Citations

Abstract Hypoxia constrains cerebral oxygen availability and challenges brain function and stability. Although hypoxia-responsive functional connectivity (HR-FC) reorganizes rapidly with declining arterial oxygen partial pressure, its relationship to local neurovascular activity remains unclear. We examined time-resolved amplitude of low-frequency fluctuations (ALFF) in blood-oxygenation-level dependent (BOLD) fMRI during graded acute hypoxia in healthy adults, performing a continuous cognitive test (Go/No-go task) with concurrent physiological monitoring. Dynamic ALFF and functional connectivity were estimated using a sliding-window approach and analyzed across large-scale brain networks defined by Schaefer’s 17-network parcellation. Severe hypoxia elicited temporally dissociated responses across modalities. Functional connectivity increased monotonically, whereas ALFF exhibited pronounced nonlinear modulation, including phase-dependent divergence across networks. During hypoxic decompensation, the default mode network (DefaultA) showed marked ALFF suppression, whereas a ventral secondary somatosensory-dominant network (SomMotB) exhibited preferential preservation despite similar engagement in HR-FC. Together, these findings indicate that network-level ALFF captures a distinct yet complementary layer of functional dynamics, with a temporal profile distinct from functional connectivity. Spontaneous BOLD dynamics during acute hypoxia reflect structured network-level modulation rather than a uniform suppression attributable solely to reduced oxygen availability. These findings support a conceptual framework of cerebral oxygen budgeting , in which metabolic constraints reshape functional dynamics across brain networks.

Abstract Objectives Patients referred for specialized care often arrive with outside medical records (OMRs) compiled into multi-report PDFs that include imaging, pathology, and clinical notes in unstructured formats. Reviewing these records is time consuming and mentally taxing, increasing the risk of delayed care, clinician frustration, and missed information affecting quality of care. This study aimed to automate the segmentation, classification, and date extraction of scanned OMRs, with a focus on records relevant to breast cancer care. Materials and Methods We used optical character recognition (OCR) to extract machine-readable text from 1303 scanned PDF documents from 116 distinct external institutions. Gemini 1.5, a large language model (LLM), was then used to segment multi-report files into individual documents, classify them into clinically meaningful categories such as mammograms and pathology reports, and extract study dates to build diagnostic timelines. Document categories were informed by clinical workflows in a breast cancer center. Results The system achieved an F1 score of 0.95 for segmentation, 0.96 for classification, and 0.90 for date extraction. In a pilot of 45 records reviewed by clinicians, only 2 classification errors and 1 date error were reported. Clinicians estimated that the tool reduced OMR review time by 40%, improved workflow efficiency, and increased satisfaction. Discussion Our findings demonstrate that combining OCR with LLMs can significantly enhance the processing of unstructured medical records, reducing manual burden and supporting timely clinical decision-making. Conclusion This study demonstrates the successful application of OCR and LLMs for organizing scanned OMRs within a specialty clinic. By automating a previously manual process, the approach supports scalable review of incoming outside records and has potential for adaptation to other clinical workflows. Future work will focus on evaluating the system across additional specialties and institutions.

Abstract Background and Aims Stroke and systemic embolism are recognized but poorly characterized complications of atrial fibrillation (AF) and left atrial flutter (AFL) catheter ablation. Their incidence, outcomes, and procedural associations remain insufficiently defined. Methods Retrospective global registry was initiated by the European Heart Rhythm Association Scientific Committee. A secure database captured data from ablation centres worldwide on general AF and left AFL ablation activity, as well as detailed information on patients with symptomatic embolic events between 2017 and 2024. Results Overall, 204 centres reported 335 743 ablation procedures and 550 embolic events (incidence 0.16%). Centre-level rate ranged from 0% to 3.1%. Most events were cerebral (94%), followed by peripheral (5%), and combined (1%). Coronary air embolism accounted for 62% of all peripheral events. Intraprocedural events occurred in 93 patients (17%), within 72 h in 357 (78%) and beyond 72 h in 100 (22%); 128 cases (23%) were diagnosed after hospital discharge. Nonparoxysmal AF (0.23% vs 0.15%; P < .001), centre experience, and ablation energy source (radiofrequency, 0.16%; cryoballoon, 0.16%; pulsed field ablation, 0.25%; laserballoon, 0.88%; P < .001) were associated with embolic risk. Median NIHSS score after stroke was 4 (interquartile range, 2–9). Three-month follow-up was available for 518 patients with embolism (95%): 181 (35%) had sequelae and 16 (3%) died. Conclusions Symptomatic embolic events are infrequent but associated with significant morbidity and mortality. Most events occur early, though a substantial proportion arise later. Higher event rates were observed with laser and possibly with pulsed field ablation. A greater centre experience was associated with a lower embolism incidence.

Abstract Increased absolute lymphocyte count (ALC) may predict risk of treatment-related mortality and atypical neurologic events among patients receiving chimeric antigen receptor (CAR) T-cell therapies for relapsed/refractory multiple myeloma. In this study, we analyzed the clinical outcomes of patients receiving ciltacabtagene autoleucel (cilta-cel) at the Colorado Blood Cancer Institute, from September 2023 to January 2025. Baseline data were collected pre/post-CAR T-cell therapy. Patients were stratified into preintervention (treated September 2023 to July 2024) and intervention (treated August 2024 to January 2025; those with ALC >5 × 103/μL received 3 days of dexamethasone prophylaxis on first identification of elevated ALC). In the preintervention group, 9 of 30 patients had peak ALC >5 × 103/μL; 5 of 9 (55.6%) experienced atypical neurologic events and all 5 died (cilta-cel therapy-related complications). In the intervention group, 7 of 23 patients had peak ALC >5 × 103/μL and received dexamethasone; 1 of 7 had an atypical neurologic event; and 1 death occured (infectious complication, 9 months posttreatment). Dexamethasone prophylaxis in patients with ALC of >5 × 103/μL resulted in rapid ALC reduction. Overall survival (OS) was significantly lower in preintervention patients with ALC of >5 × 103/μL vs intervention patients with ALC of >5 × 103/μL and patients with ALC of ≤5 × 103/μL (P = .0013). ALC >5 × 103/μL (vs ALC ≤ 5 × 103/μL) was significantly associated with atypical neurologic events (odds ratio, 6.8; P = .0157) and lower OS (hazard ratio, 6.2; P = .0106). In conclusion, ALC >5 × 103/μL after cilta-cel treatment predicted severe early neurologic events and high mortality risk. Dexamethasone prophylaxis demonstrated promise for risk mitigation.

Objective Identifying eligible patients for precision oncology clinical trials is challenging, particularly for rare molecular subpopulations. To address this challenge, A2 Biotherapeutics developed BASECAMP-1 ( NCT04981119 ), a non-interventional master screening study to identify patients eligible for interventional studies of logic-gated Tmod chimeric antigen receptor T-cell therapies. Eligible patients for these interventional trials have an advanced solid malignancy and are germline human leucocyte antigen (HLA)-A*02 heterozygous, with tumour-associated HLA-A loss of heterozygosity (LOH). HLA-A LOH occurs in ~16% of advanced solid malignancies; therefore, an efficient screening strategy is required. This report describes BASECAMP-1; compares the efficiency of two screening methods; and discusses the broader advantages of BASECAMP-1 beyond efficient enrolment. Methods and analysis Patients are identified for BASECAMP-1 using two approaches. In the traditional approach, common for clinical trials, investigators consent and screen all patients who might be good candidates for cell therapy trials, with no prior knowledge of patient HLA-A type or LOH status. To further optimise our approach, we co-developed with Tempus AI (Tempus) the bioinformatic programme Aware, which identifies potentially eligible patients with tumour-associated HLA-A*02 LOH within a clinico-genomic database that includes linked genomic and transcriptomic sequencing and clinical data collected during routine care. Results Over 42 months of using a traditional approach to identify eligible patients, 1918 patients at 13 study sites were consented and screened for BASECAMP-1; of these, 30 patients with tumour-associated HLA-A*02 LOH were enrolled (~0.7 participants per month). Over the last 30 months of that same period, Tempus Aware screening was implemented and 55 patients with tumour-associated HLA-A*02 LOH were enrolled (~1.8 participants per month). The bioinformatic approach identified more patients than the traditional approach and used sequencing results produced as part of the standard clinical tumour sequencing workflow, reducing resource use and study staff burden. Additional advantages of using a screening study, such as BASECAMP-1, include manufacturing efficiencies and collection of a large dataset of molecular and clinical parameters that can be used to supplement trial analyses. Conclusions The BASECAMP-1 study demonstrates a clinico-genomic screening approach can more efficiently identify patients for precision oncology trials. Furthermore, precision oncology can be enhanced through collaborative data-sharing. Trial registration number NCT04981119 .

RET fusions appear in 1%-2% of non–small cell lung cancers (NSCLCs). The results from the ARROW study (ClinicalTrials.gov identifier: NCT03037385 ) supported US Food and Drug Administration approval of pralsetinib, an oral selective RET inhibitor, for metastatic RET -altered NSCLC and RET fusion–positive thyroid cancers. ARROW was a phase I/II open-label study of pralsetinib 400 mg once daily in RET fusion–positive NSCLCs. Coprimary end points were overall response rate (ORR) and safety. Key secondary end points included duration of response, progression-free survival, and overall survival (OS). At data lock (May 20, 2024), 281 patients initiated pralsetinib (median treatment duration, 15.0 months). ORR (measurable disease patients; n = 259) was 78% (95% CI, 69 to 86) for treatment-naïve patients and 63% (95% CI, 54 to 71) for prior platinum-based chemotherapy patients. Median OS was 44.3 months (95% CI, 30.9 to 53.1), 50.1 months (95% CI, 28.3 to not reached) in treatment-naïve patients, and 39.7 months (95% CI, 27.8 to 53.2) in prior platinum patients. Common grade ≥3 treatment-related adverse events were anemia (21%), hypertension (15%), and decreased neutrophils (13%). Three treatment-related deaths occurred (pneumonia, n = 2; interstitial lung disease and rhabdomyolysis, n = 1 each). Safety was consistent with previous ARROW reports; no hypersensitivity was reported in patients receiving prior immunotherapies. Pralsetinib produced robust, durable responses with manageable safety in treatment-naïve and previously treated patients with RET fusion–positive NSCLCs, confirming previous findings with longer follow-up.

ABSTRACT Braak and others have proposed that Lewy body pathology (LBP) in Parkinson’s disease (PD) may arise not only in the brain but alternatively from an initial site in the gastrointestinal (GI) tract with subsequent passage to the central nervous system CNS through the vagus nerve or other routes. We tested this hypothesis by using both immunohistochemistry (IHC) and RT QuIC a form of alpha synuclein seed amplification assay (SAA) to detect alpha synuclein LBP in samples from selected brain regions and 10 GI tract sites taken from autopsies of 50 PD subjects and 128 elderly subjects without parkinsonism or dementia including 34 with IHC identified CNS incidental Lewy body disease (ILBD) and 94 with no Lewy body IHC pathology detected (NLB). A positive SAA or IHC result was restricted to the GI tract in only 2 subjects while LBP by either SAA or IHC was restricted to the brain in 11 subjects. To fairly compare GI-only with brain-only synucleinopathy, however, we would have to do SAA on brain samples from all ILBD and NLB cases in at least 4 critical brain regions: olfactory bulb, medulla, pons, and amygdala. Further SAA of brain regions is estimated, based on the proportional results to date, to potentially identify 21 additional brain-only LBP subjects, for a total of 32, if it were done on all of the NLB subjects. From this brain-only LBP is estimated to be 16 times more common than GI-only LBP. To assess the clinical impact of SAA-positive GI sites we found that the number of positive sites per subject is significantly correlated with UPDRS motor score and SCOPA-AUT GI related scores including those for salivation, straining, constipation, and bowel movement.

PURPOSE Limited access to high-speed internet (broadband [BB]) may pose challenges to video telehealth visit (VTV) utilization. This study explored barriers, facilitators, and attitudes toward VTV adoption in patients with cancer residing in low-BB settings. METHODS We examined a cohort of patients with cancer receiving longitudinal care at Mayo Clinic Cancer Practice in the Upper Midwest. Eligible patients had ≥6 in-person visits during July 2020-October 2022, received oncology care at Mayo Clinic sites, were alive at sampling, and resided in low-BB areas defined by Federal Communications Commission data as 0 or 1 internet service provider offering <25 Mbps. We enrolled 24 participants stratified into two groups: (1) Transitioned users (TUs): adopted VTVs postpandemic (November 2022-December 2023); (2) persistent nonusers (PNUs): received exclusively in-person visits. Semistructured telephone interviews were conducted in June 2024 and thematically analyzed. RESULTS The average age of participants was 71.3 years (range, 42-88), 50% was female, and all identified as White. Three themes emerged: (1) Structural and clinical constraints—physical examinations, laboratory testing, and chemotherapy administration were viewed as requiring in-person care, whereas VTVs were perceived acceptable for routine follow-ups; (2) Skills and experience—digital literacy was generally adequate, but confidence and direct exposure to VTV distinguished TU from PNU; (3) Motivations—both groups preferred in-person care for cancer-related emotional reassurance. TU cited weather, travel burden, and proactive provider offering as adoption triggers, whereas PNU reported that VTV was rarely offered. TU focused on system-level solutions, whereas PNUs preferred individual-level resources. CONCLUSION Differential VTV adoption in low-BB settings reflected exposure, provider offering, and situational necessity rather than BB access alone. Oncology practices should consider normalizing the hybrid care model combining in-person and video appointment visits and provide tailored supports to advance equitable telemedicine. Expanding video care in oncology requires more than digital access and depends on patient experience, care context, and human connection inherent in oncology care.