Diseases (Basel, Switzerland)最新文献

Background: Early recognition of renal allograft dysfunction requires biochemical markers capable of detecting molecular injury before functional decline becomes apparent. Serum creatinine, a late and nonspecific indicator of renal function, has limited value for early diagnosis. Protein biomarkers implicated in tubular injury, inflammation, and immune activation-including neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), β2-microglobulin, interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α)-have emerged as promising alternatives. This study evaluated early post-transplant serum profiles of these biomarkers and their prognostic relevance for long-term graft outcomes.

Methods: Nineteen adult recipients undergoing primary kidney transplantation were prospectively enrolled. Serum creatinine and protein biomarkers were measured 24 h post-transplant using validated immunochemical assays. Biomarker concentrations were compared with values from healthy controls, and correlations with renal function at 12 months were assessed. Receiver operating characteristic (ROC) analysis was used to evaluate predictive performance.

Results: Significant biochemical alterations were observed at 24 h post-transplant. KIM-1 levels were markedly elevated compared with controls (74.50 ± 98.45 vs. 10.54 ± 17.19 ng/mL; p = 0.01), consistent with early tubular injury. IL-1β and NGAL showed upward trends without reaching statistical significance. β2-microglobulin and TNF-α levels did not differ substantially from control values. Serum KIM-1 correlated with serum creatinine both at 24 h (r = 0.35) and at 12 months (r = 0.40). ROC analysis identified a KIM-1 threshold of 24.5 ng/mL (AUC = 0.68) as a potential indicator of future graft dysfunction, outperforming serum creatinine (AUC = 0.64). Six patients experienced graft dysfunction at 12 months post-transplant, five of whom had serum creatinine values > 5 mg/dL at 24 h. Based on early creatinine levels, patients were stratified into low-risk (creatinine < 5 mg/dL; n = 10) and high-risk groups (creatinine > 5 mg/dL; n = 9). Mean KIM-1 concentrations were significantly higher in the high-risk group (110.68 ± 115.29 vs. 26.67 ± 18.05 ng/mL; p = 0.05), consistent with more severe early tubular injury.

Conclusions: Among the evaluated biomarkers, KIM-1 demonstrated the strongest potential as an early biochemical indicator of renal allograft dysfunction. Its rapid post-transplant elevation underscores its sensitivity to early tubular injury. Further prospective validation in larger, multicenter cohorts is warranted.

Objective: The aim of this study was to evaluate the impact of chronic kidney disease (CKD) on clinical presentation, laboratory parameters, ECG, and echocardiographic features of patients with chronic heart failure (CHF).

Methods: This retrospective cross-sectional study included 2227 patients hospitalized in a tertiary care center due to CHF. Patients were divided into two groups based on the presence of CKD, defined as eGFR < 60 mL/min/1.73 m². Demographic, clinical, laboratory, and echocardiographic data were collected for all patients. Comparative analyses were performed to assess differences in cardiovascular risk factors, comorbidities, laboratory parameters, and echocardiographic findings between the two groups.

Results: The proportion of men was significantly higher in the non-CKD group, whereas women predominated in the CKD group (p < 0.001). Dyspnea, orthopnea, leg swelling, claudication, and expectoration were significantly more frequent in patients with CKD, while chest pain and palpitations were more common in the non-CKD group (all p < 0.05). A significant difference in the distribution of NYHA functional classes was observed between the groups (p < 0.001), with NYHA class IV being more prevalent in the CKD group and classes II and III more frequent in the non-CKD group. Levels of CRP and NT-proBNP were significantly higher in the CKD group (p < 0.001). In-hospital mortality was 2.5-fold higher in patients with CKD (28.6% vs. 11.1%; p < 0.001).

Conclusions: Coexistence of CKD was associated with a more severe clinical presentation, advanced functional limitation, and a distinct laboratory and echocardiographic profile in CHF patients.

Background: Postpartum haemorrhage (PPH) remains the leading cause of maternal mortality globally. Women with inherited or unexplained bleeding disorders such as von Willebrand disease (VWD), factor XI deficiency (FXI), platelet function disorders, or bleeding disorder of unknown cause (BDUC) face a higher risk. While tranexamic acid (TXA) is routinely used in obstetric care, its specific efficacy and safety in these populations remain unclear. Methods: A systematic review and meta-analysis followed PRISMA 2020 guidelines (PROSPERO: CRD420251082349). Databases searched included PubMed, Scopus, Web of Science, and Dimensions. Studies evaluating TXA for PPH prevention or treatment in women with bleeding disorders were included. Six cohort studies (2016-2024) involving 213 deliveries met the criteria. Three contributed to a meta-analysis on primary PPH; the other three were synthesised narratively. Results: TXA use was associated with a 56% reduction in primary PPH risk (risk ratio 0.44; 95% CI: 0.27-0.70; p = 0.0007), with no observed heterogeneity (I² = 0%). Because contributing cohorts were phenotypically heterogeneous (BDUC, FXI, mixed), the pooled effect reflects an average across disorders rather than disorder-specific efficacy. TXA also appeared to reduce secondary and severe PPH in some cohorts. However, bleeding occurred in 26-36% of high-risk deliveries despite prophylaxis. No maternal deaths or thromboembolic events were reported in 136 TXA-exposed cases. Attribution was complicated by concurrent use of desmopressin and platelet transfusions. Most studies had moderate to severe bias. Conclusions: TXA significantly lowers the risk of primary PPH in women with bleeding disorders and appears safe. Despite this, residual bleeding underscores the need for trials to optimise TXA use alongside disease-specific strategies. However, this conclusion is derived from only six observational studies with heterogeneous patient populations and co-interventions. The evidence remains preliminary and should be interpreted cautiously. TXA should be considered as part of a multimodal postpartum haemorrhage management algorithm rather than a stand-alone therapy.

Background/objectives: Colorectal cancer (CRC) is a leading cause of cancer morbidity and mortality worldwide. Despite therapeutic advances, prevention through dietary bioactives remains a promising strategy. The Annurca apple (Malus pumila Miller cv. Annurca), a Mediterranean food rich in chlorogenic acid, exhibits antioxidant and anti-inflammatory effects. This study evaluated, via molecular docking, the multi-target interaction profile of chlorogenic acid against key CRC-related proteins.

Methods: The optimized 3D structure of chlorogenic acid was docked to ten protein targets implicated in CRC pathogenesis, using the GOLD v.2022.3.0 software. Validation of the docking protocol was achieved by re-docking native ligands (RMSD ≤ 2.0 Å). Binding affinities were assessed by ChemPLP scoring, and interaction networks were visualized in Maestro Schrödinger.

Results: Chlorogenic acid displayed consistent binding across all evaluated targets (ChemPLP 57.12-69.66), showing the highest affinity for nAChR (69.66), CXCR2 (65.13), ERβ (63.18) and TGFBR2 (62.94). The ligand formed multiple hydrogen bonds and π-π stacking interactions involving Asp1040 (VEGFR-1), Cys919 (VEGFR-2), Lys320 (CXCR2), and Tyr195 residues (nAChR), contributing to strong complex stabilization. Interaction patterns in CYP19A1, ERβ, and ERRγ suggested potential modulation of hormonal and metabolic signaling. The compound also demonstrated stable binding to mTOR (60.01), indicating a possible inhibitory role in proliferative pathways. Collectively, these findings reveal a broad, polypharmacological binding profile involving angiogenic, inflammatory, and hormonal regulators.

Conclusions: Chlorogenic acid acts as a promising multi-target ligand in CRC prevention, with our in silico evidence supporting its ability to modulate diverse oncogenic pathways. Further experimental studies are warranted to confirm its efficacy and translational potential.

Background/Objectives: Accurate and reproducible grading of lumbar spinal stenosis (LSS) is clinically critical for guiding treatment decisions and patient management, yet manual assessment remains challenging due to imaging variability and inter-observer subjectivity. To address these limitations, this study aimed to evaluate the generalizability of deep learning-based feature extraction methods-VGG19, ConvNeXt-Tiny, and DINOv2-combined with classical machine learning classifiers for automated multi-grade LSS assessment. Automated grading enables objective, reproducible, and scalable assessment of lumbar spinal stenosis severity, addressing key limitations of manual interpretation. Methods: Axial MRI images were processed using pretrained VGG19, ConvNeXt-Tiny, and DINOv2 models to extract deep features. Logistic Regression, Support Vector Machine (SVM), and LightGBM were trained on internal datasets and externally validated using MRI data from the University of Phayao Hospital. Performance was assessed using accuracy, precision, recall, F1-score, confusion matrices, and multi-class ROC curves. Results: VGG19-based features yielded the strongest external performance, with Logistic Regression achieving the highest accuracy (0.9556) and F1-score (0.9558). External validation further demonstrated excellent discrimination, with AUC values ranging from 0.994 to 1.000 across all severity grades. SVM (0.9333 accuracy) and LightGBM (0.9222 accuracy) also performed well. ConvNeXt-Tiny showed stable cross-model performance, while DINOv2 features exhibited reduced generalizability, especially with LightGBM (accuracy 0.6222). Most classification errors occurred between adjacent grades. Conclusions: Deep convolutional features-particularly VGG19-combined with classical machine learning classifiers provide robust and generalizable LSS grading across external MRI data. Despite advances in modern architectures, CNN-based feature extraction remains highly effective for spinal imaging and represents a practical pathway for clinical decision support.

Background/objectives: Cardiovascular diseases (CVDs) remain the leading cause of morbidity and mortality worldwide and increasingly are recognized as a continuum of interconnected conditions rather than isolated entities.

Methods: A structured narrative literature search was performed in PubMed, Scopus, and Google Scholar for publications from 2015 to 2025 using combinations of different keywords: "cardiovascular disease spectrum", "multi-omics", "precision cardiology", "machine learning", and "artificial intelligence in cardiology".

Results: Evidence was synthesized across seven major clusters of cardiovascular conditions, and across these domains, common biological pathways were mapped onto heterogeneous clinical phenotypes, and we summarize how multi-omics integration, AI-enabled imaging and digital tools contribute to improved risk prediction and more informed clinical decision-making within this spectrum.

Conclusions: Interpreting cardiovascular conditions as components of a shared disease spectrum clarifies cross-disease interactions and supports a shift from organ- and syndrome-based classifications toward mechanism- and data-driven precision cardiology. The convergence of multi-omics, and AI offers substantial opportunities for earlier detection, individualized prevention, and tailored therapy, but requires careful attention to data quality, equity, interpretability, and practical implementation in routine care.

Background: High residual platelet reactivity (HRPR) and persistent dyslipidemia remain important unmet needs in cardiovascular risk management, particularly in patients undergoing coronary revascularization. Despite intensive lipid-lowering and antiplatelet therapy, a substantial proportion of patients fail to reach recommended low-density lipoprotein cholesterol (LDL-C) targets or exhibit inadequate platelet inhibition. Inclisiran, a PCSK9-targeting small interfering RNA, represents an emerging approach for long-term LDL-C reduction.

Methods: A narrative review of the literature published between 2009 and 2025 was performed using PubMed, Scopus, Web of Science, and MEDLINE. Studies evaluating the addition of inclisiran to standard lipid-lowering therapy in patients with dyslipidemia and HRPR, assessed using the VerifyNow assay, were included. Illustrative clinical cases from Kazakhstan were analyzed to demonstrate real-world changes in LDL-C levels and platelet reactivity following insufficient response to conventional treatment. The review had a descriptive design.

Results: Available evidence indicates that a significant proportion of high- and very-high-risk patients do not achieve LDL-C targets or are unable to tolerate high-intensity statin therapy. Inclisiran consistently induces sustained reductions in LDL-C and circulating PCSK9 levels. Emerging data suggest a potential indirect modulation of platelet reactivity associated with intensive lipid lowering. In patients at extreme cardiovascular risk-including those after coronary artery bypass grafting (CABG) and with long-standing multivessel coronary artery disease-inclisiran therapy was associated with marked LDL-C reduction and a trend toward normalization of platelet reactivity.

Conclusions: Assessment of platelet function using the VerifyNow assay may improve identification of residual thrombotic risk in patients with advanced atherosclerotic disease. Inclisiran appears to be a promising adjunctive therapy for dyslipidemic patients with persistently elevated cardiovascular risk and HRPR despite standard treatment. Further prospective studies are warranted to clarify the relationship between intensive LDL-C lowering, platelet reactivity, and clinical outcomes, and to optimize integrated lipid-lowering and antiplatelet strategies.

Background/Objectives: The objective was to analyze the effects of Dipeptidyl Peptidase-4 (DPP-4) inhibitors on glycemic control, insulin dose, and preservation of β-pancreatic function (C-peptide) in patients with type 1 diabetes mellitus (T1DM). Methods: A systematic review was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, with a search in the PubMed database. Five randomized clinical trials evaluating the use of different DPP-4 inhibitors in patients with T1DM were selected, measuring parameters including glycated hemoglobin (HbA1c), C-peptide, time in glycemic target/range (TIR), and daily insulin dose. Results: HbA1c showed significant reduction in some studies and no significant alterations in others. TIR increased in one study (~77.87% → ~84.40%). C-peptide showed variable effects across studies. The insulin dose did not show a substantial reduction. Conclusions: DPP-4 inhibitors demonstrated modest benefits for glycemic control and preservation of β-cell function in T1DM, but these effects were inconsistent due to methodological heterogeneity. Standardized studies are needed to define beneficial subgroups and long-term efficacy.

Background: Respiratory Syncytial Virus is a predominant source of morbidity and mortality, particularly among babies, the elderly, and immunocompromised patients. Recent developments in RSV vaccines, approved by the FDA for high-risk groups, have highlighted the necessity for post-marketing surveillance to evaluate their real-world safety and efficacy. Method: This study utilized data from the Vaccine Adverse Event Reporting System (VAERS) covering RSV vaccine administration between 2023 and May 2025. The VAERS database reported data on vaccine types, including Arexvy^®, Abrysvo^®, and mRESVIA^® was analyzed for adverse events and vaccination errors. The demographic information, vaccination trends, and hospitalizations post-vaccination among the vaccinated individuals were accessed. Results: The analysis revealed that the most common adverse events were mild, such as injection site pain, erythema, fatigue, and extremity pain. The data also showed a gradual increase in hospitalization rates from 4.8% in 2023 to 7.5% in 2025. Vaccination errors, including inappropriate administration during pregnancy and excess doses, were also observed. A notable trend was the growing proportion of patients who experienced no adverse events, with the highest rate of symptom-free reports seen in 2025 (25.9%). Conclusions: RSV vaccines demonstrate a generally acceptable safety profile based on post-marketing surveillance data. However, the observed increase in hospitalization rates, vaccination errors, and pregnancy-related outcomes warrants continued active surveillance and cautious interpretation.

Objectives: This study investigated sleeping problems in the Swedish population based on the Swedish National Board of Health and Welfare's national patient register on numbers of patients in specialized outpatient care diagnosed with codes for sleeping problems.

Methods: Numbers of patients per year and per 100,000 inhabitants in various age groups: 0-4, 5-19, 20-39, 40-59, and 60+ years diagnosed each year between 2001 and 2024 with the ICD codes G47 (sleep disorders) or F51 (non-organic sleep disorders) as main diagnosis were assessed.

Results: The highest increase for sleep disorders was seen among children, adolescents, and young adults. All results are given per 100,000 persons. In the age group 0-4 years, the numbers of sleep disorders (G47) increased from 41.5 in 2001 to 215.8 in 2024. The corresponding results in the age group 5-19 years were 13.8 and 235.6, respectively. In the age group 20-39 years, 40.4 were diagnosed in 2001 and 220.9 in 2024. For subjects aged 40-59 years, 169.5 were diagnosed in 2001 and 362.8 in 2024, and for persons aged 60+ years, 116.4 were diagnosed in 2001 and 322.9 in 2024. No major changes in the numbers of persons with F51, non-organic sleep disorders, were observed.

Conclusions: Sleeping problems can be caused by several factors; however, the rapid increase in recent years has temporally coincided with an increase in the public's exposure to microwave radiofrequency (RF) radiation and increasing use of screens. RF radiation and use of screens may negatively impact sleep.