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Background: The healthcare sector is a significant contributor to worldwide greenhouse gas emissions. The specific environmental impacts of neurosurgical operations remain largely unexplored., Objective: To identify and review existing literature on sustainability and environmental impacts in the neurosurgical operating room, with an aim to assess scope and scale, and secondarily to evaluate potential interventions pertinent to neurosurgery., Methods: PubMed, Medline, and Scopus were searched for English-language articles published through July 2023 topically related to operating room sustainability practices and environmental impacts, with attention paid to neurosurgery., Results: A primary search identified 5 articles that specifically addressed sustainability issues within neurosurgery; 3 were observational studies, 1 was retrospective, and 1 was a prospective study. A further 12 studies (4 observational, 4 systematic reviews, 3 prospective, 1 a survey on barriers to practice adoption) were evaluated to access the broader scope of environmental impacts of surgery that may be relatable to neurosurgery. Key reviewed subdomains included resource conservation, waste production, and carbon footprinting., Conclusion: There is a paucity of literature on sustainability practices within the field of neurosurgery. Here we identify the available evidence on the environmental impact of neurosurgical care and describe some avenues to reduce this impact by exploring surgical sustainability literature more broadly., (Copyright © 2023. Published by Elsevier Inc.)

Background: Few studies have evaluated frailty in the setting of aneurysmal subarachnoid hemorrhage (aSAH) using large-scale data. The risk analysis index (RAI) may be implemented at the bedside or assessed retrospectively, differentiating it from other indices used in administrative registry-based research., Methods: Adult aSAH hospitalizations were identified in the National Inpatient Sample (NIS) from 2015 to 2019. Complex samples statistical methods were performed to evaluate the comparative effect size and discriminative ability of the RAI, the modified frailty index (mFI), and the Hospital Frailty Risk Score (HFRS). Poor functional outcome was determined by the NIS-SAH Outcome Measure (NIS-SOM), shown to have high concordance with modified Rankin Scale scores > 2., Results: 42,300 aSAH hospitalizations were identified in the NIS during the study period. By both ordinal [adjusted odds ratio (aOR) 3.20, 95% confidence interval (CI) 3.05, 3.36, p < 0.001] and categorical stratification [frail aOR 3.59, 95% CI 3.39, 3.80, p < 0.001; severely frail aOR 6.67, 95% CI 5.78, 7.69, p < 0.001], the RAI achieved the largest effect sizes for NIS-SOM in comparison with the mFI and HFRS. Discrimination of the RAI for NIS-SOM in high-grade aSAH was significantly greater than that of the HFRS (c-statistic 0.651 vs. 0.615). The mFI demonstrated the lowest discrimination in both high-grade and normal-grade patients. A combined Hunt and Hess-RAI model (c-statistic 0.837, 95% CI 0.828, 0.845) for NIS-SOM achieved significantly greater discrimination than both the combined models for mFI and HFRS (p < 0.001)., Conclusion: The RAI was robustly associated with poor functional outcomes in aSAH independent of established risk factors., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Introduction: Acute kidney injury (AKI) is associated with poor outcome in aneurysmal subarachnoid hemorrhage patients (aSAH). Frailty has recently been demonstrated to correlate with elevated mortality and morbidity; its impact on predicting AKI and mortality in aSAH patients has not been investigated., Objective: Evaluating risk factors and predictors for AKI in aSAH patients., Methods: aSAH patients from a single-center's prospectively maintained database were retrospectively evaluated for development of AKI within 14 days of admission. Baseline demographic and clinical characteristics were collected. The effect of frailty and other risk factors were evaluated., Results: Of 213 aSAH patients, 53 (33.1%) were frail and 12 (5.6%) developed AKI. Admission serum creatinine (sCr) and peak sCr within 48 h were higher in frail patients. AKI patients showed a trend towards higher frailty. Mortality was significantly higher in AKI than non-AKI aSAH patients. Frailty was a poor predictor of AKI when controlling for Hunt and Hess (HH) grade or age. HH grade ≥ 4 strongly predicted AKI when controlling for frailty., Conclusion: AKI in aSAH patients carries a poor prognosis. The HH grade appears to have superior utility as a predictor of AKI in aSAH patients than mFI.

Background: Increasing evidence supports the effectiveness of venous sinus stenting (VSS) with favorable outcomes, safety, and expenses compared with shunting for idiopathic intracranial hypertension. Yet, no evidence is available regarding optimal postoperative recovery, which has increasing importance with the burdens on health care imposed by the coronavirus disease 2019 pandemic. We examined adverse events and costs after VSS and propose an optimal recovery pathway to maximize patient safety and reduce stress on health care resources., Methods: A retrospective review was undertaken of elective VSS operations performed from May 2008 to August 2021 at a single institution. Primary data included hospital length of stay, intensive care unit (ICU) length of stay, adverse events, need for ICU interventions, and hospital costs., Results: Fifty-three patients (98.1% female) met the inclusion criteria. Of these patients, 51 (96.2%) were discharged on postoperative day (POD) 1 and 2 patients were discharged on POD 2. Both patients discharged on POD 2 remained because of groin hematomas from femoral artery access. There were no major complications or care that required an ICU. Eight patients (15.1%) were lateralized to other ICUs or remained in a postanesthesia care unit because the neurosciences ICU was above capacity. Total estimated cost for initial recovery day in a neurosciences ICU room was $2361 versus $882 for a neurosurgery/neurology ward room. In our cohort, ward convalescence would save an estimated $79,866 for bed placement alone and increase ICU bed availability., Conclusions: Our findings reaffirm the safety of VSS. These patients should recover on a neurosurgery/neurology ward, which would save health care costs and increase ICU bed availability., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Intra-arterial administration of chemotherapy with or without osmotic blood-brain barrier disruption enhances delivery of therapeutic agents to brain tumors. The aim of this study is to evaluate the safety of these procedures., Methods: Retrospectively collected data from a prospective database of consecutive patients with primary and metastatic brain tumors who received intra-arterial chemotherapy without osmotic blood-brain barrier disruption (IA) or intra-arterial chemotherapy with osmotic blood-brain barrier disruption (IA/OBBBD) at Oregon Health and Science University (OHSU) between December 1997 and November 2018 is reported. Chemotherapy-related complications are detailed per Common Terminology Criteria for Adverse Events (CTCAE) guidelines. Procedure-related complications are grouped as major and minor., Results: 4939 procedures (1102 IA; 3837 IA/OBBBD) were performed on 436 patients with various pathologies (primary central nervous system lymphoma [26.4%], glioblastoma [18.1%], and oligodendroglioma [14.7%]). Major procedure-related complications (IA: 12, 1%; IA/OBBBD: 27, 0.7%; P = .292) occurred in 39 procedures including 3 arterial dissections requiring intervention, 21 symptomatic strokes, 3 myocardial infarctions, 6 cervical cord injuries, and 6 deaths within 3 days. Minor procedure-related complications occurred in 330 procedures (IA: 41, 3.7%; IA/OBBBD: 289, 7.5%; P = .001). Chemotherapy-related complications with a CTCAE attribution and grade higher than 3 was seen in 359 (82.3%) patients., Conclusions: We provide safety and tolerability data from the largest cohort of consecutive patients who received IA or IA/OBBBD. Our data demonstrate that IA or IA/OBBBD safely enhance drug delivery to brain tumors and brain around the tumor., (© The Author(s) 2022. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)

Objectives: Aneurysmal subarachnoid hemorrhage (aSAH) is an emergent neurosurgical condition associated with high morbidity and mortality. The prognostic significance of baseline frailty status in aSAH patients has not been previously evaluated in a large, nationally representative sample., Materials and Methods: Clinical outcomes data from the National Inpatient Sample from 2010-2018 were compared among sub-cohorts stratifying admissions by increasing frailty thresholds [(assessed using the 11-point modified frailty index (mFI-11)]. The previously validated NIS-SAH Severity Score (NIS-SSS) and NIS-SAH Outcome Measure (NIS-SOM) were utilized. Complex samples multivariable logistic regression and receiver operating characteristic (ROC) curve analyses were performed to assess adjusted associations and discrimination of frailty for endpoints., Results: Among 64,102 aSAH hospitalizations (mean age 55.4 years), 20.4% of admissions were classified as robust (mFI=0), 43.4% as pre-frail (mFI = 1), 24.9% as frail (mFI = 2), and 11.2% as severely frail (mFI ≥ 3). Following multivariable analysis adjusting for age and aSAH severity, increasing frailty was independently associated with NIS-SOM (OR = 1.15, 95% CI 1.09-1.21; p < 0.001), extended length of hospital stay (eLOS) (OR = 1.08, 1.02-1.13; p = 0.008), neurological complications (OR = 1.08, 1.03-1.13; p < 0.001), and medical complications (OR = 1.14, 1.08-1.21; p < 0.001). Based on ROC curve analysis, frailty achieved an AUC of 0.59 (0.58-0.60) and 0.54 (0.53-0.55) for NIS-SOM and eLOS, respectively. Age and NIS-SSS demonstrated significantly greater discrimination for NIS-SOM [AUC 0.69 (0.68-0.70) and 0.79 (0.78-0.80), respectively), while NIS-SSS achieved significantly greater discrimination for eLOS [(AUC 0.74 (0.73-0.75)] in comparison to both age and frailty., Conclusions: This national database evaluation of frailty in aSAH patients demonstrates an independent association between increasing frailty and poor functional outcome. Age and aSAH severity, however, may be more robust prognostic factors., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background and Purpose: While patients with angiogram-negative subarachnoid hemorrhages (ANSAH) have better prognoses than those with aneurysmal SAH, frailty's impact on outcomes in ANSAH is unclear. We previously showed that the modified frailty index (mFI-11) is associated with poor outcomes following ANSAH. Here, we compared the mFI-5, mFI-11, Charlson Comorbidity Index (CCI), and temporalis thickness (TMT) to determine which index was the best predictor of ANSAH outcomes and mortality rates., Methods: In this retrospective cohort analysis between 2014 and 2018, patients with non-traumatic, angiogram negative SAH (ANSAH) were identified. The admission mFI-5, mFI-11, CCI, and TMT were calculated for each patient. Primary outcomes were mortality rate, discharge location, and prolonged length of stay (PLOS; LOS >85 th percentile). Multivariate logistic regression and receiver operating characteristic (ROC) curves were used to evaluate frailty as predictors of primary endpoints., Results: We included 75 patients with a mean age of 55.4 ± 1.5 years. There were 4 patient deaths (5.3%), 53 patients (70.7%) discharged home, and 11 patients (14.7%) with PLOS. On ROC analysis, the mFI-5 had the highest discriminatory value for mortality (AUC   =   0.97) while the mFI-11 was most discriminatory for discharge home (AUC   =   0.85) and PLOS (AUC   =   0.78). On multivariate analysis, the only independent predictor of mortality was the mFI-11 (OR   =   0.46; 95%CI: 1.45-14.23; p   =   0.009) while the mFI-5 was the best predictor of discharge home (OR   =   0.21; 95% CI: 0.08-0.61; p   =   0.004). On multivariate analysis, the only independent predictor of PLOS was the Hunt and Hess score (OR   =   2.63; 95%CI: 1.38-5.00; p   =   0.003). The CCI and TMT were inferior to either mFI for predicting primary endpoints., Conclusions: Increasing frailty is associated with poorer outcomes and higher mortality following ANSAH. The mFI-5 and mFI-11 were found to be superior predictors of discharge home and mortality rate. While larger prospective study is needed, frailty, as measured by mFI-11 and -5, should be considered when evaluating ANSAH prognosis.

Objective: In this systematic review, preoperative educational interventions for patients undergoing neurosurgical treatment are identified and their impact on patient knowledge acquisition and satisfaction is assessed., Methods: The review was conducted in accordance with the PRISMA guidelines and used PubMed, Google Scholar, and MEDLINE databases. Studies evaluating before and after cohort or control group comparison were identified between 2007 and 2019 and were independently scored and evaluated by 3 authors., Results: Eighty-one articles were assessed for eligibility and 15 met the inclusion criteria. Patient educational interventions were text-based (2 studies), multimedia/video-based (3), mobile/tablet-based (5), or used virtual reality (2) or three-dimensional printing (3). Interventions were disease-specific for cerebrovascular lesions (5), degenerative spine disease (2), concussion/traumatic brain injury (2), movement disorders (1), brain tumor (1), adolescent epilepsy (1), and other cranial/spinal elective procedures (3). Eleven studies (n = 18-175) documented patient knowledge acquisition using self-reported knowledge questionnaires (5) or more objective assessments based on true/false or multiple-choice questions (6). Most studies (10/11) reported statistically significant increases in patient knowledge after implementation of the intervention. Ten studies (n = 14-600) documented patient satisfaction using validated satisfaction surveys (2), Likert scale surveys (6), or other questionnaires (2). Although all studies reported increases in patient satisfaction after the intervention, only 4 were statistically significant., Conclusions: Patient educational interventions using various modalities are broadly applicable within neurosurgery and ubiquitously enhance patient knowledge and satisfaction. Interventions should be implemented when possible., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Transcriptional analysis can be utilized to reconcile variants of uncertain significance, particularly those predicted to impact splicing. Laboratory analysis of the predicted mRNA transcript may allow inference of the in vivo impact of the variant and aid prediction of its clinical significance. We present a patient with classical features of primary ciliary dyskinesia (PCD) who was identified to have compound heterozygous variants in the DNAH11 gene (c.10691 + 2T > C, c.13523&#95;13543dup21) via trio whole-exome sequencing in 2013. These variants were originally classified as Mutation and Likely Mutation. However, these variants were downgraded to variants of uncertain significance (VUSs) during reanalysis in 2016 because of uncertainty that they caused a loss of function of the gene. c.10691 + 2T > C is predicted to abrogate the canonical splice site and lead to the skipping of exon 65, but the adjoining of exon 64 and exon 66 in the DNAH11 transcript preserves the reading frame of the resultant protein. c.13523&#95;13543dup21 is located in the last exon of the DNAH11 coding sequence, upstream of the canonical stop codon, which suggests a reduced likelihood to trigger nonsense-mediated decay (NMD). Transcriptional analysis was performed to characterize the impact of the variants, resulting in reclassification of c.10691 + 2T > C to Likely Pathogenic by providing evidence that it results in a deleterious effect and subsequent downstream reclassification of c.13523&#95;13543dup21 to Likely Pathogenic as well. Our case illustrates the potential impact of transcriptional analysis on variant resolution, supporting its usage on variants that exert an unpredictable effect on splicing., (© 2021 Ing et al.; Published by Cold Spring Harbor Laboratory Press.)

Although hyperglycemia is associated with worse outcomes after aneurysmal subarachnoid hemorrhage (aSAH), there is no consensus on the optimal glucose control metric, acceptable in-hospital glucose ranges, or suitable insulin regimens in this population. In this single-center retrospective cohort study of aSAH patients, admission glucose, and hospital glucose mean (MHG), minimum (MinG), maximum (MaxG), and variability were compared. Primary endpoints (mortality, complications, and vasospasm) were assessed using multivariate logistic regressions. Of the 217 patients included, complications occurred in 83 (38.2%), 124 (57.1%) had vasospasm, and 41 (18.9%) died. MHG was independently associated with (p < 0.001) mortality, MaxG (p = 0.017) with complications, and lower MinG (p = 0.015) with vasospasm. Patients with MHG ≥ 140 mg/dL had 10 × increased odds of death [odds ratio (OR) = 10.3; 95% CI 4.6-21.5; p < 0.0001] while those with MinG ≤ 90 mg/dL had nearly 2× increased odds of vasospasm (OR = 1.8; 95% CI 1.01-3.21; p = 0.0422). While inpatient insulin was associated with increased complications and provided no mortality benefit, among those with MHG ≥ 140 mg/dL insulin therapy resulted in lower mortality (OR = 0.3; 95% CI 0.1-0.9; p = 0.0358), but no increased complication risk. While elevated MHG and MaxG are highly associated with poorer outcomes after aSAH, lower MinG is associated with increased vasospasm risk. Future trials should consider initiating insulin therapy based on MHG rather than other hyperglycemia measures.

Objective: Understand the frailty of vestibular schwannoma surgical patients and how frailty impacts clinical course., Study Design: Retrospective Cohort., Setting: Single-tertiary academic hospital., Patients: All patients undergoing vestibular schwannoma surgery., Intervention: The modified frailty index (mFI) was calculated for all patients undergoing surgery for vestibular schwannoma between 2011 and 2018. Patient demographics and medical history, perioperative course, and postoperative complications were obtained from the medical record., Main Outcome Measures: The primary endpoint was hospital length of stay (LOS). Secondary endpoint was postoperative complications. Basic statistical analysis was performed including multivariate linear regressions to determine independent predictors of LOS., Results: There were 218 patients included and the mean age was 48.1 ± 0.9 (range 12-77). One-hundred ten patients were male (50.5%). The mean ICU LOS was 1.6 ± 0.1 days while mean total hospital LOS was 4.3 ± 0.2. There were 145 patients (66.5%) who were robust (nonfrail) with an mFI of 0, while 73 (33.5%) had an mFI of ≥1. Frailty (mFI≥2) was associated with longer hospital LOS compared with the prefrail (p = 0.0014) and robust (p = 0.0004) groups, but was not associated with increased complications (OR = 1.3; 95% CI: 0.5-3.7; p = 0.5925) or ICU LOS (p > 0.05). In multivariate analysis, increased mFI, and NOT increased age, was an independent risk factor for increased hospital LOS (p = 0.027)., Conclusion: Increasing frailty, and not increasing age, is an independent risk factor for longer hospital LOS, but not for increased postoperative complications. Patients' frailty status may be useful preoperatively in counselling patients about postoperative expectations and frail vestibular schwannoma patients may require increased health spending costs given their increased hospital LOS.

Background: Frailty is associated with worse outcomes across a variety of neurosurgical diseases. However, its effect on acute subdural hemorrhage (aSDH) outcomes is unclear. The goal of this study is to compare 3 measures of frailty with the gold standard (i.e., initial Glasgow Coma Scale [iGCS] score) for predicting outcomes after aSDH., Methods: Patients who presented between January 2016 and June 2018 were retrospectively identified based on International Classification of Diseases codes for aSDH. Patients' modified Frailty Index (mFI), temporalis muscle thickness (TMT), and age-adjusted Charlson Comorbidity Index (CCI) were calculated. Primary end points were death and discharge home., Results: Of 167 patients included, the mean age was 63.4 ± 1.9 years, the average CCI was 3.4 ± 0.2, mFI was 1.4 ± 0.1, TMT was 7.1 ± 0.2 mm, and iGCS score was 11.9 ± 0.3. Sixty-nine patients (41.3%) were discharged home and 32 (19.2%) died during hospitalization. In multivariate analysis, decreasing iGCS score (odds ratio [OR], 0.84; 95% confidence interval [CI], 0.74-0.96; P = 0.0112) and midline shift (OR, 1.27; 95% CI, 1.08-1.50; P = 0.0048), but not age or frailty, predicted mortality. In addition to iGCS score (OR, 1.26; 95% CI, 1.10-1.44; P = 0.0011), lower CCI (OR, 0.32; 95% CI, 0.14-0.74; P = 0.0071) and larger TMT (OR, 2.63; 95% CI, 1.16-5.99; P = 0.0210) independently predicted increased rates of discharge home. mFI was not independently associated with either primary end point in multivariate analysis., Conclusions: iGCS score predicts both mortality and discharge location after aSDH better than do age or frailty. However, CCI and TMT, but not mFI, are useful prognostic indicators of discharge to home after aSDH. The iGCS score should continue to be the primary prediction tool for patients with aSDH; however, frailty may be useful for resource allocation, especially when nearing discharge., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction: While recent reports underscore the significance of the gut microbiome (GM) in health and disease, its importance in burn outcomes remains unclear. Moreover, aggressive intravenous (IV) fluid resuscitation of patients may alter intestinal flora. Herein, we describe GM changes following a large burn in swine randomized to different volumes of IV Lactated Ringers' (LR)., Methods: Anesthetized Yorkshire swine sustained 40% total body surface area full-thickness burns and were randomized to different volumes of IV LR: none (n = 5), 15 mL/kg/d (low; n = 6), or 80 mL/kg/d (high; n = 6). At baseline and days 1 and 2, fecal swabs were collected for 16s rDNA sequencing. Proximal jejunum was collected immediately after euthanasia (day 2) for western blot, histopathology, and cytokine analyses., Results: Burns produced significant shifts in β-diversity and non-significant reductions in α-diversity that did not recover regardless of treatment group. Burn-induced increases in Proteobacteria and decreases in Firmicutes were attenuated by IV fluids in a dose-dependent manner, and also correlated with α-diversity. IV fluids caused a dose-dependent increase in Bacteroides and prevented a transient increase in the opportunistic pathogen Haemophilus parainfluenzae. While high volumes of IV fluids increased intestinal Hsp70 levels (P = 0.0464), they reduced SGLT1 (P = 0.0213) and caspase3 (P = 0.0139) levels. IV fluids elicited a non-specific cytokine response; however, Bacteroidetes levels correlated with intestinal IL18 levels (P = 0.0166, R = 0.4201)., Conclusions: We present the first report on the gut microbiome in a porcine burn model, and present data to suggest that IV fluids may influence GM and gut functional proteins following a burn. Overall, burn-induced GM diversity shifts may expose diagnostic and/or therapeutic targets to improve outcomes.

Background Initial Glasgow Coma Score (iGCS) is a well-known predictor of adverse outcomes following chronic subdural hemorrhage (cSDH). Frailty, i.e. a reduced physiologic reserve, is associated with poorer outcomes across the surgical literature, however, there is no consensus on the best measure of frailty. To date, no study has compared frailty's ability to predict cSDH outcomes versus iGCS. The goal of this study was to, therefore, examine the prognostic value of the 5- (mFI-5) and 11-factor (mFI-11) modified frailty index, and Charlson Comorbidity Index (CCI) versus iGCS following cSDH. Methods Between January, 2016 and June, 2018, patients who presented to the emergency department with cSDH were retrospectively identified using the International Classification of Diseases (ICD) codes. mFI-5, mFI-11, and CCI scores were calculated using patient baseline characteristics. Primary endpoints were death and discharge home and subgroup analyses were performed among operative cSDH. Univariate and multivariate logistic regressions were used to determine predictors of primary endpoints. Results Of the 109 patients identified, the average age was 72.6±1.6 years and the majority (69/109, 63.3%) were male. The average CCI, mFI-5, and mFI-11 were 4.5 ±0.2, 1.5 ±0.1, and 2.2 ±0.1, respectively. Fifty (45.9%) patients required surgical intervention, 11 (10.1%) died, and 48 (43.4%) were discharged home. In the overall cohort, while the only multivariate predictor of mortality was iGCS (OR=0.58; 95%CI:0.44-0.77; p=0.0001), the CCI (OR=0.73; 95%CI:0.58-0.92; p=0.0082) was a superior predictor of discharge home compared to iGCS (OR=1.46; 95%CI:1.13-1.90; p=0.0041). Conversely, among those who received an operative intervention, the CCI, but not iGCS, independently predicted both mortality (OR=4.24; 95%CI:1.01-17.86; p=0.0491) and discharge home (OR=0.55; 95%CI:0.33-0.90; p=0.0170). Neither mFI nor age predicted primary outcomes in multivariate analysis. Conclusion While frailty is associated with worse surgical outcomes, the clinical utility of the mFI-5, mFI-11, and CCI in cSDH is unclear. We show that the iGCS is an overall superior predictor of mortality following cSDH but is outperformed by the CCI after operative intervention. Similarly, the CCI is the superior predictor of discharge home in cSDH patients overall and following an operative intervention. These results indicate that while the iGCS best predicts mortality overall, the CCI may be considered when prognosticating post-operative course and hospital disposition., Competing Interests: This work was supported, in part, by a grant from New York Medical College for medical student research., (Copyright © 2020, McIntyre et al.)

Background and Aims: Alcohol intoxication may confound the clinical assessment of the trauma patient. Head computed tomography (h-CT) is the standard imaging technique to rule out intracranial injury in most intoxicated trauma patients. The objective of this study was to determine whether certain clinical findings (computed clinical score [CCS]) could predict the h-CT yield, admission, and neurosurgical consultation (NSC) among intoxicated trauma patients., Materials and Methods: This is a 4-year retrospective cohort study (2013-2017) of trauma patients who presented to our level 1 trauma center emergency department with alcohol intoxication. For each patient, a computed clinical score (CCS) was generated based on the following findings: age ≥50 years, Glasgow Coma Scale <13, evidence of trauma above the clavicles, amnesia, loss of consciousness, headache, vomiting, and seizures. The primary endpoints were NSC, admission, and acute h-CT finding. Univariate and multivariate regressions were used to compare predictors of the primary endpoints., Results: We identified 437 intoxicated trauma patients (median age: 35 years [interquartile range: 25-50]; 71.9% men; median blood alcohol content: 207.8 mg/dL). One hundred and twenty-four (30.4%) patients had acute findings on h-CT, 351 (80.3%) were admitted, and 112 (25.6%) received NSC. On multivariate analysis, CCS was the only predictor of acute h-CT (odds ratio [OR] =1.6; 95% confidence interval [CI]: 1.3-2.0; P < 0.0001) and the best predictor of admission (OR = 1.6; 95% CI: 1.3-1.9; P < 0.0001) and NSC (OR = 1.8; 95% CI: 1.5-2.3; P < 0.0001)., Conclusions: One-third of intoxicated trauma patients have acute findings on h-CT. While the CCS was the best predictor of acute h-CT findings, hospital admission, and NSC, h-CT scanning should continue to be a standard of care., Competing Interests: There are no conflicts of interest., (Copyright: © 2020 Journal of Emergencies, Trauma, and Shock.)

Objective: Increasing age has been associated with worse outcomes following aneurysmal subarachnoid hemorrhage (aSAH), yet frailty's effect on aSAH outcomes has never been studied. The most common frailty measurement tool is the modified frailty index (mFI). The goal of this study is to compare the effect of frailty versus age as predictors of aSAH outcomes and mortality., Patients and Methods: Our institutional aSAH series were retrospectively identified and divided into non-frail (mFI = 0-1) and frail (mFI≥2) cohorts based on admission mFI scores. Primary outcomes were mortality and discharge location. Univariate and multivariate analysis were performed., Results: There were 217 aSAH patients identified and 57 were frail (26.3%). Forty-one (18.9%) patients died and 74 (34%) were discharged home. Frail patients were significantly older (p < 0.0001) and had higher Hunt & Hess (HH) (p = 0.005) and Fisher (p = 0.0255) scores. Frail patients were less likely to receive an intervention (OR = 0.3; 95%CI:0.1-0.6); p = 0.0056), be discharged home (OR = 0.32; 95%CI:0.16-0.68; P = 0.0020), and were more likely to expire (OR = 2.4; 95%CI:1.2-5; P = 0.0183) and develop a complication (OR = 2.6; 95%CI:1.1-6.6; P = 0.0277). Multivariate regressions showed that the HH score (OR = 2.7; 95%CI: 1.9-3.0; P < 0.0001) followed by age≥65 (OR = 2.7; 95%CI:1.2-6.0; p = 0.012) were the only independent predictors of mortality. Likewise, discharge home was best predicted by HH score (OR = 0.24; 95%CI:0.15-0.37; p < 0.0001) and age (OR = 0.25; 95%CI:0.1-0.6; p = 0.003)., Conclusion: Frailty is associated with worse aSAH grades, more complications, and increased mortality, however, increasing age and HH scores were the only independent predictors of aSAH outcomes. This study suggests that HH score and increasing patient age, and not the accumulated co-morbidities at the time of aSAH, better predict outcomes., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Public interest in health monitoring devices has increased with the availability of wearable technologies or wearables such as the Apple Watch. These devices are collecting health data that may be useful to health professionals. Most studies to date have been conducted with a limited sample size and with healthy subjects. Recent studies have suggested the usefulness of long-term cardiac monitoring to reveal atrial fibrillation and prevent cryptogenic stroke. Wearable devices may become useful in cardiac monitoring, and further studies are needed.

Over 100,000 patients in the United States are currently waiting for a kidney transplant. With just over 10,000 cadaveric kidneys transplanted annually, it is of the utmost importance to optimize kidney viability upon transplantation. One exciting avenue may be xenotransplantation, which has rejuvenated interest after advanced gene editing techniques have been successfully used in swine. Simultaneously, acute kidney injury (AKI) is associated with high morbidity and mortality and currently lacks effective treatment. Animal models have been used extensively to address both of these issues, with recent emphasis on renal progenitor cells (RPCs). Due to anatomical similarities to humans we aimed to examine progenitor cells from the renal papillae of swine kidneys. To do this, RPCs were dissected from the renal papillae of healthy swine. Cell surface marker expression, proliferation, and differentiation of the RPCs were tested in vitro . Additionally, a mixed lymphocyte reaction was performed to examine immunomodulatory properties. RPCs displayed spindle shaped morphology with limited self-renewing capacity. Isolated RPCs were positive for CD24 and CD133 at early passages, but lost expression with subsequent passaging. Similarly, RPCs displayed myogenic, osteogenic, and adipogenic differentiation capacities at passage 2, but largely lost this by passage 6. Lastly, direct contact of RPCs with human lymphocytes increased release of IL6 and IL8. Taken together, RPCs from the papilla of porcine kidneys display transient stem cell properties that are lost with passaging, and either represent multiple types of progenitor cells, or a multipotent progenitor population. In instances of ischemic insult, augmentation of/with RPCs may potentiate regenerative properties of the kidney. While the use of swine for transplantation and ischemia studies confers obvious advantages, the populations of different progenitor cell populations within pig kidneys warrants further investigation. Ultimately, while gene editing techniques enhance the potential for xenotransplantation of organs or cells, the ultimate success of this strategy may be determined by the (dis)similarities of RPCs from different species.

The ecological community of microorganisms in/on humans, termed the microbiome, is vital for sustaining homeostasis. While culture-independent techniques have revealed the role of the gut microbiome in human health and disease, the role of the cutaneous microbiome in wound healing is less defined. Skin commensals are essential in the maintenance of the epithelial barrier function, regulation of the host immune system, and protection from invading pathogenic microorganisms. In this review, we summarize the literature derived from pre-clinical and clinical studies on how changes in the microbiome of various acute and chronic skin wounds impact wound healing tissue regeneration. Furthermore, we review the mechanistic insights garnered from model wound healing systems. Finally, in the face of growing concern about antibiotic-resistance, we will discuss alternative strategies for the treatment of infected wounds to improve wound healing and outcomes. Taken together, it has become apparent that commensals, symbionts, and pathogens on human skin have an intimate role in the inflammatory response that highlights several potential strategies to treat infected, non-healing wounds. Despite these promising results, there are some contradictory and controversial findings from existing studies and more research is needed to define the role of the human skin microbiome in acute and chronic wound healing.

Intravenous (IV) resuscitation of burn patients has greatly improved outcomes and become a cornerstone of modern burn care. However, the heavy fluids and vascular access required may not be feasible in austere environments, mass casualty, or delayed transport scenarios. Enteral resuscitation has been proposed for these situations; we sought to examine the effectiveness of this strategy on improving burn-induced kidney injury. Anesthetized Yorkshire swine sustaining 40% TBSA full-thickness contact burns were randomized to three groups (n = 6/group): fluid deprivation, ad libitum water access, or 70 mL/kg/d Oral Rehydration Salt solution (ORS). Urine and blood were collected at baseline (BL), 6, 12, 24, 32, and 48h post-burn, at which point tissue was harvested and CT angiography performed. Although fluid consumption by ad libitum and ORS groups were matched (132±54mL/kg versus 120±24mL/kg, respectively), ORS intake increased urine output compared with water and no water (47.3±9.0 mL/kg versus 16.1±2.5 mL/kg, and 24.5±1.7 mL/kg respectively). Plasma creatinine peaked 6h following burn (1.67±0.07mg/dL) in all animals, but at 48h was comparable to BL in animals receiving water (1.23±0.06mg/dL) and ORS (1.30±0.09mg/dL), but not fluid deprived animals (1.56±0.05mg/dL) (P<0.05). Circulating levels of blood urea nitrogen steadily increased, but also decreased by 48h in animals receiving enteral fluids (P<0.05). Water deprivation reduced renal artery diameter (-1.4±0.17mm), whereas resuscitation with water (-0.44±0.14 mm) or ORS maintained it (-0.63±0.20 mm;P< 0.02). Circulating cytokines IL-1β, IL-6, IFNγ, and GM-CSF were moderately elevated in the fluid-deprived group. Taken together, the data suggest that enteral resuscitation with ORS rescues kidney function following burn injury. Incorporating enteral fluids may improve outcomes in resource-poor environments and possibly reduce IV fluid requirements to prevent co-morbidities associated with over-resuscitation. Studies into different volumes/types of enteral fluids are warranted. While ORS has saved many lives in cholera-associated dehydration, it should be investigated further for use in burn patients.

Inhalation injury commonly accompanies thermal injury, increasing the likelihood of mortality and multiple organ dysfunction (MOD). Large animal models have given important insight into the pathophysiology of this injury; however recapitulating late MOD has remained difficult. The current report describes experiments using a smoke inhalation and burn model, with follow-up of ambulatory swine for 14days with bronchoscopy, CT scanning, and bronchoalveolar lavage fluid (BALF)/blood collection. Clinically, animals cleared airway damage in the first several days after-injury. This was mirrored with erythematous airways on day 2 after-injury, which resolved by the end of the experiment, as did parenchymal damage seen on CT. An initial rise in the protein content of BALF immediately after-injury was followed by a dramatic increase in the concentration of leukocytes. Circulating neutrophils increased while lymphocytes decreased; both correlated with cell counts in BALF. IL8 levels in BALF increased 30-fold and remained elevated throughout the experiment. IL1ra increased circulation immediately after-injury, and afterwards in BALF. Other cytokines (TNFα, IL12) transiently increased in BALF (and decreased in circulation) on day 2. Taken together, these results display a remarkable capability for the lungs to recover in the absence of intubation, with further evidence of the role of cytokines such as IL8 and IL1ra. The possible exacerbating effects of clinical practices such as ventilation and bronchoscopies should be considered., (Published by Elsevier Ltd.)

Elucidating the roles and composition of the human skin microbiome has revealed a delicate interplay between resident microbes and wound healing. Evolutionarily speaking, normal cutaneous flora likely has been selected for because it potentiates or, at minimum, does not impede wound healing. While pigs are the gold standard model for wound healing studies, the porcine skin microbiome has not been studied in detail. Herein, we performed 16S rDNA sequencing to characterize the pig skin bacteriome at several anatomical locations. Additionally, we used bacterial conditioned-media with in vitro techniques to examine the paracrine effects of bacterial-derived proteins on human keratinocytes (NHEK) and fibroblasts (NHDF). We found that at the phyla level, the pig skin bacteriome is similar to that of humans and largely consists of Firmicutes (55.6%), Bacteroidetes (20.8%), Actinobacteria (13.3%), and Proteobacteria (5.1%) however species-level differences between anatomical locations exist. Studies of bacterial supernatant revealed location-dependent effects on NHDF migration and NHEK apoptosis and growth factor release. These results expand the limited knowledge of the cutaneous bacteriome of healthy swine, and suggest that naturally occurring bacterial flora affects wound healing differentially depending on anatomical location. Ultimately, the pig might be considered the best surrogate for not only wound healing studies but also the cutaneous microbiome. This would not only facilitate investigations into the microbiome's role in recovery from injury, but also provide microbial targets for enhancing or accelerating wound healing., Competing Interests: The authors have declared that no competing interests exist.

Opioid-based analgesics provide the mainstay for attenuating burn pain, but they have a myriad of side effects including respiratory depression, nausea, impaired gastrointestinal motility, sedation, dependence, physiologic tolerance, and opioid-induced hyperalgesia. To test and develop novel analgesics, validated burn-relevant animal models of pain are indispensable. Herein we review such animal models, which are mostly limited to rodent models of burn-induced, inflammatory, and neuropathic pain. The latter two are pain syndromes that provide insight into the pain caused by systemic pro-inflammatory cytokines and direct injury to nerves (e.g., after severe burn), respectively. To date, no single animal model optimally mimics the complex pathophysiology and pain that a human burn patient experiences. No currently available burn-pain model examines effects of pharmacological intervention on wound healing. As cornerstones of pain and wound healing, pro-inflammatory mediators may be utilized for insight into both processes. Moreover, common clinical concerns such as systemic inflammatory response syndrome and multiple organ dysfunction remain unaddressed. For development of analgesics, these aberrations can significantly alter the potential efficacy and/or adverse effects of a prescribed analgesic following burn trauma. We therefore suggest that a multi-model strategy would be the most clinically relevant when evaluating novel analgesics for use in burn patients., (Published by Elsevier Ltd.)

Severe burn results in systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction (MOD). Currently, large-animal models of burn-induced SIRS/MOD mostly use secondary insults resulting in a paucity of knowledge on the effect of burn alone on different organ systems. The objective of the current study was to develop and characterize a large animal model of burn-induced SIRS over the course of 2 weeks. Yorkshire swine (n = 16) were randomized to sham controls (n = 4) or 40% total body surface area contact burns (n = 6 at 2 and 14 days post-burn). Blood chemistry and complete blood count analyses were performed at baseline and post-burn days 1, 2, 3, 7, 10, and 14. Upon euthanasia, tissue samples were taken for histopathology. Burns were found to be full thickness and did not re-epithelialize. SIRS was evidenced by increased body temperature, respiration rate, pulse, and white blood cell count for the duration of the experiment. Both acute liver injury and acute kidney injury were induced as determined biochemically and histologically. Histology also revealed atelectasis of the lungs which was associated with increased myeloperoxidase activity. Intestinal structure as well as enterocyte homeostasis was also disrupted. All of these organ abnormalities recovered to varying degrees by 14 days post-burn. We report a unique reproducible large animal model of burn-induced SIRS that can be tailored to specific organ systems for investigation into potential immunomodulatory interventions that prevent organ failure or promote organ recovery after burn injury.

Burn injuries have been identified as the primary cause of injury in 5% of U.S. military personnel evacuated from Operations Iraqi Freedom and Enduring Freedom. Severe burn-associated pain is typically treated with opioids such as fentanyl, morphine, and methadone. Side effects of opioids include respiratory depression, cardiac depression, decrease in motor and cognitive function, as well as the development of hyperalgesia, tolerance and dependence. These effects have led us to search for novel analgesics for the treatment of burn-associated pain in wounded combat service members. Tetrodotoxin (TTX) is a selective voltage-gated sodium channel blocker currently in clinical trials as an analgesic. A phase 3 clinical trial for cancer-related pain has been completed and phase 3 clinical trials on chemotherapy-induced neuropathic pain are planned. It has also been shown in mice to inhibit the development of chemotherapy-induced neuropathic pain. TTX was originally identified as a neurotoxin in marine animals but has now been shown to be safe in humans at therapeutic doses. The antinociceptive effects of TTX are thought to be due to inhibition of Na(+) ion influx required for initiation and conduction of nociceptive impulses. One TTX sensitive sodium channel, Nav1.7, has been shown to be essential in lowering the heat pain threshold after burn injuries. To date, the analgesic effect of TTX has not been tested in burn-associated pain. Male Sprague-Dawley rats were subjected to a full thickness thermal injury on the right hind paw. TTX (8 μg/kg) was administered once a day systemically by subcutaneous injection beginning 3 days post thermal injury and continued through 7 days post thermal injury. Thermal hyperalgesia and mechanical allodynia were assessed 60 and 120 min post injection on each day of TTX treatment. TTX significantly reduced thermal hyperalgesia at all days tested and had a less robust, but statistically significant suppressive effect on mechanical allodynia. These results suggest that systemic TTX may be an effective, rapidly acting analgesic for battlefield burn injuries and has the potential for replacing or reducing the need for opioid analgesics., (Published by Elsevier Ireland Ltd.)

Interactions between species, particularly where one is likely to be a pathogen of the other, as well as the geographical distribution of species, have been systematically extracted from various web-based, free-access sources, and assembled with the accompanying evidence into a single database. The database attempts to answer questions such as what are all the pathogens of a host, and what are all the hosts of a pathogen, what are all the countries where a pathogen was found, and what are all the pathogens found in a country. Two datasets were extracted from the database, focussing on species interactions and species distribution, based on evidence published between 1950-2012. The quality of their evidence was checked and verified against well-known, alternative, datasets of pathogens infecting humans, domestic animals and wild mammals. The presented datasets provide a valuable resource for researchers of infectious diseases of humans and animals, including zoonoses.

Toxoplasma gondii modifies its host cell to suppress its ability to become activated in response to IFN-γ and TNF-α and to develop intracellular antimicrobial effectors, including NO. Mechanisms used by T. gondii to modulate activation of its infected host cell likely underlie its ability to hijack monocytes and dendritic cells during infection to disseminate to the brain and CNS where it converts to bradyzoites contained in tissue cysts to establish persistent infection. To identify T. gondii genes important for resistance to the effects of host cell activation, we developed an in vitro murine macrophage infection and activation model to identify parasite insertional mutants that have a fitness defect in infected macrophages following activation but normal invasion and replication in naive macrophages. We identified 14 independent T. gondii insertional mutants out of >8000 screened that share a defect in their ability to survive macrophage activation due to macrophage production of reactive nitrogen intermediates (RNIs). These mutants have been designated counter-immune mutants. We successfully used one of these mutants to identify a T. gondii cytoplasmic and conoid-associated protein important for parasite resistance to macrophage RNIs. Deletion of the entire gene or just the region encoding the protein in wild-type parasites recapitulated the RNI-resistance defect in the counter-immune mutant, confirming the role of the protein in resistance to macrophage RNIs.

Apicomplexa are primarily obligate intracellular protozoa that have evolved complex developmental stages important for pathogenesis and transmission. Toxoplasma gondii, responsible for the disease toxoplasmosis, has the broadest host range of the Apicomplexa as it infects virtually any warm-blooded vertebrate host. Key to T. gondii's pathogenesis is its ability to differentiate from a rapidly replicating tachyzoite stage during acute infection to a relatively non-immunogenic, dormant bradyzoite stage contained in tissue cysts. These bradyzoite cysts can reconvert back to tachyzoites years later causing serious pathology and death if a person becomes immune-compromised. Like the sexual stage sporozoites, bradyzoites are also orally infectious and a major contributor to transmission. Because of the critical role of stage conversion to pathogenesis and transmission, a major research focus is aimed at identifying molecular mediators and pathways that regulate differentiation. Tachyzoite to bradyzoite development can occur spontaneously in vitro and be induced in response to exogenous stress including but not limited to host immunity. The purpose of this review is to explore the potential contributors to stage differentiation in infection and how a determination is made by the parasite to differentiate from tachyzoites to bradyzoites.

Objectives: To determine the accuracy of the OnTrak rapid urine latex agglutination immunoassay (AIA) for testing pregnant ED patients for the cocaine metabolite benzoylecgonine (BE), and to determine the frequency of urine BE in pregnant ED patients and the association of test results with patient demographics., Methods: A test performance evaluation was conducted using an inception cohort of pregnant patients at an urban teaching hospital ED. Patients with positive urine chorionic gonadotropin tests who had adequate remaining urine samples were studied. Patient demographics, ED diagnoses, and assay results were recorded without patient identifiers. Urine was tested using the rapid AIA. The first 150 samples were confirmed using a second immunoassay and gas chromatography with a nitrogen phosphorus detector. All positive samples also were confirmed with thin-layer chromatography, and quantification by gas chromatography-mass spectrometry., Results: Twenty of 342 (5.9%, 95% CI 3.4-8.4%) pregnant patients had urine samples positive by AIA testing for BE. Confirmation testing demonstrated no false-positive or -negative AIA result. Positive test results were not associated with specific patient diagnoses or demographics., Conclusions: ED screening for cocaine use among pregnant patients can be accurately performed using the OnTrak AIA for BE. In the ED population screened, 5.9% of the pregnant women had urine samples positive for BE.

Molecular mechanics techniques are used to derive structural parameters that allow carbon-13 nuclear magnetic resonance spectra of disaccharides to be modeled. On the basis of a collection of 40 disaccharide spectra, four linear models are derived that allow complete spectra to be simulated. On the basis of these 40 compounds, the average difference between simulated and observed chemical shifts is +/- 0.45 ppm. The majority of structural parameters used are based on interatomic distances computed from modeled three-dimensional atomic coordinates. Found particularly useful in modeling the disaccharide spectra are the effects of oxygen electron lone pairs and encodings of the structural environments of hydrogens alpha to the carbon whose chemical shift is being predicted. The computed models are examined, and their predictive ability is assessed. The potential application of the methodology to the structure elucidation of disaccharides is demonstrated.