Citations

Purpose: Cutaneous squamous cell carcinoma has a propensity for perineural invasion. Treating perineural spread has involved surgery and adjuvant chemoradiation, and more recently, immune checkpoint inhibitors. This study aims to evaluate motor and sensory functional outcomes in patients with cranial neuropathies from perineural spread of squamous cell carcinoma, particularly those undergoing immunotherapy. Methods: This was a multicenter case series and literature review. Results: Eighteen patients with cranial neuropathies from perineural spread had a mean age of 72.5 ± 9.7 years. Cranial nerves V and VII were most often involved. Treatments included radiotherapy (8/18; 44.4%), chemotherapy (7/18; 38.9%), and/or immunotherapy (11/18; 61.1%), with many receiving a combination of modalities (8/18; 44.4%). Of those receiving immunotherapy, 72.7% (8/11) demonstrated at least partial clinical and/or radiologic tumor response. Among those with functional outcomes documented, half had improvement in sensory/motor nerve function following immunotherapy (4/8; 50%). A literature review identified 55 articles describing 449 patients total with cranial neuropathies from squamous cell carcinoma perineural spread. Combinations of surgery, chemotherapy, and/or radiotherapy were employed, with immunotherapy used in 16 patients. From 5 patients on immunotherapy with documented functional outcomes, all demonstrated at least some improvement. Conclusion: Immunotherapy plays an evolving role in managing advanced squamous cell carcinoma. Functional improvements in cranial neuropathy were demonstrated in 50% of patients receiving treatment with immunotherapy at a mean of 32.6 months of follow-up. This may hold important implications for the timing of surgical intervention, particularly in the case of cranial nerves V and VII palsies.

Background: Vertebral body tethering (VBT) for adolescent idiopathic scoliosis (AIS) is an alternative to posterior fusion. There are limited prospective, multicenter data available on VBT following US Food and Drug Administration approval. We hypothesize that curve correction on first postoperative standing (first erect, FE) imaging is associated with higher rates of successful correction at final follow-up. Methods: All qualifying patients with AIS who underwent thoracic and lumbar VBT between 2019 and 2022 were prospectively enrolled from 9 institutions. Radiographic and clinical data were compared preoperatively, at FE, and at final follow-up with minimum of 2 years. Success was defined as major curve magnitude of ≤35° at final follow-up and no fusion surgery. Results: One hundred twenty-seven patients were enrolled (79.5% female), with mean follow-up 2.4 years. Mean age at surgery was 12.9 ± 1.4 years, most had bone age of Sanders 4 or lower (93/112, 83.0%). In average, 7.6 ± 1.7 levels were tethered. Mean preoperative major curve magnitude was 50 ± 8°, with mean initial correction at FE of 29 ± 8° (% correction, 39 ± 18%). At final follow-up, mean curve magnitude was maintained at 26 ± 11° (% correction, 45 ± 23%) despite 29% of tether breakage. Patients who had mean FE curve magnitude of ≤35° were 88% successful compared with only 60% in those with >35° on FE (p = 0.0021). Patients showed stable sagittal alignment across all timepoints. Scoliosis Research Society-22 scores improved significantly by 2 years (p < 0.0001). Conclusion: This was the first prospective, multicenter study to assess outcomes of VBT for patients with AIS. VBT shows promise, but optimal results may depend on careful patient selection and surgical technique. FE major curve magnitude of ≤35° was associated with 88% success rate compared with only 60% success for those with poor correction. Level of Evidence: Level II . See Instructions for Authors for a complete description of levels of evidence.

The mammalian lung operates under a biological paradox, requiring architectural fragility for gas exchange while maintaining robust regenerative plasticity to withstand injury. The Hippo signaling pathway has emerged as a central “rheostat” in orchestrating these opposing needs, yet the distinct roles of its downstream effectors remain underappreciated. This review synthesizes recent genetic and mechanobiological advances to propose a “Tale of Two Effectors” model, arguing for the functional non-redundancy of YAP and TAZ. We posit that YAP functions to drive airway progenitor expansion, mechanical force generation, and maladaptive remodeling. Conversely, TAZ—regulated uniquely via transcriptional mechanisms and mechanotransduction—acts as an obligate driver of alveolar differentiation and adaptive repair through an NKX2-1 feed-forward loop. Furthermore, we introduce the “See-Saw” model of tissue fitness, where mesenchymal niche collapse releases the mechanical brake on the epithelium, triggering the bronchiolization characteristic of pulmonary fibrosis. Finally, we extend this framework to malignancy, illustrating how Small Cell Lung Cancer (SCLC) subtypes mirror these developmental and regenerative states. This integrated framework offers new therapeutic distinct targets for modulating tissue fitness and resolving fibrosis.

Background Dual antiplatelet therapy (DAPT) is recommended around carotid artery stenting (CAS) to reduce periprocedural stroke risk. Clopidogrel is widely used, but response variability related to pharmacokinetics and CYP2C19 polymorphisms may limit its effectiveness. Ticagrelor is a more potent, direct acting P2Y12 inhibitor, but its comparative effectiveness in CAS remains uncertain. Methods We conducted a retrospective cohort study in the TriNetX database, identifying adults with carotid artery stenosis who underwent CAS between January 2016 and August 2025 and received either ticagrelor or clopidogrel. Primary outcomes at 180 days included ischemic stroke, major hemorrhage, intracranial hemorrhage, and all cause mortality. Secondary outcomes included inpatient readmission and emergency department (ED) visits. Propensity score matching (1:1), Kaplan–Meier survival, and Cox proportional hazards analysis were used. Results Among 6996 patients, 378 received ticagrelor and 6618 received clopidogrel; aspirin co-use was similar (89.7% vs 91.7%). After matching, 377 patients remained in each cohort. Ischemic stroke (2.7% vs 4.2%; HR 0.56, 95% CI 0.25 to 1.27; P=0.159) and major hemorrhage (2.9% vs 4.8%; HR 0.61, 95% CI 0.29 to 1.30; P=0.197) were numerically lower with ticagrelor. Rates of intracranial hemorrhage were similar (2.7% vs 2.7%; HR 0.61, 95% CI 0.14 to 2.53; P=0.488). Mortality was numerically higher with ticagrelor (3.4% vs 2.7%; HR 1.64, 95% CI 0.68 to 3.97; P=0.263). ED visits were similar (14.3% vs 14.6%; HR 0.97, 95% CI 0.67 to 1.42; P=0.895). Inpatient readmission was numerically lower with ticagrelor (15.9% vs 19.1%; HR 0.81, 95% CI 0.57 to 1.14; P=0.223). Conclusion Ticagrelor and clopidogrel showed comparable safety and effectiveness following CAS. Future prospective genotype informed trials are warranted to confirm these findings.

Abstract Introduction Accurate detection of gene fusions is critical for the diagnosis and management of sarcomas. However, occasional false-negative results may occur due to factors such as low tumor cellularity, limited assay coverage of relevant genomic regions, or mis-annotation by bioinformatic pipelines. We recently encountered a case in which our clinical SARCP fusion detection assay failed to identify an HMGA2::NCOR2 (exon 3–exon 16) fusion. Method The SARCP assay is a targeted, amplicon-based RNA-seq next-generation sequencing (NGS) assay designed to detect gene fusions across 138 genes, including HMGA2. Although NCOR2 is not among the targeted genes, the assay is capable of detecting fusions when only one gene partner is represented. Results Suspicion of a false-negative result arose when the pathologist noted that the tumor’s histologic features—keratin-positive, giant cell-rich soft tissue—were consistent with a subtype previously associated with the HMGA2::NCOR2 fusion. This prompted a review of the bioinformatic output, which had erroneously reported an HMGA2::MAML2 fusion. The misannotation was traced to sequence homology involving a CAA/CAG repeat at the 5′ end of NCOR2 exon 16, likely resulting from DNA polymerase slippage and misalignment in low-complexity, partially complementary repetitive regions. This erroneously lead to the target genomic sequence getting mapped to MAML2 exon 2 as opposed to the NCOR2 exon 16. Discussion This case highlights how bioinformatic mis-annotation can lead to occasional false-negative fusion calls. It underscores the importance of manual review in cases with strong clinical or pathologic suspicion and calls attention to the need for fusion-calling algorithms that better handle repetitive and homopolymeric sequences. Citation Format: Ganesh P. Pujari, Mitch L. Klebig, Kurt S. Willkom, Montha Chhunn, Stefan W. Nelson, Neiladri Saha, Kevin C. Halling. Mis-Annotation of an HMGA2::NCOR2 Fusion in FFPE Sarcoma Samples: A Case Illustrating Bioinformatic Limitations in Fusion Detection [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Fusion-Positive Cancer: From Discovery to Therapy; 2026 Jan 13-15; Philadelphia PA. Philadelphia (PA): AACR; Cancer Res 2026;86(1_Suppl):Abstract nr A012.

Abstract Despite promising results, it remains unclear how to optimally target and personalize closed-loop stimulation to ameliorate deficits in memory and other cognitive functions. We hypothesized that evoked connectivity – the measurement of neural pathway activation using single pulses of electrical stimulation – can guide patient-specific selection of stimulation location and parameters for memory. We characterized brain-wide evoked connectivity profiles of stimulation in memory-related brain regions recorded from 81 patients undergoing intracranial monitoring for epilepsy, showing that greater evoked connectivity between the lateral temporal cortex and the broader memory network (including the mesial temporal lobe, limbic regions and prefrontal cortex) corroborates observations of memory improvement by lateral temporal cortex stimulation. We first found that the lateral temporal cortex, compared to other stimulated regions, evokes the greatest and most distributed connectivity response throughout other memory-related regions. Evoked connectivity in downstream regions is greatest when stimulating a previously identified optimal target for memory improvement, bordering white matter at the rostrocaudal center of the middle temporal gyrus. Evoked connectivity corroborates other biomarkers of memory improvement by closed-loop stimulation, including increased resting-state functional connectivity between stimulated and recorded sites and increased modulation of oscillatory power. These results provide insight into the network mechanisms of stimulation for memory and suggest that evoked connectivity can more broadly predict the functional effects of closed-loop stimulation to prospectively guide targeting and parameter selection.