Frailty in aneurysmal subarachnoid hemorrhage: the risk analysis index.

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.

Venous Sinus Stenting: Safety and Health Care Resource Evaluation for Optimal Recovery in an Evolving Health Care Environment.

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.

Utility of frailty as a predictor of acute kidney injury in patients with aneurysmal subarachnoid hemorrhage.

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.

Safety of intra-arterial chemotherapy with or without osmotic blood-brain barrier disruption for the treatment of patients with brain tumors.

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.

Association of baseline frailty status with clinical outcome following aneurysmal subarachnoid hemorrhage.

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.

Glycemic indices predict outcomes after aneurysmal subarachnoid hemorrhage: a retrospective single center comparative analysis.

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.

A comparison of frailty indices in predicting length of inpatient stay and discharge destination following angiogram-negative subarachnoid hemorrhage.

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 >85th 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.

Evaluating the Impact of Neurosurgical Educational Interventions on Patient Knowledge and Satisfaction: A Systematic Review of the Literature.

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.

Clinical Characteristics Predict the Yield of Head Computed Tomography Scans among Intoxicated Trauma Patients: Implications for the Initial Work-up.

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.

The Effect of Frailty versus Initial Glasgow Coma Score in Predicting Outcomes Following Chronic Subdural Hemorrhage: A Preliminary Analysis.

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.

Increasing Frailty, Not Increasing Age, Results in Increased Length of Stay Following Vestibular Schwannoma Surgery.

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 ±â€Š0.9 (range 12-77). One-hundred ten patients were male (50.5%). The mean ICU LOS was 1.6 ±â€Š0.1 days while mean total hospital LOS was 4.3 ±â€Š0.2. 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.

The Effect of Frailty and Patient Comorbidities on Outcomes After Acute Subdural Hemorrhage: A Preliminary Analysis.

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.

The Effect of Burn Resuscitation Volumes on the Gut Microbiome in a Swine Model.

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 ß-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.

Age predicts outcomes better than frailty following aneurysmal subarachnoid hemorrhage: A retrospective cohort analysis.

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.

The Clinical Value of Heart Rate Monitoring Using an Apple Watch.

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.

Isolation and Characterization of Multipotent CD24+ Cells From the Renal Papilla of Swine.

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 Cutaneous Microbiome and Wounds: New Molecular Targets to Promote Wound Healing.

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.

Enteral resuscitation with oral rehydration solution to reduce acute kidney injury in burn victims: Evidence from a porcine model.

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-1ß, 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.

A model of recovery from inhalation injury and cutaneous burn in ambulatory swine.

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.