Presentation of severe brucellosis in 5-year-old boy - challenges and results.

Brucellosis is highly contagious zoonotic bacterial disease caused by gram-negative genus. It has a wide spectrum of clinical manifestations and due to variety and nonspecificity of clinical signs the diagnostics can be very complicated. We present a clinical case of severe chronic brucellosis in a 5-years old boy with long-term course of disease and multiorgan involvement. A different complication of brucellosis including severe syndrome of inappropriate ADH secretion (SIADH) are discussed. Despite severe course of disease patient achieved significant clinical improvement due to multidisciplinary approach and optimal etiotropic and pathogenetic treatment.

Apixaban versus no anticoagulation for the prevention of venous thromboembolism in children with newly diagnosed acute lymphoblastic leukaemia or lymphoma (PREVAPIX-ALL): a phase 3, open-label, randomised, controlled trial.

BACKGROUND: Paediatric patients with acute lymphoblastic leukaemia or lymphoma are at increased risk of venous thromboembolism resulting in increased mortality and morbidity. We hypothesised that apixaban, a direct oral anticoagulant, would safely reduce venous thromboembolism in this patient population. METHODS: PREVAPIX-ALL was a phase 3, open-label, randomised, controlled trial conducted in 74 paediatric hospitals in 9 countries. Participants aged 1 year or older to younger than 18 years with newly diagnosed acute lymphoblastic leukaemia (pre-B cell or T cell) or lymphoblastic lymphoma (B cell or T cell immunophenotype) and a central venous line in place throughout induction were randomly assigned 1:1 to standard of care (SOC, ie, no systemic anticoagulation) or weight-adjusted twice-daily apixaban during induction. Randomisation was performed centrally and stratified by age (those <10 years or those ≥10 years). Participants weighing 35 kg or less were administered 2·5 mg twice daily of apixaban as a 2·5 mg tablet, 0·5 mg tablets, or 0·4 mg/mL oral solution, while those weighing more than 35 kg were administered weight-adjusted prophylactic doses using 0·5 mg tablets or the 0·4 mg/mL oral solution twice daily. Primary outcomes were assessed by a blinded central adjudication committee. The primary efficacy outcome for the intention to treat population was the composite of symptomatic or clinically unsuspected venous thromboembolism, the primary safety outcome was major bleeding, and secondary safety outcomes included clinically relevant non-major (CRNM) bleeding. Patients were screened for venous thromboembolism by ultrasound and echocardiogram at the end of induction. The trial was registered with ClinicalTrials.gov (NCT02369653) and is now complete. FINDINGS: Between Oct 22, 2015, and June 4, 2021, 512 participants were randomly assigned and included in analyses (222 [43%] female and 290 [57%] male; 388 [76%] White, 52 [10%] Asian, 24 [5%] Black or African American, and 48 [9%] other races; and 122 [24%] Hispanic or Latino ethnicity). During a median follow-up period of 27 days (IQR 26-28), 31 (12%) of 256 patients on apixaban had a composite venous thromboembolism compared with 45 (18%) of 256 participants receiving SOC (relative risk [RR] 0·69, 95% CI 0·45-1·05; p=0·080). Two major bleeding events occurred in each group (RR 1·0, 95% CI 0·14-7·01; p=1·0). A higher incidence of CRNM bleeding, primarily grade 1 or 2 epistaxis, occurred in the apixaban group (11 [4%] of 256 participants) compared with the SOC group (3 [1%] of 256; RR 3·67, 95% CI 1·04-12·97, p=0·030). The most frequent grade 3-5 adverse events in both groups were thrombocytopenia (n=28 for the apixaban group and n=20 for the SOC group) or platelet count decreased (n=49 and n=45), anaemia (n=77 and n=74), febrile neutropenia (n=27 and n=20), and neutropenia (n=16 and n=17) or neutrophil count decreased (n=22 and n=25). Five deaths occurred, which were due to infection (n=3 in the SOC group), cardiac arrest (n=1 in apixaban group), and haemorrhagic cerebral sinus vein thrombosis (n=1 in the SOC group). There was one apixaban-related death (coagulopathy and haemorrhage after cardiac arrest of unknown cause). INTERPRETATION: PREVAPIX-ALL is, to our knowledge, the first trial assessing primary thromboprophylaxis using a direct oral anticoagulant in paediatric patients with acute lymphoblastic leukaemia or lymphoma. No statistically significant treatment benefit was identified in participants receiving apixaban. Major and CRNM bleeding were infrequent overall, but a higher incidence of CRNM bleeding (primarily epistaxis in younger children) occurred in participants receiving apixaban. For patients deemed to be at particularly high risk of thrombosis, PREVAPIX-ALL provides encouraging safety data for the use of apixaban in clinical settings in which the potential benefits are thought to outweigh the risk of bleeding. FUNDING: Bristol Myers Squibb-Pfizer Alliance.

Effectiveness of metronomic chemotherapy in a child with medulloblastoma: A case report.

Medulloblastoma (MB) is one of the most common pediatric malignant tumors arising from the central nervous system with an unknown etiology and variable prognosis. Relapsed or refractory MB in pediatric patients after intensive anticancer therapy (chemo-, radiotherapy) is associated with treatment resistance and poor survival prognosis. Metronomic chemotherapy in combination with mTOR inhibitors may have advantages due to an alternate mechanism of cytotoxicity and a favourable adverse effects profile. Furthermore, it is considered to be a prospective anticancer regimen regardless of the presence/absence of molecular targets. The present study reported a successful result of this treatment option with optimal tolerability in relapsed MB in a pediatric male patient and highlighted the advantages for a selected group of patients.

DNA methylation-based diagnosis confirmation in a pediatric patient with low-grade glioma: a case report.

Central nervous system (CNS) tumors in children comprise a highly heterogenous and complex group of diseases. Historically, diagnosis and confirmation of these tumors were routinely based on histological examination. However, recently obtained data demonstrate that such a diagnostic approach is not completely accurate and could lead to misdiagnosis. Also, in recent times, the quantity and quality of molecular diagnostic methods have greatly improved, which influences the current classification methods and treatment approach for pediatric CNS tumors. Nowadays, molecular methods, such as DNA methylation profiling, are an integral part of diagnosing brain and spinal tumors in children. In this paper, we present the case of an infant with a posterior fossa tumor who demonstrated a non-specific morphology and whose diagnosis was verified only after DNA methylation.

Efficacy of combined immunosuppression with or without eltrombopag in children with newly diagnosed aplastic anemia.

We compared the efficacy and safety of eltrombopag (ELTR) combined with immunosuppressive therapy (IST) and IST alone in treatment-naïve children with severe (SAA) and very severe (vSAA) aplastic anemia. Ninety-eight pediatric patients were randomized to receive horse antithymocyte globulin (hATG) and cyclosporin A (CsA) with (n = 49) or without (n = 49) ELTR. The primary endpoint was the overall response rate (ORR) at 4 months. After 4 months, nonresponders were crossed over to the alternative group. In all patients, the ORR in ELTR + IST and IST groups was similar (65% vs 53%; P = .218); however, the complete response (CR) rate was significantly higher in the ELTR + IST group (31% vs 12%; P = .027). In severity subgroups, the ORR was 89% vs 57% (P = .028) in favor of IST + ELTR in SAA, but it did not differ in patients with vSAA (52% vs 50%; P = .902). At 6 months after the crossover, 61% of initial ELTR(-) patients achieved a response compared with 17% of initial ELTR(+) patients (P = .016). No significant difference in ELTR + IST and IST groups was observed in the 3-year overall survival (OS) (89% vs 91%; P = .673) or the 3-year event-free survival (EFS) (53% vs 41%; P = .326). There was no unexpected toxicity related to ELTR. Adding ELTR to standard IST was well tolerated and increased the CR rate. The greatest benefit from ELTR combined with IST was observed in patients with SAA but not in those with vSAA. The second course of IST resulted in a high ORR in initial ELTR(-) patients who added ELTR and had limited efficacy among patients who received ELTR upfront. This trial was registered at Clinicaltrials.gov as #NCT03413306.

Case report: Somatic mutations in microtubule dynamics-associated genes in patients with WNT-medulloblastoma tumors.

Medulloblastoma (MB) is the most common pediatric brain tumor which accounts for about 20% of all pediatric brain tumors and 63% of intracranial embryonal tumors. MB is considered to arise from precursor cell populations present during an early brain development. Most cases (~70%) of MB occur at the age of 1-4 and 5-9, but are also infrequently found in adults. Total annual frequency of pediatric tumors is about 5 cases per 1 million children. WNT-subtype of MB is characterized by a high probability of remission, with a long-term survival rate of about 90%. However, in some rare cases there may be increased metastatic activity, which dramatically reduces the likelihood of a favorable outcome. Here we report two cases of MB with a histological pattern consistent with desmoplastic/nodular (DP) and classic MB, and genetically classified as WNT-MB. Both cases showed putative causal somatic protein truncating mutations identified in microtubule-associated genes: ARID2, TUBB4A, and ANK3.

Case Report: Primary Leptomeningeal Medulloblastoma in a Child: Clinical Case Report and Literature Review.

Medulloblastoma is one of the most common pediatric central nervous system malignancies worldwide, and it is characterized by frequent leptomeningeal metastasizing. We report a rare case of primary leptomeningeal medulloblastoma of an 11-year-old Caucasian girl with a long-term disease history, non-specific clinical course, and challenges in the diagnosis verification. To date, 4 cases of pediatric primary leptomeningeal medulloblastoma are reported, and all of them are associated with unfavorable outcomes. The approaches of neuroimaging and diagnosis verification are analyzed in the article to provide opportunities for effective diagnosis of this disease in clinical practice. The reported clinical case of the primary leptomeningeal medulloblastoma is characterized by MR images with non-specific changes in the brain and spinal cord and by 18FDG-PET/CT images with diffuse heterogeneous hyperfixation of the radiopharmaceutical along the whole spinal cord. The immunohistochemistry and next-generation sequencing analyses of tumor samples were performed for comprehensive characterization of the reported clinical case.

Ovarian tissue cryopreservation in prepubertal patients with oncological diseases: multidisciplinary approach and outcomes.

In children with cancer, the issues related to the quality of life are becoming increasingly important together with the improvement of survival rates. This creates an entirely new challenge - minimizing the toxicity of the antitumor therapy without reducing its effectiveness. One of the specific side effects of the antitumor therapy is gonadotoxicity, which negatively affects both the somatic and mental state of the survivors. Since ovarian stimulation is ineffective in prepubertal patients, ovarian tissue cryopreservation (OTC) remains the most promising option to preserve fertility. The primary goal of this publication is to emphasize the importance of the reproductive health problem in girls with oncological diseases, with a description of the current data of international literature on the prospects of OTC in order to preserve fertility. Another goal is to present a multidisciplinary strategy for the management of prepubertal age patients with the oncological disease within the framework of the Oncological Fertility Project at Almazov National Medical Research Center. Based on the data of Russian and international literature, as well as existing guidelines and recommendations on reproductive health, a single algorithm for selecting patients has been developed, considering the expected gonadal toxicity for the use of the OTC in prepubertal girls. The developed algorithm allows identifying patients of prepubertal age, requiring the use of new possibilities of reproductive technologies. In a long-term date, we are planning to evaluate the effectiveness of the orthotopic reimplantation technique of the cryopreserved ovarian tissue in restoring the reproductive function. A multidisciplinary team of specialists and the possibilities of the Federal Center facilitate implementing the Oncofertility Program in routine practice for girls and young women, receiving gonadotoxic treatment.