Fe-doped Cu-based bimetallic metal-organic frameworks as nanoscale microwave sensitizers for enhancing microwave thermal and dynamic therapy for hepatocellular carcinoma.

Microwave ablation (MWA) is recognized as a novel treatment modality that can kill tumor cells by heating the ions and polar molecules in these cells through high-speed rotation and friction. However, the size and location of the tumor affect the effective ablation range of microwave hyperthermia, resulting in residual tumor tissue and a high recurrence rate. Due to their tunable porous structure and high specific surface area, metal-organic frameworks (MOFs) can serve as microwave sensitizers, promoting microwave energy conversion owing to ion collisions in the porous structure of the MOFs. Moreover, iron-based compounds are known to possess peroxidase-like catalytic activity. Therefore, Fe-doped Cu bimetallic MOFs (FCMs) were prepared through a hydrothermal process. These FCM nanoparticles not only increased the efficiency of microwave-thermal energy conversion as microwave sensitizers but also promoted the generation of reactive oxygen species (ROS) by consuming glutathione (GSH) and promoted the Fenton reaction to enhance microwave dynamic therapy (MDT). The in vitro and in vivo results showed that the combination of MWA and MDT treatment effectively destroyed tumor tissues via microwave irradiation without inducing significant side effects on normal tissues. This study provides a new approach for the combined application of MOFs and microwave ablation, demonstrating excellent potential for future applications.

Prognostic value of des-γ-carboxyprothrombin in patients with AFP-negative HCC treated with TACE.

In patients with AFP-negative hepatocellular carcinoma (HCC), des-γ-carboxyprothrombin (DCP) is an important prognostic indicator for the preoperative assessment of transarterial chemoembolization (TACE). However, the association between the serum DCP levels and the degree of progression and prognosis of patients with AFP-negative HCC treated with TACE has not been thoroughly investigated to date, and the molecular mechanism is also unclear. The present study retrospectively analyzed the clinical data of 107 patients with AFP-negative HCC treated with TACE and divided them into two groups based on the median serum DCP levels. The association between DCP and the clinical characteristics of the patients was analyzed, and the survival data were analyzed using Kaplan-Meier curves and Cox regression models. The results demonstrated that the median follow-up time was 755 days (range, 64-1,556 days), and patients in the low-DCP group (n=11; 20.8%) had a lower mortality rate than those in the high-DCP group (n=20; 37.0%). Cox multivariate regression analysis suggested that preoperative lymph node metastasis [hazard ratio (HR), 3.903; 95% CI, 1.778-8.519; P=0.001] and DCP group (HR, 2.465; 95% CI, 1.038-5.854; P=0.041) were independent risk factors. Furthermore, the Gene Expression Omnibus database was utilized to screen differentially expressed mRNAs. Enrichment analyses were then performed, and a protein-protein interaction (PPI) network was constructed to identify hub genes. A total of 169 differentially expressed genes were screened. Enrichment analyses revealed that cancer-related and ribosomal pathways were significantly enriched. Furthermore, 10 hub genes were identified in the PPI network by counting the number of gene interactions, the majority of which belonged to the ribosomal protein (RPS) family, and the top three significant genes were RPS23, RPS11 and RPS3A. In patients with AFP-negative HCC, higher serum DCP levels were associated with poor prognosis after TACE. This may be associated with genes such as those belonging to the RPS family, which may contribute to future personalized therapy for this disease.

Surgical management of spontaneous middle cranial fossa defects: a systematic review and meta-analysis of available reconstructive techniques and materials.

Different materials and techniques have been proposed for surgical repair of spontaneous middle cranial fossa (MCF) defects. However, conclusive evidence supporting their selection and impact on clinical outcomes is lacking. The study aims to conduct a systematic review and meta-analysis on materials and techniques employed to repair MCF defects and evaluate complications and rates of recurrent cerebrospinal fluid (CSF) leaks. A PRISMA-guided systematic review and meta-analysis were performed using MESH terms and specific keywords including studies published before May 2022. Primary outcomes included recurrence of CSF leak and complication rates by type of reconstructive material and technique utilized. Meta-analyses of proportions were performed using random effects and confidence intervals for individual proportions were calculated using the Clopper-Pearson method. Twenty-nine studies were included (n = 471 cases). Materials employed for repair were categorized according to defect size: 65% of defects were of unknown size, 24% were small (< 1 cm), and 11% were large (≥ 1 cm). Rigid reconstruction (RR) was significantly favored over soft reconstruction (SR) for larger defects (94% of cases, p < 0.05). Complications and recurrent CSF leak rates of SR and RR techniques were comparable for defects of all sizes (p > 0.05). Complication rates reported for these procedures are low regardless of technique and material. RR was universally preferred for larger defects and analysis of complication and recurrence rates did not reveal differences regardless of defect size. While RR was more frequently reported in smaller defects, SR was used by several centers, particularly for smaller MCF floor defects.

A Cost-Effective and Reproducible Cadaveric Training Model for Internal Carotid Artery Injury Management During Endoscopic Endonasal Surgery: The Submersible Peristaltic Pump.

BACKGROUND: Internal carotid artery injury (ICAI) represents one of the most challenging complications in endoscopic endonasal neurosurgery and its rarity results in limited opportunities for trainees and surgeons to achieve proficiency in its management. Currently, available models for ICAI have employed costly systems that prevent their widespread use. The objective of this study is to validate an affordable submersible peristaltic pump (SPP)-based model as a reproducible and realistic paradigm for ICAI management training. METHODS: A laceration of the left parasellar internal carotid artery was purposely carried out in 2 human cadaveric heads. A blood substitute was perfused to ensure a perfusion flow of 1 L/min using an affordable SPP. A cohort of 20 neurosurgery and otolaryngology residents, fellows, and attendings were enrolled to evaluate the realism and content validity of the model using a validated 5-grade questionnaire. RESULTS: The model proved to mimic a real intraoperative scenario of ICAI with an expected output flow of 1 L/min. Questionnaire responses reported a realistic experience and the impact of this model on improving trainee surgical coordination and capability to rehearse the most accepted repair technique. The use of a fixed noninjected head allowed the reproducibility of the training session without the additional cost of new fresh-frozen heads. The affordable SPP allowed an impactful reduction of ICAI model training expenses maintaining high realism. CONCLUSIONS: The SPP-based ICAI model with noninjected cadaveric specimens is an affordable and cost-effective system that allows reproducibility and realism. These qualities favor greater adoption in neurosurgery and otolaryngology training curricula.

Novel prognostic signature based on HRAS, MAPK3 and TFRC identified to be associated with ferroptosis and the immune microenvironment in hepatocellular carcinoma.

OBJECTIVES: Ferroptosis, a programmed cell death, has been recognized recently. Several studies have shown the connection between ferroptosis and biological processes in cancer. However, the potential role and mechanism of ferroptosis-related genes in hepatocellular carcinoma (HCC) remain unclear, and understanding the crosstalk between the tumor immune microenvironment and ferroptosis is still a great challenge. METHOD: We retrospectively analyzed the transcriptomic and clinical data of HCC from TCGA database. 74 ferroptosis-related genes (FRGs), including 14 immune-ferroptosis-related genes (IFRGs), were identified with differential expression in tumor and normal tissues. Then, we screened and constructed a prognostic signature using survival analysis and the least absolute shrinkage and selection operator. Furthermore, we validated the performance of the signature for assessing survival prognosis and clinicopathological staging. In addition, we investigated the link between the prognostic features and tumor-infiltrating immune cells using CIBERSORT. RESULT: The results identified HRAS, MAPK3 and TFRC as prognostic IFRGs. The risk score was elevated when IFRGs were upregulated and patient outcomes worsened. In addition, the results show significant differences in tumor-infiltrating immune cells, especially immunosuppressive cells, including tumor-infiltrating macrophages cells and regulatory cells, implying that the expression of these three IFRGs may be an intrinsic barrier to strong ferritin-induced immune responses. Enrichment analysis revealed crosstalk between ferroptosis and tumor immunity. The effect of the risk score was validated in the ICGC cohort and the Human Protein Atlas database confirmed the high expression of IFRGs in tumor tissue. CONCLUSIONS: In our study, these IFRGs may provide some new ideas for the study of ferroptosis and the tumor immunity. These findings may also provide new strategies for treatment of HCC.

Exoscope-Assisted Middle Cranial Fossa Approach for Repair of Tegmental Defects: A Cadaveric and Clinical Study.

BACKGROUND: Recent studies highlighted how exoscopes may be employed to approach the lateral skull base. The use of exoscope-assisted procedures to repair middle cranial fossa (MCF) defects has not been fully explored. The surgical microscope in the same circumstances has been associated with relevant limitations, such as its physical obstruction, among others. The aim of this study was to present a proof of concept of exoscope-assisted surgery for MCF defects. METHODS: A detailed step-by-step MCF approach was performed on 2 alcohol-preserved, latex-injected cadaveric specimens under exoscopic magnification. An illustrative clinical case of encephalocele secondary to a spontaneous tegmen tympani defect repaired via an exoscope-assisted MCF approach was presented. RESULTS: The most common sites of MCF defects, the tegmen tympani and the arcuate eminence, were successfully exposed under exoscopic magnification. Dissection was easily performed; no damage to the dura mater or to vascular or neural structures occurred. In the clinical case, the exoscope-assisted technique demonstrated adequate maneuverability and magnification quality. After localization, the encephalocele was resected, and the MCF defect was repaired. The surgeon's position was comfortable, and operative time was not prolonged. CONCLUSIONS: The exoscope allows adequate exposure of the MCF floor with identification and preservation of key anatomical structures. The exoscope represents a valuable alternative to the microscope in reconstruction of MCF defects, offering high-quality magnification and proven maneuverability.