Advances in Clinical and Experimental Medicine最新文献

Background: Amputation followed by index finger pollicization is the gold-standard treatment for type III B thumb hypoplasia. However, despite its high success rate, some parents decline this procedure because it results in a four-finger hand.

Objectives: To evaluate the outcomes of reconstructive surgery in eight patients with type III B thumb hypoplasia, stabilized using a non-vascularized proximal interphalangeal (PIP) joint harvested from the foot when parental consent for pollicization was not granted.

Material and methods: The study cohort comprised 8 postoperative patients (mean follow-up: 7 years) who underwent reconstructive stabilization of a hypoplastic thumb using a PIP joint from the foot. Hand function was evaluated by measuring range of motion (ROM), thumb stability and length, grip strength, and performance on a manual manipulation test. Donor-site morbidity was assessed via foot examination following PIP joint harvest. Functional outcomes were further analyzed using specialized patient-reported questionnaires.

Results: Most patients achieved good thumb stability and a functional passive range of motion. Reconstructed thumbs averaged approx. 75% of the length of a normal thumb, and grip strength measured about 50% of that in the contralateral hand. Donor-site assessment revealed toe shortening in the majority of cases but no deficits in ambulation or weight-bearing. The overall complication rate was 25%, and most patients and their parents reported satisfaction with the treatment.

Conclusions: Thumb reconstruction with a non-vascularized PIP joint yields enhanced stability and reduced hypermobility, with outcomes comparable to those reported for similar techniques. This approach represents a viable alternative for patients whose parents decline pollicization.

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: Basket trials are an innovative type of clinical trial primarily used in oncology. A distinctive feature of these studies is the grouping of patients based on specific molecular characteristics, such as genetic mutations or immunological subtypes, rather than traditional criteria like the type of cancer.

Material and methods: This review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Medical databases were searched for studies published between 2014 and 2024. The inclusion criteria focused on basket trials as a clinical trial model in oncology.

Objectives: This work aims to outline the principles of conducting basket trials in oncology, analyze basket trials from the past decade, and highlight the emerging trends in this type of trial.

Results: The analysis of 76 articles meeting the inclusion criteria revealed that most of these studies are conducted as phase II clinical trials. The average duration of the basket trials in the analysis was 5.9 years (mean = 5.05), with an average recruitment target of 326 patients (mean = 123.5). Most of these studies were conducted in the USA, and the majority of basket trials focused on patients with solid tumors.

Conclusion: The systematic review confirms that basket trials have significant potential as a clinical trial model, as evidenced by the increasing number of basket trial projects being conducted.

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.

Background: Research on the psychological distress experienced by women with benign breast disease (BBD) remains limited, though some evidence suggests it may resemble that of women with breast cancer (BC).

Objectives: This study aimed to use the Distress Thermometer (DT) to assess the levels of psychological distress and identify influencing factors during the diagnostic phase in patients with BC and BBD.

Material and methods: From October 2022 to May 2023, a questionnaire survey incorporating the DT and Problem List (PL) was conducted among inpatients in the diagnostic phase for BC or BBD at the Breast Surgery Department of Shanxi Bethune Hospital (Taiyuan, China). Statistical analysis, including descriptive and inferential methods, was performed to examine factors affecting psychological distress in patients with BBD and BC.

Results: In this study, 373 participants were evaluated for psychological distress during the diagnostic phase. Among 255 patients diagnosed with BBD, the median distress score was 4, with a distress prevalence of 52%. The primary sources of distress included anxiety (43.5%), fear (21.2%), pain (7.1%), sleep disturbances (6.7%), and childcare responsibilities (5.1%). Among 118 BC patients, the median distress score was slightly higher at 4.5, with a distress prevalence of 63.6%. Key distress factors were anxiety (47.5%), fear (33.1%), financial worries (21.2%), depression (18.6%), and sadness (15.3%). Key predictors of distress varied between the 2 groups. For patients diagnosed with BBD, younger age, lower education levels, unemployment, and a higher Breast Imaging Reporting and Data System (BI-RADS®) classification significantly contributed to higher distress levels. In patients diagnosed with BC, younger age, lower education levels, and unemployment were the primary risk factors.

Conclusions: These findings underscore the psychological burden faced by both patient groups during diagnosis, highlighting the need for early identification and management of distress in this population.

Background: Multidrug resistance remains a major obstacle in the treatment of ovarian cancer (OC) patients. Recent research has underscored the critical role of extrachromosomal circular DNA (eccDNA) in tumor initiation and progression. However, there is limited comprehensive understanding of the role eccDNA plays in tumor resistance.

Objectives: This study investigates the involvement of WWP1-eccDNA in the resistance mechanisms of OC.

Material and methods: Human OC cells (SKOV3 and cisplatin-resistant SKOV3/DDP) were cultured and high-throughput sequencing was performed, leading to the identification of eccDNA in SKOV3/DDP cells. Female BALB/cA-nu nude mice with SKOV3 and SKOV3/DDP xenografts received cisplatin (5.5 mg/kg), hydroxyurea (50 mg/kg) or saline for 14 days, followed by tumor weight assessment. Digital droplet polymerase chain reaction (ddPCR) and real-time quantitative polymerase chain reaction (qPCR) were used to quantify WWP1-eccDNA, evaluating their sensitivity and accuracy. Linear DNA removal and BsmI digestion were tested to improve eccDNA detection.

Results: WWP1-eccDNA was among the top upregulated eccDNA in SKOV3/DDP cells. Both cisplatin and hydroxyurea reduced tumor growth in mice, with cisplatin showing limited efficacy in resistant tumors. The ddPCR outperformed RT-qPCR in sensitivity, and linear DNA removal improved WWP1-eccDNA detection. WWP1-eccDNA levels were significantly elevated in SKOV3/DDP tumors. Treatment with cisplatin further increased its expression, whereas hydroxyurea led to a reduction in WWP1-eccDNA levels.

Conclusions: WWP1-eccDNA is critical in OC resistance, with cisplatin treatment increasing WWP1-eccDNA levels, contributing to resistance. The ddPCR proves to be a superior method for eccDNA detection.

Background: Vestibular rehabilitation therapy (VRT) is widely utilized to enhance balance and mitigate dizziness in patients with vestibular disorders. However, its overall effectiveness remains to be comprehensively assessed, particularly in the context of variability among studies.

Objectives: This study aimed to address the current need for a systematic evaluation of VRT's efficacy.

Material and methods: A meta-analysis was conducted using the "meta" and "dmetar" R packages to evaluate VRT's efficacy. The analysis included statistical tools, such as Begg's test, Egger's test, Baujat plots, Galbraith plots, and influence analysis. Additionally, heterogeneity and outliers were assessed using generalized scatterplot smoothing (GOSH) diagnostics and clustering methods, including K-means, density-based spatial clustering of applications with noise (DBSCAN) and Gaussian mixture model (GMM).

Results: The meta-analysis examined the impact of VRT on the dizziness handicap inventory (DHI) and Berg balance scale (BBS). For the DHI, VRT resulted in a significant mean improvement of 7.63 points, despite high heterogeneity (I2 = 88%). Similarly, the BBS exhibited significant improvement, with a mean difference (MD) of -2.31 points in the fixed effects model, while the random effects model also suggested improvement, though with greater variability (I2 = 92%). Subgroup analysis identified outliers significantly influencing the results.

Conclusion: We showed that VRT significantly enhanced patient outcomes as measured with both the DHI and BBS. These findings provide strong evidence supporting VRT's effectiveness, though the substantial heterogeneity underscores the need for further research to refine patient selection and intervention protocols. This study advances the understanding of VRT's role in managing vestibular disorders and highlights the importance of addressing variability in future studies.

Background: The search for early and minimally invasive diagnostic approaches to pancreatic cancer (PC) remains an important issue. One of the most promising directions is to find a sensitive key in the metabolic changes during widespread causes of PC, i.e., chronic pancreatitis (CP) and diabetes mellitus (DM).

Objectives: The main objective of this study was to analyze the peptide pools in the blood plasma and pancreas of rats with modeling of CP and/or without type 1 DM in association with pancreas histopathological grading features.

Material and methods: The study was conducted on white non-linear male rats, divided into 3 groups: 1st group: control, 2nd group: rats with cerulein-stimulated CP, and 3rd group: rats with CP and streptozotocin-inducible type 1 DM. Total protein and peptide content were determined in the pancreas and blood plasma. The peptide pools were fractionated using size-exclusion chromatography.

Results: Rats with CP showed a high degree of fibrosis in the pancreas and grade 1 ductal pancreatic intraepithelial neoplasia (PanIN), associated with decreased total peptides in the pancreas. In rats with CP and DM, 2nd and 3rd grade PanIN with pronounced acinar metaplasia was observed in association with decreasing total pancreatic protein and peptide pools. While there was a decrease in total protein and an increase in total peptide in blood serum, the changes were more pronounced in rats with CP and DM. A study revealed both qualitative and quantitative differences in the distribution of peptide pools in 2 groups with pathologies. Qualitatively, plasma samples from pathological groups exhibited an increased number of peaks. Quantitatively, there was a higher proportion of peptides with molecular weights exceeding 700 Da observed in both plasma and pancreas.

Conclusions: The analysis of peptide pools obtained from plasma and PanIN development demonstrated that the peptide pool can serve as an early and complementary indicator of PC emergence.

Background: Liquid biopsy, including miRNA profiling, is a promising approach to identify breast cancer (BC) resistance. However, the effect of long-term storage on the quality of miRNA assessment in archival serum has not been fully addressed.

Objectives: We aimed to determine whether miRNAs were recoverable from long-stored serum samples to subsequently evaluate prognostic and predictive miRNA value in the archival collection of samples from patients treated with neoadjuvant chemotherapy at Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice, Poland.

Material and methods: We have evaluated miRNA quantity in serum samples stored for up to 12 years. Additionally, we compared miRNA expression in archival samples to freshly collected samples derived from advanced BC patients.

Results: Forty BC patients were included in the study. Archival samples were derived from 20 BC patients treated with radical intent between 2011 and 2015. Freshly collected samples were collected from 20 advanced BC patients in 2022. miRNA was present in archived serum samples frozen at -80C° for at least 12 years. Additionally, we found significantly different expressions between the 2 analyzed groups. Expression of circulating miR-16, -17, -18a, -20a, -21, -27a, -30b, -222, and -326 were significantly higher in archival samples, whereas expression of circulating miR-19a, -29b, -29c, -128, -145, -146a, -193b, -195, -200b, -210, -221, -424, and -451a were lower than in freshly collected samples. In 14 miRs, we observed expression in both groups; however, differences were statistically insignificant (miR-1, -7a, -10b, -19b, -34a, -99a, -106b, -122, -125b, -155, -200a, -205, -223, -340).

Conclusions: MiRNA can be identified from long-stored samples, making large prospectively collected serum repositories with long follow-up time an invaluable source for miRNA biomarker discovery.

Background: Propofol and midazolam have been widely used in patients with sepsis. However, the effectiveness of these drugs in reducing the duration of mechanical ventilation and the risk of mortality remains controversial.

Objectives: To investigate and compare effects of propofol and midazolam on 30-day mortality in patients with sepsis-associated encephalopathy (SAE).

Material and methods: A retrospective cohort study was conducted on data from 952 adult patients with SAE extracted from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Univariable and multivariable Cox proportional hazard models were utilized to investigate the associations of propofol and midazolam with 30-day mortality; and univariable and multivariable logistic regression analyses were used to explore the relationships of propofol and midazolam with ventilation duration. The outcome measures were hazard ratios (HRs), odds ratios (ORs), and 95% confidence intervals (95% CIs). In addition, subgroup analyses of age, simplified acute physiological score (SAPS)-II, Charlson Comorbidity Index (CCI), and ventilation duration were also performed to further assess the associations of propofol and midazolam with 30-day mortality.

Results: Among eligible patients, 265 (27.84%) died within 30 days. After adjusting for covariates, treatment with propofol was associated with both lower risk of 30-day mortality (HR = 0.67, 95% CI: 0.51-0.88) and lower odds of prolonged ventilation duration (OR = 0.71, 95% CI: 0.53-0.96) compared to treatment with midazolam. Moreover, the negative association between treatment with propofol and 30-day mortality was also significant in subgroups of age ≥65 years, SAPS-II score ≥47, CCI score ≥3, and ventilation duration ≥5 days (all p < 0.05).

Conclusions: Among patients with SAE, treatment with propofol was relatively more effective than treatment with midazolam in reducing the risk of 30-day mortality and the duration of mechanical ventilation. However, the causal relationships of propofol and midazolam with prognosis in patients with SAE need further clarification.