comorbid CRS with nasal polyps. Reslizumab was administered intravenously 3 mg/kg body weight once every 4 weeks for 24 weeks. These patients constituted the comparison group. Both drugs are used in treatment of eosinophilic inflammation but have different biological targets. RESULTS: Comparative analysis of the dynamics of the main indicators characterizing the clinical course of CRS with nasal polyps and asthma (SNOT-22, control of asthma symptoms - ACT, the results of SCT of the paranasal sinuses according to the Lund-Mackay score) revealed a positive trend in patients of both groups, more pronounced in patients receiving dupilumab. CONCLUSION: Changes in CT of the paranasal sinuses, characterized by the Lund-Mackay score, the results of SNOT-22 and ACT are the most demonstrative and can be used to assess the results of treatment with biologics in patients with chronic rhinosinusitis with nasal polyps.

[A case report of organ-preserving surgical treatment for large pleomorphic adenoma of the larynx]. / Klinicheskii sluchai organosokhranyayushchego khirurgicheskogo lecheniya pri pleomorfnoi adenome gortani bol'shikh razmerov.

Tumors of the salivary glands account for no more than 5% of all neoplasms of the head and neck. About 70% of all benign neoplasms of the salivary glands are pleomorphic. One of the rare localizations of pleomorphic adenoma is the larynx. Not more than 30 cases of laryngeal localization of pleomorphic adenoma are described in the literature currently. The article presents the result of organ-preserving surgical treatment of the patient with large pleomorphic adenoma of the larynx.

[Peculiarities of fungal and bacterial microorganisms persistence in the structure of fungal balls of paranasal sinuses]. / Osobennosti persistentsii gribkovykh i bakterial'nykh mikroorganizmov v strukture gribkovykh tel okolonosovykh pazukh.

OBJECTIVE: To compare the data of pathomorphological and microbiological examination of fungal balls removed at paranasal sinuses endoscopic surgery. MATERIAL AND METHODS: A total of 148 samples were obtained from patients histologically diagnosed with fungal balls. Microscopic evaluation of the specimens stained according to the Gram method, Gomori-Grocott method and PAS-reaction method, revealed phase changes in the fungal balls conditioned by their different life cycles: the areas of young, mature and degenerating mycelium were detected. Degeneration lead to detritus formation. Detritus areas contained accumulated bacterial colonies. The cultural study of the fungal balls removed from paranasal sinuses, showed fungi growth in 17.6% of cases, while the pathomorphological study confirmed presence of fungi in every investigated sample. Aerobic and anaerobic microbiota of the sinuses contents was represented by multi-agent bacterial and fungal-bacterial associations. Statistical analysis of contingency between culture-positive rate of fungi and different bacteria detected in clinical samples from fungal balls revealed inhibitory influence of Pseudomonas aeruginosa on fungi growth, which might be a reasons of their low isolation rate. Supposedly in some cases the fungal balls consisted of dead fungi, or the sampling was done in the area of the fungal balls degeneration, which might also account for the low sensibility of the cultural method.

[Impact of reslizumab on the course of chronic rhinosinusitis in patients with eosinophilic asthma]. / Vliyanie reslizumaba na techenie khronicheskogo rinosinusita u bol'nykh s eozinofil'noi astmoi.

Chronic rhinosinusitis (CRS) with polyps is associated with eosinophilic inflammation, in which the key mediator is interleukin - 5 (IL-5) and is often combined with asthma. RESEARCH OBJECTIVES: To evaluate the therapeutic potential of reslizumab-humanized anti-IL-5 monoclonal antibody for the treatment of CRS with polyps in patients with severe asthma. PATIENTS AND METHODS: We investigated the cases of 9 patients with severe asthma treated with intravenous reslizumab at a dose of 3 mg per 1 kg of weight with regularity once in 4 weeks. The presence of CRS with polyps was revealed in 7 of 9 patients, SCT scanning of the paranasal sinuses indicated changes in all the patients, 2 patients had symptoms of chronic non-allergic rhinitis (NARES).The treatment effectiveness control was carried out after 6 months from the beginning of the treatment by the dynamics of nasal symptoms (SNOT-22), endoscopic image of the nose, total polyp score (TPS), changes in the SCT of the paranasal sinuses on the Lund-Mackay scale, rhinocytogram, the content of eosinophilic cationic protein in the blood, the level of systemic eosinophilia. The effectiveness of asthma control was assessed by the reduction of the frequency of asthma exacerbations, the need for systemic corticosteroids, spirometry data and Asthma Control Test (ACT) results. Along with a marked improvement in asthma control, 8 out of 9 patients displayed clinical, endoscopic, radiological signs of weakening of nasal symptoms. More significant improvement in asthma control was achieved in patients having CRS with polyps. In the group of patients having CRS with polyps, it was possible to detect anamnestic presence of NARES symptoms in the early stages of the disease. This indicates that NARES can be a precursor to the development of eosinophilic, non-IgE-induced asthma and nasal polyps. CONCLUSION: Treatment with reslizumab in patients with eosinophilic asthma and concomitant CRS with polyps and chronic non-allergic rhinitis (NARES) leads not only to improved control of asthma symptoms, but also to a significant regression of nasal symptoms.

[Epistaxis and arterial hypertension: a pathogenic link]. / Nosovoe krovotechenie i arterial'naya gipertenziya: patogeneticheskaya svyaz'.

THE AIM OF THIS RESEARCH: Was to study changes in the nasal mucosa vessels in hypertensive patients suffering from recurrent epistaxis. PATIENTS AND METHODS: 78 hypertensive patients aged between 50 and 70, admitted due to epistaxis were studied. Diabetic, coagulopathic patients and those taking anticoagulants were excluded from the research. All the patients were divided into 2 groups: group 1 (46 people) with a single epistaxis, group 2 (32 people) with a recurrent epistaxis. At the admission time all the patients showed elevated arterial pressure, yet the differences between the patients of group 1 and group 2 were not significant. 14 patients of group 2 did not reveal any source of hemorrhage due to a severely deviated septum. These patients underwent septoplasty followed by mucoperichondrium biopsy. Histological study of samples showed multiple erosions within the epithelial layer, as well as necrotic patches spreading to the deeper mucous coat layers. The microvasculature showed dystrophic changes in the endothelium, its focal desquamation with basal membrane exposure and thrombocytes and erythrocytes adhesion at such places, erythrocyte aggregation, plasma separation, erythrocyte and fibrinous thrombi formation. Ultrastructural investigation revealed dystrophic changes in the capillary endothelium of the nasal mucosa combined with rheological disorders expressed as erythrocytes sludge. Thus, the cause of epistaxis is not high arterial pressure, but those changes in the nasal mucosa vessels promoted by long arterial hypertension.

[Proinflammatory cytokine content in the saliva of children suffering from chronic tonsillitis]. / Soderzhanie provospalitel'nykh tsitokinov v sliune detei s khronicheskim tonzillitom.

INTRODUCTION: We have examined 92 children aged between 6 and 15, suffering from chronic tonsillitis (CT). Tumor necrosis factor (TNF-α) and interleukin 1ß and 6 (IL-1ß and IL-6) contents have been defined in saliva. The control set comprised 17 healthy children. Cytokine content was defined with the enzyme multiplied immunoassay sets (Vektor Best Ltd., Russia) by enzyme-linked immunosorbent assay. The statistic analysis and data processing were carried out with statistic analysis programs (version 3.2, R Foundation for Statistical Computing, Vienna, Austria). RESULTS: The content of cytokines TNF-α, IL-1, IL-6 in CT children's saliva was high against the healthy children, yet the statistically significant differences were only noted for IL-6. In the CT group the median value of this factor (12.5) was significantly higher than in the control set (6.72) (p=0.01 in Mann-Whitney assessment). IL-6 was chosen as the basic factor for the mathematic model; its combinations in the form of a multi-factor logistic regression were given consideration. From out of the three possible models there was just one that had all the coefficients statistically significantly different from zero (TNF-α - IL-6). It was chosen as the basic diagnostic model for chronic tonsillitis. The created model's sensitivity is 80.4%, while its specificity is 82.4%. DISCUSSION: The revealed IL-6 dominance in saliva at CT can be is attributable to permanent antigenic challenge characteristic of the toxic allergic CT since, as previously shown, there are living proliferating microorganisms in the palatal tonsil tissues and their blood- and lymph vessels at CT. CONCLUSION: The conducted ROC-analysis has demonstrated high sensitivity and specificity of the mathematical model, which enabled us to recommend determination of IL-6 in the saliva of the children suffering from CT as an additional diagnostic criterion.

[Traumatic perilymphatic fistula with the luxation of the stapes into vestibule]. / Travmaticheskaia perilimfaticheskaia fistula s liuksatsiei stremeni v preddverie.

A case of perilymphatic fistula with the luxation of the stapes into vestibule was described, which was caused by a direct damage of the eardrum (the patient cleaned the right ear with a cotton swab and received a strong blow to the arm). The moment of injury was characterized by severe pain, a significant hearing loss, the appearance of tympanophonia and vertigo. Clinical examination revealed the eardrum rupture. After perforation healing the hearing did not improve, a high degree of mixed sensorineural hearing loss remained with a bone-air interval of up to 50 dB throughout the tone scale. CT of the temporal bones showed a pneumolabirinth and a change in the malleus position, which made it possible to suggest the presence of a perilymphatic fistula with the luxation of the stapes. The extent of damage was confirmed by surgery. The stapes was removed and the perilymphatic fistula was closed.

[The significance of antistreptolysin O characteristics for the determination of indications for tonsillectomy in the children]. / Znachenie pokazatelei antistreptolizina O pri opredelenii pokazanii k tonzilléktomii u detei.

The objective of the present work was to evaluate the diagnostic significance of the measurement of the antistreptolysin O (ASLO) titers in the children presenting with chronic tonsillitis for determining the indications for tonsillectomy. The study included 54 patients at the age varying from 4 to 17 years who had undergone bilateral tonsillectomy for the treatment of chronic tonsillitis. The diagnosis was confirmed by the results of the histological study of the removed amygdalae. Prior to surgery, all the patients had been subjected to the bacteriological investigation of the smears taken from the surface of the palatal tonsils. The titers of antistreptolysin O in the serum were determined with the use of the kinetic nephelometric technique before, 6 and 12 months after the surgical intervention. The results of the measurements were treated using the Statzilla software package (version 3.2, R Foundation for Statistical Computing, Vienna, Austria). Streptococcus pyogenes (group A) was identified only in 7 (13%) patients. The initially enhanced content of ASLO ranging from 273 to 1880 IU/ml was documented in 42 (77.7%) of the 54 patients. Twelve patients had the ASLO titers within the normal limits (from 13 to 124 IU/ml). The removal of palatal tonsils resulted in a significant decrease of the ASLO titers in the patients who had presented with the initially enhanced content of antistreptolysin O (p < 0.05); nevertheless, their ASLO titers remained higher than the normal values in 69% and 82% of the patients examined within 6 and 12 months after the surgical intervention, respectively. The patients who had exhibited the high levels of antistreptolysin O during the preoperative period did not experience normalization of this parameter after surgery. It is concluded, taking into account the absence of correlation between the enhancement of serum antistreptolysin O titers and the presence of group A beta-chemolytic Streptococci (BCSA), that the result of the measurement of ASLO titers can not be considered as a valid indication for tonsillectomy in the children.

[The detection of the human papilloma virus during hyperplastic processes in the nose, ears and throat]. / Obnaruzhenie virusa papillomy cheloveka pri giperplasticheskikh protsessakh v LOR-organakh.

The objective of the present work was to carry out the virological and histological studies of various neoplastic and hyperplastic processes in the nose, ears, and throat with a view to identifying the presence of human papilloma virus and Epstein-Barr virus. The brush biopsies and remote neoplasms obtained from 18 patients (including 2 children and 16 adults) presenting with various ENT diseases and tumours were available for the virological investigation with the use of the polymerase chain reaction (PCR) and a system MY09-MY11 degenerate primers . The histological study of biopsies and remote neoplasms was carried out by means of conventional light microscopy. The virological and histological studies conducted in parallel confirmed the diagnostic significance of morphological changes at the tissue and cellular levels caused by the human papilloma virus.

[Tuberculous lesion of retropharyngeal lymph nodes responsible for labored nasal breathing]. / Tuberkuleznoe porazhenie zaglotochnykh limfaticheskikh uzlov, vyzvavshee zatrudnenie nosovogo dykhaniya.

A 62 year-old patient applied for the medical aid with complaints of labored nasal breathing. She was treated for tuberculosis in the childhood, underwent radical mastectomy in connection with left breast cancer in 2007 and adenotomy at the age of 60 years with the good functional outcome. One year after adenotomy, the enlargement of lymph nodes at the left-hand antero-lateral surface of the neck was detected. The histological changes in the lymph nodes corresponded to the picture of tuberculosis. Pharyngoscopy demonstrated an asymmetric protrusion at the posterior wall of the pharynx more prominent on the left side. Examination by spiral computed tomography revealed the presence of two enlarged lymph nodes with the signs of suppurative melting in the retropharyngeal space. These lymph nodes were opened through the posterior pharyngeal wall which resulted in the restoration of the normal pharynx configuration and the normalization of nasal breathing.

[Coordinated aberranit expression of miRNAs in colon cancer].

Applying the method of multiple parallel sequencing on the MiSeq platform (Illumina, United States), a comparative analysis of miRNA expression in tumor and normal colon tissuie cells was performed. Forty miRNAs aberrantly expressed in cancer were detected. Among them, 15 and 25 miRNAs showed increased arid decreased expression, respectively, for all or most of the cases. Sixteen miRNA clusters were identified, which showed a coordinated or incompletely coordinated aberrant expression in colorectal cancer cells. In two (miR-183/182 and miR-106b/25) and four (miR-143/145, miR-497/195, miR-30e/30c-1, and miR-30a/30c-2) miRNA clusters, respectively, a statistically significant coordinated increase or decrease in expression was iegistered for all miRNAs withini the corresponding cluster. Three aberrantly expressed well-known miRNAs (miR-100-5p, mil-30d-5p, and miR-204-5p) were identified, which, however, had never 'before been associated with coloreictal cancer. The obtained results demonstrate the potential and promising application of 6 miRNA clusters with' coordinated aberrant expression as markers for colorectal cancer.

[Inheritable changes in miRNAs expression in HeLa cells after X-ray and mitomycin C treatment].

We identified 40 miRNAs with inherited aberrant expression by multiple parallel sequencing of human HeLa cells irradiated with X rays and mitomycin C. Twenty-two miRNAs were repressed and 15 miRNAs were induced after radiation and mytomycin C treatment. The expression of three miRNAs (miR-10b-5p, miR-148a-3p, and miR-340-5p) decreased after X-ray exposure and increased after mitomycin C treatment. The spectrum of aberrantly expressed miRNAs after X-ray and mitomycin C treatment is different, except for three miRNAs (mir-100-5p, miR-99b-5p, miR-501-3p), which showed the inherited decreased expression after both mutagens. It has been ascertained that for five miRNAs (miR-21-3p, miR-182-5p, miR-19b-3p, miR-30a-3p, and miR-30e-3p) with increased inherited expression, the targets are well-described tumor suppressor genes. For 9 miRNAs (miR-99b-5p, miR-148a-3p, miR-365a-3p, miR-193a-3p, miR-100-5p, miR-99a-5p, miR-29b-3p, miR-340-5p, and miR-23b-3p) with reduced inherited expression, the targets are oncogenes. The obtained results provide further support of the idea that induced epigenetic changes in the genome should be considered when assessing the long-term genetic effects of ionizing radiation and chemical compounds.

[Further improvement of the methods for the arrest of nasal bleeding].

Gauze tamponade of the nasal cavity is one of the most popular and convenient methods for the arrest of nasal bleeding. We used a polyvinyl pyrrolidone (PVP) powder that prevents local fibrinolysis by virtue of its sorption properties. PVP placed on the tampons and insufflated into the nasal cavity after their removal was shown to significantly decrease manifestations of reactive oedema and frequency of recurrent bleeding. These effects are attributable to the modifying action of PVP on fibrin thrombus and amplification of erythrocyte aggregation. On the one hand, fibrin thrombi formed close to the source of bleeding become harder due to the thickening of fibrin filaments; on the other hand, increased permeability of the fibrin network facilitates unobstructed penetration of fibrinolytic factors into the nasal cavity where they are sorbed and inactivated by PVP molecules. The hemostatic effect of PVP is promoted by enhanced erythrocyte aggregation.