Citations

Background: Cavotricuspid isthmus ablation (CTI) is a first line therapy in patients with typical atrial flutter. With the advent of Pulsed Field (PF) as a new energy source, we sought to evaluate the use of PF for CTI ablation. A systematic literature search was conducted on the use of PF for CTI-flutter up to December 2024. A meta-analysis was performed for studies reporting pooled data, while a patient-level summary was done for reports with available individual data. The mean number of PF applications, acute success rate, and prevalence of coronary vasospasm were evaluated. Results: Eleven studies with pooled data from 155 patients were included. All patients had an acute block of the CTI. The mean number of PFA applications was 7.78 (95% CI 6.53–9.48). The incidence of ST-elevation was 0.04% (95% CI 0-2.23%). Subclinical vasospasm was documented in 45% (95% CI 32%–59%) of patients who underwent periprocedural coronary angiography. Prophylactic use of nitrates showed a trend toward reducing the incidence of subclinical vasospasm (RR 0.24, 95% CI 0.06–1.06, p=0.059). Twelve cases with patient-level data were included; six reported complications, including ST elevation and conduction disturbances. Conclusion: PFA for CTI flutter demonstrates high acute success; however, evidence regarding the durability of the block is limited. Clinical vasospasm with ST segment elevation is uncommon but can lead to life-threatening complications. The incidence of subclinical vasospasm is high, and nitrates trend toward reducing this phenomenon. To date, the role of PFA for this condition appears to be limited.

Abstract Multimodal artificial intelligence (AI) has the potential to revolutionise healthcare by enabling the simultaneous processing and integration of various data types, including medical imaging, electronic health records, genomic information and real‐time data. This review explores the current applications and future potential of multimodal AI across healthcare, with a particular focus on orthopaedic surgery. In presurgical planning, multimodal AI has demonstrated significant improvements in diagnostic accuracy and risk prediction, with studies reporting an Area under the receiving operator curve presenting good to excellent performance across various orthopaedic conditions. Intraoperative applications leverage advanced imaging and tracking technologies to enhance surgical precision, while postoperative care has been advanced through continuous patient monitoring and early detection of complications. Despite these advances, significant challenges remain in data integration, standardisation, and privacy protection. Technical solutions such as federated learning (allowing decentralisation of models) and edge computing (allowing data analysis to happen on site or closer to site instead of multipurpose datacenters) are being developed to address these concerns while maintaining compliance with regulatory frameworks. As this field continues to evolve, the integration of multimodal AI promises to advance personalised medicine, improve patient outcomes, and transform healthcare delivery through more comprehensive and nuanced analysis of patient data. Level of Evidence: Level V.

Abstract Background Atypical teratoid rhabdoid tumor (ATRT) is a deadly central nervous system embryonal tumor caused by loss of SMARCB1, a core subunit of SWItch/Sucrose Non-Fermentable (SWI/SNF) chromatin remodeling complexes. SMARCB1-deficient cancers are defined by loss of cell differentiation-associated enhancers, but how SWI/SNF interacts with other arbiters of cell differentiation (specifically lineage-specific transcription factors [TFs]) remains poorly understood. Methods We leveraged a multi-omics approach, patient-derived ATRT cells, and patient-derived orthotopic xenografts to investigate the interplay of SWI/SNF with lineage-specific TFs in a clinically relevant setting. Results We observe that an activating protein 1 (AP-1)-dependent transcriptional regulatory network is lost in ATRT, and AP-1 and lineage-specific TFs TEAD1 and ZIC2 require SMARCB1 for enhancer binding. SMARCB1-dependent SWI/SNF integrates transcriptional functions of lineage-specific TFs into a core regulatory circuit that depends on the AP-1 subunit c-JUN, whose expression is determined by a SMARCB1-dependent super-enhancer that is lost in ATRT-MYC. In the absence of SMARCB1, lineage-specific TFs are sequestered to promoters, where they maintain core transcriptional programs necessary for cell survival. Targeting residual, promoter-proximal TF activity by a protein degrader of the SWI/SNF ATPase SMARCA4 or small-molecule inhibitors that indirectly inhibit AP-1 and TEAD activity abrogates expression of these networks, reducing cell viability in vitro and prolonging survival in an orthotopic patient-derived xenograft model. Conclusions These results demonstrate SWI/SNF complexes are critical for lineage-specific TF binding and activity at both promoters and enhancers. In the context of ATRT, these findings reveal a previously underappreciated therapeutic vulnerability in targeting residual promoter-proximal TF function in ATRT.

Abstract Objective Biallelic pathogenic MBOAT7 variants are associated with neurodevelopmental disorders, intellectual disability (ID), epilepsy, and neuropsychiatric disorders such as attention‐deficit/hyperactivity disorder and autism spectrum disorders. We aimed to characterize the epilepsy phenotype in a cohort of patients affected by this syndrome. Methods We describe epilepsy features, electroencephalography, magnetic resonance imaging (MRI) findings, antiseizure treatment response, and neurodevelopment of 15 patients with biallelic MBOAT7 variants. Results All 15 patients had ID or developmental delay (DD). Twelve suffered from epilepsy, with mean age at seizure onset of 36 months (range = 2 months–6.5 years) and 10 of 12 showing signs of DD before seizure onset. Patients with epilepsy presented with focal motor seizures with impaired awareness ( n = 3), focal tonic–clonic seizures and epileptic spasms ( n = 1), focal to bilateral tonic–clonic seizures ( n = 1), unknown onset bilateral tonic–clonic seizures ( n = 2), myoclonic seizures ( n = 4), myoclonic–atonic seizures ( n = 1), atonic seizures ( n = 1), tonic seizures ( n = 1), and myoclonic absences ( n = 2). Seizure freedom was achieved in 66.7% (8/12), with variable antiseizure treatment regimes. We reviewed electroencephalograms of the patients with epilepsy. Background activity was normal in 64%, whereas 36% had either a generalized or a focal slowing. Interictal epileptiform discharges (IEDs) were reported in 83%. Generalized spikes/polyspikes were found in 53%, multifocal IEDs in 23%, and parasagittal focal IEDs in 26%. The most frequent abnormal brain MRI findings, reported in 58% of patients, included high‐intensity signal in T2 and fluid‐attenuated inversion recovery (FLAIR) sequences in dentate nuclei and globus pallidus. Biallelic missense variants seemed to be associated with better cognitive and motor outcomes compared to truncating variants and in‐frame deletions. Significance Biallelic MBOAT7 variants are associated with global developmental impairment in all affected patients and epilepsy in the majority. The seizure semiology is heterogenous. One third of our cohort had persistent seizures despite treatment. The most frequent MRI findings were hyperintensities in T2/FLAIR sequences in dentate nuclei and globus pallidus.

ABSTRACTBackgroundPsychological safety is critical to early and continued engagement with healthcare providers, yet no studies have explored this concept in relationship to cancer care. Black/African American (“Black”) individuals experience disparities in breast and ovarian cancer beyond what can be explained biologically.AimsWe explored factors influencing psychological safety among Black breast and ovarian cancer patients and their family members.MethodsSocioeconomically diverse patients with a personal diagnosis or family history of breast and/or ovarian cancer were invited to complete a semi‐structured qualitative interview on their cancer and healthcare experiences between September 2020 and April 2021. Informed by principles of grounded theory, interview transcripts were qualitatively analyzed for thematic content related to psychological safety.ResultsBlack breast and ovarian cancer patients and their family members described personal and community experiences and structural components of the healthcare system that suggested they may receive differential cancer care due to their race, placing them on guard. This posture was mediated by several self‐identified factors that added to or detracted from their comfort, including provider racial and gender concordance in healthcare, personalized care, and effective communication. The priorities and perceptions of care in participants receiving care in safety net clinics were more focused on what was feasible given resource limitations rather than what was ideally desired.ConclusionsImplementation of strategies to promote psychological safety with Black cancer patients may foster improved patient experiences, as well as encourage early screening, patient engagement, and treatment continuation.

ABSTRACT Background Head and neck squamous cell carcinoma remains challenging due to high recurrence rates and poor survival outcomes. Developing precise technologies for disease burden assessment, treatment response, and minimal residual disease (MRD) surveillance is crucial for improving prognosis. Methods This review explores the potential of liquid biopsy for MRD and recurrence detection. A novel liquid TNM (LiTNM) staging system is introduced, integrating biomarkers from saliva, surgical drain lymphatic fluid (SLF), and peripheral blood. Results Proximal liquid biopsies, particularly saliva and SLF, offer advantages due to their proximity to the tumor microenvironment. Saliva demonstrates high sensitivity in HPV‐associated oropharyngeal cancers, while SLF holds potential in identifying early postoperative recurrence. Despite these advancements, standardization and validation remain challenges. Conclusions Liquid biopsy approaches show promise for postoperative disease monitoring, yet their clinical implementation remains in the early stages. The proposed LiTNM staging system could complement TNM staging by providing a molecular framework for risk stratification. However, rigorous prospective studies are necessary to validate its clinical utility and facilitate adoption.

Diagnosing pulmonary rheumatoid nodules (RN) is challenging because they are rare and share clinical, radiologic, and histopathologic features with other necrotizing granulomatous diseases such as infectious granulomas (IG) and granulomatosis with polyangiitis (GPA). Herein, we revisit the histopathologic features of RN and the findings in the adjacent lung tissue, in comparison with IG and GPA, to identify distinguishing features. Twenty-eight cases with surgically resected RN evaluated at our institution (1991 to 2024), 33 IG (10 mycobacterial infection, 10 histoplasmosis, 13 coccidiomycosis), and 10 GPA cases were included in the study. All available slides with H&E and special stains were reviewed for various histologic parameters within the nodules and in surrounding lung tissue. Many histopathologic features of RN overlap with the necrotizing granulomas seen in infections and GPA. However, some findings in the adjacent lung tissue showed significant differences. The lack of airspace granulomas/non-necrotizing granuloma and the absence of necrotizing vasculitis in the setting of RN can help to differentiate between infection cases and GPA, respectively. Given their considerable overlap, correlation with clinical context, serologic and microbiologic studies, as well as careful evaluation of special stains is crucial in the diagnosis of RN.