Epidermal Potentiation of Dermal Fibrosis: Lessons from Occlusion and Mucosal Healing.

Fibrotic skin conditions, such as hypertrophic and keloid scars, frequently result from injury to the skin and as sequelae to surgical procedures. The development of skin fibrosis may lead to patient discomfort, limitation in range of motion, and cosmetic disfigurement. Despite the frequency of skin fibrosis, treatments that seek to address the root causes of fibrosis are lacking. Much research into fibrotic pathophysiology has focused on dermal pathology, but less research has been performed to understand aberrations in fibrotic epidermis, leading to an incomplete understanding of dermal fibrosis. Herein, literature on occlusion, a treatment modality known to reduce dermal fibrosis, in part through accelerating wound healing and regulating aberrant epidermal inflammation that otherwise drives fibrosis in the dermis, is reviewed. The review focuses on epidermal-dermal crosstalk, which contributes to the development and maintenance of dermal fibrosis, an underemphasized interplay that may yield novel strategies for treatment if understood in more detail.

Repurposing mebendazole against triple-negative breast cancer CNS metastasis.

PURPOSE: Triple-negative breast cancer (TNBC) often metastasizes to the central nervous system (CNS) and has the highest propensity among breast cancer subtypes to develop leptomeningeal disease (LMD). LMD is a spread of cancer into leptomeningeal space that speeds up the disease progression and severely aggravates the prognosis. LMD has limited treatment options. We sought to test whether the common anti-helminthic drug mebendazole (MBZ) may be effective against murine TNBC LMD. METHODS: A small-molecule screen involving TNBC cell lines identified benzimidazoles as potential therapeutic agents for further study. In vitro migration assays were used to evaluate cell migration capacity and the effect of MBZ. For in vivo testing, CNS metastasis was introduced into BALB/c athymic nude mice through internal carotid artery injections of brain-tropic MDA-MB-231-BR or MCF7-BR cells. Tumor growth and spread was monitored by bioluminescence imaging and immunohistochemistry. MBZ was given orally at 50 and 100 mg/kg doses. MBZ bioavailability was assayed by mass spectrometry. RESULTS: Bioinformatic analysis and migration assays revealed higher migratory capacity of TNBC compared to other breast cancer subtypes. MBZ effectively slowed down migration of TNBC cell line MDA-MB-231 and its brain tropic derivative MDA-MB-231-BR. In animal studies, MBZ reduced leptomeningeal spread, and extended survival in brain metastasis model produced by MDA-MB-231-BR cells. MBZ did not have an effect in the non-migratory MCF7-BR model. CONCLUSIONS: We demonstrated that MBZ is a safe and effective oral agent in an animal model of TNBC CNS metastasis. Our findings are concordant with previous efforts involving MBZ and CNS pathology and support the drug's potential utility to slow down leptomeningeal spread.

Risk of developing glioblastoma following non-CNS primary cancer: a SEER analysis between 2000 and 2018.

BACKGROUND: Patients with a prior malignancy are at elevated risk of developing subsequent primary malignancies (SPMs). However, the risk of developing subsequent primary glioblastoma (SPGBM) in patients with a prior cancer history is poorly understood. METHODS: We used the Surveillance, Epidemiology, and End Results (SEER) database and identified patients diagnosed with non-CNS malignancy between 2000 and 2018. We calculated a modified standardized incidence ratio (M-SIR), defined as the ratio of the incidence of SPGBM among patients with initial non-CNS malignancy to the incidence of GBM in the general population, stratified by sex latency, and initial tumor location. RESULTS: Of the 5,326,172 patients diagnosed with a primary non-CNS malignancy, 3559 patients developed SPGBM (0.07%). Among patients with SPGBM, 2312 (65.0%) were men, compared to 2,706,933 (50.8%) men in the total primary non-CNS malignancy cohort. The median age at diagnosis of SPGBM was 65 years. The mean latency between a prior non-CNS malignancy and developing a SPGBM was 67.3 months (interquartile range [IQR] 27-100). Overall, patients with a primary non-CNS malignancy had a significantly elevated M-SIR (1.13, 95% CI 1.09-1.16), with a 13% increased incidence of SPGBM when compared to the incidence of developing GBM in the age-matched general population. When stratified by non-CNS tumor location, patients diagnosed with primary melanoma, lymphoma, prostate, breast, renal, or endocrine malignancies had a higher M-SIR (M-SIR ranges: 1.09-2.15). Patients with lung cancers (M-SIR 0.82, 95% CI 0.68-0.99), or stomach cancers (M-SIR 0.47, 95% CI 0.24-0.82) demonstrated a lower M-SIR. CONCLUSION: Patients with a history of prior non-CNS malignancy are at an overall increased risk of developing SPGBM relative to the incidence of developing GBM in the general population. However, the incidence of SPGBM after prior non-CNS malignancy varies by primary tumor location, with some non-CNS malignancies demonstrating either increased or decreased predisposition for SPGBM depending on tumor origin. These findings merit future investigation into whether these relationships represent treatment effects or a previously unknown shared predisposition for glioblastoma and non-CNS malignancy.

Predictors of spine metastases at initial presentation of pediatric brain tumor patients: a single-institution study.

PURPOSE: Given the rarity of disseminated disease at the time of initial evaluation for pediatric brain tumor patients, we sought to identify clinical and radiographic predictors of spinal metastasis (SM) at the time of presentation. METHODS: We performed a single-institution retrospective chart review of pediatric brain tumor patients who first presented between 2004 and 2018. We extracted information regarding patient demographics, radiographic attributes, and presenting symptoms. Univariate and multivariate logistic regression was used to estimate the association between measured variables and SMs. RESULTS: We identified 281 patients who met our inclusion criteria, of whom 19 had SM at initial presentation (6.8%). The most common symptoms at presentation were headache (n = 12; 63.2%), nausea/vomiting (n = 16; 84.2%), and gait abnormalities (n = 8; 41.2%). Multivariate models demonstrated that intraventricular and posterior fossa tumors were more frequently associated with SM (OR: 5.28, 95% CI: 1.79-15.59, p = 0.003), with 4th ventricular (OR: 7.42, 95% CI: 1.77-31.11, p = 0.006) and cerebellar parenchymal tumor location (OR: 4.79, 95% CI: 1.17-19.63, p = 0.030) carrying the highest risk for disseminated disease. In addition, evidence of intracranial leptomeningeal enhancement on magnetic resonance imaging (OR: 46.85, 95% CI: 12.31-178.28, p < 0.001) and hydrocephalus (OR: 3.19; 95% CI: 1.06-9.58; p = 0.038) were associated with SM. CONCLUSIONS: Intraventricular tumors and the presence of intracranial leptomeningeal disease were most frequently associated with disseminated disease at presentation. These findings are consistent with current clinical expectations and offer empirical evidence that heightened suspicion for SM may be prospectively applied to certain subsets of pediatric brain tumor patients at the time of presentation.

Socio-economic disparities influence likelihood of post-operative radiation to resection cavities of metastatic brain tumors.

PURPOSE: Irradiating the surgical bed of resected brain metastases improves local and distant disease control. Over time, stereotactic radiosurgery (SRS) has replaced whole brain radiotherapy (WBRT) as the treatment standard of care because it minimizes long-term damage to neuro-cognition. Despite this data and growing adoption, socio-economic disparities in clinical access can result in sub-standard care for some patient populations. We aimed to analyze the clinical and socio-economic characteristics of patients who did not receive radiation after surgical resection of brain metastasis. METHODS: Our sample was obtained from Clinformatics® Data Mart Database and included all patients from 2004 to 2021 who did or did not receive radiation treatment within sixty days after resection of tumors metastatic to the brain. Regression analysis was done to identify factors responsible for loss to adjuvant radiation treatment. RESULTS: Of 8362 patients identified who had undergone craniotomy for resection of metastatic brain tumors, 3430 (41%) patients did not receive any radiation treatment. Compared to patients who did receive some form of radiation treatment (SRS or WBRT), patients who did not get any form of radiation were more likely to be older (p = 0.0189) and non-white (p = 0.008). Patients with Elixhauser Comorbidity Index ≥3 were less likely to receive radiation treatment (p < 0.01). Fewer patients with household income ≥ $75,000 did not receive radiation treatment (p < 0.01). CONCLUSION: Age, race, household income, and comorbidity status were associated with differential likelihood to receive post-operative radiation treatment.

A Retrospective Cohort Study of Implantable Pulse Generator Surgical Site Infections After Deep Brain Stimulation Surgery With an Antibacterial Envelope.

INTRODUCTION: Deep brain stimulation (DBS) surgery is an established treatment for many patients with neurologic disease, and a common complication of DBS is surgical site infection (SSI). In 2016, neurosurgeons at our institution began enclosing implantable pulse generators (IPGs) within fully absorbable, antibacterial envelopes in patients who underwent initial DBS implantation. We sought to determine whether the use of antibacterial envelopes reduced IPG-related SSIs. MATERIALS AND METHODS: We performed a retrospective chart review of all adult patients who underwent initial DBS implantation at Stanford Hospital between November 14, 2012, and November 9, 2020. Operative details, perioperative antibiotics, comorbidities, and postoperative complications were extracted for all patients. Univariate and multivariate logistic regression were used to identify factors associated with SSIs within three months of surgery, and interrupted time-series analysis was performed to assess whether the departmental adoption of the antibacterial envelope led to a reduction in IPG SSIs. RESULTS: Of 344 patients who underwent initial IPG implantation with the antibacterial envelope, one developed an SSI within three months of surgery (0.3%), compared with six of 204 patients (2.9%) who underwent the same procedure without the antibacterial envelope (odds ratio: 0.10, 95% CI: 0.01-0.80, p = 0.031). Univariate logistic regression revealed that the antibacterial envelope and 2000-mg intravenous cefazolin perioperatively were associated with reduced SSI risk, whereas no other factors reached statistical significance. After adjusting for comorbidities, no association remained statistically significant. Interrupted time-series analysis showed a reduction in SSIs after 2016, but the effect was not significant. CONCLUSIONS: The adoption of antibacterial envelopes was found to reduce IPG SSIs at the univariate level, but this association did not remain significant after controlling for confounding variables including perioperative antibiotic administration. Although encouraging, this study does not conclusively establish that the use of antibacterial pouches in patients who underwent initial DBS implantation reduces the incidence of IPG SSIs. Future prospective studies that control for confounding variables are necessary to determine the efficacy of antibacterial envelopes in reducing post-DBS infections at the IPG site before clear recommendations can be made.

Focused ultrasound: growth potential and future directions in neurosurgery.

Over the past two decades, vast improvements in focused ultrasound (FUS) technology have made the therapy an exciting addition to the neurosurgical armamentarium. In this time period, FUS has gained US Food and Drug Administration (FDA) approval for the treatment of two neurological disorders, and ongoing efforts seek to expand the lesion profile that is amenable to ultrasonic intervention. In the following review, we highlight future applications for FUS therapy and compare its potential role against established technologies, including deep brain stimulation and stereotactic radiosurgery. Particular attention is paid to tissue ablation, blood-brain-barrier opening, and gene therapy. We also address technical and infrastructural challenges involved with FUS use and summarize the hurdles that must be overcome before FUS becomes widely accepted in the neurosurgical community.

Impact of socio-economic factors on radiation treatment after resection of metastatic brain tumors: trends from a private insurance database.

BACKGROUND: Stereotactic radiosurgery (SRS) to the surgical bed of resected brain metastases is now considered the standard of care due to its advantages over whole brain radiation therapy (WBRT). Despite the upward trend in SRS adoption since the 2000s, disparities have been reported suggesting that socio-economic factors can influence SRS utilization. OBJECTIVE: To analyze recent trends in SRS use and identify factors that influence treatment. METHODS: We conducted a retrospective cohort study with the Optum Commercial Claims and Encounters Database and included all patients from 2004 to 2021 who received SRS or WBRT within 60 days after resection of tumors metastatic to the brain. RESULTS: A total of 3495 patients met the inclusion and exclusion criteria. There were 1998 patients in the SRS group and 1497 patients in the WBRT group. SRS use now supersedes WBRT by a wide margin. Lung, breast and colon were the most common sites of primary tumor. Although we found no significant differences based on race among the treatment groups, patients with annual household income greater than $75,000 and those with some college or higher education are significantly more likely to receive SRS (OR 1.44 and 1.30; 95% CI 1.18-1.76 and 1.08-1.56; P = 0.001 and 0.005, respective). Patients with Elixhauser Comorbidity Index of three or more were significantly more likely to receive SRS treatment. CONCLUSION: The use of post-surgical SRS for brain metastasis has increased significantly over time, however education and income were associated with differential SRS utilization.

Epidemiological and Treatment Trends for Acute Ischemic Stroke Preceding and during the COVID-19 Pandemic.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic heralded a number of indirect perturbations to patient behavior and disease epidemiology, and mounting evidence suggests that the COVID-19 pandemic may have exacerbated underlying health disparities along racial and socioeconomic (SES) groups for acute ischemic stroke (AIS). We used 1 large national insurance database to identify whether patient demographics, disease severity, or mechanical thrombectomy (MT) rates changed for the treatment and management of AIS during COVID-19. METHODS: AIS patient records were queried from the Clinformatics® Data Mart Optum SES Database from the following 2 time periods: March 1, 2019-June 30, 2019 (pre-COVID-19), and March 1, 2020-June 30, 2020 (COVID-19). The database contains the longitudinal healthcare claims of approximately 77 million patients covered by a major insurance provider between 2003 and June 30, 2020 across all 50 states. Interrupted time-series analyses were used to assess trend differences before and after the COVID-19 pandemic. RESULTS: During the pre-COVID-19 period (March 1, 2019-June 30, 2019), there were 9,072 patients who presented for AIS, compared to 7,366 during COVID-19 (March 1, 2020-June 30, 2020). In both periods, the majority of patients were white (66.83% pre-COVID-19 and 67.91% during COVID-19). The average hospitalization duration was not different during the 2 time periods (p = 0.632), nor were rates of MT (p = 0.260). Total inpatient costs rose slightly for the COVID-19 period (USD 30,739 vs. USD 29,406; p = 0.015), and the median National Institutes of Health Stroke Scale (NIHSS) score was higher during CO-VID-19 (5 vs. 4; p = 0.023). When longitudinal trends were assessed for rates of MT and average NIHSS score for black and white patients, no differences were noted during the CO-VID-19 pandemic. Patients without any undergraduate experience did not present with AIS in increasing or decreasing incidence during COVID-19 (p = 0.268), but they did undergo declining rates of MT (p = 0.013). CONCLUSIONS: In the largest SES analysis of AIS patients during the COVID-19 era, we found that several SES factors, including race and income, did not seem to significantly impact utilization of MT for the treatment of AIS or the severity of the stroke at presentation.

The Nax (SCN7A) channel: an atypical regulator of tissue homeostasis and disease.

Within an articulately characterized family of ion channels, the voltage-gated sodium channels, exists a black sheep, SCN7A (Nax). Nax, in contrast to members of its molecular family, has lost its voltage-gated character and instead rapidly evolved a new function as a concentration-dependent sensor of extracellular sodium ions and subsequent signal transducer. As it deviates fundamentally in function from the rest of its family, and since the bulk of the impressive body of literature elucidating the pathology and biochemistry of voltage-gated sodium channels has been performed in nervous tissue, reports of Nax expression and function have been sparse. Here, we investigate available reports surrounding expression and potential roles for Nax activity outside of nervous tissue. With these studies as justification, we propose that Nax likely acts as an early sensor that detects loss of tissue homeostasis through the pathological accumulation of extracellular sodium and/or through endothelin signaling. Sensation of homeostatic aberration via Nax then proceeds to induce pathological tissue phenotypes via promotion of pro-inflammatory and pro-fibrotic responses, induced through direct regulation of gene expression or through the generation of secondary signaling molecules, such as lactate, that can operate in an autocrine or paracrine fashion. We hope that our synthesis of much of the literature investigating this understudied protein will inspire more research into Nax not simply as a biochemical oddity, but also as a potential pathophysiological regulator and therapeutic target.

A Discussion of Machine Learning Approaches for Clinical Prediction Modeling.

While machine learning has occupied a niche in clinical medicine for decades, continued method development and increased accessibility of medical data have led to broad diversification of approaches. These range from humble regression-based models to more complex artificial neural networks; yet, despite heterogeneity in foundational principles and architecture, the spectrum of machine learning approaches to clinical prediction modeling have invariably led to the development of algorithms advancing our ability to provide optimal care for our patients. In this chapter, we briefly review early machine learning approaches in medicine before delving into common approaches being applied for clinical prediction modeling today. For each, we offer a brief introduction into theory and application with accompanying examples from the medical literature. In doing so, we present a summarized image of the current state of machine learning and some of its many forms in medical predictive modeling.

Patient Experience and Satisfaction with Telemedicine During Coronavirus Disease 2019: A Multi-Institution Experience.

Introduction: The coronavirus disease 2019 (COVID-19) heralded an unprecedented increase in telemedicine utilization. Our objective was to assess patient satisfaction with telemedicine during the COVID-19 era. Methods: Telemedicine visit data were gathered from Stanford Health Care (Stanford) and the Hospital for Special Surgery (HSS). Patient satisfaction data from HSS were captured from a Press-Ganey questionnaire between April 19, 2020, and December 12, 2020, whereas Stanford data were taken from a novel survey instrument that was distributed to all patients between June 22, 2020, and November 1, 2020. Participants: There were 60,550 telemedicine visits at Stanford, each linked with a postvisit survey. At HSS, there were 66,349 total telemedicine visits with 7,348 randomly linked with a postvisit survey. Main Outcomes and Measures: Two measures of patient satisfaction were used for this study: (1) a patient's "overall visit score" and (2) whether the patient indicated the highest possible "likelihood to recommend" (LTR) score (LTR top box score). Results: The LTR top box percentage at Stanford increased from 69.6% to 74.0% (p = 0.0002), and HSS showed no significant change (p = 0.7067). In the multivariable model, the use of a cell phone (adjusted odds ratio [aOR]: 1.18; 95% confidence interval [CI]: 1.12-1.23) and tablet (aOR: 1.15; 95% CI: 1.07-1.23) was associated with higher overall scores, whereas visits with interrupted connections (aOR: 0.49; 95% CI: 0.42-0.57) or help required to connect (aOR: 0.49; 95% CI: 0.42-0.56) predicted lower patient satisfaction. Conclusions: We present the largest published description of patient satisfaction with telemedicine, and we identify important telemedicine-specific factors that predict increased overall visit score. These include the use of cell phones or tablets, phone reminders, and connecting before the visit was scheduled to begin. Visits with poor connectivity, extended wait times, or difficulty being seen, examined, or understood by the provider were linked with reduced odds of high scores. Our results suggest that attention to connectivity and audio/visual definition will help optimize patient satisfaction with future telemedicine encounters.

Differences in treatment patterns and overall survival between grade II and anaplastic pleomorphic xanthoastrocytomas.

INTRODUCTION: Pleomorphic xanthoastrocytomas (PXAs) are classified as a grade II neoplasm, typically occur in children, and have favorable prognoses. However, their anaplastic counterparts remain poorly understood and vaguely characterized. In the present study, a large cohort of grade II PXA patients were compared with primary anaplastic PXA (APXA) patients to characterize patterns in treatment and survival. METHODS: Data were collected from the National Cancer Institute's SEER database. Univariate and multivariate Cox regressions were used to evaluate the prognostic impact of demographic, tumor, and treatment-related covariates. Propensity score matching was used to balance baseline characteristics. Kaplan-Meier curves were used to estimate survival. RESULTS: A total of 346 grade II PXA and 62 APXA patients were identified in the SEER database between 2000 and 2016. Kaplan-Meier analysis revealed substantially inferior survival for APXA patients compared to grade II PXA patients (median survival: 51 months vs. not reached) (p < 0.0001). After controlling across available covariates, increased age at diagnosis was identified as a negative predictor of survival for both grade II and APXA patients. In multivariate and propensity-matched analyses, extent of resection was not associated with improved outcomes in either cohort. CONCLUSIONS: Using a large national database, we identified the largest published cohort of APXA patients to date and compared them with their grade II counterparts to identify patterns in treatment and survival. Upon multivariate analysis, we found increased age at diagnosis was inversely associated with survival in both grade II and APXA patients. Receipt of chemoradiotherapy or complete surgical resection was not associated with improved outcomes in the APXA cohort.

Improved survival and disease control following pembrolizumab-induced immune-related adverse events in high PD-L1 expressing non-small cell lung cancer with brain metastases.

INTRODUCTION: Immune checkpoint inhibitors have become standard of care for many patients with non-small cell lung cancer (NSCLC). These agents often cause immune-related adverse events (IRAEs), which have been associated with increased overall survival (OS). Intracranial disease control and OS for patients experiencing IRAEs with metastatic NSCLC and brain metastases have not yet been described. METHODS: We performed a single-institution, retrospective review of patients with NSCLC and existing diagnosis of brain metastasis, who underwent pembrolizumab treatment and developed any grade IRAE. The primary outcome of the study was intracranial time to treatment failure (TTF), defined from time of pembrolizumab initiation to new intracranial disease progression or death. Kaplan-Meier and Cox proportional hazard analyses were performed. RESULTS: A total of 63 patients with NSCLC brain metastasis were identified, and 24 developed IRAEs. Patients with any grade IRAEs had longer OS (21 vs. 10 months, p = 0.004), systemic TTF (15 vs. 4 months, p < 0.001) and intracranial TTF (14 vs. 5 months, p = 0.001), relative to patients without IRAEs. Presence of IRAEs and high PD-L1 (≥ 50%), but not absent/moderate PD-L1 (0-49%), had a positive association for OS, systemic TTF, and intracranial TTF. Following multivariable analysis, IRAE experienced on pembrolizumab was an independent predictor of OS, systemic TTF, and intracranial TTF. CONCLUSIONS: In our series of patients with NSCLC and brain metastases treated with pembrolizumab, IRAE presence was associated with a significant increase in OS, systemic TTF, and intracranial TTF. Future studies with increased cohorts will clarify how IRAEs should be interpreted among molecular subtypes.

Knockout of sodium channel Nax delays re-epithelializathion of splinted murine excisional wounds.

Mammalian wound healing is a carefully orchestrated process in which many cellular and molecular effectors respond in concert to perturbed tissue homeostasis in order to close the wound and re-establish the skin barrier. The roles of many of these molecular effectors, however, are not entirely understood. Our lab previously demonstrated that the atypical sodium channel Nax (encoded by Scn7a) responds to wound-induced epidermal dehydration, resulting in molecular cascades that drive pro-inflammatory signaling. Acute inhibition of Nax was sufficient to attenuate dermatopathological symptoms in models of hypertrophic scar and dermatitis. To date, however, the role of Nax in excisional wound healing has not been demonstrated. Here we report development of a knockout mouse that lacks expression of functional Nax , and we demonstrate that lack of functional Nax results in deficient wound healing in a murine splinted excisional wound healing model. This deficiency in wound healing was reflected in impaired re-epithelialization and decreased keratinocyte proliferation, a finding which was further supported by decreased proliferation upon Nax knockdown in HaCaT cells in vitro. Defective wound healing was observed alongside increased expression of inflammatory genes in the wound epidermis of Nax -/- mice, suggesting that mice lacking functional Nax retain the ability to undergo skin inflammation. Our observations here motivate further investigation into the roles of Nax in wound healing and other skin processes.

Racial and socioeconomic correlates of treatment and survival among patients with meningioma: a population-based study.

BACKGROUND: Though meningioma is the most common primary brain tumor, there is a paucity of epidemiologic studies investigating disparities in treatment and patient outcomes. Therefore, we sought to explore how sociodemographic factors are associated with rates of gross total resection (GTR) and radiotherapy as well as survival. METHODS: The National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database was queried to identify adult patients with meningioma diagnosed between 2005 and 2015. Socioeconomic status (SES) was determined using a validated composite index in which patients were stratified into tertiles and quintiles. Multivariable logistic regression and Cox proportional hazards analyses were used to identify predictors of treatment and survival, respectively. RESULTS: 71,098 patients met our inclusion criteria. Low SES quintile was associated with reduced odds of receiving GTR (OR 0.76, 95% CI 0.69-0.83, p < 0.0001) and radiotherapy (OR 0.83, 95% CI 0.76-0.91, p < 0.0001) as well as worse survival (HR 1.48, 95% CI 1.41-1.56) as compared to the highest SES quintile. Black patients had reduced odds of GTR (OR 0.74, 95% CI 0.67-0.71, p < 0.0001) and worse survival (HR 1.23, 95% CI 1.18-1.29, p < 0.0001) as compared to white patients. CONCLUSIONS: This national study of patients with meningioma found socioeconomic status and race to be independent inverse correlates of likelihood of GTR, radiotherapy, and survival. Limited access to care may underlie these disparities in part, and future studies are warranted to identify specific causes for these findings.

Risks, costs, and outcomes of cerebrospinal fluid leaks after pediatric skull fractures: a MarketScan analysis between 2007 and 2015.

OBJECTIVE: Skull fractures are common after blunt pediatric head trauma. CSF leaks are a rare but serious complication of skull fractures; however, little evidence exists on the risk of developing a CSF leak following skull fracture in the pediatric population. In this epidemiological study, the authors investigated the risk factors of CSF leaks and their impact on pediatric skull fracture outcomes. METHODS: The authors queried the MarketScan database (2007-2015), identifying pediatric patients (age < 18 years) with a diagnosis of skull fracture and CSF leak. Skull fractures were disaggregated by location (base, vault, facial) and severity (open, closed, multiple, concomitant cerebral or vascular injury). Descriptive statistics and hypothesis testing were used to compare baseline characteristics, complications, quality metrics, and costs. RESULTS: The authors identified 13,861 pediatric patients admitted with a skull fracture, of whom 1.46% (n = 202) developed a CSF leak. Among patients with a skull fracture and a CSF leak, 118 (58.4%) presented with otorrhea and 84 (41.6%) presented with rhinorrhea. Patients who developed CSF leaks were older (10.4 years vs 8.7 years, p < 0.0001) and more commonly had skull base (n = 183) and multiple (n = 22) skull fractures (p < 0.05). These patients also more frequently underwent a neurosurgical intervention (24.8% vs 9.6%, p < 0.0001). Compared with the non-CSF leak population, patients with a CSF leak had longer average hospitalizations (9.6 days vs 3.7 days, p < 0.0001) and higher rates of neurological deficits (5.0% vs 0.7%, p < 0.0001; OR 7.0; 95% CI 3.6-13.6), meningitis (5.5% vs 0.3%, p < 0.0001; OR 22.4; 95% CI 11.2-44.9), nonroutine discharge (6.9% vs 2.5%, p < 0.0001; OR 2.9; 95% CI 1.7-5.0), and readmission (24.7% vs 8.5%, p < 0.0001; OR 3.4; 95% CI 2.5-4.7). Total costs at 90 days for patients with a CSF leak averaged $81,206, compared with $32,831 for patients without a CSF leak (p < 0.0001). CONCLUSIONS: The authors found that CSF leaks occurred in 1.46% of pediatric patients with skull fractures and that skull fractures were associated with significantly increased rates of neurosurgical intervention and risks of meningitis, hospital readmission, and neurological deficits at 90 days. Pediatric patients with skull fractures also experienced longer average hospitalizations and greater healthcare costs at presentation and at 90 days.

Influence of Pleurectomy and Decortication in Health-Related Quality of Life Among Patients with Malignant Pleural Mesothelioma.

BACKGROUND: Complete macroscopic resection surgery, pleurectomy and decortication (PD) improve survival in selected patients with malignant pleural mesothelioma (MPM). Yet its value has been questioned because of concern that this extensive surgical procedure may disrupt health-related quality of life (HRQoL). METHODS: HRQoL was studied in patients undergoing PD surgery for MPM using EORTC QLQ-C30 instrument at baseline (prior to surgery), 1, 4-5, 7-8, and 10-11 months following surgery. Global health and variables in function and symptom domains were investigated. Sub-groups analyses were performed for ECOG performance status (PS), histological sub-types and pathological tumor volume (pTV). Within-patient comparisons to baseline scores were made using Wilcoxon signed-rank test. Trends over time were evaluated using Cuzick's nonparametric test. RESULTS: There were 114 patients with median age of 70 years (range: 50-88) and PS 0: 35 (30.7%), epithelioid histology: 61 (53.5%) and volume <600 ml: 58 (50.9%). Patients with good PS (PS 0), epithelioid histology and small pTV had greater level of functioning and were less symptomatic at baseline. Overall global health worsened at the first postoperative month (p = 0.0005) with subsequent improvement. Non-epithelioid histology and patients with large pTV demonstrated greater improvement in global health, function and symptoms domains following a PD. CONCLUSIONS: At baseline, the overall health-related quality of life, function and symptom domains were adversely affected in non-epithelioid histology and patients with large pTV. However, greatest improvement in global health, symptom and function domains were observed first month after PD and during the follow-up in these sub-groups.

Deep Learning Prediction of Cervical Spine Surgery Revision Outcomes Using Standard Laboratory and Operative Variables.

BACKGROUND: Cervical spine procedures represent a major proportion of all spine surgery. Mitigating the revision rate following cervical procedures requires careful patient selection. While complication risk has successfully been predicted, revision risk has proven more challenging. This is likely due to the absence of granular variables in claims databases. The objective of this study was to develop a state-of-the-art model of revision prediction of cervical spine surgery using laboratory and operative variables. METHODS: Using the Stanford Research Repository, patients undergoing a cervical spine procedure between 2016 and 2022 were identified (N = 3151), and recent laboratory values were collected. Patients were classified into separate cohorts by revision outcome and time frame. Machine and deep learning models were trained to predict each revision outcome from laboratory and operative variables. RESULTS: Red blood cell count, hemoglobin, hematocrit, mean corpuscular hemoglobin concentration, red blood cell distribution width, platelet count, carbon dioxide, anion gap, and calcium all were significantly associated with ≥1 revision cohorts. For the prediction of 3-month revision, the deep neural network achieved an area under the receiver operating characteristic curve of 0.833. The model demonstrated increased performance for anterior versus posterior and arthrodesis versus decompression procedures. CONCLUSIONS: Our deep learning approach successfully predicted 3-month revision outcomes from demographic variables, standard laboratory values, and operative variables in a cervical spine surgery cohort. This work used standard laboratory values and operative codes as meaningful predictive variables for revision outcome prediction. The increased performance on certain procedures evidences the need for careful development and validation of one-size-fits-all risk scores for spine procedures.