Citations

Abstract We evaluated whether spike ripples, the combination of epileptiform spikes and ripples, provide a reliable and improved biomarker for the epileptogenic zone compared with other leading interictal biomarkers in a multicentre, international study. We first validated an automated spike ripple detector on intracranial EEG recordings. We then applied this detector to subjects from four centres who subsequently underwent surgical resection with known 1-year outcomes. We evaluated the spike ripple rate in subjects cured after resection [International League Against Epilepsy Class 1 outcome (ILAE 1)] and those with persistent seizures (ILAE 2–6) across sites and recording types. We also evaluated available interictal biomarkers: spike, spike-gamma, wideband high frequency oscillation (HFO, 80–500 Hz), ripple (80–250 Hz) and fast ripple (250–500 Hz) rates using previously validated automated detectors. The proportion of resected events was computed and compared across subject outcomes and biomarkers. Overall, 109 subjects were included. Most spike ripples were removed in subjects with ILAE 1 outcome (P < 0.001), and this was qualitatively observed across all sites and for depth and subdural electrodes (P < 0.001 and P < 0.001, respectively). Among ILAE 1 subjects, the mean spike ripple rate was higher in the resected volume (0.66/min) than in the non-removed tissue (0.08/min, P < 0.001). A higher proportion of spike ripples were removed in subjects with ILAE 1 outcomes compared with ILAE 2–6 outcomes (P = 0.06). Among ILAE 1 subjects, the proportion of spike ripples removed was higher than the proportion of spikes (P < 0.001), spike-gamma (P < 0.001), wideband HFOs (P < 0.001), ripples (P = 0.009) and fast ripples (P = 0.009) removed. At the individual level, more subjects with ILAE 1 outcomes had the majority of spike ripples removed (79%, 38/48) than spikes (69%, P = 0.12), spike-gamma (69%, P = 0.12), wideband HFOs (63%, P = 0.03), ripples (45%, P = 0.01) or fast ripples (36%, P < 0.001) removed. Thus, in this large, multicentre cohort, when surgical resection was successful, the majority of spike ripples were removed. Furthermore, automatically detected spike ripples localize the epileptogenic tissue better than spikes, spike-gamma, wideband HFOs, ripples and fast ripples.

Abstract Background Although typically benign, 5% of spinal meningiomas (SMs) present with higher-grade features (World Health Organization grades 2 and 3). High-grade SMs are poorly studied and the role of adjuvant radiotherapy in their management remains controversial. We hence aimed to study the demographic characteristics of this rare tumor and investigate the outcomes associated with the use of surgery with adjuvant therapy in contrast to surgery alone. Methods The National Cancer Database was queried for patients with SMs from 2004 to 2017. Basic statistics were used to identify differences between low- and high-grade tumors in terms of baseline characteristics. Surgery with and without adjuvant radiotherapy were compared after (1:1) propensity-score matching. Kaplan–Meier survival analysis was conducted to study overall survival. All analyses were performed on R. Results A total of 13 184 patients diagnosed with SMs were included, of whom only 5% (n = 669) had high-grade SMs. Patients with high-grade SMs presented at a younger median age (57 years [IQR: 44–68] versus 65 years [54–75]; P < .001) and were more commonly males (33% vs 20%; P < .001). After propensity-score matching, survival analysis revealed similar overall survival outcomes in patients with high-grade SM undergoing both surgery and radiotherapy as compared to those only receiving surgery (P = .19). Conclusions This study reveals major demographic differences between high- and low-grade SMs. There were no benefits associated with the use of adjuvant radiotherapy. However, due to confounding, overall survival outcomes between patients receiving surgery alone and those receiving surgery with adjuvant radiotherapy are not causally interpretable.

Abstract Although Bruton tyrosine kinase inhibitors (BTKis) are generally well tolerated and less toxic than chemotherapy alternatives used to treat lymphoid malignancies, BTKis like ibrutinib have the potential to cause new or worsening hypertension (HTN). Little is known about the optimal treatment of BTKi-associated HTN. Randomly selected patients with lymphoid malignancies on a BTKi and antihypertensive drug(s) and with at least 3 months of follow-up data were sorted into 2 groups: those diagnosed with HTN before BTKi initiation (prior-HTN), and those diagnosed with HTN after BTKi initiation (de novo HTN). Generalized estimating equations assessed associations between time varying mean arterial pressures (MAPs) and individual anti-HTN drug categories. Of 196 patients included in the study, 118 had prior-HTN, and 78 developed de novo HTN. Statistically significant mean MAP reductions were observed in patients with prior-HTN who took β blockers (BBs) with hydrochlorothiazide (HCTZ), (−5.05 mmHg; 95% confidence interval [CI], 10.0 to −0.0596; P = .047), and patients diagnosed with de novo HTN who took either an angiotensin converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) with HCTZ (−5.47 mmHg; 95% CI, 10.9 to −0.001; P = .05). These regimens also correlated with the greatest percentages of normotensive MAPs. Treatment of HTN in patients taking a BTKi is challenging and may require multiple antihypertensives. Patients with prior-HTN appear to benefit from combination regimens with BBs and HCTZ, whereas patients with de novo HTN appear to benefit from ACEi/ARBs with HCTZ. These results should be confirmed in prospective studies.

Abstract Infectious diseases (ID) research is vital for global public health, typically led by physician-scientists. This Perspective addresses challenges in the ID workforce and suggests solutions. Physician-scientists have made key discoveries that have significantly impacted human health. The importance of ID research in understanding diseases, leading to treatments and vaccines, is emphasized, along with the need to address persistent and new infections, antimicrobial resistance, and threats like HIV and influenza. The paper analyzes the physician-scientist workforce's struggles, including funding, training, and research-practice integration gaps. We suggest increased funding, better training, and mentorship, more collaborative and interdisciplinary research, and improved recognition systems. The article stresses the urgency of supporting physician-scientists in ID, advocating for proactive prevention and preparedness, and calls for immediate action to enhance ID research and care.

Introduction: Patients diagnosed with ischemic stroke routinely undergo prolonged cardiac telemetry (PCT) to evaluate for occult atrial fibrillation (AF), but this approach is limited by high cost and low yield. Clinical scores including CHA2DS2-VASc and CHARGE-AF can risk stratify patients but lack desired accuracy. Therefore, we aimed to evaluate an artificial intelligence (AI)-enabled ECG algorithm to predict AF detected by PCT after index stroke. Methods: This retrospective study included all adult patients with ischemic stroke evaluated at Mayo Clinic with baseline electrocardiogram (ECG) and PCT between 2018-2020. We recorded demographics, CHA2DS2-VASc score, CHARGE-AF score, stroke etiology, duration of PCT, and if PCT detected AF. ECGs were analyzed using the AI-ECG algorithm to determine AF likelihood. Stroke etiology was adjudicated using TOAST and embolic stroke of undetermined source (ESUS) definitions. The ability of the AI-ECG algorithm, CHA2DS2-VASc, and CHARGE-AF to predict AF detected by PCT was assessed via receiver operating characteristics analysis, calculating the area under curve (AUC) (c-statistic). Sensitivity and specificity analyses were performed for each tool using optimal cutoffs (using maximum Youden indices). Results: 863 patients were included; median age was 69 years, 496 (57.5%) were male, and 561 (65%) patients were categorized as ESUS. PCT detected AF in 85 (9.8%) patients. Median duration of cardiac telemetry was 30 (IQR 25-30) days. Sensitivity and specificity analyses are outlined in Table 1. The AI-ECG algorithm outperformed the CHA2DS2-VASc score (AUC 0.690 vs. 0.597, p=0.013), but was similar to the CHARGE-AF score (AUC 0.690 vs 0.651, p=0.233). Conclusions: Our AI-ECG algorithm demonstrated improved ability to predict AF detection on PCT after index stroke when compared to the CHA2DS2-VASc score, but was similar in performance to the CHARGE-AF score. All three methods had suboptimal accuracy.

Introduction: Acute ischemic stroke (AIS) patients often require multiple passes during mechanical thrombectomy (MT) to open the vessel. Yet, at times, even numerous passes are unsuccessful. This study aims to investigate the impact of the number of passes on the outcomes of patients who underwent failed MT. Methods: We used Data from the Stroke Thrombectomy and Aneurysm Registry (STAR) from 2013 to August 2023. Patients who underwent MT for ICA, M1, or M2 with unsuccessful recanalization (modified Thrombolysis in Cerebral Infarction ≤ 2a) were included. Primary outcome was 90- day modified Rankin Scale (mRS) 0-2. Secondary outcomes included any intracranial hemorrhage (ICH) and symptomatic ICH (sICH). Outcomes were compared among patients who received ≤ 2, 3, 4, and ≥ 5 MT passes. Results: 736 patients met inclusion criteria. 90-day mRS 0-2 was found to decrease with number of passes (Figure 1). Multivariate logistic regression analysis revealed that 3 passes (OR: 0.48, 95% CI: 0.23 -0.96, P-value: 0.04), 4 passes (OR: 0.46, 95% CI: 0.19 -1.03, P-value: 0.07), and ≥ 5 passes (OR: 0.22, 95% CI: 0.08 -0.50, P-value: <0.001) were associated with lower odds of mRS 0-2 compared to ≤ 2 passes. However, there were no significant differences between groups in ICH, sICH, or 90-day mortality. Conclusion: The number of passes affects functional outcomes among stroke patients who underwent failed MT.

Introduction: Recent randomized control trials suggested that mechanical thrombectomy (MT) was associated with good functional outcomes after acute ischemic stroke (AIS) due to large vessel occlusion (LVO) in patients presenting with low Alberta Stroke Program Early CT Score (ASPECTS) (defined as ASPECTS 2-5). The aim of this study is to develop and validate a stroke prediction tool for outcome in MT for AIS patients with low ASPECTS using data from an ongoing international multicenter registry, the Stroke Thrombectomy and Aneurysm Registry (STAR). Methods: 236 AIS patients with low ASPECTS caused by LVO who undertook MT between January 2010 and December 2022 were retrospectively investigated. Univariate and multivariate logistic regression results were used to screen model predictors and construct nomograms of 90-day modified Rankin Scale scores (mRS) 0-3. The performance of the model was detected by using receiver operating characteristic analysis. The bootstrap resampling method was considered internal validation of the model. Results: Age (< 70 years), premorbid status (mRS 0), National Institutes of Health Stroke Scale (NIHSS) (< 20), and recanalization status after the MT (modified Thrombolysis in Cerebral Ischemia [mTICU] ≥2b) were related to 90-day mRS 0-3. Predictive score was calculated by adding 1 point for age (< 70 years), premorbid status (mRS 0), and NIHSS < 20 and 3 points for a mTICI ≥2b (ranging 0-6). 90-day mRS 0-3 was observed in 0% of patients with a score of 0 or 1, 6.3% with a score of 2, 17.7% with a score of 3, 22.2% with a score of 4, 45.7% with a score of 5, and 73.7% with a score of 6. The score showed relatively high performance in predicting 90-day mRS0-3 (area under the curve: 0.79 [95% CI 0.73-0.79] and 0.78 [95% CI 0.78-0.78] for derivation and validation cohorts, respectively). Conclusions: This study indicates the STAR score can be calculated with baseline and periprocedural characteristics to predict the 90-day outcome after MT in AIS patients with low ASPECTS.

Introduction: Despite comparable outcomes for different frontline techniques in mechanical thrombectomy (MT) for acute ischemic stroke (AIS), there are sparse data regarding if and when to switch techniques if the first pass is unsuccessful. We aimed to investigate the impact of converting from one MT technique to another on the second MT attempt for AIS among patients with large vessel occlusion (LVO). Methods: This was a retrospective observational study using data from the large multicenter international Stroke Thrombectomy and Aneurysm Registry (STAR). Data from 29 stroke centers for 10,229 AIS patients treated with MT for LVO between January 2010 and December 2022 was investigated. The primary outcome measure was successful recanalization defined as modified Thrombolysis in Cerebral Ischemia (mTICI) score of 2b or higher. 90-day modified Rankin score (mRS) 0-2, mortality and symptomatic hemorrhage were used as secondary outcomes. Clinical and technical outcomes after the second MT attempt were compared between those with or without technique conversion. Results: Among 10,229 AIS patients, 1,797 AIS patients with LVO failed first pass recanalization and were included in this retrospective analysis. 927 patients were female (52%) and median (interquartile range) age was 72 (61-81) years. Converting to alternative techniques following a first failed attempt was more likely to be associated with successful recanalization at the second attempt (adjusted odds ratio 2.30, 95% CI: 1.37-3.86, P = 0.002) and 90-day good clinical outcome (adjusted odds ratio 2.10, 95% CI: 1.15-3.85, P = 0.02) after multivariate adjustment. Conclusions: This study demonstrates better clinical and technical outcomes with conversion of MT technique for the second attempt in AIS patients with LVO who failed first pass recanalization.

Introduction: The benefits of intravenous thrombolysis (IVT) in acute ischemic stroke (AIS) patients with unsuccessful mechanical thrombectomy (MT) are not well established. Methods: This study included patients from the Stroke Thrombectomy and Aneurysm Registry (STAR) who underwent MT for ICA, M1, or M2 occlusions with unsuccessful MT (mTICI score ≤ 2a). Patients who received IVT prior to MT were compared to those who received MT alone. Propensity score (PS) matching was performed using age, sex, premorbid modified Rankin Scale (mRS), admission National Institute of Health Stroke Scale (NIHSS), occluded vessel, ASPECTS score, mTICI score, and symptom onset to groin puncture time. The primary outcome was favorable 90-day outcomes (mRS 0-2). Results: Of 610 patients with unsuccessful MT, 219 were matched in each group. Median ages were 70 [IQR: 61 - 80] and 73 [IQR: 62 - 81] in the IVT + MT and MT alone groups, respectively. In the IVT + MT group. Final TICI scores of 0, 1, and 2a were achieved in 92 (42.0%), 33 (15.1%), and 94 (42.9%) patients, respectively, compared to 76 (34.7%), 29 (13.2%), and 114 (52.1%) in the MT alone group. The IVT + MT group showed a significantly. higher 90-day mRS of 0-2 (aOR: 2.54, 95% CI: 1.53-4.32) and mRS of 0-3 (aOR: 2.05, 95% CI: 1.36-3.12). There were no significant differences between the groups in intracranial hemorrhage (ICH), symptomatic ICH, or 90-day mortality rates. Conclusions: IVT is associated with improved functional outcomes in patients with unsuccessful MT. Ensuring that IVT is provided to all eligible stroke patients should remain a priority.