Advances in Clinical and Experimental Medicine最新文献

Background: High sepsis mortality rates pose a serious global health problem. Machine learning is a promising technique with the potential to improve mortality prediction for this disease in an accurate and timely manner.

Objectives: This study aimed to develop a model capable of rapidly and accurately predicting sepsis mortality using data that can be quickly obtained in an ambulance, with a focus on practical application during ambulance transport.

Material and methods: Data from the Medical Information Mart for Intensive Care-IV (MIMIC-IV) dataset were used to compare the performance of 11 machine learning algorithms against the widely utilized quick Sequential Organ Failure Assessment (qSOFA) score. A dynamic updating model was implemented. Performance was evaluated using area under the curve (AUC) and precision-recall area under the curve (PRAUC) scores, and feature importance was assessed with SHapley Additive exPlanations (SHAP) values.

Results: The light gradient boosting machine (LightGBM) model achieved the highest AUC (0.79) and PRAUC (0.44) scores, outperforming the qSOFA score (AUC = 0.76, PRAUC = 0.40). The LightGBM also achieved the highest PRAUC (0.44), followed by Optuna_LightGBM (0.43) and random forest (0.42). The dynamically updated and tuned model further improved performance metrics (AUC = 0.79, PRAUC = 0.44) compared to the base model (AUC = 0.76, PRAUC = 0.39). Feature importance analysis offers clinicians insights for prioritizing patient assessments and interventions.

Conclusions: The LightGBM-based model demonstrated superior performance in predicting sepsis-related mortality in an ambulance setting. This study underscores the practical applicability of machine learning models, addressing the limitations of previous research, and highlights the importance of real-time updates and hyperparameter tuning in optimizing model performance.

Pulmonary arterial hypertension (PAH) is a rare and progressive syndrome that is frequently diagnosed at an advanced stage due to the nonspecific nature of its symptoms. Current research aims to identify novel diagnostic tools, including biomarkers, to facilitate earlier detection and differentiation of pulmonary hypertension (PH) subtypes. Matrix metalloproteinases (MMPs) play a critical role in the pathogenesis of PAH through extracellular matrix (ECM) remodeling, with their activity tightly regulated by tissue inhibitors of metalloproteinases (TIMPs). This review summarizes existing studies on the potential of MMPs and TIMPs as biomarkers for PAH. Our analysis highlights significant differences in MMP concentrations between PAH patients and healthy controls. In particular, MMP-2, MMP-7 and MMP-9 exhibit promising prognostic value, which could contribute to risk stratification and support clinical decision-making in the future. However, large-scale, randomized prospective studies involving well-characterized patient cohorts are necessary to confirm their clinical utility and clarify their mechanistic roles in PAH pathogenesis.

Breast cancer (BC) remains a leading cause of cancer-related mortality worldwide, underscoring the need for novel, more effective therapies. Neoantigen-based immunotherapy - which harnesses tumor-specific somatic mutations to boost immune recognition - has emerged as a particularly promising strategy. Advances in next-generation sequencing and computational immunopeptidomics now allow systematic mapping of the tumor mutanome and rapid identification of immunogenic neoantigens, enabling personalized vaccine design and more precise deployment of immune-checkpoint blockade. However, intratumor heterogeneity, immune-escape mechanisms and the often-limited intrinsic immunogenicity of individual neoepitopes continue to constrain clinical efficacy. This review synthesizes the current landscape of neoantigen-targeted immunotherapies in BC, outlines the principal obstacles to their broader impact and highlights emerging solutions - including improved epitope-prediction algorithms, multi-epitope vaccine constructs and synergistic combination regimens. A deeper understanding of the immunogenic mutanome is expected to translate into more durable and widely applicable treatments for patients with breast cancer.

Background: Thyroid carcinoma (TC), the most prevalent endocrine cancer worldwide, has become progressively more common, especially in women. Most TCs are epithelial-derived differentiated TCs, specifically papillary thyroid cancer (PTC). Although there are many therapeutic drugs available, curing TC is a difficult task.

Objectives: A flavone called eupatorin (EUP) obtained from herbs can prevent the growth of many types of cancerous cells. Nonetheless, the mechanisms of EUP's actions against PTC are still unknown.

Material and methods: The goal of our work was to evaluate the mechanisms of EUP (20 and 30 μM/mL) and examine its antiproliferative and apoptotic effects on human PTC cells BCPAP. The MTT test; dual acridine orange/ethidium bromide (AO/EB), rhodamine-123 (Rh-123), and 4',6-diamidino-2-phenylindole (DAPI) staining; adherence assays; and western blot analyses were used to evaluate the antiproliferative and apoptotic properties of EUP on BCPAP cells.

Results: Our research showed that the quantity-dependent administration of EUP inhibited the proliferation of BCPAP cells, which in turn caused apoptosis through the increase in caspase-9 and p53 protein expression and the reduction of proliferating cell nuclear antigen (PCNA) levels. Additionally, when P13K/AKT signaling is inhibited by nuclear factor kappa B (NF-κB), EUP reduces inflammation and BCPAP proliferation.

Conclusions: By blocking the NF-κB and P13K/AKT pathways, EUP can reduce the growth of BCPAP cells and promote cell death.

Background: There is currently no established gold standard for the treatment of calcaneal fractures.

Objectives: To conduct a clinical and radiological evaluation of patients following intra-articular calcaneal fractures treated with the Polish modification of the Ilizarov method.

Material and methods: This was a 2-center retrospective study. We evaluated 27 patients (2 women and 25 men) aged 28-73 years (mean age 50.5 years) after treatment of intra-articular calcaneal fractures with the Polish modification of the Ilizarov method. We assessed pain using a visual analogue scale (VAS), American Orthopedic Foot and Ankle Society (AOFAS) scores, patient satisfaction with treatment, use of analgesics, duration of Ilizarov treatment, length of hospital stay, duration of surgery, patient's declared willingness to choose the same treatment again, complications, degenerative changes, Böhler angle, inflection angle, and Gissane angle.

Results: The mean follow-up period was 3 years and 2 months. Following treatment, the mean VAS pain score was 2.3. Prior to surgery, all patients were taking analgesics in comparison with only 2 patients (7.4%) at long-term follow-up. The treatment was rated as satisfactory by 11 patients, with 16 patients rating it as highly satisfactory. The mean post-treatment AOFAS score was 76.6 points. The Ilizarov fixator was removed after a mean period of 88 days. The mean duration of hospital stay was 7.4 days. The mean duration of the procedure was 44 min. All patients would choose the same treatment again. Complications were observed in 5 patients. The long-term follow-up visit revealed degenerative changes in the talocalcaneal joint in 8 patients. The median Böhler angle was 5.5° preoperatively and 28.5° postoperatively, p < 0.001. The median preoperative inflection angle of 160° decreased to 145°, p < 0.001. The median preoperative Gissane's angle of 119° increased significantly to a median postoperative value of 143°, p < 0.001.

Conclusions: The patients achieved good clinical and radiological outcomes.

Background: Turmeric and boswellia supplements have gained popularity for their anti-inflammatory and antioxidant properties. It is important to critically assess the safety of such supplements for prolonged use.

Objectives: To assess the safety and tolerability of turmeric-boswellia-sesame oil formulation (TBSF) in healthy human volunteers.

Material and methods: Forty participants were supplemented with TBSF at a dose of 2,000 mg daily for 90 days. Safety assessments were performed at baseline, as well as on day 30, 60 and 90. Adverse events were monitored throughout the study period. Any evidence of hepatotoxicity injury or drug induced liver injury (DILI) was assessed using R value (R ratio/R factor), which is a relative pattern of liver enzymes. Additionally, Hy's law criteria, based on liver enzymes and bilirubin levels, were employed, along with an evaluation of drug-induced serious hepatotoxicity (eDISH) plot. The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were calculated, as these values are relevant to the safety of the intervention.

Results: The study found that TBSF supplementation did not cause any adverse effects or clinically significant variations in vital signs, hematological parameters, lipid profile, liver function enzymes, and renal function markers, and all were within the normal range after 90 days of TBSF supplementation. Platelet-to-lymphocyte ratio and NLR did not change significantly and were within the normal range. All the participants when plotted were in the normal range quadrant of the eDISH plot throughout the study period. No abnormal findings were observed in R value and Hy's law criteria, indicating that TBSF does not induce any hepatotoxicity. The present study showed a normal estimated glomerular filtration rate (eGFR), blood urea nitrogen (BUN), creatinine (Cr), Cr clearance, and BUN/Cr ratio throughout the study period. There was no significant change between these values at 4 abovementioned time points.

Conclusions: The study findings suggest that TBSF is a safe supplement for regular and long-term consumption.

Background: Dacryolithiasis can occur anywhere in the lacrimal drainage system and is frequently associated with microbial infections. The presence of dacryolithiasis is difficult to determine based on its clinical manifestations, which complicates clinical treatment.

Objectives: To analyze the clinical diagnosis, treatment and characteristics of dacryolithiasis, as well as surgical methods used to treat it and treatment effects over the past 5 years.

Material and methods: A retrospective analysis was performed on the clinical data of 338 patients who were diagnosed with dacryolithiasis at our hospital from January 2017 to December 2021. Patients diagnosed with canaliculitis were treated with canaliculotomy. Dacryocystitis complicated by canaliculitis was treated with endoscopic dacryocystorhinostomy (En-DCR) combined with canaliculotomy. Dacryocystitis accompanied by dacryoliths was treated with En-DCR. Nasolacrimal duct stones were treated with lacrimal intubation. All patients were followed up for 6-12 months.

Results: All patients underwent successful surgery. Of 302 cases (89.35%) with canaliculitis, 297 (98.34%) were cured with canaliculotomy; 5 cases (1.66%) recurred within 1 year after surgery and were cured with canaliculotomy again. Four cases (1.18%) of dacryocystitis complicated by canaliculitis were treated with En-DCR combined with canaliculotomy. In addition, 30 patients (8.88%) had dacryolithiasis; 28 (93.33%) of them were cured, and 2 (6.67%) with common canalicular atresia were cured after lacrimal intubation. Furthermore, 2 patients (0.59%) with nasolacrimal duct stones underwent lacrimal intubation. In addition, 62 cases (20.53%) with canaliculitis tested positive for bacteria, and the top 2 common bacteria were Staphylococcus epidermidis and Streptococcus mitis.

Conclusions: Secretions are the main clinical characteristic of patients with dacryolithiasis, and surgery is the primary treatment method. In addition, different surgical methods correspond to different locations of stones.

Background: Acute respiratory distress syndrome (ARDS) presents a significant challenge in the management of sepsis, with various comorbidities potentially influencing its development. Understanding the impact of these comorbidities is crucial for improving patient outcomes.

Objectives: This meta-analysis was conducted to investigate the relationship between various comorbidities and the development of ARDS in patients with sepsis, with the aim of improving understanding and management of this condition.

Material and methods: The study included adult sepsis patients from 8 studies, totaling 16,964 participants. Risk of bias was assessed using the Newcastle-Ottawa scale (NOS), and the data analysis was performed and reported as pooled odds ratios (ORs) computed using a random-effects model. Heterogeneity and publication bias were assessed using the I2 statistic and Doi plots with the Luis Furuya-Kanamori (LFK) index, respectively.

Results: Chronic obstructive pulmonary disease was significantly associated with an increased risk of ARDS (OR: 1.43, 95% confidence interval (95% CI): 1.02-2.01). Other comorbidities showed no significant associations: diabetes mellitus (DM) (OR: 0.88, 95% CI: 0.69-1.11), hypertension (HTN) (OR: 0.86, 95% CI: 0.56 to 1.34), coronary artery disease (CAD) (OR: 0.95, 95% CI: 0.86-1.06), congestive heart failure (CHF) (OR: 1.08, 95% CI: 0.61 to 1.90), chronic kidney disease (CKD) (OR: 0.89, 95% CI: 0.65-1.22), chronic liver disease (CLD) (OR: 1.13, 95% CI: 0.61-2.09), and cancer (OR: 0.90, 95% CI: 0.59-1.35). Additional analyses indicated moderate-to-high heterogeneity and some evidence of publication bias.

Conclusion: Chronic obstructive pulmonary disease is a notable risk factor for ARDS in sepsis patients, suggesting the need for enhanced surveillance and management in this group. Further research is necessary to understand the mechanisms and explore other potential ARDS risk factors in sepsis.

Keratin biomaterials, derived from natural sources, offer a promising, biocompatible solution for wound healing and tissue regeneration, though further clinical studies are needed to confirm their efficacy.

The SAPIENCE study explores the long-term psychological, social, and systemic challenges faced by caregivers of individuals with NMDAR encephalitis. It aims to inform patientand caregiver-centered strategies that support recovery and wellbeing.