Ewa Orlewska

Background: The NOS2 gene polymorphism rs2297518 is associated with an increased level of NO, which could contribute to colorectal cancer (CRC) development. We hypothesized that the potential influence of the NOS2 gene polymorphism on cancer development may vary between right-sided and left-sided colon cancers, and rectal cancers. The aim of this study was to determine the rs2297518 polymorphism influence on colorectal cancer development with regard to tumor localization. Methods: This case–control study included 199 patients with CRC and 120 controls. The qPCR endpoint genotyping was conducted using the TaqMan^® genotyping assay. Results: This study revealed significant differences in tumor characteristic and in the minor alelle A frequency in the NOS2 genotype between colorectal cancers with different localizations. The mucinous adenocarcinoma was diagnosed significantly more often in right-sided cancers than in left-sided (30.6% vs. 10.9%, p = 0.009) and rectal cancers (30.6% vs. 7.1%, p = 0.0003). The minor allele A of the NOS2 genotype was observed more frequently in right-sided cancers than in left-sided cancers (44.9% vs. 23.1%, p = 0.0137) and more frequently in rectal cancers than in left-sided cancers (40.0% vs. 23.1%, p = 0.0285). Conclusions: In conclusion, the results support the hypothesis that the SNP rs2297518 of the NOS2 gene influences colorectal cancer development with regard to tumor localization.

As the outcome of COVID-19 is associated with oxidative stress, it is highly probable that polymorphisms of genes related to oxidative stress were associated with susceptibility and severity of COVID-19. The aim of the study was to assess the association of glutathione S-transferases (GSTs) gene polymorphisms with COVID-19 severity in previously vaccinated and unvaccinated Polish patients with confirmed SARS-CoV-2 infection. A total of 92 not vaccinated and 84 vaccinated patients hospitalized due to COVID-19 were included. The WHO COVID-19 Clinical Progression Scale was used to assess COVID-19 severity. GSTs genetic polymorphisms were assessed by appropriate PCR methods. Univariable and multivariable analyses were performed, including logistic regression analysis. GSTP1 Ile/Val genotype was found to be associated with a higher risk of developing a severe form of the disease in the population of vaccinated patients with COVID-19 (OR: 2.75; p = 0.0398). No significant association was observed for any of the assessed GST genotypes with COVID-19 disease severity in unvaccinated patients with COVID-19. In this group of patients, BMI > 25 and serum glucose level > 99 mg% statistically significantly increased the odds towards more severe COVID-19. Our results may contribute to further understanding of risk factors of severe COVID-19 and selecting patients in need of strategies focusing on oxidative stress.

GST (glutathione S-transferases) are capable of influencing glucose homeostasis, probably through regulation of the response to oxidant stress. The aim of our study was to investigate the relationship between GSTP1 gene polymorphism and glycated hemoglobin (HbA1c) levels in type two diabetic (T2D) patients. A total of 307 T2D patients were included. Analysis of the GSTP1 gene polymorphism (rs1695) was conducted using the TaqMan qPCR method endpoint genotyping. HbA1c was determined using a COBAS 6000 autoanalyzer. A univariable linear regression and multivariable linear regression model were used to investigate the association between mean HbA1c level and GSTP1 gene polymorphism, age at T2D diagnosis, T2D duration, therapy with insulin, gender, BMI, smoking status. GSTP1 Val/Val genotype, age at T2D diagnosis, T2D duration and therapy with insulin were statistically significant contributors to HbA1c levels (p < 0.05). Multivariable regression analysis revealed that GSTP1 (Val/Val vs. Ile/Ile) was associated with higher HbA1c even after adjustment for variables that showed a statistically significant relationship with HbA1c in univariable analyses (p = 0.024). The results suggest that GSTP polymorphism may be one of the risk factors for higher HbA1c in T2D patients. Our study is limited by the relatively small sample size, cross-sectional design, and lack of inclusion of other oxidative stress-related genetic variants.

In 2020 COVID-19 caused 41,442 deaths in Poland. We aimed to estimate the burden of COVID-19 using years of potential life lost (YPLL) and quality-adjusted years of life lost (QALYL). YPLL were calculated by multiplying the number of deaths due to COVID-19 in the analyzed age/sex group by the residual life expectancy for that group. Standard and country-specific (local) life tables were used to calculate SPYLL and LPYLL, respectively. QALYL were calculated adjusting LPYLL due to COVID-19 death by age/sex specific utility values. Deaths from COVID-19 in Poland in 2020 caused loss of 630,027 SPYLL, 436,361 LPYLL, and 270,572 QALYL. The loss was greater among men and rose with age reaching the maximum among men aged 65–69 and among women aged 70–74. Burden of COVID-19 in terms of YPLL is proportionate to external-cause deaths and was higher than the burden of disease in the respiratory system. Differential effects by sex and age indicate important heterogeneities in the mortality effects of COVID-19 and justifies policies based not only on age, but also on sex. Comparison with YPLL due to other diseases showed that mortality from COVID-19 represents a substantial burden on both society and on individuals in Poland.

The tripeptide-glutathione (GSH, γ-L-glutamyl-L-cysteinyl-glycine) is one of the most important low molecular antioxidant in human body. Enhancing GSH and associated enzymes represents an aim in the search for cytoprotective strategies against cancer, neurologic degeneration, pulmonary and inflammatory conditions, as well as rheumatoid arthritis (RA).The objective of the study was to agree whether crenotherapy (drinking therapy) with sulfide/hydrogen sulfide (SHS) waters from “Zuzanna” spring located in the area of Busko-Zdrój in Poland leads to increasing of reduced glutathione (GSH) content in human blood. SHS water in distinct from mineral water is characterised by specific pharmacokinetic, invariable content and natural microbiological purity. SHS waters contain at least 1 g of total sulfur per kilogram of water and a treatment effect also depends on other bioelements. The method employing capillary electrophoresis with UV detector for the analysis of glutathione in human blood was developed. The group of 106 volunteers consisted of both women and men, in different age range. The therapy with SHS waters lasted 2 weeks. We recently demonstrated that the administration of hydrogen sulfide (H2S) in SHS waters increases GSH concentration in blood, and therefore crenotherapy could be used in therapeutics.

Introduction: Somatostatin analogues (SSAs) are the largest contributor to the direct medical cost of acromegaly management worldwide. The aim of this review was to identify and report available evidence on the cost-effectiveness of SSAs in the treatment of acromegaly. Areas covered: A literature search on relevant papers published up to April 2018 was performed. A total of 22 eligible studies (10 full-text articles and 12 conference abstracts) conducted in 14 countries were included in the analysis. In majority of studies, modelling technique was the principal research method. Expert commentary: The results of cost-effectiveness analyses: 1) support published recommendations where SSAs are indicated as first-line medical treatment for patients with persistent disease after surgery or who are not eligible for surgery; 2) suggest that preoperative medical therapy with SSAs may be highly cost-effective in acromegalic patients with macroadenoma, in centres without optimal surgical results 3) indicate that in some countries pasireotide and pegvisomant appeared to be cost-effective or even dominant strategies in comparison to first-generation SSAs. The main limitation of economic evaluations was the lack of high-quality studies designed to directly compare various treatment strategies in acromegaly.

Objectives To assess the link between the risks of most frequent cancer sites in Poland and selected socioeconomic variables that potentially affect health outcomes throughout the life course. Methods This is a cross-sectional ecological study. Incidence of lung, breast, and colon cancer by voivodeships in 2014 was calculated based on Polish National Cancer Registry. Socioeconomic variables in individual voivodeships were assessed based on Polish Social Cohesion Survey for 2015. Spearman’s rank correlation coefficient was used to test the association of incidence rates and socioeconomic variables. The significance level was set at p < 0.05 (two-tailed tests). Results Statistically significant negative correlation exists between: (1) friend-/neighbour-based social capital and colon and breast cancer, (2) association-based social capital and lung cancer, (3) high religiousness and lung and breast cancer, and (4) income poverty and breast cancer. Statistically significant positive correlation exists between: (1) social isolation, living conditions poverty, poverty resulting from the lack of budget balance, and lung cancer; (2) low/no involvement in religious activity and lung and breast cancer. Conclusions Our findings support public health concerns over the implication of socioeconomic environment for cancer.

To investigate the drug-class-specific changes in the volume and cost of antidiabetic medications in Poland in 2012–2015. This retrospective analysis was conducted based on the National Health Fund database covering an entire Polish population. The volume of antidiabetic medications is reported according to ATC/DDD methodology, costs—in current international dollars, based on purchasing power parity. During a 4-year observational period the number of patients, consumption of antidiabetic drugs and costs increased by 17%, 21% and 20%, respectively. Biguanides are the basic diabetes medication with a 39% market share. The insulin market is still dominated by human insulins, new antidiabetics (incretins, thiazolidinediones) are practically absent. Insulins had the largest share in diabetes medications expenditures (67% in 2015). The increase in antidiabetic medications costs over the analysed period of time was mainly caused by the increased use of insulin analogues. The observed tendencies correspond to the evidence-based HTA recommendations. The reimbursement status, the ratio of cost to clinical outcomes and data on the long-term safety have a deciding impact on how a drug is used.

The aim of our study was to estimate the health-related and economic burden of suicide in Poland in 2012 and to demonstrate the effects of using different assumptions on the disease burden estimation. Years of life lost (YLL) were calculated by multiplying the number of deaths by the remaining life expectancy. Local expected YLL (LEYLL) and standard expected YLL (SEYLL) were computed using Polish life expectancy tables and WHO standards, respectively. In the base case analysis LEYLL and SEYLL were computed with 3.5 and 0% discount rates, respectively, and no age-weighting. Premature mortality costs were calculated using a human capital approach, with discounting at 5%, and are reported in Polish zloty (PLN) (1 euro = 4.3 PLN). The impact of applying different assumptions on base-case estimates was tested in sensitivity analyses. The total LEYLLs and SEYLLs due to suicide were 109,338 and 279,425, respectively, with 88% attributable to male deaths. The cost of male premature mortality (2,808,854,532 PLN) was substantially higher than for females (177,852,804 PLN). Discounting and age-weighting have a large effect on the base case estimates of LEYLLs. The greatest impact on the estimates of suicide-related premature mortality costs was due to the value of the discount rate. Our findings provide quantitative evidence on the burden of suicide. In our opinion each of the demonstrated methods brings something valuable to the evaluation of the impact of suicide on a given population, but LEYLLs and premature mortality costs estimated according to national guidelines have the potential to be useful for local public health policymakers.

Precision medicine (PM) is an important modern paradigm for combining new types of metrics with big medical datasets to create prediction models for prevention, diagnosis, and specific therapy of chronic diseases. The aim of this paper was to differentiate PM from personalized medicine, to show potential benefits of PM for managing chronic diseases, and to define problems with implementation of PM into clinical practice. PM strategies in chronic airway diseases, diabetes, and cardiovascular diseases show that the key to developing PM is the addition of big datasets to the course of individually profiling diseases and patients. Integration of PM into clinical practice requires the reengineering of the health care infrastructure by incorporating necessary tools for clinicians and patients to enable data collection and analysis, interpretation of the results, as well as to facilitate treatment choices based on new understanding of biological pathways. The size of datasets and their large variability pose a considerable technical and statistical challenge. The potential benefits of using PM are as follows: 1) broader possibilities for physicians to use the achievements of genomics, proteomics, metabolomics, and other "omics" disciplines in routine clinical practice; 2) better understanding of the pathogenesis and epidemiology of diseases; 3) a revised approach to prevention, diagnosis, and treatment of chronic diseases; 4) better integration of electronic medical records as well as data from sensors and software applications in an interactive network of knowledge aimed at improving the modelling and testing of therapeutic and preventative strategies, stimulating further research, and spreading information to the general public.