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Aberrant internal carotid arteries (ICA) are congenital vascular anomalies that occur from involution of the cervical portion of the ICA, which leads to enlargement of the normally small collateral inferior tympanic and caroticotympanic arteries. The inferior tympanic artery is a branch of the external carotid artery, usually the ascending pharyngeal artery, which extends through the inferior tympanic canaliculus (ITC), a small foramen located along the cochlea promontory. Aberrant ICAs can also be associated with a persistent stapedial artery (PSA), which is an abnormal vessel that arises from the petrous ICA and passes through the obturator foramen of the stapes. An aberrant ICA is a very important anomaly to recognize on imaging. Accurately describing its presence is important to help prevent iatrogenic injury during intervention. It is also important to distinguish an aberrant ICA from a lateralized ICA. The improvement of spatial resolution with photon counting detector (PCD)-CT has been proven to provide higher performance in detection of sub-centimeter vascular lesions compared to conventional energy-integrated detector (EID)-CT. PCD-CT also provides superior visualization of small skull-based foramina such as the inferior tympanic canaliculus, which can aid in more accurately characterizing an aberrant ICA (variant course without ITC involvement).

Background: Artificial Intelligence (AI)-driven Decision Support Systems (DSSs) promise improvements in diagnostic accuracy and clinical workflow efficiency, but their adoption is hindered by inadequate confidence calibration, limited transparency, and poor alignment with real-world decision processes, which limit clinician trust and lead to high override rates. Methods: We developed and validated a dynamic scoring framework to enhance trust in AI-generated diagnoses by integrating AI confidence scores, semantic similarity measures, and transparency weighting into the override decision process using 6689 cardiovascular cases from the MIMIC-III dataset. Override thresholds were calibrated and validated across varying transparency and confidence levels, with override rate as the primary acceptance measure. Results: The implementation of this framework reduced the override rate to 33.29%, with high-confidence predictions (90–99%) overridden at a rate of only 1.7%, and low-confidence predictions (70–79%) at a rate of 99.3%. Minimal transparency diagnoses had a 73.9% override rate compared to 49.3% for moderate transparency. Statistical analyses confirmed significant associations between confidence, transparency, and override rates (p < 0.001). Conclusions: These findings suggest that enhanced transparency and confidence calibration can substantially reduce override rates and promote clinician acceptance of AI diagnostics. Future work should focus on clinical validation to optimize patient safety, diagnostic accuracy, and efficiency.

ABSTRACT The C9orf72 hexanucleotide repeat expansion mutation is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia, but its cell type‐specific effects on energy metabolism and immune pathways remain poorly understood. Using induced pluripotent stem cell (iPSC)‐derived motor neurons, astrocytes, and microglia from C9orf72 patients and their isogenic controls, we investigated metabolic changes at the single‐cell level under basal and inflammatory conditions. Our results showed that microglia are particularly susceptible to metabolic disturbances. While C9orf72 motor neurons exhibited impaired mitochondrial respiration and reduced ATP production, C9orf72 microglia presented pronounced increases in glycolytic activity and oxidative stress, accompanied by the upregulation of the expression of key metabolic enzymes. These metabolic changes in microglia were exacerbated by inflammatory stimuli. To investigate how these changes affect the broader cellular environment, we developed a human iPSC‐derived triculture system comprising motor neurons, astrocytes, and microglia. This model revealed increased metabolic activity in all cell types and highlighted that microglia‐driven metabolic reprogramming in astrocytes contributes to the vulnerability of motor neurons under inflammatory conditions. Our findings highlight the central role of microglia in driving metabolic dysregulation and intercellular crosstalk in ALS pathogenesis and suggest that targeting metabolic pathways in immune cells may provide new therapeutic avenues.

Abstract Uterine fibroids (leiomyomas) and adenomyosis are among the most common benign gynecological conditions affecting women of reproductive age. These disorders are frequently associated with abnormal uterine bleeding, pelvic pain, pressure symptoms on adjacent pelvic organs, and potential infertility. The incidence of fibroids increases as women enter their third and fourth decades of life. In parallel, recent trends in delayed childbearing have further emphasized the need for fertility‐preserving treatment options. Notably, fibroids have a higher prevalence in African‐American women, highlighting a significant disparity in health needs compared to white women. Historically, hysterectomy and myomectomy were considered definitive treatments. However, these procedures carry inherent surgical risks, longer recovery periods, and, in the case of hysterectomy, a complete loss of reproductive potential. Consequently, there is increasing demand for uterus‐sparing, minimally invasive alternatives that provide effective symptom control with lower morbidity and preservation of fertility. Among the evolving treatment options, three image‐guided, minimally invasive therapies have gained particular attention: Uterine Artery Embolization (UAE), Radiofrequency Ablation (RFA), and High‐Intensity Focused Ultrasound (HIFU). Uterine Artery Embolization (UAE), also known as uterine fibroid embolization (UFE), is a well‐established endovascular procedure in which embolic agents are introduced via catheterization of the uterine arteries, inducing ischemia and infarction of fibroids. Performed under conscious sedation or regional anesthesia, UAE has demonstrated significant reductions in fibroid volume and symptom relief in over 80% of appropriately selected patients. All image‐guided techniques are especially beneficial for women who desire uterine preservation, have contraindications to surgery, or wish to avoid major operative interventions. In comparison with UAE, Radiofrequency Ablation (RFA) uses targeted thermal energy to induce coagulative necrosis within fibroid tissue. This approach can be delivered via laparoscopic, transcervical, or transvaginal routes, depending on the platform. The Sonata® System integrates intrauterine ultrasound guidance with energy delivery, enabling precise fibroid targeting with minimal myometrial damage. RFA is associated with shorter recovery and less intraoperative blood loss, though it is more suitable for smaller or fewer fibroids and may be less ideal for extensive disease. Together, these advancements reflect a paradigm shift in fibroid management—driven by demographic trends, racial disparities, patient preferences, and technological innovations—toward evidence‐based, uterus‐preserving therapies tailored to individual patient needs. This article discusses details of each technique including the procedure, benefits and complications and also the impact on particular situations such as pregnancy. Some key points common to each technique are also mentioned.

Abstract Hereditary adult-onset ataxias are a heterogeneous group of phenotypically overlapping conditions, often caused by pathogenic expansions of short tandem repeats. Currently, 18 repeat disorders with a core phenotype of adult-onset ataxia are known. Diagnosis typically relies on sequential PCR-based methods, which are labour-intensive and lack precision. Long-read sequencing (LRS) has the potential to overcome these limitations and is currently implemented and validated in clinical genetics. Using clinical nanopore Cas9-targeted sequencing (Clin-CATS) for parallel in-depth repeat analysis, we evaluated a diagnostic cohort of 513 adult-onset ataxia patients, determining frequencies of all known repeat-associated ataxias except Spinocerebellar ataxia 4 (SCA4), as well as the carrier frequencies for autosomal-recessive disorders, RFC1 spectrum disorder and Friedreich’s ataxia (FRDA). Additionally, phenotypes of patients with established genetic diagnoses were characterized, especially those of patients living with RFC1 spectrum disorder and SCA27B. Repeat-associated ataxias were confirmed in 33.3% of cases, including rare ataxias, such as SCA10, SCA36 and SCA37, alongside as the most prevalent conditions SCA27B and RFC1 spectrum disorder. Potentially pathogenic expansions in FGF14 were identified in an additional 4.7% of patients. Testing of another 347 patients for ZFHX3 expansions linked to SCA4 did not identify any cases. Dual diagnoses were frequent, occurring in 6.4% of patients with repeat-associated ataxia. We confirmed a high RFC1 spectrum disorder carrier frequency (7.2%) and reclassified certain FXN expansions as likely non-pathogenic, resulting in a lower than estimated carrier frequency for FRDA of 0.8%. We also identified novel repeat configurations in several loci and illustrated the high heterogeneity of repeat expansions in RFC1, highlighting it as a potential source of false results when using PCR-based methods. This study underscores the diagnostic advantages of LRS for comprehensive repeat analysis and recommends its adoption as a standard in clinical genetics, replacing Southern blot and PCR-based approaches. Furthermore, based on our findings in a large patient cohort a re-evaluation of existing phenotype-genotype correlations is recommended as well as evaluating additional parameters alongside the repeat length to improve diagnostic precision of repeat analysis.

Achieving negative surgical margins is critical for patient outcomes in breast-conserving surgery (BCS), however positive margins require reoperation in 20% to 40% of cases currently. This study explores design criteria and current barriers and facilitators to margin definition and assessment as part of designing an intraoperative tool for margin assessment during BCS. We conducted observations of nine surgeries by four surgeons at a quaternary medical center. We analyzed the data using the Systems Engineering Initiative for Patient Safety (SEIPS) model to identify barriers and facilitators to margin assessment. We identified 38 barriers and 62 facilitators, which we inductively categorized into dimensions. The dimensions included teamwork, information display design, intraoperative tool use, and tissue characteristics. Teamwork was the most frequently observed dimension, followed by information display design and intraoperative tool use. This study provides insights to support the design of workflow-adaptive solutions and improve margin accuracy and surgical performance in breast oncology procedures.

Summary Introduction Postoperative delirium is a common complication following cardiac surgery. Despite its known impact on patient outcomes, effective preventative strategies remain elusive. We aimed to perform a comprehensive Bayesian network meta‐analysis of randomised controlled trials assessing the effect of pharmacological interventions on the incidence of postoperative delirium. Methods Databases were searched from inception to September 2024. Our search was updated in January 2025. Eligible studies included randomised controlled trials reporting the incidence of postoperative delirium in patients having cardiac surgery treated with pharmacological interventions. Bayesian models were used to estimate risk ratios (RR) and mean differences with 95%CrI through Markov chain Monte Carlo. Interventions were ranked using the surface under the cumulative ranking curve. Sensitivity analyses and grading of recommendations, assessment, development and evaluation assessment were conducted to evaluate the robustness and certainty of evidence. Results Seventy‐nine randomised controlled trials comprising 24,827 patients were included, with 29 pharmacological interventions compared. Dexmedetomidine combined with melatonin was the most effective intervention, reducing the incidence of postoperative delirium compared with placebo (risk ratio 0.31, 95%CrI 0.13–0.69; low certainty). Dexmedetomidine with melatonin also significantly decreased intensive care unit stay (2.4 days, 95%CrI ‐3.50–1.10) and hospital stay (1.32 days, 95%CrI ‐2.09 to ‐0.57). Other interventions, including ketamine and risperidone, showed potential efficacy but with low or very low certainty of evidence. Discussion We identified dexmedetomidine with melatonin as the most effective pharmacological strategy for preventing postoperative delirium following cardiac surgery. Whilst these findings highlight potential benefits, the low certainty of evidence underscores the need for more high‐quality primary evidence.

Background/importance Spinal cord stimulation (SCS) is an established therapy for chronic pain conditions when conventional treatments fail. However, global research implementation varies significantly due to patient demographics, healthcare infrastructure, and economic factors, creating disparities in access that directly impact patient care and public health outcomes. Objective To evaluate the global landscape of SCS research by analyzing patient demographics, geographic distribution, funding sources, and pain conditions treated across chronic pain populations aged 18 years and older, with primary focus on associations between geographic regions and patient age demographics. Evidence review We conducted a systematic literature review and meta-analysis following Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines, searching five major databases through October 2024. Studies from 2000 onward reporting SCS in adults with chronic pain lasting 3 months or longer were included. We included randomized trials, comparative studies, and case series with at least 10 patients, excluding commentaries, reviews, and insurance databases. Findings Analysis of 187 studies revealed heterogeneity in age distributions across geographic regions, with Asian studies showing higher mean ages compared to North America, while European showed lower mean ages. Research concentration was predominantly in high-income regions, with 57% of studies receiving industry funding and significant associations between funding source and geographic origin. Post-surgical pain syndrome-thoracolumbar emerged as the most prevalent condition globally, representing 44.9% of cases. Conclusions Significant associations exist between geographic regions and patient demographics in SCS research, with notable disparities in research concentration highlighting the need for broader investigation in underrepresented areas to optimize global application of this chronic pain management therapy. PROSPERO registration number CRD42025635147.

ABSTRACTBackgroundAchalasia is associated with an increased risk of esophageal cancer; though reported incidence rates vary widely (0.4% to 9.2%) due to differences in demographics, follow‐up duration, and diagnostic methods. This study evaluates the risk of esophageal cancer and Barrett's esophagus (BE) in achalasia using a large national database and a propensity‐matched control cohort.MethodsAchalasia patients were identified utilizing the TriNetX database based on International Classification of Diseases (ICD) and Current Procedural Terminology (CPT) codes for diagnostic procedures and lower esophageal sphincter (LES) directed therapies, including Heller myotomy, peroral endoscopic myotomy, and pneumatic dilation. A matched control group of celiac disease patients was used. A 1‐year lead time was applied to exclude secondary malignant achalasia. Outcomes included the incidence of esophageal cancer and BE, with subgroup analysis in patients following therapy.ResultsAmong 7863 achalasia patients (mean age 58.0, 51.9% female), the esophageal cancer risk was significantly higher than control (risk ratio 2.87, 95% CI: 1.56–5.27, p < 0.001). The absolute risk was low, with 40 cases (0.51%) over a mean follow‐up of 3.18 years. BE risk was also higher in achalasia (risk ratio 1.54, 95% CI: 1.24–1.90, p < 0.001), with 220 cases (2.80%). Subgroup analysis revealed no significant difference in BE risk between POEM and Heller myotomy (risk ratio 1.0, 95% CI: 0.42–2.40, p > 0.99).DiscussionThe elevated cancer risk in achalasia over a short follow‐up period warrants reconsideration of current endoscopic surveillance guidelines, despite the low absolute risk of esophageal cancer and BE.

Summary Among individuals of European Ancestry (EA), genome‐wide association studies (GWAS) have identified single nucleotide polymorphisms (SNPs) and polygenic risk scores (PRSs) associated with non‐Hodgkin lymphoma (NHL) risk. We evaluated subtype‐specific PRSs, based on established EA‐SNPs, in Israeli Jews (IJ) and Palestinian Arabs (PA) and performed a GWAS in the combined ethnic groups to identify new loci. We included three common pathologically confirmed subtypes: diffuse large B‐cell (DLBCL), follicular (FL) and marginal zone (MZL) lymphomas. Controls were frequency matched to cases by age and sex. Among 752 IJ (201—DLBCL; 130—FL; 54—MZL/367—controls) and 593 PA (203—DLBCL; 41—FL/349‐controls), we computed PRSs weighted by EA‐derived effect estimates and used logistic regression models adjusted for confounders. In the combined ethnic groups of IJ and PA, subtype‐specific PRSs were significantly associated with the corresponding subtype, with a 1.69‐fold, 2.21‐fold and 2.26‐fold risk for DLBCL, FL and MZL, respectively; however, these effect sizes were attenuated compared to those reported in EA and varied by ethnicity. In the GWAS of the combined ethnic groups, two novel SNPs in the 6p21.32 locus were associated with DLBCL risk. Additional GWAS studies are needed among Jewish and Arab populations to improve genetic risk prediction for NHL in these ethnic groups.