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PurposeTriple-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.MethodsA 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.ResultsBioinformatic 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.ConclusionsWe 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.

Dermal fibrosis is a consequence of damage to skin and is accompanied by dysfunction and cosmetic disfigurement. Improved understanding of the pathological factors driving skin fibrosis is critical to development of therapeutic modalities. Here, we describe that the Wnt signalling antagonist SFRP2 is upregulated in organotypic keratinocyte cultures upon experimental reduced hydration, a model that simulates the aberrant epidermal barrier state characteristic of several skin pathologies, including those that manifest in development of fibrosis. Consistent with this, we find that SFRP2 is overexpressed in both the dermis and epidermis of human hypertrophic scar tissue and lesional tissue of a mouse scleroderma model. Knockdown of SFRP2 expression in human fibroblasts antagonises proliferation and myofibroblast differentiation, including deposition of type I collagen, suggesting that SFRP2 signalling in fibroblasts may contribute to propagation of fibrosis in hypertrophic scar, as well as in other clinical indications characterised by skin fibrosis. [ABSTRACT FROM AUTHOR]

This article discusses the outcomes of endoscopic endonasal transcavernous surgery for pituitary adenomas. The study analyzed data from patients who underwent this surgery between 2018 and 2023. The results showed that transcavernous surgery was more common in repeat surgery patients and those with functioning adenomas. The study also examined the invasion patterns of the cavernous sinus compartments and found that the medial wall was the most frequently involved. The authors concluded that the outcomes of transcavernous surgery can vary depending on the specific compartments involved. [Extracted from the article]

This article discusses the surgical management and outcomes of pituitary adenomas with subarachnoid invasion. The study analyzed data from 321 patients who underwent an endoscopic endonasal approach for pituitary adenoma resection, and identified 13 patients with subarachnoid invasion. The surgical approach for these tumors involved careful dissection from surrounding neurovascular structures to achieve safe resection. Patients with subarachnoid invasion were more likely to have subtotal tumor resection and require additional treatment, such as medical therapy, radiation, or repeat resection. They also experienced higher rates of intra-operative CSF leak, postoperative diabetes insipidus, post-operative hematomas, and the need for adjuvant interventions. Overall, pituitary adenomas with subarachnoid invasion present unique challenges and require specialized surgical techniques. [Extracted from the article]

Background: Adult spinal deformities (ASD) are varied spinal abnormalities, often necessitating surgical intervention when associated with pain, worsening deformity, or worsening function. Predicting post-operative complications and revision surgery is critical for surgical planning and patient counseling. Due to the relatively small number of cases of ASD surgery, machine learning applications have been limited to traditional models (e.g., logistic regression or standard neural networks) and coarse clinical variables. We present the novel application of advanced models (CNN, LLM, GWAS) using complex data types (radiographs, clinical notes, genomics) for ASD outcome prediction. Methods: We developed a CNN trained on 209 ASD patients (1549 radiographs) from the Stanford Research Repository, a CNN pre-trained on VinDr-SpineXR (10,468 spine radiographs), and an LLM using free-text clinical notes from the same 209 patients, trained via Gatortron. Additionally, we conducted a GWAS using the UK Biobank, contrasting 540 surgical ASD patients with 7355 non-surgical ASD patients. Results: The LLM notably outperformed the CNN in predicting pulmonary complications (F1: 0.545 vs. 0.2881), neurological complications (F1: 0.250 vs. 0.224), and sepsis (F1: 0.382 vs. 0.132). The pre-trained CNN showed improved sepsis prediction (AUC: 0.638 vs. 0.534) but reduced performance for neurological complication prediction (AUC: 0.545 vs. 0.619). The LLM demonstrated high specificity (0.946) and positive predictive value (0.467) for neurological complications. The GWAS identified 21 significant (p < 10−5) SNPs associated with ASD surgery risk (OR: mean: 3.17, SD: 1.92, median: 2.78), with the highest odds ratio (8.06) for the LDB2 gene, which is implicated in ectoderm differentiation. Conclusions: This study exemplifies the innovative application of cutting-edge models to forecast outcomes in ASD, underscoring the utility of complex data in outcome prediction for neurosurgical conditions. It demonstrates the promise of genetic models when identifying surgical risks and supports the integration of complex machine learning tools for informed surgical decision-making in ASD. [ABSTRACT FROM AUTHOR]

Study Design: Retrospective cohort study. Purpose: Anterior cervical discectomy and fusion (ACDF) is a common surgical intervention for patients diagnosed with cervical degenerative diseases with or without myelopathy. A thorough understanding of outcomes in patients with and without myelopathy undergoing ACDF is required because of the widespread utilization of ACDF for these indications. Overview of Literature: Non-ACDF approaches achieved inferior outcomes in certain myelopathic cases. Studies have compared patient outcomes across procedures, but few have compared outcomes concerning myelopathic versus nonmyelopathic cohorts. Methods: The MarketScan database was queried from 2007 to 2016 to identify adult patients who were =65 years old, and underwent ACDF using the international classification of diseases 9th version and current procedural terminology codes. Nearest neighbor propensity-score matching was employed to balance patient demographics and operative characteristics between myelopathic and nonmyelopathic cohorts. Results: Of 107,480 patients who met the inclusion criteria, 29,152 (27.1%) were diagnosed with myelopathy. At baseline, the median age of patients with myelopathy was higher (52 years vs. 50 years, p <0.001), and they had a higher comorbidity burden (mean Charlson comorbidity index, 1.92 vs. 1.58; p <0.001) than patients without myelopathy. Patients with myelopathy were more likely to undergo surgical revision at 2 years (odds ratio [OR], 1.63; 95% confidence interval [CI], 1.54-1.73) or are readmitted within 90 days (OR, 1.27; 95% CI, 1.20-1.34). After patient cohorts were matched, patients with myelopathy remained at elevated risk for reoperation at 2 years (OR, 1.55; 95% CI, 1.44-1.67) and postoperative dysphagia (2.78% vs. 1.68%, p <0.001) compared to patients without myelopathy. Conclusions: We found inferior postoperative outcomes at baseline for patients with myelopathy undergoing ACDF compared to patients without myelopathy. Patients with myelopathy remained at significantly greater risk for reoperation and readmission after balancing potential confounding variables across cohorts, and these differences in outcomes were largely driven by patients with myelopathy undergoing 1-2 level fusions. [ABSTRACT FROM AUTHOR]

Study Design: Retrospective cohort study. Purpose: To characterize the postoperative outcomes and economic costs of anterior cervical discectomy and fusion (ACDF) procedures using synthetic biomechanical intervertebral cage (BC) and structural allograft (SA) implants. Overview of Literature: ACDF is a common spine procedure that typically uses an SA or BC for the cervical fusion. Previous studies that compared the outcomes between the two implants were limited by small sample sizes, short-term postoperative outcomes, and procedures with single-level fusion. Methods: Adult patients who underwent an ACDF procedure in 2007-2016 were included. Patient records were extracted from MarketScan, a national registry that captures person-specific clinical utilization, expenditures, and enrollments across millions of inpatient, outpatient, and prescription drug services. Propensity-score matching (PSM) was employed to match the patient cohorts across demographic characteristics, comorbidities, and treatments. Results: Of 110,911 patients, 65,151 (58.7%) received BC implants while 45,760 (41.3%) received SA implants. Patients who underwent BC surgeries had slightly higher reoperation rates within 1 year after the index ACDF procedure (3.3% vs. 3.0%, p =0.004), higher postoperative complication rates (4.9% vs. 4.6%, p =0.022), and higher 90-day readmission rates (4.9% vs. 4.4%, p =0.001). After PSM, the postoperative complication rates did not vary between the two cohorts (4.8% vs. 4.6%, p =0.369), although dysphagia (2.2% vs. 1.8%, p <0.001) and infection (0.3% vs. 0.2%, p =0.007) rates remained higher for the BC group. Other outcome differences, including readmission and reoperation, decreased. Physician's fees remained high for BC implantation procedures. Conclusions: We found marginal differences in clinical outcomes between BC and SA ACDF interventions in the largest published database cohort of adult ACDF surgeries. After adjusting for group-level differences in comorbidity burden and demographic characteristics, BC and SA ACDF surgeries showed similar clinical outcomes. Physician's fees, however, were higher for BC implantation procedures. [ABSTRACT FROM AUTHOR]

Background: Hypertrophic scars (HTS) result from injury to the skin and represent a clinical burden with limited treatment options. Previously, we demonstrated that statin drugs could attenuate HTS formation, but convenient topical delivery and retention of these drugs at the wound site remains a challenge. Aims: Here, we aimed to develop a topical cream formulation that can deliver statin drugs simply and conveniently to reduce scar hypertrophy. Methods: We formulated creams containing 10% pravastatin, 2% simvastatin, and 10% simvastatin. We tested these creams for their ability to reduce scar hypertrophy and attenuate dermal fibrosis in a clinically relevant HTS wound model performed in rabbit ear skin. We also monitored trans‐epidermal water loss (TEWL) over the course of wound healing in order to understand the effects of statin treatment on epidermal barrier recovery. Results: Of the three creams formulated, only application of 10% simvastatin cream significantly attenuated hypertrophy of resultant scars compared with vehicle cream application. Application of 10% simvastatin cream resulted in a decrease in macrophage and myofibroblast density at post‐operative day 28 (POD28) harvest. Application of 10% simvastatin cream resulted in visible symptoms of dryness and increased TEWL at POD28, but subsequent withdrawal of statin cream treatment resulted in rapid alleviation of dryness and decrease in TEWL back to normal levels. Conclusions: Our data demonstrate that topical administration of 10% simvastatin cream antagonizes dermal fibrosis and reduces hypertrophy in an HTS model, and withdrawal of the cream enables recovery of epidermal barrier and resolution of skin dryness. [ABSTRACT FROM AUTHOR]

Study Design: Retrospective cohort.Objective: Due to anterior cervical discectomy and fusion (ACDF) popularity, it is important to predict postoperative complications, unfavorable 90-day readmissions, and two-year reoperations to improve surgical decision-making, prognostication, and planning.Summary Of Background Data: Machine learning has been applied to predict postoperative complications for ACDF; however, studies were limited by sample size and model type. These studies achieved ≤0.70 area under the curve (AUC). Further approaches, not limited to ACDF, focused on specific complication types and resulted in AUC between 0.70 and 0.76.Materials and Methods: The IBM MarketScan Commercial Claims and Encounters Database and Medicare Supplement were queried from 2007 to 2016 to identify adult patients who underwent an ACDF procedure (N=176,816). Traditional machine learning algorithms, logistic regression, and support vector machines, were compared with deep neural networks to predict: 90-day postoperative complications, 90-day readmission, and two-year reoperation. We further generated random deep learning model architectures and trained them on the 90-day complication task to approximate an upper bound. Last, using deep learning, we investigated the importance of each input variable for the prediction of 90-day postoperative complications in ACDF.Results: For the prediction of 90-day complication, 90-day readmission, and two-year reoperation, the deep neural network-based models achieved AUC of 0.832, 0.713, and 0.671. Logistic regression achieved AUCs of 0.820, 0.712, and 0.671. Support vector machine approaches were significantly lower. The upper bound of deep learning performance was approximated as 0.832. Myelopathy, age, human immunodeficiency virus, previous myocardial infarctions, obesity, and documentary weakness were found to be the strongest variable to predict 90-day postoperative complications.Conclusions: The deep neural network may be used to predict complications for clinical applications after multicenter validation. The results suggest limited added knowledge exists in interactions between the input variables used for this task. Future work should identify novel variables to increase predictive power. [ABSTRACT FROM AUTHOR]

Candidates for anterior cervical discectomy and fusion (ACDF) have a higher rate of opioid use than does the public, but studies on preoperative opioid use have not been conducted. We aimed to understand how preoperative opioid use affects post-ACDF outcomes. The MarketScan Database was queried from 2007 to 2015 to identify adult patients who underwent an ACDF. Patients were classified into separate cohorts based on the number of separate opioid prescriptions in the year before their ACDF. Ninety-day postoperative complications, postoperative readmission, reoperation, and total inpatient costs were compared between opioid strata. Propensity score-matched patient cohorts were calculated to balance comorbidities across groups. Of 81,671 ACDF patients, 31,312 (38.3%) were nonusers, 30,302 (37.1%) were mild users, and 20,057 (24.6%) were chronic users. Chronic opioid users had a higher comorbidity burden, on average, than patients with less frequent opioid use (P < 0.001). Chronic opioid users had higher rates of postoperative complications (9.1%) than mild opioid users (6.0%) and nonusers (5.3%) (P < 0.001) and higher rates of readmission and reoperation. After balancing opioid nonusers versus chronic opioid users along with demographic characteristics, preoperative comorbidity, and operative characteristics, postoperative complications remained elevated for chronic opioid users relative to opioid nonusers (8.6% vs. 5.7%; P < 0.001), as did rates of readmission and reoperation. Chronic opioid users had more comorbidities than opioid nonusers and mild opioid users, longer hospitalizations, and higher rates of postoperative complication, readmission, and reoperation. After balancing patients across covariates, the outcome differences persisted, suggesting a durable association between preoperative opioid use and negative postoperative outcomes. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

In 2016, the World Health Organization revised its guidelines to retain only gemistocytic astrocytoma (GemA) as a distinct variant of diffuse astrocytoma (DA). In the past, grade II GemAs were linked with a worse prognosis than DA. However, it is unclear how consistently the tumor subtype has been diagnosed over time. We used more recent data to compare outcomes between grade II GemA and DA. Patients with grade II DA and GemA were extracted from the Surveillance, Epidemiology, and End Results database between 1973 and 2016. Kaplan-Meier curves estimated survival differences across different eras, with a focus on patients diagnosed between 2000 and 2016, and propensity score matching was used to balance baseline characteristics between DA and GemA cohorts. Of 2467 patients with grade II astrocytoma diagnosed between 2000 and 2016, 132 (5.35%) had GemA, and 2335 (94.65%) had DA. At baseline, marked demographic and treatment differences were noted between tumor subtypes, including age at diagnosis and female sex. GemA patients did not have worse survival compared with DA patients at baseline (P = 0.349) or after propensity score matching (P = 0.497). Multivariate Cox models found that surgical extent of resection was associated with a survival benefit for DA patients, and both DA and GemA patients >65 years old had dramatically inferior survival. Our data suggest that the impact of GemA versus DA histopathology depends more on the decade of queried data rather than patient-specific demographics. Using more recent longitudinal data, we found that grade II GemA and DA tumors did not have significant differences in survival. These data may prove useful for clinicians counseling patients with grade II GemA. [ABSTRACT FROM AUTHOR]

In the present study, we used a validated socioeconomic status (SES) index and population-based registry to identify and quantify the impact of SES on access to treatment and overall survival for patients diagnosed with synchronous brain metastases. The Surveillance, Epidemiology, and End Results database was used to extract all patients between 2010 and 2016 with brain metastases at initial presentation. SES was stratified into tertiles and quintiles using the validated Yost index. Multivariable logistic regressions were used to evaluate the impact of demographic, tumor, and socioeconomic covariates on receipt of radiotherapy and chemotherapy. Kaplan-Meier curves were used to estimate survival. Between 2010 and 2016, 35,595 patients presented with brain metastases at the time of primary cancer diagnosis. Most patients received radiation and/or chemotherapy as part of the initial course of their treatment; 71.6% (n = 25,484) were irradiated while 54.4% (n = 19,371) received chemotherapy and 44.9% (n = 15,984) received chemoradiation. Patients in the highest Yost tertile and quintile experienced longer overall survival (P < 0.001). Additionally, multivariable logistic regression revealed that the lowest Yost quintile was significantly less likely to receive either radiation (adjusted OR: 0.82; 95% confidence interval: 0.75–0.89; P < 0.001) or chemotherapy (adjusted OR: 0.62; 95% confidence interval: 0.58–0.67; P < 0.001). In a large, population-based analysis of brain metastasis patients, we found significant differences in treatment access and mild survival differences along socioeconomic strata. More specifically, patients in lower SES tiers suffered worse outcomes and received radiation and chemotherapy less frequently than patients in higher tiers, even after accounting for other tumor- and demographic-related information. [ABSTRACT FROM AUTHOR]