Modern Lower Extremity Bypass Outcomes by Anesthesia Type in the Veteran Population.

BACKGROUND: Lower extremity bypass (LEB) revascularization can be performed under general (GA) or neuraxial anesthesia (NA). Studies show that the use of NA may decrease morbidity, 30-day mortality, and hospital length-of-stay (LOS). The goal of our analysis is to examine the differences in postsurgical outcomes following LEB between patients who undergo GA compared to NA in the Veteran Affairs Surgical Quality Improvement Program (VASQIP) database. METHODS: After IRB approval, the VASQIP database was assessed for patients who underwent LEB between 1998-2018. Only infrainguinal bypass procedures and anesthesia type classified as "general," "epidural," or "spinal" were included. The neuraxial cohort includes both spinal and epidural anesthesia patients. The Risk Analysis Index (RAI), a validated measure of frailty, was additionally calculated for each patient. Chi squared, paired t-test, and binary logistic regression were used to compare the cohorts. RESULTS: During this period, 22,960 veterans underwent LEB recorded in VASQIP. Compared to those who underwent surgery under GA, patients with procedures performed using NA were older (66.4 ± 9.6 years vs. 65.3 ± 9 years respectively; P <0.001) and more frail (average RAI score 25.7 ± 7.0 vs. 24.9 ± 6.7; P < 0.001). Operative time was shorter in the NA group (4.1 ± 1.7 hrs vs. 4.7 ± 3.0 hrs; P < 0.001) and fewer cases were emergent (1.55% vs. 4.13%; P <0.001). Patients in the GA group had higher rates of postoperative prolonged ileus (0.31% vs. 0.00%; P = 0.03), pneumonia (1.60% vs. 1.06%; P = 0.025), deep wound infection (2.67% vs. 2.61%; P = 0.01), sepsis (1.68% vs. 0.79%; P < 0.001), reintubation (1.80% vs. 1.30%) (P = 0.04),and number of packed red blood cell (pRBC) transfused intraoperatively (0.39 ± 1.21 units vs. 0.22 ± 0.79 units; P <0.001). There was no significant difference in rate of graft failure, return to the OR, myocardial infarction, death, or LOS. In regression analysis, those undergoing NA were less likely to require pRBC transfusion intraoperatively (OR: 0.43; 95% CI: 0.31-0.61; P < 0.001), however no other outcomes reached statistical significance. CONCLUSION: Although younger and less frail, veteran patients undergoing GA for lower extremity revascularization had higher rates of postoperative ileus, pneumonia, deep wound infection, sepsis, and need for transfusion as compared to those undergoing NA. There was no significant difference in the rate of other major complications, myocardial infarction, death or LOS. After adjustment, only intraoperative transfusion remained statistically significant, likely reflecting longer and more complex cases for those that undergo general anesthesia rather than the effect of anesthetic choice itself.

Using the risk analysis index to assess frailty in a veteran cohort undergoing endovascular aortic aneurysm repair.

OBJECTIVE: Surgical frailty is strongly associated with increased perioperative morbidity and mortality. The risk analysis index (RAI) is a validated frailty score system, which has been shown to predict for short-term outcomes and long-term mortality in various surgical subspecialties. In the present study, we applied the frailty score to a veteran aneurysm population who had undergone nonemergent endovascular aortic aneurysm repair (EVAR). METHODS: After obtaining institutional review board approval, the Veteran Affairs Surgical Quality Improvement Program data were queried for endovascular repair of infrarenal abdominal aortic aneurysm or dissection using the Current Procedural Terminology codes 34,800, 34,803, and 34,805 from 2001 to 2018. The preoperative variables were used to calculate the RAI score. The patients were placed into six cohorts according to the RAI score (≤20, 21-25, 26-30, 31-35, 35-40, and ≥41). The χ2 test and analysis of variance test were used compare the cohorts. Forward logistic regression modeling was used to determine the risks of each cohort. RESULTS: From 2001 to 2018, 5568 patients had undergone EVAR. Of the 5568 patients, 99.6% were male, with a mean age of 71 ± 8 years. Of these patients, 4.5%, 43.8%, 33.9%, 11.7%, 4.2%, and 1.8% were included in the following RAI groups: ≤20, 21 to 25, 26 to 30, 31 to 35, 35 to 40, and ≥41, respectively. Frailty was associated with increased rates of overall complications, death, and an increased length of stay. When risk adjusted, frailty at the highest vs lowest level was associated with 2.7 times the odds of any complication developing and 4.4 times the odds of mortality ≤30 days. CONCLUSIONS: Frailty, as determined by the RAI, was associated with postoperative outcomes in a dose-dependent manner. Frailty was associated with higher rates of major cardiac (myocardial infarction, cardiac arrest), pulmonary (pneumonia, failure to wean from ventilation, reintubation), renal (renal failure), overall complications, length of stay, and death. We recommend the use of this frailty index as a screening tool to guide discussions with patients scheduled to undergo EVAR.

Frailty Measurement and Implications for Cerebrovascular Disease Management in a Veteran Based Population.

BACKGROUND: Rapid and objective preoperative assessment of patients undergoing carotid endarterectomy (CEA) remains difficult and variable. The Risk Analysis Index (RAI) is a validated medical record-based assessment of frailty that has been used to predict clinical outcomes for patients undergoing surgical procedures including CEA. We applied RAI to a veteran population following CEA for asymptomatic cerebrovascular disease and examined the factors related to post-operative morbidity and mortality. METHODS: After obtaining IRB approval, Veteran Affairs Surgical Quality Improvement Program data was queried for CEA procedures from 2002 to 2015 for ICD-9 codes indicating asymptomatic patients. RAI was then calculated based on Veteran Affairs Surgical Quality Improvement Program variable medical record extraction. Three groupings of patients were undertaken including non-frail (RAI < 30), frail (RAI 30-34) and very frail (RAI ≥ 35). Chi squared and ANOVA were used to assess cohort differences. Binary logistic regression was used to evaluate predictors of post-operative stroke, myocardial infarction (MI), any complication, and death. RESULTS: Between 2002 and 2015, 37,873 asymptomatic patients underwent CEA. Over 98% (37,266) of the patients were male with an average age of 68.3 ± 8.55 years. The cohorts contained 82.8% (n = 31,362), 12.4% (n = 4,678), and 4.8% (n = 1,833) for the non-frail, frail and very frail groups respectively. Frailty was associated with increased rates of post-operative stroke, MI, any complication, death, and longer hospital length of stay (P< 0.001). Operative time did not significantly differ between the groups. Increasing frailty was associated with having one or more complications (OR 1.69, 95% CI 1.50-1.90 for frail and OR 2.79, 95% CI 2.41-3.24 for very frail, (P< 0.001), post-operative stroke in frail (OR 1.33 95% CI 1.06-1.67) and very frail (OR 1.57 1 95% CI 1.14-2.16) patients, and MI in both frail (OR 1.68, CI 1.17-2.43) and very frail (OR 3.73, CI 2.52-5.51) patients. Frailty was also significantly associated with death with in very frail patients (OR 4.14, 95% CI 3.00-5.71, P< 0.001). CONCLUSION: Increasing frailty as determined by RAI was associated with worse post-operative outcomes in asymptomatic patients undergoing CEA. Higher RAI score cohorts were associated with higher rates of postoperative stroke, MI, complications, and death. We recommend the use of this frailty index as a screening tool to guide risk discussions with asymptomatic patients undergoing CEA.

Frailty Index associated with postoperative complications and mortality after lower extremity amputation in a national veteran cohort.

OBJECTIVE: Surgical frailty and its assessment have become essential considerations in perioperative management for the modern aging surgical population. The risk analysis index is a validated frailty score that has been proven to predict short-term outcomes and long-term mortality in several surgical subspecialties and high-risk procedures. We examined the association of risk analysis index scores with postoperative outcomes in a retrospective nationwide database of patients who underwent lower extremity amputation in the Veterans Health Administration Health Care System. METHODS: The Veteran Affairs Surgical Quality Improvement Program data was queried across the Veteran Affairs Health Care System with institutional review board approval for lower extremity amputations. Records of above and below knee amputation, Current Procedural Terminology codes 27590, 27591, 27592, 27594, 27596 and 27880, 27881, 27882, 27884, and 27886, respectively, from 1999 to 2018 were obtained. Incomplete and traumatic entries were removed. Risk Analysis Index score was calculated from preoperative variables and patients were separated into five score cohorts (≤15, 16-25, 26-35, 36-45, ≥46). The χ2 test and analysis of variance were used to compare the cohorts. Forward binary logistic regression modeling was used to determine covariate-adjusted odds ratios for outcomes in each cohort (SPSS software; version 25, IBM Corp). RESULTS: A total of 47,197 patients (98.9% male) with an average age of 66.4 ± 10.6 years underwent nontraumatic lower extremity amputation, including 27,098 below knee and 20,099 above knee amputations, during the study period. Frailty was associated with increased rates of deep vein thrombosis, sepsis, cardiac arrest, myocardial infarction, pneumonia, intubation for more than 48 hours, pulmonary embolism, reintubation, acute kidney injury, renal failure, increased length of stay, overall complications, and death. Increases in the frailty score were associated with up to three times the likelihood for the occurrence of a postoperative complication and up to 32 times likelihood to perish within 30 days than those with low frailty scores. CONCLUSIONS: Risk analysis index assessment of frailty was found to be associated with several postoperative outcomes in a dose-dependent manner in patients undergoing lower extremity amputation in the Veterans Health Care System, with higher scores associated with higher rates of death and major cardiac (myocardial infarction, cardiac arrest), pulmonary (pneumonia, failure to wean vent, reintubation), and renal (renal insufficiency, renal failure) complications. We recommend the use of risk analysis index score as a frailty screening tool for patients undergoing lower extremity amputation to enable providers to adequately inform and counsel patients regarding potential significant risks.

Predominant DNMT and TET mediate effects of allergen on the human bronchial epithelium in a controlled air pollution exposure study.

BACKGROUND: Epidemiological data show that traffic-related air pollution contributes to the increasing prevalence and severity of asthma. DNA methylation (DNAm) changes may elucidate adverse health effects of environmental exposures. OBJECTIVES: We sought to assess the effects of allergen and diesel exhaust (DE) exposures on global DNAm and its regulation enzymes in human airway epithelium. METHODS: A total of 11 participants, including 7 with and 4 without airway hyperresponsiveness, were recruited for a randomized, double-blind crossover study. Each participant had 3 exposures: filtered air + saline, filtered air + allergen, and DE + allergen. Forty-eight hours postexposure, endobronchial biopsies and bronchoalveolar lavages were collected. Levels of DNA methyltransferases (DNMTs) and ten-eleven translocation (TET) enzymes, 5-methylcytosine, and 5-hydroxymethylcytosine were determined by immunohistochemistry. Cytokines and chemokines in bronchoalveolar lavages were measured by electrochemiluminescence multiplex assays. RESULTS: Predominant DNMT (the most abundant among DNMT1, DNMT3A, and DNMT3B) and predominant TET (the most abundant among TET1, TET2, and TET3) were participant-dependent. 5-Methylcytosine and its regulation enzymes differed between participants with and without airway hyperresponsiveness at baseline (filtered air + saline) and in response to allergen challenge (regardless of DE exposure). Predominant DNMT and predominant TET correlated with lung function. Allergen challenge effect on IL-8 in bronchoalveolar lavages was modified by TET2 baseline levels in the epithelium. CONCLUSIONS: Response to allergen challenge is associated with key DNAm regulation enzymes. This relationship is generally unaltered by DE coexposure but is rather dependent on airway hyperresponsiveness status. These enzymes therefore warranted further inquiry regarding their potential in diagnosis, prognosis, and treatment of asthma.

Optimizing Peripandemic Care for Veteran Major Non-Traumatic Lower Extremity Amputees: A Proposal Informed by a National Retrospective Descriptive Analysis of COVID-19 Risk Factor Prevalence.

INTRODUCTION: In response to the Coronavirus 2019 (COVID-19) pandemic, vascular surgeons in the Veteran Affairs Health Care System have been undertaking only essential cases, such as advanced critical limb ischemia. Surgical risk assessment in these patients is often complex, considers all factors known to impact short- and long-term outcomes, and the additional risk that COVID-19 infection could convey in this patient population is unknown. The European Centre for Disease Prevention and Control (ECDC) published risk factors (ECDC-RF) implicated in increased COVID-19 hospitalization and case-fatality which have been further evidenced by initial reports from the United States Centers for Disease Control and Prevention. CDC reports additionally indicate that African American (AA) patients have incurred disparate infection outcomes in the United States. We set forth to survey the Veterans Affairs Surgical Quality Improvement Program (VASQIP) database over a nearly 20 year span to inform ongoing risk assessment with an estimation of the prevalence of ECDC-RF in our veteran critical limb ischemia population and investigate whether an increased COVID-19 comorbidity burden exists for AA veterans presenting for major non-traumatic amputation. MATERIALS AND METHODS: The VASQIP database was queried for all above knee amputation (AKA) and below knee amputation (BKA) completed 1999-2018 after IRB approval (MIRB:#02507). Patient race and ECDC-RF including male gender, age > 60 years, smoking status, hypertension, diabetes, chronic obstructive pulmonary disease, cancer, and cardiovascular disease were recorded from preoperative patient history. AKA and BKA cohorts were compared via χ2-test with Yates correction or unpaired t-test and a subgroup analysis was conducted between AA and all other race patients for COVID-19 comorbidities in each cohort. RESULTS: VASQIP query returned 50,083 total entries. Average age was 65.1 ± 10.4 years and 68.2 ± 10.5 years for BKA and AKA cohorts, respectively, (P < .0001) and nearly all patients were male (99%). At least one ECDC-RF comorbidity was present in 25,526 (88.7%) of BKA and 17,558 (82.4%) of AKA patients (P < .0001). AA BKA patients were significantly more likely than non-AA BKA patients to present with at least one ECDC-RF comorbidity (P = .01). CONCLUSIONS: According to a large national Veterans Affairs database, there are high rates of ECDC-RF in veteran amputees. During the present crisis, management of these patients should incorporate telehealth, expedient discharge, and ongoing COVID-19 transmission precautions.

Frailty index predicts long-term mortality and postoperative complications in patients undergoing endovascular aortic aneurysm repair.

OBJECTIVE: The Risk Analysis Index (RAI) has been used to evaluate preoperative frailty, which is associated with poor short- and long-term outcomes. We assessed this tool's ability to predict postoperative outcomes after endovascular aortic aneurysm repair. METHODS: Institutional Review Board approval was obtained for this retrospective study. All patients who underwent elective endovascular aneurysm repair at a single Veterans Affairs Medical Center from December 2010 to March 2016 were included. Patients' characteristics and clinical data were retrospectively collected and analyzed. The RAI score was calculated from preoperative data, and a standard cutoff value (RAI ≥30) was used to determine frailty. Outcomes including postoperative complications, delayed discharge, and survival were compared between frail and nonfrail groups. Multivariate analysis was performed to evaluate preoperative factors associated with these outcomes. RESULTS: There were 134 patients who met inclusion criteria. There were 44 frail patients (RAI ≥30) and 90 nonfrail patients (RAI <30). Frail patients had a longer hospital stay (3.9 ± 4.0 days vs 2.3 ± 1.6 days; P = .02), increased operative time (155 ± 30 minutes vs 138 ± 30 minutes; P = .002), and increased postoperative complications (43% vs 21%; P = .02) compared with nonfrail patients. Kaplan-Meier average survival for frail patients and nonfrail patients was 60 ± 4 months and 84 ± 3 months (P < .001), respectively. In multivariate analyses, frailty was associated with worse overall survival (hazard ratio, 3.7; 95% confidence interval [CI], 1.8-7.3) and higher odds of complications (odds ratio, 1.1; 95% CI, 1.0-1.14) and delayed discharge (odds ratio, 1.1; 95% CI, 1.05-1.2). CONCLUSIONS: Preoperative frailty as evaluated by the RAI is associated with worse short-term postoperative outcomes and long-term mortality. The RAI can be used to inform risk-benefit discussions with patients and their families.

Effect of long-acting ß-agonists/glucocorticoids on human airway epithelial cell cytokine, transcriptomic and oxidative stress responses to cannabis smoke.

LABA/GC intervention in airway epithelial cells exposed to cannabis smoke reduces levels of pro-inflammatory (CXCL8) and antiviral (CXCL10) mediators, while transcriptomic signatures of neutrophil-mediated immunity and oxidative stress remain elevated http://bit.ly/2qiSQhH.

Use of endoloop in video-assisted thoracoscopic enucleation of a very rare esophageal tumor.

A gastrointestinal stromal tumor is an infrequent tumor of the gastrointestinal tract with very rare involvement of the esophagus. We present a case of a patient with dysphagia and a 4 cm submucosal mass. The patient underwent thoracoscopic enucleation with complete resection of the mass. We present case details and operative video highlighting the important surgical steps of exposure and retraction. We believe that the Endoloop is a very useful tool in providing countertraction needed during minimally invasive resection of such lesions.

Transcriptomic and barrier responses of human airway epithelial cells exposed to cannabis smoke.

Globally, many jurisdictions are legalizing or decriminalizing cannabis, creating a potential public health issue that would benefit from experimental evidence to inform policy, government regulations, and user practices. Tobacco smoke exposure science has created a body of knowledge that demonstrates the conclusive negative impacts on respiratory health; similar knowledge remains to be established for cannabis. To address this unmet need, we performed in vitro functional and transcriptomic experiments with a human airway epithelial cell line (Calu-3) exposed to cannabis smoke, with tobacco smoke as a positive control. Demonstrating the validity of our in vitro model, tobacco smoke induced gene expression profiles that were significantly correlated with gene expression profiles from published tobacco exposure datasets from bronchial brushings and primary human airway epithelial cell cultures. Applying our model to cannabis smoke, we demonstrate that cannabis smoke induced functional and transcriptional responses that overlapped with tobacco smoke. Ontology and pathway analysis revealed that cannabis smoke induced DNA replication and oxidative stress responses. Functionally, cannabis smoke impaired epithelial cell barrier function, antiviral responses, and increased inflammatory mediator production. Our study reveals striking similarities between cannabis and tobacco smoke exposure on impairing barrier function, suppressing antiviral pathways, potentiating of pro-inflammatory mediators, and inducing oncogenic and oxidative stress gene expression signatures. Collectively our data suggest that cannabis smoke exposure is not innocuous and may possess many of the deleterious properties of tobacco smoke, warranting additional studies to support public policy, government regulations, and user practices.

Is nasotracheal intubation safe in facial trauma patients?

BACKGROUND: In the prehospital setting, oral intubation is preferred in facial trauma patients due to the potential for further injury during nasotracheal intubation. This study compared the complications of nasal vs. oral vs. nasal + oral intubations performed by first responder crews in facial trauma patients. Our objective was to assess patient outcomes and complications to determine the risk of nasal intubation in facial trauma patients in the prehospital setting. METHODS: Patients with facial trauma between 2008 and 13 were abstracted from the Miami Valley Hospital trauma registry: 50 were nasal only (n), 27 nasal + oral (no), and 135 oral only (o) intubation. Analysis of variance with the post-hoc Least Significance Difference Test and the chi square test were used in the analysis. RESULTS: The oral group was older [41.1 ± 17.6 (o) vs. 36.2 ± 14.1 (n) vs. 33.0 ± 15.7 (no), p = 0.032] and had a higher facial abbreviated injury severity (AIS) mean score (1.8 ± 0.6 vs. 1.3 ± 0.5 vs. 1.5 ± 0.5, p < 0.001). The three groups did not differ in mortality (n = 20% vs. o = 18% vs. no = 30%, p = 0.37). The n + o group was intubated longer (p < 0.001) and had longer ICU and hospital lengths of stay (p = 0.015 and p = 0.023). The three groups did not differ on the composite of any pulmonary complication - i.e., any one of sinusitis, pneumonia, atelectasis, and respiratory failure - 44% (no) vs. 24% (o) vs. 30% (n), p = 0.10). However, nasal + oral patients were more likely to have one or more of the eight complication studied [63% (no) vs. 28% (o) vs. 34% (n), p = 0.002], and have a longer ICU and HLOS. CONCLUSIONS: Prehospital nasal intubation is a viable short-term alternative to oral intubation in patients with facial trauma and warrants further research.

Outcomes of patients with human immunodeficiency virus infection undergoing cardiovascular surgery in the United States.

INTRODUCTION: Advances in highly active antiretroviral therapy have dramatically improved the lifespan of patients infected with human immunodeficiency virus (HIV). We sought to examine the impact of HIV status on outcomes in patients undergoing cardiovascular surgery. METHODS: We identified 5,621,817 patients who underwent coronary artery bypass graft (CABG), valve, aortic, or other cardiovascular surgery between 1998 and 2009 from the Nationwide Inpatient Sample. Of these, 9771 (0.17%) patients were seropositive for HIV. Using multivariable logistic regression modeling and 1:1 propensity-score matching, we determined the influence of HIV infection on outcomes. RESULTS: The percentage of HIV+ patients undergoing cardiovascular surgery increased significantly from 0.09% to 0.23%. HIV+ patients were more often male, black, younger than 55 years of age, and on Medicaid, and they were more likely to undergo valve and other cardiovascular surgeries, but less likely to have CABG. Among propensity-matched pairs, patients with HIV were at no increased risk for in-patient mortality. HIV+ patients were more likely to receive a blood transfusion and have any postoperative complication. Patients with HIV were less likely to have a postoperative stroke. Rates of pneumonia, renal complications, and wound infection were similar between the groups. The median length of stay and mean total cost were not different between the groups. Factors that predicted in-hospital death in HIV+ patients included metastatic cancer, coagulopathy, renal failure, and aortic, other, or combined surgical procedure. CONCLUSIONS: Cardiovascular surgery can be performed safely on patients with HIV with no increased hospital mortality and only minimal increased need for blood transfusion.

Loss of interleukin receptor-associated kinase 4 signaling suppresses amyloid pathology and alters microglial phenotype in a mouse model of Alzheimer's disease.

Alzheimer's disease (AD) is typified by the deposition of amyloid in the brain, which elicits a robust microglial-mediated inflammatory response that is associated with disease exacerbation and accelerated progression. Microglia are the principal immune effector cells in the brain and interact with fibrillar forms of Aß (fAß) through a receptor complex that includes Toll-like receptors (TLR) 2/4/6 and their coreceptors. Interleukin receptor-associated kinases (IRAKs) are essential intracellular signaling molecules for transduction of TLR signals. Studies of mouse models of AD in which the individual TLRs are knocked out have produced conflicting results on roles of TLR signaling in amyloid homeostasis. Therefore, we disrupted a common downstream TLR signaling element, IRAK4. We report that microglial IRAK4 is necessary in vitro for fAß to activate the canonical pro-inflammatory signaling pathways leading to activation of p38, JNK, and ERK MAP kinases and to generate reactive oxygen species. In vivo the loss of IRAK4 function results in decreased Aß levels in a murine model of AD. This was associated with diminished microgliosis and astrogliosis in aged mice. Analysis of microglia isolated from the adult mouse brain revealed an altered pattern of gene expression associated with changes in microglial phenotype that were associated with expression of IRF transcription factors that govern microglial phenotype. Further, loss of IRAK4 function also promoted amyloid clearance mechanisms, including elevated expression of insulin-degrading enzyme. Finally, blocking IRAK function restored olfactory behavior. These data demonstrate that IRAK4 activation acts normally to regulate microglial activation status and influence amyloid homeostasis in the brain.

Apolipoprotein E promotes ß-amyloid trafficking and degradation by modulating microglial cholesterol levels.

Allelic variation in the apolipoprotein E (APOE) gene is the major risk factor of sporadic Alzheimer disease. ApoE is the primary cholesterol carrier in the brain. Previously, we demonstrated that intracellular degradation of ß-amyloid (Aß) peptides by microglia is dramatically enhanced in the presence of apoE. However, the molecular mechanisms subserving this effect remain unknown. This study reports a mechanistic link between apoE-regulated cholesterol homeostasis and Aß degradation. We demonstrate that promoting intracellular Aß degradation by microglia is a common feature of HDL apolipoproteins, including apoE and apoA-I. This effect was not dependent on the direct interaction of apoE and Aß. Regulation of Aß degradation was achieved by solely manipulating cellular cholesterol levels. The expression and the activity of Aß degrading enzymes, however, were not regulated by cholesterol. We observed that reducing cellular cholesterol levels by apoE resulted in faster delivery of Aß to lysosomes and enhanced degradation. Moreover, apoE facilitated the recycling of Rab7, a small GTPase responsible for recruiting the motor complex to late endosomes/lysosomes. These data indicate that faster endocytic trafficking of Aß-containing vesicles in the presence of apoE resulted from efficient recycling of Rab7 from lysosomes to early endosomes. Thus, apoE-induced intracellular Aß degradation is mediated by the cholesterol efflux function of apoE, which lowers cellular cholesterol levels and subsequently facilitates the intracellular trafficking of Aß to lysosomes for degradation. These findings demonstrate a direct role of cholesterol in the intracellular Aß degradation.