[Quantitative analysis of orbit volume and eyeball position after resection of hyperostotic sphenoid wing meningioma and simultaneous orbital wall reconstruction using individual technologies]. / Kolichestvennyi analiz ob"emov glaznits i pozitsii glaznykh yablok posle udaleniya giperostoticheskikh meningiom kryl'ev osnovnoi kosti i odnomomentnoi rekonstruktsii stenok glaznitsy s ispol'zovaniem individual'nykh tekhnologii.

OBJECTIVE: To conduct a quantitative analysis of orbit volume at different stages of preparation and surgical treatment of patients with cranio-orbital meningiomas undergoing resection with simultaneous orbital wall reconstruction using 3D modeling and 3D printing technologies. MATERIAL AND METHODS: A prospective cohort non-randomized study included 24 patients with cranio-orbital meningiomas. The volumes were measured by segmenting the orbital structures using the planimetric method in the Inobitec PRO software package. Three expert neurosurgeons independently performed these measurements. The implants were modeled in Blender software. We used the intraclass correlation coefficient (ICC) and global similarity index (GSI) to analyze interrater agreement and ensure reproducibility of analysis. RESULTS: Interrater agreement on orbital markings was very high for both metrics (ICC and GSI). The ICC (A,3) for intact orbit volume was 0.99 (95% CI 0.981; 0.996, p=1.9962018^{-33}), 0.99 (95% CI 0.983; 0.996, p=1.903203^{-34}) for damaged orbit volume at the preoperative stage, 0.99 (95% CI 0.979; 0.995, p=3.5939828^{-32}) for damaged orbit volume at the stage of modeling of resection and reconstruction, 0.99 (95% CI 0.978; 0.995, p=1.1048941^{-30}) for damaged orbit volume in postoperative period. The ICC for measurements related to EI was 0.94-0.97 (very high). This analysis revealed a strong inverse relationship between EI and volume index at the preoperative stage (rho= -0.55, p=0.004987), as well as between dynamics of EI and volume indexes in perioperative period (rho= -0.59, p=0.003). We found significant relationship (p=0.006757) between implant displacement in the area of lateral orbital wall and differences of actual and theoretical volumes. CONCLUSION: The proposed method of planimetric contouring and segmentation of orbital volumes is highly accurate and reproducible. Significant patterns allow us to develop predictive models for preliminary calculation of target volume of the damaged orbit.

[Domestic software, medical devices and materials in surgery for hyperostotic craniofacial meningiomas]. / Primenenie otechestvennogo programmnogo obespecheniya, meditsinskikh izdelii i materialov v khirurgii giperostoticheskikh kraniofatsial'nykh meningiom. (Klinicheskii sluchai i obzor literatury).

OBJECTIVE: The modern concept of resection of hyperostotic craniofacial meningiomas involves the desire for one-stage surgery with excision of tumor and simultaneous extensive skull defect closure. MATERIAL AND METHODS: The authors present skull defect closure with an individual implant after resection of cranioorbital meningioma in a 61-year-old man. The neoplasm was accompanied by exophthalmos and eyelid edema. The patient underwent simultaneous microsurgical resection and skull reconstruction with an individual implant. At discharge (7 days after surgery), exophthalmos regressed to 3 mm. After 3 months, ophthalmologist revealed complete regression of exophthalmos. RESULTS: Domestic software and 3D printers were used for implant modeling and preparing the necessary physical models and molds. We intraoperatively used domestic polymer and titanium fixation systems for manufacturing and fixation of implant. CONCLUSION: This clinical case confirms that resection of hyperostotic craniofacial meningioma with simultaneous bone defect closure using domestic analogues of software, technical equipment, materials and methods is possible at all stages of this procedure.

[Complicated course of the postoperative period with the development of epidural hygroma and intracranial hypotension after removal of cranio-orbital meningioma. Clinical case and literature review]. / Oslozhnennoe techenie posleoperatsionnogo perioda s razvitiem epidural'noi gigromy i vnutricherepnoi gipotenzii posle udaleniya kranioorbital'noi meningiomy. Klinicheskii primer i obzor literatury.

Surgical removal of cranio-orbital meningiomas is an effective method of treating this pathology. Modern surgical techniques and technologies make it possible to perform operations with a low risk of complications. Lumbar drainage or repeated lumbar punctures are often used intraoperatively or in the early postoperative period to prevent nasal CSF leak; this rarely leads to the development of significant neurological symptoms. We present a case of the development of severe intracranial hypotension with the formation of a subdural hygroma in the early postoperative period after removal of a cranio-orbital meningioma in a 41-year-old patient. The operation was performed using an individual model and molds for simultaneous reconstruction of the bone defect with an implant made of polymethyl methacrylate. On the 1st and 2nd days after surgery, lumbar punctures were performed. From the 2nd day there was a progressive deterioration with the development of symptoms characteristic of intracranial hypotension. Computed tomography revealed an increasing displacement of the midline structures of the brain and an increasing volume of epidural fluid accumulation in the area of surgical intervention. Magnetic resonance imaging revealed characteristic signs of intracranial hypotension. Conservative treatment (bed rest, active hydration) had no effect. On the 6th day after surgery, an epidural blood patch procedure was performed and closed external drainage of the epidural hygroma was performed, and a rapid regression of neurological symptoms was noted. Our experience and literature data indicate that it is necessary to remember the possibility of developing clinically significant intracranial hypotension even after a single lumbar puncture. The formation of hygromas in the surgical area is characteristic of intracranial hypotension, but in most cases does not require additional surgical intervention and does not have a negative impact on the outcome of treatment. Conservative treatment of intracranial hypotension is the first choice and often sufficient. If there is no effect and the patient's condition worsens, it is necessary to perform an epidural blood patch procedure.

[Dural defect closure after resection of cranioorbital meningiomas]. / Rekonstruktsiya defektov tverdoi mozgovoi obolochki posle udaleniya kranioorbital'nykh meningiom.

Dural defect closure after resection of cranioorbital meningiomas has its own specifics. Extended malignant lesions and common large bone defects involving various anatomical regions require multiple implants or implants with complex geometry. The features of this stage of reconstruction were described in the previous issue of the Burdenko Journal of Neurosurgery. At the same time, contact of implant with nasal cavity and paranasal sinuses dictates additional requirements for tightness of soft tissue reconstruction and inertness of material. In this review, we describe modern and historically interesting methods of reconstruction of soft tissue defects following resection of cranioorbital meningioma. OBJECTIVE: To summarize and analyze available literature data on reconstruction of soft tissue defects following resection of cranioorbital meningioma. MATERIAL AND METHODS: The authors reviewed available data on reconstruction of soft tissue defects after resection of cranioorbital meningiomas. Effectiveness of reconstruction techniques and safety of materials were analyzed. RESULTS: The authors analyzed 42 available full-text articles. Features of growth and natural course of cranioorbital meningioma, methods of soft tissue defects closure, modern materials and sealing compositions are described. Considering these data, the authors proposed the algorithms for selecting materials for dural reconstruction after resection of cranioorbital meningioma. CONCLUSION: Improvement of surgical technique, development of new materials and technologies increase the efficiency and safety of dural defect closure. Nevertheless, high incidence of complications associated with dura mater repair necessitates further research in this area.

[Bone defect closure after resection of sphenoorbital meningioma]. / Rekonstruktsiya kostnykh defektov posle udaleniya kranioorbital'nykh meningiom.

Sphenoorbital meningiomas (SOM) are a subgroup of skull base tumors with soft tissue component in the orbit and anterior and/or middle cranial fossa. According to different authors, SOMs account for 2-12% of all intracranial meningiomas. Reconstruction of bone defects after resection of SOM has own nuances. Along with cranial vault repair, patients encounter with cosmetic defects following facial skull lesion, ophthalmic symptoms due to orbital defects, dental and functional problems associated with opening of the mouth in case of damage to maxilla and mandible. Predominant infiltrative growth of tumor and common large bone defects involving various anatomical regions require multiple implants or implants with complex shape. Moreover, contact of implantation area with nasal cavity and paranasal sinuses requires additional impermeability of soft tissue reconstruction and inertness of materials. OBJECTIVE: To summarize available modern data on bone defect closure after resection of SOM. MATERIAL AND METHODS: The authors reviewed available data on bone defect closure after resection of SOM. Effectiveness of modern methods of reconstruction and safety of materials were assessed. RESULTS: We analyzed 96 available references. Technical features of tumor resection, materials used for bone defect closure and modern possibilities of 3D technologies in reconstructive surgery were described. The authors proposed the algorithms for selecting the materials for bone defect closure after resection of SOM. CONCLUSION: Improvement of surgical technique and development of new materials and technologies significantly improve cosmetic and functional results. A large percentage of negative ophthalmologic outcomes and high risk of complications in SOM surgery require further studies and elaboration of modern techniques.

[Long-term results of carotid endarterectomy and carotid artery stenting in patients with high bifurcation of common carotid artery: a multiple-center study]. / Otdalennye rezul'taty karotidnoi endarterektomii i karotidnoi angioplastiki so stentirovaniem u patsientov s vysokim raspolozheniem bifurkatsii obshchei sonnoi arterii. Rezul'taty mnogotsentrovogo issledovaniya.

OBJECTIVE: To analyze in-hospital and long-term results of eversion carotid endarterectomy (CEE), carotid endarterectomy with patch repair and carotid artery stenting (CAS) in patients with high bifurcation of common carotid artery. MATERIAL AND METHODS: A retrospective multiple-center open study included 1983 patients who underwent internal carotid artery (ICA) repair for severe stenosis between 2010 and 2021. Three groups of patients were distinguished depending on revascularization option: group 1 (n=638) - eversion CEE; group 2 (n=351) - CEE with patch repair; group 3 (n=994) - CAS. RESULTS: In-hospital postoperative mortality and incidence of stroke and myocardial infarction were similar. All bleedings (n=39) occurred after CEE. ICA thrombosis was diagnosed in groups 1 and 2 due to intimal detachment after insertion of temporary bypass tube. Incidence of laryngeal paresis, neuropathy of hypoglossal and glossopharyngeal nerves, Horner syndrome, damage to salivary glands was comparable in groups 1 and 2. Long-term mortality was the highest (n=10; 2.8%) after CEE with patch repair due to fatal stroke. In turn, the highest incidence of ICA restenosis and restenosis-induced ischemic stroke was observed after CEE with patch repair and CAS. CONCLUSION: 1. Classical and eversion CEE in patients with high CCA bifurcation is followed by high in-hospital incidence of damage to cranial nerves and salivary glands, laryngeal paresis, Horner syndrome, bleeding and risk of ICA thrombosis. 2. In patients with high CCA bifurcation, CAS and CEE with patch repair are accompanied by high incidence of ICA restenosis, restenosis-induced stroke and mortality in long-term postoperative period. 3. Eversion CEE demonstrates the lowest rates of all adverse cardiovascular events in long-term follow-up period.

[Carotid endarterectomy in patients with internal carotid artery thrombosis in the acutest period of ischemic stroke with COVID-19]. / Karotidnaya endarterektomiya u patsientov s trombozom vnutrennei sonnoi arterii v ostreishem periode ishemicheskogo insul'ta na fone COVID-19.

OBJECTIVE: Analysis of the results of emergency carotid endarterectomy (CEE) in internal carotid artery (ICA) thrombosis in the acute period of acute cerebrovascular accident (ACVI) in patients with COVID-19. MATERIAL AND METHODS: During the COVID-19 pandemic (April 1, 2020 - May 1, 2021), 43 patients with ICA thrombosis and a positive polymerase chain reaction (PCR) result for SARS-CoV-2 were included in this prospective study. In all cases, CEE was performed in the acutest period of ACVA. These patients were included in group 1. The comparison group was represented by 89 patients who underwent CEE in the acute period of stroke, in the period before the COVID-19 pandemic (April 1, 2019 - March 1.2020). RESULTS: In the hospital postoperative period, the groups were comparable in terms of the incidence of deaths (group 1: 2.3%, n=1; group 2: 1.1%, n=1; p=0.81; OR=2.09; 95% CI=0.12-34.3) myocardial infarction (group 1: 2.3%, n=1; group 2: 0%; p=0.7; OR=6.3; 95% CI=0.25-158.5), CVA (group 1: 2.3%, n=1; group 2: 2.2%, n=2; p=0.55; OR=1.03; 95% CI=0.09-11.,7). ICA thrombosis and hemorrhagic transformations were not recorded. However, in view of severe coagulopathy with ongoing anticoagulant/antiplatelet therapy, patients with COVID-19 more often developed bleeding in the operation area (group 1: 11.6%, n=5; group 2: 1.1%, n=1; p=0.02; OR=11.5; 95% CI=1.3-102.5). CONCLUSION: Emergency CEE in the acute period of stroke is an effective and safe method of cerebral revascularization in case of ICA thrombosis in conditions of COVID-19.

[A multicenter study on the influence of different kinds of carotidal endarterectomy on the course of resistant arterial hypertension]. / Mnogotsentrovoe issledovanie vliyaniya razlichnykh vidov karotidnoi endarterektomii na techenie rezistentnoi arterial'noi gipertenzii.

OBJECTIVE: To analyze the dynamics of systolic blood pressure (SBP) and the results of various types of carotid endarterectomy (CEE) in patients with resistant arterial hypertension (RAH). MATERIALS AND METHODS: The study included 1577 patients with hemodynamically significant stenosis of the internal carotid artery (ICA) and RAH for more than 3 years. Patients were enrolled from January 2014 to December 2020. Depending on the implemented revascularization strategy, 5 groups were formed: group 1 (n=289 (18.3%)) with classical CEE with plasty of the reconstruction zone with a patch, group 2 (n=472 (29.9%)) with eversional CEE with cut-off of carotid glomus (CG); group 3 (n=109 (6.9%)) with the formation of a new bifurcation; group 4: (n=117 (7.4%)) with autoarterial reconstruction; group 5: (n=590 (37.4%)) with glomus-saving CEE. RESULTS: In the postoperative period, no significant differences were obtained in the frequency of deaths (0.34% for group 1; 0.63% for group 2; 0% for groups 3, 4 and 5), myocardial infarction (0.34%, 0.84%, 1.83, 0.85%, 0.33%, respectively); ischemic stroke (0.34%, 1.27%, 0.91%, 0.85%, 0.17%, respectively), hemorrhagic transformation (0%, 0.84%, 0.91%, 0.85%, 0%, respectively). However, according to the frequency of the combined endpoint (death + myocardial infarction + ischemic stroke + hemorrhagic transformation), the lowest rates were observed in the group of classical carotid endarterectomy with plasty of the reconstruction zone with a patch and glomus-sparing CEE (1.03%, 3.6%, 3.67%, 2.56%, 0.5%, respectively). This is due to the absence of cases of labile AH and hypertensive crises among patients of groups 1 and 5, which was ensured by the preservation of carotid glomus (CG). As a result, the number of patients with 2 and 3 degrees of hypertension in these groups decreased statistically significantly. The vast majority of patients after these operations achieved a stable target SBP. In groups 2, 3, and 4, there was a statistically significant increase in the number of patients with 2 and 3 degrees of AH, which is associated with excision of the CG. CONCLUSION: Classical CEE and glomus-sparing CEE techniques make it possible to achieve a stable target SBP level in patients with RAH as a result of CG preservation. Removal or traumatization of the latter during eversional CEE, the formation of a new bifurcation, autoarterial reconstruction is accompanied by the development of labile hypertension, an increase in the degree of hypertension and a high risk of hemorrhagic transformation in the brain. Thus, the most effective and safe types of CEE in the presence of RAH are classical CEE with plasty of the reconstruction zone with a patch and glomus-sparing CEE.

[Extended lesion of the internal carotid artery: carotid autotransplantation, creation of a neobifurcation or prosthetic repair?] / Protiazhennoe porazhenie vnutrennei sonnoi arterii: karotidnaia autotransplantatsiia, formirovanie novoi bifurkatsii ili protezirovanie?

AIM: The aim of our investigation was to analyse the results of autotransplantation, creation of a neobifurcation or prosthetic repair of the internal carotid artery during the in-hospital and long-term follow-up periods. PATIENTS AND METHODS: The study included a total of 241 patients presenting with and treated for extended atherosclerotic lesions of the internal carotid artery from 2016 to 2019. The patients were divided into three groups depending on the surgical modality employed: group 1 - autotransplantation of the internal carotid artery (27.8%, n=67), group 2 - creation of a neobifurcation (55.2%, n=133), and group 3 - prosthetic repair of the internal carotid artery (17.0%, n=41). The duration of the postoperative follow-up period amounted to 24.8±11.9 months. The outcome measures selected were as follows: all-cause mortality, myocardial infarction, ischaemic stroke, haemodynamically significant restenosis, and a composite endpoint (death + myocardial infarction + ischaemic stroke + haemodynamically significant restenosis). RESULTS: During the in-hospital postoperative period we registered 1 (2.4%) ischaemic stroke in the group of prosthetic repair, with no significant inter-group difference revealed (p=0.08). In the remote period of follow-up, no statistical differences were revealed for the following outcome measures: all-cause mortality (group 1: 7.5%, n=5; group 2: 10.5%, n=14; group 3: 14.6%, n=6; p=0.49); cardiovascular-related death (group 1: 4.5%, n=3; group 2: 6.7%, n=9; group 3: 12.2%, n=5; p=0.31); myocardial infarction (group 1: 1.5%, n=1; group 2: 3%, n=4; group 3: 4.9%, n=2; p=0.59). However, the patients in the group of prosthetic repair of the internal carotid artery were found to have the highest incidence rates of ischaemic stroke (group 1: 3%, n=2; group 2: 3%, n=4; group 3: 14.6%, n=6; p1-2=0.1; p1-3=0.02; p2-3=0.008), haemodynamically significant restenosis (group 1: 0%, n=0; group 2: 0%, n=0; group 3: 14.6 %, n=6; p1-2>0.99; p1-3=0.000; p2-3=0.000), and higher values of the composite endpoint (group 1: 12 %, n=8; group 2: 16.5%, n=22, group 3: 48.8%, n=20; p1-2>0.99; p1-3=0.000; p2-3=0.000). CONCLUSION: Prosthetic repair of the internal carotid artery for an extended atherosclerotic lesion is a less preferable method compared with autotransplantation and creation of a neobifurcation, as evidenced by the highest incidence rates of ischaemic stroke, haemodynamically significant restenosis, and higher values of the composite endpoint in the remote period of follow up.

[The prognostic value of ASXL1 mutation in primary myelofibrosis. Literature review and clinical case description].

Primary myelofibrosis is a myeloproliferative neoplasm that occurs de novo, characterized by clonal proliferation of stem cells, abnormal expression of cytokines, bone marrow fibrosis, hepatosplenomegaly as a result of extramedullary hematopoiesis, symptoms of tumor intoxication, cachexemia, peripheral blood leukoerythroblastosis, leukemic progression and low survival. Primary myelofibrosis is a chronic incurable disease. The aims of therapy: preventing progression, increasing overall survival, improving quality of life. The choice of therapeutic tactics is limited. Allogenic hematopoietic stem cell transplantation is the only method that gives a chance for a cure. The role of mutations in a number of genes in the early identification of candidates for allogeneic hematopoietic stem cell transplantation is being actively studied. The article describes the clinical case of the detection ofASXL1gene mutations in a patient with prefibrous primary myelofibrosis. The diagnosis was established on the basis of WHO criteria 2016. The examination revealed a mutation ofASXL1. Interferon alfa therapy is carried out, against the background of which clinico-hematological remission has been achieved. Despite the identified mutation, the patient is not a candidate for allogeneic hematopoietic stem cell transplantation. Given the unfavorable prognostic value of theASXL1mutation, the patient is subject to active dynamic observation and aggressive therapeutic tactics when signs of disease progression appear.

Cepeginterferon alfa-2b in the treatment of chronic myeloproliferative diseases.

AIM: A comparative evaluation of the effectiveness of different therapeutic strategies in patients with polycythemia vera (PV) and essential thrombocythemia (ET). MATERIALS AND METHODS: Patients with PV or ET, diagnosed according to the criteria WHO 2016 were included in the study. The primary endpoint - 6 months of therapy (clinical-hematological and molecular responses). The secondary endpoint - 12 months of therapy (clinico-hematologic, molecular, histological responses). Sixty three patients were included in the analysis: the first group consisted of 33 patients who received the therapy with ce-pegiterferone alpha-2b (ce-pegalpha-INF-α-2b), 10 of them received previous treatment; the second group - 23 patients btained hydroxycarbamide; the third group - 7 patients were treated with recombinant interferon alpha therapy (rINFα). In comparison groups, differences in age were revealed: patients receiving hydroxycarbamide therapy were older. Phlebotomy occurred in 36% of patients in the first group, 9% in the second group, and 14% in the third group. RESULTS: By the 6th month of therapy, 43% of the patients receiving the ce-pegalpha-INF-α-2b had complete clinical-hematologic response, 36% had partial clinical-hematologic remission and stabilization of the disease was established in 21% cases. No disease progression occured. By the 12th month of therapy, statistically significant differences in terms of efficacy between the different therapeutic groups (p = 0.2462, Fisher's exact test). In all three groups, the allelic load of JAK2V617F decreased: from 50 to 19%, from 22.3 to 15.8%, from 50 to 7.19%, respectively. The lower the allele load positively correlated with better response to therapy, which was observed in all analyzed groups. Hematologic adverse events (AEs) were more frequently observed in patients receiving ce-pegalpha-INF-α-2b therapy. Local reactions developed on 3-7 days of therapy as a hyperemic macula at the injection site. Both these reactions and hair loss did not influence on patient's condition. In the second group (patients with hydroxycarbamide therapy) there were changes in the skin and mucous membranes: dry skin, stomatitis, and in older patients new keratomas appeared. The flu-like syndrome was the most common adverse event associated with the therapy of ce-pegalpha-INF-α-2b, which fully relived during the first month of therapy. There was only one case with the flu-like syndrome we observed at the 11th month of therapy. As a rule, the biochemical blood test changes did not influence on patient's condition, were mostly associated with dietary violations, had a tendency to self-resolution and did not require medical interventions. Serious AEs were reported in one case - pulmonary embolism in a patient treated with rINFα. The reasons for the therapy discontinue in group 1: toxic hepatitis, intolerance, by the request of the patient, inadequate efficacy of therapy; in group 2: skin toxicity, in group 3: thromboses. CONCLUSION: Treatment of ce-pegalpha-INF-α-2b in patients with PV and ET is highly effective - the most patients pbtained clinical and hematological responses. There were no statistically significant differences in these parameters in comparison with hydroxycarbamide and rINFα. The use of the ce-pegalpha-INF-α-2b had an acceptable safety profile. The estimated therapeutic dose should be calculated according to body weight. To reduce the frequency of hematologic AE, titration of the drug dose is required.

Coinheritance of HbD-Punjab/ß+-thalassemia (IVSI+5 G-C) in patient with Gilbert's syndrome.

Thalassemia and qualitative hemoglobinopathy are hereditary disorders of Hb synthesis that lead to change in the Hb conformation or a decrease in the synthesis of structurally normal Hb, and consequently, to erythron pathology. Many variants of Hb are unstable or have altered affinity for oxygen, and, in heterozygous form can be associated with clinical and hematological manifestations (hemolytic anemia, hypochromic microcytic anemia, erythrocytosis). HbD-Punjab [ß121 (GH4) Glu → Gln; HBB: C.364G> C] is variant of Hb carrying the amino acid substitution in the 121 position of ß-globin chain. In all cases reported so far, patients with HbD-Punjab/ß+-thalassemia (IVSI+5 G-C) combination experienced typical thalassemia with hypochromic microcytosis. HbD-Punjab was detected by electrophoresis from 37 to 94% of total Hb. The article describes rare clinical case of the cohabitation of HbD-Punjab/ß+-thalassemia (IVSI+5 G-C) in a patient with homozygous variant of Gilbert's syndrome observed in AS Loginov Moscow Clinical Scientific Center.

[Allele-specific polymerase chain reaction and electrophoretic detection in the detection algorithm clinically significant somatic mutations in the gene of calreticulin (calr).]

The detection of somatic mutations in the 9 exon of the calreticulin gene (CALR) is regulated by the clinical recommendations as a diagnostic criterion for chronic Ph-negative myeloproliferative neoplasms (MPN). Some methods of nucleic acids testing are used to identify CALR gene mutations with different requirements for special skills of personnel and expensive equipment. The purpose of this work is to compare the results of the detection of CALR gene mutations in venous blood samples by allele-specific RT-PCR with subsequent electrophoresis, fragment analysis and Sanger- or pyro- sequencing. We used 1284 blood samples of patients with suspected MPN and 20 blood donor samples. Mutations in the CALR gene of the I and II type were identified using PCR-RT with the original primers and TaqMan probes. Also, all samples were tested for mutations in the CALR gene by electrophoretic detection of PCR results in an agarose gel. The use of allele-specific RT-PCR followed by electrophoretic detection made it possible to determine clinically significant mutations in the CALR gene in 81 venous blood samples of JAK2- and MPL-negative patients, including 42 cases of type I mutation, 33 cases of type II mutation and 8 rare CALR mutations. Mutations in the 9 exon of the CALR gene were not detected in any of the 20 blood donor samples or in 121 blood samples of patients with polycythemia vera. In randomly selected 20 negative samples, CALR gene mutations were also not detected using Sanger sequencing. All positive samples were confirmed by fragment analysis, as well as with Sanger- sequencing and pyro- sequencing. The described combined approach to detect mutations of the CALR gene in peripheral blood samples can be used in clinical diagnostic laboratories that have a standard set of equipment for electrophoresis of nucleic acids and a PCR-RT. We also propose a confirmatory test based on the pyrosequencing of DNA using the system of genetic analysis "PyroMark Q24".

[Clinical features of essential thrombocythemia and primary myelofibrosis, depending on the molecular characteristics of disease]. / Klinicheskie osobennosti éssentsial'noi trombotsitemii i pervichnogo mielofibroza v zavisimosti ot molekuliarnykh kharakteristik zabolevaniia.

The aim of the present paper was to evaluate the clinical features and risk of thrombotic events (TE) in patients with essential thrombocythemia (ET) and primary myelofibrosis (PMF), depending on the molecular characteristics of disease. Clinical data and laboratory parameters were analyzed in 50 ET patients and 50 PMF ones who had been followed up at the Department for Standardization of Treatments, National Research Center for Hematology, Ministry of Health of the Russian Federation, from February 2015 to September 2016. The patients with ET and those with PMF were found to have a high risk of TE. The risk for TE in the patients with ET is higher (24% in the entire group) than in those with PMF (14% in the study group). In ET, there is a high thrombosis risk in the detection of JAK2 and CALR gene mutations as compared with triple-negative cases. The PMF patients with JAK2 V617F mutations are at high risk for TE compared to those who are CALR mutation carriers and in triple-negative cases. There was no significant association of TE with high thrombocytosis. A factor, such as age, was found to be of no negative prognostic value in the patients with PMF.

[Results of following up patients with chronic myeloid leukemia and a deep molecular response without tyrosine kinase inhibitor therapy]. / Rezul'taty nabliudeniia bol'nykh khronicheskim mieloleikozom s glubokim molekuliarnym otvetom bez terapii ingibitorami tirozinkinaz.

AIM: To assess the results of following up patients with chronic myeloid leukemia (CML) and a deep molecular response (MR) without tyrosine kinase inhibitor (TKI) therapy. SUBJECTS AND METHODS: The reasons for TKI discontinuation in 70 patients with CML and a deep MR of more than 1 year's duration were adverse events, pregnancy, and patients' decision. Information was collected retrospectively and prospectively in 2008-2016. RESULTS: The median follow-up after TKI therapy discontinuation was 23 months (2 to 100 months). At 6, 12 and 24 months after TKI therapy discontinuation, the cumulative incidence of major MR (MMR) loss was 28, 41 and 48%, respectively; the survival rates without TKI therapy were 69, 50, and 39%, respectively. MMR loss was noted in 28 (88%) patients at 12 months; it was not seen without TKI therapy at 2-year follow-up. Deaths due to CML progression were absent. The Sokal risk group was a reliable factor influencing MMR loss (p ≤ 0.05). The cumulative recovery rate for deep MR after resumption of TKI use was 73 and 100% at 12 and 24 months, respectively, with a median follow-up of 24 months (1 to 116 months). Deep MR recovered at a later time when the therapy was resumed more than 30 days after MMR loss. CONCLUSION: Safe follow-up is possible in about 50% of the patients with CML and stable deep MRs without TKI therapy. The introduction of this approach into clinical practice requires regular molecular genetic monitoring and organizational activities. Biological factors in maintaining remission after TKI discontinuation need to be separately studied.

[Diagnosis of latent polycythemia vera: A clinician's opinion]. / Diagnostika latentnoi istinnoi politsitemii (vzglyad klinitsista).

AIM: to identify the clinical features of latent polycythemia vera (PV) as an independent nosological entity. SUBJECTS AND METHODS: The investigation enrolled 81 patients (50 with extensive (manifest) PV and 31 with latent PV) who had visited the Outpatient Department, Hematology Research Center, Ministry of Health of Russia, in 2014 to October 2015. RESULTS: The gender distribution of the patients was statistically comparable in the analyzed groups. The patients with manifest PV were slightly older than those with latent PV: the median age in the compared groups was 56 and 44 years, respectively. Red blood cell counts, hemoglobin concentrations, and packed cell volume were higher in the patients with manifest PV. Blood platelet counts were higher in the latent PV group. There were no differences in the number of white blood cells in the compared groups. All the patients were JAK2 V617F mutation carriers. The JAK2 allele load was significantly higher in the manifest PV group than in the latent PV group. The compared patient groups differed in the rate of thromboses in the history or at diagnosis. In the patients with latent PV, thromboses were detected in 38% of cases versus 16% in those with manifest PV. In latent PV, there were mainly venous thromboses; abdominal vascular thromboses were diagnosed with a high frequency. Arterial thromboses were revealed in only 2 cases. CONCLUSION: Chronic myeloproliferative disease that is characterized by the JAK2 V617F mutation, borderline hemoglobin counts, and morphological features of a bone marrow trephine biopsy specimen, which are specific for PV, is an independent PV variant, namely: latent PV.

[Efficiency of interferon therapy in patients with essential thrombocythemia or polycythemia vera]. / Effektivnost' interferonoterapii u bol'nykh essentsial'noi trombotsitemiei i istinnoi politsitemiei.

AIM: To evaluate the efficiency of interferon (IFN) therapy in patients with essential thrombocythemia (ET) and polycythemia vera (PV). SUBJECTS AND METHODS: A total of 61 patients (41 with ET and 20 with PV) were examined. Prior to study enrolment, 44 (72%) patients with ET or PV received one or other therapy (aspirin was not taken into account). The mean Jak2V617F mutant allele at baseline was 23% (6-54%) in the patients with ET and 40% (11-88%) in those with PV. The median time from diagnosis to enrollment was 49 months. RESULTS: The paper presents the clinical and molecular findings of long-term INF-α therapy in patients with ET or PV. The median follow-up was 52 months. Recombinant IFN-α2 showed its ability to induce complete hematologic remission (ET (76%), PV (70%)) and a complete molecular response. 22 (69%) out of 32 patients were noted to have a smaller number of cells with the Jak2V617F mutation. In the patients with PV and in those with ET, the relative reduction in the proportion of cells with the Jak2V617F mutant gene averaged 85% and 56% of the baseline values, respectively. There was a reduction in the proportion of cells expressing the Jak2V617F mutation in both the ET (from 12 to 2.2%; p=0.001) and PV (from 32.7% to 3.2%) groups (р=0.001). Ten (31%) patients achieved a deep molecular remission (≤2% Jak2V617F allele); among them, 5 patients were not found to have Jak2V617F mutation. The obtained molecular response remained in 7 of the 10 patients untreated for 11 to 86 months. The long-term treatment with IFN-α led to normalization of the morphological pattern of bone marrow in 5 of the 7 PV or ET patients. CONCLUSION: Significant molecular remissions achieved by therapy with recombinant interferon-α2 confirm the appropriateness of this treatment option in in the majority of patients with ET or PV.

Reducing thermal crosstalk in ten-channel tunable slotted-laser arrays.

Given the tight constraints on the wavelength stability of sources in optical networks, the thermal crosstalk between operating devices in a ten-channel thermally-tunable slotted laser array for DWDM applications has been investigated. It was found experimentally the current standard thermal solution with the laser array chip mounted on an AlN carrier does not allow for wavelength stability of ± 25 GHz ( ± 2 K) with a temperature rise of 5 K measured in a device with 100 mA (CW) applied to a neighbouring laser (device spacing = 360 µm). A combined experimental/numerical approach revealed solid state submounts comprising diamond or highly ordered pyrolytic graphite are inadequate to reduce crosstalk below an allowable level. Numerical simulations of advanced cooling technologies reveal a microfluidic enabled substrate would reduce thermal crosstalk between operational devices on the chip to acceptable levels. Critically our simulations show this reduced crosstalk is not at the expense of device tunability as the thermal resistance of individual lasers remains similar for the base and microfluidic cases.

[Significance of papillary muscle function of the mitral valve and adjacent left ventricular segments in the progression of ischemic mitral regurgitation in patients with coronary heart disease after surgical treatment]. / Znachenie funktsii papillyarnykh myshts mitral'nogo klapana i prilezhashchikh segmentov miokarda levogo zheludochka v progressirovanii ishemicheskoi mitral'noi regurgitatsii u bol'nykh ishemicheskoi bolezn'yu serdtsa posle khirurgicheskogo lecheniya.

AIM: To determine the significance of papillary muscle (PM) dysfunction of the mitral valve (MV) and adjacent left ventricular (LV) segments in the genesis of ischemic mitral regurgitation (MR) by myocardial tissue Doppler (MTD) in patients with coronary heart disease (CHD) after surgical treatment. SUBJECTS AND METHODS: One hundred and one CHD patients with moderate (grade I-II) MR were examined before surgical treatment. For analysis, the patients were divided into 4 groups: 1A) 40 patients without progressive, none or moderate MR after isolated aortocoronary bypass surgery (ACBS); 1B) 17 patients with progressive MR to its clinically relevant degree after isolated ACBS; 2A) 30 patients without progressive, none, or moderate MR after ACBS and surgical repair of postinfarction LV aneurysm; 2B) 14 patents with progressive MR to its clinically relevant degree after ACBS and surgical LV repair. The mean follow-up after surgery was 5.35±0.58 years. RESULTS: MTD analysis of the PM function of the MV and adjacent LV segments in the patients with CHD after surgical treatment indicated that those with progressive MR had 1) a decrease in the contractility of both PMs and adjacent LV segments; 2) a restrictive pattern of segmental diastolic dysfunction caused by the high myocardial rigidity of both PMs and adjacent LV segments; 3) an inverse correlation of the posterior PM systolic velocity S with the severity of MR, which is suggestive of the clinically important contribution of posterior PM contractility to the development of MR. There were correlations indicating that the high LV and PM rigidities leading to the restrictive pattern of myocardial diastolic impairments are involved in the development of MR in the patients with CHD. CONCLUSION: The results confirm that PM and adjacent LV segment dysfunctions are of significance in the mechanisms of progressive ischemic MR in the patients with CHD after surgical treatment.