Mucormycosis is a severe mycotic infection with high mortality among immunocompromised patients. Its in- cidence in solid organ transplant recipients is 2–8% of all invasive fungal infections. In most cases, it occurs in the late posttransplant period. Risk factors in this patient cohort are graft-versus-host disease (GvHD) and use of immunosuppressive drugs. The article describes clinical cases of mucormycosis and analysis of literature data on the problem of invasive mucormycosis in solid organ transplant recipients. It also reviews the main methods of diagnosis and treatment of the disease according to international guidelines.

Invasive fungal infections (IFIs) are a serious threat to patients with hematological diseases. These infections are characterized by high mortality and lead to significant financial costs for treatment. The most common pathogens of IFIs are Aspergillus spp. and Candida spp., but in recent years, cases of infections caused by rare pathogens have become more frequent. Diagnosis of IFIs and choice of treatment remain challenging due to the nonspecificity of symptoms and the diversity of clinical cases. In this regard, the problem of start time and choice of antifungal therapy remains of current interest. This review briefly describes diagnostic criteria, challenges associated with IFIs diagnosing, provides evidence for empiric and preventive strategies as two early treatment approaches, and examines the impact of therapy initiation on patient outcomes. Treatment of IFIs in hematologic patients should be individualized. At the same time, early administration of therapy with broad-spectrum drugs for febrile neutropenia and parallel diagnostic measures can improve treatment outcomes. There is a lack of current data on the benefits of specific treatment strategies, highlighting the need for further research.

We studied the risk factors, etiology, clinical manifestations, and treatment outcomes of COVID-19-associated invasive candidiasis (COVID-IC) in adult patients admitted to six medical facilities in St. Petersburg. (November 2020–December 2022). In this retrospective study, we included 72 patients with COVID-IC with a median age of 61 years (range 29–96), 51% of whom were women. The predisposing factors for COVID-IC were a central venous catheter (CVC) for more than 10 days (the odds ratio (OR) = 70 [15–309]), abdominal surgical treatment performed in the previous 2 weeks (OR = 8.8 [1.9–40.3]), bacteremia (OR = 10.6 [4.8–23.3]), pulmonary ventilation (OR = 12.9 [5.9–28.4]), and hemodialysis (OR = 11.5 [2.5–50.8]). The signs and symptoms of COVID-IC were non-specific: fever (59%), renal failure (33%), liver failure (23%), and cardiovascular failure (10%). Candida albicans (41%) predominated among the pathogens of the candidemia. The multidrug-resistant Candida species C. auris (23%) and C. glabrata (5%) were also identified. Empirical therapy was used in 21% of COVID-IC patients: azole-93%, echinocandin–7%. The majority of COVID-IC patients (79%) received, after laboratory confirmation of the diagnosis of IC, fluconazole (47%), voriconazole (25%), echinocandin (26%), and amphotericin B (2)%. The 30 days overall survival rate was 45%. The prognosis worsened concomitant bacteremia, hemodialysis, and long-term therapy by systemic glucocorticosteroids (SGCs), bronchial colonization with Candida spp. The survival prognosis was improved by the early change/replacement of CVC (within 24 h), the initiation of empirical therapy, and the use of echinocandin. Conclusions: We highlighted the risk factors that predispose COVID-19 patients to candidiasis and worsen the survival prognosis. Their individual effects in patients with COVID-19 must be well understood to prevent the development of opportunistic co-infections that drastically lower chances of survival.

Целью исследования является определение перечня опорных населённых пунктов, составляющих опорный каркас расселения Чувашской Республики с помощью авторской методики, базирующейся на анализе социально-демографических факторов. Методологическую базу исследования составляют общелогические методы, методы исследования статистики, геоинформационные методы (построение карт-схем, метод изохрон). Для подготовки и обработки данных использовались MS Excel и MS Power BI, для построения карт — ESRI ArcGis и Here Studio. Источниками данных выступили краеведческие источники, данные «Всероссийской переписи населения-2010», оценочные данные о численности населения в населённых пунктах за 2020 год, а также данные о наличии и качестве объектов социальной инфраструктуры в населённых пунктах Чувашии, представленные на официальном геоинформационном портале Чувашии. Результаты. В статье представлена методика выявления «опорного каркаса расселения» региона на основе анализа социально-демографических факторов. В данном случае «опорный каркас расслоения» представлен как сеть наиболее устойчивых населённых пунктов с точки зрения их демографической динамики, а также наиболее перспективных в плане наличия необходимой социальной инфраструктуры. Методика позволила выявить «опорный каркас расселения» Чувашской Республики. «Каркас» включает в себя 10 узловых центров, один из которых представлен Чебоксарской агломерацией, тогда как остальные 9 — «опорными населёнными пунктами» (включая 3 потенциальных и 3 состоящих из пары сопредельных населённых пунктов). Результат представлен в виде карты-схемы. Проанализированы и визуализированы зоны 30 и 60-минутной транспортной доступности от узловых центров «опорного каркаса». Перспективы исследования. Представленная в статье методика определения «опорного каркаса расселения» на примере Республики Чувашии может служить инструментом для принятия обоснованных управленческих решений по формированию приоритетов в финансировании и модернизации узловых центров. Данный подход позволит создать ситуацию «управляемого сжатия» и обеспечить подавляющее большинство населения региона качественными услугами социальной сферы.

We present a case of fungal peritonitis in a patient secondary to intestinal perforation and repeated laparotomy. An analysis of data from the register of patients with invasive candidiasis is also presented. In the study were included 42 patients with candida peritonitis. The risk factors: antibiotics (100%), vascular catheters (95%), total parenteral nutrition (81%), repeated abdominal surgery (69%), sepsis (69%), bacteremia (50%), repeated perforations on the gastrointestinal tract (43%), oncopathology of the gastrointestinal tract (36%), infected pancreatic necrosis (26%). The etiology agents were C. albicans (50%), C. glabrata (14%), C. parapsilosis (7%). 45% of patients received prophylactic treatment (100% fluconazole). Empirical therapy was carried out by 52% of patients (triazoles – 38%, echinocandins – 14%). After receiving the results of the microbiological study, 3% of patients began to receive antifungal therapy (echinocandins). The 30 days overall survival rate was 66%.

РУБРИКА ОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯ Синдром хронического кандидоза кожи и слизистых у детей с мутациями гена STAT 1 1 Федеральное государственное бюджетное образовательное учреждение высшего образования «Северо-Западный государственный медицинский университет имени И.И.Мечникова» Министерства здравоохранения Российской Федерации, 191015, г.Санкт-Петербург, Российская Федерация 2 Федеральное государственное бюджетное образовательное учреждение высшего образования «Санкт-Петербургский государственный педиатрический медицинский университет» Министерства здравоохранения Российской Федерации, 194100, г

Objective. To study risk factors, clinical and radiological features and effectiveness of the treatment of invasive aspergillosis (IA) in adult patients with COVID-19 (COVID-IA) in intensive care units (ICU). Materials and Methods. A total of 60 patients with COVID-IA treated in ICU (median age 62 years, male – 58%) were included in this multicenter prospective study. The comparison group included 34 patients with COVID-IA outside the ICU (median age 62 years, male – 68%). ECMM/ISHAM 2020 criteria were used for diagnosis of CAPA, and EORTC/MSGERC 2020 criteria were used for evaluation of the treatment efficacy. A case-control study (one patient of the main group per two patients of the control group) was conducted to study risk factors for the development and features of CAPA. The control group included 120 adult COVID-19 patients without IA in the ICU, similar in demographic characteristics and background conditions. The median age of patients in the control group was 63 years, male – 67%. Results. 64% of patients with COVID-IA stayed in the ICU. Risk factors for the COVID-IA development in the ICU: chronic obstructive pulmonary disease (OR = 3.538 [1.104–11.337], p = 0.02), and prolonged (> 10 days) lymphopenia (OR = 8.770 [4.177–18.415], p = 0.00001). The main location of COVID-IA in the ICU was lungs (98%). Typical clinical signs were fever (97%), cough (92%), severe respiratory failure (72%), ARDS (64%) and haemoptysis (23%). Typical CT features were areas of consolidation (97%), hydrothorax (63%), and foci of destruction (53%). The effective methods of laboratory diagnosis of COVID-IA were test for galactomannan in BAL (62%), culture (33%) and microscopy (22%) of BAL. The main causative agents of COVID-IA are A. fumigatus (61%), A. niger (26%) and A. flavus (4%). The overall 12-week survival rate of patients with COVID-IA in the ICU was 42%, negative predictive factors were severe respiratory failure (27.5% vs 81%, p = 0.003), ARDS (14% vs 69%, p = 0.001), mechanical ventilation (25% vs 60%, p = 0.01), and foci of destruction in the lung tissue on CT scan (23% vs 59%, p = 0.01). Conclusions. IA affects predominantly ICU patients with COVID-19 who have concomitant medical conditions, such as diabetes mellitus, hematological malignancies, cancer, and COPD. Risk factors for COVID-IA in ICU patients are prolonged lymphopenia and COPD. The majority of patients with COVID-IA have their lungs affected, but clinical signs of IA are non-specific (fever, cough, progressive respiratory failure). The overall 12-week survival in ICU patients with COVID-IA is low. Prognostic factors of poor outcome in adult ICU patients are severe respiratory failure, ARDS, mechanical ventilation as well as CT signs of lung tissue destruction.

The prevalence of invasive candidiasis (IC) in pediatric hospitals is from 4,3 to 15,2 per 10,000 hospitalized, in ICU – from 3,5 to 7 cases per 1,000, with HSCT – 2,9%. The average length of stay of a patient in the hospital before the development of IC varies from 21 to 56 days, in the ICU – more than 15 days. Knowledge of risk factors (ICU stay for ≥15 days, use of antibacterial drugs and parenteral nutrition, active malignant neoplasm, etc.) makes it possible to identify patients with a high (10-46%) risk of developing IC. Candida albicans remains the leading causative agent of IC in children, but infections with non-albicans Candida spp. have increased and an increase in the resistance of IC pathogens to azole antimycotics was noted. The main clinical variant of IC in children is candidemia, other forms include the central nervous system, abdominal organs, eyes, heart, bones and joints, kidneys, skin and subcutaneous tissue involvement, as well as chronic disseminated (hepatolienal) candidiasis. Blood culture, the main method of laboratory diagnostics of IC, is characterized by low sensitivity and requires a long time. Methods of noncultural diagnostics of IC (1,3-β-D-glucan, mannan and antimannan antibodies, T2 Candida etc) in children have not been sufficiently studied. The main drugs for the treatment of IC in children are echinocandins (anidulafungin, etc.), and CVC removal/replacement is necessary. The overall mortality rate in pediatric patients within 30 days after the diagnosis of IC is 37% to 44%.

Introduction. In children with rheumatic diseases, severe fungal infections (invasive mycoses – IM) are not well understood.Objectives. To analyze risk factors, disease course of IM in children with systemic rheumatic diseases.Materials and methods. For diagnosis of IM were used criteria EORTC/MSGERC, 2019. We reviewed the literature over the past 15 years on IM in children with rheumatic diseases from the international databases Pubmed and Web of Science.Results. In retrospective multicenter study were included 8 children with IM and systemic rheumatic diseases: ANCA-associated vasculitis (n=4), systemic lupus erythematosus (n=3), juvenile rheumatoid arthritis (n=1). Median age was 13,5 (8-17) y., boys – 67%. Invasive aspergillosis was diagnosed in 5 patients and invasive candidiasis – 3. The risk factors of invasive mycoses were high rheumatic disease activity (100%), corticosteroids (prednisolone ≥ 0,3 mg/kg/d) use for ≥21 d (87,5%), immunosuppressive therapy (87,5%), recent (≤ 2 weeks) pulse steroid therapy (75%), hemophagocytic lymphohistiocytosis (62,5%), prolonged (≥ 10 days) severe neutropenia (≤ 0,5х109/l) (62,5%), and prolonged (≥10 days lymphopenia (≤ 1,0х109/l) (37,5%). In patients with invasive aspergillosis the involved organ was the lung, in patients with invasive candidiasis a candidemia was diagnoses. All patients received antifungal therapy. The overall 30 days survival rate was 37,5%.Сonclusions. Children with high rheumatic diseases activity and intensive treatment with immunosuppressive agents should be considered as patients with a high risk of invasive mycoses with a high mortality.

We studied the risk factors, etiology, clinical features and the effectiveness of therapy of COVID-19-associated pulmonary aspergillosis (CAPA) in adult patients. In this retrospective study, we included 45 patients with proven (7%) and probable (93%) CAPA. The ECMM/ISHAM, 2020 criteria were used to diagnose CAPA. A case-control study was conducted to study the risk factors of CAPA; the control group included 90 adult COVID-19 patients without IA. In CAPA patients, the main underlying diseases were diabetes mellitus (33%), and hematological and oncological diseases (31%). The probability of CAPA developing significantly increased with lymphocytopenia >10 days (OR = 8.156 (3.056–21.771), p = 0.001), decompensated diabetes mellitus (29% vs. 7%, (OR = 5.688 (1.991–16.246), p = 0.001)), use of glucocorticosteroids (GCS) in prednisolone-equivalent dose > 60 mg/day (OR = 4.493 (1.896–10.647), p = 0.001) and monoclonal antibodies to IL-1ß and IL-6 (OR = 2.880 (1.272–6.518), p = 0.01). The main area of localization of CAPA was the lungs (100%). The clinical features of CAPA were fever (98% vs. 85%, p = 0.007), cough (89% vs. 72%, p = 0.002) and hemoptysis (36% vs. 3%, p = 0.0001). Overall, 71% of patients were in intensive care units (ICU) (median—15.5 (5–60) days), mechanical ventilation was used in 52% of cases, and acute respiratory distress syndrome (ARDS) occurred at a rate of 31%. The lung CT scan features of CAPA were bilateral (93%) lung tissue consolidation (89% vs. 59%, p = 0.004) and destruction (47% vs. 1%, p = 0.00001), and hydrothorax (26% vs. 11%, p = 0.03). The main pathogens were A. fumigatus (44%) and A. niger (31%). The overall survival rate after 12 weeks was 47.2%.

Primary immune deficiencies are usually attributed to genetic defects and, therefore, frequently referred to as inborn errors of immunity (IEI). We subjected the genomic DNA of 333 patients with clinical signs of IEI to next generation sequencing (NGS) analysis of 344 immunity-related genes and, in some instances, additional genetic techniques. Genetic causes of the disease were identified in 69/333 (21%) of subjects, including 11/18 (61%) of children with syndrome-associated IEIs, 45/202 (22%) of nonsyndromic patients with Jeffrey Modell Foundation (JMF) warning signs, 9/56 (16%) of subjects with periodic fever, 3/30 (10%) of cases of autoimmune cytopenia, 1/21 (5%) of patients with unusually severe infections and 0/6 (0%) of individuals with isolated elevation of IgE level. There were unusual clinical observations: twins with severe immunodeficiency carried a de novo CHARGE syndrome-associated SEMA3E c.2108C>T (p.S703L) allele; however, they lacked clinical features of CHARGE syndrome. Additionally, there were genetically proven instances of Netherton syndrome, Х-linked agammaglobulinemia, severe combined immune deficiency (SCID), IPEX and APECED syndromes, among others. Some patients carried recurrent pathogenic alleles, such as AIRE c.769C>T (p.R257*), NBN c.657del5, DCLRE1C c.103C>G (p.H35D), NLRP12 c.1054C>T (p.R352C) and c.910C>T (p.H304Y). NGS is a powerful tool for high-throughput examination of patients with malfunction of immunity.

Objectives. Actinomycosis in children has not been studied enough, the number of publications is limited. Actinomycosis of the knee joint is very rare, the disease mimics tuberculosis or malignant neoplasms, which can lead to late diagnosis and inadequate treatment. Materials and methods. We report on the first case of an 8-year-girl with actinomycosis knee. Diagnosis is based on histological examination. Results. Surgical resection of infected tissue and longterm antibiotic therapy for 4.5 months was effective in the treatment of pediatric patient with knee actinomycosis. In the scientific literature no such clinical case was found. Сonclusion. Case of successful treatment of pediatric patient with knee actinomycosis is presented for the first time.