Balkan Medical Journal最新文献

Prostate cancer (PCa) is the second most common cancer in men and has a significant health and social burden, necessitating advances in early detection, prognosis, and treatment strategies. Improvement in medical imaging has significantly impacted early PCa detection, characterization, and treatment planning. However, with an increasing number of patients with PCa and comparatively fewer PCa imaging experts, interpreting large numbers of imaging data is burdensome, time-consuming, and prone to variability among experts. With the revolutionary advances of artificial intelligence (AI) in medical imaging, image interpretation tasks are becoming easier and exhibit the potential to reduce the workload on physicians. Generative AI (GenAI) is a recently popular sub-domain of AI that creates new data instances, often to resemble patterns and characteristics of the real data. This new field of AI has shown significant potential for generating synthetic medical images with diverse and clinically relevant information. In this narrative review, we discuss the basic concepts of GenAI and cover the recent application of GenAI in the PCa imaging domain. This review will help the readers understand where the PCa research community stands in terms of various medical image applications like generating multi-modal synthetic images, image quality improvement, PCa detection, classification, and digital pathology image generation. We also address the current safety concerns, limitations, and challenges of GenAI for technical and clinical adaptation, as well as the limitations of current literature, potential solutions, and future directions with GenAI for the PCa community.

Background: Given the growing incidence of pleural effusions and the limited availability of medical thoracoscopy (MT) in clinical practice, ultrasound (US)-guided pleural needle biopsies using Abrams or cutting needles are increasingly being used for the histopathological diagnosis of pleural diseases.

Aims: To assessed the diagnostic yield and safety of US-guided Abrams and cutting needles to determine the optimal needle type for specific clinical situations.

Study design: Prospective randomized study.

Methods: The study included 174 patients with undiagnosed pleural effusion requiring histopathological evaluation. Patients were randomized into two arms: those who underwent US-guided cutting needle biopsy (US-CNPB) and those who underwent US-guided Abrams needle biopsy (US-ANPB).

Results: The US-CNPB group exhibited a false-negative rate of 36.9% and diagnostic accuracy of 63.0%. compared to 21.3% and 78.7% in the US-ANPB group, with significant differences between the groups (p = 0.036 and 0.045, respectively). In patients with pleural thickening < 1 cm or absent on US, US-CNPB exhibited 55.2% diagnostic accuracy and a negative likelihood ratio (-LR) of 0.57. For US-ANPB, the corresponding rates were 77.3% and 0.32. The difference in diagnostic accuracy between the two groups was significant (p = 0.009). In patients with pleural thickening ≥ 1 cm, the diagnostic accuracy of US-CNPB was 93.3% and 88.9% for US-ANPB, with no significant difference between the groups. The corresponding -LR values were 0.08 and 0.17. In patients with pleural thickening < 1 cm, four major bleeding events (6.9%) occurred in the US-CNPB group. No deaths were reported in this study.

Conclusion: US-CNPB should be preferred in patients with pleural thickness ≥ 1 cm on US. MT is recommended for patients with pleural thickening < 1 cm or those presenting with pleural effusion without pleural thickening. However, in the absence of MT, US-ANPB is the preferred alternative because of its superior diagnostic accuracy and procedural safety.

Background: Lattice radiotherapy (LRT) is a novel spatially fractionated radiotherapy technique specifically designed to treat large tumors more effectively. By alternating high-dose and low-dose regions within the tumor, LRT generates a highly diverse dose distribution.

Aims: To review recent literature on LRT to determine its therapeutic efficacy, survival outcomes, and adverse event rates in treating large-volume tumors, thereby strengthening the evidence base for clinical application.

Study design: Systematic review and meta-analysis.

Methods: We conducted a meta-analysis of all relevant LRT studies identified in four databases-PubMed, Embase, the Cochrane Library, and Web of Science-from their inception to September 2024. Only full-text articles were considered eligible. This study adhered to the 2020 PRISMA guidelines.

Results: The meta-analysis included seven single-arm studies comprising 187 patients. The pooled 3-month complete response rate and partial response rate were 36.67% and 42.49%, respectively, while the three-month progressive disease rate was 7.10%. The tumor volume was reduced by 48.95%. According to survival analysis, the pooled 6-month overall survival rate was 79.27%, with a median response time of 4.25 months. The pooled rates of mild and moderate-to-severe adverse events were 19.40% and 3.37%, respectively. LRT has demonstrated high local control rates and a favorable safety profile in managing large-volume tumors.

Conclusion: This is the first systematic meta-analysis examining the efficacy and safety of LRT in treating large-volume tumors. Although further high-quality studies are needed for validation, LRT exhibits encouraging efficiency and safety in patients with large solid tumors exceeding 5 cm in diameter.

Background: The association between the triglyceride-glucose (TyG) index and the occurrence of major adverse cardiovascular and cerebrovascular events (MACCEs) in individuals without diabetes has not been clearly established.

Aims: To investigate the potential of the TyG index to predict MACCEs in a non-diabetic population.

Study design: Prospective cohort study.

Methods: This study analyzed data from 88,946 participants without diabetes, who were divided into four groups based on their TyG index values. The primary outcome was the occurrence of MACCEs, defined as myocardial infarction (MI) or stroke. Multivariable Cox proportional hazards regression models were used to assess the association between the TyG index and MACCEs.

Results: Participants in the higher TyG index quartiles exhibited a greater risk of MACCEs. Moreover, a significant interaction between the TyG index and sex was identified, with a stronger association observed in women than in men. A significant interaction was also found between the TyG index and age in relation to MI risk, indicating a stronger associations in individuals younger than 60 compared to those aged 60 or older.

Conclusion: The TyG index may serve as a useful prognostic marker for MACCEs among individuals without diabetes.

Multiple myeloma (MM) treatment becomes a major challenge once triple-class or penta-refractoriness develops. Emerging immunotherapies, including bispecific antibodies or chimeric antigen receptor (CAR)-T cell therapy, are promising options for such patients. However, the requirement for specialized expertise and staff under stringent manufacturing conditions results in high costs and restricted production. This article explores the manufacturing and clinical application of CAR T-cells in MM, highlighting their potential, limitations, and strategies to enhance efficacy. CAR-T can be manufactured by pharmaceutical companies or accredited academic centers authorized to produce and market gene-edited cellular products. This process includes sequential steps: T cell apheresis from the patient, selection of the cells, activation, gene transfer, expansion of the produced cells, cryopreservation, and reinfusion of the cells into a lymphodepleted patient. While CD3+ T cells are typically employed for CAR-T production in clinical studies, studies have demonstrated the potential advantages of specific T cell subgroups, such as naive, central memory, and memory stem cells, in enhancing efficacy. Following T cell harvesting, the subsequent phase involves genetic modification. CAR-T cells are frequently produced by applying viral vectors such as γ-retrovirus or lentivirus. Although viral vectors are commonly used, non-viral methods-including CRISPR/Cas9 and integrative mRNA transfection methods produced by transposons-are also employed. Five different CAR-T cell generations have been developed. The myeloma-specific targets B-cell maturation antigen (BCMA), signaling lymphocyte activation molecular family 7, and G protein-coupled receptor class C group 5 member D are the most extensively studied in clinical trials. Emerging CAR-T cell targets under investigation include CD138, CD19, kappa light chain, CD56, NY-ESO-1, CD70, TACI, and natural killer G2D. In 2021, idecabtagene vicleucel, a BCMA-targeting agent, became the first CAR-T therapy approved for relapsed/refractory MM, marking a significant milestone in MM treatment. Subsequently, ciltacabtagene autoleucel has also been approved. However, CAR-T resistance is an emerging issue. Resistance mechanisms include T cell exhaustion, antigen escape (loss of BCMA), and tumor microenvironment-related inhibitors. To address these challenges, strategies such as BCMA non-targeted or dual-targeted CAR-T, memory T cells, humanized CAR-T, and rapidly manufactured PHE885 cells have been developed. To enhance specificity, ongoing investigations include bicistronic CAR/co-stimulator receptors, formation of memory-phenotype T cells, combination with immunomodulators or checkpoint inhibitors, armored CAR-T cells, cancer-associated fibroblast inhibitors, and CAR approaches that inhibit exhaustion signals. In conclusion, studies are exploring the use of CAR-T at an earlier stage, including at diagnosis, with an aim to rep

Background: MRP8/14, a calcium-binding protein of the S100 family, is predominantly expressed in myeloid cells and exhibits proinflammatory and prothrombotic properties. Platelet-neutrophil interactions can trigger MRP8/14 release, but their role in atherosclerosis (AS) remains unclear.

Aims: To investigate the effect of MRP8/14 on AS progression and the underlying mechanisms involved, focusing on neutrophil activation and the toll-like receptor 4 (TLR4)-ERK1/2-p90RSK and NRF2-ARE pathways.

Study design: Ex vivo and animal study.

Methods: Neutrophils isolated from mouse bone marrow were stimulated with P-selectin to induce MRP8/14 release, which was subsequently quantified using ELISA. Neutrophil extracellular traps (NET) formation was induced by phobolol 12-myristate 13-acetate, and Mrp8/14 expression was examined via fluorescence labeling. Cytokine release and CD11b expression were assessed using flow cytometry. An AS mouse model was established by administering a high-fat diet. Atherosclerotic plaque size was analyzed using Oil Red O staining. Proteins from the TLR4-ERK1/2-p90RSK and NRF2-ARE pathways were analyzed by Western blotting.

Results: P-selectin induced MRP8/14 release, which was inhibited by P-selectin antagonists. NET formation also contributed to MRP8/14 secretion. hMRP8/14 treatment enhanced CD11b expression, neutrophil adhesion, and proinflammatory cytokine secretion. In AS mice, MRP8/14 secretion was linked to TLR4 upregulation, ERK1/2-p90RSK signaling activation, and NRF2-ARE pathway inhibition. Paquinimod, an MRP8/14 antagonist, mitigated neutrophil activation, inflammation, and arterial plaque formation.

Conclusion: MRP8/14 secreted from neutrophils activates the ERK1/2-p90RSK pathway via TLR4 and suppresses the NRF2-ARE pathway, driving inflammation and promoting AS progression.