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Abstract Background Although many well-known factors affect the maximum standardized uptake value (SUVmax), it remains the most requested and used parameter, especially among clinicians, despite other parameters, such as the standardized uptake value corrected for lean body mass and the metabolic tumor volume, being proven to be less sensitive to the same factors, more robust, and eventually more informative. This study intends to provide robust evidence regarding the diagnostic and prognostic value of SUVmax in a large cohort of subjects with suspected malignant lung nodules imaged by [18F]FDG PET/CT. Materials and methods We performed a retrospective analysis of patients with suspected/confirmed primary lung tumours undergoing [18F]FDG PET/CT. The sample size was 567 patients. Demographics, imaging, surgical, histological, and follow-up data were collected. SUVmax was analysed according to histology, stage, scanner, and outcome. The impact on measured values of different reconstruction protocols was assessed. All potential predictors of patients’ outcome were assessed. Results 91% cases were primary lung tumours. Lung benign nodules or metastases accounted for 5% and 4% of cases. Most patients presented with adenocarcinoma (70%) and stage I disease (51%); 144 patients relapsed and 55 died. SUVmax failed to effectively differentiate benign lesions from primary tumours or metastases. Stage I patients presented lower SUVmax. SUVmax significantly correlated with patient weight, injected [18F]FDG activity, and lesion size and differed between reconstructions’ protocols. Survival analyses revealed no independent prognostic significance for SUVmax in progression-free after adjusting for other variables. SUVmax correlated with overall survival, disease stage and tumour histotype. Conclusion Our study confirms that SUVmax, though widely employed, present relevant limitations in discriminating between benign lesion and lung cancer, in classifying cancer histotypes, and in predicting patient outcomes independently. Known influencing factors significantly impact on numerical values, thus SUV values should be regarded with caution in clinical practice.

Background. The Ilizarov method is a recognized technique for treating severe skeletal injuries, allowing for a comprehensive restoration of both bone and soft tissue components. Despite the fact that bone lengthening and transport are widely known techniques, distraction of a longitudinally split fragment is still used extremely rarely. The aim of the study is to describe a series of clinical cases involving patients operated on using this technique. Methods. We present a series of observations of five patients who underwent distraction of a longitudinally split fragment using the Ilizarov method between January 2006 and December 2022. Clinical information was obtained from case histories, all surgical interventions were documented. Postoperative examination was performed using radiography. Results. A case series demonstrates the successful application of this technique for reconstruction of partial bone defects resulting from trauma or osteomyelitis. The study included five patients (4 men and 1 woman) who underwent surgery 4.8-34.0 months after trauma for a partial defect of the proximal tibia ranging from 4 to 8 cm in length. Distraction was performed in different directions along the sagittal and longitudinal axes. The time of external fixation ranged from 3.5 to 4.8 months, the external fixation index ranged from 0.49 to 1.22. The ASAMI (Association for the Study and Application of the Methods of Ilizarov) functional score at the follow-up examination was excellent in all five patients. The ASAMI bone tissue assessment showed excellent results in all patients, except for one patient with residual equinus (good result). No other complications were reported. Conclusions. The Ilizarov method provides a minimally invasive and comprehensive approach to the elimination of partial bone defects, affecting simultaneously the skeletal and soft tissue components. Due to the longitudinal splitting during fragment transport and distraction osteogenesis, this method promotes bone and tissue regeneration and helps to avoid a volumetric bone defect and more complex segmental bone transport. Moreover, the role of transverse transport of the tibial cortex increases in the treatment of peripheral arterial diseases.

Background. Changes in the level of the patella position are a well-known complication of knee replacement, reconstruction of the anterior cruciate ligament, high tibial osteotomy and consequences of injuries. However, this problem has not been disclosed in the literature in relation to distraction osteogenesis using the Ilizarov method. The aim of the study is to describe such a rare iatrogenic complication as patella baja during limb lengthening by the Ilizarov method using a clinical case as an example. Case description. In 2017, a 17-year-old teenager was injured in a head-on collision of cars at high speed. The patient was diagnosed with an open fracture of the left femur and fibula and tibia of the left leg. He was treated in another clinic using the Ilizarov apparatus for osteosynthesis of the femur, tibia and proximal osteotomy of the tibia to move the bone to fill the distal bone defect. At the end of the treatment, the patient had a moderate limitation of the knee flexion (180-80°). In 2018, the patient was admitted to our clinic due to osteomyelitis at the level of the consolidated fracture. A new resection of the osteomyelitis lesion and proximal osteotomy for bifocal osteogenesis were performed. During the treatment, limitation of knee flexion (180-120°) was developed and radiographic signs of low position of the patella were obtained. Given the progression of patella baja (the Caton-Deschamps index = 0.51), we were forced to return the patient to the operating room to restore the correct height of the patella. Conclusions. The presented clinical case emphasizes the need for a more thorough assessment of the patella height after surgical treatment on the proximal tibia using the Ilizarov method. It is also noted that it is important to conduct a control MRI, which allows for a more detailed study of the initial position of the anterior tibial tubercle. In our case, early detection of complications allowed us to achieve complete recovery without any consequences.

Background. Most patients with chronic myeloid leukemia (CML) treated with tyrosine kinase inhibitors achieve durable optimal responses. Loss of the achieved molecular response is observed in 15–30 % of patients. Mutations in the BCR::ABL kinase domain are one of the most common mechanisms for the development of resistance to tyrosine kinase inhibitors.Aim. To conduct a retrospective analysis of the BCR::ABL kinase domain mutational profile in patients with CML observed at the Russian Research Institute of Hematology and Transfusiology from 2012 to 2023. To assess the impact of mutations type and number on the rate of achieving a major molecular response (MMR). To study the risk of MMR loss depending on the therapy line and existing mutational status.Materials and methods. 1831 patients with CML were examined at different times. The mutational status of the BCR::ABL kinase domain was analyzed by direct Sanger sequencing. A standard cytogenetic study was carried out using GTG banding technology with the analysis of at least 20 metaphase plates.Results. Mutations in the BCR::ABL kinase domain were identified in 27.6 % of the total studied patients. The most common mutation, 6.3 % in the overall group or 22.7 % among patients with mutations, was the T315I mutation. Additional chromosomal aberrations (ACAs) were detected in Ph-positive cells in 20.5 % of patients, in Ph-negative clones in 3.9 % of cases (p = 0.0001). The frequency of ACAs detection did not statistically significantly differ (p = 0.25) between patients with BCR::ABL mutations (23.5 %) and with a negative mutation status (17.7 %), and the presence of mutations in the kinase domain did not correlate with ACAs in Ph-positive clones (p = 0.73). However, the frequency of T315I mutation detection in Ph-positive cells had significant differences: 40.9 % in combination with ACAs and 21 % without ACAs (p = 0.032). Patients with the T315I mutation had significantly worse MMR than patients with mutations in other BCR::ABL regions (p = 0.04) and patients without mutations (p = 0.02). The probability of MMR achieving did not differ significantly between patients with different numbers of BCR::ABL mutations (p = 0.14). Loss of MMR occurred more often in patients with mutations (p = 0.04) and not depend on the line of therapy (p = 0.03).Conclusion. For complete monitoring and optimal choice of therapy, CML patients require not only monitoring of BCR::ABL relative expression level, but also standard cytogenetic and analysis of the mutational status.

Background. Indocyanine green (ICG) fluorescence imaging is a surgical tool with increasing applications in various surgical disciplines. During nonunion resection, the assessment of bone vascularization is currently based only on the surgeon’s experience. We introduced the use of indocyanine green (ICG) angiography in orthopedics. The aims of the study: 1) to use ICG fluorescence angiography to evaluate the bone perfusion in patients with atrophic nonunion, where poor or absent ICG flow reveals avascular tissue associated with bone necrosis requiring surgical resections; 2) to describe our case series of patients operated with this technique. Methods. We used ICG angiography in patients operated for tibial nonunion resection. We administered 0.5 mg/kg of ICG powder dissolved in sterile saline at 2.5 mg/ml concentration. The time from the injection to the beginning of appreciation of the green dye was measured. Non-viable bone was resected accordingly. Patient underwent routine follow-up. We enrolled all the suitable patients operated from April 2019 to June 2021 and matched three control patients for each of them. We reviewed their medical records and noted any relevant data. Results. We enrolled 4 cases and 12 controls, all male. The mean age was 30.8±6.9 years. The mean duration from trauma to surgery was 10.5 (0.7-25.0) months. The mean duration of surgery was 190.8±40.3 min. The defect size was 4.89±2.03 cm. ICG allowed rapid visualization of bone vascularization after 25-45 sec. No adverse events were observed. The mean external fixation time was 11.8±5.0 months. The mean external fixation index was 2.69±1.10. Seven patients needed a surgical revision during treatment. Three patients underwent reintervention after frame removal. There are no statistically significant differences between cases and controls. Conclusions. The research findings of this study are limited by the small number of observations. However, this technique is safe, easy, and rapid and may contribute to intraoperative decision of how much to resect. Using ICG could objectively demonstrate bone perfusion to help surgeons to avoid massive bone defects.

Abstract Medical imaging represents the primary tool for investigating and monitoring several diseases, including cancer. The advances in quantitative image analysis have developed towards the extraction of biomarkers able to support clinical decisions. To produce robust results, multi-center studies are often set up. However, the imaging information must be denoised from confounding factors—known as batch-effect—like scanner-specific and center-specific influences. Moreover, in non-solid cancers, like lymphomas, effective biomarkers require an imaging-based representation of the disease that accounts for its multi-site spreading over the patient’s body. In this work, we address the dual-factor deconfusion problem and we propose a deconfusion algorithm to harmonize the imaging information of patients affected by Hodgkin Lymphoma in a multi-center setting. We show that the proposed model successfully denoises data from domain-specific variability (p-value < 0.001) while it coherently preserves the spatial relationship between imaging descriptions of peer lesions (p-value = 0), which is a strong prognostic biomarker for tumor heterogeneity assessment. This harmonization step allows to significantly improve the performance in prognostic models with respect to state-of-the-art methods, enabling building exhaustive patient representations and delivering more accurate analyses (p-values < 0.001 in training, p-values < 0.05 in testing). This work lays the groundwork for performing large-scale and reproducible analyses on multi-center data that are urgently needed to convey the translation of imaging-based biomarkers into the clinical practice as effective prognostic tools. The code is available on GitHub at this https://github.com/LaraCavinato/Dual-ADAE .

Materials are presented on the history of formation and the current state of the arboretum of V. N. Sukachev Institute of Forest Siberian Branch of the Russian Academy of Sciences, established in 1977 with the aim of testing woody plants from various botanical and geographical areas in the conditions of the city of Krasnoyarsk, which will subsequently be a source of seeds and planting material for introduction into green building in the territory of the settlements of Krasnoyarsk Krai. During almost half a century of the existence of the arboretum, about 450 species of woody plants were tested for gradual acclimatization. Currently, 203 winter-hardy species of trees and shrubs grow on its territory (4.17 ha). This collection is the basis for diverse bioecological studies, in which specialists from most laboratories of the Institute of Forest are involved. Observations are made on the seasonal growth, development, physiological and phenological characteristics of woody plants. The reproductive processes and possibilities of seed and vegetative propagation of introduced plants are being studied. The karyological features and microclonal propagation of conifers are studied. The arboretum is a test site for studies of damage to introduced plants by insects and fungal phytopathogens. Modern problems of arboretum conservation associated with the intention to build a multi-storey residential building on its territory are characterized, in which 628 specimens of woody plants (36.8 % of the total number) will be cut down, and 165 specimens will suffer indirectly, being within the area that falls under development. The efforts made in this regard by the authorities and the public to protect the arboretum, to preserve this unique object for future generations of scientists and all residents of the city of Krasnoyarsk are reflected.

The living ground cover species composition under the various tree species canopy in the Arboretum of V. N. Sukachev Institute of Forest, Siberian Branch, Russian Academy of Sciences, in the city of Krasnoyarsk was studied. The purpose of the work is to determine the ground cover species composition, structure and phytomass in the various tree species biogroups. The studies were carried out in 2020–2022 at the 13 tree species biogroups growing on the Arboretum territory. The floristic composition, projective cover and occurrence of species growing in the studied biogroups were determined. Based on the analysis of floristic data, biodiversity indices were calculated. The taxonomic, belt-zonal, ecological, biomorphological features of the flora structure were determined. It was established that 12 shrub layer species and 47 living ground cover species (44 – the grass-shrub layer and 3 moss taxons) were recorded in the studied woody plant biogroups. Species diversity indices were calculated for each biogroup. The ground cover ecological and ecological-coenotic structures have been determined. The most important groups have been identified. The factors influencing the ground cover characteristics were identified. It has been established that the living ground cover floristic composition is influenced by both biotic (phytogenic field) and abiotic factors in the arboretum 46 years after its creation. The phytogenic field species-specific influence on the living ground cover species composition was revealed in six tree species. The ground projective cover and phytomass as well as the species occurrence are significantly affected by abiotic factors, in particular, illumination.

ABSTRACTThe multidrug-resistant pathogen Pseudomonas aeruginosa is a common nosocomial respiratory pathogen that continues to threaten the lives of patients with mechanical ventilation in intensive care units and those with underlying comorbidities such as cystic fibrosis or chronic obstructive pulmonary disease. For over 20 years, studies have repeatedly demonstrated that the major siderophore pyoverdine is an important virulence factor for P. aeruginosa in invertebrate and mammalian hosts in vivo. Despite its physiological significance, an in vitro, mammalian cell culture model that can be used to characterize the impact and molecular mechanisms of pyoverdine-mediated virulence has only been developed very recently. In this study, we adapt a previously-established, murine macrophage-based model to use human bronchial epithelial (16HBE) cells. We demonstrate that conditioned medium from P. aeruginosa induced rapid 16HBE cell death through the pyoverdine-dependent secretion of cytotoxic rhamnolipids. Genetic or chemical disruption of pyoverdine biosynthesis decreased rhamnolipid production and mitigated cell death. Consistent with these observations, chemical depletion of lipids or genetic disruption of rhamnolipid biosynthesis abrogated the toxicity of the conditioned medium. Furthermore, we also examine the effects of exposure to purified pyoverdine on 16HBE cells. While pyoverdine accumulated within cells, it was largely sequestered within early endosomes, resulting in minimal cytotoxicity. More membrane-permeable iron chelators, such as the siderophore pyochelin, decreased epithelial cell viability and upregulated several pro-inflammatory genes. However, pyoverdine potentiated these iron chelators in activating pro-inflammatory pathways. Altogether, these findings suggest that the siderophores pyoverdine and pyochelin play distinct roles in virulence during acute P. aeruginosa lung infection.IMPORTANCEMultidrug-resistant Pseudomonas aeruginosa is a versatile bacterium that frequently causes lung infections. This pathogen is life-threatening to mechanically-ventilated patients in intensive care units and is a debilitating burden for individuals with cystic fibrosis. However, the role of P. aeruginosa virulence factors and their regulation during infection are not fully understood. Previous murine lung infection studies have demonstrated that the production of siderophores (e.g., pyoverdine and pyochelin) is necessary for full P. aeruginosa virulence. In this report, we provide further mechanistic insight into this phenomenon. We characterize distinct and novel ways these siderophores contribute to virulence using an in vitro human lung epithelial cell culture model.

Abstract Background The value of Prostate Specific Membrane Antigen (PSMA) in thyroid carcinoma (TC) is still unknown. We aimed to test the potential complementary role of PSMA expression and 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG) uptake on PET/CT as biomarkers for TC outcome prediction. Materials and methods From a retrospective cohort of TC patients we selected those fulfilling the following inclusion/exclusion criteria: thyroidectomy in our Institution, available primary tumor tissue PSMA immunostaining, [18F]FDG PET/CT and follow-up data. PSMA staining was visually assessed. PET/CT was considered positive in case of [18F]FDG uptake higher than the background at the site of TC confirmed by cyto-/histology, and/or follow-up. Disease recurrence, radioiodine refractoriness (RAI-R) and status at last follow-up (LFU) were used as outcome endpoints. Results We included 23 subjects. Disease recurrence occurred in 18 patients (median time 11 months, range 1–40); among these 12/18 developed RAI-R (median time 28 months, range 2–221), and 13/18 had evidence of disease at LFU. PSMA expression was negative in 6/23 cases. PET/CT was negative in 11/23 patients (7/11 experienced recurrence). PET/CT was positive in 9/12 patients showing RAI-R and 10/13 cases with evidence of disease at LFU. All patients with positive PET/CT had a positive PSMA immunostaining. Six out of 11 patients with negative PET/CT were positive at immunostaining, showing lower PSMA expression (median score of 30%, range 0–80%) than patients with positive PET/CT. The TC samples without PSMA expression belonged to patients who resulted negative also at PET/CT (3 experienced recurrence, 2 were RAI-R, and 1 had disease at LFU). Four out of 11 patients who resulted negative at PET/CT exhibited very high PSMA expression (≥ 70%) and although 3 of them experienced recurrence, none resulted RAI-R, and only 1 had persistent disease at LFU. Conclusions Primary tumor PSMA expression and [18F]FDG uptake seem to play a complementary prognostic role in TC. The majority of patients who expressed PSMA recurred. In the intermediate ATA risk class, patients with negative PSMA immunostaining recurred less than patients expressing PSMA. Additionally, although patients with a negative [18F]FDG PET/CT had a favourable long-term outcome, PSMA assessment might be useful to timely identify subjects at higher risk of recurrence.

ABSTRACTColonization is generally considered a prerequisite for infection, but this event is context-dependent, as evidenced by the differing ability of the human pathogen Pseudomonas aeruginosa to efficiently colonize Caenorhabditis elegans on agar but not in liquid . In this study, we examined the impact of the environment, pathogen, host, and their interactions on host colonization. We found that the transition to a liquid environment reduces food uptake by about two-fold. Also expression of specific adhesins was significantly altered in liquid-based assays for P. aeruginosa, suggesting that it may be one factor driving diminished colonization. Unexpectedly, host immune pathways did not appear to play a significant role in decreased colonization in liquid. Although knocking down key immune pathways (e.g. daf-16 or zip-2), either alone or in combination, significantly reduced survival, the changes in colonization were very small. In spite of the limited bacterial accumulation in the liquid setting, pathogenic colonization was still required for the virulence of Enterococcus faecalis. In addition, we found that a pathogen-induced dormancy was displayed by C. elegans in liquid medium after pathogen exposure, resulting in cessation of pharyngeal pumping and a decrease in bacterial intake. We conclude that poor colonization in liquid is likely due to a combination of environmental factors and host-pathogen interactions. These results provide new insights into mechanisms for colonization in different models, enabling pathogenesis models to be fine-tuned to more accurately represent the conditions seen in human infections so that new tools for curbing bacterial and fungal infections can be developed.

Background. The indication for radiotherapy in oncological practice are metastases of differentiated thyroid cancer after thyroidectomy, the presence of distant metastases, or stage N1b, or negative dynamics of blood thyroglobulin levels after thyroidectomy for thyroid cancer. The mechanism of action of radiotherapy is based on provoking double-stranded DNA breaks. It is important to study the role of polymorphisms of NFKB1, ATM, ATG16L2 and ATG10 genes, products of which are involved in the processes of DNA damage response pathway and autophagy, in the formation of resistance to radioiodine therapy of thyroid cancer patients. Aim. To examine the association between NFKB1, ATM, ATG16L2 and ATG10 polymorphisms and resistance to radioiodine therapy in thyroid cancer patients. Materials and methods. The study included 181 patients (37 men, 144 women; mean age 53.515.7 years) with histologically confirmed thyroid cancer and a history of thyroidectomy who received radioiodine therapy. Carriage of single-nucleotide polymorphisms (rs230493) NFKB1, (rs11212570) ATM, (rs10898880) ATG16L2 and (rs10514231, rs1864183, rs4703533) ATG10 was determined by real-time PCR using TaqMan kits. Results. Among 181 patients, resistance to radioiodine therapy was observed in 11 (6.1%) cases. No significant associations between the individual polymorphisms and resistance to radioiodine therapy were obtained, p0.05. Haplotype analysis showed that carriage of the C-C ATG10 rs10514231-rs1864183 haplotype was associated with an increased risk of developing resistance to radioiodine therapy, p=0.04. Conclusion. Further studies on large samples of radioiodine therapy-resistant patients using whole-genome sequencing methods are required to specify the role of genetic factors in the response to 131I therapy.

The woody and shrubby plants species composition and vital status at the territory of Krasnoyarsk Central Park were studied. The purpose of the work is to determine the tree and shrub species composition at the territory of the Central Park, to assess their vital status, to study the arboriflora structure and biodiversity, to identify dominant and single species, to give recommendations for improving the species composition and plantings quality. The studies were carried out in August 2021. The assessment of the species diversity, vital and sanitary condition of the park’s tree and shrub vegetation was carried out by the method of a complete enumeration of trees. The planting vital index determination was carried out using the generally accepted method of visual assessment of tree and shrub vegetation. It has been established that the Central Park arboriflora is represented by 86 species of plants, including: 39 species of trees, 46 species of shrubs and 1 species of vines. Arboriflora consists of 4470 plant (4133 trees, 337 shrubs), growing in the alley cropping, group planting, solitaires, boskets (total length 582 m) as well as hedge grow (50 m). The plantings vitality index is 1.99, which corresponds to a weakened or slightly damaged stands. The arboriflora structure was determined, its features were identified. The species that make the main contribution were identified. The most stable and weakened species of the park’s arboriflora were identified. Recommendations to stand developing of Krasnoyarsk Central Park were formulated based on the obtained results. It is advisable to apply park reconstruction proposals for urban spaces landscaping in similar environmental conditions.