RT-1 Treatment results of salvage gamma knife stereotactic radiosurgery and bevacizumab (AVAgamma therapy) for recurrent malignant glioma

Purpose: We report the treatment results of AVAgamma therapy combining gamma knife (GK) and bevacizumab for recurrent malignant glioma. Subjects: From August 2013 to January 2021, 71 patients (Grade 2:8 patients, Grade3:16 patients, Grade 4:47 patients) with recurrent malignant glioma treated with AVAgamma therapy as salvage therapy at the time of relapse after initial treatment. The average age is 55.7 years, with 44 men and 27 women. The tumor volume is 150 ml or less, and KPS is 40% or more as the indication of AVAgamma therapy. When the irradiation volume of the gamma knife was 15 ml or less, the marginal dose was 20 to 26 Gy, and when the irradiation volume was 15 ml or more, the marginal dose was 12 to 15 Gy in two divided doses.The mean therapeutic borderline dose was 24 Gy. Bevacizumab was administered 10 mg / kg or 15 mg / kg 1 to 10 times after GK. Methods: Median progression-free survival (mPFS) from AVAgamma treatment, median survival (mOS), and mOS from initial treatment were examined and compared with mOS in the RPA classification of recurrent glioma. Results: In relapsing glioma RPA classification, NABTT CNC class 2 mOS is 17.2 months, class 3 mOS is 3.8 months, class 5 mOS is 5.6 months, class 6 mOS is 6.4 months, but mOS from AVAgamma therapy is 18 months in class 3, 11 months in class 5, 9 months in class 6. The survival time has been extended in class3, class5, class6. Discussion: By AVAgamma therapy, it was thought that recurrent lesions were locally controlled and life prognosis was prolonged. Conclusion: AVAgamma therapy is thought to prolong the survival of recurrent malignant glioma and play an important role as salvage treatment.

Passive Microwave Radiometry (MWR) as a Component of Imaging Diagnostics in Juvenile Idiopathic Arthritis (JIA)

Juvenile idiopathic arthritis (JIA) is a disease with unknown causes within all forms of arthritis in children under 16 years of age. The diagnosis is made when another joint pathology is excluded. Difficulties in early and differential diagnosis lead to the rapid disability of patients and an unfavourable life prognosis. Therefore, timely diagnosis is necessary to prevent irreversible damage to the joints and preserve their function. Due to the widespread use of new technologies, modern multimodal imaging has gained recognition, which includes X-ray, ultrasound, and MRI. The combination of methods plays a key role in confirming the diagnosis, monitoring disease activity, prognosis during the course, and outcome in children with JIA. Each method has its own advantages and disadvantages. The introduction of the method of passive microwave radiometry (MWR), in combination with other imaging methods, makes it possible to expand the possibilities of screening the disease in the preclinical and early clinical phases.

Exosomes and Brain Metastases: A Review on Their Role and Potential Applications

Brain metastases (BM) are a frequent complication in patients with advanced stages of cancer, associated with impairment of the neurological function, quality of life, prognosis, and survival. BM treatment consists of a combination of the available cancer therapies, such as surgery, radiotherapy, chemotherapy, immunotherapy and targeted therapies. Even so, cancer patients with BM are still linked to poor prognosis, with overall survival being reported as 12 months or less. Intercellular communication has a pivotal role in the development of metastases, therefore, it has been extensively studied not only to better understand the metastization process, but also to further develop new therapeutic strategies. Exosomes have emerged as key players in intercellular communication being potential therapeutic targets, drug delivery systems (DDS) or biomarkers. In this Review, we focus on the role of these extracellular vesicles (EVs) in BM formation and their promising application in the development of new BM therapeutic strategies.

Halo-gravity traction in the treatment of complex spinal deformities in children with respiratory dysfunctions

HGT is a safe technique as the world literature describes complications in the form of loosening of the pins or superficial infections of the skin around the pins, which are not significant and do not pose a threat to the patient’s life. Purpose – to improve the results of the ventilation function of the lungs in patients with complex spinal deformities through the preliminary use of halo gravity traction and to introduce an effective and safe method for the treatment of complex spinal deformities in children with respiratory dysfunctions. Materials and methods. 64 children with complex spinal deformities (>100°) were treated in the orthopedic and traumatology department of the Okhmatdet NSPU using halo gravity traction during the period from 2003 until 2018. Of these, 38 are boys and 26 are girls. The average age of the patients was 11.6 years. The average Risser score was 3.8 (P>0.01). Results. According to the data of spirography performed, 46% of patients had moderate ventilation disorders and 54% – severe ventilation disorders (FVC<60% – grade 3 and 4 of ventilation failure). Mixed type disorders were recorded in 83% of patients, and restrictive type disorders in 17% (8/48) of children. After HGT, there was an improvement in pulmonary function indicators: an increase in FVC from 63.19% to 71.77% and FEV1 from 54.71% to 65.46%, Tiffeneau-Pinelli index – from 74.59% to 85.33%. Compared with the initial level of indicators, the improvement in FVC was 13.6% after HGT and 14.6% in dynamics during the year, and FEV1 – 19.6% and 21.6%, respectively. The results obtained indicate a significant improvement in the ventilation function of the lungs, especially due to the degree of FEV1 increase, which correlates with the degree of improvement in performance, mortality and life prognosis. Conclusions. The use of HGT makes it possible to improve the results of the final correction of spinal deformity, which in turn significantly improves the ventilation function of the lungs, which in turn helps to reduce the risks of mortality due to pulmonary insufficiency in adulthood. The choice of the appropriate methods of surgical correction for complex deformity of the spine is a prerequisite for successful treatment and the achievement of three-dimensional correction of the spine to maximally approximate its parameters to the physiological norm. The indication for halo gravity traction is a rigid scoliotic deformity of the spine with a deformity angle (>100°). This study was conducted in accordance with the principles of the Helsinki Declaration. The research protocol was approved by the Local Ethics Committee of the institutions mentioned in the work. Informed parental agreement was obtained for the research. No conflict of interests was declared by the authors. Key words: spinal deformity, respiratory dysfunctions, halo-gravity traction.

UBE2L3, a Partner of MuRF1/TRIM63, Is Involved in the Degradation of Myofibrillar Actin and Myosin

The ubiquitin proteasome system (UPS) is the main player of skeletal muscle wasting, a common characteristic of many diseases (cancer, etc.) that negatively impacts treatment and life prognosis. Within the UPS, the E3 ligase MuRF1/TRIM63 targets for degradation several myofibrillar proteins, including the main contractile proteins alpha-actin and myosin heavy chain (MHC). We previously identified five E2 ubiquitin-conjugating enzymes interacting with MuRF1, including UBE2L3/UbcH7, that exhibited a high affinity for MuRF1 (KD = 50 nM). Here, we report a main effect of UBE2L3 on alpha-actin and MHC degradation in catabolic C2C12 myotubes. Consistently UBE2L3 knockdown in Tibialis anterior induced hypertrophy in dexamethasone (Dex)-treated mice, whereas overexpression worsened the muscle atrophy of Dex-treated mice. Using combined interactomic approaches, we also characterized the interactions between MuRF1 and its substrates alpha-actin and MHC and found that MuRF1 preferentially binds to filamentous F-actin (KD = 46.7 nM) over monomeric G-actin (KD = 450 nM). By contrast with actin that did not alter MuRF1–UBE2L3 affinity, binding of MHC to MuRF1 (KD = 8 nM) impeded UBE2L3 binding, suggesting that differential interactions prevail with MuRF1 depending on both the substrate and the E2. Our data suggest that UBE2L3 regulates contractile proteins levels and skeletal muscle atrophy.