Citations

BACKGROUND AND OBJECTIVES: Intraneural ganglion cysts (IGCs) can arise in different nerves but are uncommon in the tibial nerve (TN) and its branches near the ankle. According to the unified articular theory, a joint connection is always present in IGCs. This study aimed to identify joint connections of tibial-region IGCs and characterize their clinical, radiological, and propagation patterns. METHODS: A prospectively collected international database of >1100 IGCs was reviewed to identify tibial and medial plantar nerve (MPN) and lateral plantar nerve (LPN) IGCs around the ankle. RESULTS: Sixty-two ankle region IGCs were identified: 29 involving the TN (46.8%), 25 the MPN (40.3%), and 4 the LPN (6.4%); in 4 cases, the parent nerve was indeterminate. Thirty-one (50%) cases demonstrated joint connections. Of these, all TN at/distal to the tarsal tunnel (n = 4/4, 100%), MPN (n = 16/16, 100%) and LPN IGCs (n = 2/2, 100%) had a connection to the subtalar (ST) joint. A tibial IGC just proximal to the tarsal tunnel was connected to the tibiotalar (TT) joint in 75% of cases (n = 3/4) and the ST joint in 25% of cases (n = 1/4). Surgical ligation/disconnection of the articular branch was associated with markedly lower recurrence (0/13, 0%) compared with incision or resection of cyst without ligation (8/29, 27.6%; P = .04). CONCLUSION: Our findings support the unified articular theory. All IGCs in the ankle primarily ascend. Two distinct propagation patterns emerged: (1) those that ascend and enter the parent nerve proximal to the tarsal tunnel continue to ascend in the leg, without affecting the plantar nerves, and (2) those that ascend and enter the parent nerve at/distal to the tarsal tunnel have the potential to undergo crossover at the TN bifurcation and subsequently descend down the plantar nerves seen only in ST-origin cysts. Recognizing these pathways enhances diagnostic accuracy, directs identification of the joint of origin, and guides articular branch disconnection to reduce recurrence.

Abstract Aims Pulsed field ablation for atrial fibrillation offers shorter procedural times and improved safety compared with thermal ablation, but the optimal anaesthesia strategy remains uncertain. Most centres in the USA use general anaesthesia with endotracheal intubation, whereas monitored anaesthesia care without endotracheal intubation may be a safe and efficient alternative. Objectives To compare procedural efficiency and safety between monitored anaesthesia care and general anaesthesia for pulsed field ablation. Methods and results Consecutive adults who underwent pulsed field ablation for atrial fibrillation between 2024 and 2025 at Marshfield Clinic Health System were included. The anaesthesia approach was determined by operator preference. Procedural times, medication use, complications, and patient tolerance were recorded prospectively. Among 200 patients, 100 received monitored anaesthesia care without endotracheal intubation, and 100 received general anaesthesia. The mean age was 67 years, 42% were female, and the mean body mass index was 33 kilograms per square metre. Monitored anaesthesia care shortened case duration (77 vs. 95 min; P < 0.001) and laboratory time (118 vs. 153 min; P = 0.002) and required fewer adjunct medications (P < 0.001). Twenty-five procedures (25%) were challenging due to cough or motion but were all completed safely. Complications occurred in one monitored anaesthesia care case and six general anaesthesia cases (P = 0.054). Pulmonary vein isolation was achieved in all patients. Conclusion Monitored anaesthesia care without endotracheal intubation was safe, efficient, and resource-sparing compared with general anaesthesia for pulsed field atrial fibrillation ablation.

Abstract Context Incidental thyroid findings (ITFs) are increasingly detected on imaging performed for non-thyroid indications. Their prevalence, features, and consequences remain undefined. Objective To develop, validate, and deploy a natural language processing (NLP) pipeline to identify ITFs in radiology reports and assess their prevalence, features, and clinical outcomes. Design Retrospective cohort study. Setting Mayo Clinic sites (Rochester, Arizona, Florida, Mayo Clinic Health System). Participants Adults without prior thyroid disease undergoing thyroid-capturing imaging from July 1, 2017, to September 30, 2023. A transformer-based NLP pipeline identified ITFs and extracted nodule characteristics from image reports from multiple modalities and body regions. Outcomes ITF prevalence, downstream thyroid ultrasound, biopsy, thyroidectomy, and cancer diagnosis. Logistic regression identified demographic and imaging-related factors. Results Among 115 683 patients (mean age, 56.8 [SD 17.2]; 52.9% women), 9077 (7.8%) had an ITF (92.9% nodular). ITFs were more likely in women, older adults, higher BMI, and in imaging ordered by specialties different from Emergency Medicine. Compared with chest CT, ITFs were more likely via neck CT, PET, and nuclear medicine scans. Nodule characteristics were poorly documented, with size reported in 44% and other features in fewer than 15%. Compared with patients without ITFs, those with ITFs had higher odds of thyroid nodule diagnosis (OR 45, 95%CI 41.1-49.3), biopsy (OR 46.8, 95%CI 39.0-56.2) thyroidectomy (OR 55.8, 95%CI 31.3-99.3), and thyroid cancer diagnosis (OR 61.7, 95%CI 38.6-98.5). Most cancers were papillary (88.5%) and larger when detected after ITFs (2 cm SD 1.4) vs no ITF (1.3 cm SD 0.8). Conclusion ITFs were common and strongly associated with cascades leading to the detection of small, low-risk cancers, highlighting their role in overdiagnosis and the need for standardized reporting and more selective follow-up.

Abstract Background Capillary self-collection (CSC) devices allow patients to collect blood samples at home, potentially reducing outpatient phlebotomy visits. This study aimed to (a) assess the patient experience with multiple commercially available CSC devices; (b) determine which laboratory tests are commonly ordered together, which could reduce the need for appointments; and (c) evaluate the analytical performance of these tests using CSC samples. Methods User experience for 3 CSC devices was evaluated. Clinical feasibility was determined by comparing test results in paired sera collected by venipuncture (VP) and CSC devices. VP samples were centrifuged within 2 h and tested immediately. CSC sera were centrifuged and tested both immediately and after delayed processing to simulate shipping temperature extremes (−20°C or 40°C). Basic metabolic panel, lipid panel, thyroid function cascade, and prostate-specific antigen were evaluated. Differences between VP and CSC collections were characterized according to their statistical and clinical differences. Results Patients reported CSC devices were easy to use and painless. Clinically significant differences between VP and CSC sera processed immediately were limited to potassium and bicarbonate. Following delayed processing of CSC serum samples (48 h at room temperature), clinically significant differences in potassium, bicarbonate, and glucose were observed. Frozen samples could not be analyzed. A 48 h delay at 40°C caused clinically significant differences in all analytes except creatinine, lipid panel, prostate-specific antigen, and the thyroid cascade. Conclusion Potassium, bicarbonate, and glucose were not stable at room temperature in CSC sera. CSC serum specimens may be a viable option but require analyte-specific evaluation and consideration of transportation conditions.

ABSTRACT Background Older adults experience age‐related physiological changes that alter the pharmacokinetics and pharmacodynamics of certain medications, which may necessitate reduced dosing. Our objective was to assess emergency department (ED) and hospital outcomes of older patients administered opioids by emergency medical services (EMS) clinicians. Methods Retrospective cohort study of adults ≥ 65 years who received an opioid between 2019 and 2024 within a health system‐affiliated EMS agency. We excluded patients with an advanced airway and those with no documented weight. Maximum single and cumulative weight‐based opioid dosages were classified as low, therapeutic, or high. Outcomes were measured in the ED/hospital and compared using Poisson regression with Huber/White standard errors, adjusted for age, sex, vitals, Glascow Coma Scale, emergency severity index, and chief concern. Results were reported as adjusted risk ratios (aRRs). Results A total of 6406 patients, including 747 (11.7%, 95% CI: 10.9–12.5) with a high opioid dose, 3663 (57.2%, 95% CI: 56.0–58.4) with a therapeutic dose, and 1996 (31.2%, 95% CI: 30.0–32.3) with a low dose, were included. Receipt of a high maximum single opioid dose versus a low/therapeutic dose (excluding patients receiving a concomitant sedative) was associated with increased risk of altered responsiveness (aRR = 1.28, 95% CI: 1.03–1.58) and delirium (aRR = 2.43, 95% CI: 1.08–5.45) in the ED/hospital setting. When 311 (4.9%) patients who received a concomitant sedative were included, patients who received a high opioid dose similarly had an increased risk of altered responsiveness (aRR = 1.28, 95% CI: 1.06–1.56) and delirium (RR = 2.65, 95% CI: 1.25–5.59), compared to a low/therapeutic dose. There was no difference in outcomes of hypoxia, death within 30 days, or ED length of stay between dose groups. Conclusion Prehospital administration of high opioid doses to older patients was associated with increased rates of altered responsiveness and delirium. These findings highlight how out‐of‐hospital care can impact a patient's ED and hospital course.

Summary Functional high‐risk (FHR) multiple myeloma (FHRMM) is often defined as progression within 12–24 months of front‐line autologous hematopoietic stem cell transplantation (AHSCT). For patients with early progression after suboptimal front‐line therapies, it is challenging to assign the disease progression to a true FHR phenotype versus less effective front‐line therapy. In this study, we combined data from three Center for International Blood and Marrow Transplant Research studies (MM18‐02, MM19‐01 and MM20‐03). We included patients who received front‐line AHSCT between 2008 and 2018 and had progression <12 (FHR12, n = 465), <18 (FHR18, n = 672) or <24 months (FHR24, n = 853) after AHSCT. We classified induction therapy as standard lenalidomide‐containing triplets (bortezomib, lenalidomide, dexamethasone [VRD]/carfilzomib, lenalidomide, dexamethasone [KRD]) versus other (bortezomib, thalidomide, dexamethasone [VTD]/bortezomib, cyclophosphamide, dexamethasone [VCD]/bortezomib, dexamethasone [VD]/lenalidomide, dexamethasone [RD]) and studied the impact of front‐line therapy on post‐FHR overall survival (OS). In the FHR12 cohort (follow‐up 48 months), the OS after VRD/KRD ( n = 238) was 21 versus 17 months with other regimens ( n = 227, hazard ratio [HR] = 1.2, 95% confidence interval [CI]: 0.6–1.06). In a multivariable model, the HR for OS was 0.94 (95% CI: 0.7–1.3, p = 0.69) for VRD/KRD versus other regimens. There was no significant interaction between type of first‐line (1L) therapy and time from 1L AHSCT to first relapse in predicting OS. Similar results were seen for FHR18 and FHR24. FHRMM remains a negative prognostic factor irrespective of front‐line therapy and warrants consideration of T‐cell engagers' second‐line therapy.

ABSTRACT Background Retrospective evaluations of multidisciplinary team (MDT) review of pancreatic cystic lesions (PCL) demonstrate improved PCL management. Endoscopic ultrasound (EUS) evaluates PCL for worrisome features; however, its influence on MDT is unclear and may be attenuated by anchoring/confirmation bias. We aimed to evaluate the impact of EUS and the overall performance of MDT evaluation of PCL. Methods Four mock MDT sessions at two institutions were presented imaging from 40 consecutive PCL cases (20 “high‐risk” with advanced neoplasia, 20 “low‐risk” with pathologic low‐grade dysplasia or ≥ 3 years of non‐progression on surveillance), with and without upfront EUS/FNA (cytology, CEA, Amylase), in a randomized, crossover design. Group 1 adjudicated without EUS, Group 2 adjudicated with EUS, and Group 3 adjudicated with EUS after initially adjudicating without it. Results The cohort included branch‐duct ( n = 20), mixed type ( n = 6), and main duct ( n = 4) IPMN, MCN ( n = 5), and non‐mucinous PCL ( n = 5). Group 2 (EUS) correctly identified mucinous PCL with 97% sensitivity and 70% specificity, significantly higher than Group 1 (No EUS) (Sensitivity 91%, Specificity 20%; p = 0.04). Group 3 (Unblinded to EUS) performed significantly worse in mucinous PCL identification compared with Group 2, indicating cognitive bias (Sensitivity 97%, Specificity 10% ( p = 0.0003)). Group 2 correctly identified high‐risk PCL that required surgical intervention with 85% sensitivity and 85% specificity, significantly higher than Group 1 (Sensitivity 60%, Specificity 75%; p = 0.0016) and Group 3 (Sensitivity 73%, Specificity 80%, p = 0.0485). Conclusion While susceptible to cognitive bias, EUS significantly improves MDT assessment of PCL. MDT establishes a high bar for iterative additions of biomarkers to PCL analysis.

ABSTRACT IDH-mutant astrocytomas maintain telomeres through the alternative lengthening of telomeres (ALT) pathway, producing extreme inter-arm telomere length heterogeneity, yet how this heterogeneity shapes structural genome evolution remains unknown. Using Oxford Nanopore long-read sequencing of 20 IDH-mutant astrocytomas, we profiled structural variants (SVs), copy number variants, extrachromosomal DNA (ecDNA) and measured allele-specific telomere lengths from individual long reads. We identified pervasive complex rearrangements, including chromothripsis and foldback events consistent with breakage-fusion-bridge cycles, and widespread ecDNAs. SV breakpoints were enriched at telomeric and centromeric regions regardless of local telomere length, revealing constitutive structural fragility. Arm-level telomere length analysis uncovered a dual-mode model: arms with short telomeres preferentially harbored breakage-associated events, while arms with long ALT-maintained telomeres were enriched for ecDNA and amplification-associated events. These findings identify chromosome-arm-specific telomere length as a determinant of structural genome evolution in ALT-driven tumors.

Abstract Purpose: Neurocognitive and endocrine dysfunction are potential complications of cranial irradiation. However, risk factors are poorly understood, impeding accurate prognostication and exploration of potential preventive interventions. The objective of this study was to evaluate the prognostic value of various vascular and genotypic risk factors for the development of radiation-related toxicities. Methods: This single-institution retrospective cohort study included patients with metastatic and malignant primary brain tumors who received cranial irradiation as part of their initial tumor-directed therapy. Demographic and treatment characteristics were collected, as well as putative vascular and genotypic risk factors. Univariate, multivariate, and machine-learning analyses were performed using five pre-specified measures of radiation-related toxicity. The primary outcome was change in mini-mental status exam (MMSE). Results: Eighty patients (53% male, mean age 55.7, 53% primary and 44% metastatic brain tumors) were included. Elevated homocysteine and ApOE4genotype were the strongest predictors of MMSE decline in the multivariate model (OR 3.96 [6.5-200, p<0.001 and 2.85 [1.92-27.6], p=0.004). Elevated homocysteine was associated white matter change on MRI and both physician and patient assessment. ApoE4allele was associated with new endocrine deficiency, and physician assessment. An online nomogram provides risk predictions for each of the five late toxicity outcomes: (https://afranklin22.shinyapps.io/PRMMSERadiationRiskFactors/) Conclusion: Two pre-treatment laboratory values (elevated homocysteine and ApOE genotype) were strongly associated with post-radiation neurocognitive and endocrine dysfunction using a variety of simple but clinically meaningful definitions of dysfunction. Our predictive algorithm can aid clinicians in stratifying baseline risk and should be validated in prospective trials.