Anna Chudek

Background: Fixed-dose combination medications (FDCs) are recognized methods of increasing adherence to polytherapy in chronic diseases. However, the role of FDCs in patients with benign prostatic hyperplasia (BPH) associated with lower urinary tract symptoms (LUTS) remains uncertain. We designed this study to assess persistence, adherence, and patient satisfaction with FDCs recently introduced to the Polish pharmaceutical market, which contain tamsulosin (an α1-adrenergic receptor antagonist) in combination with solifenacin (a muscarinic receptor antagonist) or dutasteride (a 5-α reductase inhibitor). Methods: The analysis included 50,435 men (67.8 ± 8.8 years old) managed by urologists for BPH-associated LUTS, who had been on combination therapies for at least 3 months. Two study visits, with an interval of 2.1 ± 1.4 months, were conducted between February and December 2024. Results: Single-component drugs (83.1%) were more common forms of therapy compared to FDCs (16.9%). ARAs (α1-adrenergic receptor antagonists) with 5-α reductase inhibitors comprised 70.2%, while ARAs with muscarinic receptor antagonists or β3-adrenergic agonists comprised 29.5%. Persistence with therapy across two visits was 82.0% for single-component drugs and 93.6% for FDCs (p < 0.001); OR = 1.31 (95% CI: 1.02–1.63). Similarly, adherence was better in patients treated with FDCs (96.6% vs. 91.0% at visit 1, p < 0.001; 99.3% vs. 97.9% at visit 2, p < 0.05). Patients prescribed FDCs were satisfied with therapy more often than those prescribed single-component drugs (62.6% and 76.8% vs. 50.6% and 67.5% at visits 1 and 2, respectively; p < 0.001). Conclusions: 1. Combination therapies are still more commonly administered as separate tablets than FDCs in patients with BPH-associated LUTS. 2. The use of FDCs increases short-term satisfaction and persistence with therapy, with a mild effect on adherence.

The knowledge concerning mild-to-moderate renal toxicity of adjuvant chemotherapy (CTH) in colon cancer patients is scarce. We retrospectively evaluated changes in the estimated glomerular filtration rate (eGFR) after three months of adjuvant treatment and the overall renal risk of the 6-month regimen in 145 patients who completed three months of therapy at three oncological centers. A decrease in eGFR of at least 1.5 mL/min/1.73 m² after three months and 3.0 mL/min/1.73 m² after six months was considered relevant in terms of kidney-related cardiovascular risk. Out of 114 patients who completed a 6-month regimen, kidney function deterioration occurred in 62 (54.4%) after 3 months and in 54 (47.4%) after 6 months. Age ≥ 70 years (RR = 2.66; 95% CI: 1.15–6.16) and diabetes (RR = 2.52; 95% CI: 0.98–6.45) were risk factors for kidney outcomes during the first three months of CTH. However, renal function decline during the first three months did not increase the risk of further deterioration on CTH continuation. In conclusion, older age and diabetes are factors increasing the risk of renal function deterioration during adjuvant CTH in colon cancer patients without preexisting chronic kidney disease. However, the decline during the first three months does not allow for predicting further changes under continued adjuvant therapy.

Objective: There are no published data on the associations between plasma concentration of pentraxin-3 (PTX-3) - a marker of vascular inflammation and mortality in older subjects with or without metabolic syndrome (MS). Therefore, we aimed to compare the prognostic significance of increased PTX-3 and CRP levels on overall survival in subjects aged 60 and older with and without MS. Materials and methods: Study participants (N = 3534) were categorized according to the presence or absence of MS and then each of these groups was stratified into 3 subgroups based on concentrations of CRP (≤ 3 mg/dL and > 3 mg/dL) and PTX-3 (< and ≥ the sex-specific cut-off values, based on the ROC curve analysis with the Youden index): double-negative inflammatory markers (low CRP and PTX-3 plasma concentrations); single-positive inflammatory marker (increased CRP or PTX-3 plasma concentrations) and double-positive inflammatory markers subgroup (increased CRP and PTX-3 plasma concentrations). During the 4.19-year follow-up, 678 (19.2% of the entire cohort) individuals died including 401 men (22.9%) and 277 women (15.5% ). Results: The optimal cut-off for PTX-3 plasma concentration associated with an increased risk of death was 2.07 ng/mL for men and 2.23 ng/mL for women. The death rates were increased for single-positive and were highest in double-positive subgroups both for men and women, with or without MS. Kaplan-Meier analysis showed no effect of MS on survival in men and women in subgroups within specific inflammatory marker categories. Of note, the inflammatory markers class effect on survival was already significant in the single-positive subgroups (34% and 44% higher risk for death for men and women), and even more pronounced for the double-positive subgroup (more than two and almost three times higher risk of death for men and women, respectively). In the entire study group, a weak correlation was found between plasma concentrations of PTX-3 and hs-CRP (ρ = 0.11, p < 0.001) and slightly higher in undernourished subjects with hs-CRP > 3 mg/dL (ρ = 0.28, p < 0.001). Conclusion: Our study suggests that in the age-advanced Caucasian population, the inflammatory status with increased plasma levels of both PTX-3 and CRP is associated with a higher risk of all-cause mortality, regardless of the occurrence of MS. However, due to the retrospective study design, these results require confirmation in prospective studies with an analysis of the underlying causes of death.

Systemic sclerosis, a connective tissue disease of unknown etiology and unpredictable outcomes, is characterized by the fibrosis of the skin and internal organs, vasculopathy, and immune system dysregulation. The disease is classified into two main subtypes, which differ in clinical presentation, complications, and prognosis. While several biomarkers have been proposed to distinguish between these subtypes, none have achieved high sensitivity and specificity. The search for dependable markers that can differentiate between the two primary subtypes of systemic sclerosis continues. To address this gap, our study evaluated the utility of novel cardiac biomarkers, including growth differentiation factor 15 (GDF15), galectin-3, mid-regional pro-atrial natriuretic peptide (MR-proANP), glutathione S-transferase π, mid-regional adrenomedullin, and soluble urokinase plasminogen activator receptor (suPAR), in a cohort of 79 patients with both lcSSc and dSSc subtypes. The results demonstrated a significant elevation of GDF15 (medians: 2.07 vs. 1.10 ng/L; p < 0.001) and MR-proANP (92.55 vs. 65.60 pmol/L; p < 0.05) levels in SSc patients compared to healthy controls. Moreover, GDF15 (1.65 vs. 2.34 ng/mL; p < 0.05), MR-proANP (80.87 vs. 109.27 pmol/L; p < 0.05), and suPAR (1.83 vs. 2.44 ng/mL; p < 0.05) levels were notably higher in patients with dSSc compared to those with lcSSc. In the ROC analysis, only GDF-15, MR-proANP, and suPAR proved to have a statistically significant area under the curve (AUC). Patients with the GDF-15 ≥ 2182 ng/mL, MR-prANP ≥ 85.808 pmol/L, and suPAR ≥ 2.315 ng/mL have more than six-, eight-, and seven-times-higher odds for dcSSc, respectively. These findings highlight the potential of GDF15, suPAR, and MR-proANP as biomarkers for differentiating between the two main subtypes of systemic sclerosis.

Objective: In developed countries, stroke is the fifth cause of death, with a high mortality rate, and with recovery to normal neurological function in one-third of survivors. Atherosclerotic occlusive disease of the extracranial part of the internal carotid artery and related embolic complications are common preventable causes of ischemic stroke (IS), attributable to 7–18% of all first-time cases. Osteoprotegerin (OPG), a soluble member of the tumor necrosis factor receptor (TNFR) superfamily, is considered a modulator of vascular calcification linked to vascular smooth muscle cell proliferation and collagen production in atherosclerotic plaques. Therefore, OPG emerges as a potential biomarker (BM) of calcified carotid plaques and carotid artery stenosis (CAS). Methods: We performed a literature search of PubMed on OPG in CAS and atherosclerosis published until 2024. Results: Increased levels of serum OPG were reported in both patients with symptomatic and asymptomatic CAS, and higher values were observed in those with unstable atherosclerotic plaques. Notably, increased OPG levels were observed regardless of the location of atherosclerosis, including coronary and other peripheral arteries. In addition, chronic kidney disease, the most significant confounder disturbing the association between vascular damage and circulating OPG levels, decreases the usefulness of OPG as a BM in CAS. Conclusions: Osteoprotegerin may be considered an emerging BM of global rather than cerebrovascular atherosclerosis. Its diagnostic significance in identifying patients with asymptomatic CAS and their monitoring is limited.

Background: Inflammation leads to a decrease in the excitation threshold and the sensitization of peripheral nociceptors. However, little is known about the effect of inflammation on the sensing of regional (CRegP) and widespread chronic pain (CWP) in older adults. This analysis aimed to characterize the prevalence and associates of both types of chronic pain in a population-based cohort. Methods: Our analysis was based on the Polish nationwide PolSenior study database. We excluded participants with moderate-to-severe dementia. Respondents answered questions concerning the occurrence of pain in 10 regions. CWP was defined as chronic pain present in the axial region (neck, upper back, lower back) and any part of both the lower (lower leg, hip, knee, foot) and upper (shoulder, hand) extremities. Inflammatory status was divided into three subgroups: no inflammation (CRP < 3 mg/dL), mild inflammation (CPR 3–10 mg/dL and IL-6 < 10 ng/mL), and significant inflammation (CRP ≥ 10 mg/dL or IL-6 ≥ 10 ng/mL). Results: CRegP was more frequent (33.9%) than CWP (8.8%). The occurrence of CWP was more frequent in subgroups with significant inflammation than in both subgroups with mild or no inflammation (11.4% vs. both 8.4%). Women (OR 3.67; 95% CI: 2.58–5.21) and subjects with major depression symptoms were more likely to experience CWP (OR 2.85; 95% CI: 1.68–4.82), while, malnourished participants were more likely to report CRegP (OR 2.00; 95% CI: 1.52–2.62). Conclusions: Significant inflammation is associated with increased occurrence of CWP in older adults. Female sex and major depression are the most significant associates of CWP, while malnutrition is the most significant associate of CRegP.

Little is known about the occurrence of antibodies in older subjects. We analyzed the prevalence of anticitrullinated protein antibodies (anti-CCP) in a representative cohort of Polish older adults, participants of PolSenior substudy. Randomly selected 1537 serum samples of community-dwelling participants aged 65 and over. Questionnaires were completed by qualified interviewers and laboratory assessments served as a database for this analysis. The frequency of anti-CCP seropositivity (N = 50) was estimated at 3.25% (95% CI: 2.45–4.30%), being higher among women—4.05% (2.83–5.73%) than men—2.41% (1.48–3.86%). The frequency of anti-CCP seropositivity was decreasing with age from 4.29% in aged 65–74 years and 4.07% in 70–84 years to 1.50% in aged 85 years or above (p < 0.05). Hypoalbuminemia, inflammatory status (C-reactive protein >10 mg/dL or interleukin-6 ≥10 pg/mL), and female gender were associated with increased, while age ≥85 years with decreased risk of seropositivity. Multivariable logistic regression revealed that hypoalbuminemia, inflammatory status, and age ≥85 years were independently associated factors of anti-CCP seropositivity. The decreased frequency of anti-CCP seropositivity in the oldest old suggests shorter survival of the seropositive individuals who developed rheumatoid arthritis. It seems that low symptomatic RA remains frequently undiagnosed in older subjects.

Background: Little is known about sex differences in the risk of type 2 diabetes (DM2) development related to body fat depot. The main aim of this study was to assess sex-specific differences in the prevalence of diabetes in the relation to body mass, body mass index (BMI), waist circumference (WC), and calculated body fat percentage (BF), adjusted by physical activity, in younger and older hypertensive adults. Subjects/Methods: The survey enrolled 12,289 adult hypertensive outpatients with body weight, height, and WC reported by their physicians across Poland. Prevalence of diabetes was plotted against body mass, BMI, WC, and calculated BF and adjusted by the self-reported level of physical activity. Results: In our cohort, younger women (2 had lower adjusted prevalence of diabetes than corresponding men (3.4% vs. 6.5%), while among older (≥60 years) with BMI < 25.0 kg/m², the prevalence of diabetes was greater in women than in men (19.4% vs. 11.2%). A 25% probability of diabetes was observed for younger women with lower BMI than younger men (32.1 kg/m² and 35.3 kg/m², respectively) and WC (100.7 cm and 116.1 cm, respectively) but greater BF (45.5% and 38.9%, respectively). The corresponding differences in BMI and WC in older ones were much smaller (27.6 kg/m² and 27.2 kg/m², respectively; 83.7 cm and 85.6 cm, respectively), but not for BF (40.7% and 30.1%, respectively). A doubling of diabetes probability (from 25% to 50%), adjusted by physical activity, was attributable to the lower increase in BMI and WC and BF in women than in men (6.3 vs. 9.8 kg/m², 25.0 vs. 36.1 cm, and 6.5 vs. 10.8%, for younger, and 8.1 vs. 11.3 kg/m², 26.2 vs. 73.2 cm and 8.8 vs. 13.3%, for older). Conclusions: This study shows a lower probability of diabetes in younger women than younger men with normal weight BMI ranges, adjusted to physical activity. This probability is greater for hypertensive women, regardless of age, due to the increase in BMI/WC and BF values adjusted for physical activity.