МУКОРМИКОЗ У ДЕТЕЙ С ГЕМАТОЛОГИЧЕСКИМИ И ОНКОЛОГИЧЕСКИМИ ЗАБОЛЕВАНИЯМИ В САНКТ-ПЕТЕРБУРГЕ

In prospective multicenter study were included 20 pediatriconcohematologic patients with mucormycosis. Age: 3 – 17 yy (median – 11), females – 60%. The diagnosiswas made according to EORTC/MSG 2008 criteria (post mortem – 25%). The main underlying disease was acutel eukemia (70%), risk factors – prolong severe neutropenia (median – 31 d) and lymphocytopenia (median – 33 d) after cytostatic chemotherapy or hematopoietic stem cells transplantation. Etiology agents were Lichtheimia corуmbifera, Rhizopus spp. and Rhizomucor spp. Main sites of infection were lungs (65%) and paranasal synuses (30%), dissemination – 45%. Antifungal therapy (amphotericin B lipid coplex, posaconazole, caspofungin, amphotericin B) was used in 75% patients, surgery – 30%. Overall mortality in 12 weeks was 70%.В проспективное многоцентровое исследование включили 20 детей с гематологическими и онкологическими заболеваниями, осложнившимися мукормикозом. Возраст – от 3 до 17 лет (медиана – 11 лет), девочки – 60%. Диагноз мукормикоза был установлен согласно критериям EORTC/MSG, 2008 (post mortem – 25%). Установлено, что мукормикоз развивается преимущественно у больных острым лейкозом (70%), на фоне длительного агранулоцитоза (медиана – 31 день) и лимфоцитопении (медиана – 33 дня) после интенсивной цитостатической и/или иммуносупрессивной терапии, а также трансплантации гемопоэтических стволовых клеток. Возбудители: Lichtheimia corуmbifera, Rhizopus spp. и Rhizomucor spp. Заболевание начинается с поражения легких (65%) и придаточных пазух носа (30%), диссеминацию выявили у 45% пациентов. Антимикотическую терапию (липидный комплекс амфотерицина В, позаконазол, каспофунгин, амфотерицин В) проводили 75% больных, хирургическое лечение – 30%. Общая летальность в течение 12 недель составила 70%

Rivaroxaban Compared with Standard Anticoagulants for the Treatment of Acute Venous Thromboembolism in Children: a Randomised, Controlled, Phase 3 Trial

Background: Treatment of venous thromboembolism in children is based on data obtained in adults with little direct documentation of its efficacy and safety in children. The aim of our study was to compare the efficacy and safety of rivaroxaban versus standard anticoagulants in children with venous thromboembolism. Methods: In a multicentre, parallel-group, open-label, randomised study, children (aged 0–17 years) attending 107 paediatric hospitals in 28 countries with documented acute venous thromboembolism who had started heparinisation were assigned (2:1) to bodyweight-adjusted rivaroxaban (tablets or suspension) in a 20-mg equivalent dose or standard anticoagulants (heparin or switched to vitamin K antagonist). Randomisation was stratified by age and venous thromboembolism site. The main treatment period was 3 months (1 month in children <2 years of age with catheter-related venous thromboembolism). The primary efficacy outcome, symptomatic recurrent venous thromboembolism (assessed by intention-to-treat), and the principal safety outcome, major or clinically relevant non-major bleeding (assessed in participants who received ≥1 dose), were centrally assessed by investigators who were unaware of treatment assignment. Repeat imaging was obtained at the end of the main treatment period and compared with baseline imaging tests. This trial is registered with ClinicalTrials.gov, number NCT02234843 and has been completed. Findings: From Nov 14, 2014, to Sept 28, 2018, 500 (96%) of the 520 children screened for eligibility were enrolled. After a median follow-up of 91 days (IQR 87–95) in children who had a study treatment period of 3 months (n=463) and 31 days (IQR 29–35) in children who had a study treatment period of 1 month (n=37), symptomatic recurrent venous thromboembolism occurred in four (1%) of 335 children receiving rivaroxaban and five (3%) of 165 receiving standard anticoagulants (hazard ratio [HR] 0·40, 95% CI 0·11–1·41). Repeat imaging showed an improved effect of rivaroxaban on thrombotic burden as compared with standard anticoagulants (p=0·012). Major or clinically relevant non-major bleeding in participants who received ≥1 dose occurred in ten (3%) of 329 children (all non-major) receiving rivaroxaban and in three (2%) of 162 children (two major and one non-major) receiving standard anticoagulants (HR 1·58, 95% CI 0·51–6·27). Absolute and relative efficacy and safety estimates of rivaroxaban versus standard anticoagulation estimates were similar to those in rivaroxaban studies in adults. There were no treatment-related deaths. Interpretation: In children with acute venous thromboembolism, treatment with rivaroxaban resulted in a similarly low recurrence risk and reduced thrombotic burden without increased bleeding, as compared with standard anticoagulants. Funding: Bayer AG and Janssen Research & Development. © 2020 Elsevier Ltd

HEREDITARY BREAST CANCER

Hereditary breast cancer occurs in 5–20 % of cases and it is associated with inherited mutations in particular genes, such as BRCA1 и BRCA2 in most cases. The CHEK2, PTEN, TP53, ATM, RAD51, BLM, PALB2, Nbs genes are associated with low and median risks ofdeveloping breast cancer. Molecular genetic studies identify germinal mutations underlying hereditary breast cancer. In most cases hereditary breast cancer refers to triple-negative phenotype, which is the most aggressive type of breast cancer, that does not express the genes for estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 (HER2). The review presents the diagnostic and treatment methods of hereditary breast cancer. Clinical-morphological aspects allow the new diagnostic and treatment methods of hereditary breast cancer to be identified. Poly (ADP-ribose) polymerase (PARP) inhibitors demonstrate the potential for effective treatment of BRCA-associated breast cancer

diagnostic utility of procalcitonin in children with infectious complications during chemotherapy-induced neutropenia: single center experience, literature review

Background. Infectious complications cause significant mortality in children with oncological diseases during chemotherapy-induced neutropenia. The absence of sensitive and specific signs and symptoms of infectious conditions as well as its microbiological identification, leads to inappropriate antibiotic exposure. The use of laboratory biomarkers (procalcitonin (PCT) and C-reactive protein (CRP)) may be helpful for differential diagnostics of inflammatory conditions and for rational antimicrobial therapy.Objective: to assess the current value of PCT as an additional marker for differentiating inflammatory conditions in children with chemotherapy-induced neutropenia.Materials and methods. We presented the analysis of infectious complications in pediatric patients with oncological and onco- / hematological diseases between 2017–2020 (54 patients from 2 mnths – 17 years). PCT and CRP with clinical and instrumental diagnostic data were used for differential diagnosis of fever and development of antimicrobial therapy decision rules. Literature review concerning the discussed theme from 2006–2018 was done.Results. Eighty-five infectious episodes in 36 months were registered, among them 42 in pts with onco- / hematological diseases and 43 – with solid tumors. In the group of bacterial infectious complications mean CRP and PCT values were significantly higher than in group of nonbacterial, moreover the discriminative value was higher for PCT. We revealed the correlation between severity of infectious complications and values of markers of acute-phase reactions. In case of non-severe bacterial complications and other types of infections significant difference was revealed only for PCT mean values.Conclusion. Specificity of PCT concentration in bacterial infections exceeds that of CRP, which confirms the hypothesis of advantages in using PCT as differential marker of inflammatory conditions in children with malignancies

The microbiome role in pathogenesis of inflammatory and immune alterations of gastrointestinal tract in pediatric patients with cancer

Infectious complications remain one of the most significant problem associated with anticancer therapy in oncological patients. Cytotoxic, radiation and antibacterial therapy induce dysbiosis and gastrointestinal mucosal barrier injury. These changes lead to the mucositis, thereby increasing the risk of endogenous microflora translocation with following probable development of severe infectious and inflammatory diseases. In addition, current evidence suggests that there is a relationship between gut microbiome disturbances and post-transplant graft versus host disease development. The article presents the existing paradigms of determining the role of gastrointestinal tract functional condition in cancer patients in order to optimize prevention and antimicrobial treatment approaches

Breakthrough invasive candidiasis in pediatric patient with Ewing’s sarcoma: dinical case report and literature review

We presented clinical case of invasive candidiasis in 13 years old girl with Ewing's sarcoma during intensive treatment with combined chemotherapy according EWING 2008 protocol. The most significant risk factors were recurrent chemotherapy induced neutropenia gr IV, multifocal Candida colonization, prolonged central venous catheter use, combined antibiotic therapy in the previous &gt;10 days, parenteral nutrition. In spite of provided prophylaxis and antifungal therapy patient died because of progression of invasive candidiasis. We analyzed literature data on frequency of invasive candidiasis in children with Ewing's sarcoma and cases of breakthrough candidiasis in pediatric malignancies

Atypical hemolytic uremic syndrome in high-risk neuroblastoma patient: case report

Atypical hemolytic uremic syndrome is a rare disorder uncontrolled complement activation, which is classically manifested by anemia, thrombocytopenia and renal failure. Extrarenal manifestations are observed in 20 % of patients, most of which are associated with damage of the central nervous system. Eculizumab is effective treatment option. The article describes a case report of the severe atypical hemolytic uremic syndrome in a 20 m. o. patient who received immunotherapy with anti-GD2 antibodies (dinutuximab beta) for a high-risk neuroblastoma