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Background. Post-registration observational studies with switching therapy from the original drug to a biosimilar for non-medical indications allow us to assess the safety and effectiveness of this type of switching in real clinical practice. Aim. Evaluation of the safety and effectiveness of non-medical switching from the original drug Keytruda® to the biosimilar drug Pembroria® in patients with various oncological pathologies in real clinical practice (REFLECTION). Materials and methods. A retrospective analysis of data from electronic medical records from 21 medical institutions of the Russian Federation for the period 2020–2023 was carried out. Data were included from patients with cancer of various locations who received at least 2 injections of Keytruda® followed by switching to Pembroria® for non-medical indications (at least 2 injections). Primary criteria: incidence of immune-mediated adverse reactions (ImARs) of any severity. Secondary indicators: incidence of ImARs of various degrees of severity and infusion reactions, frequency of objective response rate (according to RECIST 1.1 criteria). Results. The analysis included data from 382 patients (male/female 200/182, median age 62 years) with NSCLC (24.1%), RCC (23.3%), melanoma (20.4%) and cancer of other localization. Patients received Keytruda® on 1st and 2nd lines (54.2 and 25.4% of patients, respectively), on 3 or 4 lines (14.1%), or as part of adjuvant therapy (6.3%). 50.5% of patients received pembrolizumab as monotherapy. The median number of administrations was 7.0 and 5.0 for Keytruda® and Pembroria®, respectively. ImARs were registered in 44 (11.5%) patients (60 ImARs), including 40 ImARs in 35 (9.2%) patients while using Keytruda® and 20 ImARs in 17 (2.4%) patients with Pembroria®. The most common ImARs were hypothyroidism, hyperthyroidism, and hepatitis; the frequency of these ImARs was higher with Keytruda® (EAER for hypothyroidism 0.00422 and 0.00144, for hepatitis – 0.00124 and 0.00096, respectively). All 5 reported cases of hyperthyroidism in patients on Keytruda® (EAER 0.00124), were resolved before switching to Pembroria®. No infusion-related reactions or deaths due to ImARs have been reported. The objective response rate was comparable – 104 (32.6%) and 90 (29.2%) patients оn Keytruda® and Pembroria® therapy, respectively. Most patients maintained disease control after switching to Pembroria® [progression was recorded in 29 (9.4%) patients after switching to a biosimilar]. Conclusion. The safety profiles of Keytruda® and Pembroria® were satisfactory and comparable in this study. Switching from therapy with Keytruda® to Pembroria® is not accompanied by an increase in the frequency or severity of ImARs. Switching from Keytruda® to Pembroria® maintains disease control in most patients.

Abstract Background In addition to the other uses for macroalgae, since the 1970s, there has been interest in using macroalgae as a source of biofuels, due to the high rates of productivity and intrinsic advantages over other biofuel crops such as not requiring land use or significant freshwater input. A wide range of conversion processes exist but anaerobic digestion was one of the first demonstrated and is still a widely proposed conversion pathway. To be economically viable and scalable within Europe, the industry will need to be based on a small number of fast growing, high-yielding European macroalgae species. There is a wide body of scientific work on the conversion of seaweeds to biofuel via anaerobic digestion. Main text These studies demonstrate that the efficiency of this conversion pathway is highly variable between species, processing techniques, composition and digestor conditions. In this paper, we review this body of work specifically linking it to candidate species for European macroalgae bio-energy cultivation with the aim to promote the future development of the European macroalgal cultivation sector and allow for a better alignment with the requirements for biofuel production from macroalgae. Conclusions Overall, anaerobic digestion of seaweed offers opportunities for large-scale energy production which avoids some of the issues that have faced previous generations of biofuels, but there are a number of key challenges to overcome to ensure wider adoption and economic viability. (1) Optimising the biomass production to ensure an economic and uniform feedstock with the composition optimised to increase desirable characteristics such as sugar content and the carbon and nitrogen ratio and to reduce inhibitory factors such as halogenated secondary metabolites, sulphur and heavy metals. (2) Improving conversion rates through co-digestion, pre-treatments and tailored microbial communities, using scalable and economically feasible technology. (3) Developing tailored microbial communities capable of utilising the diverse polysaccharides in seaweed feedstock and being tolerant of the saline conditions associated with them. Addressing these issues will deliver significant benefits towards the development of a bio-energy industry based on the anaerobic digestion of cultured seaweeds.

Background. Prior to the introduction of new agents — immune checkpoint inhibitors — for inoperable and/or metastatic melanoma (IMM), chemotherapy outcomes were generally poor. The median (Me) overall survival (OS) in IMM was no more than 6-9 months, and the Me of progression-free survival (PFS) was about 2 months. The introduction of immune checkpoint inhibitors and targeted therapy changed the prognosis for the life of IMM patients dramatically. The development, studies, and approval of a new original PD-1 inhibitor, prolgolimab, in Russia in 2020 prompted the professional community to conduct a prospective observational study in the Russian Federation to assess its real-world efficacy and safety. Aim To evaluate the real-world efficacy and safety of prolgolimab in patients with IMM. Materials and methods. From October 2020 to October 2022, 700 patients with IMM receiving prolgolimab in real clinical settings in oncological institutions of various levels in the Russian Federation were included in the study. The main inclusion criteria were: pathology-confirmed diagnosis of melanoma; metastatic and/or inoperable type; use of prolgolimab outside of clinical trials; and signed informed consent. Objective response rate in the general population and the Intention-to-treat and Per Protocol populations was considered the main criterion for evaluating the efficacy of therapy, and the safety criterion was the incidence of grade 3-4 adverse events (AEs). PFS and OS rates were also assessed. Statistical analysis was performed using the SPSS 25.0 software package. Results. The objective response rate for the Per Protocol population (with radiographic assessment available) was 42% (n=235/559). Disease progression was reported in 26.7% (n=149) of patients, stabilization in 31.3% (n=175), and disease control in 73.3% of patients with IMM, regardless of the line of therapy. At the follow-up Me of 12 months (0-36), PFS for all patients regardless of the line of therapy was 8 months (95% confidence interval [Cl] 6.537-9.463), 6-month PFS was 55%, and 12-month PFS was 41%. OS Me for all included patients was 32 months, 6-month OS was 82%, and 12-month OS was 69%. Depending on the line of therapy, the OS Me was: line 1 - not reached, line 2-30 months (95% Cl 16.007-43.993), line 3 and subsequent- 22 months (95% Cl 14.264-29.736); p=0.736. According to the CTCAE 5.0 general terminology criteria for AEs, a total of 136/693 (19.6%) AEs of varying degrees were reported, in particular: grade 1-2 - 105/693 (15.2%), grade 3-4 - 25/693 (3.6%), unknown grade - 5/693 (0.7%), as well as one fatal case (0.1%) due to thromboembolism in the vascular center with an unclear (according to the investigator's assessment) relation with prolgolimab. Conclusion The results obtained at 12 months of follow-up confirm the high efficacy and satisfactory tolerability of prolgolimab in patients with IMM in real-world practice, regardless of the line of therapy and other characteristics.

BackgroundThere is limited insight into the current disease burden and everyday clinical management of moderate-to- severe AD in Poland, Czechia, Russia, and Turkiye. Therefore, this study aimed to get information-driven insights regarding the current disease burden and clinical management of patients with moderate-to-severe AD with common and differentiating aspects of the patient journey and establish a consensus.MethodsIn this modified 2-round Delphi panel, 133 questions were asked in total to 27 dermatologists. A consensus was achieved when 70% of the panel members strongly agreed or agreed (or strongly disagreed or disagreed) with an item. Statements with

IntroductionThe role of upadacitinib in the management of moderate to severe atopic dermatitis seems promising, but more data on its efficacy and safety are needed. This study endeavors to assess the practical impact and safety of upadacitinib in patients with moderate to severe atopic dermatitis. The study aims to evaluate the efficacy and safety of upadacitinib in the treatment of moderate to severe atopic dermatitis, focusing on analyzing patient responses to the treatment.MethodsIn this study, adult patients diagnosed with moderate to severe atopic dermatitis received upadacitinib at daily doses of 15 mg or 30 mg, as prescribed by their attending physicians. The therapeutic efficacy of upadacitinib was meticulously assessed using established clinical metrics. Simultaneously, a comprehensive safety assessment was conducted through monthly monitoring, including the evaluation of potential effects of upadacitinib intake on hepatic function, lipid profile, and hematopoiesis using the pertinent laboratory tests.ResultsSixteen participants were enrolled in the study. At 1month follow-up, there was a significant reduction in the mean Eczema Area and Severity Index (EASI) score to 18.8 points, which further increased to 24 points at the 4-month mark. Additionally, 9 participants (56%) demonstrated an EASI-50 response after 1 month of treatment, with this response increasing to 9 participants (90%) after 4 months. Furthermore, enhanced therapeutic responses were observed at 4 months, with 6 patients (38%) achieving an EASI-75 response at 1month and 8 patients (80%) achieving this milestone at the 4-month follow-up. This study highlights the potential of upadacitinib as an effective treatment option for moderate to severe atopic dermatitis. While it demonstrates improved symptom management, close monitoring for potential adverse events, particularly infections and the known risks of Janus kinase inhibitors, is essential. Further research is essential to determine the long-term safety and efficacy of upadacitinib.

There are several models for predicting remission of type 2 diabetes mellitus (T2D) a year after bariatric surgery — DiaRem, ABSD, IMS, etc. However, these models cannot be used to predict the early normalization of glycemia (within a few months after surgery). These models also do not include the assessment of insulin resistance (IR).AIM. To assess the effect of insulin resistance on the development of remission of T2D after bariatric surgery.METHODS: The study included 42 patients with T2D and severe obesity, who underwent bariatric surgery. Baseline assessment included hyperinsulinemic euglycemic clamp test (with the determination of the M-index (mg/kg/min), and evaluation of HOMA-IR index. Glycemia normalization was determined by self-monitoring ( 1.876 mg/kg/min can be used to predict the glycemia normalization early after bariatric surgery.

Despite their B cell origin, Reed-Berezovsky-Sternberg tumor cells (RBS) in classic Hodgkin's lymphoma (cHL) demonstrate an absolutely unique phenotype. Immunohistochemistry of RBS cells is positive for CD15 antigen in most of cases, CD30, PAX-5; they do not express the T cell antigen CD3, В cell CD19, and in most cases are negative for the B cell antigen CD20, as well as for common leukocyte antigen CD45. Taking into account such unequivocal immunophenotype, RBS cells can be identified by multiparameter flow cytometry. Thus, J.R. Fromm et al. (2006, 2014) have convincingly shown the possibility to identify RBS cells in a puncture and/or biopsy sample of lymphatic nodes in cHL and were of the fair opinion that such rather simple and reproducible technique as flow cytometry could be an additional diagnostic instrument in cHL. We have tested the technique proposed by J.R. Fromm et al. for the assessment of lymphatic node involvement in cHL and used 8 to 10-parameter flow cytometry for detection RBS cells in cHL in 8 biopsy samples of a lymphatic node, and confirmed the feasibility to identify RBS cells by high performance flow cytometry. We also performed morphological and immunohistochemical assessment of the biopsy samples of lymphatic nodes from patients with suspected cHL. The study included clinical cases with immunohistochemically confirmed cHL (n = 8), and the control samples were from those with other diagnoses than Hodgkin's lymphoma. In all cases of cHL we found RBS cells. In future we plan to analyze larger case samples by flow cytometry.

Background. Novel agents immune checkpoint inhibitors fundamentally changed the prognosis for life in patients with metastatic and/or inoperable melanoma. The development, studies, and approval of a new original PD1 inhibitor in Russia in 2020 prompted the professional community to conduct a prospective observational study in the Russian Federation to assess the real-world efficacy and safety of prolgolimab, as real-world patients differ from the refined population in clinical trials. Aim. To evaluate the real-world efficacy and safety of prolgolimab in patients with metastatic and/or inoperable melanoma. Materials and methods. From October 2020 to October 2022, the study enrolled 700 patients with metastatic and/or inoperable melanoma receiving prolgolimab in real clinical settings in oncological institutions of various levels in the Russian Federation. The main inclusion criteria were: pathology-confirmed diagnosis of melanoma, metastatic and/or inoperable type, use of prolgolimab outside of clinical trials, and signed informed consent by the patient. Objective response rate (ORR) was considered the main criterion for evaluating the efficacy of therapy, and the safety criterion was the incidence of grade 34 adverse events. Statistical analysis was performed using the SPSS 20.0 software package. Results. The ORR for patients with skin melanoma treated with prolgolimab in the first line therapy (n= 207/337) was 48.3% (n=100), the disease stabilization was reported in 30.4% (n=63), and progression in 21.3% (n=44) of patients. There were no significant differences in response to therapy between patients with/withoutBRAFmutation, although ORR was higher in patients withBRAFmutation: the ORR for patients withBRAFmutation was 57.9% (n=33), and forBRAFnon-mutated patients, 44.4% (n=52;p=0.222). At a median follow-up of 5 months, the median PFS was 10 months (95% confidence interval 7.3512.64). The incidence of grade 34 treatment-related adverse events according to CTCAE 5.0 was 2% (n=12), and 12% (n=82) for grade 12 adverse events. Conclusion. The results confirm the high efficacy and satisfactory tolerability of prolgolimab in patients with metastatic and/or inoperable melanoma in real-world settings. There were no significant differences in ORR between patients with or withoutBRAFmutation.

Objective: to describe musculoskeletal immune-mediated adverse events (iAEs) associated with the therapy of solid tumors with immune checkpoint inhibitors (ICIs, inhibitors of the PD-1/PD-L1 pathway).Patients and methods. 13 patients receiving ICIs therapy with musculoskeletal iAEs were examined. The average age of patients was 59±10 years. All cases had a histologically verified diagnosis of a malignant solid neoplasm: melanoma (n=5), kidney cancer (n=3), bladder cancer (n=2), non-small cell lung cancer (n=1), breast cancer (n=1), cervical cancer (n=1). All patients were prescribed inhibitors of the PD-1/PD-L1 signaling pathway: nivolumab (n=6), pembrolizumab (n=3), atezolizumab (n=3), prolgolimab (n=1). In 7 (54%) patients, in addition to musculoskeletal disorders, other AEs were also detected: thyroiditis (n=3), neuropathy (n=2), rash (n=1), dry syndrome (n=1), hepatitis (n=1). The median time from the start of antitumor immunotherapy (IT) to the onset of musculoskeletal pathology was 20 [9; 48] weeks.Results and discussion. Clinical manifestations of musculoskeletal pathology included: synovitis in 9 (69%) patients, tenosynovitis in 11 (85%), enthesitis in 4 (31%), morning stiffness in the joints for more than 30 minutes in 4 (31%). In 11 cases, musculoskeletal pathology was persistent (in 9 patients with arthritis and 2 with periarthritis) and in 2 – transient. The knee (77%), shoulder (69%) and hand (54%) joints were most frequently affected, with bilateral involvement in 9 (69%) patients. Inflammatory changes in the joints were represented by mono- (n=1), oligo- (n=3) and polyarthritis (n=5), including those involving the small joints of the hands and/or feet (n=5) and predominantly affecting the joints of the lower limbs (n=3). In 3 patients with arthritis, periarticular changes dominated in clinical picture (in 2 patients with symmetrical polyarthritis and severe tenosynovitis, in another 1 patient – with RS3PE syndrome). The severity of musculoskeletal pathology was assessed using the CTCAE v5.0 toxicity criteria: grade 1 was documented in 2 (15.5%), grade 2 in 9 (69%), and grade 3 in 2 (15, 5%) patients. Laboratory workup revealed elevation of ESR ≥30 mm/h (median – 34 [14; 42] mm/h) in 7 out of 12 (58%) patients, elevation of CRP level >5 mg/l (median – 7.2 [4.6; 12.9] mg/l) – in 7 out of 10 (70%). In 7 out of 10 patients, antinuclear antibodies (Hep2) were detected in titers: 1:160 (n=2), 1:320 (n=3), 1:640 (n=2). Rheumatoid factor and antibodies to cyclic citrullinated peptide were not detected in any case. Therapy for musculoskeletal AEs included non-steroidal anti-inflammatory drugs (n=10), oral systemic glucocorticoids – GC (n=5), methotrexate – MT (n=1) and hydroxychloroquine (n=5), intra-articular administration of GC (n=1). Five patients with arthritis required long-term therapy (median duration – 12 [3; 12] months), in 1 patient with polyarthritis and severe tenosynovitis, antitumor IT was interrupted for the duration of the course of MTX treatment.Conclusion. It has been shown that musculoskeletal iAEs have heterogeneous manifestations and may require long-term treatment and in rare cases, anticancer therapy interruption. Additional studies and close cooperation between rheumatologists and oncologists are needed to obtain a more complete understanding of the nature and spectrum of musculoskeletal AEs, to identify their clinical, laboratory and instrumental features, and to develop an management of patients algorithm.

Classical Hodgkin's lymphoma is one of the most treatable lymphoproliferative diseases with current chemotherapy regimens. The 5-year overall survival rate among patients after initial chemotherapy reaches 95 %, however, despite the significant success achieved, the problem of refractoriness/relapse remains very relevant. A standard approach to the treatment of refractory/recurrent Hodgkin's lymphoma among young patients with preserved general status and chemoresponsive to salvage therapy tumor is high-dose consolidation chemotherapy followed by transplantation of autologous hematopoietic stem cells. The intensification of chemotherapy regimens is highly difficult task for a doctor during the COVID-19 pandemic, which requires careful assessment of a risk-benefit ratio.In current conditions, new targeted and immune drugs are used to overcome resistance and reduce toxicity among pretreated patients, which allows not only to improve the results of a treatment, but also to preserve the high quality of life among patients with extremely unfavorable prognosis.We show our experience of using a checkpoint inhibitor in combination with a dose-intensive regimen of DHAP (dexamethasone, cytarabine, cisplatin) in the treatment of a refractory classical Hodgkin's lymphoma followed by high-dose consolidation chemotherapy and allogeneic hematopoietic stem cells transplantation, among patients complicated with a new coronavirus infection in the post-transplant period.

Mineral weathering is a balanced interplay among physical, chemical, and biological processes. Fundamental knowledge gaps exist in characterizing the biogeochemical mechanisms that transform microbe-mineral interfaces at submicron scales, particularly in complex field systems. Our objective was to develop methods targeting the nanoscale by using high-resolution microscopy to assess biological and geochemical drivers of weathering in natural settings. Basalt, granite, and quartz (53-250 µm) were deployed in surface soils (10 cm) of three ecosystems (semiarid, subhumid, humid) for one year. We successfully developed a reference grid method to analyze individual grains using: (1) helium ion microscopy to capture micron to sub-nanometer imagery of mineral-organic interactions; and (2) scanning electron microscopy to quantify elemental distribution on the same surfaces via element mapping and point analyses. We detected locations of biomechanical weathering, secondary mineral precipitation, biofilm formation, and grain coatings across the three contrasting climates. To our knowledge, this is the first time these coupled microscopy techniques were applied in the earth and ecosystem sciences to assess microbe-mineral interfaces and in situ biological contributors to incipient weathering.

This article discusses current approaches to first-line chemotherapy for non-resectable head and neck squamous cell carcinoma and describes factors affecting the choice of treatment regimen according to the results of randomized clinical trials. We provide a rationale for creating a long-term strategy of chemotherapy in different clinical situations. We also report two cases of concomitant administration of cetuximab and platinum-based therapy as an example of high efficacy of monoclonal antibodies.

Follicular lymphoma (FL) refers to indolent mature B-cell lymphomas and, despite the recurrent course, is generally characterized by a favorable prognosis with long-term overall survival. However, in about 20 %, the disease has an aggressive course with early progression and 5-year overall survival of only 50 %, which indicates the biological heterogeneity of FL. Due to the extremely poor prognosis, cases with disease progression within 2 years from the start of treatment represent a major clinical problem.What predictive risk models of FL early progression are available to us and what regimens of the second and subsequent lines of anticancer therapy should be used? Is high-dose consolidation necessary and when?Choosing the optimal therapy in early progression of FL is a complex task and depends both on the variant of the previous treatment and the patient’s status, as well as the objectively available therapeutic options. In the case of FL early progression after immunochemotherapy, an alternative regimen is used based on a previously unused anti-CD20 monoclonal antibody (rituximab or obinutuzumab) and non-cross-acting chemotherapeutic agents. For CHOP-like induction therapy, the optimal second-line drug is bendamustine. In addition to cytostatics in combination with anti-CD20 monoclonal antibodies, new agents are currently actively used in FL therapy (such as immunomodulators, inhibitors of B-cell receptor and histone methyltransferase signaling pathways, BCL-2 inhibitors, etc.). Numerous clinical trials continue to actively search for promising therapeutic options for the treatment of FL, with testing of new drugs to other B-cell targets and with different mechanisms of action.We present a clinical case of FL with early generalized progression, ineffectiveness of subsequent intensification of treatment with autologous hematopoietic stem cell transplantation and the choice of salvage therapy in the realities of 2009–2012.

Background: There are gaps in our understanding of the epidemiology of atopic dermatitis (AD) in adults. Objective: To evaluate the prevalence and severity of AD in adults from countries/regions within Asia, Eurasia, Latin America, Middle East, and Russia. Methods: This international, web-based survey was performed in Argentina, Brazil, China, Colombia, Egypt, Hong Kong, Israel, Malaysia, Mexico, Russia, Kingdom of Saudi Arabia (KSA), Singapore, Taiwan, Thailand, Turkey, and United Arab Emirates. Questionnaires were sent to adult members of online respondent panels for determination of AD and assessment of severity. A diagnosis of AD required respondents to meet the modified United Kingdom (UK) Working Party criteria and to self-report they had a physician diagnosis of AD. Severity of AD was determined using Patient-Oriented Scoring of Atopic Dermatitis (PO-SCORAD), Patient-Oriented Eczema Measure (POEM), and Patient Global Assessment (PGA). Results: Among respondents by country/region the prevalence of AD ranged from 3.4% in Israel to 33.7% in Thailand. The prevalence was generally higher in females versus males. Severity varied by scale, although regardless of scale the proportion of respondents with mild and moderate disease was higher than severe disease. PGA consistently resulted in the lowest proportion of severe AD (range 2.4% China – 10.8% Turkey) relative to PO-SCORAD (range 13.4% China – 41.6% KSA) and POEM (range 5.1% China – 16.6% Israel). Conclusions: This survey highlights the importance of AD in adults, with high prevalence and high morbidity among respondents and emphasizes that AD is not just a disease of childhood—there is disease persistence and chronicity in adults.

Malignant tumors of the sinuses and nasal cavity are rare diseases. Squamous cell carcinoma is the most common histological type (55–70 % of tumors of the sinuses and nasal cavity). The frequency of neuroendocrine tumors reaches 5 %. Currently, there is no generally accepted standard for the treatment of neuroendocrine tumors of sinonasal localization. If surgical treatment is associated with a significant deterioration of the quality of life or poor outcomes, chemoradiotherapy can be recommended. This article describes a clinical case of combined treatment of neuroendocrine cancer of the maxillary sinus and brief review of the literature on malignant tumors of the paranasal sinuses and the nasal cavity.

A dense concentration of old-growth forest and a wet, cold climate promote mineral weathering and leaching in coastal temperate rainforest soils. Our objective was to assess soil development and soil organic carbon (SOC) distribution across 18 soil profiles in remote, upland terrain of southeast Alaska where pedon data are sparse. We made soil morphological observations, collected samples, and completed laboratory analyses to measure SOC content, pH, and particle size distribution. The survey of upland backslope soils included north- and south-facing hillslopes derived from three lithologies (slate, metavolcanic, and phyllite). The soils across all sites were very gravelly (51.8 ± 20.4% coarse fragments), acidic (mineral soil pH 4.85 ± 0.45), and moderately deep (96.56 ± 37.80 cm); thin, broken E horizons were underlain by thick, carbon-rich spodic horizons. Soil development was relatively consistent as demonstrated by the Profile Development Index with values from 15 to 26 and Podzolization Index values spanning 8 to 14. A mean pedon SOC stock of 198.02 ± 81.42 Mg C ha−1 (n = 18) was calculated using data collected for all upland organic and mineral soils from our work. The accumulation of SOC was similar among soils formed from contrasting lithologies with averages of 182 ± 15.70 Mg C ha−1 for slate, 188 ± 53.80 Mg C ha−1 for metavolcanic, and 218 ± 124 Mg C ha−1 for phyllite. Our work contributes to soil morphological observations, laboratory data, and SOC stock estimates required to better constrain and model pedogenic processes and SOC stock in remote forests where data sets are limited. [ABSTRACT FROM AUTHOR]

Quantifying soil redistribution rates, including both erosion and deposition, is critical for understanding erosion processes, landscape evolution, land management strategies, and the carbon cycle. In the Northeast Pacific coastal temperate rainforest, the interaction of perhumid climate and dense coniferous forest tends to form Spodosols which are soils characterized by a subsurface accumulation of organic matter and iron and aluminum oxides, across a range of contrasting lithologies. Deep Spodosols are frequently found on steep backslopes (up to 60%) of colluvial deposits, where shallower soils would typically be expected. We hypothesized that deep Spodosols in Southeast Alaska indicate slope stability, exhibiting negligible soil redistribution rates and stable surfaces regardless of the lithology. Our objective was to quantify soil redistribution rates for Spodosols formed on steep slopes across a range of lithologies in hilly and mountainous areas of Juneau, AK. We used 239+240Pu isotopes to quantify soil erosion and deposition rates in Spodosols formed on colluvial deposits from tonalite, slate, metavolcanic rock, and phyllite. 239+240Pu measurements revealed negligible soil redistribution rates for all studied pedons, ranging from erosion rates of 0.51 t/ha/year to deposition rates up to 0.43 t/ha/year. No difference was detected between the hill and mountain landforms, further supporting the idea that Spodosols could indicate slope stability over decadal timescales across the region. Understanding the resilience of Spodosols to erosion processes in varied lithologies and landforms on steep slopes is paramount for making informed decisions regarding sustainable land use, landslide risk mitigation, and effective carbon sequestration strategies. [ABSTRACT FROM AUTHOR]

Objective. To assess the effect of the combined treatment method including preoperative denosumab therapy on the results of treatment of patients with giant cell tumors of the spine. Material and Methods. A single-center retrospective-prospective study of a series of clinical cases included 15 patients with giant cell tumors of vertebrae. The average follow-up period was 56 months. A total of 11 patients received denosumab therapy according to the following scheme: 120 mg subcutaneously on the 1st, 8th, 15th and 28th days of the first month and then once every 28 days. Surgical options included marginal resection, segmental resection, or en-bloc resection with or without spinal reconstruction/stabilization. In the case of locally advanced and inoperable disease, long-term therapy with denosumab was carried out until the disease progressed or seri- ous adverse events appeared. Results. Thoracic vertebrae were involved in 7 (46.6 %) of 15 cases, lumbar in 4 (26.7 %) and cervical in 4 (26.7 %). Local recurrence rate after surgery alone was 40 % (2/5), average time to recurrence onset was 4.5 months. No relapses were observed after combined treatment performed in four patients. Disease progression during long-term denosumab therapy for inoperable disease recurrence was not recorded (0/7). The average number of denosumab injections before surgery and during long-term therapy was 15 and 24 injections, respectively. Denosumab therapy allows reducing the duration of surgery and the volume of blood loss. Conclusion. Combined therapy of giant cell vertebral tumor allows to reduce the risk of recurrence of the disease, as well as to reduce surgery duration and blood loss. Long-term continuous therapy for inoperable cases allows achieving long-term stabilization of the effect. Due to the rarity of giant cell tumors of the spine, a further prospective recruitment of patients is required to study the efficacy and safety of combined therapies.

Gastric cancer remains one of the most common malignancies in Russia. Despite steady decrease of gastric cancer incidence it still reaches 24.65 per 100 000 population (crude rate) in 2019 with about 36 000 new cases annually. More than 29 000 people die of gastric cancer every year. High mortality rate is mostly caused by an extremely significant proportion of patients with metastatic disease which reached 40.1% in 2019. The majority of cases is related to Helicobacter pylori infection, salty diet, tobacco exposure as well as hereditary syndromes. Staging of locally advanced gastric cancer includes contrast-enhanced computed tomography of the thorax, abdomen and pelvis as well as diagnostic laparoscopy with peritoneal washings. In patients with inoperable or disseminated cancer of the stomach additional analysis for HER2, microsatellite instability and PD-L1 status is recommended. Endoscopic or laparoscopic resection remains the mainstay of treatment in patients with early cancer. Laparoscopic gastrectomy in patients with locally advanced cancer is reserved for high-volume centers with extensive experience with the procedure. Recently, perioperative cytotoxic therapy became the standard of treatment in patients with locally advanced gastric cancer. FLOT regimen is recommended while FOLFOX6 or XELOX are considered possible in the elderly or frail patients. Drug therapy includes standard doublet or triplet chemotherapy regimens for metastatic disease with trastuzumab for HER2(+++) patients. Patients with MSI-H tumors can be treated with pembrolizumab starting with 2nd line while nivolumab is reserved for the 3rd and further lines regardless of PD-L1 status. Importantly, this year guidelines include multimodal prehabilitation including physical exercise, nutritional support and psychological counselling as a possibility in all patients in need of surgery. Also standardized enhanced recovery protocols are recommended for usage during the perioperative period.

Prostate cancer is one of the most common neoplasms in men. It currently ranks second in Russian Federation amongst male population in overall number of cases after only lung cancer and third in cancer mortality. Prostate cancer is rarely diagnosed in patients younger than 40 years old, with overage age of diagnosis being between 50 and 70 years. A lot of different new treatment options were developed in the last decade for patients with metastatic prostate cancer (mPC). Despite androgen-deprivation remaining the standard of therapy, it has been proven that the addition of cytotoxic and hormonal drugs of new generation improves overall survival of patients with castration-sensitive and castration-resistant metastatic disease. Recently, enzalutamide became the new standard of care not only in castration-resistant mPC, but also in the setting of metastatic castration-sensitive prostate cancer, due to the data acquired in two large randomized trials ARCHES and ENZAMET. This article provides clinical examples demonstrating the effectiveness of enzalutamide in various forms of prostate cancer. In the first clinical case enzalutamide was used in the treatment of castration-sensitive mPC. Currently, patient continues to receive this therapy with progression-free interval exceeding 11 months. In the second clinical case, enzalutamide has shown its efficacy in the setting of castration-resistant PC. Stable disease was achieved and as of right now patient has shown no signs of progression for 9 months, which is already a significantly better result in comparison with previous lines of treatment.

Lung cancer has the highest morbidity rate among all malignant tumors in men and the highest mortality rate in men and women in Russia. In total, 49 145 new cases of lung cancer were registered (diagnosed) in Russia in 2019. The majority of cases are related to exogenic carcinogens and mainly tobacco smoke. For several decades surgical resection with preoperative cytotoxic therapy was an optimal approach for maximal cure rate. This year recommendations were updated with new strategies including adjuvant anti-PD-L1 atezolizumab following completion of chemotherapy in PD-L1 positive patients and osimertinib for EGFR mutated cases. For this moment available data suggest the increase in disease free survival. Strategic approach to treatment for inoperable patients varies according to the status of driver mutations. New approach includes pretreatment option of testing for a wide spectrum of alterations with NGS based panels. Significant changes were incorporated into treatment of ALK mutated NSCLC with two new options of brigatinib for TKI naive patients and lorlatinib for those who progress on second generation drugs. Treatment strategy for patients without activating mutations is based on PD-L1 status. Tsis year recommendations included atezolizumab as a new monotherapy option for patients with high depression of PD-L1. Also treatment options for pembrolizumab, nivolumab and atezolizimab were widened with prolonged treatment schedules.

Sinonasal undifferentiated carcinoma is a rare and aggressive tumor with an extremely poor prognosis. In the vast majority of cases, this tumor can not be resected due to its rapid local growth. Correct morphological diagnosis is impossible without a thorough differential diagnosis between sinonasal undifferentiated carcinoma and a number of lowgrade tumors of the nasal cavity and paranasal sinuses. Very few case reports and retrospective studies on sinonasal undifferentiated carcinoma have been published so far. No unified widely accepted guidelines on sinonasal undifferentiated carcinoma treatment are currently available due to the lack of statistically significant data from randomized clinical trials. The optimal treatment strategy should be based on an aggressive multimodal approach involving radical surgery, precision radiation therapy, and intensive chemotherapy. The benefits of systemic targeted therapy for patients with sinonasal undifferentiated carcinoma are still unclear. The best results can be achieved by employing tailored treatment approaches preferably in multidisciplinary cancer centers, where healthcare professionals experienced in managing patients with head and neck tumors can be involved. In this article, we report a case of complete radiological response after induction chemotherapy with docetaxel and doxorubicin and proton radiation therapy for the primary tumor area in a 53‑year-old female patient with non-resectable platinum-resistant sinonasal undifferentiated carcinoma.

Prostate cancer (RPP) is a malignant neoplasm that arises from the epithelium of the prostate gland gland (PJ). Thethiology and pathogenesis of this disease remain poorly studied. Many studies are aimed at studying diet, food, hormonal impact, as well as infections in the etiology of the RLPG. The prevalence of RPL depends on ethnic and geographical features. The highest incidence of African Americans living in the United States (60% higher than that of white Americans), the least high - in the Chinese living in China [1]. In addition to racial features, the risk factors of the RPG are considering the genetic predisposition, the age of men and nutritional features. The probability of developing a PJ tumor in a man who has one of the closest relatives of the first degree of kinship (father or brother) sick of the RLPG, is 1.8 times higher than in the population. If two relatives were sick or more (father and brother or both brothers), the risk of RPG increases in 5.51 and 7.71 times, respectively [2, 3]. African Americans have an increased risk of identifying RPG, as well as a greater probability of detecting aggressive RPG [4]. Also, the risk of RLPG is rising in men who use a large amount of animal fats [5].

Solid pseudopapillary neoplasm (SPN) of the pancreas is an extremely rare tumor, associated with favorable prognosis and long-term survival in patients with advanced disease. However, limited data exist on systemic therapy for such patients. Herein, we present a case of a young woman with a history of SPN, who progressed after multiple surgical resections and chemotherapy regimens. The immunohistochemistry (IHC) showed overexpression of estrogen receptors (ER) and progesterone receptors (PR) in tumor tissue. The patient started to receive tamoxifen and showed a durable response to endocrine therapy.

PARP inhibitors have recently emerged as a maintenance treatment option for metastatic pancreatic cancer patients with germline BRCA mutations. However, the possibility of PARP-inhibitor use as a standalone-targeted therapy for patients with various homologous repair pathway alterations remains mostly undetermined. Here we report a clinical case of a 56-year-old woman with pancreatic ductal adenocarcinoma harboring a somatic PALB2 mutation. Following disease progression after 10 cycles of FOLFIRINOX chemotherapy and two cycles of second-line gemcitabine, she was switched to talazoparib and achieved a complete clinical response after 25 months of treatment. The patient remains alive without clinical or radiological signs of disease progression three years after the start of talazoparib with no targeted therapy-related toxicities. This case highlights the role of broad molecular profiling as a window of opportunity to achieve a durable response for selected pancreatic cancer patients while pinpointing our gaps in understanding the whole picture of management of these patients since a new puzzle element represented by PARP inhibitors was introduced to clinical practice.

Objective. Comparative evaluation of the effectiveness and toxicity profile of intensified chemotherapy regimens BEACOPP escalated (esc.), BEACOPP-14 and EACOPP‑14 in primary patients with classical Hodgkin’s lymphoma of an unfavorable prognostic group.Materials and methods. The study included 149 patients: 84 women (56 %) and 65 men (44 %) with a newly diagnosed classic Hodgkin’s lymphoma, who received antitumor treatment in the Department of high-dose chemotherapy with a bone marrow transplantation unit at the Р. A. Hertzen Moscow Oncology Research Institute from 2006 to 2018. The median age was 31 years (17–69). The majority of patients were diagnosed with Hodgkin’s lymphoma nodular sclerosis (88.6 %). All patients belonged to an unfavorable prognostic group, despite the fact that more than 1/3 of them had local stages of the disease. The most frequent adverse factors identified in the majority of patients were: massive lymph node lesion (bulky disease) – in 111 patients (74.5 %), B-symptoms – in 84 (56.4 %), increased erythrocyte sedimentation rate – in 55 (36.9 %), extranodal lesion – in 105 (70.5 %), including bones and bone marrow – in 10 (6.7 %) and 14 (9.4 %), respectively. Antitumor treatment was performed under the BEACOPP program in the following modifications: BEACOPP‑14 – 94 (63.1 %), EACOPP-14 – 32 (21.5 %), BEACOPP-esc. – 23 patients (15.4 %). Consolidating radiotherapy was performed in the majority of patients – 132 (88.6 %).Results. After the chemotherapy, remission of the disease was achieved in 141 patients (94.6 %), a complete response was in 101 of them (67.8 %). The immediate antitumor effect was more expressed when using the program BEACOPP‑14 (in 72.3 %), compared to EACOPP‑14 and BEACOPP-esc. (in 59.4 % and 60.9 %, respectively).Chemotherapy resistance was observed in 8 patients (5.4 %). Chemotherapy results were improved in combination with radiation therapy in 40 patients (26.8 %). After the end of chemoradiotherapy, complete remissions were achieved in more than 93.6 % of patients. Relapses occurred in 8 patients: early – in 3 (2.1 %) and late – in 5 (3.5 %). Four patients died (2.7 %): 1 – from disease progression, 2 – from resistant relapse, and 1 patient from other causes.With a median follow-up of 46 months, the 5-year overall survival rate was more than 93.7 %, event-free-more than 83 %, and relapse-free – 90.3 % or more. When evaluating long-term treatment results depending on the induction chemotherapy program, the outcome was better when using the BEACOPP-esc. in comparison with EACOPP‑14 and BEACOPP‑14. The most frequent myelotoxic complication – more than 90 % – on all chemotherapy programs was deep leukopenia. Thrombocytopenia III–IV degree developed more often on the BEACOPP-esc. (in 52.2 %), severe anemia – on EACOPP‑14 (in 44 %). Among infectious complications, mucositis prevailed and was most often observed on BEACOPP-esc. (in 74 %). Febrile neutropenia and herpetic infection developed less frequently, mainly in the BEACOPP-esc. and EACOPP‑14 program. Another serious complication was pneumonia, which was more frequently reported during BEACOPP‑14 (18.1 %). Secondary tumors, as a later complication, were less likely to be detected in the treatment program BEACOPP‑14 (1 %), compared to BEACOPP-esc. and EACOPP-14 (4.3 % and 3.1 %, respectively).Conclusion. All modifications of the BEACOPP program showed good direct effectiveness. However, the best long-term results, despite slightly more expressed toxicity, were noted on the BEACOPP-esc. program.

Primary lymphoma of the central nervous system (PLCNS) is a rare form of extranodal lymphoma characterized by an aggressive course. In recent decades, the treatment of this disease has undergone significant changes. Modern treatment of PLCNS consists of two steps – induction and consolidation of remission. Improved overall survival of PLCNS patients was achieved through the use of combined immunochemotherapy regimens with high doses of methotrexate and/or cytarabine, which are currently the standard of induction therapy. High-dose chemotherapy followed by autologous hematopoietic stem cell transplantation at the consolidation stage provides the most complete elimination of the residual tumor clone. The most effective modes of conditioning are those with the inclusion of tiotepa. In elderly and comorbid patients who are not candidates for autologous hematopoietic stem cell transplantation, promising results were obtained while using maintenance therapy with procarbazine or temozolomide, and further researches will allow us to study the effectiveness of monocolonal anti-CD20 antibodies – rituximab and obinutuzumab.Treatment options for patients with relapses and / or refractory forms of PLCNS are limited. Certain successes were obtained with the use of new drugs – ibrutinib, nivolumab, lenalidomide, obinutuzumab.

The objective of the study a detailed, systematic review of the world literature data, which includes all aspects of recommendations for vaccination against SARS-COV‑2 in cancer patients.Materials and methods. Information search was carried out in PubMed, MedLine, Scopus, Web of Science, RSCI.The work included data from literature and information sources that were published before February 2021.Results. The data of retrospective and prospective clinical studies are analyzed. This paper reflects considerations and recommendations for the vaccination of cancer patients by Russian and foreign specialists in the context of COVID‑19 pandemic. The review presents current recommendations for vaccination against SARS-COV‑2 in patients with solid tumors, hematological malignancies, recipients of hematopoietic stem cells and cell therapy.Conclusion. To date, groups at increased risk of infection with the new coronavirus have been identified. These groups include patients with cancer. The presence of tumor does not allow a delay in start of therapy, and requires careful monitoring and observation. In this regard, despite the pandemic, the treatment of cancer patients must be continued regardless of the circumstances. Cancer patients should not be deprived of the opportunity to be vaccinated against SARS-COV‑2. Every patient should be decided individually. At the moment, there are no officially approved recommendations for vaccination against SARS-COV‑2 for cancer patients. Before the creation and approval of final recommendations for cancer patients, it is necessary to focus on compliance with sanitary and anti-epidemic measures and the prevention of COVID‑19 infection. The global cancer community continues to actively develop recommendations for the optimal vaccination against SARS-COV‑2 in cancer patients.The most relevant ones are outlined in this article.

Abstract Background This observational, retrospective effort across Europe, US, Australia, and Asia aimed to assess the activity of systemic therapies in EHE, an ultra‐rare sarcoma, marked by WWTR1‐CAMTA1 or YAP1‐TFE3 fusions. Methods Twenty sarcoma reference centres contributed data. Patients with advanced EHE diagnosed from 2000 onwards and treated with systemic therapies, were selected. Local pathologic review and molecular confirmation were required. Radiological response was retrospectively assessed by local investigators according to RECIST. Progression free survival (PFS) and overall survival (OS) were estimated by Kaplan‐Meier method. Results Overall, 73 patients were included; 21 had more than one treatment. Thirty‐three patients received anthracyclines regimens, achieving 1 (3%) partial response (PR), 25 (76%) stable disease (SD), 7 (21%) progressive disease (PD). The median (m‐) PFS and m‐OS were 5.5 and 14.3 months respectively. Eleven patients received paclitaxel, achieving 1 (9%) PR, 6 (55%) SD, 4 (36%) PD. The m‐PFS and m‐OS were 2.9 and 18.6 months, respectively. Twelve patients received pazopanib, achieving 3 (25%) SD, 9 (75%) PD. The m‐PFS and m‐OS were.2.9 and 8.5 months, respectively. Fifteen patients received INF‐α 2b, achieving 1 (7%) PR, 11 (73%) SD, 3 (20%) PD. The m‐PFS and m‐OS were 8.9 months and 64.3, respectively. Among 27 patients treated with other regimens, 1 PR (ifosfamide) and 9 SD (5 gemcitabine +docetaxel, 2 oral cyclophosphamide, 2 others) were reported. Conclusion Systemic therapies available for advanced sarcomas have limited activity in EHE. The identification of new active compounds, especially for rapidly progressive cases, is acutely needed.

Ewing sarcoma is a primitive neuroectodermal tumor which seldom presents with primary disease in people over age 40 and outside of the appendicular or axial skeleton. We examine a case of primary thoracic Ewing Sarcoma diagnosed initially by CT-guided biopsy in a woman at the age of 74 years. The disease progressed after initial combined modality therapy consisting of neoadjuvant chemotherapy, surgical resection, and adjuvant radiation therapy and two additional courses of multiagent chemotherapy. After relapse of her disease, subsequent second- and third-line systemic agents which included chemotherapy and targeted agents were given with disease stabilization achieved now over 30 months from initial diagnosis. To our knowledge, this is the first report of a primary pulmonary Ewing sarcoma diagnosed in a patient greater than 70 years of age in whom multiple remissions have been achieved with tolerable toxicities.

Background. The use of modern induction chemotherapy programs for primary Hodgkin’s lymphoma allows achievement of high long-term outcomes even in patients with initially poor prognosis. However, the toxicity of treatment is quite high. Despite the effectiveness of chemotherapy, the frequency of relapses and resistant forms varies from 20 to 30 %. In extremely rare cases, the use of intensive chemotherapy regimens, including high-dose chemotherapy, leads to long-term remissions.Description of the clinical case. We present a case of advanced-stage Hodgkin’s lymphoma in a young patient with symptoms of intoxication and adverse risk factors, such as: massive lesion in the mediastinum, increased ES R, infiltration of soft tissues, pleura, pericardium, multiple lesions of both lungs, damage to more than 3 areas of the lymphatic collectors. Given all these factors, the disease prognosis was extremely unfavorable, with a low probability of achieving remission and a high risk of early progression. The use of the intensive EACOPP -14 program allowed the achievement of short-term partial remission. Due to poor treatment tolerance, but taking into account the achievement of a partial response, further treatment was continued using the ABVD chemotherapy regimen. Follow-up examination revealed disease progression. Further courses of chemotherapy using various combinations of chemotherapy drugs resulted in a short-term positive effect with subsequent disease progression. Considering the fact that the disease was resistant to most basic chemotherapeutic agents, immunotherapy with nivolumab (PD -1 inhibitor) was administered. This alternative treatment method allowed the disease to be stabilized.Conclusion. The use of the immunological drug in a patient with chemoresistant Hodgkin’s lymphoma made it possible to stop the progression of the disease and to improve the patient’s quality of life, without significant infectious complications and adverse events.

There are some types of breast cancer (BC) that depend on their molecular characteristics. However, lately researchers provide date regarding the presence of additional receptors of triple negative breast cancer (TNBC). One of them is LA R-subtype that has androgen receptors (AR) on breast cancer cells. The role of AR in the development of this pathology is still controversial. According to some authors, stimulation of AR leads to the proliferation suppression, in the opinion of others – to the activation and potentiation of tumor invasion. There is also a version of the dichotomous effect of androgens that depends on the concentration of this hormone. The various effects of LA R-subtype therapy of BC are also explained by the presence of many other regulator proteins that interact with AR. The first attempts to treat BC with androgen have begun since the 40s of the last century, but in those years it did not have the desired effect and was not used until recently. Currently, the basic mechanisms of the effect of androgens on BC cells on the molecular level are known, and researches try to use androgen therapy, also in combination with aromatase inhibitors to increase the concentration of endogenous testosterone. The effects of selective androgen receptor modulators and anabolic steroids are being studied. However, in the last decade, the largest number of studies focused on the study of anti-androgen therapy. Patients receive AR antagonists, such as enzalutamide, bicalutamide, that are prescribed for prostate cancer. Enzalutamide blocks both androgen- and estrogen-mediated tumor growth, and therefore can be used regardless of the presence of estrogen receptors (ER), in contrast to bicalutamide. The results showed a significant increase in disease free survival up to 16.5 months in patients with hormone positive BC.