Advances in Clinical and Experimental Medicine最新文献

Background: Hyperlipidemia is a major risk factor for cardiovascular diseases and is associated with complications such as atherosclerosis and tendon injury. Though atorvastatin reduces cholesterol, genetic variants (CYP2D6-4, SULT1A1, CYP2C192) affect its response. These genetic variations influence atorvastatin metabolism, thereby affecting its therapeutic effectiveness.

Objectives: To advance personalized therapeutic drug monitoring and improve lipid profile management, this study aims to develop a robust and LC-MS/MS method for quantifying atorvastatin levels in human plasma. Additionally, to investigate the influence of genetic polymorphisms - particularly CYP2D6-4-on plasma concentrations of atorvastatin in patients with hyperlipidemia.

Material and methods: Ethical approval for the study was obtained from the appropriate institutional review boards, and written informed consent was obtained from all participants. Atorvastatin was measured using LC-MS/MS. PCR-based methods were used for genotyping. Statistical analyses were performed to evaluate relationships between plasma atorvastatin levels and genetic variants.

Results: The LC-MS/MS method demonstrated excellent linearity, accuracy, precision, and stability, for the quantification of atorvastatin in human plasma. Higher atorvastatin concentrations were tied to CYP2D6-4. Furthermore, the study validated the analytical method for consistent and reliable measurement of atorvastatin levels in clinical samples.

Conclusions: This study successfully developed and validated a straightforward and reliable LC-MS/MS method for quantifying atorvastatin levels in human plasma. Significant CYP2D64 - atorvastatin links highlight the value of pharmacogenetic dosing. Integrating pharmacogenetics - especially in the Jordanian population - may enhance the safety, efficacy, and individualization of atorvastatin therapy.

Background: Acute cholecystitis (AC) is a common biliary disorder, most often caused by gallstones obstructing the cystic duct and leading to gallbladder inflammation.

Objectives: This study aimed to compare the therapeutic efficacy and complication rates of laparoscopic cholecystectomy (LC) performed using the Calot's triangle approach vs traditional LC techniques in the treatment of AC.

Material and methods: A retrospective analysis was conducted on 120 patients diagnosed with AC, with 60 patients undergoing LC using the Calot's triangle approach (study group) and 60 patients treated with traditional LC techniques (control group). Surgical parameters, including operation time, intraoperative hemorrhage, postoperative recovery times, and 30-day postoperative complications were recorded. Intraoperative adhesion formation was evaluated through direct visualization and graded based on severity. Postoperative pain was assessed using the visual analogue scale (VAS).

Results: There was no statistically significant difference in the baseline characteristics between the 2 groups, confirming their comparability. The study group (Calot's triangle approach) demonstrated significantly shorter average operation time, postoperative exhaust time, and diet recovery time compared to the control group. Additionally, patients in the study group had significantly lower intraoperative bleeding, lower VAS pain scores at 24 h and 72 h postoperatively, and a lower overall complication rate compared to the control group (p < 0.05).

Conclusions: The LC Calot's triangle approach demonstrated shorter operation times and lower rates of certain complications compared with traditional LC techniques. However, the absence of statistically significant differences in some key outcomes highlights the need for further research to fully evaluate its clinical advantages and long-term benefits.

Background: The precise causal relationship between circulating inflammatory factors and sepsis has not yet been fully elucidated.

Objectives: To identify biomarkers that enable earlier and more accurate diagnosis of sepsis.

Material and methods: The causal relationships between 41 circulating inflammatory factors, C-reactive protein (CRP), and procalcitonin (PCT) with sepsis and 28-day sepsis-related mortality were evaluated using two-sample bidirectional Mendelian randomization (MR) analyses.

Results: This study revealed negative causal associations between genetically predicted circulating inflammatory factors-interleukin-6 (IL-6) (odds ratio [OR] = 0.923; 95% confidence interval [CI], 0.854-0.998; p = 0.044), RANTES (OR = 0.926; 95% CI, 0.862-0.994; p = 0.033), and macrophage inflammatory protein-1β (MIP1β) (OR = 0.957; 95% CI, 0.919-0.996; p = 0.032) - and the risk of sepsis. Furthermore, positive causal relationships were observed between CRP and sepsis (OR = 1.140; 95% CI: 1.055-1.232; p = 0.001), as well as between CRP and 28-day sepsis-related mortality (OR = 1.241; 95% CI: 1.034-1.489; p = 0.020). Platelet-derived growth factor-BB (PDGF-BB) levels were also elevated in sepsis (OR = 1.136; 95% CI: 1.003-1.286; p = 0.044). Mediation analysis indicated that CRP mediated the effects of IL-6 and RANTES on sepsis, accounting for 25.87% (OR = 0.980; 95% CI: 0.961-0.998) and 2.04% (OR = 1.002; 95% CI: 0.991-1.012) of the total effect, respectively. The robustness of these associations was confirmed through leave-one-out sensitivity analysis and funnel plots.

Conclusions: This study enhances our understanding of the mechanisms underlying sepsis and its associated mortality, and underscores the therapeutic potential of targeting inflammatory factors in its management.

Background: Initiating orthodontic treatment before the pubertal peak results in more pronounced long-term craniofacial changes in the maxilla and adjacent structures. Dental malocclusion correction through maxillary expansion has been shown to significantly increase the patency and decrease the airflow resistance in several airway compartments, ranging from the nares to the epiglottis plane.

Objectives: We aimed to assess the impact of treatment with a removable functional orthodontic appliance on the dimensions of selected sections of the upper respiratory tract in pediatric patients, with the goal of identifying the nasopharyngeal and oropharyngeal regions most susceptible to lateral maxillary and mandibular expansion.

Material and methods: We retrospectively reviewed the medical records and lateral cephalometric radiographs (LCRs) of all consecutive pediatric patients with deciduous or mixed dentition treated with a functional appliance between 2014 and 2019 at a private orthodontic practice in Racibórz, Poland. To assess the impact of the study group and gender on the dependent variables, a Multivariate Analysis of Covariance (MANCOVA) was performed. The variable T1 (age at treatment initiation) was included as a covariate in the model to control for its potential effect on the outcomes.

Results: The treatment group comprised 55 patients, while 24 subjects served as the control group. In contrast to the nasopharyngeal variables, the average annual increase in the oropharyngeal linear measurements was significantly greater in the treatment group. For the gender factor, after applying the Benjamini-Hochberg correction, no statistically significant differences were observed in any of the assessed variables. In contrast, after correction, the covariate T1 was statistically significant for the following variables: CVM1 and CVM2 (skeletal age before treatment initiation and after treatment completion, respectively), and T2 (chronological age after treatment completion).

Conclusions: Although treatment with a removable functional appliance does not significantly impact the nasopharyngeal airspace, it significantly increases oropharyngeal dimensions, which may help reduce the future risk associated with abnormal breathing patterns in treated patients.

Background: Vascular injury is a central and early feature of systemic sclerosis (SSc) pathogenesis. Although nailfold capillaroscopy (NC) effectively visualizes characteristic peripheral arteriolar and capillary changes, the retinal microcirculation provides a noninvasive, high-resolution view into subtler vascular dysfunction. Consequently, retinal vascular imaging may offer an ideal modality for monitoring microvascular injury and detecting early manifestations of SSc.

Objectives: To compare retinal microvascular parameters between SSc patients and healthy controls using adaptive optics (AO) imaging, and to evaluate the correlation between adaptive optics-derived retinal measurements and NC findings in SSc.

Material and methods: The study included 31 patients with SSc and 41 healthy controls. The AO images of the retinal arteries were obtained in both groups and the measurements were compared. Nailfold capillaroscopy was also performed in the SSc cohort, and its findings were directly compared with the AO imaging results.

Results: Retinal arterial wall thickness was significantly lower in SSc patients than in healthy controls (p = 0.016), and the wall-to-lumen ratio was similarly reduced in the SSc group (p = 0.048). Within the SSc cohort, hypertensive patients exhibited a significantly greater wall cross-sectional area compared to those without hypertension (p = 0.026).

Conclusions: Adaptive optics retinal imaging demonstrated a significant reduction in mean arterial wall thickness in SSc patients compared with healthy controls. However, no correlation was identified between the AO findings and the NC parameters or the disease stage. Our analysis revealed that alterations in retinal vascular parameters were confined to SSc patients with comorbid hypertension or those receiving sildenafil therapy. To fully establish the clinical utility of adaptive optics imaging in SSc, and to elucidate its relationship with NC findings, larger, multicenter studies with more diverse patient cohorts are warranted.

Background: The two-drug regimen Kd-70 (carfilzomib at a dose of 70 mg/m2 with dexamethasone) is a recommended treatment option for patients with relapsed or refractory multiple myeloma, according to both American and European guidelines. However, aside from the A.R.R.O.W. trial, real-world data on its effectiveness remain limited.

Objectives: We aimed to assess the effectiveness of the two-drug regimen Kd-70 in real-world practice.

Material and methods: We analyzed data from the Polish Ministry of Health registry, which included 412 patients treated with the Kd-70 regimen in Poland.

Results: The overall response rate (ORR) was 67.15%, comparable to the A.R.R.O.W. trial. However, the complete response (CR) rate (5.3%) and very good partial response (VGPR) rate (9.59%) were lower than those reported in the A.R.R.O.W. study. Notably, Kd-70 showed significantly lower efficacy in patients who required treatment for primary resistance or disease progression within the 1st year after diagnosis. In contrast, the number of prior treatment lines did not impact the regimen's effectiveness.

Conclusions: In real-world clinical practice, the Kd-70 regimen demonstrated an ORR comparable to that observed in the A.R.R.O.W. trial. However, the CR and VGPR rates were lower. These findings underscore the need for further investigation into factors influencing treatment outcomes in this patient population.

This study examines soft tissue injuries secondary to the prevalence of local anesthesia, differential diagnosis and therapeutic approaches. In October 2024, a comprehensive search was performed in PubMed, Web of Science and Scopus along with gray literature sources, adhering to the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) guidelines, using the following keywords: "bite", "traumatic injuries", "soft tissue injuries", "self-inflicted injuries", "topical anesthesia", "local anesthesia", "pediatric", or "children". The search was limited to English-language publications. Additional manual screening of reference lists was performed. The risk of bias was assessed using the checklist developed by the Joanna Briggs Institute (JBI). Out of 574 identified studies, 21 were included in the qualitative analysis (9 randomized controlled trials (RCTs), 6 case reports and 6 cohort studies), mainly focusing on children aged 6-12. Anesthesia methods included traditional techniques (12 studies) and computer-controlled injection (5 studies). The role of articaine (9) and lidocaine (10) was analyzed. Suggested interventions to mitigate injury risks and improve recovery included the use of phentolamine mesylate (2 studies) and non-pharmacological strategies: intraoral appliances (2 studies) and photobiomodulation (2 studies). The included studies varied in design, sample size and duration, limiting direct comparisons. Effect sizes and confidence intervals were inconsistently reported, and the risk of bias assessment using the Cohen's kappa test highlighted methodological heterogeneity and potential reporting bias. Soft tissue injuries from local anesthesia in children can cause significant pain and cooperation issues. Effective strategies include early intervention with pharmacological and non-pharmacological approaches. Increased awareness and patient-specific management are essential for reducing risks and improving outcomes.

Background: Recurrent miscarriage (RM), the loss of 2 or more consecutive pregnancies before 28 weeks' gestation, has become increasingly common in recent years, imposing significant physical and psychological burdens on affected women. Despite comprehensive evaluation, approx. 40-50% of RM cases remain unexplained and are therefore classified as idiopathic.

Objectives: This study aimed to investigate the expression of SMAD2 and SMAD3 and characterize Th1, Th2 and Th17 cytokine profiles in placental villous tissues from women with idiopathic RM.

Material and methods: Forty-nine women with idiopathic RM in early pregnancy and 41 gestational age-matched women with normal pregnancies (NP) were recruited at Shanxi Maternal and Child Health Hospital (Taiyuan, China) . Following informed consent, placental villous tissues were obtained via ultrasound-guided vacuum aspiration, rinsed in saline and stored at -80°C. Total RNA was extracted from each sample, and SMAD2 and SMAD3 mRNA levels were quantified using real-time quantitative PCR (qPCR) using the 2-ΔΔCq method. Parallelly, tissue homogenates were assayed with enzyme-linked immunosorbent assay (ELISA) for Th1 cytokines (interleukin (IL)-2, intereron gamma (IFN-γ), tumor necrosis factor alpha (TNF-α)), Th2 cytokine (IL-10), and Th17 cytokines (IL-6, IL-17). Spearman's rank correlation was used to evaluate associations between SMAD2/3 expression and cytokine concentrations. All statistical analyses were performed in IBM SPSS v. 27.0, with two-tailed p < 0.05 denoting significance.

Results: The qPCR analysis demonstrated that SMAD2 mRNA levels in villous tissues were significantly higher in the RM group than in NP controls (p < 0.05). Consistent with this, ELISA revealed a marked increase in IL-6 concentration (p < 0.05) alongside significant reductions in IL-2, IL-10, TNF-α, and IFN-γ levels in RM samples vs NP (all p < 0.05). Spearman correlation analysis showed that SMAD2 expression was inversely correlated with IFN-γ (ρ < 0, p < 0.05), while SMAD3 expression was negatively associated with both IL-2 and IFN-γ levels (ρ < 0, p < 0.05).

Conclusions: SMAD2/3 can affect the expression of Th1 and Th17 cytokines, which may in turn affect normal embryonic development.

Cornelia de Lange syndrome (CdLS) is a complex genetic disorder affecting multiple body systems. It is characterized by distinctive facial features, skeletal anomalies, neurological and developmental impairments, physiological cutaneous manifestations such as hirsutism and synophrys, and numerous other signs and symptoms. Among affected individuals, the clinical presentation of CdLS varies widely, ranging from relatively mild to severe forms. Additionally, CdLS increases the frequency of certain dermatoses, including cutaneous bacterial infections and idiopathic thrombocytopenic purpura. Six genes have been identified in association with CdLS: NIPBL (Nipped-B-like protein), RAD21 (double-strand break repair protein rad21 homolog), SMC1A and SMC3 (structural maintenance of chromosomes 1A and 3), BRD4 (bromodomain-containing protein 4), and HDAC8 (histone deacetylase 8). Cornelia de Lange syndrome is estimated to occur in 1 out of every 10,000-30,000 live births, making it a rare condition and posing diagnostic challenges due to its low incidence. The present review aims to raise awareness of CdLS among dermatologists by providing a brief overview of the syndrome and summarizing the current literature on its dermatological manifestations.

Cardiovascular prevention guidelines are based on robust evidence, yet their implementation in primary healthcare remains inconsistent due to systemic barriers, workload pressures and insufficiently adapted tools. The 2025 European consensus emphasizes the need for multidisciplinary teamwork, digital innovation and equity-focused strategies to strengthen prevention across diverse healthcare systems. Translating these recommendations into actionable, context-specific approaches is essential to close the evidence-practice gap and improve population cardiovascular outcomes.