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Purpose: Patients with brain metastases (BrM) from esophageal cancer have poor prognosis, the incidence of which is expected to rise due to improved survival from the primary tumor and increased neuroimaging. We aimed to identify patient and esophageal cancer characteristics associated with shorter survival in patients with BrM and, secondly, to compare the prognosis of patients with HER2 overexpression., Methods: We retrospectively reviewed patients with BrM from esophageal cancer at a single institution from 2008-2021. We collected patient demographics, primary tumor and BrM characteristics, and treatment. Our primary outcome was median survival from the time of BrM., Results: The median age at primary diagnosis was 66.5 years and 86% were male. Of the 49 patients, 71% had adenocarcinoma, 20% squamous cell carcinoma and 8% other. 71% of patients presented with stage III or IV disease, including 16% with synchronous primary and BrM. The median time to BrM was 10.1 months (IQR 1.7-22.8) and the median survival from BrM was 8.4 months (95%CI 4.8-16.8). On multivariable analysis, treatment with stereotactic radiosurgery (HR=0.19;p=0.04), surgical resection (HR 0.24;p=0.03) and immunotherapy (HR 0.19;p=0.04) were associated with increased survival while KPS ≤70 (HR=13.2;p<0.001) was associated with decreased survival. HER2 overexpression was found in 22% of patients, but we noted no survival difference (5.2 months HER2+ versus 9.8 months HER2neg;p=0.95)., Conclusion: The median survival from esophageal-to-brain metastasis was 8.4 months. Patients with a single lesion, KPS score >70, and treatment with surgical resection was correlated with improved survival. Further, HER2+ patients had distinct patient and BrM characteristics., (Copyright © 2024. Published by Elsevier Inc.)

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., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: Lumbar laminectomy is often utilized in the treatment of degenerative lumbar spondylolisthesis. Risk factors that contribute to reoperation rates, in particular to progression to fusion, are poorly understood. We aimed to identify rate and risk factors of lumbar fusion surgery following lumbar laminectomy for the treatment of degenerative lumbar spinal spondylolisthesis., Methods: Our sample was obtained from the national MarketScan Commercial Claims and Encounters Database. We reviewed patients undergoing lumbar laminectomy for stable degenerative lumbar spondylolisthesis (Grade-1) at one or two levels between January 2007 and December 2016., Results: A total of 33,681 patients were included. By 2 years after the index operation, 2.48 % of patients had required lumbar fusion surgery. Female sex was associated with lower odds (OR 0.8, 95 %CI 0.7-0.9) of reoperation for fusion. Diabetes (OR 1.2, 95 %CI 1.1-1.4), rheumatoid arthritis (OR 1.5, 95 %CI 1.2-1.7) and clinical presentation with LBP (OR 2.1, 95 %CI 1.6-2.9), lower extremity weakness (OR 1.4, 95 %CI 1.1-1.5), as well as occurrence of a postoperative neurological complications (OR 2.0, 95 %CI 1.1-3.4) increased the odds ratio for requiring fusion surgery within two years after lumbar laminectomy., Conclusion: In this large cross-sectional sample of a national claims database consisting of lumbar laminectomy patients for the treatment of spondylolisthesis, approximately 2.5 % required subsequent lumbar fusion. Several modifiable risk factors for fusion progression were identified, which may guide clinicians in shared decision-making and to help identify patients with elevated post-operative risk providing potential leverage point for prevention., Competing Interests: Conflict of Interest None., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The prevalence of fibrotic diseases and the lack of pharmacologic modalities to effectively treat them impart particular importance to the discovery of novel antifibrotic therapies. The repurposing of drugs with existing mechanisms of action and/or clinical data is a promising approach for the treatment of fibrotic diseases. One paradigm that pervades all fibrotic diseases is the pathological myofibroblast, a collagen-secreting, contractile mesenchymal cell that is responsible for the deposition of fibrotic tissue. In this study, we use a gene expression paradigm characteristic of activated myofibroblasts in combination with the Connectivity Map to select compounds that are predicted to reverse the pathological gene expression signature associated with the myofibroblast and thus contain the potential for use as antifibrotic compounds. We tested a small list of these compounds in a first-pass screen, applying them to fibroblasts, and identified the retinoic acid receptor agonist Ch55 as a potential hit. Further investigation exhibited and elucidated the antifibrotic effects of Ch55 in vitro as well as showing antiscarring activity upon intradermal application in a preclinical rabbit ear hypertrophic scar model. We hope that similar predictions to uncover antiscarring compounds may yield further preclinical and ultimately clinical success., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: We assessed whether the insurance type reflects a patient's quality of care after an anterior discectomy and fusion (ACDF) procedure by comparing differences in the postoperative complications, readmission rates, reoperation rates, lengths of hospital stay, and cost of treatment between patients with Medicare versus private insurance., Methods: Propensity score matching was used to match patient cohorts insured by Medicare and private insurance in the MarketScan Commercial Claims and Encounters Database (2007-2016). Age, sex, year of operation, geographic region, comorbidities, and operative factors were used to match cohorts of patients who had undergone an ACDF procedure., Results: A total of 110,911 patients met the inclusion criteria. Of these patients, 97,543 patients (87.9%) were privately insured and 13,368 patients (12.1%) were insured by Medicare. The propensity score matching algorithm matched 7026 privately insured patients to 7026 Medicare patients. After matching, no significant differences were found in the 90-day postoperative complication rates, lengths of stay, or reoperation rates between the Medicare and privately insured cohorts. The Medicare group had had lower postoperative readmission rates for all time points: 30 days (1.8% vs. 4.6%; P < 0.001), 60 days (2.5% vs. 6.3%; P < 0.001), and 90 days (4.2% vs. 7.7%; P < 0.001). The median payment to physicians was significantly lower for the Medicare group ($3885 vs. $5601; P < 0.001)., Conclusions: In the present study, propensity score matched patients covered by Medicare and private insurance who had undergone an ACDF procedure had had similar treatment outcomes., (Copyright © 2023 Elsevier Inc. All rights reserved.)

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., (Copyright © 2023 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

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., (Copyright © 2022 International Neuromodulation Society. Published by Elsevier Inc. All rights reserved.)

Damage to epidermis results in loss of barrier function and resultant pathological inflammatory signaling, triggering further damage to the skin. Here we investigate transcriptomic datasets generated from varied skin pathologies associated with disrupted epidermis and pinpoint CD14/S100 signaling as a conserved pathway upregulated in dermatopathologies characterized by a compromised epidermal barrier. We show that dermatitic and fibrotic tissues of humans and mouse models, which are associated with compromised epidermal barrier, demonstrate upregulation of CD14 and S100 proteins, damage-associated molecular patterns (DAMPs), in the epidermis. In vitro stratified keratinocyte cultures exposed to reduced hydration conditions show upregulated CD14/S100 family genes and pro-inflammatory gene expression, as well as decreased barrier gene expression. Knockdown and overexpression of CD14 in stratified keratinocyte cultures suppresses and induces expression, respectively, of S100 family genes and CXCL8. Taken together, these data suggest that upregulation of CD14 and/or S100 family genes in pathological epidermis results in potentiated inflammatory signaling, leading to diminished epidermal barrier function that may yield further inflammation. Future strategies to target CD14 may be utilized to dampen the response to epithelial injury for conditions of the skin and other organs., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objective: 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., Methods: 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., Results: 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., Conclusions: 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., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: 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., Methods: 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., Results: 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)., Conclusions: 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., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: 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., Methods: 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., Results: 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., Conclusions: 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., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: Immunotherapy for patients with melanoma with brain metastasis has significantly improved outcomes; however, it has also been characterized by potentially dangerous immune-related adverse events (IRAEs). Several reports have suggested that these reactions can precede improved treatment responses. For intracranial disease control, we sought to identify if such an association exists., Methods: We conducted a retrospective chart review of patients with melanoma who underwent immunotherapy treatment after diagnosis of brain metastasis. The study cohort was then stratified into 2 groups based on their history of developing an IRAE that prompted discontinuation of that regimen. The primary outcome variable included intracranial progression-free survival (PFS). Kaplan-Meier and Cox proportional hazard analyses were used to evaluate survival and predictors of outcomes., Results: Fifty-two patients met the inclusion criteria, 17 of whom experienced severe IRAEs that led to discontinuation of immunotherapy. Median intracranial PFS was 19.9 versus 10.5 months (P = 0.053) in patients who did and did not experience severe IRAEs prompting discontinuation, respectively. No additional outcome benefits were identified for systemic PFS or overall survival (mean, 33.1 months and 27.6 months, respectively). Multivariable analysis identified BRAF mutation status as a negative prognosticator of brain progression (P = 0.013; hazard ratio, 3.90). Initial treatment with BRAF inhibitor was also a negative predictor of all-cause mortality (P = 0.015; hazard ratio, 10.73)., Conclusions: Immune-related adverse events may signify an underlying immunogenic response that has intracranial disease control benefits. Despite their associated side effects, immunotherapies continue to show promising outcomes as a first-line agent for melanoma with brain metastasis., (Copyright © 2020 Elsevier Inc. All rights reserved.)