LANGERHANS CELL HISTIOCYTOSIS IN A CHILD WITH MULTISYSTEMIC LESIONS ASSOCIATED WITH INFECTED POLIOMYELITIS AND SARS-COV-2, FEATURES OF DIAGNOSTICS. CLINICAL CASE.

Langerhans cell histiocytosis (LCH) is an abnormal clonal proliferation of Langerhans cells. The prognosis varies depending on the form of the disease and organ damage. Any organs and systems can be involved in the pathological process in various combinations. A poor response to standard therapy and an unfavorable prognosis are characteristic of patients with a multisystem form of LCH and involvement of organs at risk. Skin lesions are a classic sign of LCH. Purpose - to describe the complexity and duration of diagnosis of LCH with multisystem damage in a boy aged 2 years and 2 months, infected with poliomyelitis and coronavirus. Clinical case. The first clinical manifestations of LCH in the child debuted with an eczematous-seborrheic rash on the scalp with spread to the limbs and trunk. The child was treated for toxicoderma, hemorrhagic vasculitis at the place of residence for 6 months. The boy lost 1.5 kg of body weight in 1 month. At the time of hospitalization, seborrheic-eczematous rashes on the skin with a hemorrhagic component, trophic-inflammatory changes in the nails of the hands, signs of protein-energy deficiency, stomatitis, gingivitis, hepatosplenomegaly, polyserositis, diabetes insipidus, osteolytic foci of the frontal bones were found. Results of the tests: anemia, thrombocytopenia, hypoproteinemia and hypoalbuminemia, coagulation disorders. The patient had the onset of lower flaccid paraparesis, muscle hypotonia. The boy was diagnosed with a number of infectious complications, including poliomyelitis (a derivative of vaccine poliovirus type 2), COVID-19. The child received LCH-III cytostatic therapy with a positive effect. The research was carried out in accordance with the principles of the Helsinki Declaration. The informed consent of the patient was obtained for conducting the studies.Copyright © 2023 Institute of Physics of the Russian Academy of Sciences. All rights reserved.

Rapid tissue prototyping with micro-organospheres.

In vitro tissue models hold great promise for modeling diseases and drug responses. Here, we used emulsion microfluidics to form micro-organospheres (MOSs), which are droplet-encapsulated miniature three-dimensional (3D) tissue models that can be established rapidly from patient tissues or cells. MOSs retain key biological features and responses to chemo-, targeted, and radiation therapies compared with organoids. The small size and large surface-to-volume ratio of MOSs enable various applications including quantitative assessment of nutrient dependence, pathogen-host interaction for anti-viral drug screening, and a rapid potency assay for chimeric antigen receptor (CAR)-T therapy. An automated MOS imaging pipeline combined with machine learning overcomes plating variation, distinguishes tumorspheres from stroma, differentiates cytostatic versus cytotoxic drug effects, and captures resistant clones and heterogeneity in drug response. This pipeline is capable of robust assessments of drug response at individual-tumorsphere resolution and provides a rapid and high-throughput therapeutic profiling platform for precision medicine.

Incidence of acute intestinal infections in Saint Petersburg during COVID-19 pandemic.

The results of a study of modern epidemiological and characteristics of acute intestinal infections against the backdrop of the COVID-19 pandemic are presented. The article reflects current trends in the frequency of detection of acute intestinal infections of viral and bacterial etiology, in particular, the growing prevalence of norovirus infection is shown. Particular attention is paid to the increase in the incidence of salmonellosis and campylobacteriosis. An increase in the incidence of salmonellosis in 2019 by 25.7% is shown, which is higher than the average long-term incidence rate by 28.1%. Age features of the incidence of viral and bacterial intestinal infections among children have been established. Given the widespread use of antibiotics or other drugs that change the intestinal microbial landscape (cytostatics, chemotherapy drugs), as well as a significant increase in the number of hospitalizations of patients, there is a high risk of developing antibiotic-associated diarrhea. Undoubted attention requires the problem of registration, diagnosis of clostridium infections, which make it difficult to obtain data on the prevalence of infection caused by Clostridium difficile in the Russian Federation and St. Petersburg. The article discusses in detail the possibilities for further improvement of measures to prevent the transmission of acute intestinal infections.Copyright © 2022 Authors. All rights reserved.

Features of the course of COVID-19 in patients withsarcoidosis

Concomitant pathology is a risk factor for severe COVID-19. Bilateral changes characteristic of sarcoidosis onCTscan can also occur with coronavirus infection.The purpose of the study: based on our own data to study the features of the course of a new coronavirus infectionin patients with lung sarcoidosis.Materials and methods: 47 patients have been under observation which accounted for 22.4% of the total number ofobserved patients with sarcoidosis. Concomitant pathology: cardiovascular system - 24.9%, gastrointestinal tractpathology - 23.3%, COPD and bronchial asthma in 11.7%, diabetes mellitus in 5.25%. As a basic therapy, 74.5%received GCS, 5.2% - methotrexate, 16.2% - GCS +methotrexate. In addition, 32% took vitamin E and 19.8% -pentoxifylline.Results and discussion: The average age of patients is 37.2+/-3.4 (men 12, women 35). In 8 patients - pneumoniawas not detected;in 21 patients (CT stage 1) SpO2 95.2+/- 2.4%, in 15 patients (CT stage 2) SpO2 86.0+/- 4.5%, in 4patients (CT stage 3) COVID-19 had a severe SpO2 68.1+/- 7.3%, which required treatment in the intensive care unit. Blood parameters: IL-6 - 94.3+/-7.8 (N less than 3.4 ng/ml), CRP 103.4+/-8.9 (N 0-5 mg/L), ACE 82.3+/-7.3 (N 8-52 units/L), D-dimer 485+/-20.8 (N less than 442 ng/ml), ferritin 643.4+/-10.7 (N 28-365 ng/ml), GGT 104.5+/-3.7 (N 1-55 Units/L), procalcitonin 0.17 +/- 0.01 (N less than 0.1ng/ml). Conclusion(s): based on the data obtained, a severe course of COVID-19 was noted in 6.38% of patients with sarcoidosis, the course of moderate severity in 32%. The factors contributing to the severe course include the use of cytostatics and GCS.

Catheter-related venous thrombosis: Experience with blue advance peripherally inserted central catheter (PICC) in a day hospital during the pandemic

Background: The PICC in our Day Hospital (DH) has become the central line of choice for the therapeutic management of oncological and hematological patients when the duration does not exceed 6 months. The impact of COVID-19 in these patients led to an increase in risk factors for the occurrence of venous thrombosis (VT) and catheter-related venous thrombosis (CRVT), forcing admission-like immobility, intensification of supportive treatment with granulocyte colony growth factors (G-CSF) and a higher number of PICC insertions in metastatic patients. Given these circumstances, it was decided to use the Blue Advance PICC with antithrombogenic coverage. The objective was record the incidence of symptomatic CRVT related to Blue Advance PICC in oncological and hematological patients in active treatment, as well as the incidence of other complications and causes of withdrawal. Methods: A retrospective observational study was performed, in a consecutive series of patients from November 2019 to June 2021. All catheters were inserted in DH for oncospecific treatment, using PICC Blue Advance Teleflex Medical®, 4'5Fr, 1 lumen, by ultrasound-guided puncture and tip confirmation by fluoroscopy. Variables recorded: demographic data, diagnosis and stage, treatment administered, date of insertion and removal, vein diameter, cause of removal and complications. Results: A total of 295 blue PICC were analyzed, with a total length of stay of 46,150 days and a mean of 156 days per catheter. Ninety-eight percent of the PICCs were placed at the first attempt, and the predominant access was the basilic and brachial veins, with diameter between 2.9-5.6mm. There were 9 cases of symptomatic CRVT (3%, 0.19/1000 catheter days), confirmed by Echo-Doppler, which did not require catheter removal and treatment was completed. Six CRVT were diagnosed between the first and third week of insertion in female patients, with cytostatic Adriamycin and G-CSF. The main cause of withdrawal was end of treatment in 94.9%. Conclusions: The use of the antithrombogenic Blue Advance PICC during the pandemic period, despite the increase in risk factors, kept the incidence rate of symptomatic CRVT unchanged in our historical pre-COVID cohort. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.

Rationale for the Use of Cyclophosphamide in COVID 19-Associated Pulmonary Fibrosis

Pneumonia is a serious complication of the new coronavirus infection, also known as COVID-19. Patients if risk groups who require ICU care and mechanical ventilation are at the highest risk to develop lung fibrosis. This review analyzes the use of cytostatic agents such as cyclophosphamide with his proven efficacy against lung fibrosis of various etiologies and considers its potential effectiveness in the treatment of post-Covid pulmonary fibrosis.

CLINICAL CASE OF SUCCESSFUL TREATMENT OF COVID-19 INFECTION MANIFESTED WITH B-CELL ACUTE LYMPHOBLASTIC LEUKEMIA

Background. The novel Corona virus disease 2019 (COVID-19) is currently a global threat. Cancer patients constitute a group that is at high risk of COVID-19 infection with a more severe disease course and higher mortality rate. Case description. We report a case of COVID-19 occurring concurrently with B-cell acute lymphoblastic leukemia (ALL) in a young male patient. After verification of the morphological and immunophenotypic profiles of leukemia, the patient received ALL treatment (ALL-2009 protocol) with concurrent administration of antiviral and antibacterial drugs, as well as immunoglobin replacement therapy. Neutropenia caused by cytostatic treatment led to the progression of lung damage and respiratory failure, which required the withdrawal of cytostatic drugs. The patient was transferred to the Intensive Care Department, where dexamethasone therapy as well as antibacterial and antifungal therapy was continued. Since the lung damage reached 75 % and respiratory failure began to increase, non-invasive ventilation of the lungs was started. Clinical and hematological remission with hematologic recovery and subsequent pneumonia regression was achieved. However, long-term persistence of the virus was observed, and therefore the strategy for treating acute lymphoblastic leukemia was revised. Maintenance therapy with mercaptopurine and methotrexate was administered. After elimination of the virus on the 56th day from the initial positive test, therapy according to the ALL-2009 protocol was continued. Conclusion. The tactics of treating cancer patients with hemoblastosis during a pandemic should be selected individually with an assessment of the potential benefits and risk of life-threatening complications.

Novel N-Substituted 3-Aryl-4-(diethoxyphosphoryl)azetidin-2-ones as Antibiotic Enhancers and Antiviral Agents in Search for a Successful Treatment of Complex Infections.

A novel series of N-substituted cis- and trans-3-aryl-4-(diethoxyphosphoryl)azetidin-2-ones were synthesized by the Kinugasa reaction of N-methyl- or N-benzyl-(diethyoxyphosphoryl)nitrone and selected aryl alkynes. Stereochemistry of diastereoisomeric adducts was established based on vicinal H3-H4 coupling constants in azetidin-2-one ring. All the obtained azetidin-2-ones were evaluated for the antiviral activity against a broad range of DNA and RNA viruses. Azetidin-2-one trans-11f showed moderate inhibitory activity against human coronavirus (229E) with EC50 = 45 µM. The other isomer cis-11f was active against influenza A virus H1N1 subtype (EC50 = 12 µM by visual CPE score; EC50 = 8.3 µM by TMS score; MCC > 100 µM, CC50 = 39.9 µM). Several azetidin-2-ones 10 and 11 were tested for their cytostatic activity toward nine cancerous cell lines and several of them appeared slightly active for Capan-1, Hap1 and HCT-116 cells values of IC50 in the range 14.5-97.9 µM. Compound trans-11f was identified as adjuvant of oxacillin with significant ability to enhance the efficacy of this antibiotic toward the highly resistant S. aureus strain HEMSA 5. Docking and molecular dynamics simulations showed that enantiomer (3R,4S)-11f can be responsible for the promising activity due to the potency in displacing oxacillin at ß-lactamase, thus protecting the antibiotic from undesirable biotransformation.

Metronomic chemotherapy for patients with metastatic breast cancer: Review of effectiveness and potential use during pandemics.

Metronomic chemotherapy (M-CT) is defined as dose dense administration of chemotherapy at lower doses than maximum tolerated dose but at shorter free intervals, to obtain a near continuous exposure of cancer cells to those potentially effective drugs. M-CT is a useful strategy to obtain response, overcome resistance and reduce side effects, with low costs. This review will focus on the use of M-CT in advanced breast cancer (ABC). Cytostatic and cytotoxic effect on cancer cells, the anti-angiogenic and the immunomodulatory effects are its main mechanisms of actions. Many clinical trials proved the efficacy and tolerability of different monotherapies and combinations of chemotherapeutic agents administered in metronomic doses and frequencies in ABC. M-CT is a reasonable option for second and later lines of chemotherapy in metastatic breast cancer including those with prior anthracycline or taxane exposure, older patients and patients with comorbidities, and even as first-line in certain groups of patients. The acceptable efficacy and low toxicity of oral metronomic chemotherapy makes it a reasonable option during COVID-19 pandemic as well as in the post-COVID era which is projected to last for some time.