Hepatitis C virus (HCV) is a major cause of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma in humans. We showed previously that HCV induces autophagy for viral persistence by ...preventing the innate immune response. Knockdown of autophagy reduces extracellular HCV release, although the precise mechanism remains unknown. In this study, we observed that knockdown of autophagy genes enhances intracellular HCV RNA and accumulates infectious virus particles in cells. Since HCV release is linked with the exosomal pathway, we examined whether autophagy proteins associate with exosomes in HCV-infected cells. We observed an association between HCV and the exosomal marker CD63 in autophagy knockdown cells. Subsequently, we observed that levels of extracellular infectious HCV were significantly lower in exosomes released from autophagy knockdown cells. To understand the mechanism for reduced extracellular infectious HCV in the exosome, we observed that an interferon (IFN)-stimulated BST-2 gene is upregulated in autophagy knockdown cells and associated with the exosome marker CD63, which may inhibit HCV assembly or release. Taken together, our results suggest a novel mechanism involving autophagy and exosome-mediated HCV release from infected hepatocytes.
Autophagy plays an important role in HCV pathogenesis. Autophagy suppresses the innate immune response and promotes survival of virus-infected hepatocytes. The present study examined the role of autophagy in secretion of infectious HCV from hepatocytes. Autophagy promoted HCV trafficking from late endosomes to lysosomes, thus providing a link with the exosome. Inhibition of HCV-induced autophagy could be used as a strategy to block exosome-mediated virus transmission.
Purpose
Both laser interstitial thermal therapy (LITT) and bevacizumab have been used successfully to treat radiation necrosis (RN) after radiation for brain metastases. Our purpose is to compare ...pre-treatment patient characteristics and outcomes between the two treatment options.
Methods
Single-institution retrospective chart review identified brain metastasis patients who developed RN between 2011 and 2018. Pre-treatment factors and treatment responses were compared between those treated with LITT versus bevacizumab.
Results
Twenty-five patients underwent LITT and 13 patients were treated with bevacizumab. The LITT cohort had a longer overall survival (median 24.8 vs. 15.2 months for bevacizumab, p = 0.003) and trended to have a longer time to local recurrence (median 12.1 months vs. 2.0 for bevacizumab), although the latter failed to achieve statistical significance (p = 0.091). LITT resulted in an initial increase in lesional volume compared to bevacizumab (p < 0.001). However, this trend reversed in the long term follow-up, with LITT resulting in a median volume decrease at 1 year post-treatment of − 64.7% (range − 96.0% to + > 100%), while bevacizumab patients saw a median volume increase of + > 100% (range − 63.0% to + > 100%), p = 0.010.
Conclusions
Our study suggests that patients undergoing LITT for RN have longer overall survival and better long-term lesional volume reduction than those treated with bevacizumab. However, it remains unclear whether our findings are due only to a difference in efficacy of the treatments or the implications of selection bias.
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
To characterize smoking and alcohol use, and to describe predictors of oral cancer knowledge among a predominantly African-American population.
A cross-sectional study was conducted between ...September, 2013 among drag racers and fans in East St. Louis. Oral cancer knowledge was derived from combining questionnaire items to form knowledge score. Covariates examined included age, sex, race, marital status, education status, income level, insurance status, tobacco and alcohol use. Adjusted linear regression analysis measured predictors of oral cancer knowledge.
Three hundred and four participants completed questionnaire; 72.7% were African Americans. Smoking rate was 26.7%, alcohol use was 58.3%, and mean knowledge score was 4.60 ± 2.52 out of 17. In final adjusted regression model, oral cancer knowledge was associated with race and education status. Compared with Caucasians, African Americans were 29% less likely to have high oral cancer knowledge (β = -0.71; 95% CI: -1.35, -0.07); and participants with a high school diploma or less were 124% less likely to have high oral cancer knowledge compared with college graduates (β = -1.24; 95% CI: -2.44, -0.41).
There was lower oral cancer knowledge among African Americans and those with low education. The prevalence of smoking was also very high. Understanding predictors of oral cancer knowledge is important in future design of educational interventions specifically targeted towards high-risk group for oral cancer.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The authors performed a study to evaluate the hemorrhagic rates of cerebral dural arteriovenous fistulas (dAVFs) and the risk factors of hemorrhage following Gamma Knife radiosurgery (GKRS).
Data ...from a cohort of patients undergoing GKRS for cerebral dAVFs were compiled from the International Radiosurgery Research Foundation. The annual posttreatment hemorrhage rate was calculated as the number of hemorrhages divided by the patient-years at risk. Risk factors for dAVF hemorrhage prior to GKRS and during the latency period after radiosurgery were evaluated in a multivariate analysis.
A total of 147 patients with dAVFs were treated with GKRS. Thirty-six patients (24.5%) presented with hemorrhage. dAVFs that had any cortical venous drainage (CVD) (OR = 3.8, p = 0.003) or convexity or torcula location (OR = 3.3, p = 0.017) were more likely to present with hemorrhage in multivariate analysis. Half of the patients had prior treatment (49.7%). Post-GRKS hemorrhage occurred in 4 patients, with an overall annual risk of 0.84% during the latency period. The annual risks of post-GKRS hemorrhage for Borden type 2-3 dAVFs and Borden type 2-3 hemorrhagic dAVFs were 1.45% and 0.93%, respectively. No hemorrhage occurred after radiological confirmation of obliteration. Independent predictors of hemorrhage following GKRS included nonhemorrhagic neural deficit presentation (HR = 21.6, p = 0.027) and increasing number of past endovascular treatments (HR = 1.81, p = 0.036).
Patients have similar rates of hemorrhage before and after radiosurgery until obliteration is achieved. dAVFs that have any CVD or are located in the convexity or torcula were more likely to present with hemorrhage. Patients presenting with nonhemorrhagic neural deficits and a history of endovascular treatments had higher risks of post-GKRS hemorrhage.
In an unprecedented era of soaring healthcare costs, payers and providers alike have started to place increased importance on measuring the quality of surgical procedures as a surrogate for operative ...success. One metric used is the length of hospital stay (LOS) during index admission. For the treatment of unruptured cerebral aneurysms, the determinants of extended length of stay are relatively unknown. The aim of this study was to identify the patient- and hospital-level factors associated with extended LOS following treatment for unruptured cerebral aneurysms.
The National Inpatient Sample years 2010 – 2014 was queried. Adults (≥18 years) with unruptured aneurysms undergoing either clipping or coiling were selected using the International Classification of Diseases, Ninth Revision, Clinical Modification coding system. Extended LOS was defined as greater than 75th percentile for the entire cohort (>5 days). Weighted patient demographics, comorbidities, complications, LOS, disposition and total cost were recorded. Multivariate logistic regression was used to determine the odds ratio for risk-adjusted extended LOS. The primary outcome was the degree which patient comorbidities or postoperative complications correlated with extended LOS.
A total of 46,880 patients were identified for which 9,774 (20.8%) patients had extended LOS (Normal LOS: 37,106; Extended LOS: 9,774). Patients in the extended LOS cohort presented with a greater number of comorbidities compared to the normal LOS cohort. A greater proportion of the normal LOS cohort was coiled (Normal LOS: 63.0% vs. Extended LOS: 33.5%, P<0.001), while more patients in the extended LOS cohort were clipped (Normal LOS: 37.0% vs. Extended LOS: 66.5%, P<0.001). The overall complication rate was higher in the extended LOS cohort (Normal LOS: 7.3% vs. Extended LOS: 43.8%, P<0.001). On average, the extended LOS cohort incurred a total cost nearly twice as large (Normal LOS: $26,050 ± 13,430 vs. Extended LOS: $52,195 ± 37,252, P<0.001) and had more patients encounter non-routine discharges (Normal LOS: 8.5% vs. Extended LOS: 52.5%, P<0.001) compared to the normal LOS cohort. On weighted multivariate logistic regression, multiple patient-specific factors were associated with extended LOS. These included demographics, preadmission comorbidities, choice of procedure, and inpatient complications. The odds ratio for extended LOS was 5.14 (95% CI, 4.30 – 6.14) for patients with 1 complication and 19.58 (95% CI, 15.75 – 24.34) for patients with > 1 complication.
Our study demonstrates that extended LOS after treatment of unruptured aneurysms is influenced by a number of patient-level factors including demographics, preadmission comorbidities, type of aneurysm treatment (open surgical versus endovascular), and, importantly, inpatient complications. A better understanding of these independent predictors of prolonged length of hospital stay may help to improve patient outcomes and decrease overall healthcare costs.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background
Timely imaging is essential for patients undergoing mechanical thrombectomy (MT). Our objective was to evaluate the safety and feasibility of low‐field portable magnetic resonance imaging ...(pMRI) for bedside evaluation following MT.
Methods
Patients with suspected large‐vessel occlusion undergoing MT were screened for eligibility. All pMRI examinations were conducted in the standard ferromagnetic environment of the interventional radiology suite. Clinical characteristics, procedural details, and pMRI features were collected. Subsequent high‐field conventional MRI within 72±12 hours was analyzed. If a conventional MRI was not available for comparison, computed tomography within the same time frame was used for validation.
Results
Twenty‐four patients were included (63% women; median age, 76 years interquartile range, 69–84 years). MT was performed with a median access to revascularization time of 15 minutes (interquartile range, 8–19 minutes), and with a successful outcome as defined by a thrombolysis in cerebral infarction score of ≥2B in 90% of patients. The median time from the end of the procedure to pMRI was 22 minutes (interquartile range, 16–32 minutes). The median pMRI examination time was 30 minutes (interquartile range, 17–33 minutes). Of 23 patients with available subsequent imaging, 9 had infarct progression compared with immediate post‐MT pMRI and 14 patients did not have progression of their infarct volume. There was no adverse event related to the examination.
Conclusion
Low‐field pMRI is safe and feasible in a post‐MT environment and enables timely identification of ischemic changes in the interventional radiology suite. This approach can facilitate the assessment of baseline infarct burden and may help guide physiological interventions following MT.
Highlights 1. First report and series of “Awake” High-flow EC-IC Bypass surgery. 2Institutional Clinical Trial (IRB-approved Prospective Trial). 3. Report of current outcomes of HF EC-IC bypass for ...complex ICA aneurysms.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
The coronavirus (COVID-19) pandemic has caused unprecedented suspensions of neurosurgical elective surgeries, a large proportion of which involve spine procedures. The goal of this study is to report ...granular data on the impact of early COVID-19 pandemic operating room restrictions upon neurosurgical case volume in academic institutions, with attention to its secondary impact upon neurosurgery resident training. This is the first multicenter quantitative study examining these early effects upon neurosurgery residents caseloads.
A retrospective review of neurosurgical caseloads among seven residency programs between March 2019 and April 2020 was conducted. Cases were grouped by ACGME Neurosurgery Case Categories, subspecialty, and urgency (elective vs. emergent). Residents caseloads were stratified into junior (PGY1-3) and senior (PGY4-7) levels. Descriptive statistics are reported for individual programs and pooled across institutions.
When pooling across programs, the 2019 monthly mean (SD) case volume was 214 (123) cases compared to 217 (129) in January 2020, 210 (115) in February 2020, 157 (81), in March 2020 and 82 (39) cases April 2020. There was a 60% reduction in caseload between April 2019 (207 101) and April 2020 (82 39). Adult spine cases were impacted the most in the pooled analysis, with a 66% decrease in the mean number of cases between March 2020 and April 2020. Both junior and senior residents experienced a similar steady decrease in caseloads, with the largest decreases occurring between March and April 2020 (48% downtrend).
Results from our multicenter study reveal considerable decreases in caseloads in the neurosurgical specialty with elective adult spine cases experiencing the most severe decline. Both junior and senior neurosurgical residents experienced dramatic decreases in case volumes during this period. With the steep decline in elective spine cases, it is possible that fellowship directors may see a disproportionate increase in spine fellowships in the coming years. In the face of the emerging Delta and Omicron variants, programs should pay attention toward identifying institution-specific deficiencies and developing plans to mitigate the negative educational effects secondary to such caseloads reduction.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
INTRODUCTION:
Current literature examining the mechanisms delineating intracranial aneurysm development and subsequent rupture is sparse. Studies from decades prior defined the aneurysm model as ...being one largely driven by flow changes. However, the scope of these models is limited and does not fully explain why only a subset of patients with existing intracranial aneurysms subsequently go on to rupture.
METHODS:
We obtained aneurysm endothelial lining from 20 patients with ruptured, unruptured, sentinel hemorrhage, and recurrent aneurysms during endovascular coil embolization, which were processed and analyzed using mass spectrometry.
RESULTS:
Compared to unruptured aneurysms, ruptured aneurysms had significantly increased infiltrating populations of NK cells (5.5% vs 1.4%, p < 0.01), regulatory B cells (27.6% vs 16.0%, p < 0.05), and cytotoxic CD8 T cells (23.7% vs 13.5%, p < 0.05). To understand whether these cells were recruited at the time of rupture or whether they were present prior to the ictus event, we examined aneurysms that were treated after presenting with sentinel hemorrhages – again these patients had that same population of early-NK cells (7.5%, p = 0.2), suggesting that these cells were present at the nexus point immediately prior to rupture. Further, the regulatory B cells were even more prominent in the sentinel population, (45.6%, p < 0.01).
CONCLUSIONS:
These findings all point to a complex, coordinated immune response that is driving the remodeling of the aneurysm vessel wall. We interpret the results to suggest that regulatory B cell driven destabilization of the aneurysmal wall leads to a series of events; namely the recruitment of NK cells, subsequent inflammatory cascade, and ultimate rupture. While there remains much to be understood about this multi-faceted picture, these findings provide the basis for further studies looking at targets for adjunctive immune therapies in both our unruptured and ruptured patient populations.
INTRODUCTION:
Cranial nerve (CN) neuropathies are rare presenting symptoms of intracranial aneurysms. Ophthalmological outcomes for symptomatic aneurysms treated with flow diversion are not well ...established.
METHODS:
We conducted a retrospective review of our institutional database for patients with intracranial aneurysms presenting with CN neuropathies who underwent treatment with flow diversion between 2015 and 2023. Systematic review of the literature was performed using Medline, EMBASE, Cochrane, and manual citation searches. Random effects meta-analysis was used.
RESULTS:
Twelve out of 136 studies were included in this meta-analysis, totaling 261 patients. The results were combined with our institutional data. The pooled rate of improvement in any CN neuropathies following flow diversion was 76% (95% CI, 67%-84%, n = 272). Patients presenting with CNII deficits were less likely to improve following treatment compared to other CN neuropathies (pooled OR pOR 0.32, 95% CI, 0.16-0.63, n = 224). The pooled rate of clinical improvement was 53% in CNII deficits (95% CI, 42%-65%, n = 80) and 80% in other CN deficits (95% CI, 71%-88%, n = 106). Intervention within one month of presentation was associated with improvement (pOR 6.53, 95% CI, 1.34-31.81, n = 33). Adjunctive coiling did not demonstrate effect on the improvement rate (pOR 0.38, 95% CI, 0.07-2.13, n = 31). Near total occlusion (Raymond Roy Occlusion Classification of 1 or 2, or O'Kelly-Marotta scale of C or D) was associated with symptomatic improvement (pOR 5.29, 95% CI, 1.66-16.90, n = 118), but not total occlusion (pOR 2.83, 95% CI, 0.97-8.23, n = 118).
CONCLUSIONS:
Flow diversion improves CN outcomes in patients with symptomatic intracranial aneurysms. These results support the theory that CN neuropathies depend more on the pulsatility of the aneurysm sac rather than mass effect. The inferior rate of improvement in CNII deficits compared to other CN symptoms may imply an additional, more irreversible mechanism contributing to CNII visual deficits.
PDF
