Advances in Clinical and Experimental Medicine最新文献

Alzheimer's disease (AD) remains one of the most pressing challenges in contemporary neurology, with growing evidence highlighting the limitations of the amyloid hypothesis and monomodal therapies. This editorial advocates for a shift toward multidimensional research and therapeutic frameworks that integrate molecular, electrophysiological, neuroimaging, and behavioral data. Emphasis is placed on the potential of microRNA-based biomarkers, electroencephalography (EEG) analysis, and non-invasive methods to improve early diagnosis. Emerging multimodal treatment strategies - including immunotherapy, neurostimulation, and nutraceuticals - are discussed alongside ethical and regulatory challenges in implementing novel interventions. The authors propose an integrated, patient-centered model that combines precision medicine with preventive approaches rooted in lifestyle, digital biomarkers, and AI-powered personalization. A paradigm shift toward systemic, translational, and ethically grounded strategies is urgently needed to meet the growing burden of AD.

The 2025 Nobel Prize in Physiology or Medicine honored the seminal discovery that regulatory T cells (Tregs) restrain immune responses and prevent autoimmunity through peripheral immune tolerance. However, to obtain a holistic view of peripheral immune tolerance, it is also necessary to consider the role of mesenchymal stem/stromal cells (MSCs) in this process. Therefore, I propose a two-tier model that incorporates both Tregs and MSCs, with Tregs acting within the immune system as an "internal checkpoint" to temper effector cell activity, and tissue-resident MSCs - or "master signaling cells" - serving as an "external checkpoint." Injuryor pathogen-induced inflammation activates MSCs, which in turn secrete a broad repertoire of immunomodulatory molecules, create a local anti-inflammatory milieu, promote tissue repair, and directly dampen excessive immune activity at the site of damage. The concerted actions of Tregs and MSCs are essential for effective peripheral immune tolerance, shielding the host from pathogens and collateral tissue injury. This model helps explain the pathophysiology of autoimmunity and tumor immune evasion, as well as the therapeutic potential of MSC-based interventions.

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: Cognitive impairment (CI) is common in patients with alcohol-use disorder (AUD)-related liver cirrhosis, especially those awaiting liver transplantation (LT). There are conflicting results in terms of the role of hepatic encephalopathy (HE) in CI development and persistence.

Objectives: This study investigated the impact of hyperammonemia on CI and evaluated the role of routine magnetic resonance imaging (MRI) in detecting CI among patients with AUD-related cirrhosis listed for LT at a single center.

Material and methods: Fifty-two adults (36 males, 69%) with AUD-related liver cirrhosis (mean age: 51 ±11 years; mean Model for End-Stage Liver Disease (MELD) score 16 ±6) were evaluated. Cognitive function was assessed using the Addenbrooke's Cognitive Examination III (ACE-III), with scores below 82 indicating probable dementia. Magnetic resonance imaging evaluations focused on cortical-subcortical atrophy, vascular-origin changes, and chronic HE.

Results: Magnetic resonance imaging revealed HE-related changes in 38 patients (73%), vascular-origin changes in 32 patients (62%), and cortical-subcortical atrophy in 15 patients (29%). Cognitive impairment was present in 46 patients (88%), with 30 (58%) suspected of having dementia. Patients with MRI evidence of HE scored lower in the ACE III language subdomain (p = 0.032) and tended toward a higher Child-Pugh classification (p = 0.083). No significant differences were found in ACE-III results or clinical data between patients with and without vascular-origin changes or cortical-subcortical atrophy. Additionally, no correlations were observed between radiological findings, ammonia levels, ACE-III scores, and liver-related mortality.

Conclusions: These findings reveal a high prevalence of CI and significant MRI abnormalities in AUD patients awaiting LT. Further studies are needed to clarify the role of routine MRI in detecting cognitive deficits.