Citations

BACKGROUND: Left atrial (LA) diverticula are focal outpouchings of the LA wall and may increase ischemic stroke risk. We studied recurrent ischemic stroke in patients with acute ischemic stroke and LA diverticula detected on cardiac computed tomography. METHODS: We used data from a prospective cohort study of patients with acute ischemic stroke undergoing cardiac computed tomography acquired during the acute stroke imaging protocol. Cardiac radiologists systematically assessed the presence and characteristics of LA diverticula, defined as LA wall outpouchings with a length/ostium width ratio >0.5 and length ≥3 mm. We compared recurrent ischemic stroke and functional outcome (modified Rankin Scale) after 2 years between patients with and without LA diverticula, adjusting for age, history of atrial fibrillation and ischemic stroke, and anticoagulation use. RESULTS: Of 447 included patients (median age 72 [interquartile range (IQR), 62–81], 59% male), 126 (28%) had LA diverticula: median length 6 mm (IQR, 4–8), width 5 mm (IQR, 4–7), and volume 113 mm 3 (IQR, 52–254). There was no statistically significant difference in age (median 70 [IQR, 58–79] versus 73 [IQR, 63–81]; P =0.06), sex (64% versus 57% male; P =0.28), history of ischemic stroke (21% versus 17%; P =0.48), atrial fibrillation (11% versus 19%; P =0.09), or baseline National Institutes of Health Stroke Scale score (median 5 [IQR, 2–14] versus 5 [IQR, 3–14]; P =0.54) between patients with and without LA diverticula, respectively. Recurrent ischemic stroke was more common in patients with LA diverticula (18/124 [15%] versus 24/314 [8%], adjusted hazard ratio, 2.01 [95% CI, 1.08–3.77]), and recurrence risk increased with diverticulum volume (adjusted hazard ratio, 1.02 [95% CI, 1.01–1.03] per 10 mm 3 ). Functional outcome was better in patients with diverticula (median modified Rankin Scale score of 2 [IQR, 1–3] versus 3 [IQR, 1–6], adjusted common odds ratio, 0.62, [95% CI, 0.42–0.92]). CONCLUSIONS: LA diverticula are a common finding on cardiac computed tomography in patients with acute ischemic stroke, and the risk of recurrent ischemic stroke was increased in these patients, particularly in those with larger diverticula. Atrial diverticula may be a risk factor for recurrent ischemic stroke. REGISTRATION: URL: https://www.onderzoekmetmensen.nl/nl/trial/50352 ; Unique identifier: NL6413901818.

Cancer continues to be a leading cause of global mortality, necessitating innovative therapeutic strategies to address its complexity and heterogeneity. Protein engineering has emerged as a transformative approach in developing cancer biotherapeutics, enabling the creation of highly specific, potent, and adaptable treatments. This paper provides a comprehensive review of the state-of-the-art in protein engineering, highlighting key techniques such as directed evolution, rational design, and hybrid approaches that underpin the development of monoclonal antibodies, bispecific antibodies, and novel fusion proteins. Case studies of FDA-approved therapies, including engineered monoclonal antibodies like trastuzumab and bispecific T-cell engagers such as blinatumomab, are discussed to illustrate the impact of these advancements. Furthermore, emerging trends, including AI-driven protein design and synthetic biology applications, are explored alongside their potential to revolutionize future cancer treatments. Challenges such as immunogenicity, stability, and scalability are critically evaluated, offering insights into potential solutions and future research directions. By synthesizing advancements in protein science and oncology, this paper aims to guide researchers and clinicians in harnessing the full potential of engineered proteins for cancer therapy.

ABSTRACT Left bundle branch block (LBBB) is the most common conduction abnormality following transcatheter aortic valve replacement (TAVR) and has been associated with adverse clinical outcomes. While multiple predictors of post‐TAVR LBBB have been proposed, data remain limited. This systematic review and meta‐analysis aims to identify and summarize predictors of new‐onset LBBB post‐TAVR. A systematic literature search was performed to identify studies that reported predictors of new‐onset post‐TAVR LBBB. Extracted data included patient factors, electrocardiographic (ECG) and anatomic parameters, and device‐related factors. A random‐effects model was used to calculate crude risk ratios (RRs), mean differences, and 95% confidence intervals (CI) of the predictors. Of 450 articles screened, 17 studies comprising a total of 6357 patients were included. Among these, 26.4% developed post‐TAVR LBBB. Increased risk was associated with diabetes mellitus (RR: 1.22, p < 0.001), use of 29‐mm valve (RR: 1.59, p < 0.001), and use of Medtronic CoreValve (MCV) (RR: 2.25, p = 0.008). Significant differences were found between patients with and without LBBB in interventricular septal thickness (IVS; by −0.66 mm), membranous septal length (MSL; by −0.9 mm), left ventricular outflow tract (LVOT) diameter (by −0.48 mm), PR interval (by +13.95 ms), and prosthesis implantation depth (by +2.6 mm). Diabetes Mellitus, use of 29‐mm valve or MCV, decreased IVS thickness, shorter MSL, smaller LVOT diameter, increased prosthesis implantation depth, and prolonged PR duration were all associated with an elevated risk of post‐TAVR LBBB. Early identification of these predictors may help reduce the risk of conduction abnormalities after TAVR.

BACKGROUND Lipomatosis of the nerve (LN) is a rare peripheral nerve pathology characterized by abundant proliferation of fat within the epineurium giving it pathognomonic features on MRI. Any nerve may be affected, but major nerves such as the median and sciatic nerves are most reported. One of the clinical hallmarks of LN is associated bony and soft tissue overgrowth occurring distal to the nerve lesion. While macrodactyly and limb length overgrowth are well known in LN, this study aims to look at nerve territory bony overgrowth affecting the knee. OBSERVATIONS An initial search revealed 59 cases of LN in the Mayo Clinic system. Of 19 patients with LN of the lower limbs, 12 cases involved nerves in the pelvis, buttock, or thigh. Three cases fulfilled the criteria (LN of lower extremity with available MR images and knee radiographs) that affected the femoral, sciatic, and combined femoral/sciatic nerves. Knee radiographs revealed bony overgrowth in the respective nerve territories in each case: anterior, posterior, and both anterior and posterior portions of the knee. LESSONS These illustrative cases of LN with overgrowth of the knee demonstrate that bone overgrowth follows the territory of the associated nerve in LN, which supports the previously published evidence on LN-associated nerve territory overgrowth. https://thejns.org/doi/10.3171/CASE25132

Aberrant internal carotid artery (ICA) is a vascular anomaly in which a segment of the ICA courses through the middle ear. The association of aberrant ICAs and pseudoaneurysm formation is not well known and can be an important finding to recognize on imaging. In this series, we present three cases of aberrant ICAs having asymmetric contour deformities consistent with pseudoaneurysms diagnosed utilizing CT of the temporal bone.

Abstract Clinicians struggle to accurately classify biliary strictures as benign or malignant. Current endoscopic retrograde cholangiopancreatography (ERCP)-based sampling modalities including brush cytology and forceps biopsy have poor sensitivity for pathologic confirmation of malignancy. Cholangioscopy allows for direct visualization and sampling of biliary pathology; however, this technology is also associated with inaccurate classification of biliary disease. Previously, an artificial intelligence (AI) system that analyzes cholangioscopy footage was found to be more accurate in diagnosing biliary malignancy than ERCP sampling techniques. The aim of this study was to validate this AI system on a new series of examinations. Three academic centers collected all available unedited cholangioscopy recordings. The videos were processed by the cholangioscopy AI system. After analyzing videos, the AI system provided predictions as to whether malignancy was present. AI performance in classifying strictures was compared with the performance of brush cytology and forceps biopsy. 112 cholangioscopy examinations (containing 4 817 081 images) were generated from 99 patients. Of those examinations, 61 (54.5%) were for investigation of biliary strictures (31 [50.8%] benign, 30 [49.2%] malignant). For the correct classification of strictures, the AI system was 80.0% sensitive and 90.3% specific. It was also significantly more accurate for stricture classification (85.2%) than brush cytology (52.5%; P<0.001), forceps biopsy (68.2%; P=0.04), and the combination of brush cytology and forceps biopsy (66.7%; P=0.02). A previously developed cholangioscopy AI system was found to continually outperform standard ERCP sampling modalities for accurate identification of malignancy, without additional retraining, in a multicenter validation cohort.