Tumor Mortality Research Articles

Результаты эпидемиологического мониторинга заболеваемости, смертности, распространенности злокачественных новообразований на основе действующего государственного ракового регистра.

Today, the cancer registry is an information and analytical system for collecting, storing and analyzing information about malignant neoplasms throughout the Russian Federation, as well as about the state of specialized oncological care. The value of the cancer registry is that its information can and should be analyzed: the registry allows for a statistical assessment of the disease, to see differences in morbidity, including depending on the region. Purpose of the study is to analyze the morbidity, mortality and prevalence of malignant neoplasms in the Russian Federation for the period 2012–2022. Materials and methods. Calculation and analysis of indicators were carried out in accordance with the recommendations of the International Agency for Research on Cancer for calculating indicators. The calculation of indicators was carried out with a 95% confidence interval. To calculate standardized morbidity and mortality rates, the world standard for the age distribution of the population was used. The calculation of the increase/decrease of indicators over a 10-year period was carried out with preliminary alignment of the time series. Results. Indicators of morbidity, mortality and prevalence of malignant neoplasms in the Russian Federation for the period 2012–2022 were analyzed, general trends in changes in indicators were determined for all cancers and several of the most common localizations that make the greatest contribution to the morbidity and mortality from cancer, the male and female population of the Russian Federation. Findings. Based on the results obtained, it is necessary to expand the implementation of the developed screening measures and strengthen control over existing programs for the early detection of cancer.

Saturation association between serum 25-hydroxyvitamin D levels and mortality in elderly people with hyperlipidemia: a population-based study from the NHANES (2001-2016).

25-hydroxyvitamin D is the body's main storage form of vitamin D and is internationally recognized as the best indicator of vitamin D status in the human body. There is a scarcity of research investigating the interrelationship between serum 25-hydroxyvitamin D (25(OH)D) levels and mortality among elderly individuals with hyperlipidemia. To address this knowledge gap, we examined the association between serum 25(OH)D levels and mortality in an older hyperlipidemic population from NHANES, while controlling for other influential factors. The study sought to elucidate the correlation between serum 25(OH)D levels and mortality about all-cause mortality, cardiovascular disease (CVD), malignant neoplasms, and mortality from other causes. The data from NHANES 2001-2016, including 9,271 participants were analyzed to examine the association between serum 25(OH)D levels and mortality. The interrelationship was illustrated using Kaplan-Meier curves and restricted cubic splines, while the Cox proportional hazards model was utilized to estimate the multifactor adjusted hazard ratio (HR). This study included 9,271 participants (43.28% male) with an average age of 69.58 years, and the average duration of participant follow-up was 88.37 months. Kaplan-Meier curves demonstrated that lower serum 25(OH)D levels were associated with increased risks of all-cause mortality, cardiovascular mortality, malignant neoplasm mortality, and mortality from other causes. This negative association was further confirmed by the Cox proportional hazards models. Additionally, restricted cubic splines not only revealed this negative association but also highlighted the saturated serum 25(OH)D levels. Moreover, subgroup analyses indicated that the inverse correlation between serum 25(OH)D levels and all-cause mortality was more pronounced in the non-obese and smoking population. And the inverse correlation with mortality from other causes was even stronger in the non-obese population. In the elderly population with hyperlipidemia, 25(OH)D serum levels were negatively correlated with both cause-specific mortality and all-cause mortality. Moreover, there was a threshold effect in this negative association.

Solar Alpha Particle Radiation Increases Human Mortality – Examples from the Neoplasms Mortality in the Europe and Mediterranean

A dangerous phenomenon for humanity is described. In the joint analysis of data from satellites in orbit around the Earth and from the health statistics source EUROSTAT, it became clear that, by some mechanism, flows of positively charged particles with high energy entering the Earth's orbit increase mortality on the planet's surface. The increase in mortality is in a band of maximum risk in the Northern Hemisphere, parallel to the Equator and bounded by the parallels of 30° and 50° north latitude. Examples are given for the European Union mortality from neoplasms, confirming the described phenomenon. A hypothetical mechanism based on observational evidence has been proposed, according to which this dangerous phenomenon is due to solar alpha particles of high energy sufficient to overcome the atmosphere's resistance and reach the Earth's surface in a limited area of maximum death impact.

Sociodemographic Heterogeneity in the Associations of Social Isolation With Mortality

There are limited data on whether the vulnerabilities and impacts of social isolation vary across populations. To explore the association between social isolation and mortality due to all causes, cardiovascular diseases (CVD), and malignant neoplasms focusing on heterogeneity by sociodemographic factors. This cohort study used a moderator-wide approach to examine the heterogeneity in the association of social isolation with all-cause, CVD, and malignant neoplasm mortality using baseline data from the Japan Gerontological Evaluation Study in 2010 and 2011. Eligible participants were adults aged 65 years or older without heart disease, stroke, cancer, or impaired activity of daily living across 12 Japanese municipalities. Follow-up continued until December 31, 2017, identifying 6-year all-cause, cardiovascular disease (CVD), and malignant neoplasm mortality. Logistic regression assessed effect modification by age, gender, education, income, population density, marital status, and employment on mortality associations. Data analysis was performed from September 13, 2023, to March 17, 2024. Social isolation, determined by a 3-item scale (scores of 2 or 3 indicating isolation) was the primary exposure variable. Six-year all-cause, CVD, and malignant neoplasms mortality. This study included 37 604 older adults, with a mean (SD) age of 73.5 (5.9) years (21 073 women [56.0%]). A total of 10 094 participants (26.8%) were classified as experiencing social isolation. Social isolation was associated with increased all-cause (odds ratio [OR], 1.20 [95% CI, 1.09-1.32]), CVD (OR, 1.22 [95% CI, 0.98-1.52]), and malignant neoplasm mortality (OR, 1.14 [95% CI, 1.01-1.28]). Stratified analysis showed associations of social isolation with all-cause and malignant neoplasm mortality among people with high income (highest tertile all cause: OR, 1.27 [95% CI, 1.06-1.53]; malignant neoplasm: OR, 1.27 [95% CI, 1.02-1.60]), living in areas with high population density (highest tertile all cause: OR, 1.47 [95% CI, 1.26-1.72]; malignant neoplasm: OR, 1.38 [95% CI, 1.11-1.70]), not married (all cause: OR, 1.33 [95% CI, 1.15-1.53]; malignant neoplasm: OR, 1.25 [95% CI, 1.02-1.52]), and retirees (all cause: OR, 1.27 [95% CI, 1.14-1.43]; malignant neoplasm: OR, 1.27 [95% CI, 1.10-1.48]). Formal testing for effect modification indicated modification by population density and employment for all-cause mortality and by household income and employment for neoplasm mortality. Social isolation was associated with increased risks of all-cause, CVD, and malignant neoplasm mortality, with associations varying across populations. This study fills an important gap in research on social isolation, emphasizing its varied associations across demographic and socioeconomic groups.

Small Airways Obstruction and Mortality: Findings From the UK Biobank

BackgroundSmall airways obstruction (SAO) is common in general populations. It has been associated with respiratory symptoms, cardiometabolic diseases and progression to chronic obstructive pulmonary disease over time. Whether SAO predicts mortality is largely unknown. Research QuestionIs spirometry-defined SAO associated with increased mortality? MethodsWe analysed data from 252,877 adult participants, aged 40-69 at baseline, in the UK Biobank who had provided good quality spirometry measurements. We defined SAO as the ratio of the forced expiratory volume in three seconds to the forced expiratory volume in six seconds less than the lower limit of normal (FEV3/FEV6<LLN). We considered SAO to be isolated if present when the forced expiratory volume in one second to FEV6 ratio was normal (FEV1/FEV6≥LLN). We used a multivariable Cox regression model to assess the association of SAO, and isolated SAO, with all-cause and disease-specific mortality. We investigated sex differences in these associations and repeated the primary analysis excluding ever smokers. All models were adjusted for potential confounders such as sex, body mass index, smoking status, smoking pack-years, assessment centre, Townsend deprivation index and ethnicity. ResultsWe identified 59,744 participants with SAO of which 24,004 had isolated SAO. A total of 5,009 deaths were reported over a median of 12.8 years of follow-up. Participants with SAO had increased all-cause (HR=1.31, 95%CI 1.26-1.36), cardiovascular (HR=1.39, 95%CI 1.29-1.51), respiratory (HR=2.20, 95%CI 1.92-2.51), and neoplasm (HR=1.23, 95%CI 1.17-1.29) mortality risk. These associations were not modified by sex. However, in never smokers, only respiratory and cardiovascular mortality risk was associated with SAO. Isolated SAO was also associated with an increased mortality risk (HR=1.14, 95%CI 1.07-1.20). InterpretationIndividuals with SAO have an increased risk of all-cause and disease-specific mortality. Further studies are needed to determine whether SAO causes mortality or is a marker of underlying disease.

RETROSPECTIVE ANALYSIS OF ESOPHAGEAL CANCER MORTALITY IN BRAZIL (1998-2022): Gender disparities, ethnic contrasts, temporal dynamics, and regional variations

Introduction: The esophageal cancer is derived from numerous dysplastic mutations usually located in the most distal portion of the esophagus, and is an aggressive neoplasm with a low survival rate. Environmental factors and gastroesophageal reflux disease (GERD) are the main precursors of this pathology, and its risk factors include males aged over 50, obesity, smoking and alcohol consumption. Its diagnosis can be made through upper digestive endoscopy (UDE). Methodology: Data was collected from the Mortality Information System (SIM) from 1998 to 2022 in order to analyse the evolution of esophageal cancer mortality and compare demographic, temporal and regional trends in esophageal malignant neoplasm mortality in Brazil. Results and discussion: There has been an increase in mortality over time, with a predominance of Caucasians and males in all races. The southeast and south regions have the highest incidence and mortality rates. The disparity between the sexes is attributed to men's greater exposure to smoking and alcohol. In the South, the consumption of mate is highlighted as a significant risk factor, and its higher incidence in white people is explained by the high proportion of elderly people in this region, as esophageal cancer is more common in the elderly due to prolonged exposure to carcinogens. Conclusion: The scientific analysis carried out provides mortality trends in Brazil with regard to esophageal cancer and allows these data to be correlated with the ethnic groups, sexes and regions most affected. Finally, the study highlights the importance of environmental factors in causing this pathology, indicating public health interventions mainly in the South and Southeast regions in order to reduce mortality figures.

Unveiling sex-based geographical disparities in myelodysplastic syndrome mortality trends in Spain (1999-2022).

To comprehensively analyze trends in myelodysplastic neoplasm (MDS) mortality across Spain (1999-2022), examining sex and regional differences. We analyzed nationwide death records and population data, calculating age-standardized mortality rates (ASMRs) and standardized mortality ratios (SMRs) stratified by sex and Autonomous Community (AC). Joinpoint regression identified significant shifts in trends. Across Spain, MDS mortality risk varied among men, with rates ranging from 1.08 to 4.38 per 100,000 across regions, while women's rates ranged from 1.23 to 2.02. Five regions had higher risks than the national average, while six had lower risks. Joinpoint analysis revealed three periods nationally: a decline until 2008, and an increase until 2017, followed by a significant decrease. Despite the overall stable national trend (-0.5% annual change), significant regional variations emerged. Andalusia stood out with a worrying increase in MDS mortality, while Aragon and Murcia demonstrated promising declines. Extremadura displayed a unique trajectory with an initial rise followed by stabilization, while Galicia exhibited a contrasting trend with an initial decline and subsequent increase. Notably, men consistently faced a higher risk of MDS mortality compared to women, with significant disparities across regions. Extremadura, in particular, showed a marked difference in risk between genders. MDS mortality trends in Spain are complex, and influenced by gender, region, and time. Further research is needed to understand regional disparities, recent national decline, and higher risk in specific demographics. Tailored interventions based on local factors and targeted research are crucial to address these complexities and improve patient outcomes.

The comparison of effectivity in breast cancer prevention between skin sparing and subcutaneous mastectomy - 20 years of experience.

Breast cancer is the leading cause of neoplasm mortality among women. Several prevention strategies have been implemented to early detect and prevent the cancer occurrence. The most effective protocol includes prevention mastectomy for the high-risk patients. In our study, we have compared the efficacy of subcutaneous mastectomy (SCM) and skin sparing mastectomy (SSM) in long-term follow up. We have included 201 female patients who have been treated at our department over the course of 20 years between 2000 and 2019. All the patients were at high risk of developing breast cancer and therefore were indicated for the prophylactic mastectomy. The main indication was the presence of the mutation in the BRCA1 or BRCA2 cluster, however, even in the lack of such mutation, the family history was sufficient for the mastectomy indication. Patients underwent either SCM, SSM or areola sparing mastectomy (ASM), and were allocated to aforementioned groups, respectively. We have collected the data regarding the reconstruction method along with age, weight, height, body mass index (BMI) and presence of predisposing genetic mutations such as BRCA positivity. The patients who underwent SSM compared to those who underwent SCM were of higher age, with higher BMI and body mass. The patients in SSM group had statistically significantly higher BMI than in ASM. There was no difference in efficacy between patients who underwent SSM and SCM. The majority of patients (91.5%) were positive for BRCA1 or BRCA2 mutation. In our study, only four patients were tested negative for known breast cancer inducing mutation (three in SCM and one in SSM). The most common reconstruction method was an abdominal flap and breast implant. Prophylactic mastectomy is a reliable strategy for significantly reducing the number of breast cancer incidence in high-risk patients regardless of the selected method of mastectomy. These operations allow for the subsequent reconstruction with the whole spectrum of reconstructive options.

Malignant Neoplasms in Serbia – Epidemiology, Risk Factors, Prevention

The paper deals with the analysis of the incidence and mortality of malignant neoplasms in Serbia. The study aimed to present the epidemiological situation regarding malignant diseases in Serbia, in comparison with some relevant data from around the world, and to provide an overview of the possibility of preventive interventions. In this paper, only publicly available data was used from The Population Register for Cancer of the Republic of Serbia, the WHO, and the work of other researchers. All data were used according to established best practices in research. It was concluded that malignant neoplasms rank second in terms of morbidity and mortality in Serbia. The incidence of malignant tumors by location is the highest for lung and bronchial cancers in men, and breast cancer in women. Notably, the morbidity rate in Serbia is lower compared to Western Europe, while the mortality rate is significantly higher. The cause of such outcomes certainly lies, at least partially, with certain risk factors and the lifestyle choices associated with them, but also in poorer material conditions. Material conditions are directly related to the level of health care development. It is necessary to focus efforts on the reduction of risk factors, the promotion of healthy lifestyles and the improvement of health care in general, which is a basic human right.

Mid and long-term effects of air pollution on cardiovascular outcomes: estimating risk with the PM-years index (EP-PARTICLES study)

Abstract Background Scores and medical calculators are important tools for planning health strategies. Air pollution is one of the main risk factors, especially for the cardiovascular system. In this study, we present and test our concept of estimating the risk associated with exposure to air pollution: Particulate Matters years index (PM-years index). Objective The long-term predictive performance of the PM-years index. Methods The PM-years index is an indicator of hypothetical exposure to air pollution. It is estimated by multiplying the number of years spent in a given environment by the difference between the average annual PM2.5 concentration and the allowed level of pollution given by World Health Organization guidelines. We collected data from 2010 to 2020 on PM2.5 concentration, mortality, and hospitalizations from Inspectorates for Environmental Protection, Central Statistical Office, and National Health Fund in Poland, respectively. County-specific associations of PM-years with multi-outcomes were estimated using Poisson regression panel models. The analysis used an age-standardized rate (SR), which was established on the European Standard Population structure. Models were adjusted for weather conditions. In the first stage, we checked the mid-term association between PM2.5 concentration, and in the second, we examined the association between PM-years index. Results In the analysis, we used data of 831,246 deaths, including 377,344 deaths due to cardiovascular disease (CVD), 198,133 deaths from neoplasm, 159,952 hospitalizations due to ischemic stroke (IS), and 152,055 due to myocardial infarction (MI). The mean standardized rate (SR) for STEMI was 87 (SD=23.1), NSTEMI – 110.1 (31.8), ischemic stroke – 212.4 (51.7), CVD mortality - 544.8 (190.5), cerebrovascular (CbVD) mortality 84.7 (56.8), neoplasm mortality 266.3 (133.9). Total mortality was 1171.2 (398.7). In the mid-term, we recorded the association between PMs and STEMI (OR=1.133 95%CI 1.12-1.15), NSTEMI (OR=1.02, 95%CI 1.004-1.03), IS (OR=1.04 95%CI 1.03-1.04), CVD mortality (OR=1.06 95%CI 1.03-1.04), CbVD mortality (OR=1.07 95%CI 1.06-1.08) but not total mortality and neoplasm mortality. The risk of STEMI significantly increased with each PM-year exposure (OR=1.21 95%CI 1.19-1.12). OR for NSTEMI for each PM-year was 1.08 (95%CI 1.07-1.09), for IS 1.09 (95%CI 1.08-1.11), for CVD mortality 1.07 (95%CI 1.06-1.073), and for CbVD 1.23 (95%CI 1.22-1.25). It is worth noting that PM-year also had an effect on neoplasm mortality (OR=1.02 95%CI 1.01-1.03). P&amp;lt;0.001 for all tests. Conclusions The PM-years index is an independent predictor of major cardiovascular events and neoplasm mortality in patients. It can be used as a tool for risk stratification for patients or incorporated into a prediction model to improve efficacy in primary and secondary prevention. Moreover, the level of long-term exposure can allow for the adjustment of appropriate primary and secondary prevention schemes.

Assessing the Feasibility of Thromboprophylaxis with Apixaban in JAK2-Positive Myeloproliferative Neoplasm Patients: The Airport-MPN Trial

Introduction: Thrombosis is a major cause of mortality and morbidity in myeloproliferative neoplasms (MPN). In patients classified as high-risk for thrombosis, current guidelines recommend the use of cytoreduction therapy and low-dose aspirin (e.g., ASA 81 mg daily) to decrease the risk of thrombotic events. However, use of low-dose aspirin is based on limited evidence and is associated with a significant failure rate. Thromboprophylaxis with low-dose direct oral anticoagulants (e.g., apixaban 2.5 mg BID) is an appealing option in MPN, specifically when patients carry the JAK2 mutation, based on the pathophysiology of thrombus formation associated with this driver mutation. In other populations, thromboprophylaxis with a low-dose direct oral anticoagulant has been associated with a reduced risk of arterial and venous thrombotic complications, when compared to low-dose aspirin. Hence, we conducted a pilot trial to assess the feasibility of conducting a randomized controlled trial evaluating the efficacy and safety of apixaban (2.5 mg BID) compared to aspirin (81 mg daily) to prevent thrombotic complications in patients with JAK2-positive MPN (JAK2MPN). Methods: This was a multi-centre, prospective, open-label, blinded endpoint pilot trial (NCT04243122), conducted in three Canadian centers (Ottawa, Calgary, Sherbrooke). Adult patients with a confirmed diagnosis of polycythemia vera, JAK2-positive essential thrombocythemia or JAK2-positive pre-fibrotic myelofibrosis (per local clinical definitions) requiring low-dose aspirin for thromboprophylaxis were eligible. Both patients with an incident diagnosis of JAK2MPN (defined as diagnosed within 1 year) and patients with prevalent disease were targeted for recruitment. Exclusion criteria included a contraindication to thromboprophylaxis or the need for a specific anticoagulant or non-aspirin anti-platelet agent. Patients with a prior history of venous thromboembolism were eligible if they had completed a minimum of 6 months of anticoagulation therapy. Participants were randomized 1:1 to receive apixaban 2.5mg BID or aspirin 81mg daily, along with cytoreductive therapy (per guidelines). The study treatment duration was 6 months. Follow-up occurred at 3, 6 and 7 months after allocation of the study medication. The primary study outcome for feasibility was the monthly recruitment rate per study site over a 6-month follow-up period. Secondary outcomes included rates of thrombotic and bleeding complications. The total estimated sample size was 44 participants (22 per arm). Due to the COVID-19 pandemic, not all sites were able to start recruitment at the same time and the total recruitment period spanned over 24 months. Results: During this 24-month recruitment period, 93 JAK2MPN patients were screened for eligibility. Of these, 69 were eligible and 64% of eligible patients consented to participate. We therefore recruited 44 participants, for a recruitment rate of 0.8 patient per centre per month. Baseline characteristics of participants are presented in Table 1. A total of 29 prevalent cases and 15 incident cases were included. Secondary efficacy, safety, and feasibility outcomes (relating to thrombotic events, bleeding complications, and study compliance) will be available at the ASH Meeting, since all participants will have completed the 6-month treatment duration by October 2023. Discussion: Despite the challenges of the COVID-19 pandemic, we have recruited 100% of our target population. Given the chronicity of MPN, most outpatient clinics functioned remotely during the pandemic, precluding recruitment. Nevertheless, by adapting to the realities of the pandemic, we achieved our recruitment target demonstrating feasibility of a larger trial. The strategies adopted during this pilot trial to recruit participants, such as active screening of clinic lists for potential participants and direct communication with MPN specialists, will be applied to our larger scale trial. Conclusion: This pilot trial demonstrated the feasibility of conducting a large-scale trial evaluating the superiority of apixaban over aspirin for the thromboprophylaxis of JAK2MPN patients. As JAK2MPN are rare diseases, we have partnered with counterparts in France to conduct an international study on the efficacy and safety of direct oral anticoagulant thromboprophylaxis in JAK2MPN patients.

Sexual dimorphism in cancer

The incidence and mortality of malignant neoplasms of non-reproductive organs both carcinomas and sarcomas in men is one and a half times higher than in women. This is based on genetic differences, which are superimposed by patterns of epigenetic regulation of the expression of sex chromosome genes that determine sex differences in the processes of tissue differentiation, which, in turn, mediates the formation of the hormonal status of the body. Compared to the Y chromosome, the mammalian X chromosome contains several dozen times more genes encoding major regulators of proliferation, metabolism, immunity, and tumor growth inhibitors, as well as X-linked microRNAs affecting transcription factors and cross-regulation by other non-coding RNAs. This results in a female or male gene expression profile that accounts for phenotypic differences. This peculiarity, along with the fact that in female cells on the second inactivatedX chromosome epigenetic repression of the most important genes is reversed and, accordingly, their expression level is doubled, may largely explain the sex disparity in carcinogenesis. The influence of sex hormones and disparity in the expression of antitumor immunity contribute significantly to this difference. A detailed study of the mechanisms underlying sex dimorphism in carcinogenesis will be an essential contribution to fundamental oncology and to the practice of diagnosis, prognosis and personalized treatment of malignances with regard to their gender-specific course. These studies are especially relevant in relation to insufficiently studied soft tissue sarcomas, the ratio of the frequencies of which in men and women varies greatly depending on the histological subtype of the tumor.

Predicting response to combination evofosfamide and immunotherapy under hypoxic conditions in murine models of colon cancer.

The goal of this study is to develop a mathematical model that captures the interaction between evofosfamide, immunotherapy, and the hypoxic landscape of the tumor in the treatment of tumors. Recently, we showed that evofosfamide, a hypoxia-activated prodrug, can synergistically improve treatment outcomes when combined with immunotherapy, while evofosfamide alone showed no effects in an in vivo syngeneic model of colorectal cancer. However, the mechanisms behind the interaction between the tumor microenvironment in the context of oxygenation (hypoxic, normoxic), immunotherapy, and tumor cells are not fully understood. To begin to understand this issue, we develop a system of ordinary differential equations to simulate the growth and decline of tumors and their vascularization (oxygenation) in response to treatment with evofosfamide and immunotherapy (6 combinations of scenarios). The model is calibrated to data from in vivo experiments on mice implanted with colon adenocarcinoma cells and longitudinally imaged with [18F]-fluoromisonidazole ([18F]FMISO) positron emission tomography (PET) to quantify hypoxia. The results show that evofosfamide is able to rescue the immune response and sensitize hypoxic tumors to immunotherapy. In the hypoxic scenario, evofosfamide reduces tumor burden by $ 45.07 \pm 2.55 $%, compared to immunotherapy alone, as measured by tumor volume. The model accurately predicts the temporal evolution of five different treatment scenarios, including control, hypoxic tumors that received immunotherapy, normoxic tumors that received immunotherapy, evofosfamide alone, and hypoxic tumors that received combination immunotherapy and evofosfamide. The average concordance correlation coefficient (CCC) between predicted and observed tumor volume is $ 0.86 \pm 0.05 $. Interestingly, the model values to fit those five treatment arms was unable to accurately predict the response of normoxic tumors to combination evofosfamide and immunotherapy (CCC = $ -0.064 \pm 0.003 $). However, guided by the sensitivity analysis to rank the most influential parameters on the tumor volume, we found that increasing the tumor death rate due to immunotherapy by a factor of $ 18.6 \pm 9.3 $ increases CCC of $ 0.981 \pm 0.001 $. To the best of our knowledge, this is the first study to mathematically predict and describe the increased efficacy of immunotherapy following evofosfamide.

PANORAMA OF GASTRIC AND INTESTINAL CARCINOGENESIS: LITERATURE REVIEW

Purpose. The aim of the review is to analyze the modern data on the molecular mechanisms of stomach and intestinal carcinogenesis, which can be the basis for managing of malignant stomach and intestine neoplasms mortality risks’ reduction.&#x0D; Materials and methods. The review includes data from foreign and domestic studies published in the electronic bibliographic databases PubMed, Cyberleninka, Elibrary over the past 10 years.&#x0D; Results. It is given the analysis of Wnt and β-catenin gene family role in the pathogenesis of stomach and colon malignant tumors and the carcinogenic potential of Helicobacter pylori in gastric cancer, as well as the driver bacteria contributing to the development of colon cancer.&#x0D; Conclusion. Stomach cancer and colon cancer are heterogeneous diseases with diverse molecular and histological subtypes, having both similarities and differences in the patterns of cancer promotion. Progress in transparency genesis of these diseases is associated with an understanding of cytotoxic and genotoxic effects, oxidative stress and chronic inflammation mechanisms.

Phenotypic Profiles Among 72 Caucasian and Afro-Caribbean Patients with Antisynthetase Syndrome Involving Anti-PL7 or Anti-PL12 Autoantibodies

ObjectivesAntisynthetase syndrome (ASyS) is a rare autoimmune disease. We aimed to determine clinical, biological, radiological, and evolutive profiles of ASyS patients with anti-PL7 or anti-PL12 autoantibodies. MethodsWe performed a retrospective study that included adults with overt positivity for anti-PL7/anti-PL12 autoantibodies and at least one Connors’ criterion. ResultsAmong 72 patients, 69% were women, 29 had anti-PL7 and 43 anti-PL12 autoantibodies, median age was 60.3 years, and median follow-up period was 52.2 months. At diagnosis, 76% of patients had interstitial lung disease, 61% had arthritis, 39% myositis, 25% Raynaud's phenomenon, 18% mechanic's hands, and 17% had fever. The most frequent pattern on initial chest computed tomography was non-specific interstitial pneumonia and 67% had fibrosis at last follow-up. During follow-up, 12 patients had pericardial effusion (18%), 19 had pulmonary hypertension (29%), 9 (12.5%) had neoplasms, and 14 (19%) died. Sixty-seven patients (93%) received at least one steroid or immunosuppressive drug. Patients with anti-PL12 autoantibodies were younger (p=0.01) and more frequently exhibited anti-SSA autoantibodies (p=0.01); patients with anti-PL7 autoantibodies had more severe weakness and higher maximum creatine kinase levels (p=0.03 and 0.04, respectively). Initial severe dyspnoea was more common in patients from the West Indies (p=0.009), with lower predicted values of forced vital capacity, forced expiratory volume in 1s, and total lung capacity (p=0.01, p=0.02, p=0.01, respectively) contributing to a more severe ‘respiratory’ initial presentation. ConclusionsThe high mortality and significant numbers of cardiovascular events, neoplasms and lung fibrosis in anti-PL7/12 patients justify close monitoring and question addition of antifibrotic drugs.

Association between long-term exposure to wildfire-related PM2.5 and mortality: A longitudinal analysis of the UK Biobank

Little is known about the associations between long-term exposure to wildfire-related fine particulate matter (PM2.5) and mortality. We aimed to explore theses associations using the data from the UK Biobank cohort. Long-term wildfire-related PM2.5 exposure was defined as the 3-year cumulative concentrations of wildfire-related PM2.5 within a 10-km buffer surrounding the residential address for each individual. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated using the time-varying Cox regression model. We included 492,394 participants aged between 38 and 73 years. We found that after adjusting for potential covariates, a 10 μg/m3 increase of wildfire-related PM2.5 exposure was associated with a 0.4% higher risk of all-cause mortality (HR = 1.004 [95% CI: 1.001, 1.006]) and nonaccidental mortality (HR = 1.004 [95% CI: 1.002, 1.006]), and a 0.5% higher risk of neoplasm mortality (HR = 1.005 [95% CI: 1.002, 1.008]). However, no significant associations were observed between wildfire-related PM2.5 exposure and mortality from cardiovascular, respiratory, and mental diseases. Additionally, no significant modification effects of a series of modifiers were observed. Targeted health protection strategies should be adopted in response to wildfire-related PM2.5 exposure, in order to reduce the risk of premature mortality.

Trends in mortality caused by neoplasms of the heart in the United States between 2000 and 2019: An observational analysis of disparities by gender and race.

10532 Background: Neoplasms of the heart, primary and metastatic, are relatively rare diseases in the US. Metastatic neoplasms are 30 times more common than primary neoplasms and constitute more than 99.3% of the total neoplasms of the heart. Only a few studies have evaluated the mortality trends of this rare disease. Therefore, we aim to analyze the trends of mortality caused by benign and malignant neoplasms of the heart from 2000-2019 and compare them based on gender and race. Methods: We utilized the CDC WONDER database to extract data on Heart Benign Neoplasms (ICD 10 D15.1), Heart Malignant Neoplasms (C38.0), and overlapping lesions of Heart, Mediastinum, and pleura (C38.8) mortality in the United States between 2000 to 2019. ICD codes were applied to multiple causes of death. Age-standardized mortality rates (ASMR) per 1,000,000 with a 95% confidence interval were presented for the total population, stratified by gender and race. We assessed the mortality trends using joinpoint trend analysis. Results: From 2000 to 2019, 3493 deaths were reported due to neoplasms of the heart, out of which 1672 (47.86%) were due to benign neoplasms, and 1821 (52.13%) were due to malignant neoplasms. Overall, total deaths and ASMR decreased from 221 to 139 and 0.82 to 0.35, respectively, with an Average Annual Percentage change (AAPC) of -3.5. Out of 3493, the majority were females (2254, 64.5%). On evaluating ASMR based on gender, it decreased from 0.65 to 0.32 (AAPC -2.6) for males and from 0.89 to 0.35 for females (AAPC -3.9). On dividing based on racial subgroups, 2962 deaths were in whites, 413 were in African Americans (AA), and 118 were from other races (Asian, Pacific Islanders, Native Indians). On further comparison between Whites and AA, ASMR was found to be higher in AA throughout the study period. For AA, ASMR decreased from 1.18 to 0.51 (AAPC -4.9), and for Whites, from 0.76 to 0.33 (AAPC -2.5). Conclusions: This study has shown a decline in overall mortality trends across genders and races. This could be attributed to increased cardiac workups for cardiovascular conditions and advances in imaging modalities, cardiac oncology, and therapeutic interventions. Although the mortality trend in females is decreasing, they still have higher mortality rates than males. At the same time, although AA showed a higher rate of reduction in ASMR, they showed an overall higher ASMR throughout the study period. Further studies are needed to assess if increased screening, early detection, and management plans are causing a decrease in overall mortality in neoplasms of the heart. [Table: see text]

Melatonin, circadian rhythms and breast cancer

Breast cancer (BC) is the leading cause of morbidity and mortality of malignant neoplasms in women worldwide. In spite of a large number of studies devoted to the etiopathogenesis of this group of malignant tumors, many questions concerning specific mechanisms of their origin and development are still unresearched. Based on numerous studies in recent years, in addition to traditional risk factors (such as hereditary factors, hormonal disorders, environmental factors, etc.), foreign and Russian authors have identified a new risk factor for BC development - the sphere of molecular disorders affecting circadian rhythms and circadian genes, as well as metabolic and regulatory intracellular pathways regulated by them. It has been shown that the balance between oncogenes and suppressor genes and processes such as neoangiogenesis, metastasis and antitumor immune response depend on the functioning of the circadian rhythm system. One of the key metabolites in the circadian rhythm regulation system is melatonin, which physiological effects extend not only to the central nervous system, but also to peripheral tissue cells. The study of the relationship between circadian rhythm disturbances, melatonin secretion and malignant tumors is one of the important tasks of modern oncology. In the present review the following aspects of this problem are considered in detail: relationships between circadian rhythms, melatonin and BC; molecular mechanisms of melatonin antitumor action in BC; therapeutic potential of melatonin in prevention and treatment of malignant breast tumors as a direct antitumor agent, a component of accompanying treatment, and as a radiosensitizer and radioprotector for radiotherapy. The purpose of this review is to investigate the problem of the relationship between the circadian rhythm system, melatonin and molecular mechanisms of development and progression of breast malignancies, as well as the therapeutic potential of melatonin in their prevention and treatment. The review is based on the study of relevant and reliable scientific articles, reviews, meta-analyses, systematic reviews, and clinical trials published in Scopus, PubMed, Web of Science and in peer-reviewed Russian journals mainly during the last 5 years.

Current Application of Different Kinds of COVID-19 Vaccines

Nowadays, the mortality and morbidity of malignant neoplasms in people is rising, which pose serious risk to human beings. Therefore, finding suitable methods to treat these diseases effectively is arousing more and more attention. Among them, phototherapy, such as PDT and PTT is a good strategy due to the advantage of antibiotic-free. This review focused on the near-infrared light-induced materials involving in conjugated polymer, organic small mole-cule, quantum dots, metal organic frameworks, covalent organic frameworks and inorganic semiconductor, and discussed their applications in NIR-guided PDT/PTT synergistic therapy. The review further provides a critical analysis of the future development of PDT and PTT. It is believed that NIR-guided PDT/PTT synergistic therapy will promote the therapeutic devel-opment of cancer.

An occupational health risk index: definition, description and mapping at municipality level.

to develop an occupational health risk index that can help to introduce the occupational risk component into epidemiological studies and assess the level of occupational risk in Italian municipalities useful for supporting prevention measures. defi nition of a municipal index as a combination of occupational and territorial indicators derived from national registers of occupational data and environmental archives. the index composition is based on data on work injuries, occupational diseases and workers exposed to carcinogens in the years 2015-2019 available at the municipal level, as well as data on municipalities hosting sites of national interest for environmental remediation (SIN) and those in which big industrial facilities (GIE), registered as pollutant emitters, are located. standardized rates of occupational injuries and occupational diseases occurred in Italian municipalities were calculated from data collected by the Italian National Institute for Insurance against Accidents at Work (Inail) in relation to the working-age population (15-69 and 15+ for injuries and occupational diseases, respectively), estimated by the Italian National Statistical Institute (Istat) in 2018. In addition, data from the National Information System on Occupational Exposure to carcinogens (SIREP) were included, from which raw rates were calculated at municipal level. Finally, two other indicators were included, describing the presence/absence of a SIN and the number of GIEs industrial facilities in each municipality. The index of occupational health risk (INDORS) is calculated by summing standardised values of the above fi ve indicators as a continuous variable and it was also classifi ed by quintiles of population as a categorical variable. The association between cause-specific mortality and INDORS levels was evaluated using data on mortality occurring in 2015. during the observation period 2,011,457, 131,353 and 140,183 events were recorded for injuries, occupational diseases and workers exposed to carcinogens, mainly among male workers. A municipal map of INDORS levels (1-5) shows a strong South-North gradient, in line with the Italian industrial geographical context. The contributions of the SIN and GIE indicators are higher in the hot spot municipalities located in the Southern regions and islands. Among the municipalities analysed 1,099 were classifi ed in the lowest risk level, 1,331 in the low-medium level, 1,619 in the medium level, 2,621 in the medium-high level and 1,284 in the highest risk level. The index shows a direct correlation with accidental mortality and an inverse correlation with all-cause and malignant neoplasm mortality. the proposed index can be useful to introduce the occupational risk dimension in ecological studies and results as a flexible tool to rank Italian municipalities in terms of occupational risk.