[PET/CT with 11C-methionine in assessment of brain glioma metabolism]. / Pozitronnaya emissionnaya tomografiya v sochetanii s komp'yuternoi tomografiei i 11S-metioninom v otsenke metabolizma gliom golovnogo mozga.

OBJECTIVE: To study 11C-methionine (MET) metabolism in gliomas using CNS tumor biobank imaging data. MATERIAL AND METHODS: MRI and 11C-MET PET/CT were performed in 225 patients (49±14 years, M/F=84/101) according to standard protocols with analysis of 11C-MET accumulation index and volumetric parameters (V_FLAIR, V_PET and V_PET/FLAIR). These results were compared with molecular genetic testing and 2-year overall survival. RESULTS: We examined 225 patients with gliomas (97 glioblastomas, 70 astrocytomas, 58 oligodendrogliomas). Accumulation index and volume of 11C-MET in glioblastomas were significantly higher in the general group (AI=2.90, Se 69%, Sp 76%, AUC 0.76; V_PET=24.3 cm3, Se 67%, Sp 60%, AUC 0.65; V_PET/FLAIR 0.46, Se 60%, Sp 69%, AUC 0.67) and within the group of astrocytomas (AI=2.93, Se 68%, Sp 89%, AUC 0.84; V_PET=8.06 cm3, Se 91%, Sp 35%, AUC 0.66; V_PET/FLAIR 0.27, Se 77%, Sp 60%, AUC 0.71). The median 2-year overall survival in patients with glioblastomas was 13 months that was significantly lower compared to IDH «+¼ gliomas (p<0.0001). There was a relationship between high accumulation index of 11C-MET and shorter overall survival in patients with glioblastomas. Significantly higher AI >3.59 (Se 89%, Sp 67%, AUC 0.79) was additionally obtained in subgroup of patients with glioblastomas >50 years (n=34) for EGFR «+¼ tumors. CONCLUSION: We found variable 11C-MET metabolism in WHO 2021 gliomas and confirmed significant difference in metabolic activity and volume of 11C-MET accumulation in glioblastomas compared to IDH «+¼ gliomas. Moreover, we revealed the relationship between high accumulation index and shorter survival. Analysis of 11C-MET metabolism in patients over 50 years old revealed higher accumulation index in the EGFR «+¼ group. Further comparison of these imaging methods and assessment of other significant mutations are necessary to identify the anatomical and metabolic patterns of IDH «+¼ gliomas.

[Prognosis of overall and disease-free survival in patients with grade 3 astrocytomas (anaplastic astrocytoma, WHO 2016)]. / Faktory, opredelyayushchie prognoz obshchei i bezretsidivnoi vyzhivaemosti u patsientov s astrotsitomami grade 3 (anaplasticheskimi astrotsitomami, WHO 2016).

Anaplastic astrocytoma (AA) is a rare intracerebral tumor. Therefore, the number of studies devoted to risk factors of overall and disease-free survival is small. This single-center clinical study is devoted to various factors influencing prognosis of treatment in this group of patients. MATERIAL AND METHODS: A retrospective study included 389 patients diagnosed with grade 3 astrocytoma. We analyzed dependence of overall and disease-free survival from the following factors: gender, age of onset of disease, tumor extent, surgery, neurological disorders before and after surgery (NANO grading system), Ki67 index, postoperative radio- and chemotherapy (number courses, treatment regimens). RESULTS: Significant risk factors for overall and disease-free survival were spread and volume of tumor, postoperative neurological aggravation, Ki67 index, IDH mutation, radio- and chemotherapy. Age, frontal lobe tumor and disease manifestation variant were significant only for overall, but not for disease-free survival. CONCLUSION: This study was based on material of one of the largest clinical series of patients with AA operated on in one center in «molecular¼ era. Our results are consistent with previous data. Analysis of tumor biology and risk factors for IDH-negative AA without molecular signs of glioblastoma may be perspective.

[Hypersomnia in mental disorders]. / Gipersomniya pri psikhicheskikh rasstroistvakh.

Hypersomnia is a group of diseases that share the main symptom - excessive daytime sleepiness, not caused by disturbances in nocturnal sleep or circadian rhythms. Excessive daytime sleepiness is present in 15.6% of adults in the world, a Russian study showed a prevalence of 39.2%. It is associated with a wide range of comorbidities, including obesity and mental disorders, on the other hand, the presence of hypersomnia increases the likelihood of mental illness. People with hypersomnia are more likely to take medications, have a decreased quality of life, spend more health care resources, and more often receive social benefits. The heritability is estimated to be about 40% for sleep duration and 17% for excessive daytime sleepiness. Hypersomnia in mental disorders is secondary. It most often occurs in patients with depression or bipolar disorder. To assess the severity of daytime sleepiness, self-observation and objective methods, including the multiple sleep latency test, actigraphy, polysomnography, are used. In the differential diagnosis of hypersomnia in psychiatric disorders, it is necessary to make a differential diagnosis with hypersomnia caused by taking medications or other substances and insufficient sleep syndrome. The etiology of prolonged sleep in psychiatric disorders is complex, and includes biological and psychological causes. The relationship between self-reported hypersomnia and sleep actually obtained is still unclear. Results of daily polysomnography show a significant increase in time in bed during the day and night (clinophilia). Therapy of hypersomniac syndromes should be done taking into account the etiology of the disease. In cases of secondary nature, the main efforts should be directed to the treatment of the underlying mental disorder causing somnolence.

Sleep Disorders in Post-COVID Syndrome: A Psychiatric or Neurological Problem?

The coronavirus pandemic that began in 2019 continues. COVID-19 adversely affects human health not only in the acute, but also in the long-term period of the disease: in a large percentage of cases, health is not fully restored after long periods, requires medical intervention, and is often difficult to correct. Researchers noted during the first wave of the pandemic in 2020 that about 10-20% of patients did not fully recover by three weeks from disease onset and the possible duration of the recovery period remains insufficiently clear, as do the reasons for differences in course during this period. Prolonged recovery after viral infection is not a feature exclusive to COVID-19, which does not facilitate the management of patients with post-COVID syndrome (PCS). The mental health impact of COVID-19 is significant, with at least 30% of recovered patients likely to have symptoms of anxiety and/or depression after the acute phase has passed. Since the onset of COVID-19, there has been an increase in sleep disorders by 42%, with every third COVID-19 survivor reporting sleep complaints. In PCS, this condition is referred to as coronasomnia. The success of therapy for this condition depends on identifying and correcting patients' mental disorders, as anxiety and depression are often accompanied by sleep disorders this results in a bidirectional interaction between mental disorders and sleep quality. This article presents data on the anti-anxiety drugs Noofen and Adaptol, which help to correct the manifestations of PCS with sleep disorders.

[NMDA receptors expression activity in anaplastic astrocytomas]. / Aktivnost' ekspressii NMDA-retseptorov glutamata v anaplasticheskikh astrotsitomakh.

OBJECTIVE: To study the relationship of NMDA receptors expression activity with proliferative activity and genetic properties of anaplastic astrocytomas, as well as the survival of patients with this disease. MATERIAL AND METHODS: To solve this problem, we compared the expression activity of the least studied NMDA receptors in the context under consideration, detected using immunofluorescent studies and polymerase chain reaction, with the results of histological and molecular studies, the proliferative activity of neoplasms, and the survival of patients. RESULTS: The expression activity of NMDA receptors is higher in astrocytomas, grade 3, which do not carry mutations in IDH1 and IDH2 genes. In addition, the activity of NMDA receptors expression directly correlates with proliferative activity in the tumors. The activity of NMDA receptor expression has a significant impact on the prognosis of disease-free survival. CONCLUSION: We have shown for the first time the significant role of NMDA receptors in the progression of diffuse astrocytomas, which can become the basis for creating new therapeutic and diagnostic tools.

[Clinical aspects of the use of imidazopyridine derivatives in the treatment of sleep disorders associated with post-COVID syndrome]. / Klinicheskie aspekty primeneniya preparatov gruppy imidazopiridinov v terapii narushenii sna, assotsiirovannykh s postkovidnym sindromom.

In 2019, a pandemic caused by the SARS-CoV-2 virus began. The fight against COVID-19 required the introduction of a number of restrictive measures, in particular the introduction of quarantine for the population and isolation of the sick, which, along with the direct effect of the virus on the nervous system, led to a significant spread of sleep disorders. In this regard, questions have become relevant about the choice of drugs for the correction of sleep disorders, about which sleeping pills will be safe in conditions of acute illness and during the recovery period after COVID-19. The article discusses the prevalence and therapy of insomnia in patients with acute COVID-19 and in patients with postcovid syndrome. The pharmacological effects and safety of zolpidem, a non-benzodiazepine short-acting hypnotic drug belonging to the class of imidazopyridines, which is used in short courses for both acute and transient insomnia and chronic insomnia, are described. The data on the ability of zolpidem to improve memory after a night's sleep are given. The possibility of its use in acute COVID-19 and postcovid syndrome is being evaluated.

[Role of TERT mutation for treatment prognosis in patients with IDH-negative anaplastic astrocytoma]. / Znachenie TERT-mutatsii v opredelenii prognoza lecheniya patsientov s IDH-negativnymi anaplasticheskimi astrotsitomami.

OBJECTIVE: To study the effect of TERT mutation on overall and relapse-free survival in patients with IDH-negative diffuse astrocytomas grade III (anaplastic gliomas). MATERIAL AND METHODS: The study included 45 patients aged 45.5 years. Forty-two patients underwent resection of tumor, other 3 ones - stereotactic biopsy. TERT mutation was identified in 21 patients. External beam radiation therapy was performed in 35 patients (60 Gy), chemotherapy - in 34 patients (mainly temozolomide). Follow-up data were available in 44 patients. RESULTS: Median of overall survival in patients with TERT mutation was 15.3 months, in patients with TERT-negative tumors - 65.1 months. Median of relapse-free survival in patients with TERT-positive anaplastic astrocytoma (AA) was 13.3 months, in patients with TERT-negative glioma - 57.7 months. These differences were not significant. Relapse-free survival was higher in patients with AA and no TERT mutation at all intervals, but especially at early stages (12 and 24 months). CONCLUSION: Inclusion of TERT mutation in mandatory examination panel for gliomas in general and, in particular, gliomas grade II/III without IDH mutation can lead to sub-classification of these tumors in the near future. Routine analysis of TERT mutation in these patients will be valuable for correct medical consultation regarding prognosis and adequate adjuvant treatment.

[Sleep disorders in post-COVID syndrome - a problem of psychiatry or neurology?] / Rasstroistva sna pri postkovidnom sindrome ­ problema psikhiatrii ili nevrologii?

The pandemic of coronavirus infection, which has begun in 2019, has not ended to this day. COVID-19 adversely affects human health not only in the acute period of the disease, but also in the long-run: in a large percentage of cases, recovery takes very long, patients require and often have problems returning to their baseline. During the first wave of the pandemic in 2020, researchers noted that about 10-20% of patients didn't fully recover three weeks after the onset of the disease. It is still not clear how long the recovery period can last, and what are the reasons of different time course of the recovery. Long-term recovery after a viral infection is a non-unique feature of COVID-19, which does not facilitate the management of patients with post-COVID syndrome. The impact on mental health after COVID-19 is significant, and at least 30% of those, who have been ill, may have symptoms of anxiety and/or depression after the acute phase of the disease. Since the emergence of the SARS-CoV-2 virus, there has been an increase in somnological disorders by 42%, while every third COVID-19 patient reports altered sleep patterns. In post-COVID-19 syndrome, this condition is referred to as Coronasomnia (COVID-somnia). The success of therapy of this condition depends on reporting and treating mental disorders in patients, as anxiety and depression are often accompanied by sleep disorders, that is, there is a bidirectional influence of mental disorders on the quality of sleep. The article provides data on two anti-anxiety drugs (noofen and adaptol) that help to treat the manifestations of post-COVID syndrome accompanied by sleep disorders.

[A multidisciplinary approach in the treatment of elderly and senile patients with complications of colon cancer.]

The article presents the results of treatment of elderly and senile patients with complications of colon cancer, in whose perioperative management a multidisciplinary approach was used. The peculiarity of patients in older age groups, caused by polymorbidity, the phenomenon of mutual complication, requires the use of a non-standard approach in the treatment of complicated colon cancer, since the latter is accompanied by negative results. A comparative analysis of the results of treatment of 289 elderly and senile patients with complicated colon cancer by the traditional method and using a multidisciplinary approach was carried out. The patients were divided into two groups: study and control. In addition to the introduction of the principles of a multidisciplinary approach, additional diagnostic methods were used in the main group in order to more specifically determine the type, severity of complications, staging of the window process and determine functional operability. Patients of the main group, taking into account the implementation of a multidisciplinary approach, were operated using endovideosurgical technologies. In the group of patients where a multidisciplinary approach was used using additional diagnostic methods and minimally invasive treatment methods, a more favorable course of the postoperative period was noted with a decrease in postoperative complications (from 44,9 to 27,8%) and mortality (from 8,9 to 5,3%).

[Anaplastic pleomorphic xanthoastrocytoma - single-center analysis of 42 patients]. / Anaplasticheskaya pleomorfnaya ksantoastrotsitoma ­ analiz 42 nablyudenii iz odnoi kliniki.

Anaplastic pleomorphic xanthoastrocytoma is a rare tumor. There are still no objective data on the incidence of its diagnosis. OBJECTIVE: To study neuroimaging, morphological features of tumors, as well as factors affecting treatment and prognosis. MATERIAL AND METHODS: A retrospective study enrolled 42 patients operated on at the Burdenko Neurosurgery Center between 2003 and 2020. MR characteristics of anaplastic pleomorphic xanthoastrocytoma were analyzed. All patients underwent resection of tumor (total resection in 83.3% of cases). Redo surgeries were performed in 1/3 of patients. Mutational status of BRAF V600E was assessed in all patients. Adjuvant radio- and chemotherapy was performed in more than 80% of cases. Tyrosine kinase inhibitors were administered in 19% of cases. The follow-up period was 152 months (median 34 months). RESULTS: We found no pathognomonic MR signs of this disease. Indeed, anaplastic pleomorphic xanthoastrocytoma have the same signal characteristics as other malignant gliomas. The BRAF V600E mutation status was positive in 54.8% of cases. None patient had IDH-1 mutation. Mean Ki-67 index was 12.5%. The overall survival was 79 months (range 4-152). Seven (17%) patients are alive for more than 90 months. Only Ki-67 index and BRAF mutation significantly influenced the treatment prognosis and overall survival regardless the use of tyrosine kinase inhibitors. CONCLUSION: Such well-known factors for malignant glioma as patient age, total resection and adjuvant therapy did not significantly affect overall survival. Perhaps, searching for new molecular genetic features will reveal additional significant factors of prognosis in patients with anaplastic pleomorphic xanthoastrocytoma.

3D pCASL-perfusion in preoperative assessment of brain gliomas in large cohort of patients.

The aim of the study was to evaluate the role of pseudocontinuous arterial spin labeling perfusion (pCASL-perfusion) in preoperative assessment of cerebral glioma grades. The study group consisted of 253 patients, aged 7-78 years with supratentorial gliomas (65 low-grade gliomas (LGG), 188 high-grade gliomas (HGG)). We used 3D pCASL-perfusion for each patient in order to calculate the tumor blood flow (TBF). We obtained maximal tumor blood flow (maxTBF) in small regions of interest (30 ± 10 mm2) and then normalized absolute maximum tumor blood flow (nTBF) to that of the contralateral normal-appearing white matter of the centrum semiovale. MaxTBF and nTBF values significantly differed between HGG and LGG groups (p < 0.001), as well as between patient groups separated by the grades (grade II vs. grade III) (p < 0.001). Moreover, we performed ROC-analysis which demonstrated high sensitivity and specificity in differentiating between HGG and LGG. We found significant differences for maxTBF and nTBF between grade III and IV gliomas, however, ROC-analysis showed low sensitivity and specificity. We did not observe a significant difference in TBF for astrocytomas and oligodendrogliomas. Our study demonstrates that 3D pCASL-perfusion as an effective diagnostic tool for preoperative differentiation of glioma grades.

[COVID-19 and stress-related disorders]. / Kovid-19 i stress-svyazannye rasstroistva.

Since the WHO declared the COVID-19 outbreak a pandemic, the most actual problem has been a change in the lifestyle of the population of Russia and the rest of the world. Fear of illness, self-isolation/quarantine, and decreased quality of life have dramatically increased the level of stress-related disorders in the population. The main mental disorders arising from stress refer to anxiety disorders (post-traumatic stress disorder (PTSD), panic disorder, agoraphobia, social phobia, generalized anxiety disorder), obsessive-compulsive disorder, depressions of varying severity and conversion reactions. The symptoms and early warning signs of stress-related disorders may be chronic or episodic. Stress-related disorders are corrected with psychotropic therapy, which aims to restore the balance of neurotransmitters. Current first choice agents for the treatment of both pathological anxiety and depression are selective serotonin reuptake inhibitors (SSRIs). During the pandemic, the SSRI fluvoxamine is of special interest. Its mechanisms of action are recognized as potentially useful for treating COVID-19 infection. Two studies confirming the efficacy and safety of fluvoxamine in the treatment of coronavirus infection are described.

[Anaplastic astrocytoma and anaplastic oligodendroglioma of the brain: current state of the problem]. / Anaplasticheskie astrotsitomy i anaplasticheskie oligodendrogliomy golovnogo mozga: sovremennoe sostoyanie problemy.

This review is devoted to the problem of anaplastic cerebral gliomas. The authors consider classification, neuroimaging of these tumors including comparison of magnetic resonance imaging and positron emission tomography data. Clinical manifestations of anaplastic gliomas, issues of their histological and molecular genetic classification are discussed. Moreover, the authors compare the data of neuroimaging and genetic examinations of tumors. Other issues are multicomponent treatment and prognosis in patients with anaplastic glioma of the brain.

[Menopausal hormonal therapy and breast cancer.]

The most common treatment for menopausal syndrome is menopausal hormone therapy (MHT), however, the safety of MHT, due to the risk of developing and recurrent breast cancer (BC), is still a matter of debate. The review presents the results of randomized cohort studies of this issue. It has been shown that MHT increases the risk of developing of breast cancer and disease recurrence after treatment. Risk of breast cancer developing in women getting MHT, depends on body mass index (BMI), duration of hormone use and dose of drugs, and is greater in thin women comparing with women with increased BMI, and also greater in estrogen-progestin combined MHT users comparing with estrogen-only users. It was found that in women using MHT hormone-dependent forms of cancer developed more often, but by the time of diagnosis, disease was found in more advanced stage and metastases in lymph nodes were found more often comparing with patients who did not use MHT. Risk of breast cancer recurrence is less with the use of low doses of vaginal estrogen. An alternative option for the relief of menopausal disorders in breast cancer patients during and after treatment is using of pineal gland hormone melatonin, since, along with its anti-aging properties, it is able to suppress cancer at the stages of initiation, progression and metastasis and has the ability to reduce the toxic effects of anticancer drugs while increasing their effectiveness.

Measurement of single-crystal piezo modulus by the method of diffraction of synchrotron radiation at angles near π.

This article presents measurements of the piezoelectric modulus d 11 of a single crystal of lanthanum gallium silicate (LGS, La3Ga5SiO14). The piezoelectric modulus was measured by X-ray diffraction at angles close to backscattering. Experiments in such schemes are very sensitive to relative changes in the lattice constant in crystals caused by external influences (constant or alternating electric field, mechanical load, temperature change etc.). The development opportunity of the technique is shown, its applicability is evaluated and results of measurement of the LGS single-crystal piezo modulus by the method of diffraction of synchrotron radiation at angles near π are discussed.

[The first results of the analysis of the activity of the cancer service of the North-Western Federal district of the Russian Federation, conducted on the basis of the created population cancer register of the Federal district.]

The completely formed database of the Population Cancer Registry (PCR database) of the North-Western Federal district of the Russian Federation in February 2019 has significantly expanded the ability to objectively assess the activities of the cancer service on a more reliable basis of analytical materials. In Russia, for the first time, it was possible to conduct epidemiological studies of malignant tumors for rare tumor locations, any age groups, and calculations of patient survival rates. The PCR database has more than 1 million observations and includes all the headings and subheadings of ICD-10 for class II - codes C00-96. The article will present the dynamics of morbidity and mortality of the population of the northwestern Federal district of the Russian Federation in comparison with the national average, the reliability of accounting and survival of patients with malignant tumors. For 8 years, the growth of cancer incidence in the Northwestern Federal district of the Russian Federation by 10,4% in standardized indicators and a decrease in population mortality in the Northwestern Federal district of the Russian Federation by 11,4% in the same indicators. The dynamics of the 5-year observed survival rate of patients with Northwestern Federal district of the Russian Federation, taking into account age groups, is calculated. The reliability of the PCR database of the Northwestern Federal district of the Russian Federation is confirmed by the fact that the materials of 3 administrative territories are included in the IARC monograph «Cancer incidence in five continents. Vol. XI¼ (Saint-Petersburg, Arkhangelsk region and the Republic of Karelia).

[The role of comprehensive geriatric assessment in the treatment of cancer patients in elderly and senile age.]

Modern approaches to the organization of diagnosis and treatment of elderly and senile patients with malignant tumors allow to maintain the necessary level of health, improve the quality of life and increase life expectancy. Assessment of geriatric status in Oncology allows: to predict complications during the complex treatment, including drug treatment; to modify treatment to reduce the risk factors of adverse outcomes; to select patients for specialized treatment using standard schemes. So, timely assessment of geriatric syndromes and their correction can expand the indications for specialized treatment of elderly and senile patients.

Directed, Elliptic, and Higher Order Flow Harmonics of Protons, Deuterons, and Tritons in Au+Au Collisions at sqrt[s_{NN}]=2.4 GeV.

Flow coefficients v_{n} of the orders n=1-6 are measured with the High-Acceptance DiElectron Spectrometer (HADES) at GSI for protons, deuterons, and tritons as a function of centrality, transverse momentum, and rapidity in Au+Au collisions at sqrt[s_{NN}]=2.4 GeV. Combining the information from the flow coefficients of all orders allows us to construct for the first time, at collision energies of a few GeV, a multidifferential picture of the angular emission pattern of these particles. It reflects the complicated interplay between the effect of the central fireball pressure on the emission of particles and their subsequent interaction with spectator matter. The high precision information on higher order flow coefficients is a major step forward in constraining the equation of state of dense baryonic matter.

[Individual preoperative 3D modeling of vascular brain pathology]. / Individual'noe predoperatsionnoe 3D-modelirovanie sosudistoi patologii golovnogo mozga.

The possibility of segmenting three-dimensional objects by DICOM-series is well known and available both on specialized workstations and on personal computers. The technique, however, is relatively rarely used in clinical practice, and we believe that the benefits of preoperative preparation using segmented 3D models are underestimated. The article is devoted to our experience in using segmentation of anatomical structures based on CT and MRI for preoperative preparation for surgical operations performed in neurosurgical departments on patients with vascular pathology. The paper discusses the types and possibilities of segmentation, provides some examples describing the clinical use of the technique.

Strong Absorption of Hadrons with Hidden and Open Strangeness in Nuclear Matter.

We present the first observation of K^{-} and ϕ absorption within nuclear matter by means of π^{-}-induced reactions on C and W targets at an incident beam momentum of 1.7 GeV/c studied with HADES at SIS18/GSI. The double ratio (K^{-}/K^{+})_{W}/(K^{-}/K^{+})_{C} is found to be 0.319±0.009(stat)_{-0.012}^{+0.014}(syst) indicating a larger absorption of K^{-} in heavier targets as compared to lighter ones. The measured ϕ/K^{-} ratios in π^{-}+C and π^{-}+W reactions within the HADES acceptance are found to be equal to 0.55±0.04(stat)_{-0.07}^{+0.06}(syst) and to 0.63±0.06(stat)_{-0.11}^{+0.11}(syst), respectively. The similar ratios measured in the two different reactions demonstrate for the first time experimentally that the dynamics of the ϕ meson in nuclear medium is strongly coupled to the K^{-} dynamics. The large difference in the ϕ production off C and W nuclei is discussed in terms of a strong ϕN in-medium coupling. These results are relevant for the description of heavy-ion collisions and the structure of neutron stars.