Optimizing workflow of urgent stroke endovascular intervention: A focused lean six sigma project.

INTRODUCTION: Urgent endovascular intervention is currently accepted as the primary and critical therapeutic approach to patients whose acute ischemic stroke results from a large arterial occlusion (LAO). In this context, one of the quality metrics most widely applied to the assessment of emergency systems performance is the "door-to-puncture" (D-P) time. We undertook a project to identify the subinterval of the D-P metric causing the most impact on workflow delays and created a narrowly focused project on improving such subinterval. METHODS: Using the DMAIC (i.e., define, measure, analyze, improve and control) approach, we retrospectively reviewed our quality stroke data for calendar year (CY) 2021 (i.e., baseline population), completed a statistical process control assessment, defined the various subintervals of the D-P interval, and completed a Pareto analysis of their duration and their proportional contribution to the D-P interval. We retooled our workflow based on these analyses and analyzed the data resulting from its implementation between May and December 2022 (i.e., outcome population). RESULTS: The baseline population included 87 patients (44 men; mean age = 67.2 years). Their D-P process was uncontrolled, and times varied between 35-235 minutes (Mean = 97; SD = 38.40). Their door to angiography arrival (D-AA) subinterval was significantly slower than their arrival to puncture (AA-P) (73.4 v. 23.5 minutes; p < 0.01), accounted for 73% of the average length of the D-P interval. The group page activation to angiography arrival (GP-AA) subinterval accounted for 41.5% of the entire D-AA duration, making it the target of our project. The outcome population originally consisted of 38 patients (15 men; mean age = 70.3 years). Their D-P process was controlled, its times varying between 43-177 minutes (Mean = 85.8; SD = 34.46), but not significantly difference than the baseline population (p = 0.127). Their target subinterval GP-AA varied between 0-37 minutes and was significantly improved from the baseline population (Mean = 13.21 v. 29.68; p < 0.001). CONCLUSIONS: It seems feasible and reasonable to analyze the subinterval components of complex quality metrics such as the D-P time and carry out more focused quality improvement projects. Care must be exercised when interpreting the impact on overall system performance, due to unexpected variations within interdependent subprocesses. The application of a robust and comprehensive LSS continuous quality improvement process in any CSC will have to include individualized focused projects that simultaneously control the different components of overall system performance.

Effect of post thrombolytic intracerebral hemorrhage volume on 90-day outcomes in acute ischemic stroke patients.

BACKGROUND AND PURPOSE: Post thrombolytic intracerebral hemorrhage (ICH) is associated with higher rate of death or disability in acute ischemic stroke patients. We investigated the relationship between post thrombolytic ICH volume and change in volume and death or disability at 90 days in acute ischemic stroke patients. METHODS: We analyzed 110 patents recruited in the Safety Evaluation of 3K3A-APC in Ischemic Stroke (RHAPSODY) trial who received intravenous tissue plasminogen activator (tPA) followed by mechanical thrombectomy (if indicated) and 3K3A-APC or placebo. ICH volume was measured at Day 2 and Day 7 using susceptibility weighted sequence (SWI) on magnetic resonance imaging (MRI). We also calculated the post thrombolytic ICH volume change between Day 2 and Day 7. Outcomes were determined by using utility weighted modified Rankin scale (UW-mRs) at 90-days, Outcomes were determined by using utility weighted modified Rankin scale (UW-mRS) at 90 days. To minimize interpretation bias, outcome assessors were blinded to the treatment allocation and clinical data.We adjusted for age, gender, National Institutes of Health Stroke Scale (NIHSS) score (<10,10-19 and ≥20), location of hemorrhage (single basal ganglia hemorrhage, single lobar, single cerebellum, and multiple sites) in multivariate regression analysis. RESULTS: A total of 88 (80%) of 110 patients had post thrombolytic ICH (mean volume 28.3 ml ± SD 62 ml). The strata of ICH volume were not associated with UW-mRs at 90 days: <20 cc (regression coefficient (RC)-0.05, p= 0.58), 20-39 cc (RC-0.22, p=0.17), or ≥40 cc (RC-0.34, p= 0.083) compared with no ICH after adjusting for potential confounders. Change in ICH mean volume 26.78 ml ±59.68, 52 had increase in volume) between Day 2 and day 7 was not associated with UW-mRS at 90 days (RC -67.71, p= 0.06). CONCLUSIONS: We did not observe any independent effect of post thrombolytic ICH volume on death or disability in acute ischemic stroke patients. Although further studies must be done, our data suggest that strategies to prevent ICH expansion such as antifibrinolytic medications and reduction in ICH volume such as surgical evacuation may not reduce death or disability in acute ischemic stroke patients with post thrombolytic ICH.

Development and testing of "Is Lung Cancer Screening for You?" A computer-based decision aid.

PURPOSE: To reduce lung cancer mortality, individuals at high-risk should receive a low-dose computed tomography screening annually. To increase the likelihood of screening, interventions that promote shared decision-making are needed. The goal of this study was to investigate the feasibility, acceptability, usability, and preliminary effectiveness of a computer-based decision aid. METHODS: Thirty-three participants were recruited through primary-care clinics in a small southeastern-US city. Participants used a computer-based decision aid ("Is Lung Cancer Screening for You?") during a clinic appointment. Paper surveys collected self-reported feasibility, acceptability, and usability data. A research coordinator was present to observe each patient's and health-care provider's interactions, and to assess the fidelity of shared decision-making. RESULTS: The decision aid was feasible, acceptable for use in a clinic setting, and easy for participants to use. Patients had low decisional conflict following use of the decision aid and had high screening intention and actual screening rates. Shared decision-making discussions using the decision aid were nearly 6 min on average. CONCLUSION: Computer-based decision aids are feasible for promoting shared lung cancer-screening decisions. A more robust study is warranted to measure the added value of a computer-based version of this aid versus a paper-based aid.

Recognition and Management of the Long-term Effects of Cranial Radiation.

OPINION STATEMENT: Cranial radiation is ubiquitous in the treatment of primary malignant and benign brain tumors as well as brain metastases. Improvement in radiotherapy targeting and delivery has led to prolongation of survival outcomes. As long-term survivorship improves, we also focus on prevention of permanent side effects of radiation and mitigating the impact when they do occur. Such chronic treatment-related morbidity is a major concern with significant negative impact on patient's and caregiver's respective quality of life. The actual mechanisms responsible for radiation-induced brain injury remain incompletely understood. Multiple interventions have been introduced to potentially prevent, minimize, or reverse the cognitive deterioration. Hippocampal-sparing intensity modulated radiotherapy and memantine represent effective interventions to avoid damage to regions of adult neurogenesis. Radiation necrosis frequently develops in the high radiation dose region encompassing the tumor and surrounding normal tissue. The radiographic findings in addition to the clinical course of the patients' symptoms are taken into consideration to differentiate between tissue necrosis and tumor recurrence. Radiation-induced neuroendocrine dysfunction becomes more pronounced when the hypothalamo-pituitary (HP) axis is included in the radiation treatment field. Baseline and post-treatment evaluation of hormonal profile is warranted. Radiation-induced injury of the cataract and optic system can develop when these structures receive an amount of radiation that exceeds their tolerance. Special attention should always be paid to avoid irradiation of these sensitive structures, if possible, or minimize their dose to the lowest limit.

Effect of race/ethnicity on arterial recanalization following intravenous thrombolysis in acute ischemic stroke patients.

INTRODUCTION: Several reports have identified that clinical outcomes such as death or disability in acute ischemic stroke (AIS) patients following intravenous (IV) tissue plasminogen activator (tPA) treatment can vary according to race and ethnicities. We determined the effect of race/ethnicity on rates of arterial recanalization in AIS patients with large vessel occlusion (LVO) after IV tPA. METHODS: We analyzed 234 patients with LVO detected on computed tomographic angiography (CTA) who received IV tPA and subsequently underwent angiography for potential thrombectomy. The primary occlusion sites on CTA and digital subtracted angiography (DSA) were compared and a score was given to the level of recanalization with values ranging from 1 (complete recanalization), 2 (partial recanalization), or 3 (no recanalization).The effect of race/ethnicity were assessed for predicting vessel recanalization using the covariates of age, gender, time since stroke onset, tPA dose received, NIHSS (National Institute of Health Stroke Scale) score at baseline, and location of the occlusion, using logistic regression analysis. RESULTS: Five patients (2.1%) were Hispanic or Latino, 8 (3.4%) Asian, 24 (10.3%) African American, and 197 (84.2%) White. A total of 50% had a distal ICA/proximal M1 occlusion, 20% distal M1 occlusion, and 16% single M2 occlusion. At the primary occlusion site, 44 (18.8%) had complete recanalization on post IV tPA angiogram, 17 (7.3%) had partial recanalization, and 165 (70.5%) had no recanalization. We did not find any association between race/ethnicity and vessel recanalization post IV tPA (Nonwhite combined [OR=1.49, p=0.351]; Asian [OR=1.460, p=0.650]; African American [OR=1.508, p=0.415]; White [OR=0.672, p=0.351]; ethnicity (Hispanic or Latino) [OR= 1.008, p=0.374]); Occlusion location (OR=0.189, p<0.001). Final TICI scores and mRS at 90 days were similar among the different groups. CONCLUSION: Approximately 19% of patients had complete recanalization after IV tPA, but race and ethnicity did not seem to have an effect on arterial recanalization. Arterial recanalization was only affected by location of occlusion.

Outcomes with IV tenecteplase and IV alteplase for acute ischemic stroke with or without thrombectomy in real-world settings in the United States.

BACKGROUND AND PURPOSE: Although many stroke centers in United States are using intravenous (IV) tenecteplase (TNK) for acute ischemic stroke patients, there is paucity of comparative data between IV TNK and IV alteplase from real-world settings. MATERIALS AND METHODS: We analyzed the data from 122 healthcare facilities in Cerner Real World Data and included patients admitted between February 2016 to April 2022 to determine the effect of IV TNK (compared with IV alteplase) on occurrence of two outcomes in acute ischemic stroke patients stratified by use of thrombectomy: non-routine discharge or death, and intracranial hemorrhage after adjusting for potential confounders. RESULTS: Among 30,643 acute ischemic stroke patients analyzed, 29,480 (96.2%) and 1,163 (3.8%) patients received IV alteplase and IV TNK, respectively. The proportion of patients who received thrombectomy was significantly higher among patients who received IV TNK compared with those who received IV alteplase (16.7% versus 11.0%, p<0.001). Occurrence of intracranial hemorrhage was more common among patients treated with IV TNK in acute ischemic stroke patients who did not receive thrombectomy (7.9% versus 5.1%, p<0.001) but not in those who received thrombectomy (20.1% versus 16.8%, p = 0.234). In the logistic regression analysis, patients treated with IV TNK who did not receive thrombectomy were at higher risk of intracranial hemorrhage (OR, 1.34, 95% CI 1.05-1.72, p = 0.02) after adjusting for age (age strata), gender, race/ethnicity, hypertension, diabetes mellitus, atrial fibrillation, hyperlipidemia, malignancy, nicotine dependence, previous ischemic stroke, previous transient ischemic attack, previous intracerebral hemorrhage, previous subarachnoid hemorrhage, previous acute myocardial infarction, atherosclerosis of aorta, previous AKI, congestive heart failure, peripheral vascular disease, and hospital type, aphasia, hemiplegia, neglect, somnolence, stupor and coma, dysphagia, and homonymous hemianopsia. There was no difference in the rate of non-routine discharge or death between patients treated with IV TNK and those treated with IV alteplase in the multivariate analyses. CONCLUSIONS: In an analysis of real-world data, IV TNK was associated with higher rates of intracranial hemorrhage compared with IV alteplase in patients with acute ischemic stroke who did not undergo thrombectomy.

Intracerebral Hemorrhage and Coronavirus Disease 2019 in a Cohort of 282,718 Hospitalized Patients.

BACKGROUND: To identify whether the risk of intracerebral hemorrhage is higher in patients with coronavirus disease 2019 (COVID-19), we compared the risk factors, comorbidities, and outcomes in patients intracerebral hemorrhage and COVID-19 and those without COVID-19. METHODS: We analyzed the data from the Cerner deidentified COVID-19 data set derived from 62 health care facilities. The data set included patients with an emergency department or inpatient encounter with discharge diagnoses codes that could be associated with suspicion of or exposure to COVID-19 or confirmed COVID-19. RESULTS: There were a total of 154 (0.2%) and 667 (0.3%) patients with intracerebral hemorrhage among 85,645 patients with COVID-19 and 197,073 patients without COVID-19, respectively. In the multivariate model, there was a lower risk of intracerebral hemorrhage in patients with COVID-19 (odds ratio 0.5; 95% confidence interval 0.5-0.6; p < .0001) after adjustment for sex, age strata, race/ethnicity, hypertension, diabetes mellitus, nicotine dependence/tobacco use, hyperlipidemia, atrial fibrillation, congestive heart failure, long-term anticoagulant use, and alcohol abuse. The proportions of patients who developed pneumonia (58.4% versus 22.5%; p < .0001), acute kidney injury (48.7% versus 31.0%; p < .0001), acute myocardial infarction (11% versus 6.4%; p = .048), sepsis (41.6% versus 22.5%; p < .0001), and respiratory failure (61.7% versus 42.3%; p < .0001) were significantly higher among patients with intracerebral hemorrhage and COVID-19 compared with those without COVID-19. The in-hospital mortality among patients with intracerebral hemorrhage and COVID-19 was significantly higher compared with that among those without COVID-19 (40.3% versus 19.0%; p < .0001). CONCLUSIONS: Our analysis does not suggest that rates of intracerebral hemorrhage are higher in patients with COVID-19. The higher mortality in patients with intracerebral hemorrhage and COVID-19 compared with those without COVID-19 is likely mediated by higher frequency of comorbidities and adverse in-hospital events.

Effect of angioplasty and stent placement on sensorineural hearing loss and pulsatile tinnitus in a patient with severe internal carotid artery stenosis.

BACKGROUND: Pulsatile tinnitus occurs due to turbulent blood flow through a stenotic vessel including the internal carotid artery. The presence of sensorineural hearing loss suggests involvement of the posterior circulation vasculature. CLINICAL PRESENTATION: A 58-year-old woman presented to the ear, nose and throat clinic with acute onset of right ear pulsations and high-pitched tinnitus. An audiogram demonstrated mild sensorineural hearing loss in the right ear. Her computed tomography angiogram revealed moderate stenosis of the right internal carotid artery and she underwent revascularization with angioplasty and stent placement. A repeat audiogram demonstrated improvement in sensorineural hearing loss in the right. CONCLUSION: Pulsatile tinnitus and unilateral sensorineural hearing loss maybe a reversible manifestation of a stenotic internal carotid artery.

Annual Direct Cost of Dysphagia Associated with Acute Ischemic Stroke in the United States.

BACKGROUND: Dysphagia after acute ischemic stroke is frequent and increases the risk of pneumonia, insertion of feeding tube, hospital length-of-stay and rates of discharge to institutional care. However, the financial impact of dysphagia after acute ischemic stroke is not well understood. METHODS: Estimates were derived from published medical and economic literature to provide a range of estimates for the annual direct hospital cost of dysphagia associated with acute ischemic stroke in the United States. We also estimated the cost savings associated with a hypothetical new therapeutic intervention under a variety of assumptions. RESULTS: The 1-year costs per patient of acute hospital and post hospitalization care were $67,100 to $112,400 in acute ischemic stroke patient with dysphagia and $54,0310 to $51,979.8 in acute ischemic stroke patient without dysphagia in the two models. The estimated incremental cost in United States for ischemic stroke patients with dysphagia was $ 4,610,038,961.13 (95% confidence interval [CI] $3,796,502,674-$5,423,575,248) according to assumptions of Model 1. The estimated incremental cost in United States for ischemic stroke patients with dysphagia was $ 20,114,218,586.23 (95% CI $16564650600.42-$23663786572.04) according to assumptions of Model 2. The cost savings per year with a new therapeutic intervention ranged from $509,444,886.6 to $3,601,651,036 depending upon the magnitude of benefit. CONCLUSION: Our analysis provides additional justification using financial basis for a much larger investment in research and development for treatment of dysphagia associated with ischemic stroke.

Utilization and Outcomes of Acute Revascularization Treatments in Ischemic Stroke Patients with SARS-CoV-2 Infection.

OBJECTIVES: Acute ischemic stroke patients with severe acute respiratory syndrome coronavirus maybe candidates for acute revascularization treatments (intravenous thrombolysis and/or mechanical thrombectomy). MATERIALS AND METHODS: We analyzed the data from 62 healthcare facilities to determine the odds of receiving acute revascularization treatments in severe acute respiratory syndrome coronavirus infected patients and determined the odds of composite of death and non-routine discharge with severe acute respiratory syndrome coronavirus infected and non-infected patients undergoing acute revascularization treatments after adjusting for potential confounders. RESULTS: Acute ischemic stroke patients with severe acute respiratory syndrome coronavirus infection were significantly less likely to receive acute revascularization treatments (odds ratio 0.6, 95% confidence interval 0.5-0.8, p = 0.0001). Among ischemic stroke patients who received acute revascularization treatments, severe acute respiratory syndrome coronavirus infection was associated with increased odds of death or non-routine discharge (odds ratio 3.0, 95% confidence interval 1.8-5.1). The higher odds death or non-routine discharge (odds ratio 2.1, 95% confidence interval 1.9-2.3) with severe acute respiratory syndrome coronavirus infection were observed in all ischemic stroke patients without any modifying effect of acute revascularization treatments (interaction term for death (p = 0.9) or death or non-routine discharge (p = 0.2). CONCLUSIONS: Patients with acute ischemic stroke with severe acute respiratory syndrome coronavirus infection were significantly less likely to receive acute revascularization treatments. Severe acute respiratory syndrome coronavirus infection was associated with a significantly higher rate of death or non-routine discharge among acute ischemic stroke patients receiving revascularization treatments.

Early Hyperchloremia and Outcomes After Acute Ischemic Stroke.

OBJECTIVE: Based on the relationship between hyperchloremia and mortality in critically ill patients, we investigated the effect of early hyperchloremia on 90-day outcomes in acute ischemic stroke patients. MATERIALS AND METHODS: Acute ischemic stroke patients recruited within 5 h of symptom onset were analyzed. Hyperchloremia (defined as 110 mmol/L or greater) at either baseline, or 24, or 48 h after randomization was identified and classified as one occurrence or two or more occurrences. Logistic regression analyses were performed to determine the effects of hyperchloremia on: favorable outcomes (defined by a National Institutes of Health Stroke Scale and/or modified Rankin scale scores of 0-1) at 90-day, death or disability at 90-day, and death within 90-day after accounting for potential confounders. RESULTS: Among the total of 1275 patients, one and two or more occurrence of hyperchloremia within 48 h were seen in 191 patients and 108 patients, respectively. Compared with patients without hyperchloremia, patients with two or more occurrences of hyperchloremia at significantly higher odds of lack of favorable outcomes (odds ratio 3.0, 95% confidence interval 1.8-5.1) and death or disability (odds ratio 2.6, 95% confidence interval 1.6-4.1) at 90-day after adjustment for age, National Institutes of Health Stroke Scale score strata (6-9, 10-19, ≥ 20), study intervention, initial SBP, and intra-arterial treatment. CONCLUSIONS: The independent association between sustained hyperchloremia and lack of favorable outcomes at 90-day suggest that avoidance of hyperchloremia may reduce the rate of lack of favorable outcomes and death or disability in patients with acute ischemic stroke.

Acute Ischemic Stroke and COVID-19: An Analysis of 27 676 Patients.

BACKGROUND AND PURPOSE: Acute ischemic stroke may occur in patients with coronavirus disease 2019 (COVID-19), but risk factors, in-hospital events, and outcomes are not well studied in large cohorts. We identified risk factors, comorbidities, and outcomes in patients with COVID-19 with or without acute ischemic stroke and compared with patients without COVID-19 and acute ischemic stroke. METHODS: We analyzed the data from 54 health care facilities using the Cerner deidentified COVID-19 dataset. The dataset included patients with an emergency department or inpatient encounter with discharge diagnoses codes that could be associated to suspicion of or exposure to COVID-19 or confirmed COVID-19. RESULTS: A total of 103 (1.3%) patients developed acute ischemic stroke among 8163 patients with COVID-19. Among all patients with COVID-19, the proportion of patients with hypertension, diabetes, hyperlipidemia, atrial fibrillation, and congestive heart failure was significantly higher among those with acute ischemic stroke. Acute ischemic stroke was associated with discharge to destination other than home or death (relative risk, 2.1 [95% CI, 1.6-2.4]; P<0.0001) after adjusting for potential confounders. A total of 199 (1.0%) patients developed acute ischemic stroke among 19 513 patients without COVID-19. Among all ischemic stroke patients, COVID-19 was associated with discharge to destination other than home or death (relative risk, 1.2 [95% CI, 1.0-1.3]; P=0.03) after adjusting for potential confounders. CONCLUSIONS: Acute ischemic stroke was infrequent in patients with COVID-19 and usually occurs in the presence of other cardiovascular risk factors. The risk of discharge to destination other than home or death increased 2-fold with occurrence of acute ischemic stroke in patients with COVID-19.

Acute Kidney Injury in Acute Ischemic Stroke Patients in Clinical Trials.

OBJECTIVES: Acute ischemic stroke patients are at risk of acute kidney injury due to volume depletion, contrast exposure, and preexisting comorbid diseases. We determined the occurrence rate and identified predictors associated with acute kidney injury in acute ischemic stroke patients. SETTING: Multiple specialized ICUs within academic medical centers. DESIGN: Post hoc analysis of pooled data from prospective randomized clinical trials. PATIENTS: Acute ischemic stroke patients recruited within 3 hours or within 5 hours of symptom onset. INTERVENTIONS: IV recombinant tissue plasminogen activator, endovascular treatment, IV albumin, or placebo. MEASUREMENTS AND MAIN RESULTS: Serum creatinine levels from baseline and within day 5 or discharge were used to classify acute kidney injury classification into stages. Any increase in serum creatinine was seen in 697 (36.1%) and acute kidney injury was seen in 68 (3.5%) of 1,931 patients with acute ischemic stroke. Severity of acute kidney injury was grade I, II, and III in 3.1%, 0.4%, and 0.05% patients, respectively. Patients with albumin (5.5% compared with 2.6%; p = 0.001), preexisting hypertension (4.3% compared with 1.5%; p = 0.0041), and preexisting renal disease (9.1% compared with 3.0%; p < 0.0001) had higher risk of acute kidney injury. The risk of acute kidney injury was lower between those who either underwent CT angiography (2.0% compared with 4.7%; p = 0.0017) or endovascular treatment (1.6% compared with 4.2%; p = 0.0071). In the multivariate analysis, hypertension (odds ratio, 2.6; 95% CI, 1.2-5.6) and renal disease (odds ratio, 3.5; 95% CI, 1.9-6.5) were associated with acute kidney injury. The risk of death was significantly higher among patients with acute kidney injury (odds ratio, 2.7; 95% CI, 1.4-4.9) after adjusting for age and National Institutes of Health Stroke Scale score strata. CONCLUSIONS: The occurrence rate of acute kidney injury in acute ischemic stroke patients was low and was not higher in patients who underwent CT angiogram or those who received endovascular treatment. Occurrence of acute kidney injury increased the risk of death within 3 months among acute ischemic stroke patients.

Preprocedure Intravenous Recombinant Tissue Plasminogen Activator and Risk of Distal Embolization with Thrombectomy in Acute Ischemic Stroke.

BACKGROUND: Intravenous recombinant tissue plasminogen activator (IV rt-PA) prior to thrombectomy may reduce the risk of intraprocedural distal embolization in acute ischemic stroke patients. METHODS: We analyzed the diffusion-weighted imaging acquired with 1.5- or 3-T magnetic resonance imaging (MRI) scans obtained within 24 hours of thrombectomy in consecutive acute ischemic stroke patients. An independent physician identified distal embolization, defined as discrete foci of restricted diffusion independent of the primary area of infarction on MRI scan. Patients were stratified based on whether they had or did not receive IV rt-PA prior to thrombectomy. RESULTS: Distal embolization was seen in 59 (ipsilateral in 56) of 63 patients (mean age ± SD; 64.6 ± 15.3 years) who underwent thrombectomy (mean number 8.6; range 0-32). There was no difference in mean number of ipsilateral hemispheric distal embolization between the 2 groups (7.9 ± 6.1 versus 7.5 ± 7.6, P = .82). After adjusting for age, admission National Institutes of Health Stroke Scale score, the time interval between symptom onset and thrombectomy, there was no association between receiving IV rt-PA prior to thrombectomy and number of ipsilateral distal emboli (P = .90). There was no relationship between the number of ipsilateral emboli and rates of favorable outcome after adjusting for other confounders (adjusted odds ratio 1.0; 95% confidence interval .89 - 1.0; P = .40). CONCLUSIONS: Although distal embolization is very common after thrombectomy, IV rt-PA prior to procedure does not reduce the risk of intraprocedural distal embolization.

Chemoradiation-induced hearing loss remains a major concern for head and neck cancer patients.

OBJECTIVE: Review of the literature regarding hearing loss in patients with head and neck cancer treated with chemoradiation. DESIGN: Studies in the literature are reviewed that pertain to hearing loss sustained in head and neck cancer patients receiving cisplatin-based chemoradiation. Personal observations noted while treating these patients are also detailed. STUDY SAMPLE: PubMed was searched for pertinent articles regarding hearing loss in head and neck cancer patients receiving cisplatin chemotherapy and/or radiation. RESULTS: Studies on the incidence and severity of hearing loss in head and neck cancer patients are limited, but those studies suggest that the risk of hearing loss is greater with higher-dose regimens. CONCLUSIONS: Newer cisplatin chemotherapy regimens using lower, weekly doses may be associated with a lower incidence and severity of hearing loss; however, large prospective studies are needed. Such information will be paramount to effective pre-treatment counselling of head and neck cancer patients.

Prediction of new brain metastases after radiosurgery: validation and analysis of performance of a multi-institutional nomogram.

Stereotactic radiosurgery (SRS) without whole brain radiotherapy (WBRT) for brain metastases can avoid WBRT toxicities, but with risk of subsequent distant brain failure (DBF). Sole use of number of metastases to triage patients may be an unrefined method. Data on 1354 patients treated with SRS monotherapy from 2000 to 2013 for new brain metastases was collected across eight academic centers. The cohort was divided into training and validation datasets and a prognostic model was developed for time to DBF. We then evaluated the discrimination and calibration of the model within the validation dataset, and confirmed its performance with an independent contemporary cohort. Number of metastases (≥8, HR 3.53 p = 0.0001), minimum margin dose (HR 1.07 p = 0.0033), and melanoma histology (HR 1.45, p = 0.0187) were associated with DBF. A prognostic index derived from the training dataset exhibited ability to discriminate patients' DBF risk within the validation dataset (c-index = 0.631) and Heller's explained relative risk (HERR) = 0.173 (SE = 0.048). Absolute number of metastases was evaluated for its ability to predict DBF in the derivation and validation datasets, and was inferior to the nomogram. A nomogram high-risk threshold yielding a 2.1-fold increased need for early WBRT was identified. Nomogram values also correlated to number of brain metastases at time of failure (r = 0.38, p < 0.0001). We present a multi-institutionally validated prognostic model and nomogram to predict risk of DBF and guide risk-stratification of patients who are appropriate candidates for radiosurgery versus upfront WBRT.

Acute Ischemic Stroke: Current Status and Future Directions.

The evolving knowledge on stroke in conjunction with advances in the field of imaging, treatment approaches using recombinant tissue plasminogen activator (rtPA) or thrombectomy devices in recanalization, and efficient emergency stroke workflow processes have opened new frontiers in managing patients with an acute ischemic stroke. These frontiers have been reformed and overcome in overcoming the decades-long watch and wait approach towards patients with ischemic stroke. In this article, we focus on the current strategies for managing ischemic stroke and conclude by providing a brief overview of anticipating developments that can transform future stroke treatments.

Protective properties of vaccinia virus-based vaccines: skin scarification promotes a nonspecific immune response that protects against orthopoxvirus disease.

The process of vaccination introduced by Jenner generated immunity against smallpox and ultimately led to the eradication of the disease. Procedurally, in modern times, the virus is introduced into patients via a process called scarification, performed with a bifurcated needle containing a small amount of virus. What was unappreciated was the role that scarification itself plays in generating protective immunity. In rabbits, protection from lethal disease is induced by intradermal injection of vaccinia virus, whereas a protective response occurs within the first 2 min after scarification with or without virus, suggesting that the scarification process itself is a major contributor to immunoprotection. importance: These results show the importance of local nonspecific immunity in controlling poxvirus infections and indicate that the process of scarification should be critically considered during the development of vaccination protocols for other infectious agents.

Genomic predictors of patterns of progression in glioblastoma and possible influences on radiation field design.

We present a retrospective investigation of the role of genomics in the prediction of central versus marginal disease progression patterns for glioblastoma (GBM). Between August 2000 and May 2010, 41 patients with GBM and gene expression and methylation data available were treated with radiotherapy with or without concurrent temozolomide. Location of disease progression was categorized as within the high dose (60 Gy) or low dose (46 Gy) volume. Samples were grouped into previously described TCGA genomic groupings: Mesenchymal (m), classical (c), proneural (pn), and neural (n); and were also classified by MGMT-Methylation status and G-Cimp methylation phenotype. Genomic groupings and methylation status were investigated as a possible predictor of disease progression in the high dose region, progression in the low dose region, and time to progression. Based on TCGA category there was no difference in OS (p = 0.26), 60 Gy progression (PN: 71 %, N: 60 %, M: 89 %, C: 83 %, p = 0.19), 46 Gy progression (PN: 57 %, N: 40 %, M: 61 %,C: 50 %, p = 0.8) or time to progression (PN: 9 months, N:15 months, M: 9 months, C: 7 months, p = 0.58). MGMT methylation predicted for improved OS (median 25 vs. 13 months, p = 0.01), improved DFS (median 13 vs. 8 months, p = 0.007) and decreased 60 Gy (p = 0.003) and 46 Gy (p = 0.006) progression. There was a cohort of MGMT methylated patients with late marginal disease progression (4/22 patients, 18 %). TCGA groups demonstrated no difference in survival or progression patterns. MGMT methylation predicted for a statistically significant decrease in in-field and marginal disease progression. There was a cohort of MGMT methylated patients with late marginal progression. Validations of these findings would have implications that could affect radiation field size.