Citations

Abstract Introduction Hypoglossal nerve stimulators (HGNS) are used in patients with moderate-to-severe obstructive sleep apnea (OSA) who are unable to tolerate or do not respond to continuous positive airway pressure (CPAP) therapy. However, a subgroup of patients fail to achieve resolution of OSA with HGNS alone. Previous studies have shown that lower BMI, lower nadir oxygenation, decreased sleep latency, and higher VOTE score on drug-induced sleep endoscopy (DISE) predict better treatment outcome. We hypothesize that baseline diagnostic polysomnography (PSG) may further predict which patients will achieve successful therapeutic outcome with HGNS therapy. Methods We conducted a retrospective analysis of all adult patients who underwent HGNS implantation at Mayo Clinic Arizona between 2019-2025 and had a pre-implantation diagnostic PSG available for review. Treatment success was defined by Sher Criteria: >50% reduction in post-treatment apnea hypopnea index (AHI) to a final AHI of < 20/hr. Responders met Sher criteria and non-responders did not meet Sher criteria. Demographics, sleep questionnaire results, PSG variables, and VOTE score on DISE were collected and analyzed using Spearman’s rank correlation of reduction in AHI. Results Twenty-three patients (11M/12F, median age: 69[IQR:64,75] years) met inclusion criteria. Median baseline AHI was 24[IQR:19,37]/hr. Median post-implant AHI was 8 [IQR:3, 14]/hr. Responders (n=15, 65%) and non-responders (n=8, 35%) demonstrated median post-implant AHI of 4.5[IQR:2.3,7.3]/hr and 15.7[IQR:12.3,28.5]/hr, respectively. Treatment response was associated with less time with SpO2 < 88% (T88%) (21min [IQR:3,64] vs. 73[IQR:36,105mins]; p=0.023) and higher central apnea index (CAI) (1[IQR:0.1,3] vs. 0[IQR:0,1], p=0.03) on pre-implantation PSG. Conclusion In this small cohort of OSA patients, less nocturnal hypoxemia as defined by T88% and higher baseline central apnea index were predictors of better treatment response to HGNS therapy as measured by Sher criteria. We hypothesize that greater nocturnal hypoxemia likely reflects more severe airway obstruction during sleep. Our analysis also showed that responders had higher baseline CAI than non-responders, however we believe this association is not clinically significant and likely driven by one outlier (CAI 13/hr). Further analysis in a larger HGNS cohort is needed to confirm these findings. Data enrichment efforts and more sophisticated analyses are underway. Support (if any)

Abstract Introduction Positive airway pressure (PAP) therapy is the standard treatment for obstructive sleep apnea (OSA); however, its use may be contraindicated in patients with recurrent pneumothorax, particularly in the presence of emphysematous lung disease and bleb formation. Hypoglossal nerve stimulation (HGNS) offers a non–positive-pressure alternative for appropriately selected patients. We describe what is, to our knowledge, the first reported case of successful HGNS therapy in an older adult with severe OSA and multiple recurrent pneumothoraces. Methods An 87-year-old man with severe OSA (baseline AHI 38, predominantly obstructive events) experienced multiple right-sided pneumothoraces beginning in December 2022, several of which were temporally associated with BiPAP use at 17/9 cm H₂O. His episodes required repeated interventions, including chest tubes, thoracoscopy with apical bleb resection and pleurodesis, and several pigtail catheter placements. Chest CT imaging demonstrated emphysema with multiple blebs, raising concern for the safety of continued PAP therapy. A mandibular advancement device was deemed inappropriate due to disease severity. The patient’s BMI was 27 kg/m2. HGNS was considered a suitable alternative. Results HGNS implantation was completed without complications. At activation, both the sensation and functional thresholds measured 0.8 V, with excellent tongue protrusion and waveform quality. The device was programmed to 0.8–1.8 V with a 30-minute start delay, 12-hour nightly duration, and 15-minute pause. On follow-up, the patient demonstrated excellent adherence (average 70 hours/week), progressed to level 8 (1.6 V), and reported significant clinical improvement with resolution of snoring and apneas. Functional threshold and waveform analysis at 1.6 V remained optimal. Importantly, the patient tolerated HGNS well without any further episodes of pneumothorax following implantation. Conclusion HGNS may represent a safe and effective alternative to PAP therapy in patients at risk for pneumothorax. While positive pressure ventilation can theoretically worsen pneumothorax by increasing pleural pressure, HGNS operates through an entirely different mechanism: it maintains upper airway patency without altering intrathoracic pressure dynamics, making it a potentially safer option for select high-risk OSA patients. Support (if any)

Abstract This work presents a first-of-its-kind artificial intelligence (AI-)integrated MR pulse sequence that detects out-of-voxel (OOV) artifacts in real-time (within-TR) and responds prospectively by updating the crusher gradient scheme. Per Excitation Real-time Execution & Guided Responses with Integrated Neural-network Evaluation (PEREGRINE), allows for deployment of deep learning models and pulse sequence updates. In this study, PEREGRINE operated a time-domain (TD) and frequency-domain (FD) convolutional autoencoder that detect OOV artifacts. Scans without (AI-off) and with (AI-on) updates were collected from the medial prefrontal cortex of healthy volunteers using a MEGA-edited MRS experiment. The degree of OOV contamination (OOV Score) was quantified per transient based upon the prevalence of OOV signals in the TD and FD data. OOV Scores above a user-defined threshold triggered an update of the crusher gradient scheme, iterating through 48 permutations (6 axis transpositions × 8 polarity flips). Within each 2-second TR, PEREGRINE successfully provided single-transient OOV Scores and updated gradients accordingly. No difference was observed between the OOV Scores from the full (“Full” condition) AI-on and AI-off sessions due to the AI-on scan cycling over better and worse gradient permutations relative to the AI-off scan. However, the AI-on scan had significantly lower OOV Scores than the AI-off scan when selecting the transients where PEREGRINE persisted (“Dwell” condition) on a given gradient permutation. Ultimately, Fit Quality Number (FQN) from linear combination modeling improved significantly for the AI-on compared to the AI-off scan. PEREGRINE enabled an adaptive and AI-integrated sequence allowing for real-time evaluation and response to OOV artifacts, identifying gradient modifications that produced less OOV contamination. Graphical Abstract Graphical Abstract Summary PEREGRINE, Per Excitation Real-time Execution & Guided Responses with Integrated Neural-network Evaluation, allows for pulse sequence updates using on-scanner deployed neural networks. To demonstrate the utility, PEREGRINE was used to operate two neural networks (time/frequency domain), trained to detect out-of-voxel artifacts, during a MEGA-edited MRS experiment in the prefrontal cortex. When artifacts were detected, PEREGRINE updated the crusher gradients within the same TR. Real-time, adaptive, and AI-driven MR will provide a long-awaited solution for combatting artifacts and poor data quality. Graphical Abstract Figure

Background The middle meningeal artery (MMA) has emerged as an endovascular route for treating chronic subdural hematoma (CSDH), meningioma, and refractory headaches. The third ARISE roundtable convened experts from neurology, neurosurgery, neuroradiology, industry, and regulatory agencies to develop consensus guidance on current evidence for MMA-based therapies Methods Over 50 experts participated in a multi-stakeholder discussion. Evidence from randomized and observational studies, early-phase interventional series, and preclinical work was reviewed. Breakout groups focused on four domains: (1) MMA embolization (MMAE) for CSDH, (2) preoperative embolization of meningiomas, (3) MMA-targeted therapies for headache, and (4) transvascular access for endovascular drainage of subdural hematomas. Consensus recommendations were developed by a writing committee Results Randomized trials support MMAE as an adjunct to surgery or medical management for selected patients with non-acute, symptomatic CSDH to reduce recurrence, progression, and reoperation. Evidence remains insufficient to support MMAE for acute or asymptomatic subdural hematomas. For meningioma, observational data suggest that preoperative embolization in experienced centers can reduce blood loss and operative time and may delay recurrence in large, hypervascular tumors with predominant dural or external carotid supply; primary embolization and intra-arterial oncologic therapies remain investigational. Early series of MMA-directed lidocaine infusion for refractory migraine, status migrainosus, and post-subarachnoid hemorrhage headache show short-term benefit, highlighting the need for controlled trials. Preclinical and first-in-human studies of combined MMAE and transvascular drainage for CSDH demonstrate high technical success, rapid radiographic and clinical improvement, and no early recurrences Conclusion The MMA represents a vascular pathway for an expanding spectrum of neurointerventional therapies.

Abstract INTRODUCTION Alzheimer's disease neuropathologic change (ADNC) classification identifies not/low and intermediate/high levels of neuropathology. Our goal was to assess how frequently a positive amyloid positron emission tomography (PET) scan indicates not/low ADNC and whether this autopsy finding can occur >10 years after a positive amyloid PET. METHODS Participants with positive amyloid PET scans were categorized by levels of ADNC at autopsy, grouped by time from initial positive amyloid PET to time of death (<5 years, 5 to <10 years, or 10+ years). RESULTS Among those with a positive amyloid PET scan, the majority had intermediate/high ADNC at autopsy (234/259, 90%). In the group with 10+ years between a positive amyloid PET and death ( n = 39) not/low ADNC occurred in 3/39 (8%). DISCUSSION Not/low ADNC is uncommon among those with positive amyloid PET scans. After 10+ years, it is possible but rare for a positive amyloid PET scan to represent an indolent state of neuropathology.

Introduction Endovascular abdominal aortic aneurysm repair (EVAR) is the primary treatment for abdominal aortic aneurysm (AAA). Despite favorable early outcomes, lifelong surveillance is essential as endoleaks remain a major cause of reintervention. Among these, type II endoleaks (T2E) remain controversial regarding optimal management. This study aimed to identify factors associated with intervention for T2E using time-to-event analysis and predefined anatomic thresholds. Secondary objectives included comparing outcomes between T2E patients with (intT2E) and without (nointT2E) intervention. Methods A retrospective review of EVAR procedures from 2011-2024 was performed. Patients with newly diagnosed or persistent T2E were identified on completion and follow-up CT angiography. Patients were categorized as intT2E or nointT2E. Multivariable Cox regression evaluated time to first intervention, and logistic regression served as sensitivity analysis. Kaplan-Meier curves assessed freedom from intervention by inferior mesenteric artery (IMA) size. Results Among 207 EVAR patients, 78 (37.6%) developed T2E over a mean 3.4 ± 2.4 years. Nineteen (24.3%) required intervention. IntT2E patients were younger (74.9 ± 6.8 vs 78.3 ± 7.9 years, P = 0.02), had more frequent anticoagulation use (47.4% vs 20.3%, P = 0.02), larger IMAs (4.2 ± 0.6 vs 3.3 ± 0.7 mm, P < 0.01), and more lumbar arteries (6.0 ± 1.2 vs 5.0 ± 1.3, P = 0.02). IMAs >4 mm occurred in 68.4% of intT2E vs 8.5% of nointT2E ( P < 0.01). Mean sac growth was greater in intT2E (9.7 ± 5.3 mm vs −1.9 ± 6.5 mm, P < 0.01). Thirty-day complications following the index EVAR procedure, mid-term reinterventions, and overall mortality were similar between groups. Post-embolization, T2E resolved in 36.9%, with sac regression in 63.1%. Among embolized patients, 26.3% required a second embolization and one patient required 3 attempts without achieving resolution. IMA >4 mm independently predicted intervention (HR 7.18, 95% CI 1.97-26.16, P < 0.01). Logistic regression confirmed IMA >4 mm (OR 23.4, 95% CI 6.17-88.6, P < 0.01), >6 lumbar arteries (OR 4.2, 95% CI 1.10-15.98, P = 0.02), and anticoagulation (OR 3.4, 95% CI 1.17-10.6, P = 0.02) as predictors. Conclusions Approximately one-quarter of T2E patients required embolization. IMA >4 mm was the strongest predictor of intervention, while anticoagulation and increased lumbar artery number also increased risk. Management should prioritize risk-stratified surveillance and selective intervention.

Summary Cancer genome sequencing is essential for understanding tumor evolution and advancing precision medicine. 1 However, reference gaps and germline variants obscure detection of small and large somatic variants and methylation in repetitive regions. 1–3 It is common for tumor cells to gain or lose chromosome arms due to somatic structural changes that occur inside highly repetitive satellite DNA sequences in the centromeres. 4 To identify the full spectrum of somatic variants, including complex rearrangements, we construct and curate near-complete, haplotype-resolved assemblies of the most recent common ancestor of an early-passage broadly-consented hypodiploid pancreatic cancer cell line and matched normal tissues. The tumor assembly completely recapitulates all 35 tumor chromosomes observed with karyotyping, with multiple translocation-induced hybrid chromosomes. The hybrid chromosomes contain putative functional dicentric and fused centromeres, nested foldback inversions causing 14 breakpoints with a haplotype switch in a single event, and centromeric satellite tandem duplications up to 136 kbp. Direct comparison of tumor and normal assembly haplotypes uncovers >7,000 variants altering >1 Mbp of sequence in repetitive regions that have been hidden by reference gaps and germline variants. 44 % of somatic small variants change representation because they alter germline variants on GRCh38, impacting mutational signatures and kataegis/omikli clusters. Most somatic LINE insertions originate from two hypomethylated non-reference germline LINE insertions, highlighting their impact on insertion mutation burden. These assemblies demonstrate that centromeric, acrocentric, and telomeric regions conventionally excluded from analysis harbor extensive somatic and epigenetic changes. Resolving complete tumor genomes enables a deeper understanding of cancer structural plasticity and the endpoints of breakage-fusion-bridge cycles. These assembled, curated paired normal-tumor benchmarks will serve as a critical foundation for developing future algorithms to characterize the most intractable regions of cancer genomes.

Background: Several special tests for detecting medial ulnar collateral ligament (MUCL) injuries of the elbow have been described, but data on the clinical utility of these tests are limited. Purpose: To determine the clinical utility of selected elbow special tests to detect MUCL injuries in an athletic population. Study Design: Cross-sectional study; Level of evidence, 3. Methods: A total of 84 consecutive patients with sports-related elbow pain underwent a standardized clinical examination. Overall, 6 special tests (moving valgus stress test, static valgus stress test, modified valgus stress test, milking maneuver, pronation flexion resistance test, and temple/cheek press test) were performed. Sensitivity, specificity, accuracy, positive/negative predictive value, and positive/negative likelihood ratio (LR+ and LR–, respectively) were calculated for individual tests and combinations of tests to detect MUCL injuries. Higher values for the LR+ and lower values for the LR– represent stronger clinical utility. Results: For detecting MUCL injuries, the moving valgus stress test resulted in the highest sensitivity (98%) and accuracy (93%) with the lowest LR– (2%). The milking maneuver had the highest LR+ (5.1) with the second highest sensitivity (77%) and accuracy (79%). The pronation flexion resistance test and the temple/cheek press test had the lowest LR+ (1.5 and 1.8, respectively) and highest LR– (94% and 95%, respectively) in addition to the lowest sensitivity (16% and 9%, respectively) and accuracy (33% and 30%, respectively). No combination of tests resulted in increased clinical utility. Conclusion: The moving valgus stress test and milking maneuver demonstrated acceptable clinical utility in which the moving valgus stress test was better for ruling out MUCL injuries and the milking maneuver was better at ruling in MUCL injuries. There was no added value when combining the 2 tests together or with other maneuvers.