Citations

Abstract Background/Objective: Maintaining acid-base balance within the central nervous system (CNS) is essential for neuronal homeostasis. Disruptions in this balance can result in respiratory disturbances, elevated intracranial pressure, or coma. These disturbances can occur concurrently with stroke, or CNS infection. However, they are augmented by various neurosurgical procedures involving CSF manipulation, either through direct ventricular irrigation during endoscopic neurosurgical procedures or by CSF exchange technologies. The IRRAflow active cerebrospinal fluid (CSF) exchange system (IRRA flow ) manages acid-base balance changes in the ventricular system through continuous irrigation with fluids and medications and removal of endogenous CSF. We describe a novel clinical syndrome of iatrogenic metabolic acidosis and respiratory compensation in response to exogenous fluid introduction in the ventricular fluid system using IRRAflow. The syndrome was previously seen with endoscopic neurosurgical procedures that require irrigation with normal saline. We also recommend fluid alternatives for more effective use of the IRRAflow system or different endoscopic procedure and increased awareness of CSF derangements. Methods We describe 2 cases involving patients with subarachnoid hemorrhage who developed a syndromic response characterized by tachypnea, conjunctival hyperemia, encephalopathy, and fluctuating language deficits due to continuous 0.9% normal saline irrigation. Results Both patients exhibited reproducible symptoms that persisted despite stable neuroimaging until normal saline was replaced with lactated Ringer solution, after which clinical parameters normalized within 3 hours. We named this condition SALT-CRAMD syndrome (saline acidosis leading to tachypnea, central respiratory alkalosis, and metabolic derangements). Pathophysiologic analysis based on the literature suggests that normal saline induced central hyperchloremia and dilutional acidosis, leading to heightened chemoreceptor activation in the medulla oblongata, triggering excessive respiratory drive and compensatory hypocapnia. Conclusion Awareness of SALT-CRAMD syndrome is crucial for understanding the profound pathophysiologic concepts of CSF dynamics, whether induced during treatment with active CSF exchange, endoscopic neurosurgical procedures, stroke, or CNS infections.

Abstract Introduction Intracerebral hemorrhage (ICH) carries higher morbidity and mortality than ischemic stroke. Recent studies have demonstrated improved patient outcomes by applying ultra-early bundled interventions including blood pressure management, coagulopathy reversal, and osmotic therapy. Effective strategies to deliver these ultra-early treatment options are currently being explored. On December 19th, 2022, the Mayo Clinic Comprehensive Stroke Center (CSC) launched the “ICH Phases” communication system to accelerate ICH patient care. Objective To evaluate adherence to the AHA/ASA guidelines in acute ICH care following the implementation of our novel-tiered paging system. Methods We retrospectively reviewed patients admitted with spontaneous ICH during 2024 and 2025. We excluded traumatic cases. We extracted clinical data such as time to imaging, documentation of ICH score, blood pressure control, reversal of anticoagulation, venous thrombo-embolism (VTE) prophylaxis and discharge disposition. Results Among 67 patients, 68.7% underwent CT imaging within 25 minutes. We documented the ICH score within 6 hours in 82.9% of patients. Nearly 94.7% of patients with SBP>140 mm Hg received antihypertensive therapy, yet only 18% reached target BP within 60 minutes. We completed the reversal of anticoagulation within 120 minutes in 75% of patients. VTE prophylaxis was initiated within 24 hours in 91% of patients. Discussion Our novel system demonstrated adherence to the AHA/ASA guidelines, and time sensitive benchmarks in neuroimaging, reversal of anticoagulation, and VTE prophylaxis. Early BP control remains a challenge, that highlights the discrepancy between guidelines and real-ground implementation. Conclusion A novel tiered paging system is effective for enhancing early ICH care. Such a holistic system remains critical for sustained improvement in quality of care.

Abstract Background aneurysmal subarachnoid hemorrhage (aSAH) is neurological emergency associated with substantial mortality and disability. Current grading systems such as the modified Fisher Scale (mFS) and World Federation of Neurological Societies (WFNS) score, rely on semiquantitative and examination based assessments. Hence, they demonstrate limited predictive precision. The enhanced subarachnoid hemorrhage (eSAH) score is a simplified quantitative model integrating age, Glasgow Coma Scale (GCS), and cisternal subarachnoid hemorrhage volume (SAHV) to predict clinical outcomes after aSAH. Methods We performed a retrospective multicenter cohort study that included 1088 patients across three tertiary-care centers the United States. Predictive performance for unfavorable functional outcome, in-hospital mortality and delayed cerebral ischemia (DCI) was evaluated using receiver operating characteristic (ROC) analysis and area under the curve (AUC). Comparative analyses were performed and compared to the WFNS and mFS grading systems. Results the eSAH score demonstrated excellent discrimination for unfavorable functional outcome at discharge ( AUC 0.89 ) and in-hospital mortality (AUC 0.87). The DCI subscore demonstrated good discriminatory performance for predicting DCI (AUC 0.77). Compared with conventional grading systems, this was superior to both the WFNS (AUC 0.75) and the mFS ( AUC 0.70). increasing eSAH scores were additionally associated with progressively higher rates of mortality and unfavorable functional outcomes. Conclusion the eSAH score demonstrates strong external validity, reproducibility and superior predictive performance compared with conventional grading systems in a large multicenter cohort. These findings support the clinical utility of quantitative hemorrhage burden integration for early risk stratification in patients with aSAH.

Abstract Objective Shunt-dependent hydrocephalus is a common and costly complication of aneurysmal subarachnoid hemorrhage (aSAH), affecting up to 28% of survivors. Existing prediction tools, including the Chronic Hydrocephalus Ensuing from SAH Score (CHESS), have limited discriminative accuracy. We developed the CHECKMATE score, a clinically practical tool to improve prediction of ventriculoperitoneal shunt dependency after aSAH. Methods In this multicenter retrospective cohort of 486 patients with aSAH from Mayo Clinic (January 1, 2006-December 31, 2021), we used multivariable logistic regression and machine learning to identify independent predictors of ventriculoperitoneal shunt placement. The CHECKMATE score was derived from 5 weighted variables: symptomatic hydrocephalus (10 points), intraventricular hemorrhage (5 points), SAH volume greater than 10 mL (3 points), neutrophil-to-lymphocyte ratio greater than 12 (2 points), and 10-year incremental age thresholds starting at older than 60 years (1 point each). Results Of 486 patients (mean age, 56.3 years; 64.6% female), 137 (28.2%) required ventriculoperitoneal shunt placement. The CHECKMATE score achieved an area under the curve of 0.808 (compared to 0.737 for CHESS), with a sensitivity of 0.85, specificity of 0.67, and negative predictive value of 0.92 at the optimal cutoff of 14 points. Conclusions The CHECKMATE score outperforms CHESS for predicting ventriculoperitoneal shunt dependency after aSAH and is easily used at the bedside. Its high negative predictive value helps identify low-risk patients who may benefit from earlier external ventricular drain weaning and shorter hospital stays.

Abstract Background and Objectives: Neurosurgery is a distinctive realm with a tight and strict margin of error. IRRAflow (IRRA flow ) is a US Food and Drug Administration–approved active cerebrospinal fluid exchange system that can irrigate up to 180 mL/h. The system is tightly secured, safe, and continuously monitors intracranial pressure, using a 9F dual-lumen catheter. Inserting an IRRAflow catheter is more complex than standard external ventricular drains, with a higher risk of cerebrospinal fluid leak or catheter displacement. Particularly, the extracranial component of the IRRAflow catheter insertion is prone to errors and necessitates dedicated training. We aimed to design an affordable, reusable, and easy-to-use 3-dimensional printed model that simulates the extracranial component of the IRRAflow catheter insertion. Methods: The IRRAsert simulator was designed according to recent publications. The skull was printed with polylactic acid, and the Kocher point was drilled. A mold was cast to make the scalp, and Dragon Skin FX-Pro Part A and Part B (Smooth-On, Inc) was used to create a skin flap to cover the drilled Kocher point. Results: The IRRAsert simulator replicated the external parts of the skull starting from the bone outward. It allowed measurements for designating the Kocher point, incising the skin to reveal the drilled Kocher point, tunneling under the scalp, and creating a 5-cm posterior exit incision. The endogenous property of the mixed 1:1 ratio between parts A and B allowed adhesion with the underlying skull due to the attraction between polylactic acid and silicone in a stick-and-peel fashion. This adhesion allowed for dissection of skin from the bone during tunneling for the catheter under the scalp, as well as lifting and rotating the scalp for the next user. The final cost of our simulator was $20 to print the skull permanently, with another $5 to produce the skin that can be rotated 3 times for 3 different users. Conclusion: IRRAsert is the result of multidisciplinary efforts to produce an affordable simulator for the extracranial component of IRRAflow catheter insertion.

BACKGROUND: Intraventricular hemorrhage and subarachnoid hemorrhage are associated with neuroinflammation and increased morbidity and mortality. Rapid clearance of blood from the cerebrospinal fluid space may mitigate neuroinflammatory cascades and improve clinical outcomes. This systematic review and meta-analysis aimed to compare the clinical effectiveness of active cerebrospinal fluid exchange, including neuroendoscopic lavage and IRRAflow systems, versus external ventricular drainage in patients with intraventricular hemorrhage or subarachnoid hemorrhage. METHODS: The study followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and thoroughly assessed databases, including PubMed, Embase, Scopus, Cochrane, and Web of Science, up to September 18, 2025. Statistical analysis, both fixed-effect and random-effect model analyses, was performed by the Comprehensive Meta-Analysis software. In addition, the Cochran Q test was conducted to determine the statistical heterogeneity. In terms of low heterogeneity, the fixed-effect model is reported. RESULTS: This review included 7 studies with a total sample size of 834. Our analysis showed that active cerebrospinal fluid exchange was associated with significantly higher hematoma clearance (odds ratio, 2.72 [95% CI, 1.22–6.08]; P =0.015), better functional outcomes (odds ratio, 1.66 [95% CI, 1.12–2.48]; P =0.012), lower shunt dependency (odds ratio, 0.22 [95% CI, 0.10–0.50]; P <0.001), and reduced infection rates (odds ratio, 0.22 [95% CI, 0.12–0.42]; P <0.001). Subgroup analysis showed that neuroendoscopic lavage was most effective for hematoma clearance, while IRRAflow reduced infection rates. Also, younger patients had better neurological recovery. CONCLUSIONS: Active cerebrospinal fluid exchange techniques demonstrated superior outcomes over external ventricular drainage in managing intraventricular hemorrhage and subarachnoid hemorrhage, particularly in clot resolution and neurological recovery. Large-scale trials are warranted.

Glioblastoma (GBM) is a devastating cancer with a dismal prognosis. Current treatment includes temozolomide (TMZ), which is more effective in about 50% of GBMs that have O 6 - methylguanine DNA methyltransferase ( MGMT ) promoter methylation. MGMT is a DNA repair protein that reverses TMZ-induced DNA damage. EGFR is a prime oncogene in GBM. Here, we report that EGFR inhibition induced the down-regulation of MGMT in GBM cells, revealing a previously unidentified link between EGFR signaling and response to TMZ. EGFR inhibition led to activation of two transcription factors, activator protein-1 (AP-1), which repressed MGMT transcription, and nuclear factor κB (NF-κB), which up-regulated MGMT transcription. EGFR inhibition also induced AP-1–mediated transcription of miR-616. miR-616 inhibited both MGMT translation and NF-κB activation. Thus, the overall effect of EGFR inhibition was down-regulation of MGMT expression. In addition, we provided an explanation for the prior failure of clinical trials that used concomitant EGFR tyrosine kinase inhibitors (TKIs) and TMZ. TMZ up-regulated MGMT, and concomitant treatment with EGFR TKIs and TMZ failed to down-regulate MGMT. However, pretreatment with EGFR TKIs followed by TMZ efficiently down-regulated MGMT and enhanced TMZ sensitivity in experimental models. Posttreatment tumor tissues from two clinical trials were used to validate these findings. We demonstrated that EGFR inhibitors induced down-regulation of MGMT in posttreatment resected tumor tissues from patients with GBM and the failure of EGFR inhibition to down-regulate MGMT if TMZ was used concomitantly. These data support using EGFR TKIs before TMZ treatment as a therapeutic approach in MGMT unmethylated GBM.

Abstract Background Climate-related stressors such as heat, wildfires, and extreme weather are increasingly recognized as determinants of cardiovascular and oncologic health. However, their joint impact on overlapping cancer–cardiovascular disease (CVD) burdens remains unknown. We developed a Cardio-Oncology Burden Index (COBI) to quantify the co-prevalence of cancer and CVD at the community level and examined its association with climate vulnerability across U.S. census tracts. Methods We conducted a cross-sectional ecological analysis of 82,679 census tracts (328,683,841 residents) using the CDC PLACES database. COBI was derived using principal component analysis of age-adjusted prevalence of cancer, coronary artery disease, and stroke. The Climate Burden Index (CBI, 0–1 percentile) integrates multiple climate-related exposures, including extreme temperature, wildfire frequency, and severe weather events. Population-weighted mixed-effects regression models with county-level random effects estimated associations between CBI and COBI, adjusting for region, rurality, and environmental justice indicators. β coefficients represent percentage-point differences in COBI per unit (or category) increase in climate burden. Exposure–response relationships were examined using restricted cubic splines (RCS). Robustness was assessed via geographically matched (&lt;50 km) and fully matched (region, rural–urban commuting area, and environmental justice) analyses. Results Marked spatial heterogeneity was observed in both CBI and COBI across the U.S. (Fig. A–B). Higher climate burden was consistently associated with greater cardio-oncology burden (Fig. C), demonstrating a dose–response relationship: second vs lowest quartile β=0.92 (95% CI, 0.61–1.24); third vs lowest quartile β=1.61 (95% CI, 1.30–1.92); highest vs lowest quartile β=3.44 (95% CI, 3.11–3.76). The RCS model revealed a significant non-linear association (p_non-linear&lt;0.001), with a plateau at moderate exposures and a steep rise at the highest CBI levels (Fig. D). Results remained robust in sensitivity analyses (β=4.17 [95% CI, 3.62–4.71] for geographically matched; β=4.39 [95% CI, 4.10–4.69] for fully matched tracts; Table). Conclusions Greater climate burden is independently associated with higher cardio-oncology burden across U.S. communities, with disproportionate effects in the most climate-vulnerable areas. This novel, population-level linkage between climate stress and onco-cardiovascular disease burden, highlights an emerging syndemic at the intersection of environment, cancer, and CVD. Targeted mitigation and prevention strategies integrating environmental resilience into chronic disease prevention are urgently needed.For image description, please refer to the figure legend and surrounding text.

Background Anomalous aortic origin of the right coronary artery (AAORCA) with an intramural course is a rare but potentially life-threatening anomaly due to its association with exertional ischemia and sudden cardiac death. Surgical correction aims to eliminate the ischemic mechanism. This study reports a single-center experience with adult patients who underwent right coronary artery (RCA) reimplantation for AAORCA. Methods A retrospective review was conducted of symptomatic adult patients with AAORCA who underwent RCA reimplantation between June 2017 and August 2024. Baseline clinical features, perioperative outcomes, and follow-up data were assessed. Results Forty patients (85% [34/40] male; median age 44 years) were included. The most common presenting symptom was exertional chest pain (82.5%, [33/40]), followed by dyspnea (45%, [18/40]) and syncope or presyncope (30%, [12/40]). Coronary computed tomography angiography (CCTA) was performed to diagnose the high-risk coronary features. All patients underwent RCA reimplantation into the right sinus of Valsalva. One patient also received a saphenous-vein graft to the distal-RCA. There was no in-hospital or follow-up mortality. At a mean follow-up of 30.3 ± 20.5 months, 8/40 patients (20%) reported recurrent symptoms, including chest pain (10%, [4/40]), dyspnea on exertion (5%, [2/40]), and palpitation (5%, [2/40]). Surveillance CCTA or invasive angiography performed in 14 patients, including 8 symptomatic patients, confirmed the widely patent RCA with no ostial stenosis or kinking. Post operative exercise testing in all these patients was negative. Conclusions In adults with AAORCA and an intramural or interarterial course; reimplantation of the RCA into the right-sinus of Valsalva achieves excellent early- to midterm outcomes, with low mortality, symptom resolution, and durable coronary patency.