[Russian study on brain aneurysm surgery: a continuation (RIHA II)]. / Rossiiskoe issledovanie po khirurgii anevrizm golovnogo mozga: prodolzhenie (RIKhA II).

OBJECTIVE: To assess the main performance indicators of neurosurgical departments in surgical treatment of cerebral aneurysms in the Russian Federation. MATERIAL AND METHODS: We analyzed 22 neurosurgical departments (19 regional and 3 federal hospitals) in 2017 and 2021. The study enrolled 6.135 patients including 3.160 ones in 2017 and 2.975 ones in 2021. We studied the features of surgical treatment of cerebral aneurysms in different volume hospitals and factors influencing postoperative outcomes. RESULTS: The number of surgeries for cerebral aneurysms decreased from 2.950 in 2017 to 2.711 in 2021. Postoperative mortality rate was 6.3% and 5.6%, respectively. The number of microsurgical interventions decreased from 60% in 2017 to 48% in 2021. The share of endovascular interventions increased from 40% to 52%, respectively. Endovascular embolization was accompanied by stenting in 55% of cases. Simultaneous revascularization was carried out in 2% of cases. In 2021, the number of patients undergoing surgery in acute period of hemorrhage increased to 70% (in 2017 - 61%). The number of hospitals performing more than 50 surgical interventions for cerebral aneurysms annually increased from 14 in 2017 to 17 in 2021. CONCLUSION: Certain changes in neurosurgical service occurred in 2021 compared to 2017. Lower number of surgical interventions for cerebral aneurysms, most likely caused by the COVID-19 pandemic, is accompanied by lower postoperative mortality. Endovascular interventions and revascularization techniques became more common. The number of surgeries in acute period after aneurysm rupture and hospitals performing more than 50 surgical interventions for cerebral aneurysms annually increased.

Combination of Multimodal MRI, Neuronavigation, and Awake Craniotomy in Removing Tumors of Eloquent Areas.

The aim of the study is to assess the possibilities of the combined approach to using multimodal MRI, neuronavigation, and awake craniotomy in resecting tumors of eloquent areas. Materials and Methods: The results of 30 successive awake surgical interventions performed in 2017-2019 years in patients with tumors of eloquent areas have been analyzed. The main selection criterion for this type of operations was the location of the tumor in the projection or in the immediate proximity to the cortical centers of speech and motion. To minimize the damage, patients underwent functional MRI and DTI tractography at the prehospital stage to identify cortical regions and white matter tracts involved in the motor and language functions; immediately before the operation the acquired data was loaded into the navigation StealthStation S7 (Medtronic, USA) to plan and monitor surgery stages; during the surgery, direct cortical and subcortical stimulation was performed to identify the motor and speech centers (asleep-awake-asleep technique) with neurolinguistic testing. Karnofsky performance status, assessment of the patient's neurological status, frequency of epileptic seizures before and after the operation, the extent of the tumor resection, and the data analysis after the linguistic testing were used to determine the patients' condition and surgery outcomes. Results: Improvement of the general state after the operation has been noted in 30% of patients compared to the preoperative condition, no neurological deficit dynamics has been observed in 33% of patients. Postoperative multimodal MRI showed that total tumor removal was achieved in 37% of cases, subtotal in 40%, partial removal resection in 23% of cases. Conclusion: The combined approach to the brain tumor resection using multimodal MRI, neuronavigation, and awake craniotomy with motor and language areas mapping allows neurosurgeons to minimize the risk of persistent neurological deficit occurrence and provides the possibility to perform maximal resection possible preserving the patients' functional status. The presented methodology is reproducible, permitting one to expand the options of surgical treatment when lesions are localized in eloquent areas.

[Cytologic control of the resection margins of hemispheric gliomas and metastases]. / Tsitologicheskii kontrol' granits rezektsii polusharnykh gliom i metastazov.

INTRODUCTION: Postoperative MRI is the conventional method for assessing the radicalness of hemispherical tumors excision, but the method has limitations on sensitivity in the assessment of tumor infiltration of the peritumoral zone. The 'gold standard' for detecting tumor cells is the microscopic visualisation. AIM: To study the possibilities of a cytological study of the excision margins of glial and metastatic tumors for an objective assessment of the radical nature of the operation. MATERIAL AND METHODS: The study included 35 patients with intracerebral tumors who underwent open surgery at a university clinic of Volga Research Medical University in 2018-2019: 15 patients with metastasis, 13 patients with MRI-contrasting gliomas Grade III-IV and 7 patnents with non-MRI-contrasting gliomas Grade II-III. During the surgery, samples for cytological examination were taken from the following sites: from the tumor, from the nearest perifocal zone, and at a distance of 5-7 mm, along the border of the extended resection. 154 samples were examined: from 2 to 5 for each patient. RESULTS: The data on the radicalness of the operation, obtained by methods of cytological analysis of the resection margins and postoperative MRI, are not only consistent (p=0.001), but also complement each other, in particular, in some cases, tumor cells were found even in those areas where the tumor tissue was not detected with MRI. In cases of cerebral metastases excision, tumor cells in the nearest perifocal zone were found in 8 out of 28 samples (28.6%), at the extended resection margins - in 3 out of 29 (10.3%). In cases of resection of MRI-contrasting gliomas Grade III-IV, tumor cells in the nearest perifocal zone were found in 22 out of 32 samples (68.8%), at the extended resection margins - in 14 out of 20 (70%). In cases of excision of diffuse gliomas Grade II-III, tumor cells in the nearest perifocal zone were found in 10 out of 17 samples (58.9%), at the extended resection margins - in 4 out of 11 (36.4%). CONCLUSION: The first data obtained demonstrated sufficient informativeness of the cytologic examination of the peritumoral zone as an additional tool for assessing the radicalness of glioma and metastasis surgery. Cytologic analysis of the perifocal zone shows that the extension of the borders of the removal of Grade III-IV gliomas has no advantages, because tumor cells were found both in the nearest perifocal zone and at the extended resection margins with with approximately the same frequency.

[Surgical treatment of cerebral aneurysms in the Russian Federation]. / Khirurgicheskoe lechenie tserebral'nykh anevrizm v Rossiiskoi Federatsii.

OBJECTIVE: The objective of this study was to evaluate the results of surgical treatment of cerebral aneurysms in the Russian Federation. MATERIAL AND METHODS: We analyzed performance indicators in neurosurgical departments of regional and federal health institutions of the Russian Federation for 2017. The results of surgical treatment of cerebral aneurysms (CAs) were analyzed in 19 regional vascular centers (RVCs) in several federal districts and in 3 federal centers (FCs) with the most dynamically developing vascular neurosurgery and smoothly running system of statistical data processing. RESULTS: The study included 3160 patients hospitalized to 22 medical institutions in 2017. Of these, 1808 patients were treated in RVCs, and 1352 patients were treated in FCs. We analyzed factors affecting the treatment outcome in CA patients. We identified features of CA treatment in clinics with a different amount of surgical intervention. CONCLUSION: An increase in the surgical activity in centers and simultaneous development of microsurgical and endovascular treatments for cerebral aneurysms reduce postoperative mortality. Due to the presence of a RVC network in the Russian Federation, many patients could receive necessary specialized treatment. The number of operations for cerebral aneurysms has increased 6-fold for the past 10 years.

[Delayed surgical operations in benign supratentorial gliomas].

Benign gliomas are slowly growing primary brain tumors with prolonged natural course and tendency to malignization. Selection of methods of treatment of patients with good quality of life is being discussed. 'Conservative' as well as active surgical tactics are supported. The paper describes results of treatment of 19 patients with benign supratentorial gliomas. Follow-up period varied from 4 months to 17 years. Aspects of volume evolution and surgical excision of tumor are highlighted.

Ligand for EPH-related kinase (LERK) 7 is the preferred high affinity ligand for the HEK receptor.

HEK is a member of the EPH-like receptor tyrosine kinase family, which appear to have roles in development and oncogenesis. Recently, we purified a soluble HEK ligand which is also a ligand (AL1) for the HEK-related receptor EHK1. Promiscuity appears to be a characteristic feature of interactions between the EPH-like receptors and their ligands, termed ligands for EPH-related kinases (LERKs). This prompted us to analyze the interactions between the HEK exodomain and fusion proteins comprising candidate LERKs and the Fc portion of human IgG1 (Fc) or a FLAGTM-peptide tag by surface plasmon resonance, size exclusion high performance liquid chromatography, sedimentation equilibrium, and transphosphorylation. Our results indicate that AL1/LERK7 is the preferred high-affinity ligand for HEK, forming a stable 1:1 complex with a dissociation constant of 12 nM. As expected the apparent affinities of bivalent fusion proteins of LERKs and the Fc portion of human IgG1 had significantly reduced dissociation rates compared with their monovalent, FLAGTM-tagged derivatives. High-avidity binding of monovalent ligands can be achieved by antibody-mediated cross-linking of monovalent ligands and with LERK7 results in specific phosphorylation of the receptor. By extrapolation, our findings indicate that some of the reported LERK-receptor interactions are a consequence of the use of bivalent ligand or receptor constructs and may be functionally irrelevant.

Purification of a ligand for the EPH-like receptor HEK using a biosensor-based affinity detection approach.

Advances in screening technologies allowing the identification of growth factor receptors solely by virtue of DNA or protein sequence comparison call for novel methods to isolate corresponding ligand growth factors. The EPH-like receptor tyrosine kinase (RTK) HEK (human EPH-like kinase) was identified previously as a membrane antigen on the LK63 human pre-B-cell line and overexpression in leukemic specimens and cell lines suggested a role in oncogenesis. We developed a biosensor-based approach using the immobilized HEK receptor exodomain to detect and monitor purification of the HEK ligand. A protein purification protocol, which included HEK affinity chromatography, achieved a 1.8 X 10(6)-fold purification of an approximately 23-kDa protein from human placental conditioned medium. Analysis of specific sHEK (soluble extracellular domain of HEK) ligand interactions in the first and final purification steps suggested a ligand concentration of 40 pM in the source material and a Kd of 2-3 nM. Since the purified ligand was N-terminally blocked, we generated tryptic peptides and N-terminal amino acid sequence analysis of 7 tryptic fragments of the S-pyridylethylated protein unequivocally matched the sequence for AL-1, a recently reported ligand for the related EPH-like RTK REK7 (Winslow, J.W., Moran, P., Valverde, J., Shih, A., Yuan, J.Q., Wong, S.C., Tsai, S.P., Goddard, A., Henzel, W.J., Hefti, F., Beck, K.D., & Caras, I.W. (1995) Neuron 14, 973-981). Our findings demonstrate the application of biosensor technology in ligand purification and show that AL-1, as has been found for other ligands of the EPH-like RTK family, binds more than one receptor.

[Surgical treatment of complications after surgery for traumatic compression of the brain]. / Khirurgicheskoe lechenie oslozhnenii u bol'nykh, operirovannykh po povodu travmaticheskogo sdavleniia golovnogo mozga.

From the analysis of 123 cases in which operations were performed after relieving compression of the brain the authors give a classification of operations according to their etiological trend: relief of persisting compression of the brain, correction of respiratory disorders, provision for enteral feeding, control of purulent inflammatory complications, rehabilitation. Indications for repeated operations and specific features of their performance were developed.

[Effects of neutral salts and temperature on skeletal muscle sarcolemmal Ca-TPase]. / Vliianie neitral'nykh solei i temperatury na Ca-ATPazu sarkolemmy skeletnykh myshts.

The temperature dependence and effects of sodium and potassium chloride on purified preparations of sarcolemmal Ca2+-activated ATPase were investigated. It was shown that within the concentration range of 0,1--1,0 M both salts have the same effect on the enzyme activity. A low ionic strength and concentration of the salts of 0,1 M the temperature maximum was 45 degrees and the shapes of temperature curves were the same. The Arrhenius plots showed a break at 16--19 degrees. The apparent activation energies were 27,3 kcal/mole below and 17,1 kcal/mole above the break point. At high ionic strength (0,5 M) the temperature maximum was observed at 40 degrees and the apparent activation energies decreased down to 18,0 kcal/mole below and 11,5 kcal/mole above the break point.

[Purification and some properties of skeletal muscle sarcolemma Ca2+-ATPase]. / Ochistka i nekotorye svoistva Ca-ATPazy sarkolemmy skeletnykh myshts.

Ca2+-ATPase of skeletal muscle sarcolemma has been isolated and purified. It is prepared from salt extract of sarcolemma by ammonium sulfate fractionation and further purified by gel chromatography on Sepharose 4B. The purity of preparations was evaluated by polyacrylamide gel electrophoresis in sodium dodecyl sulfate. It has been shown that Ca2+-ATPase possesses the same mobility as skeletal muscle myosin under gel chromatography on Sepharose 4B and the same mobility as myosin heavy chains in sodium dodecyl sulfate--polyacrylamide gel electrophoresis. Membrane protein binds to rabbit skeletal muscle actin, and this complex dissociates by ATP. Interaction with actin does not change Ca2+- or Mg2+-stimulated ATPase activity. Enzyme has only one pH optimum at 7,0-7,6. Membrane protein is highly specified to calcium--ATPase activity in the presence of Mn2+ is 10% and in the presence of Sr2+, Mg2+ or Co2+ are 3-5% of the activity in the presence of Ca2+. Other nucleoside triphosphate (UTP and ITP) are hydrolyzed at lower rates than is ATP.

[Kinetic properties of skeletal muscle sarcolemmal Ca2+-ATPase]. / O kineticheskikh svoistvakh Ca2+-ATPazy sarkolemmy skeletnykh myshts

Calcium activation of skeletal muscle sarcolemma Ca2+-ATPase is investigated. The investigation of a dependency of the initial rate of ATP hydrolysis on total concentration of substrate and on total and free calcium concentrations showed that the role of calcium ions is not limited by the formation of the substrate complex (CaATP2-). Calcium is absolutely necessary for the enzyme transition from inactive into active form. The inhibitory effect of free ATP is due to a decrease of free calcium concentration as a result of complexation with ATP, but not of competition with substrate in the active site. It is shown also that magnesium competitively inhibits the interaction of the enzyme with the substrate and non-competively suppress the activation of Ca2+-ATPase by free calcium.