The partnership between statisticians and the Institutional Animal Care and Use Committee (IACUC).

In this tutorial we explore the valuable partnership between statisticians and Institutional Animal Care and Use Committees (IACUCs) in the context of animal research, shedding light on the critical role statisticians play in ensuring the ethical and scientifically rigorous use of animals in research. Pharmaceutical statisticians have increasingly become vital members of these committees, contributing expertise in study design, data analysis, and interpretation, and working more generally to facilitate the integration of good statistical practices into experimental procedures. We review the "3Rs" principles (Replacement, Reduction, and Refinement) which are the foundation for the humane use of animals in scientific research, and how statisticians can partner with IACUC to help ensure robust and reproducible research while adhering to the 3Rs principles. We also highlight emerging areas of interest, such as the use of virtual control groups.

A Narrative Review of Interhospital Transfers for Intracerebral Hemorrhage.

Of the 750,000 strokes in the United States every year, 15% patients suffer from hemorrhagic stroke. Intracerebral hemorrhage (ICH) is a subtype of hemorrhagic stroke. Despite advances in acute management, patients with hemorrhagic stroke continue to suffer from high mortality and survivors suffer from multidomain impairments in the physical, cognitive, and mental health domains which could last for months to years from their index stroke. Long-term prognosis after ICH is critically dependent on the quality and efficacy of care a patient receives during the acute phase of care. With ongoing care consolidation in stroke systems of care, the number of ICH patients who need to undergo interhospital transfers (IHTs) is increasing. However, the associations between IHT and ICH outcomes have not been well described in literature. In this review, we describe the epidemiology of IHT for ICH, the relationship between IHT and ICH patient outcomes, and proposed improvements to the IHT process to ensure better long-term patient outcomes. Our review indicates that evidence regarding the safety and benefit of IHT for ICH patients is conflicting, with some studies reporting poorer outcomes for transferred patients compared to direct admissions via emergency rooms and other studies showing no effect on outcomes. The American Heart Association guidelines for ICH provide recommendations for timely blood pressure control and anticoagulation reversal to improve patient outcomes. The American Heart Association stroke systems of care guidelines provide recommendations for transfer agreements and but do not provide details on how patients should be managed while undergoing IHT. Large, prospective, and multicenter studies comparing outcomes of IHT patients to direct admissions are necessary to provide more definitive guidance to optimize IHT protocols and aid clinical decision-making.

Field Study and Correlative Studies of Factor IX Variant FIX-R338L in Participants Treated with Fidanacogene Elaparvovec.

BACKGROUND: Fidanacogene elaparvovec, an adeno-associated virus-based gene therapy vector expressing the high-activity factor IX (FIX) variant FIX-R338L, is in development for hemophilia B. One-stage clotting (OS) assays and chromogenic substrate (CS) assays are commonly used to measure FIX-R338L variant activity. Data from ongoing trials suggest FIX activity varies between different OS and CS assays. MATERIAL AND METHODS: To better understand FIX-R338L activity in clinical samples, an international multisite field study was conducted across a central laboratory and 18 local laboratories, using standard protocols, reagents, and instrumentation, with individual participant samples from a phase 1/2a study of fidanacogene elaparvovec. RESULTS: Unlike the wild-type FIX control, FIX-R338L activity was higher with the OS silica-based assay versus OS ellagic acid-based and CS assays. Variation in FIX activity was greater at the lowest activity levels. Activated FIX (FIXa) in plasma could result in higher OS assay activity or increased thrombin generation, which could overestimate FIX activity. However, FIXa was not detected in the participant samples, indicating that it was not contributing to the OS assay differences. Since individuals on gene therapy may receive exogenous replacement FIX products, replacement products were spiked into patient plasma samples to target a therapeutic concentration. Exogenous FIX was additive to endogenous FIX-R338L, with no interference from FIX-R338L. CONCLUSION: These results demonstrate FIX-R338L activity can be measured with OS and CS assays in clinical laboratories and provide insight into assay variability when measuring FIX with endogenously produced FIX-R338L. The findings may help establish best practices for measuring FIX-R338L activity (Clinicaltrials.gov identifier: NCT02484092).

How and why do species break a developmental trade-off? Elucidating the association of trichomes and stomata across species.

PREMISE: Previous studies have suggested a trade-off between trichome density (Dt) and stomatal density (Ds) due to shared cell precursors. We clarified how, when, and why this developmental trade-off may be overcome across species. METHODS: We derived equations to determine the developmental basis for Dt and Ds in trichome and stomatal indices (it and is) and the sizes of epidermal pavement cells (e), trichome bases (t), and stomata (s) and quantified the importance of these determinants of Dt and Ds for 78 California species. We compiled 17 previous studies of Dt-Ds relationships to determine the commonness of Dt-Ds associations. We modeled the consequences of different Dt-Ds associations for plant carbon balance. RESULTS: Our analyses showed that higher Dt was determined by higher it and lower e, and higher Ds by higher is and lower e. Across California species, positive Dt-Ds coordination arose due to it-is coordination and impacts of the variation in e. A Dt-Ds trade-off was found in only 30% of studies. Heuristic modeling showed that species sets would have the highest carbon balance with a positive or negative relationship or decoupling of Dt and Ds, depending on environmental conditions. CONCLUSIONS: Shared precursor cells of trichomes and stomata do not limit higher numbers of both cell types or drive a general Dt-Ds trade-off across species. This developmental flexibility across diverse species enables different Dt-Ds associations according to environmental pressures. Developmental trait analysis can clarify how contrasting trait associations would arise within and across species.

Cellularity of mucus is a prognostic variable in low-grade appendiceal mucinous neoplasms.

For peritoneal metastases from a primary appendiceal mucinous neoplasm to exist, the thin wall of the appendix must perforate to allow mucus or mucus plus tumor cells to gain access to the peritoneal spaces. The proportion of specimens containing tumor cells within mucus as compared to mucus only outside the appendix may have prognostic significance. The histopathology of tumor masses was determined from the specimens resected at the cytoreductive surgery (CRS). The presence versus absence of tumor cells in mucus and the proportion of specimens with tumor cells was determined and correlated with the overall survival of these patients. In 418 patients with a complete cytoreduction for a low-grade appendiceal mucinous neoplasm (LAMN), the cellularity of all resected specimens was determined. The hazard ratio of overall survival of patients whose specimens had no cells as compared to specimens with cells in mucus by histology was 4.41 (1.61, 12.1) (p = 0.0039). If overall survival of patients with all specimens without tumor cells was compared to patients with specimens with 1-99 % tumor and compared to patients with 100 % of specimens with tumor cells, the hazard ratios were 4.3 (1.34, 13.8) (p = 0.0143) and 9.62 (2.93, 31.6) (p = 0.0002), respectively. The cellularity of mucus within the specimens removed by a complete CRS has strong prognostic implications in LAMN patients. LAMN with acellular specimens (LAMNa) as compared to LAMN with tumor cells in specimens (LAMNb) should be staged as different histologic subtypes of mucinous appendiceal neoplasms.

Multimodal monitoring in patients with acute brain injury - A survey from critical care providers.

BACKGROUND: Multimodal neuromonitoring (MMM) aims to improve outcome after acute brain injury, and thus admission in specialized Neurocritical Care Units with potential access to MMM is necessary. Various invasive and noninvasive modalities have been developed, however there is no strong evidence to support monitor combinations nor is there a known standardized approach. The goal of this study is to identify the most used invasive and non-invasive neuromonitoring modalities in daily practice as well as ubiquitousness of MMM standardization. METHODS: In order to investigate current availability and protocolized implementation of MMM among neurocritical care units in US and non-US intensive care units, we designed a cross-sectional survey consisting of a self-administered online questionnaire of 20 closed-ended questions disseminated by the Neurocritical Care Society. RESULTS: Twenty-one critical care practitioners responded to our survey with a 76% completion rate. The most commonly utilized non-invasive neuromonitoring modalities were continuous electroencephalography followed by transcranial doppler. The most common invasive modalities were external ventricular drain followed by parenchymal intracranial pressure (ICP) monitoring. MMM is most utilized in patients with subarachnoid hemorrhage and there were no differences regarding established institutional protocol, 24-h cEEG availability and invasive monitor placement between teaching and non-teaching hospitals. MMM is considered standard of care in 28% of responders' hospitals, whereas in 26.7% it is deemed experimental and only done as part of clinical trials. Only 26.7% hospitals use a computerized data integration system. CONCLUSION: Our survey revealed overall limited use of MMM with no established institutional protocols among institutions. Ongoing research and further standardization of MMM will clarify its benefit to patients suffering from severe brain injury.

Provider Experience With the Use of Ketamine for Refractory Status Epilepticus.

OBJECTIVE: Refractory status epilepticus (RSE) treated with anesthetic agents can be associated with complications including respiratory depression and hypotension. Ketamine is an emerging RSE treatment, but optimal dosing and timing are unknown. We studied provider attitudes and practices regarding the use of ketamine for RSE. METHODS: A literature review informed the creation of the survey, developed by professionals in epilepsy, pharmacy, and neurocritical care. The survey was distributed to members of the Critical Care EEG Monitoring and Research Consortium, Neurocritical Care Society, American Academy of Neurology Synapse community, American Epilepsy Society, and the Canadian League Against Epilepsy. Descriptive statistics were calculated. RESULTS: There were 109 respondents. First-line agents for RSE were midazolam (53%), propofol (42%), pentobarbital (2%), and ketamine (1%). Reasons for ketamine use included failure of midazolam/propofol to control seizures (81%) or hypotension on another anesthetic (35%). Perceived contraindications included hypertension (37%), elevated intracranial pressure (24%), and heart failure (18%). Perceived benefits included decreased use of vasopressors (53%) and more rapid RSE control when used adjunctively (49%). Routine ketamine users often treated more than 10 RSE cases per year, worked as intensivists or at academic institutions. Of the respondents, 59% found ketamine useful for RSE and 94% were interested in learning more about its use. CONCLUSIONS: Although most participants found ketamine helpful for RSE, it is mainly used as a second-line agent adjunctively with midazolam or propofol. Perceived ketamine benefits included decreased need for hemodynamic support and more rapid seizure control when used in conjunction with other anesthetics. Perceived contraindications centered on cardiac and intracranial pressure concerns.

Leaving no culture undrawn: Time to revisit the CLABSI and CAUTI metrics.

Central line-associated bloodstream infections (CLABSIs) and catheter-associated urinary tract infections (CAUTIs) are quality metrics for many ICUs, and financial ramifications can be applied to hospitals and providers who perform poorly on these measures. Despite some perceived benefits to tracking these metrics, there are a range of issues associated with this practice: lack of a solid evidence base that documenting them has led to decreased infection rates, moral distress associated with identifying these infections, problems with their definitions, and others. We discuss each of these concerns while also including international perspectives then recommend practical steps to attempt to remediate use of the CLABSI and CAUTI metrics. Specifically, we suggest forming a task force consisting of key stakeholders (e.g., providers, Centers for Medicare & Medicaid Services (CMS), patients/families) to review CLABSI and CAUTI-related issues and then to create a summary statement containing recommendations to improve the use of these metrics.

Coronary artery bypass grafting for triple vessel disease in cardiac amyloidosis.

Cardiac amyloidosis is a rare condition with an estimated incidence of 18-55 per 100 000 person-years. It is associated with either immunoglobulin light chain (AL) or transthyretin amyloid (ATTR), both of which result in a restrictive cardiomyopathy complicated initially by diastolic dysfunction and subsequently followed by biventricular systolic heart failure. Untreated cardiac amyloidosis carries an extremely poor prognosis with an estimated median survival time of less than 1 year in AL and 4 years in ATTR amyloidosis. This is the sixth described report of coronary artery bypass grafting in patients with underlying cardiac amyloidosis.

A Longitudinal Study of Group A Streptococcal Colonization and Pharyngitis in US Children.

BACKGROUND: Group A streptococci (GAS) are a major cause of pharyngitis in children. Recently, there were severe GAS outbreaks. The aims of this study were to assess pharyngeal colonization prevalence in healthy children, to assess different diagnostic definitions for GAS pharyngitis and to estimate incidence rates for these infections. METHODS: A 2-year longitudinal study was conducted in healthy children in the United States. Pharyngeal swabs were cultured every 3 months for GAS colonization. Serum antistreptolysin O, antideoxyribonuclease B (DNaseB) and antistreptococcal C5a peptidase (SCP) antibody titers were assessed at baseline. When participants developed a sore throat, pharyngeal swabs were collected for rapid antigen detection test (RADT) and culture, and antibody titers were determined in serum samples. A range of case definitions were used for GAS pharyngitis. RESULTS: A total of 422 children 3-12 years old were enrolled (140, 141 and 141 were 3-5, 6-9 and 10-12 years of age, respectively). The overall prevalence of GAS colonization during the study was 48%. Baseline antistreptolysin O, anti-DNaseB and anti-SCP antibody titers were higher for children older than 5 years. The incidence of GAS pharyngitis per 100 person-years was 15.9 for RADT/culture-proven and 4.6 for serologically confirmed pharyngitis. CONCLUSIONS: GAS throat colonization and pharyngitis were frequent in children 3-12 years old. The case definition employed impacted the measured incidence of GAS pharyngitis, with higher rates detected using RADT/culture-based definitions. These data suggest that case definition is important and that young children are exposed to GAS, which may inform plans for vaccine development and implementation.

Preoperative cerebral angiography nearly doubles the rate of diffusion-weighted imaging lesion detection following minimally invasive surgery for intracerebral hemorrhage.

BACKGROUND: Diffusion-weighted imaging (DWI) lesions have been linked to poor outcomes after intracerebral hemorrhage (ICH). We aimed to assess the impact of cerebral digital subtraction angiography (DSA) on the presence of DWI lesions in patients who underwent minimally invasive surgery (MIS) for ICH. METHODS: Retrospective chart review was performed on ICH patients treated with MIS in a single health system from 2015 to 2021. One hundred and seventy consecutive patients who underwent postoperative MRIs were reviewed. Univariate analyses were conducted to determine associations. Variables with p<0.05 were included in multivariate analyses. RESULTS: DWI lesions were present in 88 (52%) patients who underwent MIS for ICH. Of the 83 patients who underwent preoperative DSA, 56 (67%) patients demonstrated DWI lesions. In this DSA cohort, older age, severe leukoaraiosis, larger preoperative hematoma volume, and increased presenting National Institutes of Health Stroke Score (NIHSS) were independently associated with DWI lesion identification (p<0.05). In contrast, of 87 patients who did not undergo DSA, 32 (37%) patients demonstrated DWI lesions on MRI. In the non-DSA cohort, presenting systolic blood pressure, intraventricular hemorrhage, and NIHSS were independently associated with DWI lesions (p<0.05). Higher DWI lesion burden was independently associated with poor modified Rankin Scale (mRS) at 6 months on a univariate (p=0.02) and multivariate level (p=0.02). CONCLUSIONS: In this cohort of ICH patients who underwent minimally invasive evacuation, preprocedural angiography was associated with the presence of DWI lesions on post-ICH evacuation MRI. Furthermore, the burden of DWI lesions portends a worse prognosis after ICH.

Transcranioplasty Ultrasonography Through a Sonolucent Prosthesis: A Review of Feasibility, Safety, and Benefits.

Data on the effectiveness of transcranioplasty ultrasonography through sonolucent cranioplasty (SC) are new and heterogeneous. We performed the first systematic literature review on SC. Ovid Embase, Ovid Medline, and Web of Science Core Collection were systematically searched and published full text articles detailing new use of SC for the purpose of neuroimaging were critically appraised and extracted. Of 16 eligible studies, 6 reported preclinical research and 12 reported clinical experiences encompassing 189 total patients with SC. The cohort age ranged from teens to 80s and was 60% (113/189) female. Sonolucent materials in clinical use are clear PMMA (polymethylmethacrylate), opaque PMMA, polyetheretherketone, and polyolefin. Overall indications included hydrocephalus (20%, 37/189), tumor (15%, 29/189), posterior fossa decompression (14%, 26/189), traumatic brain injury (11%, 20/189), bypass (27%, 52/189), intracerebral hemorrhage (4%, 7/189), ischemic stroke (3%, 5/189), aneurysm and subarachnoid hemorrhage (3%, 5/189), subdural hematoma (2%, 4/189), and vasculitis and other bone revisions (2%, 4/189). Complications described in the entire cohort included revision or delayed scalp healing (3%, 6/189), wound infection (3%, 5/189), epidural hematoma (2%, 3/189), cerebrospinal fluid leaks (1%, 2/189), new seizure (1%, 2/189), and oncologic relapse with subsequent prosthesis removal (<1%, 1/189). Most studies utilized linear or phased array ultrasound transducers at 3-12 MHz. Sources of artifact on sonographic imaging included prosthesis curvature, pneumocephalus, plating system, and dural sealant. Reported findings were mainly qualitative. We, therefore, suggest that future studies should collect quantitative measurement data during transcranioplasty ultrasonography to validate imaging techniques.

Evaluation of Safety Outcomes of Undiluted Levetiracetam Intravenous Push Compared to Intravenous Piggyback.

BACKGROUND: Breakthrough seizures and status epilepticus require urgent management. Administration of intravenous push (IVP) levetiracetam has been demonstrated to be safe as compared to intravenous piggyback (IVPB). This transition can potentially offer faster time to administration and reduced drug and material cost. The objective of this study was to observe safety of administration in patients receiving levetiracetam via IVP compared to IVPB in acute care settings. METHODS: This is a multi-center, observational, retrospective cohort study of 1214 adult patients who received levetiracetam pre- and post-implementation of IVP over a 6 month timespan. Primary outcome was time from order verification to administration of urgent first-time doses. Secondary outcomes included time to administration of loading doses and cost. Safety outcome was infusion site related reactions. RESULTS: Time from order verification to administration of urgent first-time doses pre- and post-implementation of IVP administration was reduced from 61 minutes to 47 minutes (P=0.0002). Infusion site related reactions were observed in 6 out of 5432 doses in the IVPB arm and in 5 out of 4700 doses in the IVP arm (P=1). Total estimated cost was $76,171.96 for the 5449 IVPB total doses and $11,484.33 for the 4721 IVP total doses. CONCLUSIONS: Transition from IVPB to IVP administration reduced time from order verification to administration of urgent first-time doses with both administrations having similar incidence of infusion site related reactions. Cost savings and improved workflow were observed. Levetiracetam administered via IVP may be considered as a safe alternative method of administration in the acute care setting.

Characterization of length of stay after minimally invasive endoscopic intracerebral hemorrhage evacuation.

BACKGROUND: Minimally invasive evacuation may help ameliorate outcomes after intracerebral hemorrhage (ICH). However, hospital length of stay (LOS) post-evacuation is often long and costly. OBJECTIVE: To examine factors associated with LOS in a large cohort of patients who underwent minimally invasive endoscopic evacuation. METHODS: Patients presenting to a large health system with spontaneous supratentorial ICH qualified for minimally invasive endoscopic evacuation if they met the following inclusion criteria: age ≥18, premorbid modified Rankin Scale (mRS) score ≤3, hematoma volume ≥15 mL, and presenting National Institutes of Health Stroke Scale (NIHSS) score ≥6. Demographic, clinical, radiographic, and operative characteristics were included in a multivariate logistic regression for hospital and ICU LOS dichotomized into short and prolonged stay at 14 and 7 days, respectively. RESULTS: Among 226 patients who underwent minimally invasive endoscopic evacuation, the median intensive care unit and hospital LOS were 8 (4-15) days and 16 (9-27) days, respectively. A greater extent of functional impairment on presentation (OR per NIHSS point 1.10 (95% CI 1.04 to 1.17), P=0.007), concurrent intraventricular hemorrhage (OR=2.46 (1.25 to 4.86), P=0.02), and deep origin (OR=per point 2.42 (1.21 to 4.83), P=0.01) were associated with prolonged hospital LOS. A longer delay from ictus to evacuation (OR per hour 1.02 (1.01 to 1.04), P=0.007) and longer procedure time (OR per hour 1.91 (1.26 to 2.89), P=0.002) were associated with prolonged ICU LOS. Prolonged hospital and ICU LOS were in turn longitudinally associated with a lower rate of discharge to acute rehabilitation (40% vs 70%, P<0.0001) and worse 6-month mRS outcomes (5 (4-6) vs 3 (2-4), P<0.0001). CONCLUSIONS: We present factors associated with prolonged LOS, which in turn was associated with poor long-term outcomes. Factors associated with LOS may help to inform patient and clinician expectations of recovery, guide protocols for clinical trials, and select suitable populations for minimally invasive endoscopic evacuation.

Pathogenesis of histologic variations of appendiceal mucinous neoplasms.

BACKGROUND: In order for peritoneal metastases from a primary appendiceal mucinous neoplasm to occur, the wall of the appendix must perforate to allow mucus with tumor cells access to the peritoneal spaces. With progression the peritoneal metastases show a broad spectrum of tumor biology varying from indolent to aggressive activity. METHODS: The histopathology of peritoneal tumor masses was determined from the clinical material resected at the time of cytoreductive surgery (CRS). All groups of patients were treated by a uniform strategy that involved complete CRS and perioperative intraperitoneal chemotherapy. Overall survival was determined. RESULTS: From a database of 685 patients, four histologic subtypes were identified and long-term survival determined. Four hundred and fifty patients (66.0%) had low-grade appendiceal mucinous neoplasm (LAMN), 37 patients (5.4%) had mucinous appendiceal adenocarcinoma of intermediate subtype (MACA-Int), 159 patients (23.2%) had mucinous appendiceal adenocarcinoma (MACA), and 39 patients (5.4%) had a mucinous appendiceal adenocarcinoma with positive lymph nodes (MACA-LN). The mean survival of the four groups was 24.5, 14.8, 11.2 and 7.4 years, respectively (p < 0.0001). These four subtypes of mucinous appendiceal neoplasms were shown to have distinct survival estimates. CONCLUSIONS: The estimated survival of these four histologic subtypes in patients having a complete CRS plus HIPEC is of value to the oncologist managing these patients. A mutations and perforations hypothesis was offered in an attempt to explain the broad spectrum of mucinous appendiceal neoplasms that exist. Inclusion of MACA-Int and MACA-LN as standalone subtypes was thought to be necessary.

Similar Survival Among All Subtypes of Mucinous Appendiceal Adenocarcinoma Except the Intermediate Subtype, Which Shows an Improved Survival.

BACKGROUND: Limited success in the management of mucinous appendiceal adenocarcinoma (MACA) has been reported. METHODS: Cytoreductive surgery with perioperative intraperitoneal chemotherapy was used to treat a cohort of patients with peritoneal dissemination of MACA. The clinical and histopathologic variables were assessed for their impact on overall survival. RESULTS: The study analyzed 196 patients during a median follow-up period of 8 years. The patients had a median age was 46 years, a median survival of 12 years, and a mean survival of 12.4 years. Preoperative systemic chemotherapy and a high prior surgical score had a negative impact on prognosis. Survival was better for 37 patients (18.9%) with mucinous appendiceal adenocarcinoma-Intermediate (MACA-Int) histology than for 159 patients (81.1%) with MACA grade 1, 2, or 3, or signet ring cells (S) (p = 0.0004). Although MACA-1 and MACA-2 versus MACA-3 and MACA-S had a difference in survival of 63.9 versus 43.2 years at 5 years, with long-term follow-up evaluation, the differences in survival became insignificant (p = 0.5841). CONCLUSION: The histologic subtype of MACA-Int had a 10-year survival of 81.1%, which was markedly superior to that of MACA-1, -2, -3, or -S (32.7%). With long-term follow-up evaluation, MACA-1, -2, -3, and -S did not differ significantly in survival.

Long-term functional independence after minimally invasive endoscopic intracerebral hemorrhage evacuation.

OBJECTIVE: Intracerebral hemorrhage (ICH) is a devastating form of stroke with no proven treatment. However, minimally invasive endoscopic evacuation is a promising potential therapeutic option for ICH. Herein, the authors examine factors associated with long-term functional independence (modified Rankin Scale [mRS] score ≤ 2) in patients with spontaneous ICH who underwent minimally invasive endoscopic evacuation. METHODS: Patients with spontaneous supratentorial ICH who had presented to a large urban healthcare system from December 2015 to October 2018 were triaged to a central hospital for minimally invasive endoscopic evacuation. Inclusion criteria for this study included age ≥ 18 years, hematoma volume ≥ 15 ml, National Institutes of Health Stroke Scale (NIHSS) score ≥ 6, premorbid mRS score ≤ 3, and time from ictus ≤ 72 hours. Demographic, clinical, and radiographic factors previously shown to impact functional outcome in ICH were included in a retrospective univariate analysis with patients dichotomized into independent (mRS score ≤ 2) and dependent (mRS score ≥ 3) outcome groups, according to 6-month mRS scores. Factors that reached a threshold of p < 0.05 in a univariate analysis were included in a multivariate logistic regression. RESULTS: A total of 90 patients met the study inclusion criteria. The median preoperative hematoma volume was 41 (IQR 27-65) ml and the median postoperative volume was 1.2 (0.3-7.5) ml, resulting in a median evacuation percentage of 97% (85%-99%). The median hospital length of stay was 17 (IQR 9-25) days, and 8 (9%) patients died within 30 days of surgery. Twenty-four (27%) patients had attained functional independence by 6 months. Factors independently associated with long-term functional independence included lower NIHSS score at presentation (OR per point 0.78, 95% CI 0.67-0.91, p = 0.002), lack of intraventricular hemorrhage (IVH; OR 0.20, 95% CI 0.05-0.77, p = 0.02), and shorter time to evacuation (OR per hour 0.95, 95% CI 0.91-0.99, p = 0.007). Specifically, patients who had undergone evacuation within 24 hours of ictus demonstrated an mRS score ≤ 2 rate of 36% and were associated with an increased likelihood of long-term independence (OR 17.7, 95% CI 1.90-164, p = 0.01) as compared to those who had undergone evacuation after 48 hours. CONCLUSIONS: In a single-center minimally invasive endoscopic ICH evacuation cohort, NIHSS score on presentation, lack of IVH, and shorter time to evacuation were independently associated with functional independence at 6 months. Factors associated with functional independence may help to better predict populations suitable for minimally invasive endoscopic evacuation and guide protocols for future clinical trials.

Cerebral vasospasm following arteriovenous malformation rupture: a population-based cross-sectional study.

OBJECTIVE: Studies examining the risk factors and clinical outcomes of arterial vasospasm secondary to cerebral arteriovenous malformation (cAVM) rupture are scarce in the literature. The authors used a population-based national registry to investigate this largely unexamined clinical entity. METHODS: Admissions for adult patients with cAVM ruptures were identified in the National Inpatient Sample during the period from 2015 to 2019. Complex samples multivariable logistic regression and chi-square automatic interaction detection (CHAID) decision tree analyses were performed to identify significant associations between clinical covariates and the development of vasospasm, and a cAVM-vasospasm predictive model (cAVM-VPM) was generated based on the effect sizes of these parameters. RESULTS: Among 7215 cAVM patients identified, 935 developed vasospasm, corresponding to an incidence rate of 13.0%; 110 of these patients (11.8%) subsequently progressed to delayed cerebral ischemia (DCI). Multivariable adjusted modeling identified the following baseline clinical covariates: decreasing age by decade (adjusted odds ratio [aOR] 0.87, 95% CI 0.83-0.92; p < 0.001), female sex (aOR 1.68, 95% CI 1.45-1.95; p < 0.001), admission Glasgow Coma Scale score < 9 (aOR 1.34, 95% CI 1.01-1.79; p = 0.045), intraventricular hemorrhage (aOR 1.87, 95% CI 1.17-2.98; p = 0.009), hypertension (aOR 1.77, 95% CI 1.50-2.08; p < 0.001), obesity (aOR 0.68, 95% CI 0.55-0.84; p < 0.001), congestive heart failure (aOR 1.34, 95% CI 1.01-1.78; p = 0.043), tobacco smoking (aOR 1.48, 95% CI 1.23-1.78; p < 0.019), and hospitalization events (leukocytosis [aOR 1.64, 95% CI 1.32-2.04; p < 0.001], hyponatremia [aOR 1.66, 95% CI 1.39-1.98; p < 0.001], and acute hypotension [aOR 1.67, 95% CI 1.31-2.11; p < 0.001]) independently associated with the development of vasospasm. Intraparenchymal and subarachnoid hemorrhage were not associated with the development of vasospasm following multivariable adjustment. Among significant associations, a CHAID decision tree algorithm identified age 50-59 years (parent node), hyponatremia, and leukocytosis as important determinants of vasospasm development. The cAVM-VPM achieved an area under the curve of 0.65 (sensitivity 0.70, specificity 0.53). Progression to DCI, but not vasospasm alone, was independently associated with in-hospital mortality (aOR 2.35, 95% CI 1.29-4.31; p = 0.016) and lower likelihood of routine discharge (aOR 0.62, 95% CI 0.41-0.96; p = 0.031). CONCLUSIONS: This large-scale assessment of vasospasm in cAVM identifies common clinical risk factors and establishes progression to DCI as a predictor of poor neurological outcomes.

Portable stroke detection devices: a systematic scoping review of prehospital applications.

BACKGROUND: The worldwide burden of stroke remains high, with increasing time-to-treatment correlated with worse outcomes. Yet stroke subtype determination, most importantly between stroke/non-stroke and ischemic/hemorrhagic stroke, is not confirmed until hospital CT diagnosis, resulting in suboptimal prehospital triage and delayed treatment. In this study, we survey portable, non-invasive diagnostic technologies that could streamline triage by making this initial determination of stroke type, thereby reducing time-to-treatment. METHODS: Following PRISMA guidelines, we performed a scoping review of portable stroke diagnostic devices. The search was executed in PubMed and Scopus, and all studies testing technology for the detection of stroke or intracranial hemorrhage were eligible for inclusion. Extracted data included type of technology, location, feasibility, time to results, and diagnostic accuracy. RESULTS: After a screening of 296 studies, 16 papers were selected for inclusion. Studied devices utilized various types of diagnostic technology, including near-infrared spectroscopy (6), ultrasound (4), electroencephalography (4), microwave technology (1), and volumetric impedance spectroscopy (1). Three devices were tested prior to hospital arrival, 6 were tested in the emergency department, and 7 were tested in unspecified hospital settings. Median measurement time was 3 minutes (IQR: 3 minutes to 5.6 minutes). Several technologies showed high diagnostic accuracy in severe stroke and intracranial hematoma detection. CONCLUSION: Numerous emerging portable technologies have been reported to detect and stratify stroke to potentially improve prehospital triage. However, the majority of these current technologies are still in development and utilize a variety of accuracy metrics, making inter-technology comparisons difficult. Standardizing evaluation of diagnostic accuracy may be helpful in further optimizing portable stroke detection technology for clinical use.