Archives of Medical Science最新文献

Introduction: Previous studies have reported a potential association between trimethylamine N-oxide (TMAO) and Parkinson's disease (PD). The objective of this study was to examine the potential relationship between the levels of circulating TMAO and its precursors and the risk of PD using a two-sample Mendelian randomization (MR) approach.

Material and methods: We aggregated data from three genome-wide association studies (International Parkinson's Disease Genomics Consortium, Parkinson's Research: The Organized Genetics Initiative and GenePD, and FinnGen) to extract single-nucleotide polymorphisms (SNPs) associated with circulating concentrations of TMAO, choline, carnitine, and betaine. These SNPs were employed as instrumental variables in a random-effects model to evaluate the causal relationship between circulating concentrations of TMAO and its precursors and the risk of Parkinson's disease, by estimating odds ratios with accompanying 95% confidence intervals. The primary analysis employed the inverse variance-weighted (IVW) method, which was complemented with MR-Egger regression analysis.

Results: The analysis using the IVW method, which aggregated data from the three databases, did not show any causal relationship between circulating concentrations of TMAO and its precursors, and the risk of PD (p > 0.05). This finding was further confirmed by the results of the MR-Egger analysis. A sensitivity analysis demonstrated that the results were not influenced by any biases, and a heterogeneity test indicated no significant variation among the SNPs.

Conclusions: This study did not identify any conclusive evidence of a causal association between the circulating concentrations of TMAO or its precursors and the risk of PD. Further investigation is warranted to determine whether such an association indeed exists.

Cardiovascular diseases (CVD) prevention does not only mean effective fight against the existing and well-recognized cardiovascular risk factors, but also against their complications, including micro- and macrovascular complications. Only then we might comprehensively reduce CVD burden and cardiovascular and cause-specific morbidity and mortality. In relation to obesity, prediabetes and especially diabetes, we recognize a number of potential dangerous non-cardiovascular complications, such as neuropathy, nephropathy and retinopathy. The latter's prevalence is even 30-40% and may appear in as many as 15% of patients with prediabetes. If not treated well it might result in the need for eye surgery or even vision loss. Fenofibrate has had a long history of evidence suggesting its preventive role in primary and especially secondary prevention of retinopathy, what has been investigated since the FIELD trial 19 years ago. Thus, given the obesity (the prevalence of 30% in Poland) and diabetes (10% which is predicted to be doubled in next 25 years) epidemic, we should look for the effective methods not only to optimize fasting blood glucose and haemoglobin A_1C, but also atherogenic dyslipidaemia and their complications, including retinopathy. In this Position Paper by the Polish Lipid Association (PoLA) we have reviewed the current stage of knowledge on possible mechanisms by which fenofibrate may contribute to retinopathy prevention, available data on safety and efficacy, to finally recommend administering fenofibrate in prevention of this dangerous diabetic complication, which significantly affects quality of life and disability-adjusted life-years (DALY). This intervention - well-recognized and already in common use in diabetic patients - may significantly improve population health in Poland and worldwide.

Lipoprotein(a) [Lp(a)], a low-density lipoprotein-like particle containing a highly polymorphic apolipoprotein(a) [apo(a)] homologous in > 80% to plasminogen, was identified as a genetically determined independent risk factor for cardiovascular disease. Elevated Lp(a) levels, found in about 20% of Europeans, are strongly linked to higher rates of myocardial infarction, major adverse cardiac events, accelerated plaque progression, ischemic stroke (especially in younger adults), and calcific aortic valve disease. However, its role in venous thromboembolism, including atypical locations like cerebral and retinal vein thrombosis, remains controversial despite several shared mechanisms underlying arterial and venous thromboembolism. The most robust evidence supports antifibrinolytic properties of elevated Lp(a), particularly smaller apo(a) isoforms, which inhibit plasminogen activation mainly by interacting with the tissue-type plasminogen activator, plasminogen, and fibrin. Other prothrombotic mechanisms include increased synthesis of plasminogen activator inhibitor (PAI-1), formation of denser fibrin networks composed of thinner fibers, less susceptible to lysis, increased platelet activation, enhanced oxidation of phospholipids leading to a low-grade proinflammatory state, upregulated tissue factor expression, and suppression of tissue factor pathway inhibitor. Targeted Lp(a) lowering therapies are currently being tested in randomized clinical trials and could potentially have clinically relevant antithrombotic effects, evidenced by the reduced risk of thromboembolism. This review summarizes the available data on the prothrombotic and antifibrinolytic actions of Lp(a), along with clinical evidence for the increased risk of thromboembolic events related to elevated Lp(a). It also introduces new concepts to explain discrepant clinical results regarding venous events, highlighting the impact of oxidized phospholipids on a prothrombotic state under conditions of high Lp(a).

The use of chemotherapeutic agents during childhood, adolescence, and early adulthood has a detrimental effect on ovarian functions, leading to a decrease in ovarian reserves, thus adversely affecting fertility. Alkylating agents are one of the most frequently used groups of chemotherapeutics in this age group. An important and effective chemotherapeutic drug, procarbazine is used to treat brain tumors and Hodgkin lymphoma in children, adolescents, and young adults. This agent is also an indispensable component of combination-type chemotherapy. Procarbazine has a detrimental impact on ovarian reserve by directly targeting the oocyte or indirectly through somatic cell destruction. Evidence gathered thus far indicates that procarbazine's mode of action in the ovaries may involve apoptosis, inflammation, and oxidative stress. This review seeks to clarify the processes by which procarbazine might induce apoptosis, inflammation, and oxidative stress, hence affecting ovarian reserve and functioning.

Introduction: Osteoarthritis (OA) is a debilitating chronic disease with a high prevalence, characterized by progressive degeneration of articular cartilage that leads to joint dysfunction, pain, and disability. Observational studies investigating the link between cheese intake and OA have yielded inconclusive results and may be susceptible to confounding.

Material and methods: We performed a two-sample Mendelian randomization (MR) investigation to evaluate the causal association between cheese intake and OA based on genome-wide association studies (GWAS). The primary analysis employed the inverse variance weighted (IVW) method, while complementary analyses were conducted using the weighted median, MR-Egger, and weighted mode methods. Moreover, we weighted each single nucleotide polymorphism's (SNP) effect on OA by its effect on cheese intake and subsequently meta-analyzed these estimates utilizing a fixed-effects model to provide a summary effect estimate. To assess the robustness of the outcomes, we performed a sensitivity analysis.

Results: Our two-sample MR analysis revealed an inverse causal relationship between cheese intake and several types of OA, including self-reported OA (odds ratio (OR) = 0.96, 95% confidence interval (CI) = 0.94-0.97, p = 6.70 × 10^-7), OA of the hip or knee (OR = 0.59, 95% CI = 0.48-0.72, p = 1.38 × 10^-7), knee OA (OR = 0.52, 95% CI = 0.42-0.66, p = 4.11 × 10^-8), and hip OA (OR = 0.72, 95% CI = 0.53-0.96, p = 0.0268). Additionally, the fixed-effects model also demonstrated a causal inverse association between cheese intake and OA, with a pooled meta-analysis OR of 0.95 (95% CI = 0.94-0.97, p < 0.0001).

Conclusions: Our findings provided compelling genetic evidence of causal inverse associations between cheese intake and various types of OA, including self-reported OA, OA of the hip or knee, knee OA, and hip OA, which may enhance the efficacy of OA prevention by deepening our comprehension of the involved risk factors.

Introduction: Currently, knowledge on relationships between blood concentrations of cadmium, lead, mercury, selenium, and manganese and the risk of chronic kidney disease (CKD) is lacking. The aim of the study was to ex-plore the relationships between blood concentrations of heavy metals and the occurrence of CKD.

Material and methods: Data from the National Health and Nutrition Examination Survey (NHANES) 2011-2018 were used to investigate the relationships between blood concentrations of mercury, lead, cadmium, selenium, and manganese and the occurrence of CKD using a weighted logistic recession analysis. Restrictive cubic spline analysis was applied to assess the dose-response relationship. The sample population was divided into four groups based on the quartiles of heavy metal concentrations (Q1: < 25^th percentile, Q2: 25^th-50^th percentile, Q3: 50^th-75^th percentile, Q4: ≥ 75^th percentile).

Results: A total of 15,450 participants were included. With regard to blood lead concentrations, the odds ratio (OR) for CKD in Q4 relative to Q1 was 1.36 (95% confidence interval [CI]: 1.20-1.61), indicating an increased oc-currence of CKD in Q4. With regard to blood cadmium concentrations, the ORs for CKD in Q2, Q3, and Q4 were 1.06 (95% CI: 0.92-1.22), 1.21 (95% CI: 1.05-1.39), and 1.52 (95% CI: 1.31-1.76), respectively. Non-linear dose-response relationships were identified between blood cadmium and lead concentrations and the occurrence of CKD. Further, blood lead and cadmium concentrations showed statistically significant interaction effects with age, hypertension, and obesity on CKD.

Conclusions: Higher cadmium and lead concentrations in blood are asso-ciated with increased occurrence of CKD, especially in older adults, people with hypertension, and people with obesity.

Familial hypercholesterolemia (FH) is the most common monogenic disease leading to the accelerated development of atherosclerotic cardiovascular disease (ASCVD). Despite increasing medical knowledge, diagnostic testing, and a growing number of therapeutic options, the effectiveness of detecting and treating FH remains highly insufficient. Only early detection (as early as possible) and optimal treatment in pediatric patients will lead to a significant reduction in morbidity and mortality from atherosclerotic cardiovascular disease (ASCVD) in later years. We present the guidelines for the management of FH in children and adolescents in Poland. This document is an update of the 2014 Position Paper of the Lipid Expert Forum.