Predictive value of 18F-fluorodeoxyglucose accumulation in visceral fat activity to detect colorectal cancer metastases (prospective observational cohort study) [version 1; peer review: 2 approved]

Background: To evaluate functional visceral adipose tissue (VAT) activity assessed by 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) as a predictive factor of metastases in colorectal cancer (CRC) patients. Methods: We reviewed study protocols and PET/CT data of 534 CRC patients; 474 patients were subsequently excluded for various reasons. The remaining 60 patients with histologically confirmed adenocarcinoma were then prospectively assessed and were exposed to 18F-FDG PET/CT after a surgical treatment and chemoradiotherapy. Age, histology, stage, and tumor grade data were recorded. Functional VAT activity was verified with maximum standardized uptake value (SUVmax) using 18F-FDG PET/CT and tested as a predictive factor of later metastases in eight subdomains of abdominal regions (RE – epigastric region, RLH – left hypochondriac region, RRL – right lumbar region, RU – umbilical region, RLL – left lumbar region, RRI – right inguinal region, RP – hypogastric (pubic) region, RLI – left inguinal region) and pelvic cavity (P) in the adjusted regression models. In addition, we studied the best areas under the curve (AUC) for SUVmax with the corresponding sensitivity (Se) and specificity (Sp). Results: In both adjusted for age regression models and receiver operating characteristic (ROC) curve analysis, 18F-FDG accumulation in RLH (cut-off SUVmax 0.74; Se 75%; Sp 61%; AUC 0.668; p=0.049), RU (cut-off SUVmax 0.78; Se 69%; Sp 61%; AUC 0.679; p=0.035), RRL (cut-off SUVmax 1.05; Se 69%; Sp 77%; AUC 0.682; p=0.032) and RRI (cut-off SUVmax 0.85; Se 63%; Sp 61%; AUC 0.672; p=0.043) could predict later metastases in CRC patients, as opposed to age, sex, primary tumor location, tumor grade and histology. Conclusions: Functional VAT activity was importantly related to later metastases in CRC patients and can be used as their predictive factor

Новые возможности в коррекции микронутриентной недостаточности у больных со злокачественными новообразованиями

The cancer cell metabolism leads to micronutrient deficiency of micronutrient deficiency, especially in patients with advanced disease. Various studies in patients with malignant tumors revealed the deficit of certain amino acids (glycine, arginine, cysteine, asparagine, lysine, methionine), vitamins (C, E, D, group B), and a number of trace elements (zinc, manganese, selenium). However, the problem of micronutrient deficiency, as well as the necessity of its correction in cancer patients are not widely recognized and poorly implemented by oncologists. The clinical studies in patients with terminal stage of hepatocellular carcinoma have shown that the use of food supplements affecting the micronutrient metabolism (e. g. Oncoxin) can improve appetite, quality of life and well-being. Furthermore, the ability to improve the 2 months overall survival in this group of patients by using of Oncoxin was demonstrated. Thus, the rational correction of micronutrient deficiency can have a positive effect on the general condition of patients and treatment results.Метаболизм опухолевых клеток при онкологических заболеваниях является причиной дефицита микронутриентов, особенно при распространенном опухолевом процессе. На сегодняшний день доказано, что у пациентов со злокачественными новообразованиями имеется дефицит отдельных аминокислот (глицин, аргинин, цистеин, аспарагин, лизин, метионин), витаминов (С, Е, D, группы B) и ряда микроэлементов (цинк, марганец, селен). К сожалению, проблеме микронутриентного дефицита и необходимости ее коррекции при онкологических заболеваниях не уделяется должного внимания. В современных исследованиях, в частности, проведенных у больных гепатоцеллюлярной карциномой в терминальной стадии, показано, что использование препаратов, влияющих на микронутриентный метаболизм (например, Онкоксин), позволяет увеличить аппетит, улучшить качество жизни, общее самочувствие и 2-месячную выживаемость. Таким образом, рациональная коррекция определенных микронутриентов может положительно влиять на общее состояние больных, результаты лечения и открывает новые перспективы в коррекции нарушений метаболизма у онкологических больных

LB Crystallization and Preliminary X-ray Diffraction Analysis of L-Asparaginase from Rhodospirillum rubrum

Protein X-ray crystallography will remain the most powerful method to obtain the protein 3D atomic structures in foreseeable future. However, the production of the protein crystal as well as it quality (order, intensity of diffraction, radiation stability) remains the major problem. Many important proteins including those of life science interest and pharmaceutical industry impact are difficult to crystallize. The second major problem in protein crystallography is radiation damage of obtaining crystals which can only be partially overcome by existing methods. In the present work we use the protein LB nanotemplate crystallization method - generalized procedure for triggering of crystallization of any given protein, which allows to obtain radiation stable and high quality diffracting crystals for further X-ray analysis by synchrotron radiation. We apply LB nanotemplate method to crystallization of L-asparaginase from Rhodospirillum rubrum. This protein has potential application for combined chemical and enzymatic therapy of malignant blood disorders and therefore for new anticancer drug development. We also compare the diffraction quality of asparagines crystal obtained by classical method and LB nanotemplate and report preliminary X-ray diffraction characterization by synchrotron radiation

The Russian database of HIV antiretroviral drug resistance

The development of sequencing technologies and bioinformatic analysis made it possible to conduct molecular and epidemiological studies, in which nucleotide sequences of the human immunodeficiency virus (HIV) are used as information added to the patient profile. From a practical perspective, studies of prevalence of HIV drug resistance (HIVDR) are of the highest significance. To promote such studies, different countries use databases that serve as repositories of genetic and epidemiological information. The Russian HIVDR database (https://hivresist.ru/) was created in 2009. Nevertheless, it was characterized by limited applicability for a long time. Since 2021, after the regulatory documents had been revised and updated, the entry of HIVDR research results into the Russian HIVDR database has been mandatory. Therefore, the priority attention has been given to upgrading the database and improving its functional capabilities. Different methods have been developed to enter clinical, epidemiological and genetic data. At the time of this study, the Russian database HIVDR contained 10,626 unique records about patients and 13,126 nucleotide sequences deposited by 10 institutions. The following functions have been provided for data analysis: quality control of the epidemiological and clinical information about a patient, quality control of nucleotide sequences, contamination check, subtyping, detection of DR mutations, identification of viral tropism and generation of standardized reports. The efforts toward further development of the Russian HIVDR database will be focused on designing tools for detection and analysis of molecular clusters, adaptation to routine application for epidemiological surveillance of HIV infection

Long-acting injectable Cabotegravir + Rilpivirine for HIV maintenance therapy: Week 48 pooled analysis of phase 3 ATLAS and FLAIR trials

BACKGROUND: Long-acting (LA) injectable regimens are a potential therapeutic option in people living with HIV-1. SETTING: ATLAS (NCT02951052) and FLAIR (NCT02938520) were 2 randomized, open-label, multicenter, multinational phase 3 studies. METHODS: Adult participants with virologic suppression (plasma HIV-1 RNA <50 copies/mL) were randomized (1:1) to continue with their current antiretroviral regimen (CAR) or switch to the long-acting (LA) regimen of cabotegravir (CAB) and rilpivirine (RPV). In the LA arm, participants initially received oral CAB + RPV once-daily for 4 weeks to assess individual safety and tolerability, before starting monthly injectable therapy. The primary endpoint of this combined analysis was antiviral efficacy at week 48 (FDA Snapshot algorithm: noninferiority margin of 4% for HIV-1 RNA ≥50 copies/mL). Safety, tolerability, and confirmed virologic failure (2 consecutive plasma HIV-1 RNA ≥200 copies/mL) were secondary endpoints. RESULTS: The pooled intention-to-treat exposed population included 591 participants in each arm [28% women (sex at birth), 19% aged ≥50 years]. Noninferiority criteria at week 48 were met for the primary (HIV-1 RNA ≥50 copies/mL) and key secondary (HIV-1 RNA <50 copies/mL) efficacy endpoints. Seven individuals in each arm (1.2%) developed confirmed virologic failure; 6/7 (LA) and 3/7 (CAR) had resistance-associated mutations. Most LA recipients (83%) experienced injection site reactions, which decreased in incidence over time. Injection site reactions led to the withdrawal of 6 (1%) participants. The serious adverse event rate was 4% in each arm. CONCLUSION: This combined analysis demonstrates monthly injections of CAB + RPV LA were noninferior to daily oral CAR for maintaining HIV-1 suppression

EFFECTS, CONNECTED WITH THE PHASE SLIPPAGE OF A CHARGED DENSITY WAVE IN TaS*003 QUASI-ONE-DIMENSIONAL CONDUCTOR

The experimental investigation of thermo-e.m.f. (electric motive force) and resistance fluctuations, connected with the phase slippage and deformations of a charged density wave, is the aim of the paper. As a result the model, describing the influence of phase slippage acts on the deformation of a charged density wave, has been created. Spontaneous fluctuations of resistance in TaS*003 samples near the Pajerls's transition have been detected. The of principle possibility of the quasi-one-dimensional sample use for the recording and reading of information with the help of a laser beam has been shown. The paper results may find their field of application in the creation of storage elements, theory of phase transitionsAvailable from VNTIC / VNTIC - Scientific & Technical Information Centre of RussiaSIGLERURussian Federatio

L-Asparaginase for newly diagnosed extra-nodal NK/T-cell lymphoma: systematic review and meta-analysis

Objectives: The aim of this review was to compare the efficacy of asparaginase (ASP)-containing vs ASP-absent regimens in the first-line treatment of ENKTL patients

Defining the toxicity of current regimens for extranodal NK/T cell lymphoma: a systematic review and metaproportion

Objectives: The aim of this study is to compare the toxicity profiles of SMILE versus less intense L-asparaginase-containing regimens, CCRT or "sandwich" RT+CT regimens. Methods: PRISMA protocol was used to search Pubmed and Embase for studies of treatment regimens for extranodal NK/T-cell lymphoma, nasal type (ENKTL) in English published before March 2018. Pooled data were grouped into five categories: A) CHOP-like regimens; B) Gemcitabine-based regimens; C) SMILE-like regimens; D) Concurrent and "sandwich" RT + CT; and E) Methotrexate-based combinations. We pooled prevalence of selected adverse events from each study to calculate the weighted overall prevalence using meta-proportion in Stata. Results: Group C was the most toxic with the pooled neutropenia 72% (95 CI 64;80) and thrombocytopenia 48% (95% CI 40;55) prevalence. The use of Group D treatment regimens was associated with the lowest anemia (10% (95% CI 1;19)) prevalence. Group E was the least toxic with regard to thrombocytopenia (6% (95% CI 1;11). Conclusion: Our analysis confirms that SMILE regimen, which is current standard to treat advanced-stage ENKTL may be associated with more severe hematological toxicity compared to other L-asparaginase combinations, including methotrexate-based (AspaMetDex, MESA and MEDA) or gemcitabine-based (GELOX, PGEMOX, DDGP, GDL, GOLD, GLIDE) or CCRT-based regimens

L-Asparaginase for newly diagnosed extra-nodal NK/T-cell lymphoma: systematic review and meta-analysis

Objectives: The aim of this review was to compare the efficacy of asparaginase (ASP)-containing vs ASP-absent regimens in the first-line treatment of ENKTL patients