[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.

[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.

[COVID-19 associated sino-orbital mucormycosis]. / COVID-19-assotsiirovannyi sinoorbital'nyi mukormikoz.

OBJECTIVE: To analyze the dynamics of symptoms in patients with COVID-19 associated sino-orbital mucormycosis. MATERIAL AND METHODS: We describe a series of 13 patients with COVID-19 associated sino-orbital mucormycosis aged 43 to 80 years diagnosed from August to October 2021. All of the patients had a severe disease and required noninvasive ventilation or intubation and administration of dexamethasone. 12 out of 13 patients (92.3%) suffered from diabetes mellitus. Symptoms of fungal infections of the nose and paranasal sinuses appeared in the interval from 7 to 25 days of hospital stay, most often in the second week (from 8 to 12 days). According to clinical and CT features the patients were divided into three groups, combining similar phenotypes of the disease. Group 1 - 1 patient with sinonasal mucormycosis, destruction of the alveolar ridge and the hard palate. Group 2 - 12 patients with sino-orbital mucormycosis. We noted, that in cases of bilateral sinus lesions orbital complications were unilateral in all patients, on the side of more severe lesion. Group 2 was divided into 2 subgroups: subgroup 2a included 2 patients with the superior orbital fissure syndrome: ptosis, proptosis, ophthalmoplegia, periorbital pain, pain or hypoesthesia of half face; subgroup 2b included 10 patients with the orbital apex syndrome, who, in addition to the above symptoms, had loss of vision and conjunctival chemosis. Group 3 - rhino-sino-cerebral mucormycosis. 2 patients from subgroup 2b were transferred to this group due to the intracranial spread of the process and focal neurological symptoms. CONCLUSION: Clinical forms of mucormycosis reflect successive stages of invasive spread of fungi.

[Children's rhinosinusitis orbital complications]. / Orbital'nye oslozhneniya rinosinusita u detei.

The number of cases of children's sinogenic orbital complications does not reduce in spite of the advanced methods of paranasal sinuses visualization, wide use of antibacterial therapy against sinusitis, and preventive vaccination against pneumococcal disease. Orbital complications are more common with children than with adults, the basic reason of their development being ethmoiditis. The prevailing classification of orbital complications proposed by J. Chandler et al. divides these into preceptal and postceptal forms and gives description to 5 development stages of orbital complications in the order of their increasing severity. At an early age preceptal and orbital cellulites prevail, and these commonly need conservative treatment only. In case of orbital cellulitis, the major treatment method is endovenous antibiotic therapy in which the chosen antibiotic is to cover the whole spectrum of aerobic and anaerobic microbes often extracted in such cases. At small subperiostal abscesses (<0.5-1 ml), conservative treatment during 24-48 hours is possible. If there is no positive dynamics, or abscess grows in size, or eye symptoms progress, abscess and affected sinuses drain is recommended. Orbital abscess is to be given surgical treatment; at the same time endoscopic management of paranasal sinuses might by complemented with external surgical approaches (lateral and medial orbitotomy).

[Presbyvestibulopathy in clinical practice.]

With increasing life expectancy, there is an increase in the number of patients with symptoms caused by aging of the vestibular system - presbyvestibulopathy. Presbyvestibulopathy is based on degenerative processes in various parts of the vestibular analyzer - from the semicircular canals and otolithic receptors to the conduction tracts and vestibular nuclei. When examining such patients, it is necessary to take into account the multiplicity of damage to sensory systems in the elderly (impaired balance, vision, cognitive functions). Recognizing presbyvestibulopathy as part of the multifaceted aging process will help to develop comprehensive approaches to the treatment of patients who are always at risk for deterioration of the condition. In this review, we discuss the association of presbyvestibulopathy with neurodegenerative diseases, as well as the correlation between presbyvestibulopathy and balance, visual, cognitive, and psychological disorders.

[Small salivary glands in the paratonsillar space in children]. / Malye slyunnye zhelezy v paratonzillyarnom prostranstve u detei.

THE AIM OF THE STUDY: Was to study the changes in the small salivary glands in chronic tonsillitis and paratonsillar abscess in children. A histological examination of the palatine tonsils of 22 children aged 5 to 14 years old who had a paratonsillar abscess and 18 children suffering from chronic tonsillitis was carried out. Fragments of small salivary glands, located both superficially, in the mucous membrane between the stratified squamous non-keratinizing epithelium and the lymphoid tissue of the palatine tonsils, and between the muscles of the amygdala were found in 42 of the 80 (52.5%) tonsils studied. Along with the unchanged glandular structure, 26 (61.9%) samples revealed areas of destruction foci in small salivary glands with signs of inflammatory and compensatory regenerative activity. The presence of separate interlobular ducts of the salivary glands with pronounced periductal lymph - macrophage infiltration was noted. The subepithelial lymph-macrophage infiltrates found in the lamina propria are associated with the exit of the excretory ducts of the salivary glands to the surface of the mucous membrane. Many thin-walled veins are surrounded by perivascular lymphocellular infiltrates. The inflammatory and post-inflammatory changes in the small salivary glands revealed by us in children with chronic tonsillitis do not exclude their participation in the pathogenesis of paratonsillitis. At the same time, inflammation in the salivary gland can be both primary, as a result of its infection with live microorganisms from the tissues of the tonsil, and secondary, due to the compression of the excretory ducts by the edematous tissue of the tonsil in acute tonsillitis.

[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.

[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 influence of corticosteroids on the frequency of vestibular crises]. / Vliianie kortikosteroidov na chastotu vestibuliarnykh krizov.

The objective of the present study was to elucidate the dynamics of the hormonal status of the adrenal glands in the patients suffering from Menière's disease in its different clinical forms. We examined a total of 26 patients at the age from 29 to 47 years presenting with this condition. All the patients were divided into two groups depending on the character of the disease. Group 1 was comprised of 20 patients experiencing the crises from 2 to 6 times during a year. Group 2 was composed of six patients in whom the crises occurred with a frequency of 2-4 times per week within at least two weeks. The serum levels of cortisol and aldosterone were measured both during the crises and between them with the use of the proper immunoenzyme assays. The control group was formed of 20 practically healthy volunteers. It was shown that the blood cortisol level during a fit of dizziness in the patients of group 1 increased in comparison with that in the control subjects (798.7±71.2 nmol/l and 453.68±49.39 nmol/l respectively; p<0.05). The patients having recurrent crises (group 2) experienced a significant decrease in the blood cortisol levels down to 293.5±38.1 nmol/l during a crisis in comparison with the control subjects (453.68±49.39 nmol/l; p<0.05). During the inter-crisis periods , the blood cortisol level in the patients of the first group remained within normal bounds whereas in the patients of the second group its mean value was 18.7% lower (p>0.05). The serum aldosterone level in the patients of the first group was not significantly different from that in the second group both during crises and in the periods of remission. It is concluded that the results of the study provide the data for the pathogenetic substantiation of the possibility for the use of corticosteroids in the treatment of the patients suffering from frequent crisis of Menière's disease.

[Acute and chronic frontitis: the current view of the problem].

The number of patients presenting with the inflammatory diseases of paranasal sinuses remains rather high both in this country and all over the world despite the development of new methods for diagnostics and treatment of this pathology and their extensive application in the clinical practice. The present paper offers a systematic review of the literature concerned with diagnostics of acute and chronic diseases of frontal sinuses published during the period from 2005 to 2011. The analysis of these publications has demonstrated that these diseases still constitute a challenging problem for otorhinolaryngology despite the improvement of technologies for their diagnostics and management. It is concluded that systematization of the available methods for this purpose is needed in conjunction with the standardization of the approaches to the choice of adequate surgical strategies.

[Significance of local pain syndrome in patients with frontitis].

The diagnostic value of local pain symptom as a key sign of frontitis is currently regarded as rather low. It occurred only in 69 (14%) of the 487 patients with this disease examined in the present study. Patients presenting with ambiguous symptoms of uncomplicated unilateral frontitis were studied by rheofrontography using coefficient of asymmetry as a diagnostic criterion (its value in excess of 24% indicates the presence of exudate in the sinus cavity. The electron microscopic study demonstrated the presence of morphologically different cells in frontal sinus mucosa of patients with uncomplicated frontitis with and without local pain symptom. These findings are in excellent agreement with the data on the relationship between immunological and neurogenic components of the inflammatory reaction in patients with diseases of the upper respiratory tract.