Dendrimer nanotherapy targeting of glial dysfunction improves inflammation and neurobehavioral phenotype in adult female Mecp2-heterozygous mouse model of Rett syndrome.

Rett syndrome is an X-linked neurodevelopmental disorder caused by mutation of Mecp2 gene and primarily affects females. Glial cell dysfunction has been implicated in in Rett syndrome (RTT) both in patients and in mouse models of this disorder and can affect synaptogenesis, glial metabolism and inflammation. Here we assessed whether treatment of adult (5-6 months old) symptomatic Mecp2-heterozygous female mice with N-acetyl cysteine conjugated to dendrimer (D-NAC), which is known to target glia and modulate inflammation and oxidative injury, results in improved behavioral phenotype, sleep and glial inflammatory profile. We show that unbiased global metabolomic analysis of the hippocampus and striatum in adult Mecp2-heterozygous mice demonstrates significant differences in lipid metabolism associated with neuroinflammation, providing the rationale for targeting glial inflammation in this model. Our results demonstrate that treatment with D-NAC (10 mg/kg NAC) once weekly is more efficacious than equivalently dosed free NAC in improving the gross neurobehavioral phenotype in symptomatic Mecp2-heterozygous female mice. We also show that D-NAC therapy is significantly better than saline in ameliorating several aspects of the abnormal phenotype including paw clench, mobility, fear memory, REM sleep and epileptiform activity burden. Systemic D-NAC significantly improves microglial proinflammatory cytokine production and is associated with improvements in several aspects of the phenotype including paw clench, mobility, fear memory, and REM sleep, and epileptiform activity burden in comparison to saline-treated Mecp2-hetereozygous mice. Systemic glial-targeted delivery of D-NAC after symptom onset in an older clinically relevant Rett syndrome model shows promise in improving neurobehavioral impairments along with sleep pattern and epileptiform activity burden. These findings argue for the translational value of this approach for treatment of patients with Rett Syndrome.

Chemogenetics as a neuromodulatory approach to treating neuropsychiatric diseases and disorders.

Chemogenetics enables precise, non-invasive, and reversible modulation of neural activity via the activation of engineered receptors that are pharmacologically selective to endogenous or exogenous ligands. With recent advances in therapeutic gene delivery, chemogenetics is poised to support novel interventions against neuropsychiatric diseases and disorders. To evaluate its translational potential, we performed a scoping review of applications of chemogenetics that led to the reversal of molecular and behavioral deficits in studies relevant to neuropsychiatric diseases and disorders. In this review, we present these findings and discuss the potential and challenges for using chemogenetics as a precision medicine-based neuromodulation strategy.

Strategies to improve surgical technical competency: a systematic review.

BACKGROUND: A cornerstone of surgical residency training is an educational program that produces highly skilled and effective surgeons. Training structures are constantly being revised due to evolving program structures, shifting workforces, and variability in the clinical environment. This has resulted in significant heterogeneity in all surgical resident education, training tools utilized, and measures of training efficacy. METHODS: We systematically reviewed educational interventions for technical skills in neurosurgery published across PubMed, Embase, and Web of Science over four decades. We extracted general characteristics of each surgical training tool while categorizing educational interventions by modality and neurosurgical application. RESULTS: We identified 626 studies which developed surgical training tools across eight different training modalities: textbooks and literature (11), online resources (53), didactic teaching and one-on-one instruction (7), laboratory courses (50), cadaveric models (63), animal models (47), mixed reality (166), and physical models (229). While publication volume has grown exponentially, a majority of studies were cited with relatively low frequency. Most training programs were published in the development and validation phase with only 2.1% of tools implemented long-term. Each training modality expressed unique strengths and limitations, with limited data reported on the educational impact connected to each training tool. CONCLUSIONS: Numerous surgical training tools have been developed and implemented across residency training programs. Though many creative and cutting-edge tools have been devised, evidence supporting educational efficacy and long-term application is lacking. Increased utilization of novel surgical training tools will require validation of metrics used to assess the training outcomes and optimized integration with clinical practice.

Non-pharmacological interventions for sleep promotion in hospitalized children.

BACKGROUND: Healthy sleep is an important component of childhood development. Changes in sleep architecture, including sleep stage composition, quantity, and quality from infancy to adolescence are a reflection of neurologic maturation. Hospital admission for acute illness introduces modifiable risk factors for sleep disruption that may negatively affect active brain development during a period of illness and recovery. Thus, it is important to examine non-pharmacologic interventions for sleep promotion in the pediatric inpatient setting. OBJECTIVES: To evaluate the effect of non-pharmacological sleep promotion interventions in hospitalized children and adolescents on sleep quality and sleep duration, child or parent satisfaction, cost-effectiveness, delirium incidence, length of mechanical ventilation, length of stay, and mortality. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, CINAHL, three other databases, and three trials registers to December 2021. We searched Google Scholar, and two websites, handsearched conference abstracts, and checked reference lists of included studies. SELECTION CRITERIA: Randomized controlled trials (RCTs) or quasi-RCTs, including cross-over trials, investigating the effects of any non-pharmacological sleep promotion intervention on the sleep quality or sleep duration (or both) of children aged 1 month to 18 years in the pediatric inpatient setting (intensive care unit [ICU] or general ward setting). DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial eligibility, evaluated risk of bias, extracted and synthesized data, and used the GRADE approach to assess certainty of evidence. The primary outcomes were changes in both objective and subjective validated measures of sleep in children; secondary outcomes were child and parent satisfaction, cost-effectiveness ratios, delirium incidence or delirium-free days at time of hospital discharge, duration of mechanical ventilation, length of hospital stay, and mortality. MAIN RESULTS: We included 10 trials (528 participants; aged 3 to 22 years) in inpatient pediatric settings. Seven studies were conducted in the USA, two in Canada, and one in Brazil. Eight studies were funded by government, charity, or foundation grants. Two provided no information on funding. Eight studies investigated behavioral interventions (massage, touch therapy, and bedtime stories); two investigated physical activity interventions. Duration and timing of interventions varied widely. All studies were at high risk of performance bias due to the nature of the intervention, as participants, parents, and staff could not be masked to group assignment. We were unable to perform a quantitative synthesis due to substantial clinical heterogeneity. Behavioral interventions versus usual care Five studies (145 participants) provided low-certainty evidence of no clear difference between multicomponent relaxation interventions and usual care on objective sleep measures. Overall, evidence from single studies found no clear differences in daytime or nighttime sleep measures (33 participants); any sleep parameter (48 participants); or daytime or nighttime sleep or nighttime arousals (20 participants). One study (34 participants) reported no effect of massage on nighttime sleep, sleep efficiency (SE), wake after sleep onset (WASO), or total sleep time (TST) in adolescents with cancer. Evidence from a cross-over study in 10 children with burns suggested touch therapy may increase TST (391 minutes, interquartile range [IQR] 251 to 467 versus 331 minutes, IQR 268 to 373; P = 0.02); SE (76, IQR 53 to 90 versus 66, IQR 55 to 78; P = 0.04); and the number of rapid eye movement (REM) periods (4.5, IQR 2 to 5 versus 3.5, IQR 2 to 4; P = 0.03); but not WASO, sleep latency (SL), total duration of REM, or per cent of slow wave sleep. Four studies (232 participants) provided very low-certainty evidence on subjective measures of sleep. Evidence from single studies found that sleep efficiency may increase, and the percentage of nighttime wakefulness may decrease more over a five-day period following a massage than usual care (72 participants). One study (48 participants) reported an improvement in Children's Sleep Habits Questionnaire scores after discharge in children who received a multicomponent relaxation intervention compared to usual care. In another study, mean sleep duration per sleep episode was longer (23 minutes versus 15 minutes), and time to fall asleep was shorter (22 minutes versus 27 minutes) following a bedtime story versus no story (18 participants); and children listening to a parent-recorded story had longer SL than when a parent was present (mean 57.5 versus 43.5 minutes); both groups reported longer SL than groups who had a stranger-recorded story, and those who had no story and absent parents (94 participants; P < 0.001). In one study (34 participants), 87% (13/15) of participants felt they slept better following massage, with most parents (92%; 11/12) reporting they wanted their child to receive a massage again. Another study (20 participants) reported that parents thought the music, touch, and reading components of the intervention were acceptable, feasible, and had positive effects on their children (very low-certainty evidence). Physical activity interventions versus usual care One study (29 participants) found that an enhanced physical activity intervention may result in little or no improvement in TST or SE compared to usual care (low-certainty evidence). Another study (139 participants), comparing play versus no play found inconsistent results on subjective measures of sleep across different ages (TST was 49% higher for the no play groups in 4- to 7-year olds, 10% higher in 7- to 11-year olds, and 22% higher in 11- to 14-year olds). This study also found inconsistent results between boys and girls (girls in the first two age groups in the play group slept more than the no play group). No study evaluated child or parent satisfaction for behavioral interventions, or cost-effectiveness, delirium incidence or delirium-free days at hospital discharge, length of mechanical ventilation, length of hospital stay, or mortality for either behavioral or physical activity intervention. AUTHORS' CONCLUSIONS: The included studies were heterogeneous, so we could not quantitatively synthesize the results. Our narrative summary found inconsistent, low to very low-certainty evidence. Therefore, we are unable to determine how non-pharmacologic sleep promotion interventions affect sleep quality or sleep duration compared with usual care or other interventions. The evidence base should be strengthened through design and conduct of randomized trials, which use validated and highly reliable sleep assessment tools, including objective measures, such as polysomnography and actigraphy.

Isolated ventricular inversion with hypoplastic right ventricle and pulmonary stenosis in an adolescent with situs solitus: a rare combination.

Isolated ventricular inversion with situs solitus is a severe and rare congenital cardiac malformation characterised by an atrioventricular discordance but with ventriculo-arterial concordance. Here, we present the rare case of an adolescent with isolated ventricular inversion and hypoplasia of the left-sided morphological right ventricle and pulmonary stenosis, a first of its kind to be reported in the literature.

Early Mobilization in a PICU: A Qualitative Sustainability Analysis of PICU Up!

OBJECTIVES: To identify staff-reported factors and perceptions that influenced implementation and sustainability of an early mobilization program (PICU Up!) in the PICU. DESIGN: A qualitative study using semistructured phone interviews to characterize interprofessional staff perspectives of the PICU Up! program. Following data saturation, thematic analysis was performed on interview transcripts. SETTING: Tertiary-care PICU in the Johns Hopkins Hospital, Baltimore, MD. SUBJECTS: Interprofessional PICU staff. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Fifty-two staff members involved in PICU mobilization across multiple disciplines were interviewed. Three constructs emerged that reflected the different stages of PICU Up! program execution: 1) factors influencing the implementation process, 2) staff perceptions of PICU Up!, and 3) improvements in program integration. Themes were developed within these constructs, addressing facilitators for PICU Up! implementation, cultural changes for unitwide integration, positive impressions toward early mobility, barriers to program sustainability, and refinements for more robust staff and family engagement. CONCLUSIONS: Three years after implementation, PICU Up! remains well-received by staff, positively influencing role satisfaction and PICU team dynamics. Furthermore, patients and family members are perceived to be enthusiastic about mobility efforts, driving staff support. Through an ongoing focus on stakeholder buy-in, interprofessional engagement, and bundled care to promote mobility, the program has become part of the culture in the Johns Hopkins Hospital PICU. However, several barriers remain that prevent consistent execution of early mobility, including challenges with resource management, sedation decisions, and patient heterogeneity. Characterizing these staff perceptions can facilitate the development of solutions that use institutional strengths to grow and sustain PICU mobility initiatives.

Implications of left atrial enlargement and patent foramen ovale creation on early surgical outcomes in patients with total anomalous pulmonary venous connection.

INTRODUCTION: In patients with total anomalous pulmonary venous connection (TAPVC), left atrium (LA) is small and suprasystemic pulmonary artery (PA) pressures may be present in some patients. In our study, we studied the relationship between surgical LA enlargement and patent foramen ovale (PFO) creation separately on the outcomes of patients with TAPVC. MATERIALS AND METHODS: Out of the 130 patients operated in our institute between January 2014 and December 2020, LA was enlarged in 60 patients. LA enlargement was done using a larger patch for atrial septal defect (ASD) closure. Thus, the LA volume was increased by shifting the patch towards the right atrium (RA). Suprasystemic or high PA pressures were present in 60 patients. In 33 patients, PFO was created. Early surgical outcomes were determined on the basis of vasoactive inotropic score (VIS), hours of ventilation, hours of inotropic support, intensive care unit (ICU) stay, and hospital stay. RESULT: Between the LA enlarged and nonenlarged group there was statistically significant less VIS score (18 [13-27.5] vs. 24 [18-30], p value .019), hours of ventilation (23 [16-46.5] vs. 26 [18-60], p value .039), hours of inotropic support (45.5 [30-72] vs. 55 [38-84], p value .038), and ICU stay (7 [5-9] vs. 8 [7-10] p value .0352) and statistically nonsignificant less hospital stay (11.5 [9-13] vs. 12 [9-14], p value .424). In patients with preoperative suprasystemic or high PA pressures, there was a statistically significant less VIS score (16 [11-23.5] vs. 18 [13-25], p value .044), hours of ventilation (20 [14-37] vs. 22 [18-39], p value .038), hours of inotropic support (34 [29.5-71] vs. 38 [30-78], p value .042), and hospital stay (9 [5-12] vs. 11 [9-14], p value .038) and statistically nonsignificant less ICU stay (7 [5.5-9] vs. 7 [6-9], p value .886) in the group with a PFO with respect to the other group in which no PFO was created. CONCLUSION: In patients with TAPVC, LA can be enlarged by using a large ASD patch and thus shifting the septum towards RA. Early surgical outcomes were improved with LA enlargement. In patients with suprasystemic or high PA pressures, leaving a PFO improved the postoperative outcomes.

Successful Surgical Management of a Rare Combination of Intrapericardial Teratoma and Thymoma in an Infant.

Primary cardiac tumors are rare, accounting for <0.2% of all childhood tumors. They can be diagnosed prenatally. Intrapericardial teratoma is a rare benign tumor that presents either due to the mass effect of the tumor or secondary pericardial effusion. Thymus is an important part of the immune system in the pediatric age group. Thymic lesions are rare causes of anterior mediastinal pathology. Their occurrence in children is rarer, nevertheless knowledge about their pathologies helps in clinching the correct diagnosis. We report a case of combined intrapericardial teratoma and thymoma that has not been reported previously in the literature.

Emergency valve preserving ascending aorta replacement following iatrogenic right coronary artery dissection: A life-saving procedure.

Iatrogenic aortocoronary dissection is a rare but potentially fatal complication of coronary catheterizations. Although the incidence is comparatively low, dissection often leads to procedure failure with increased risk of myocardial infarction and death. Iatrogenic aortocoronary dissection is principally caused by disruption of intima at the ostia of the right or left coronary artery during interventional procedures and appears as luminal filling defects, the persistence of contrast or intimal tear outside the coronary lumen. We present a case of right coronary artery dissection leading to type-A aortic dissection suffered during diagnostic coronary catheterization. This required emergency supracoronary replacement of the ascending aorta with an aortic interposition tube graft and venous grafts to coronary arteries.

Pulmonary valve neocuspidisation with glutaraldehyde-treated autologous pericardium-A novel technique in pulmonary valve endocarditis.

Infective endocarditis (IE) is a serious condition leading to heart failure, persistent sepsis. The management of IE involving valve is mainly excision of the infected valve and replacement with a heart valve; which are also at the risk of prosthetic valve endocarditis. Hence repair of the valve with autologous pericardium is much more physiological. We had a 20-year-old male presented with features of heart failure and high-grade fever not responding to optimum medical management. Two-dimensional echocardiogram revealed vegetation on pulmonary valve cusps with the erosion of the left and right cusps. Neo cusps with autologous pericardium offered good hemodynamics with trivial regurgitation. The patient is doing well with normal pulmonary valve function 3 months after surgery. This technique is reliable, economic, and easily reproducible.

Benefits of perioperative sildenafil therapy in children with a ventricular septal defect with pulmonary artery hypertension on early surgical outcomes.

OBJECTIVES: Pulmonary hypertension is a common association in children with nonrestrictive ventricular septal defect. It increases perioperative mortality and morbidity. Oral sildenafil is an effective pulmonary vasodilator. In this study, we assessed effects of perioperative oral sildenafil therapy on pulmonary artery pressure and early surgical outcomes. METHODS: This was a single centre, prospective randomized control study. Thirty children with nonrestrictive ventricular septal defects with pulmonary hypertension were divided into two groups. In the sildenafil group (n = 15, mean age 23.3 months), oral sildenafil was administered two weeks before surgery. In the control group (n = 15, mean age 36 months), preoperative sildenafil was not given. Sildenafil was continued postoperatively in both groups, provided the postoperative pulmonary artery pressure was over 50% of systemic pressure. RESULTS: There was no perioperative mortality, pulmonary hypertensive crisis and there were no intolerable side effects related to sildenafil in either group. Mean pulmonary artery pressure showed a reduction in both groups. Sildenafil group showed statistically significant improvement in duration of cardiopulmonary bypass (100.27 ± 21.09 min vs. 125.40 ± 26.83 min, p = .008), mechanical ventilation requirement (22.79 ± 17.13 h vs. 30.53 ± 13.05 h; p = .04), epinephrine requirement (22% patients vs. 48% patients; p = .03) and hospital stay (6.13 ± 1.40 days vs. 7.53 ± 1.92 days; p = .05). CONCLUSION: Oral Sildenafil therapy is an inexpensive and well-tolerated method for reducing pulmonary hypertension secondary to non-restrictive ventricular septal defect. It has noteworthy advantages regarding early surgical outcomes like reduced cardiopulmonary bypass time, improved mechanical ventilation time, lower inotrope requirement and shorter hospital stay if used preoperatively in select patient population.

Neurosurgical gene therapy for central nervous system diseases.

Viral vector mediated gene therapies for neurodegenerative and neurodevelopmental conditions that require neurosurgical administration continue to expand. We systematically reviewed the National Institutes of Health (NIH) ClinicalTrials.gov database to identify all clinical trials studying in-vivo viral vector mediated gene therapies targeted to the CNS for neurodegenerative and neurodevelopmental diseases. We isolated studies which delivered therapies using neurosurgical approaches: intracisternal, intraventricular, and/or intraparenchymal. Clinical trials primarily registered in international countries were included if they were referenced by an NIH registered clinical trial. We performed a scoping review to identify the preclinical studies that supported each human clinical trial. Key preclinical and clinical data were aggregated to characterize vector capsid design, delivery methods, gene expression profile, and clinical benefit. A total of 64 clinical trials were identified in active, completed, terminated, and long-term follow-up stages. A range of CNS conditions across pediatric and adult populations are being studied with CNS targeted viral vector gene therapy, including Alzheimer's disease, Parkinson's disease, AADC deficiency, sphingolipidoses, mucopolysaccharidoses, neuronal ceroid lipofuscinoses, spinal muscular atrophy, adrenoleukodystrophy, Canavan disease, frontotemporal dementia, Huntington's disease, Rett syndrome, Dravet syndrome, mesial temporal lobe epilepsy, and glutaric acidemia. Adeno-associated viral vectors (AAVs) were utilized by the majority of tested therapies, with vector serotypes, regulatory elements, delivery methods, and vector monitoring varying based on the disease being studied. Intraparenchymal delivery has evolved significantly, with MRI-guided convection-enhanced delivery established as a gold standard method for pioneering novel gene targets.

Surgical outcomes of right atrial mass: 5 years of experience.

Cardiac masses are relatively rare, with a right atrial mass being even more rare. Right atrial masses pose a diagnostic dilemma owing to the diverse range of potential diagnoses, even when the clinical context and initial imaging modalities are thoroughly evaluated. A right atrial mass can have a varied etiology as it can be a physiological variant, or a neoplastic or a non-neoplastic mass with each having a separate line of management. This paper aims to highlight the etiology and the surgical outcomes of patients having a right atrial mass.

Spatial Distribution of Meningiomas: A Magnetic Resonance Image Atlas.

BACKGROUND AND OBJECTIVES: The size and anatomic location of meningiomas have been shown to correlate with distinct clinical manifestations, histopathological subtypes, and surgical risk. However, meningioma anatomic origin sites can be obscured in large tumors and those crossing compartments. We therefore sought to apply unbiased lesion mapping to localize intracranial meningioma distributions and their association with biology and grade. METHODS: MRI scans, World Health Organization (WHO) grade, and a molecularly Integrated Grade (IG) derived from cytogenetics were analyzed from adult patients with intracranial meningiomas. Semi-automated tumor segmentation was performed on T1-weighted contrast-enhanced MRI. We used the voxel-based lesion mapping technique to generate a meningioma atlas, mapping spatial frequency and correlating with tumor grades. RESULTS: Of 881 patients with meningioma (median age: 57 years, 68.8% female), 589 were WHO grade 1 (66.8%), 265 WHO grade 2 (30.1%), and 27 WHO grade 3 (3.1%) with a median tumor volume of 14.6 cm3. After molecular reclassification, 585 were IG-1 (66.4%), 160 IG-2 (18.2%), and 136 IG-3 (15.4%). Benign tumors were concentrated in and around the midline anterior skull base while malignant meningiomas were enriched in the falcine/parasagittal region and the sphenoid wing, similar to the distribution when stratified by chromosome 1p loss. Meningiomas exhibited sharper spatial clustering when stratified by the molecular IG than by WHO grade. WHO grade 2 meningiomas divided equally across IG 1-3, with corresponding partition of spatial distribution in the midline anterior skull base (in WHO grade 2, IG-1) and falcine/parasagittal and sphenoid regions (WHO grade 2, IG-3). Meningioma volumes significantly varied across age, sex, and WHO/IG grades. CONCLUSION: We demonstrate the utility of voxel-based lesion mapping for intracranial tumors, characterizing distinct meningioma distribution patterns across histopathological and molecularly defined grades. Molecular grading associated with sharper tumor spatial clusters, supporting a phenotype-genotype association in meningiomas.

Role of Hospital Connectedness in Brain Metastasis Outcomes.

Importance: Although patients with brain metastases receive interdisciplinary and multi-institutional care, the association between neuro-oncologic care networks and patient outcomes remains unknown. As patients often interact with multiple facilities, quantifying this association across a network of hospitals is critical to capture the complexity of the health care journey for patients with brain metastases. Objective: To evaluate how statewide health care network metrics are associated with inpatient mortality and hospital length of stay (LOS) for patients with brain metastases. Design, Setting, and Participants: This multicenter, statewide cohort study used data from the 2018 to 2019 Healthcare Cost and Utilization Project State Inpatient and Emergency Department Databases. Primary analyses were completed by August 2023. Participants included adults with a brain metastases receiving care in Massachusetts. Exposure: All inpatient and emergency department visits mapped for patients following the first diagnosis of brain metastasis. Main Outcomes and Measures: Inpatient mortality and hospital LOS were the main outcomes assessed. Hospital interdependence in brain metastases care was calculated using a connectedness score (weighted degree: weighted sum of ties to other care facilities). The association between hospital connectedness and clinical outcomes was analyzed using mixed-effects logistic and linear regression models, adjusting for hospital-level features. Results: In this cohort study, 4679 patients with brain metastases were identified with inpatient or ED encounters in Massachusetts (from 2018 to 2019). The median (IQR) age was 64 (57-73) years, and 2559 (55%) were female. There was interdependence in brain metastases care, with 993 patients (21%) visiting 2 or more unique hospitals. Highly connected hospitals were heterogeneous, with many being small and one-half lacking subspecialty neuro-oncologic care or teaching status. Increased hospital connectedness was significantly associated with improved inpatient mortality for patients with brain metastases, with the lowest connectedness quartile associated with more than double the risk of mortality compared with the highest quartile (odds ratio, 2.34; 95% CI, 1.33-4.11; P = .003). A stepwise increase in inpatient mortality risk was observed as hospital connectedness decreased, independently of hospital volume. Furthermore, intermediate hospital connectedness was associated with increased hospital LOS (coefficient, 1.08; 95% CI, 0.17-1.95; P = .006). Conclusions and Relevance: This study found that hospital-to-hospital interconnectedness was significantly associated with improved clinical outcomes for patients with brain metastases. The salience of network metrics highlights their potential role alongside other patient-level and hospital-level variables to evaluate and improve oncology care delivery.

Sustainability of a PICU Situation Awareness Intervention: A Qualitative Study.

Introduction: We aimed to investigate facilitators and barriers that impact the sustainability of an interprofessional situation awareness bundle. Methods: This is a single-center qualitative study at a tertiary care pediatric center examining the sustainability of an interprofessional situation awareness bundle to reduce in-hospital cardiac arrests. The bundle includes an automated clinical decision support tool, twice-daily safety huddles, and a bedside mitigation plan. A trained research staff member interviewed participants in October 2022. Interviews were audio recorded and transcribed verbatim, and recruitment continued until data saturation. Inductive and deductive analyses were used here. Results: The authors interviewed twelve staff members via individual semistructured interviews: registered nurses (RN, n = 2) and clinicians [(advanced practice providers, n = 2), pediatric critical care fellows, n = 4 and attendings, n = 4)]. Five main themes were identified: (1) the situation awareness bundle is ingrained into daily practice and culture, (2) the bundle has strengthened communication, decision-making, and improved outcomes, (3) standardized processes, stakeholder buy-in, and support of team members are key to adoption and sustainability, (4) variation in processes and fast-changing clinical context remains a challenge for reliable use, and (5) the situation awareness bundle excluded families. Conclusions: The situation awareness bundle has become ingrained, strengthened, and sustained over the last 5 years through integration into daily practice and culture and leveraging standardized processes, tools and technology. It is associated with improved communication and shared decision-making. Understanding the key components for implementation and sustainability is necessary for ongoing spread and improvement in the future.

Interhospital transfer dynamics for patients with intracranial hemorrhage in Massachusetts.

Introduction: Intracranial hemorrhages present across a spectrum of clinical phenotypes, with many patients transferred across hospitals to access higher levels of neurocritical care. We sought to characterize patient dispositions following intracranial hemorrhage and examine disparities associated with interhospital transfers. Methods: Using the Healthcare Cost and Utilization Project database, we mapped and identified factors influencing the likelihood of patient transfers and receipt of specialist interventional procedures following intracranial hemorrhage. Results: Of 11,660 patients with intracranial hemorrhage, 59.4% had non-traumatic and 87.5% single compartment bleeds. After presentation, about a quarter of patients were transferred to another facility either directly from the ED (23.0%) or after inpatient admission (1.8%). On unadjusted analysis, patients who were white, in the upper income quartiles, with private insurance, or resided in suburban areas were more frequently transferred. After adjusting for patient-and hospital-level variables, younger and non-white patients had higher odds of transfer. Hospital capabilities, residence location, insurance status, and prior therapeutic relationship remained as transfer predictors. Transferred patients had a similar hospital length of stay compared to admitted patients, with 43.1% having no recorded surgical or specialist interventional procedure after transfer. Discussion: Our analysis reveals opportunities for improvement in risk stratification guiding transfers, as well as structural challenges likely impacting transfer decisions.

Generation and applications of synthetic computed tomography images for neurosurgical planning.

OBJECTIVE: CT and MRI are synergistic in the information provided for neurosurgical planning. While obtaining both types of images lends unique data from each, doing so adds to cost and exposes patients to additional ionizing radiation after MRI has been performed. Cross-modal synthesis of high-resolution CT images from MRI sequences offers an appealing solution. The authors therefore sought to develop a deep learning conditional generative adversarial network (cGAN) which performs this synthesis. METHODS: Preoperative paired CT and contrast-enhanced MR images were collected for patients with meningioma, pituitary tumor, vestibular schwannoma, and cerebrovascular disease. CT and MR images were denoised, field corrected, and coregistered. MR images were fed to a cGAN that exported a "synthetic" CT scan. The accuracy of synthetic CT images was assessed objectively using the quantitative similarity metrics as well as by clinical features such as sella and internal auditory canal (IAC) dimensions and mastoid/clinoid/sphenoid aeration. RESULTS: A total of 92,981 paired CT/MR images obtained in 80 patients were used for training/testing, and 10,068 paired images from 10 patients were used for external validation. Synthetic CT images reconstructed the bony skull base and convexity with relatively high accuracy. Measurements of the sella and IAC showed a median relative error between synthetic CT scans and ground truth images of 6%, with greater variability in IAC reconstruction compared with the sella. Aerations in the mastoid, clinoid, and sphenoid regions were generally captured, although there was heterogeneity in finer air cell septations. Performance varied based on pathology studied, with the highest limitation observed in evaluating meningiomas with intratumoral calcifications or calvarial invasion. CONCLUSIONS: The generation of high-resolution CT scans from MR images through cGAN offers promise for a wide range of applications in cranial and spinal neurosurgery, especially as an adjunct for preoperative evaluation. Optimizing cGAN performance on specific anatomical regions may increase its clinical viability.