Advances in Clinical and Experimental Medicine最新文献

Background: Heart failure (HF) is marked by a poor prognosis, heightened mortality risk, and recurrent hospitalizations. Poland consistently ranks among the highest of all Organization for Economic Co-operation and Development (OECD) countries, with a hospitalization rate of 616 per 100,000 citizens in 2019 - nearly 3 times the 34-country average.

Objectives: This study aims to provide essential insights into the management of HF patients in Poland, with a particular focus on individuals experiencing recurrent hospitalizations, over the period 2014-2021.

Material and methods: This observational study analyzes long-term registry data from the Polish Ministry of Health and the Health Needs Map. It includes more than 1,000,000 patients diagnosed with HF (ICD-10: I50) or pulmonary edema (ICD-10: J81), treated across all medical facilities operating under a uniform national healthcare system. This study inherently employs a population-based approach, encompassing all medical facilities that treat patients with these ICD-10 codes.

Results: Here, we present data on HF prevalence, incidence, and the healthcare pathway. The number of diagnosed HF cases in Poland increased to 1.02 million by December 31, 2019. In 2021, the standardized HF prevalence rate reached 2,626 per 100,000 population, with the highest prevalence observed in individuals aged 80-89 years (32%). Heart failure hospitalizations (HFH) in 2019 were 1022 per 100,000, decreasing to 205,000 in 2021. Notably, the number of hospitalizations exceeded the number of patients receiving treatment by 18-25%. Between 2014 and 2021, more than 9.2 million healthcare services were recorded, accounting for 48% of all HF-related encounters.

Conclusions: This study, relevant to both Polish and international cardiologists, provides a comprehensive overview of HF trends and associated risks, offering insights that may help refine diagnosis and treatment strategies in Central and Eastern European populations.

Progressive familial intrahepatic cholestasis type 3 (PFIC3) is a rare liver disorder caused by biallelic mutations in the ABCB4 gene, leading to multidrug resistance protein 3 (MDR3) deficiency. PFIC3 often presents with clinical and biochemical features that overlap with Wilson's disease (WD), including hepatic copper accumulation and elevated urinary copper excretion. These similarities contribute to frequent misdiagnosis, resulting in inappropriate chelation therapy and delayed appropriate management. This systematic review examines reported cases of PFIC3 initially misdiagnosed as WD to highlight diagnostic challenges and assess patient outcomes. A comprehensive search across PubMed, ScienceDirect and Google Scholar identified 11 eligible studies involving 16 patients. Most cases were first treated as WD, receiving chelation therapy without clinical improvement. Diagnosis was later revised to PFIC3 following negative ATP7B mutation testing and identification of ABCB4 variants, often via whole-genome sequencing. Upon switching to ursodeoxycholic acid (UDCA), most patients experienced clinical stabilization. The findings underscore the need for heightened awareness of PFIC3 as a differential diagnosis in atypical WD cases, especially when ceruloplasmin is normal and Kayser-Fleischer (KF) rings are absent. Early genetic testing is essential to avoid mismanagement. Further observational studies are warranted to estimate misdiagnosis frequency and guide diagnostic protocols.

Hypophosphatasia (HPP) is an inherited metabolic disorder caused by loss-of-function mutations in the ALPL gene encoding a tissue-nonspecific alkaline phosphatase (TNSALP). It has been classified based on age at first disease manifestation, including lethal perinatal, benign perinatal, infantile, juvenile, adult, and odontohypophosphatasia. Diagnosis is based on clinical presentation, alkaline phosphatase (ALP) assay and genetic testing. The main diagnostic clue is the low (for age and sex) ALP activity. In any patient with suspected HPP or skeletal/bone deformities/dysplasia, it is recommended to evaluate phospho-calcium metabolism, which is useful in differential diagnosis. Genetic diagnosis of HPP requires identification of a disease-causing variant(s) (pathogenic). In Europe, the most frequent ALPL variants are c.571G>A, c.407G>A and c.1250A>G, while the most frequently detected variants in the world are c.1250A>G, c.571G>A and c.1133A>T. Asfotase alfa, a recombinant human TNSALP enzyme replacement therapy, is now available for the treatment of HPP. The article provides an up-to-date overview of clinical, biochemical and molecular features of HPP. Treatment strategy in HPP was also described.

Third-generation cephalosporins have been widely used in clinical practice for many years. Among them, cefotaxime and ceftriaxone are the most commonly administered agents. Despite their nearly identical spectra of antibacterial activity, these antibiotics differ substantially in their pharmacokinetic and pharmacodynamic profiles. Such dissimilarities may influence the course and outcome of antimicrobial therapy. Furthermore, several additional factors can affect the antimicrobial efficacy of these agents. Cefotaxime and ceftriaxone exhibit markedly different degrees of albumin binding - approx. 25-40% and 95%, respectively. Hypoalbuminemia increases the proportion of the free, pharmacologically active fraction of the drug in the bloodstream; however, it may also lead to prolonged exposure to sub-MIC concentrations. This situation not only reduces the likelihood of therapeutic success but also increases the risk of selecting resistant bacterial strains. Although cefotaxime and ceftriaxone share a similar antibacterial spectrum, antibiotic selection should always be individualized according to the patient's clinical status and treatment context. A direct comparison of their clinical efficacy undoubtedly warrants further investigation, as suggested by the clear differences in their pharmacokinetic profiles.

Background: Early identification of individuals at increased risk for type 1 diabetes (T1D) is essential to prevent diabetic ketoacidosis (DKA) at onset and to facilitate the development of disease-modifying therapies. The INNODIA EU115797 project (2015-2023) conducted a Europe-wide screening of individuals with recent-onset T1D (<6 weeks) and their first-degree relatives (aged 1-45 years).

Objectives: To evaluate the risk of T1D development among first-degree relatives of individuals with T1D, based on data from the Polish INNODIA center at the Medical University of Silesia in Katowice, Poland.

Material and methods: Data on the incidence of autoantibodies were obtained from the INNODIA project platform. The analysis included first-degree relatives of individuals with T1D, aged 1-45 years, who met the inclusion criteria and were recruited at the Polish center. Samples were collected at the Medical University of Silesia in accordance with the INNODIA protocol. Participants were stratified based on the number of autoantibodies detected (1 or ≥2). The analysis considered age, sex, prevalence of specific autoantibodies (GAD65, IAA, IA-2A, ZnT8), and familial relationship.

Results: Among 817 screened individuals, 65 (7.96%) tested positive for autoantibodies (AA): 48 (5.88%) had 1AA and 17 (2.08%) had ≥2AA. The highest prevalence was observed in the 10-23-year age group (27.7%, 18/65). In this subgroup, 11.04% (18/163) were autoantibody-positive, whereas prevalence in other age groups (1-9, 24-36, 37-40, and 41-45 years) ranged from 5.98% to 8.97%. GAD65 (5.51%) and IAA (3.43%) were the most frequent autoantibodies. Individuals with 1AA were predominantly parents (32/48; 66.7%), while ≥2AA were more common among siblings (13/17; 72.2%). During follow-up, 2 participants progressed to stage 3 T1D.

Conclusions: In the Polish cohort of the INNODIA study, autoantibodies were detected in 7.96% of first-degree relatives of individuals with T1D. Early screening is crucial for accurate risk stratification, guiding the development of therapeutic interventions and reducing the risk of severe complications at disease onset.

Peri-implantitis poses a persistent challenge in implant dentistry, driving interest in laser therapy as a potential treatment option. Despite encouraging outcomes, clinical applications of laser therapy differ significantly in terms of wavelength, power setting and session frequency, hindering the development of standardized protocols. This scoping review aimed to map and synthesize current clinical evidence on the efficacy of laser therapy in peri-implantitis management, identify knowledge gaps and provide a foundation for future clinical recommendations. Following the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) and Joanna Briggs Institute (JBI) guidelines, a comprehensive search was conducted across 5 databases (Scopus, PubMed, Cochrane Library, Embase, and Web of Science) between May and July 2024, covering studies published from 2000 to 2024, with no language restrictions. Two independent reviewers extracted data with high inter-rater agreement (κ = 0.97). A total of 98 clinical studies were included: 56 randomized controlled trials (RCTs), 38 cohort studies and 4 retrospective studies. Diode lasers were the most frequently studied (n = 50), followed by Er:YAG, aPDT, Nd:YAG, and Er,Cr:YSGG lasers. Exposure times ranged from 10 s to 700 s, most commonly around 60 s. Key clinical outcomes included probing depth (PD) reduction, bleeding on probing (BoP) and plaque index (PI), with additional outcomes related to bone loss, clinical attachment level (CAL), gingival recession (REC), cytokine levels, microbial analysis, suppuration, and gingival index (GI). Overall, laser therapy was associated with reduced inflammation, accelerated epithelialization, improved bone parameters, fewer complications, and better patient-reported outcomes. While laser therapy shows considerable promise in the treatment of peri-implantitis, further robust and standardized clinical research is essential to confirm its efficacy, optimize treatment parameters and inform evidence-based clinical guidelines.

Background: Percutaneous renal biopsy (PRB) is the gold standard for diagnosing nephropathies but, despite being generally safe, it carries the risk of hemorrhagic complications, particularly perirenal hematomas (PHs). Ultrasound, although commonly used, tends to underestimate hematoma volumes, whereas computed tomography (CT) accurately measures volumes but poses radiation concerns and often requires contrast media. Magnetic resonance imaging (MRI), free of these risks, offers high tissue resolution but remains underutilized for PH evaluation post-PRB.

Objectives: To evaluate the utility of MRI-based segmentation techniques for accurately quantifying PH volumes after PRB, as a complementary imaging modality to ultrasound and CT.

Material and methods: We retrospectively analyzed MRI data from 85 patients who underwent PRB between July 2020 and May 2024. MRI-derived PH volumes were measured using manual segmentation. Clinical data were extracted from patient records, and the results were compared with data from a previous CT-based study.

Results: Perirenal hematoma was detected in 63 patients (74.1%) with a median volume of 26.2 mL (interquartile range (IQR): 7.2-59.3 mL), slightly smaller than CT-derived volumes (median: 38 mL, IQR: 18-85 mL). Using Spearman's rank correlation coefficient (rs), we found that serum creatinine (Cr; rs = 0.299, p = 0.039) and systolic blood pressure (SBP; rs = 0.333, p = 0.017) correlated positively with PH volume, while hemoglobin levels showed a negative correlation (rs = -0.322, p = 0.021). Hemodialysis was associated with larger PHs (odds ratio (OR) = 4.59, 95% confidence interval (95% CI): 1.20-17.58, p = 0.026); however, this finding is based on a model with modest predictive performance and requires further validation.

Conclusions: Although its routine use may be limited, MRI could serve as a complementary tool for the detailed evaluation of PHs, offering a radiation-free and contrast media-free alternative to CT in clinical scenarios where immediate decision-making is not critical.

Background: Plasma ceramides are recognized biomarkers of cardiovascular risk; however, racial and ethnic differences in their levels, as well as their association with cardiovascular health (CVH) among African-American populations, remain insufficiently studied.

Objectives: This study aimed to assess the association between ceramide scores and CVH, as well as atherosclerotic cardiovascular disease (ASCVD) risk, among African-American adults, and to compare ceramide scores between African-American and White adults.

Material and methods: We conducted a secondary analysis of 2 U.S. studies including African-American and White adults. Collected data encompassed demographics, behavioral factors (e.g., diet) and clinical measures (e.g., plasma ceramide levels). Atherosclerotic cardiovascular disease risk was assessed using the American College of Cardiology/American Heart Association (ACC/AHA) 10-year pooled cohort equations, while CVH was evaluated using the American Heart Association (AHA) Life's Essential 8 (LE8) scoring system.

Results: Fifty-eight African-American adults (mean age: 54.6 years; 67.2% women) and 1,103 White adults (mean age: 64.5 years; 52.1% women) were included. Compared with White participants, African-Americans had significantly higher prevalence of obesity, hypertension, diabetes, and hyperlipidemia, but similar ASCVD risk (12.8% vs 12.6%; p = 0.65). No significant associations were observed between ceramide scores and either LE8 or ASCVD risk in African-Americans. Ceramide levels differed by race/ethnicity, with African-Americans showing lower concentrations of 18:0 (0.08 vs 0.10 μmol/L) and 24:1 (0.91 vs 1.17 μmol/L) species compared with White adults (both p < 0.001).

Conclusion: No association was observed between ceramide scores and CVH or ASCVD risk in African-American adults. Despite having a less favorable cardiometabolic profile, African-Americans exhibited lower ceramide levels than White adults. These findings suggest that ceramide scores may not accurately reflect cardiovascular risk in African-American populations.

Background: Human monkeypox is a zoonotic disease with increasing global prevalence. Although several studies have identified its potential risk factors, findings remain inconsistent, highlighting the need for a systematic evaluation.

Objectives: To systematically investigate risk factors associated with human monkeypox infections using meta-analysis.

Material and methods: A comprehensive search of PubMed, Scopus, Web of Science, Embase, and The Cochrane Library databases was conducted on all records up to February 19, 2024. Eligible studies assessing risk factors for monkeypox were included. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated, and heterogeneity was evaluated using I2 statistics.

Results: Of the 1,844 articles identified, 9 studies met the inclusion criteria after screening, no publication bias was identified, and the meta-analysis results showed strong robustness. Human immunodeficiency virus (HIV) infection significantly increased monkeypox risk (OR = 2.21, 95% CI: 1.13-4.34, p = 0.02, I2 = 93%). Concurrent sexually transmitted infections (STIs) were also a significant risk factor (OR = 1.84, 95% CI: 1.46-2.33), as was body mass index (BMI) higher than 30 kg/m2 (OR = 1.18, 95% CI: 0.19-7.53, p = 0.86), lower economic status (OR = 0.33, 95% CI: 0.01-9.36, p = 0.52), education level (OR = 0.74, 95% CI: 0.30-1.79, p = 0.50), or men who have sex with men (MSM) status (OR = 1.22, 95% CI: 0.84-1.75, p = 0.29).

Conclusion: HIV infection and concurrent STIs significantly increase monkeypox risk, underscoring the need for targeted prevention, including screening and risk reduction strategies in vulnerable populations, particularly MSM.

Background: Late diagnosis and chemotherapy resistance, particularly to 5-fluorouracil (5-FU), contribute to the low survival rate in cholangiocarcinoma (CCA) patients. Identifying relevant genes and pathways, as well as novel targeted molecules, is crucial to overcoming 5-FU resistance and improving treatment outcomes for CCA patients.

Objectives: This study aimed to determine the potential molecules associated with 5-FU resistance in CCA cells.

Material and methods: Transcriptomic datasets from 4 stable 5-FU-resistant cell lines and their corresponding parental lines were retrieved from the Gene Expression Omnibus. A series of bioinformatics analyses were conducted to identify key genes upregulated in 5-FU-resistant cells compared to their parental counterparts. The expression levels of candidate genes identified through bioinformatics analysis were validated in CCA tissues and cell lines.

Results: Differential gene expression, protein-protein interaction, and Hub genes analysis revealed 8 genes that were significantly upregulated in 5-FU resistance cells compared to their parental cells. Six of the 8 genes, including TCP1, RPS6, RPS29, HSPA5, RPS15A, and NOTCH1, were upregulated in patient CCA tissues. Using real-time PCR, only the expression levels of NOTCH1 and TCP1 were significantly higher in the 5-FU insensitive CCA cell lines, KKU-213A and KKU-213B, than that of the 5-FU sensitive CCA cell line, KKU-055. A similar result was observed in stable 5-FU-resistant cell lines (KKU-213A-FR and KKU-213B-FR) compared to their parental cells.

Conclusions: The bioinformatic analysis and PCR results revealed that NOTCH1 and TCP1 might be associated with 5-FU resistance and serve as potential molecular targets to enhance 5-FU sensitivity in CCA cells.