Chronic Infectious Process Research Articles

The paradigm of possibilities leading to the formation of autoimmune and infectious phenotypes of common variable immune deficiency

The term variable in the definition of CVID is associated with the heterogeneity of the genetic nature and clinical manifestation of this variant of PI. Deciphering of the mechanisms or identifying biomarkers of clinical heterogeneity may be important in the timely diagnosis and prognosis of the course of CVID. The purpose of the study was to identify distinctive features in the parameters of the innate and adaptive immune response of the patients with infectious and autoimmune manifestations of CVID in remission and clinical manifestation. Fifteen patients, 11 women and 4 men with an average age 39.7±11.7 years were examined, and they were divided into two subgroups depending on clinical verification: infectious phenotype (10 people) and autoimmune phenotype (5 people). In the absence of clinical signs of activation of autoimmune pathology or exacerbation of chronic infectious processes, peripheral blood monocytes became the application point of distinctive values. An increase in the number of TLR9-expressing monocytes has been shown in patients with autoimmune clinical verification of CVID. The differences in the parameters of the immune status of patients conducted during the period of clinical manifestation consisted of a decrease in the relative content and absolute number of T regulatory lymphocytes, and an increase in the number of monocytes containing TLR9, TLR2 and HLA-DR in patients with an autoimmune phenotype relative to the subgroup with infectious manifestation. The data obtained reflect the involvement of the immunoregulatory potential of the immune system in the clinical manifestation of primary immunodeficiency, even under the conditions of pathogenetic substitution therapy. The evidence of the stated position is a decrease in immunosuppression in autoimmune manifestation due to a decrease in the number of peripheral T-regulatory cells and a smaller proportion of monocyte cells belonging to the M2 suppressive category. Attention is also drawn to the increased potential of primary response to patterns of various nature in autoimmune manifestation due to an increase in the number of monocytes expressing Toll-like receptors of various specificity. The presented results can be proposed as a diagnostic and prognostic indicator of the difference in clinical phenotypes of CVID.

Nonmalignant tracheal stenosis: presentation, management and outcome in limited resources setting

BackgroundNonmalignant tracheal stenosis is a potentially life threatening conditions that develops as fibrotic healing from intubation, tracheostomy, caustic injury or chronic infection processes like tuberculosis. This is a report of our experience of its management with tracheostomy, rigid bronchoscopic dilation and surgery.MethodsRetrospective study design was used. 60 patients treated over five years period were included.ResultsMean age was 26.9 ± 10.0 with a range of 10–55 years. Majority (56 patients (93.3%)) had previous intubation as a cause for tracheal stenosis. Mean duration of intubation was 13.8 days (range from 2 to 27 days). All patients were evaluated with neck and chest CT (Computed Tomography) scan. Majority of the stenosis was in the upper third trachea − 81.7%. Mean internal diameter of narrowest part was 5.5 ± 2.5 mm, and mean length of stenosed segment was 16.9 ± 8 mm. Tracheal resection and end to end anastomosis (REEA) was the most common initial modality of treatment followed by bronchoscopic dilation (BD) and primary tracheostomy (PT). The narrowest internal diameter of the tracheal stenosis (TS) for each initial treatment category group was 4.4 ± 4.3 mm, 5.1 ± 1.9 mm and 6.7 ± 1.6 mm for PT, tracheal REEA and BD respectively, and the mean difference achieved statistical significance, F (10,49) = 2.25, p = 0.03. Surgery resulted in better outcome than bronchoscopic dilation (89.1% vs. 75.0%).Discussion and conclusionNonmalignant tracheal stenosis mostly develops after previous prolonged intubation. Surgical resection and anastomosis offers the best outcome.

Prospects for the development of adaptive medical immunology

The processes of adaptation of the human immune system to negative internal and external influences, including stress, infectious, environmental factors, are controlled by the neuroimmunoendocrine complex (NIEC). The normal functioning of the NIEC is the close interaction between the nervous, immune and endocrine systems. The normal NIEC allows the immune system show its adaptive capabilities, remain resistant to various negative influences, while maintaining the ability to repel attacks of various pathogens, neutralize allergic and autoimmune reactions. In case of violations of the normal functioning of the NIEC, adaptive processes in the immune system, the interaction of the immune, nervous and endocrine systems suffer, which leads to persistent violations of the functioning of the immune system and can manifest the formation of diseases of the immune system, including acquired immunodeficiency. We have justified the need to create a new promising scientific direction – adaptive medical immunology, which is based on the study of the features of disorders of the human immune system under acute or chronic exposure to negative internal and external, stressful, infectious, urban factors, resulting in a “breakdown of the adaptive capabilities of the immune system” and, as a result, the diseases exist of the immune system, including acquired immunodeficiency and related immune-dependent diseases. The aim of adaptive medical immunology is to develop an algorithm for complex immunodiagnostics and to create integrative interdisciplinary programs for correction immune system, including immunotherapeutic approaches that affect acquired disorders and restore an adaptive activities of the immune system. The main task is the restoration of an adequate response of the immune system to the existing atypically occurring acute or chronic infectious and inflammatory process, as well as the leveling of disorders of the nervous and endocrine systems with restoration their balanced interaction in the NIEC. Such an integration approach contributes to the restoration of the normal functioning of the immune system, the formation of positive clinical efficacy and the exit of patients into long-term clinical remission. Another task of adaptive medical immunology is the creation of promising innovative diagnostic technologies and, on this basis, the development of new integration programs for targeted restoration of damage to the immune system, as well as the nervous and endocrine systems in immunocompromised patients suffering from various immune-dependent diseases.

Implant tuberculosis: A rare but possible cause in nonhealing surgical wound!

Tuberculosis is most commonly involving lungs and less than 20% cases were showing extrapulmonary involvement. Tuberculosis at surgical site is described in medical literature with very few cases in caesarean section surgical incision site. Implant tuberculosis is first time described in literature and is defined as “tuberculosis developed after implantation of mycobacterium tuberculosis bacilli by artificial means without involvement of primary organ or secondary lymphatic and/or hematogenous dissemination.” Caesarean section delivery is a common method of delivery of baby. Surgical site infections resulting to slowly healing to nonhealing wound are commonly reported and usually depend on various factors. Patient factors are immune status and comorbidities of patient. Hospital management factors such as operation theatre infection control policies, sterilization techniques for surgical instruments, and local wound care methods are established and implemented by hospital staff. In this case report, a 34-year-old female with history of caesarean delivery 1 month back presented with nonhealing wound at surgical site. We have done surgical repair with biopsy of wound margins. Wound discharge microscopy was negative for acid fast bacilli with few Gram-positive cocci. Cartridge-based nucleic acid amplification testes were positive for mycobacterium tuberculosis genome. Histopathology shows tuberculous pathology and underlying chronic infectious process for nonhealing wound. We have offered antituberculosis treatment (ATT) as per protocol and observed healing of tuberculous ulcer after 3 months with reappearance of ulcer in the 4th month of ATT. We have topically applied isoniazid and streptomycin over tuberculous ulcer along with systemic ATT. Tuberculous ulcer has responded and noted “cure” as completely healed surgical wound after 6 months of ATT.

Chronic Periodontal Infection and Not Iatrogenic Interference Is the Trigger of Medication-Related Osteonecrosis of the Jaw: Insights from a Large Animal Study (PerioBRONJ Pig Model).

Background and Objectives: Antiresorptive drugs are widely used in osteology and oncology. An important adverse effect of these drugs is medication-induced osteonecrosis of the jaw (MRONJ). There is scientific uncertainty about the underlying pathomechanism of MRONJ. A promising theory suspects infectious stimuli and local acidification with adverse effects on osteoclastic activity as crucial steps of MRONJ etiology. Clinical evidence showing a direct association between MRONJ and oral infections, such as periodontitis, without preceding surgical interventions is limited. Large animal models investigating the relationship between periodontitis and MRONJ have not been implemented. It is unclear whether the presence of infectious processes without surgical manipulation can trigger MRONJ. The following research question was formulated: is there a link between chronic oral infectious processes (periodontitis) and the occurrence of MRONJ in the absence of oral surgical procedures? Materials and Methods: A minipig large animal model for bisphosphonate-related ONJ (BRONJ) using 16 Göttingen minipigs divided into 2 groups (intervention/control) was designed and implemented. The intervention group included animals receiving i.v. bisphosphonates (zoledronate, n = 8, 0.05 mg/kg/week: ZOL group). The control group received no antiresorptive drug (n = 8: NON-ZOL group). Periodontitis lesions were induced by established procedures after 3 months of pretreatment (for the maxilla: the creation of an artificial gingival crevice and placement of a periodontal silk suture; for the mandible: the placement of a periodontal silk suture only). The outcomes were evaluated clinically and radiologically for 3 months postoperatively. After euthanasia a detailed histological evaluation was performed. Results: Periodontitis lesions could be induced successfully in all animals (both ZOL and NON-ZOL animals). MRONJ lesions of various stages developed around all periodontitis induction sites in the ZOL animals. The presence of MRONJ and periodontitis was proven clinically, radiologically and histologically. Conclusions: The results of this study provide further evidence that the infectious processes without prior dentoalveolar surgical interventions can trigger MRONJ. Therefore, iatrogenic disruption of the oral mucosa cannot be the decisive step in the pathogenesis of MRONJ.

AIUM Practice Parameter for the Performance and Interpretation of Diagnostic Ultrasound of the Thyroid and Extracranial Head and Neck.

AIUM Practice Parameter for the Performance and Interpretation of Diagnostic Ultrasound of the Thyroid and Extracranial Head and Neck.

Progressive multifocal leukoencephalopathy (PML) treated with pembrolizumab in a patient with mosaic STAT3 gain-of-function mutation

Progressive multifocal leukoencephalopathy (PML) is a rare and often fatal disease of the central nervous system caused by JC virus. It occurs exclusively in immunocompromised hosts and is strongly associated with HIV infection and iatrogenic immunosuppression. Monogenic defects underlying the pathogenesis and reactivation of JC virus are not well understood, although some reports of primary immunodeficiencies (including four cases of STAT1 gain-of-function) have been previously described.A 77 year old male with history of prostate cancer (in remission; treated with radiation and hormonal therapy >10 years ago) presented with dysarthria, ataxia, left-sided weakness, diagnosed with CSF and biopsy-confirmed PML. He underwent an extensive workup upon which no other chronic infectious or oncologic processes were identified. He has never received any form of immunomodulation (including chemotherapy) in the past. Workup revealed low CD4 (347/mm3) and CD8 (282/mm3) T cell counts with normal proportions of naive vs. memory populations. Mitogen stimulation demonstrated poor CD8T cell proliferation. Targeted sequencing revealed a heterozygous mosaic mutation in the DNA-binding domain of STAT3 (c.1229 A > G p.H410R, 14% in 96 reads). This variant had been previously identified in two individuals with large granular lymphocyte (LGL) leukemia and validated as a gain-of-function via downstream signaling assays.Our patient demonstrated a favorable response to PD-1 blockade with pembrolizumab (2 mg/kg) and was discharged to a rehabilitation facility. His MRI brain showed no further progression of cerebellar white matter lesions following three doses of pembrolizumab.To our knowledge, this is the first case to implicate that STAT3 gain-of-function may confer a predisposition to JC virus reactivation and/or control in the pathogenesis of PML. Furthermore, we propose that this patient’s response to pembrolizumab may be partially attributed to STAT3-mediated regulation of the PD-1/PD-L1 axis. Further studies are currently underway to characterize this patient’s mosaic variant in flow cytometry-sorted subsets (including CD8T cells). Additional studies may include measurement of PD-1/PD-L1 expression and basal vs. induced STAT3 phosphorylation in sorted cell populations.

A Rare Case of Hepatic MALT Lymphoma with Coexistence of Hepatitis B Virus and Echinococcus Infection

Primary hepatic extranodal mucosa-associated lymphoid tissue (MALT) lymphoma is seen extremely rare compromising 0,016% among non-Hodgkin lymphomas. Association of chronic inflammatory conditions or infectious processes mostly hepatitis B virus (HBV) infection has been reported by scarce number of case presentations. Whereas MALT lymphoma accompanied by echinococcus granulosus infection was described only in one primary pulmonary lymphoma case. We herein present a primary hepatic MALT lymphoma case with both HBV carrier state and liver hydatid cyst history. A 86 years old male patient referred to our clinic with a sole liver mass and was diagnosed with primary hepatic MALT lymphoma by core biopsy. Positron emission tomography detected increased uptake in the liver lesion without any other uptake site. He was successfully treated with rituximab-chemotherapy, tenofovir and albendazole. By adding one more case to the literature we aimed to emphasize the probable etiologic causative role of echinococcus infection in MALT lymphoma.

FEATURES OF CHANGES IN INTEGRATIVE INDICATORS OF ENDOGENOUS INTOXICATION, REACTIVITY, INFLAMMATION ACTIVITY IN PATIENTS WITH CHRONIC VIRAL HEPATITIS AND CHRONIC RENAL FAILURE

The aim: to study the peculiarities of changes in integrative indicators of endogenous intoxication, reactivity and activity of inflammation in patients with chronic viral hepatitis B and C, and with chronic renal failure undergoing hemodialysis. Materials and methods. 19 patients with chronic viral hepatitis B (HBV) and chronic viral hepatitis C (HCV) with chronic renal failure and patients with chronic kidney disease (KD) were examined. Comparison group included 40 healthy blood donors. Epidemiological, clinical and laboratory examination was performed. Indicators of endogenous intoxication, nonspecific reactivity and inflammatory activity were calculated and analyzed using statistical criteria (M±m, Student's test and Mann–Whitney test). Results: an increase in the integrative indicators of endogenous intoxication in patients with the combined pathology of chronic KD and chronic viral hepatitis (VH) is a consequence of the activation of tissue disintegration, cytolysis of hepatocytes and a significant impairment of liver function. A change in the indices of non-specific inflammation indicate expressed activity of the inflammatory process and immunological disorder of reactivity. These changes also suggest decompensated endotoxicosis, as a possible consequence of a chronic infectious process and decompensated endogenous intoxication. Indicators of leukocyte intoxication index (LII), leukocyte shift index (ISL), hematological intoxication index (HII), intoxication index severity (IIS), immunoreactivity index (IR), neutrophil-monocyte ratio (NMR) are increased in all patients with chronic KD, which may be related to the actual cause of development – glomerulonephritis, chronic pyelonephritis, concomitant pathology. More pronounced deviations were found in men of both groups than in women, which may be related to greater adherence to diet, water load between hemodialysis procedures in the latter. Conclusions. Patients receiving invasive manipulations, including hemodialysis, belong to the risk group and are more susceptible, taking into account immunodeficiency, to infection with hepatitis viruses than the general population. CVH is one of the most common types of lesions in them. The obtained changes, namely, a more pronounced increase in the integrative indicators of endogenous intoxication, in patients with the combined pathology of CKD and CVH indicate the activation of the processes of tissue decay, cytolysis of hepatocytes and significant liver function impairment. At the same time, a change in indices of non-specific inflammation indicates a pronounced activity of the inflammatory process and an immunological disorder of reactivity. A clear systemic reaction to inflammatory processes in the body of patients is determined, the probable development of decompensated endogenous intoxication, which is possible consequence of a chronic infectious process. A simultaneous increase in ISL and a decrease in ILG was established, which is associated with the development of endogenous intoxication and a violation of immunological reactivity due to autointoxication of the body. A decrease in Ilymph indicates an active adaptive reaction of white blood cells and a cell-type immunodeficiency, in particular, a decrease in non-specific anti-infective protection. Indicators of LII, ISL, HII, IIS, IR, NMR are increased in all patients with CKD, which may be related to the actual cause of development – glomerulonephritis, chronic pyelonephritis, etc. The difference of integrative indicators between men and women was established, more pronounced deviations from normal were found in men of both groups than in women, which may be associated with greater adherence to diet, water load between hemodialysis procedures in the latter.

Figurate erythemas and herpetic infection in children

Herpetic infections are distinguished by a diverse clinical picture — this is primarily the so-called «recurrent respiratory diseases» or a recurrent variant of a chronic infectious process in the form of a so-called «mononucleosis-like syndrome,» characteristic of almost every «herpetic nosology,» persistent subfebrile condition, and febrile condition. Often, against the background of herpetic infections, various kinds of exanthems manifest, and this is not only a vesicular rash during infection with the herpes simplex virus. In practice, pediatricians often have to deal with other types of exanthems, one way or another associated with herpes infections. The article discusses 2 clinical observations of relatively unusual manifestations of chronic herpetic infections accompanied by erythema in patients aged 16 years. Photo documents of the dynamics of the skin process and laboratory parameters against the background of antiviral therapy are presented.

Роль вирусных инфекций нижних мочевыводящих путей в развитии нарушений мочеиспускания у женщин

Currently, an increase in the incidence and reactivation of the lower urinary tract viral infections is seen in women that often manifest as various micturition disorders. The most common viral agents are herpes simplex virus types 1 and 2, Varicella-Zoster virus, Epstein-Barr virus, cytomegalovirus, and human papillomavirus. Since micturition disorders in bacterial cystitis and viral infections of the lower urinary tract are identical, urologists often prescribe antimicrobial drugs. This, in turn, not only has no effect in the treatment of micturition disorders, but also leads to the imbalances in the microflora of vagina and lower urinary tract, and, as a result, to the development of a chronic infectious process. This review presents the main characteristics, as well as features of the pathogenesis, diagnosis and treatment of the most common lower urinary tract viral infections.

Non-drug treatments for bronchiectasis

In recent decades, attention to lung diseases associated with bronchiectasis has increased significantly. Despite the availability of modern effective therapy methods, primarily inhalation therapy, the problems of improving mucociliary clearance, reducing hypersecretion in pathologically deformed bronchi do not lose relevance. In patients with bronchiectasis, cystic fibrosis, COPD with bronchiectasis, methods of kinesitherapy to improve lung drainage function come to the fore. One of modern effective methods of kinesitherapy is the use of simulators with positive expiratory pressure. This includes the PARI O-PEP and the PARI PEP S system. These simulators are effective and easy to use. The PARI PEP S system is attached to a nebulizer and the patient can perform basic mucolytic therapy with exhaled resistance, which is more effective in influencing lung drainage function. The use of expiratory simulators is even more effective if included in a pulmonary rehabilitation course, conducted in conjunction with the improvement of breathing pattern (breathing pattern) through the use of aspiratory simulators, with training of the upper and lower muscle groups that are affected by chronic infectious process. The use of hardware methods to improve lung drainage function, such as vibration and compression therapy, is important to manage exacerbations of bronchiectasis. Due to the pandemic of new coronavirus infection (COVID-19), it is necessary to prevent worsening of the course or exacerbation of lung diseases associated with bronchiectasis, so the daily use of physical training, aspiration training and expiratory exercise machines is essential.

An Unusual Entity Mimicking Hepatocellular Carcinoma

Introduction: Reactive lymphoid hyperplasia (RLH) or Pseudolymphoma of the liver is a benign lesion which etiology remains unknown, although it is considered to result from a reactive immunological response to a chronic infection or inflammatory process. It has been described in multiple organs but the liver involvement is extremely unusual. Imaging findings resemble other malignant lesions of the liver and laboratory tests are also unspecific. We report a case of RHL of the liver mimicking an hepatocellular carcinoma.

AUTO IMMUNE HEPATITIS AS A LIVER MANIFESTATION OF COMMON VARIABLE IMMUNODEFICIENCY: A CASE REPORT

Common variable immunodeficiency (CVID) is a primary immunodeficiency disorder characterized by impaired differentiation of B cells with defective immunoglobulin production and paradoxically the development of autoimmune disorders. It is estimated that the prevalence of the liver disease is less than 10%. The most reported is focal nodular hyperplasia and, to a lesser extent, primary biliary cholangitis, primary sclerosing cholangitis and autoimmune hepatitis (AIH). present the case of a 22-year-old male who was admitted for hematemesis. He was diagnosed with immune thrombocytopenia 12 years ago without treatment and common variable immunodeficiency six years ago, currently three years without treatment. No family history of autoimmune or liver diseases. After extraction of the 4th molars, he presented swelling, redness, heat in the left submandibular region, unquantified fever, for which he received antibiotic treatment and non-steroidal anti-inflammatory drugs; 12 hours before admission, he began with hematemesis and hematochezia with data of hemodynamic instability, for which crystalloids are administered, the physical examination presents scleras with jaundice, an edematous, erythematous area with local heat in the left submandibular region, flat, symmetrical abdomen, absence of collateral circulation, Non-painful hepatomegaly, without shifting dullness. Laboratory admission with anemia, thrombocytopenia, cholestatic pattern in liver biochemistry tests, chronic viral infectious processes are ruled out and antibodies are made for autoimmune diseases, ANA 1:1200 is documented, other antibodies negative. Esophagogastroduodenoscopy where large esophageal varices of Baveno and severe portal hypertensive gastropathy (image 1 panel A). Doppler ultrasound reports diffuse liver disease, 14mm portal vein, with the presence of free fluid perihepatic and perisplenic, without biliary obstruction data (image 1 panel B). Percutaneous liver biopsy: fibrosis F2-3 on the scale of Metavir, interface hepatitis, associated with infiltrate lymphoplasmacytic integrating diagnosis of AIH (image 1 panel C). The prevalence of this condition is estimated at 1 in every 50,000 people worldwide. Up to 25% of patients with CVID will have an association with autoimmune diseases, representing the heterogeneous nature of the disease. The presentation of liver disease commonly reported in case series is anicteric cholestasis, and biopsies show evidence of non-cirrhotic portal hypertension. However, the association of CVID and AIH is rare; its diagnosis requires biopsies due to the lack of expression of antibodies in most cases. In CVID patients with altered liver function tests, the association with autoimmune liver diseases should be ruled out to initiate timely treatment and avoid late complications. The authors declare that there is no conflict of interest.

Delta-He a new biomarker for a surgical clinic

Delta-He the difference between hemoglobin content in reticulocytes and erytrocytes is a relatively new laboratory indicator that is easily measured in everyday practice. This parameter is directly related to iron bioavailability for hemoglobin synthesis and can reflect various conditions accompanied by cytokine expression including systemic inflammation. To analyze the prospects for practical application of hemoglobin delta in assessment of neurosurgical patients throughout in-hospital treatment. We analyzed complete blood counts (Sysmex XN-1000 analyzer) with optical determination of reticulocyte hemoglobin and automatic calculation of Delta-He in 82 neurosurgical patients. Exclusion criteria were severe decompensated comorbidities, exacerbation of chronic infectious processes, cancer of other organs. Blood sampling for analysis of delta-hemoglobin was carried out before all diagnostic and therapeutic measures. Reference interval is indicated by the analyzer manufacturer as 1.7-4.4 pg. Delta-He values at admission ranged from -1.8 to 6.1 pg. There was a consistent decrease of these values throughout 3-4 postoperative days. Then, the values could increase or continued to decrease. Increment of the index was noted in 76 patients (92.7%). Such dynamics was observed in case of uncomplicated postoperative period. Further decrease of Delta-He was observed in 6 patients (7.3%). These ones were characterized by a longer recovery after surgery, and the events required additional medical or surgical correction were recorded. Negative dynamics of Delta-He values could precede clinical manifestations of certain complication. Clarification of diagnosis and correction of therapy were accompanied by gradual increase of Delta-He values. Estimation of Delta-He values over time can be used for monitoring of patients and effectiveness of therapy. From a practical point of view, it is important that examination can be performed at any time of the day.

Repurposing potential of rimantadine hydrochloride and development of a promising platinum(II)-rimantadine metallodrug for the treatment of Chikungunya virus infection

Most of the patients infected with Chikungunya virus (CHIKV) develop chronic manifestations characterized by pain and deformity in joints, impacting their quality of life. The aminoadamantanes, in their turn, have been exploited due to their biological activities, with amantadine and memantine recently described with anti-CHIKV activities. Here we evaluated the antiviral activity of rimantadine hydrochloride (rtdH), a well-known antiviral agent against influenza A, its platinum complex (Pt-rtd), and the precursor cis-[PtCl2(dmso)2], against CHIKV infection in vitro. The rtdH demonstrated significant antiviral activity in all stages of CHIKV replication (29% in pre-treatment; 57% in early stages of infection; 60% in post-entry stages). The Pt-rtd complex protected the cells against infection in 92%, inhibited 100% of viral entry, mainly by a virucidal effect, and impaired 60% of post-entry stages. Alternatively, cis-[PtCl2(dmso)2] impaired viral entry in 100% and post-entry steps in 60%, but had no effect in protecting cells when administered prior to CHIKV infection. Collectively, the obtained data demonstrated that rtdH and Pt-rtd significantly interfered in the early stages of CHIKV life cycle, with the strongest effect observed to Pt-rtd complex, which reduced up to 100% of CHIKV infection. Moreover, molecular docking analysis and infrared spectroscopy data (ATR-FTIR) suggest an interaction of Pt-rtd with CHIKV glycoproteins, potentially related to the mechanism of inhibition of viral entry by Pt-rtd. Through a migration retardation assay, it was also shown that Pt-rtd and cis-[PtCl2(dmso)2] interacted with the dsRNA in 87% and 100%, respectively. The obtained results highlight the repurposing potential of rtdH as an anti-CHIKV drug, as well as the synthesis of promising platinum(II) metallodrugs with potential application for the treatment of CHIKV infections.Importance Chikungunya fever is a disease that can result in persistent symptoms due to the chronic infection process. Infected patients can develop physical disability, resulting and high costs to the health system and significant impacts on the quality of life of affected individuals. Additionally, there are no licensed vaccines or antivirals against the Chikungunya virus (CHIKV) and the virus is easily transmitted due to the abundance of viable vectors in epidemic regions. In this context, our study highlights the repurposing potential of the commercial drug rimantadine hydrochloride (rtdH) as an antiviral agent for the treatment of CHIKV infections. Moreover, our data demonstrated that a platinum(II)-rimantadine metallodrug (Pt-rtd) poses as a potent anti-CHIKV molecule with potential application for the treatment of Chikungunya fever. Altogether, rtdH and Pt-rtd significantly interfered in the early stages of CHIKV life cycle, reducing up to 100% of CHIKV infection in vitro.

ИНФЕКЦИОННЫЙ ЭНДОКАРДИТ АОРТАЛЬНОГО И МИТРАЛЬНОГО КЛАПАНОВ СЕРДЦА ПРИ ХРОНИЧЕСКОМ УРОСЕПСИСЕ

Infective endocarditis (IE) is a multisystem disease that results from an infection, usually a bacterial one, on the endocardial heart surface. A clinical case of a patient admitted to the department of cardiovascular surgery with a diagnosis of active infectious endocarditis of the aortic and mitral valves with concomitant chronic urosepsis is described. According to the bacteriological study an etiological relationship between the origin of heart pathology and chronic urosepsis was established. The results of current methods of visual diagnostics on the basis of which the preoperative diagnosis was formed are also described. Prosthetics of the On-X 19 aortic valve and On-X 27/29 mitral valve was performed. The postoperative period and the features of its course were assessed, taking into account the etiological nature of infective endocarditis. This clinical case clearly shows that any chronic infectious process can cause damage to the endocardium, even with slowly developing processes of atypical origin, for example, the urinary system. Thus, this case indicates that it is necessary to examine a patient with acute and chronic infectious processes carefully and comprehensively for infective endocarditis, since in the early stages the disease manifests itself gradually; and this helps prevent serious complications in the future.

ENDOTHELIAL DYSFUNCTION AND POLYHYPOVITAMINOSIS IN PATIENTS WITH COMPLICATED DESTRUCTIVE ONYCHOMYCOSIS AND THE COMORBID METABOLIC SYNDROME

In the pathogenesis of chronic infectious fungal processes, an important role is determined by the weakening of the body's protective factors. There are endogenous and exogenous that contribute to the transformation of fungi from vegetation to pathogenic. Endogenous factors (age, general infections, metabolic diseases, hypo- and avitaminosis, metabolic syndrome, gastrointestinal diseases, neuropathy) are define some clinical variants. Destructive fungal lesions predominate in middle-aged and elderly people, in elderly patients nail pathology is half of all observations of purulent-necrotic chronic lesions of the distal parts of the hand and foot. The purpose of the work was to introduce minimally invasive nail removal or resection of nails by block-shaped eponychectomy access with the use of pedicure instruments, study of biochemical changes in the background of pathology, detection of correlations between hypo- and avitaminosis with the development of destructive onychomycosis. It has been established that conservative, podiatric and orthopedic treatment of mycotic surgical lesions and secondary nail incarnation are not very effective, while some classical methods are Dupuytren's nail removal, Emmert-Schmiden operation and others in 2-20% of cases (depending on the absence or presence of onychocryptosis and associated fungal lesions) determine recurrences. Instead, the proposed low-trauma removal or resection of nails by block-shaped eponychectomy access using pedicure instruments, excision of dermatophytoma with partial marginal matrixectomy, which significantly reduces the number of recurrences of ingrowth (respectively 1-3% in the early stages and , 3,25% та 6,42% periods of growth, χ2 = 28,17, p<0,01) and determines the improvement of quality of life. The study of endothelial function revealed the presence of endothelial dysfunction in most patients, which confirms our previous studies and literature data. Blood lipid spectrum was significantly higher in both groups of patients (main and comparison group), compared with almost healthy individuals (p<0.01 for both groups, compared with controls), which is consistent with the literature. It was found that the supply of vitamins B1, B2, PP, B6 and C directly correlated with the severity of the underlying disease. In patients with polyonychomycosis with significant symptoms of background polyhypovitaminosis , some purulent complications of mycotic onychodestruction were detected – subungual abscess / panaritium, complicated nail incarnation and mycotic-associated paronychia with purulent onychia / onycholysis of more than three nail plates. For comparison, in the other half of the sample of persons with less pronounced symptoms of polyhypovitaminosis, some purulent complications were found in only 37.5% of the subsample, which suggests that there is a relationship between the manifestations of multivitamin deficiency and the severity of necrotic complications. Low-traumatic mobilization of the nail through a block-like eponihectomy and nail plates removal or resection (some nail incarnation ) of through areas of onycholysis/onychomadesis, or resection of nails through hyperkeratosis / onycholized structures using our methods, according to our comp lex analysis, due to reduction of intraoperative injury, determines increasing the rate of wound healing ( χ 2=32,14, p<0,01) and statistically significant minimization of the risk of mixed and reinfection of adjacent anatomical structures.

BACTERIAL BIOFILM IN CHILDREN WITH CHRONIC RHINOSINUSITIS AND CHRONIC ADENOIDITIS

Chronic rhinosinusitis with chronic adenoiditis in children represents a global public health issue, seriously affecting the quality of parents and children life, because of its irritating symptoms like intermittent snoring, mouth breathing, dry mouth, nasal obstruction, headaches increased irritability and focus disorders on children. Bacterial biofilms are highly associated with the chronic infectious processes in children. Correct therapeutical management of this diagnostic combination is mandatory to improve the quality of one’s life. Objectives. The aim of the study is: to observe the ratio of adenoid mucosa covered with bacterial biofilm extracted from the nasopharynx of 50 paediatric patients suffering of chronic rhinosinusitis (RSC) and chronic adenoiditis (CA); and to point the fact that the adenoids contaminated with bacterial biofilm are a generator for chronic upper airway infections in children. Material and methods. We have measured using an image analysis program the bacterial biofilm covering the entire surface of the extracted adenoids mases, from 28 girls and 22 boys aged between 5 and 12 years diagnosed with CRS and CA. Control visits were performed to verify symptom improvement at 1, 3 and 6 months. Outcomes. Adenoids extracted from paediatric patients diagnosed with CRS and CA presented bacterial biofilms coverage on almost the entire mucosa (86.75%). Conclusions. Adenoid mases removed from paediatric patients with CSR and CA have most of their mucosal covered with bacterial biofilm. In the nasopharynx of paediatric patients with CSR and CA, bacterial biofilm can play the role of a constant fountain of infection. Adenoid mass removal explains the symptomatic improvement observed post operatory in the CRS with CA paediatric patients that do not respond to antibiotic therapy.

Антибиотикорезистентность как фактор вирулентности условно-патогенных микроорганизмов

Introduction: A large number of infectious processes are associated with opportunistic microorganisms. The phenotype of antibiotic resistance of such pathogens is multidrug-resistant strains with the presence of various β-lactamases. Our objective was to determine the phenotypic and genotypic features of antibiotic resistance of staphylococci, enterobacteria, and non-fermenting Gram-negative bacteria – the cause of infectious diseases in patients of various health facilities of Nizhny Novgorod. Material and methods : Using classical microbiological methods and molecular genetic studies, we analyzed 486 strains of microorganisms isolated from the upper respiratory tract, intestines, urine, and wound discharge of patients in 2019–2020. In all isolates, the phenotype of antibiotic resistance was determined by the disco-diffusion method (Bioanalyse, Turkey) and using the Multiscan FC spectrophotometer (ThermoScientific, Finland) with Microlatest tablets (PLIVA-Lachema, Czech Republic), along with molecular features of resistance mechanisms by PCR on the CFX96 device (BioRad, USA) using AmpliSens kits (Russia). Results and discussion : The results showed that the most prevalent causative agents of infectious diseases (40.7 %) were Gram-negative bacteria, of which Enterobacteriaceae and non-fermenting bacteria accounted for 27.1 % and 13.6 % of cases, respectively. Staphylococci were isolated in 37.6 % of patients: S. aureus and coagulase-negative staphylococci induced 13.4 % and 24.2 % of cases, respectively. The analysis of antibiotic resistance of the isolates showed a high level of antimicrobial resistance in all hospitals, regardless of the isolation locus. The phenotype of methicillin-resistant strains was found in 26.3 % and 37.9 % of S. aureus and coagulase-negative staphylococci, respectively; the mecA gene was found in 89.0 % of methicillin-resistant staphylococci. The highest number of antibiotic-resistant strains among Gram-negative microorganisms was observed in K. pneumoniae , A. baumannii , and P. aeruginosa . We established that 61.7 % of K. pneumoniae , 75.1 % of A. baumannii , and 58.2 % of P. aeruginosa were resistant to carbapenems. The results of molecular genetic studies confirmed the presence of serine carbapenemases KPC and OXA groups in all multidrug-resistant K. pneumoniae and A. baumannii ; genes of the metallo-β-lactamase of VIM group were found in 40.9 % strains of P. aeruginosa . The production of numerous β-lactamases and the presence of determinants of antibiotic resistance in the genome determine the virulent properties of opportunistic microorganisms. Conclusion: The antibiotic resistance of opportunistic microorganisms is the cause of developing a chronic infectious process. Today, a wide spread of antibiotic-resistant infectious agents is a serious public health problem, which determines the need for constant microbiological monitoring and studies of molecular mechanisms of resistance to identify the most potent antibiotics and to determine the ways of eradication of multidrug-resistant strains.