Blood Pressure and Spot Sign in Spontaneous Supratentorial Subcortical Intracerebral Hemorrhage.

BACKGROUND: Spontaneous intracerebral hemorrhage is a potentially devastating cause of brain injury, often occurring secondary to hypertension. Contrast extravasation on computed tomography angiography (CTA), known as the spot sign, has been shown to predict hematoma expansion and worse outcomes. Although hypertension has been associated with an increased rate of the spot sign being present, the relationship between spot sign and blood pressure has not been fully explored. METHODS: We retrospectively analyzed data from 134 patients (40 women and 94 men, mean age 62.3 ± 15.73 years) presenting to a tertiary academic medical center with spontaneous supratentorial subcortical intracerebral hemorrhage from 1/1/2018 to 1/4/2021. RESULTS: A spot sign was demonstrated in images of 18 patients (13.43%) and correlated with a higher intracerebral hemorrhage score (2.61 ± 1.42 vs. 1.31 ± 1.25, p = 0.002), larger hematoma volume (53.49cm3 ± 32.08 vs. 23.45cm3 ± 25.65, p = 0.001), lower Glasgow Coma Scale on arrival (9.06 ± 4.56 vs. 11.74 ± 3.65, p = 0.027), increased risk of hematoma expansion (16.67% vs. 5.26%, p = 0.042), and need for surgical intervention (66.67% vs. 15.52%, p < 0.001). We did not see a correlation with age, sex, or underlying comorbidities. The presence of spot sign correlated with higher modified Rankin scores at discharge (4.94 ± 1.00 vs. 3.92 ± 1.64, p < 0.001). We saw significantly higher systolic blood pressure at the time of CTA in patients with a spot sign (184 mm Hg ± 43.11 vs. 153 mm Hg ± 36.99, p = 0.009) and the highest recorded blood pressure (p = 0.019), although not blood pressure on arrival (p = 0.081). Performing CTA early in the process of blood pressure lowering was associated with a spot sign (p < 0.001). CONCLUSIONS: The presence of spot sign correlates with larger hematomas, worse outcomes, and increased surgical intervention. There is a significant association between spot sign and systolic blood pressure at the time of CTA, with the highest systolic blood pressure being recorded prior to CTA. Although the role of intensive blood pressure management in spontaneous intracerebral hemorrhage remains a subject of debate, patients with a spot sign may be a subgroup that could benefit from this.

Interfacing with the nervous system: a review of current bioelectric technologies.

The aim of this study is to discuss the state of the art with regard to established or promising bioelectric therapies meant to alter or control neurologic function. We present recent reports on bioelectric technologies that interface with the nervous system at three potential sites-(1) the end organ, (2) the peripheral nervous system, and (3) the central nervous system-while exploring practical and clinical considerations. A literature search was executed on PubMed, IEEE, and Web of Science databases. A review of the current literature was conducted to examine functional and histomorphological effects of neuroprosthetic interfaces with a focus on end-organ, peripheral, and central nervous system interfaces. Innovations in bioelectric technologies are providing increasing selectivity in stimulating distinct nerve fiber populations in order to activate discrete muscles. Significant advances in electrode array design focus on increasing selectivity, stability, and functionality of implantable neuroprosthetics. The application of neuroprosthetics to paretic nerves or even directly stimulating or recording from the central nervous system holds great potential in advancing the field of nerve and tissue bioelectric engineering and contributing to clinical care. Although current physiotherapeutic and surgical treatments seek to restore function, structure, or comfort, they bear significant limitations in enabling cosmetic or functional recovery. Instead, the introduction of bioelectric technology may play a role in the restoration of function in patients with neurologic deficits.

Cofactors of LIM Domains Associate with Estrogen Receptor α to Regulate the Expression of Noncoding RNA H19 and Corneal Epithelial Progenitor Cell Function.

Cofactors of LIM domain proteins, CLIM1 and CLIM2, are widely expressed transcriptional cofactors that are recruited to gene regulatory regions by DNA-binding proteins, including LIM domain transcription factors. In the cornea, epithelium-specific expression of a dominant negative (DN) CLIM under the keratin 14 (K14) promoter causes blistering, wounding, inflammation, epithelial hyperplasia, and neovascularization followed by epithelial thinning and subsequent epidermal-like differentiation of the corneal epithelium. The defects in corneal epithelial differentiation and cell fate determination suggest that CLIM may regulate corneal progenitor cells and the transition to differentiation. Consistent with this notion, the K14-DN-Clim corneal epithelium first exhibits increased proliferation followed by fewer progenitor cells with decreased proliferative potential. In vivo ChIP-sequencing experiments with corneal epithelium show that CLIM binds to and regulates numerous genes involved in cell adhesion and proliferation, including limbally enriched genes. Intriguingly, CLIM associates primarily with non-LIM homeodomain motifs in corneal epithelial cells, including that of estrogen receptor α. Among CLIM targets is the noncoding RNA H19 whose deregulation is associated with Silver-Russell and Beckwith-Wiedemann syndromes. We demonstrate here that H19 negatively regulates corneal epithelial proliferation. In addition to cell cycle regulators, H19 affects the expression of multiple cell adhesion genes. CLIM interacts with estrogen receptor α at the H19 locus, potentially explaining the higher expression of H19 in female than male corneas. Together, our results demonstrate an important role for CLIM in regulating the proliferative potential of corneal epithelial progenitors and identify CLIM downstream target H19 as a regulator of corneal epithelial proliferation and adhesion.

Interplay between synaptonemal complex, homologous recombination, and centromeres during mammalian meiosis.

The intimate synapsis of homologous chromosome pairs (homologs) by synaptonemal complexes (SCs) is an essential feature of meiosis. In many organisms, synapsis and homologous recombination are interdependent: recombination promotes SC formation and SCs are required for crossing-over. Moreover, several studies indicate that initiation of SC assembly occurs at sites where crossovers will subsequently form. However, recent analyses in budding yeast and fruit fly imply a special role for centromeres in the initiation of SC formation. In addition, in budding yeast, persistent SC-dependent centromere-association facilitates the disjunction of chromosomes that have failed to become connected by crossovers. Here, we examine the interplay between SCs, recombination, and centromeres in a mammal. In mouse spermatocytes, centromeres do not serve as SC initiation sites and are invariably the last regions to synapse. However, centromeres are refractory to de-synapsis during diplonema and remain associated by short SC fragments. Since SC-dependent centromere association is lost before diakinesis, a direct role in homolog segregation seems unlikely. However, post-SC disassembly, we find evidence of inter-centromeric connections that could play a more direct role in promoting homolog biorientation and disjunction. A second class of persistent SC fragments is shown to be crossover-dependent. Super-resolution structured-illumination microscopy (SIM) reveals that these structures initially connect separate homolog axes and progressively diminish as chiasmata form. Thus, DNA crossing-over (which occurs during pachynema) and axis remodeling appear to be temporally distinct aspects of chiasma formation. SIM analysis of the synapsis and crossover-defective mutant Sycp1⁻/⁻ implies that SCs prevent unregulated fusion of homolog axes. We propose that SC fragments retained during diplonema stabilize nascent bivalents and help orchestrate local chromosome reorganization that promotes centromere and chiasma function.

Artificial Intelligence for Automatic Analysis of Shunt Treatment in Presurgery and Postsurgery Computed Tomography Brain Scans of Patients With Idiopathic Normal Pressure Hydrocephalus.

BACKGROUND AND OBJECTIVES: Ventriculo-peritoneal shunt procedures can improve idiopathic normal pressure hydrocephalus (iNPH) symptoms. However, there are no automated methods that quantify the presurgery and postsurgery changes in the ventricular volume for computed tomography scans. Hence, the main goal of this research was to quantify longitudinal changes in the ventricular volume and its correlation with clinical improvement in iNPH symptoms. Furthermore, our objective was to develop an end-to-end graphical interface where surgeons can directly drag-drop a brain scan for quantified analysis. METHODS: A total of 15 patients with 47 longitudinal computed tomography scans were taken before and after shunt surgery. Postoperative scans were collected between 1 and 45 months. We use a UNet-based model to develop a fully automated metric. Center slices of the scan that are most representative (80%) of the ventricular volume of the brain are used. Clinical symptoms of gait, balance, cognition, and bladder continence are studied with respect to the proposed metric. RESULTS: Fifteen patients with iNPH demonstrate a decrease in ventricular volume (as shown by our metric) postsurgery and a concurrent clinical improvement in their iNPH symptomatology. The decrease in postoperative central ventricular volume varied between 6 cc and 33 cc (mean: 20, SD: 9) among patients who experienced improvements in gait, bladder continence, and cognition. Two patients who showed improvement in only one or two of these symptoms had <4 cc of cerebrospinal fluid drained. Our artificial intelligence-based metric and the graphical user interface facilitate this quantified analysis. CONCLUSION: Proposed metric quantifies changes in ventricular volume before and after shunt surgery for patients with iNPH, serving as an automated and effective radiographic marker for a functioning shunt in a patient with iNPH.

Friedman's Gradient-Boosting Algorithm Predicts Lactate-Pyruvate Ratio Trends in Cases of Intracerebral Hemorrhages.

OBJECTIVE: The local effects of an intracerebral hemorrhage (ICH) on surrounding brain tissue can be detected bedside using multimodal brain monitoring techniques. The aim of this study is to design a gradient boosting regression model using the R package boostmtree with the ability to predict lactate-pyruvate ratio measurements in ICH. METHODS: We performed a retrospective analysis of 6 spontaneous ICH and 6 traumatic ICH patients who underwent surgical removal of the clot with microdialysis catheters placed in the perihematomal zone. Predictors of glucose, lactate, pyruvate, age, sex, diagnosis, and operation status were used to design our model. RESULTS: In a holdout analysis, the model forecasted lactate-pyruvate ratio trends in a representative in-sample testing set. We anticipate that boostmtree could be applied to designs of similar regression models to analyze trends in other multimodal monitoring features across other types of acute brain injury. CONCLUSIONS: The model successfully predicted hourly lactate-pyruvate ratios in spontaneous ICH and traumatic ICH cases after the hemorrhage evacuation and displayed significantly better performance than linear models. Our results suggest that boostmtree may be a powerful tool in developing more advanced mathematical models to assess other multimodal monitoring parameters for cases in which the perihematomal environment is monitored.

Neurosurgery compared to orthopedic spine consultation: A single level I trauma center experience.

Introduction: Both Orthopedic Surgery (OS) and Neurosurgery (NS) perform spine surgery in the setting of trauma. However, it is unknown whether outcomes differ between these specialties. This study compares management and outcomes for vertebral fractures between NS and OS, hypothesizing similar operation rate, length of stay (LOS), and readmission. Research question: Do outcomes differ between NS and OS in the management of vertebral fractures following trauma? Methods: A retrospective single-center study was conducted on adult patients with cervical, thoracic, lumbar, and sacral fractures treated at a single trauma center, where no standardized pathway exists across NS and OS. Patients were compared for injury profile, diagnostic imaging, and operative techniques as well as LOS, mortality, and complications. Results: A total of 630 vertebral fracture patients (OS:350 (55.6%); NS:280 (44.4%)) were included. NS utilized magnetic resonance imaging (MRI) more commonly (36.4% vs. 22.6%, p < 0.001). NS patients more often underwent operation (13.2% vs. 7.4%, p = 0.016) despite similar fracture number and severity (p > 0.05). Post-operative complications, LOS, and readmission rates were similar between cohorts (p > 0.05). Discussion and conclusion: Despite similar injury profiles, NS had higher rates of MRI usage and operative interventions in the context of traumatic spine fractures. Despite differences in management, major clinical outcomes were similar between NS and OS. However, we do call for further standardization of evaluation and treatment of patients based on established algorithms from such as the AOSpine Thoracolumbar Spine Injury Classification System (ATLICS).

iPad-Based Neurocognitive Testing (ImPACT-QT) in Acute Adult Mild Traumatic Brain Injury/Concussion: Study on Practicality and Bedside Cognitive Scores in a Level-1 Trauma Center.

BACKGROUND: There lacks rapid standardized bedside testing to screen cognitive deficits following mild traumatic brain injury (mTBI). Immediate Post-Concussion Assessment & Cognitive Testing-Quick Test (ImPACT-QT) is an abbreviated-iPad form of computerized cognitive testing. The aim of this study is to test ImPACT-QT utility in inpatient settings. We hypothesize ImPACT-QT is feasible in the acute trauma setting. METHOD: Trauma patients ages 12-70 were administered ImPACT-QT (09/2022-09/2023). Encephalopathic/medically unstable patients were excluded. Mild traumatic brain injury was defined as documented-head trauma with loss-of-consciousness <30 minutes and arrival Glasgow Coma Scale 13-15. Patients answered Likert-scale surveys. Bivariate analyses compared demographics, attention, motor speed, and memory scores between mTBI and non-TBI controls. Multivariable logistic regression assessed memory score as a predictor of mTBI diagnosis. RESULTS: Of 233 patients evaluated (36 years [IQR 23-50], 71% [166/233] female), 179 (76%) were mTBI patients. For all patients, mean test-time was 9.3 ± 2 minutes with 93% (73/76) finding the test "easy to understand." Mild traumatic brain injury patients than non-TBI control had lower memory scores (25 [IQR 7-100] vs 43 [26-100], P = .001) while attention (5 [1-23] vs 11 [1-32]) and motor score (14 [3-28] vs 13 [4-32]) showed no significant differences. Multivariable-regression (adjustment: age, sex, race, education level, ISS, and time to test) demonstrated memory score predicted mTBI positive status (OR .96, CI .94-.98, P = .004). DISCUSSION: Immediate Post-Concussion Assessment & Cognitive Testing-Quick Test is feasible in trauma patients. Preliminary findings suggest acute mTBIs have lower memory but not attention/motor scores vs non-TBI trauma controls.

Mesenchymal Stromal Cell Implants for Chronic Motor Deficits After Traumatic Brain Injury: Post Hoc Analysis of a Randomized Trial.

BACKGROUND AND OBJECTIVES: Traumatic brain injury (TBI) is frequently characterized by chronic motor deficits. Therefore, this clinical trial assessed whether intracranial implantation of allogeneic modified mesenchymal stromal (SB623) cells can improve chronic motor deficits after TBI. METHODS: Post hoc analysis of the double-blind, randomized, prospective, surgical sham-controlled, phase 2, STEMTRA clinical trial (June 2016 and March 2019) with 48 weeks of follow-up was conducted. In this international, multicenter clinical trial, eligible participants had moderate-to-severe TBI, were ≥12 months postinjury, and had chronic motor deficits. Participants were randomized in a 1:1:1:1 ratio to stereotactic surgical intracranial implantation of SB623 cells (2.5 × 106, 5.0 × 106, 10 × 106) or surgical sham-controlled procedure. The prespecified primary efficacy end point was significantly greater change from baseline of the Fugl-Meyer Motor Scale (FMMS) score, a measure of motor status, for the SB623 pooled vs control arm at 24 weeks. RESULTS: A total of 211 participants were screened, 148 were excluded, and 63 underwent randomization, of which 61 (97%; mean age, 34 [SD, 12] years; 43 men [70.5%]) completed the trial. Single participants in the SB623 2.5 × 106 and 5.0 × 106 cell dose groups discontinued before surgery. Safety and efficacy (modified intent-to-treat) were assessed in participants who underwent surgery (N = 61; SB623 = 46, controls = 15). The primary efficacy end point (FMMS) was achieved (least squares mean [SE] SB623: +8.3 [1.4]; 95% CI 5.5-11.2 vs control: +2.3 [2.5]; 95% CI -2.7 to 7.3; p = 0.04), with faster improvement of the FMMS score in SB623-treated groups than in controls at 24 weeks and sustained improvement at 48 weeks. At 48 weeks, improvement of function and activities of daily living (ADL) was greater, but not significantly different in SB623-treated groups vs controls. The incidence of adverse events was equivalent in SB623-treated groups and controls. There were no deaths or withdrawals due to adverse events. DISCUSSION: Intraparenchymal implantation of SB623 cells was safe and significantly improved motor status at 24 weeks in participants with chronic motor deficits after TBI, with continued improvement of function and ADL at 48 weeks. Cell therapy can modify chronic neurologic deficits after TBI. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov Identifier: NCT02416492. Submitted to registry: April 15, 2015. First participant enrolled: July 6, 2016. Available at: classic.clinicaltrials.gov/ct2/show/NCT02416492. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that intracranial implantation of allogeneic stem (SB623) cells in adults with motor deficits from chronic TBI improves motor function at 24 weeks.

Successful resuscitation after multiple injuries in the wilderness.

BACKGROUND: Survival of blunt trauma associated with hypothermic and hemorrhagic cardiac arrest in wilderness areas is extremely rare. CASE REPORT: We describe a case of a 19-year-old female college sophomore who, while glissading down Mt. Adams, had a 400-pound boulder strike her back and left pelvis, propelling her 40 feet down the mountain to land face down in the snow at 7000 feet. It took 4 h from the time of injury until the arrival of the helicopter at our Emergency Department and Trauma Center. The patient lost vital signs en route and had no CO(2) production. A cardiothoracic surgeon was the trauma surgeon on call. The patient was taken directly from the helipad to the operating room, where cutdowns enabled initial intravenous access, median sternotomy and pericardiotomy open heart massage, massive transfusion, chest and abdominal cavity irrigations with warm saline, correction of acid base imbalances and coagulopathies, and epicardial pacing that led to a successful reanimation of the patient. The patient was rewarmed without extracorporeal membrane oxygenation or heat exchangers. The ensuing multiple organ failures (heart, lungs, kidneys, intestines, brain, and immune system) and rhabdomyolysis led to a 2-month intensive care unit stay. She received over 120 units of blood and blood products. The patient regained cognitive function, mobility, and overcame multiple organ failure. CONCLUSION: This report is presented to increase awareness of the potential survivability in hypothermia, and to recognize the heroic efforts of the emergency services personnel whose efforts saved the patient's life.

The Public Perception of CT Colonography Versus Colonoscopy via Sentiment Analysis of Social Media.

PURPOSE: The purpose of this study was to understand the public perception of CT colonography (CTC) in comparison with optical colonoscopy as a colorectal cancer screening technique. METHODS: In this observational study, all English-language tweets from January 1, 2015, until September 1, 2021, containing terms related to CTC and terms related to optical colonoscopy were collected. The tweets were given sentiment scores using Twitter-roBERTa-base, a natural language processing model. These scores were then used to classify tweets into positive, neutral, and negative categories. The numbers of negative, positive, and neutral tweets were tabulated. RESULTS: A total of 4,709 tweets from 2,194 users relating to CTC were collected. Of these tweets, 9.81% were negative, 68.52% were neutral, and 21.63% were positive. In comparison, a total of 445,969 tweets from 261,209 users were collected relating to optical colonoscopy. Of these tweets, 31.8% were negative, 51.3% were neutral, and 16.9% were positive. CONCLUSIONS: The public awareness of CTC remains limited in comparison with optical colonoscopy, with Twitter volume relating to CTC being about 1% the volume for optical colonoscopy. There was a higher proportion of negative tweets regarding colonoscopy. The lower proportion of negative tweets regarding CTC may be helpful in encouraging its use as an alternative to optical colonoscopy, with the aim of increasing uptake of colorectal cancer screening.

Cerebral microdialysis demonstrates improvements in brain metabolism with cerebrospinal fluid diversion in spontaneous intracerebral hemorrhage.

Background: Cerebral microdialysis (CMD) is an FDA-approved multimodal invasive monitoring technique that provides local brain metabolism measurements through continuous interstitial brain fluid sampling at the bedside. The past applications in traumatic brain injury and subarachnoid hemorrhage show that acute brain injury (ABI) can lead to a metabolic crisis reflected by changes in cerebral glucose, pyruvate, and lactate. However, limited literature exists on CMD in spontaneous intracerebral hemorrhage (ICH). Case Description: A 45-year-old woman presented with a Glasgow Coma Scale of 8T and left frontal ICH with a 6 mm midline shift. She underwent craniotomy and ICH evacuation. Intraoperatively, CMD, brain tissue oxygenation (PbtO2), intracranial pressure (ICP), and cerebral blood flow (CBF) catheters were placed, targeted toward the peri-hematoma region. Postoperatively, ICP was normal; however, PbtO2, CBF, glucose, and lactate/ pyruvate ratio were abnormal. Due to concern for the metabolic crisis, poor examination, and hydrocephalus on computed tomography of the head (CTH), she underwent external ventricular drainage (EVD). Post-EVD, all parameters normalized (P < 0.05 on Student's t-test). Monitors were removed, and she was discharged to a nursing facility with a modified Rankin scale of 4. Conclusion: Here, we demonstrate the safe implementation of CMD in ICH and the use of CMD in tandem with PbtO2/ICP/CBF to guide treatment in ICH. Despite a normal ICP, numerous cerebral metabolic derangements existed and improved after cerebrospinal fluid diversion. A normal ICP may not reflect underlying metabolic-substrate demands of the brain during ABI. CMD and PbtO2/CBF monitoring augment traditional ICP monitoring in brain injury. Further prospective studies will be needed to understand further the interplay between ICP, PbtO2, CBF, and CMD values in ABI.

IRX5 promotes DNA damage repair and activation of hair follicle stem cells.

The molecular mechanisms allowing hair follicles to periodically activate their stem cells (HFSCs) are incompletely characterized. Here, we identify the transcription factor IRX5 as a promoter of HFSC activation. Irx5-/- mice have delayed anagen onset, with increased DNA damage and diminished HFSC proliferation. Open chromatin regions form near cell cycle progression and DNA damage repair genes in Irx5-/- HFSCs. DNA damage repair factor BRCA1 is an IRX5 downstream target. Inhibition of FGF kinase signaling partially rescues the anagen delay in Irx5-/- mice, suggesting that the Irx5-/- HFSC quiescent phenotype is partly due to failure to suppress Fgf18 expression. Interfollicular epidermal stem cells also show decreased proliferation and increased DNA damage in Irx5-/-mice. Consistent with a role for IRX5 as a promoter of DNA damage repair, we find that IRX genes are upregulated in many cancer types and that there is a correlation between IRX5 and BRCA1 expression in breast cancer.

Early Minimally Invasive Parafascicular Surgery for Evacuation of Spontaneous Intracerebral Hemorrhage in the Setting of Computed Tomography Angiography Spot Sign: A Case Series.

BACKGROUND: Spontaneous intracerebral hemorrhage (sICH) is associated with high morbidity and mortality, and the role of surgery is uncertain. Spot sign on computed tomography angiography (CTA) has previously been seen as a contraindication for minimally invasive techniques. OBJECTIVE: To demonstrate the use of minimally invasive parafascicular surgery (MIPS) for early evacuation of sICH in patients with spot sign on CTA. METHODS: Retrospective review of patients presenting to a US tertiary academic medical center from 2018 to 2020 with sICH and CTA spot sign who were treated with MIPS within 6 h of arrival. RESULTS: Seven patients (6 men and 1 woman, mean age 54.4 yr) were included in this study. There was a significant decrease between preoperative and postoperative intracerebral hemorrhage volumes (75.03 ± 39.00 cm3 vs 19.48 ± 17.81 cm3, P = .005) and intracerebral hemorrhage score (3.1 ± 0.9 vs 1.9 ± 0.9, P = .020). The mean time from arrival to surgery was 3.72 h (±1.22 h). The mean percentage of hematoma evacuation was 73.78% (±21.11%). The in-hospital mortality was 14.29%, and the mean modified Rankin score at discharge was 4.6 (±1.3). No complications related to the surgery were encountered in any of the cases, with no abnormal intraoperative bleeding and no pathology demonstrating occult vascular lesion. CONCLUSION: Early intervention with MIPS appears to be a safe and effective means of hematoma evacuation despite the presence of CTA spot sign, and this finding should not delay early intervention when indicated. Intraoperative hemostasis may be facilitated by the direct visualization provided by a tubular retractor system.

Technical notes on the placement of cerebral microdialysis: A single center experience.

Background: Cerebral microdialysis enables monitoring of brain metabolism and can be an important part of multimodal monitoring strategies in a variety of brain injuries. Microdialysis catheters can be placed in brain parenchyma through a burr hole, a cranial bolt, or directly at the time of an open craniotomy or craniectomy. The location of catheters in relation to brain pathology is important to the interpretation of data and guidance of interventions. Methods: Here we retrospectively review the use of cerebral microdialysis at a US Regional Medical Center between March 2018 and February 2022 and provide detailed descriptions and technical nuances of the different methods to place microdialysis catheters. Results: Eighty two unique microdialysis catheters were utilized in 52 patients. 35 (42.68%) were placed via a quad-lumen bolt and 47 (57.32%) were placed through craniotomies. 27 catheters (32.93%) were placed in a perilesional location, 50 (60.98%) were located in healthy tissue, and 6 (7.32%) were mispositioned. No significant difference was seen between placement by bolt or craniotomy in regard to perilesional location, mispositioning, or complications. Conclusion: With careful planning and thoughtful execution, cerebral microdialysis catheters can be successfully placed though a variety of strategies to optimize and individualize brain monitoring in different clinical settings. This paper provides a detailed guide for the various methods of catheter placement to help providers begin or expand their use of cerebral microdialysis.

Neurosurgery Lectures Benefit from a Flipped Class Approach.

BACKGROUND: In a flipped classroom, students learn lecture material before class and then participate in active learning during in-person sessions. This study examines preferences for flipped classroom activities during a neurosurgery presentation on traumatic brain injury. METHODS: Two hundred twenty-five third- and fourth-year medical students on their core neurology rotation watched an online podcast about traumatic brain injury before meeting for in-person, active learning activities with a neurological surgeon. Before and after the class, students were given rank-based surveys with an optional section for comments. The initial survey assessed preference for specific active learning activities, and the final survey assessed satisfaction with the experience. The students also answered an online 20-question postlecture test as part of the standard neurology class assessment. RESULTS: Every student scored over 90% on the postlecture test. Of the 81 students who answered the first survey, most students (83.95%) strongly preferred or preferred case scenarios with group discussion. The average Likert score for case scenario preference (4.37/5) was significantly higher than the score for all other activities (P < 0.05). Of the 207 students who answered the second survey, 80.19% of students reported that they would probably or definitely like to see more flipped classroom activities. CONCLUSIONS: Medical students highly preferred case scenarios because according to their comments, this method was relevant to real-life situations and led to higher information retention. This information suggests that the flipped classroom model for neurosurgical-based lectures is preferred, is beneficial, and should incorporate case scenarios. This methodology may also apply to neurosurgical residency training.

The M3 Muscarinic Acetylcholine Receptor Promotes Epidermal Differentiation.

The M3 muscarinic acetylcholine receptor is predominantly expressed in the basal epidermal layer where it mediates the effects of the autocrine/paracrine cytotransmitter acetylcholine. Patients with the autoimmune blistering disease pemphigus develop autoantibodies to M3 muscarinic acetylcholine receptor and show alterations in keratinocyte adhesion, proliferation, and differentiation, suggesting that M3 muscarinic acetylcholine receptor controls these cellular functions. Chmr3-/- mice display altered epidermal morphology resembling that seen in patients with pemphigus vulgaris. In this study, we characterized the cellular and molecular mechanisms through which M3 muscarinic acetylcholine receptor controls epidermal structure and function. We used single-cell RNA sequencing to evaluate keratinocyte heterogeneity and identify differentially expressed genes in specific subpopulations of epidermal cells in Chmr3-/- neonatal mice. We found that Chmr3-/- mice feature abnormal epidermal morphology characterized by accumulation of nucleated basal cells, shrinkage of basal keratinocytes, and enlargement of intercellular spaces. These morphologic changes were associated with upregulation of cell proliferation genes and downregulation of genes contributing to epidermal differentiation, extracellular matrix formation, intercellular adhesion, and cell arrangement. These findings provide, to our knowledge, previously unreported insights into how acetylcholine controls epidermal differentiation and lay a groundwork for future translational studies evaluating the therapeutic potential of cholinergic drugs in dermatology.

7-Year Experience with Automated Pupillometry and Direct Integration With the Hospital Electronic Medical Record.

INTRODUCTION: Manual pupillary assessments are an integral part of the neurologic evaluation in critically ill patients. Automated pupillometry provides reliable, consistent, and accurate measurement of the light response. We established a computer interface that allows for direct download of pupillometer information to our hospital electronic medical record (EMR). Here, we report our single-center experience. METHODS: An interface allowing direct download of pupillometer data to our EMR was developed. We then performed a prospective study using an electronic survey distributed to nurses that used pupillometers in 2015, 2018, and 2020 using a 5-point Likert-style format to evaluate the acceptance of this implementation. RESULTS: In 2015, 22 nurses were surveyed, with 50% of the respondents citing lack of pupillometers and 41% citing the labor intensity associated with data entry as the reason for the reluctance to use the pupillometer. The number of nurse responses in 2018 increased to 123, with 78% of nurses finding that the direct download to hospital EMR improved the efficiency of their neurologic exams. In 2020, 108 nurses responded with similar responses to those in 2018. We added 3 additional questions regarding utility of the pupillometer during the COVID-19 pandemic. Fifty-eight percent of nurses were reassured of the neurologic exam when using the pupillometer in lieu of a full exam to limit infectious exposure. CONCLUSIONS: This is the first report of the implementation of a direct interface to download pupillometer data to the EMR. The positive effect on nursing workflow and documentation of pupillary findings is discussed.

Automated Segmentation and Connectivity Analysis for Normal Pressure Hydrocephalus.

Objective and Impact Statement. We propose an automated method of predicting Normal Pressure Hydrocephalus (NPH) from CT scans. A deep convolutional network segments regions of interest from the scans. These regions are then combined with MRI information to predict NPH. To our knowledge, this is the first method which automatically predicts NPH from CT scans and incorporates diffusion tractography information for prediction. Introduction. Due to their low cost and high versatility, CT scans are often used in NPH diagnosis. No well-defined and effective protocol currently exists for analysis of CT scans for NPH. Evans' index, an approximation of the ventricle to brain volume using one 2D image slice, has been proposed but is not robust. The proposed approach is an effective way to quantify regions of interest and offers a computational method for predicting NPH. Methods. We propose a novel method to predict NPH by combining regions of interest segmented from CT scans with connectome data to compute features which capture the impact of enlarged ventricles by excluding fiber tracts passing through these regions. The segmentation and network features are used to train a model for NPH prediction. Results. Our method outperforms the current state-of-the-art by 9 precision points and 29 recall points. Our segmentation model outperforms the current state-of-the-art in segmenting the ventricle, gray-white matter, and subarachnoid space in CT scans. Conclusion. Our experimental results demonstrate that fast and accurate volumetric segmentation of CT brain scans can help improve the NPH diagnosis process, and network properties can increase NPH prediction accuracy.