Citations

Abstract Aims Syncope remains a diagnostic challenge despite advancements in testing and treatment. Cardiac syncope is an independent predictor of mortality and can be difficult to distinguish from other causes of transient loss of consciousness (TLOC). This paper explores whether artificial intelligence (AI) can improve the evaluation and management of patients with syncope. Methods and results We conducted a literature review and incorporated the opinions of experts in the fields of syncope and AI. The cause of TLOC is often unclear, hospitalization criteria are ambiguous, diagnostic tests are frequently non-informative, and assessments are costly. Patients are left with unanswered questions and limited guidance. Artificial intelligence (AI) has the potential to optimize syncope evaluation by processing large data sets, detecting imperceptible patterns, and assisting clinicians. However, AI has limitations, including errors, lack of human empathy, and uncertain clinical utility. Liability issues further complicate its integration. We present three viewpoints: (i) AI is crucial for advancing syncope management; (ii) AI can enhance the patient experience; and (iii) AI in syncope care is inevitable. Conclusion Artificial intelligence may improve syncope diagnosis and management, particularly through machine learning–based test interpretation and wearable device data. However, it has yet to surpass human clinical judgment in complex decision-making. Current challenges include gaps in understanding syncope mechanisms, AI interpretability, generalizability, and clinical integration. Standardized diagnostic approaches, real-world validation, and curated data sets are essential for progress. Artificial intelligence may enhance efficiency and communication but raises concerns regarding confidentiality, bias, inequities, and legal implications.

OBJECTIVE In the treatment of skull base chordoma (SBC) surgery is considered the mainstay approach, and gross-total resection has an established relationship with progression-free survival (PFS) and overall survival (OS). However, the tumor’s location often interferes with attempts at complete resection. In this case, surgery for maximal resection followed by high-dose radiotherapy has been demonstrated to be the standard treatment. In this context, various modalities are available, yet no consensus exists on the most effective. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of different radiotherapy modalities for SBC. METHODS Following PRISMA guidelines, the authors systematically searched for the treatment of SBC with radiation modalities in the PubMed, Cochrane, Web of Science, and EMBASE databases. Outcomes assessed for each modality were as follows: OS, PFS, local control (LC), and complications. The random-effects model was adopted. A single-proportion analysis with 95% CI was used to measure the effects in single-arm analysis. For the comparative analysis, the OR with 95% CI was used to compare outcome treatment effects. Heterogeneity was assessed using I 2 statistics, and statistical significance was defined as p < 0.05. RESULTS A total of 32 studies comprising 3663 patients, with 2322 patients who were treated with radiotherapeutic modalities, were included. Regarding 5-year OS findings in each modality study, the findings were as follows: in photon fractionated radiotherapy, an estimated rate of 77% (69%–84%, 568 patients); in conventional fractionated radiotherapy, 76% (65%–87%, 517 cases); in proton-based + carbon ion–based radiotherapy, 85% (82%–88%, 622 cases); and in a comparative analysis of proton-based and carbon ion–based therapy, there was an OR of 1.2 (95% CI 0.59–2.43, 306 cases). Regarding the 5-year PFS estimate, the rates were as follows: 35% (26%–45%, 95 cases) for photon fractionated therapy; 35% (25%–45%, 85 cases) for stereotactic radiotherapy; 77% (50%–100%, 180 cases) for proton-based and carbon ion–based radiotherapy; and 74% (45%–100%, 102 cases) for proton-based radiotherapy. Regarding LC in periods of 3 and 5 years after proton- and carbon ion–based therapy, the overall estimated rates were 84% (78%–90%, 326 cases) and 75% (65%–85%, 448 cases), respectively. For proton-based radiotherapy and carbon ion–based therapy, the 5-year LC rates were 76% (67%–86%, 259 cases) and 75% (59%–91%, 189 cases), respectively. CONCLUSIONS The analysis highlights the finding that particle-based modalities like proton beam radiotherapy and carbon ion radiotherapy are the most effective radiation therapies available for the treatment of SBC. Furthermore, it reinforces the idea that surgery followed by radiotherapy constitutes the standard treatment.

Chronic antigen stimulation is thought to generate dysfunctional CD8 T cells. Here, we identify a CD8 T cell subset in the bone marrow tumor microenvironment that, despite an apparent terminally exhausted phenotype (T PHEX ), expressed granzymes, perforin, and IFN-γ. Concurrent gene expression and DNA accessibility revealed that genes encoding these functional proteins correlated with BATF expression and motif accessibility. IFN-γ + T PHEX effectively killed myeloma with comparable efficacy to transitory effectors, and disease progression correlated with numerical deficits in IFN-γ + T PHEX . We also observed IFN-γ + T PHEX within CD19-targeted chimeric antigen receptor T cells, which killed CD19 + leukemia cells. An IFN-γ + T PHEX gene signature was recapitulated in T EX cells from human cancers, including myeloma and lymphoma. Here, we characterize a T EX subset in hematological malignancies that paradoxically retains function and is distinct from dysfunctional T EX found in chronic viral infections. Thus, IFN-γ + T PHEX represent a potential target for immunotherapy of blood cancers.

AimsPatients with Crohn's disease (CrD) have an elevated risk for the development of small bowel adenocarcinomas (SBAs). Actionable isocitrate dehydrogenase 1 (IDH1) mutations have been reported to be more frequent in CrD‐SBAs than in sporadic SBAs. The present study aimed to investigate the clinicopathological and immunophenotypical features, as well as methylation profiles, of IDH1‐mutated CrD‐SBAs.Methods and resultsAn international multicentre series of surgically resected CrD‐SBAs was tested for IDH1 mutation. Clinicopathological features, immunophenotypical marker expression and O6‐methylguanine‐DNA methyltransferase (MGMT) and long interspersed nuclear element‐1 (LINE‐1) methylation were compared between IDH1‐mutated and IDH1 wild‐type CrD‐SBAs. Ten (20%) of the 49 CrD‐SBAs examined harboured an IDH1 mutation and all the mutated cancers harboured the R132C variant. Compared to IDH1 wild‐type cases, IDH1‐mutated CrD‐SBAs showed significantly lower rates of cytokeratin 7 expression (P = 0.005) and higher rates of p53 overexpression (P = 0.012) and MGMT methylation (P = 0.012). All three dysplastic growths associated with IDH1‐mutated SBAs harboured the same IDH1 variant (R132C) of the corresponding invasive cancer, and all were of non‐conventional subtype (two serrated dysplastic lesions and one goblet cell‐deficient dysplasia). In particular, non‐conventional serrated dysplasia was significantly associated with IDH1‐mutated CrD‐SBAs (P = 0.029). No significant cancer‐specific survival difference between IDH1‐mutated CrD‐SBA patients and IDH1 wild‐type CrD‐SBA patients was found (hazard ratio = 0.55, 95% confidence interval = 0.16–1.89; P = 0.313).ConclusionsIDH1‐mutated CrD‐SBAs, which represent approximately one‐fifth of total cases, are characterised by distinctive immunophenotypical features and methylation profiles, with potential therapeutic implications. Moreover, IDH1‐mutated non‐conventional, serrated dysplasia is likely to represent a precursor lesion to such CrD‐SBAs.

AbstractHospitals, payors, and patients increasingly expect us to report our outcomes in more detail and to justify our treatment decisions and costs. Although there are many stakeholders in surgical outcomes, physicians must take the lead role in defining how outcomes are assessed. Skull base lesions interact with surrounding anatomy to produce a complex spectrum of presentations and surgical challenges, requiring a wide variety of surgical approaches. Moreover, many skull base lesions are relatively rare. These factors and others often preclude the use of prospective randomized clinical trials, thus necessitating alternate methods of scientific inquiry. In this paper, we propose a roadmap for implementing a skull base registry, along with expected benefits and challenges.

Platinum-based chemotherapy is the standard of care with concern to first-line systemic therapy for metastatic disease in urothelial cancer (UC). Resistance to chemotherapy despite an initial response is linked with the ability to remove platinum-based DNA adducts and to repair chemotherapy-induced DNA lesions by various DNA repair proteins. The Rad9-Rad1-HUS1 complex that is loaded onto DNA at sites of damage is involved in checkpoint activation as well as DNA repair. Here, we addressed for the first time the potential influence of HUS1 expression in urothelial carcinogenesis (using two human basal urothelial cancer cell lines UM-UC-3 and HT1197) and its role as a potential therapeutic target for predicting responses to platinum-based chemotherapy. Specific inhibition of HUS1 expression in both cell lines was achieved by specific siRNA and validated by Western blot. In order to define the possible importance of HUS1 in the regulation of cellular proliferation, parental and resistant cells were treated with increasing concentrations of either control or HUS1 siRNA. HUS1 protein expression was observed in both human basal urothelial cancer cell lines UM-UC-3 and HT1197. In cisplatin-sensitive cells, knock-down of HUS1 inhibited cellular proliferation in the presence of cisplatin. On the contrary, knock-down of HUS1 in resistant cells did not result in a re-sensitization to cisplatin. Finally, RNAseq data from the Cancer Genome Atlas provided evidence that HUS1 expression is a significant prognostic factor for poor survival in UC patients. In summary, HUS1 may acts as an oncogene in UC and might be a key determinant of the cellular response to cisplatin-based chemotherapy.

Background and Objectives: Knowledge of the incidence and time frames of the adverse events of patients presenting syncope at the ED is essential for developing effective management strategies. The aim of the present study was to perform a meta-analysis of the incidence and time frames of adverse events of syncope patients. Materials and Methods: We combined individual patients’ data from prospective observational studies including adult patients who presented syncope at the ED. We assessed the pooled rate of adverse events at 24 h, 72 h, 7–10 days, 1 month and 1 year after ED evaluation. Results: We included nine studies that enrolled 12,269 patients. The mean age varied between 53 and 73 years, with 42% to 57% females. The pooled rate of adverse events was 5.1% (95% CI 3.4% to 7.7%) at 24 h, 7.0% (95% CI 4.9% to 9.9%) at 72 h, 8.4% (95% CI 6.2% to 11.3%) at 7–10 days, 10.3% (95% CI 7.8% to 13.3%) at 1 month and 21.3% (95% CI 15.8% to 28.0%) at 1 year. The pooled death rate was 0.2% (95% CI 0.1% to 0.5%) at 24 h, 0.3% (95% CI 0.1% to 0.7%) at 72 h, 0.5% (95% CI 0.3% to 0.9%) at 7–10 days, 1% (95% CI 0.6% to 1.7%) at 1 month and 5.9% (95% CI 4.5% to 7.7%) at 1 year. The most common adverse event was arrhythmia, for which its rate was 3.1% (95% CI 2.0% to 4.9%) at 24 h, 4.8% (95% CI 3.5% to 6.7%) at 72 h, 5.8% (95% CI 4.2% to 7.9%) at 7–10 days, 6.9% (95% CI 5.3% to 9.1%) at 1 month and 9.9% (95% CI 5.5% to 17) at 1 year. Ventricular arrhythmia was rare. Conclusions: The risk of death or life-threatening adverse event is rare in patients presenting syncope at the ED. The most common adverse events are brady and supraventricular arrhythmias, which occur during the first 3 days. Prolonged ECG monitoring in the ED in a short stay unit with ECG monitoring facilities may, therefore, be beneficial.

The aims of this study were (1) to identify research publications studying noninvasive electrocardiogram (ECG) monitoring devices, (2) to define and categorize current technology in noninvasive ECG recording, and (3) to discuss desirable noninvasive recording features for personalized syncope evaluation to guide technological advancement and future studies. We performed a systematic review of the literature that assessed noninvasive ECG-monitoring devices, regardless of the reason for monitoring. We performed an Internet search and corresponded with syncope experts and companies to help identify further eligible products. We extracted information about included studies and device features. We found 173 relevant papers. The main reasons for ECG monitoring were atrial fibrillation (n = 45), coronary artery disease (n = 10), syncope (n = 8), palpitations (n = 8), other cardiac diseases (n = 67), and technological aspects of monitoring (n = 35). We identified 198 devices: 5 hospital telemetry devices, 12 patches, 46 event recorders, 70 Holter monitors, 23 external loop recorders, 20 mobile cardiac outpatient telemetries, and 22 multifunctional devices. The features of each device were very heterogeneous. There are a large number of ECG-monitoring devices with different features available in the market. Our findings may help clinicians select the appropriate device for their patients. Since there are only a few published articles analyzing their usefulness in syncope patients, further research might improve their use in this clinical setting.

AbstractSevere aortic stenosis and coronary artery disease often coexist. Coronary angiography (CA) and percutaneous coronary intervention (PCI) can be challenging in patients with prior transcatheter aortic valve implantation (TAVI). Depending on the type and position of the implanted valve, the procedure can be challenging or even unfeasible due to interference of diagnostic catheters and valve parts. The correct positioning of the TAVI prosthesis during TAVI was identified as an important factor with regard to the feasibility of subsequent CA or PCI. TAVI has been also associated with vascular, cerebrovascular and conduction complication. One is rare but life-threatening complication, coronary ostial obstruction. Coronary ostial obstruction can develop, especially if a safety check of more than 10 mm of coronary ostial height is not taken into consideration during TAVI. This complication can cause recurrent episodes of angina and can severely worsen the patient′s cardiac systolic function.