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Clopidogrel bolus is an option used before carotid artery stent (CAS) placement when sustained clopidogrel pretreatment is not used.To compare the effect of clopidogrel bolus (450 mg administered ≥4 hours) with sustained clopidogrel pretreatment (48 hours or greater) before CAS among patients recruited in the Carotid Revascularization Endarterectomy versus Stenting Trial.We compared the rates of primary end point (either any stroke, myocardial infarction, or death during the periprocedural period or any ipsilateral stroke within 4 years) between patients who received clopidogrel bolus and those who received sustained clopidogrel pretreatment using Cox proportional hazards analysis after adjusting for age, sex, symptomatic status, and initial severity of stenosis (≥70% vs70%) over 4 years.The rate of periprocedural stroke (7.3% vs 3.4%, P = .03) and primary end point (11.3% vs 5.9%, P = .02) was significantly higher among patients who received clopidogrel bolus. The risk of primary end point was significantly higher in patients who received clopidogrel bolus (hazards ratio 1.9, 95% CI 1.1-3.4, P = .02) after adjusting for potential confounders. The overall mean (±standard deviation) primary end point-free survival based on Kaplan-Meier analysis was 7.0 ± 0.2 years for patients who received clopidogrel bolus and 8.9 ± 0.1 years for those who received sustained clopidogrel pretreatment (log-rank test P = .011).Clopidogrel bolus was associated with higher rates of adverse outcomes compared with sustained clopidogrel pretreatment in patients who underwent CAS. Therefore, clopidogrel bolus may not be equivalent to sustained clopidogrel pretreatment.

Rare, recurrent balanced translocations occur in a variety of cancers but are often not functionally interrogated. Balanced translocations with the immunoglobulin heavy chain locus (IGH; 14q32) in chronic lymphocytic leukemia (CLL) are infrequent but have led to the discovery of pathogenic genes including CCND1, BCL2, and BCL3. Following identification of a t(X;14)(q28;q32) translocation that placed the mature T cell proliferation 1 gene (MTCP1) adjacent to the immunoglobulin locus in a CLL patient, we hypothesized that this gene may have previously unrecognized importance. Indeed, here we report overexpression of human MTCP1 restricted to the B cell compartment in mice produces a clonal CD5+/CD19+ leukemia recapitulating the major characteristics of human CLL and demonstrates favorable response to therapeutic intervention with ibrutinib. We reinforce the importance of genetic interrogation of rare, recurrent balanced translocations to identify cancer driving genes via the story of MTCP1 as a contributor to CLL pathogenesis., Some genes that are part of balanced translocations are reported as drivers for tumourigenesis. Here, the authors report a translocation involving MTCP1 in chronic lymphocytic leukemia and show that MTCP1 overexpression leads to the disease in a murine model.

Background and purpose We report the results of intra-arterial injection of lidocaine in the middle meningeal artery in patients with intractable headache or status migrainosus. Methods We treated four patients with intra-arterial lidocaine (2 mg/ml) in doses up to 50 mg in each middle meningeal artery via a microcatheter bilaterally (except in one patient). In two patients with intractable headache, the daily maximum intensity of headache (graded by 11-point numeric rating scale) was recorded for 7 days postprocedure. In two patients with status migrainosus, migraine-related disability 3 months prior and after treatment using MIDAS (Migraine Disability Assessment) questionnaire was recorded. Results Intra-arterial lidocaine reduced the headache intensity from 8/10 and 10/10 to 0/10 in the two patients with intractable headaches for 2 days (day 0 and day 1) postprocedure. Despite recurrence of headache on day 2, the intensity was less than preprocedure intensity up to the last day recorded (by 3 and 2 points on day 7). In the two patients with status migrainosus, there was immediate reduction in headache intensity following intra-arterial lidocaine. The post treatment 3-month MIDAS score was lower in both patients compared with pretreatment 3-month score; 3 versus 30 and 55 versus 90. Severe disability preprocedure by MIDAS was reduced to little or no disability postprocedure in one patient. Conclusions Intra-arterial lidocaine resulted in amelioration of headache in patients with intractable headache and those with status migrainosus with improvement lasting longer than the short half-life of lidocaine possibly related to central desensitization.

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.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.Pulsatile tinnitus and unilateral sensorineural hearing loss maybe a reversible manifestation of a stenotic internal carotid artery.

Purpose To explore receptivity of and preferences for risk-reducing health behavior changes among African American survivors of early-stage lung cancer and their family members. Participants & setting 26 African American non-small cell lung cancer survivor-family member dyads were recruited from two cancer programs in the southeastern United States. Methodologic approach Social cognitive theory principles guided the design and implementation of focus groups. Descriptive statistics were used to summarize the data, and thematic analysis was used to interpret the transcripts from the focus groups. Findings The following four themes were identified. Implications for nursing Participants emphasized the need for improved provider communication. Pragmatic communication interventions for providers, survivors, and family members may facilitate behavior change and improve outcomes among underserved populations.

Brain metastasis velocity (BMV) is a prognostic metric that describes the recurrence rate of new brain metastases after initial treatment with radiosurgery (SRS). We have previously risk stratified patients into high, intermediate, and low-risk BMV groups, which correlates with overall survival (OS). We sought to externally validate BMV in a multi-institutional setting.Patients from nine academic centers were treated with upfront SRS; the validation cohort consisted of data from eight institutions not previously used to define BMV. Patients were classified by BMV into low (4 BMV), intermediate (4-13 BMV), and high-risk groups (13 BMV). Time-to-event outcomes were estimated using the Kaplan-Meier method. Cox proportional hazards methods were used to estimate the effect of BMV and salvage modality on OS.Of 2829 patients, 2092 patients were included in the validation dataset. Of these, 921 (44.0%) experienced distant brain failure (DBF). Median OS from initial SRS was 11.2 mo. Median OS for BMV 4, BMV 4-13, and BMV 13 were 12.5 mo, 7.0 mo, and 4.6 mo (p 0.0001). After multivariate regression modeling, melanoma histology (β: 10.10, SE: 1.89, p 0.0001) and number of initial brain metastases (β: 1.52, SE: 0.34, p 0.0001) remained predictive of BMV (adjusted RThis multi-institutional dataset validates BMV as a predictor of OS following initial SRS. BMV is being utilized in upcoming multi-institutional randomized controlled trials as a stratification variable for salvage whole brain radiation versus salvage SRS after DBF.

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.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.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.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.

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.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.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.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.

Supplemental Digital Content is available in the text., Background: To determine the exposure risk for coronavirus 2019 (COVID-19) during neurology practice. Neurological manifestations of COVID-19 are increasingly being recognized mandating high level of participation by neurologists. Methods: An American Academy of Neurology survey inquiring about various aspects of COVID-19 exposure was sent to a random sample of 800 active American Academy of Neurology members who work in the United States. Use of second tier protection (1 or more including sterile gloves, surgical gown, protective goggles/face shield but not N95 mask) or maximum protection (N95 mask in addition to second tier protection) during clinical encounter with suspected/confirmed COVID-19 patients was inquired. Results: Of the 81 respondents, 38% indicated exposure to COVID-19 at work, 1% at home, and none outside of work/home. Of the 28 respondents who did experience at least 1 symptom of COVID-19, tiredness (32%) or diarrhea (8%) were reported. One respondent tested positive out of 12 (17%) of respondents who were tested for COVID-19 within the last 2 weeks. One respondent received health care at an emergency department/urgent care or was hospitalized related to COVID-19. When seeing patients, maximum protection personal protective equipment was used either always or most of the times by 16% of respondents in outpatient setting and 56% of respondents in inpatient settings, respectively. Conclusions: The data could enhance our knowledge of the factors that contribute to COVID-19 exposure during neurology practice in United States, and inform education and advocacy efforts to neurology providers, trainees, and patients in this unprecedented pandemic.

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.

PURPOSE Radiotherapy (RT) treatment at public hospitals in Nigeria is often interrupted by prolonged periods of machine breakdown because of insufficient funds for maintenance and repair. These delays have prompted the uptake of public-private partnerships (PPPs) to acquire and maintain RT equipment. This study aimed to understand Nigeria's current RT capacity and the impact of PPPs on RT availability and cost. METHODS Eleven radiation oncologists, each representing one of the 11 RT centers in Nigeria (eight public and three private), were invited to complete a survey on the type, status, acquisition, and maintenance plan of existing RT equipment, cost incurred by patients for external-beam radiation (EBRT) and brachytherapy treatment, and number of patients treated per year on each machine. Type and status of equipment at nonresponding facilities were obtained through literature review and confirmed with the facility. RESULTS A total of eight (81%) respondents completed the survey, all representing public centers, three of which reported PPP use. They reported 11 megavoltage units in total (seven linear accelerators [LINACs] and four Cobalt-60s) and 10 brachytherapy afterloaders. Of those, 57% (4/7) of the LINACs, 100% (4/4) of the Cobalt-60s, and 63% (7/11) of the afterloaders were in clinical use. All commissioned equipment supported by PPPs (three LINACs and one afterloader) were in operation. The public EBRT equipment were nonfunctional 35% of the year (resulting in 60% fewer patients treated per year). The PPP EBRT and afterloaders did not experience any periods of breakdown, but PPP costs were 338% higher than public equipment. CONCLUSION This study characterizes the use of PPP as a more reliable method of RT delivery in Nigeria, albeit at higher costs.

Several studies evaluating stereotactic radiosurgery (SRS) for patients with4 brain metastases (BM) demonstrated similar outcomes after treatment of 1, 2 to 4, and 5 to 15 BM; others found clinically significant survival decrements in the latter group. In this review of 8 academic centers, we compared outcomes of patients undergoing initial SRS for 1, 2 to 4, and 5 to 15 BM.A total of 2089 patients treated with initial SRS for BM were included. Overall survival (OS) was estimated using the Kaplan-Meier method and compared using the log-rank test. Patient and disease characteristics were evaluated for association with OS and cumulative incidence of distant brain failure (DBF) using stepwise multivariable Cox proportional hazards and competing risk regression modeling.In this series, 989 (47%) patients had 1 metastasis, 882 (42%) had 2 to 4 metastases, and 212 (10%) had 5 to 15 metastases treated. Median OS for the 1, 2 to 4, and 5 to 15 BM groups was 14.6, 9.5, and 7.5 months, respectively (log-rank P .01). Univariate and multivariable analyses revealed no difference in survival between 2 to 4 and 5 to 15 BM. DBF at 1 year was 30%, 41%, and 50%, respectively (Gray's P .01). Two-year cumulative incidence of salvage SRS decreased with increasing number of BM (1: 21% vs 2-4: 19% vs 5-15: 13%; P .01), but no difference in salvage whole brain radiation therapy was observed (1: 12% vs 2-4: 15% vs 5-15: 16%, P = .10). At the time of DBF, median brain metastasis velocity was 3.9, 6.1, and 11.7 new metastases per year in the 1, 2 to 4, and 5 to 15 BM groups, respectively (P .01).Patients treated with initial SRS for 5 to 15 BM experienced survival similar to that in patients with 2 to 4 BM. Lower rates of salvage SRS were observed in the 5 to 15 BM group, with no difference in rates of salvage whole brain radiation therapy.

Modern medicine, including the care of the cancer patient, has significantly advanced, with the evidence-based medicine paradigm serving to guide clinical care decisions. Yet we now also recognize the tremendous heterogeneity not only of disease states but of the patient and his or her environment as it influences treatment outcomes and toxicities. These reasons and many others have led to a reevaluation of the generalizability of randomized trials and growing interest in accounting for this heterogeneity under the rubric of precision medicine as it relates to personalizing clinical care predictions, decisions, and therapy for the disease state. For the cancer patient treated with radiation therapy, characterizing the spatial treatment heterogeneity has been a fundamental tenet of routine clinical care facilitated by established database and imaging platforms. Leveraging these platforms to further characterize and collate all clinically relevant sources of heterogeneity that affect the longitudinal health outcomes of the irradiated cancer patient provides an opportunity to generate a critical informatics infrastructure on which precision radiation therapy may be realized. In doing so, data science-driven insight discoveries, personalized clinical decisions, and the potential to accelerate translational efforts may be realized ideally within a network of institutions with locally developed yet coordinated informatics infrastructures. The path toward realizing these goals has many needs and challenges, which we summarize, with many still to be realized and understood. Early efforts by our group have identified the feasibility of this approach using routine clinical data sets and offer promise that this transformation can be successfully realized in radiation oncology.

To identify rates of and factors associated with repeat revascularization in a large cohort of patients prospectively followed over 10 years in Carotid Revascularization Endarterectomy versus Stenting Trial.We compared the effect of carotid angioplasty and stenting (CAS) versus carotid endarterectomy (CEA) on risk of repeat revascularization after adjusting for age, sex, symptomatic status, and initial severity of stenosis (≥70% vs.70%) using Cox proportional hazards analysis. We used Kaplan-Meier analysis to assess repeat revascularization-free survival for the overall cohort.Repeat revascularization was performed in 90 (3.9%, 95% confidence interval [CI] 3.1%-4.8%) of 2318 patients; 6 (6.7%, 95% CI 2.5%-14.0%) patients experienced the composite end point of any stroke, myocardial infarction, or death within 30 days after repeat revascularization. There was no difference in risk of repeat revascularization in patients who underwent CAS (compared with CEA) as the index procedure (hazard ratio 0.92, 95% CI 0.69-1.23, P = 0.5765). Patient's age (hazard ratio 1.01, 95% CI 1.01-1.02, P0.0001) was associated with performance of repeat revascularization. Mean ± SD repeat revascularization-free survival was 8.2 ± 0.1 years and 8.0 ± 0.1 years for CAS and CEA, respectively (log-rank test P = 0.0823).A low rate of repeat revascularization was seen without any significant difference among patients who underwent CEA or CAS over 10 years. The 6.7% rate of composite end point within 30 days after procedure highlights the need for standardizing the indications for repeat revascularization.

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

BACKGROUND: Intracranial hemorrhage (including subarachnoid hemorrhage [SAH]) has been reported in 0.3%-1.2% of patients with coronavirus disease 2019 (COVID-19). However, no study has evaluated the risk of SAH in patients with COVID-19. METHODS: We analyzed data from 62 health care facilities using the Cerner de-identified COVID-19 dataset. RESULTS: There were 86 (0.1%) and 376 (0.2%) patients with SAH 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 SAH in patients with COVID-19 (odds ratio 0.5, 95% confidence interval 0.4-0.7, P < 0.0001) after adjusting for sex, age strata, race/ethnicity, hypertension, and nicotine dependence/tobacco use. The proportions of patients who developed pneumonia (58.1% vs. 21.3%, P < 0.0001), acute kidney injury (43% vs. 27.7%, P = 0.0005), septic shock (44.2% vs. 20.7%, P < 0.0001), and respiratory failure (64.0% vs. 39.1%, P < 0.0001) were significantly higher among patients with SAH and COVID-19 compared with patients without COVID-19. The in-hospital mortality among patients with SAH and COVID-19 was significantly higher compared with patients without COVID-19 (31.4% vs. 12.2%, P

Objective: Symptom burden remains a distressing problem for survivors with non-small-cell lung cancer (stages I-IIIa). This pilot study evaluated feasibility and preliminary effects of a tailored mindfulness-based intervention, Breathe Easier, which encompasses meditation, 2 levels of mindful hatha yoga, breathing exercises, and participant interaction. Methods: Participants were recruited from 2 cancer programs in the US Southeast. A family member was required for participation. Sixty-two participants enrolled (20% recruitment) and 49 completed the intervention (79% retention). Participants chose level 1 yoga (basic) or level 2 (more advanced). Of the completers, survivors were 39% male and 65% Black. A community-based participatory research framework helped identify the specific needs and interests of potential participants and foreseeable barriers to implementation. A 2-month prospective, 1-group, pre-post design evaluated feasibility. Intervention dosage was measured using written protocols. Attendance and completion of daily home assignments measured adherence. Acceptability was assessed using a 10-item questionnaire, completed at three time points. Preliminary outcome data collected pre- and post-intervention tested the hypothesis that participants who received the 8-week intervention Breathe Easier would, post-intervention, demonstrate (a) less dyspnea, (b) less fatigue, (c) less stress, (d) improved sleep, (e) improved anxiety and depression, and (f) improved functional exercise capacity. Exit interviews were conducted, transcribed verbatim, and analyzed for content using descriptive statistics. Results: Quantitative and qualitative measures indicated strong feasibility. Over time, level 1 participants had statistically less dyspnea, fatigue and improved exercise capacity, as well as improved sleep, and stress scores. Level 2 participants experienced slightly increased dyspnea and fatigue but improved sleep, stress, and exercise capacity. All participants experienced anxiety and depression within normal limits pre- and post-intervention. Five major themes emerged out of exit interviews: Learning to Breathe Easier; Interacting with Others as a Personal Benefit; Stretching, Releasing Tension, and Feeling Energized; Enhancing Closeness with Committed Partners; Refocusing on Living; and Sustaining New Skills as a Decision. Conclusions: The study offers insight into the feasibility of an 8-week in-person mindfulness-based intervention with a unique subset of understudied survivors of lung cancer and family members. Outcome data interpretation is limited by the 1-group design and sample size.

Background and purpose The prevalence and characteristics of intraprocedural back pain is not well studied in awake patients undergoing neuroendovascular procedures. Methods We performed a prospective study as part of quality improvement initiative in which all patients who underwent neuroendovascular procedures in awake state were inquired regarding presence, severity (using a numeric rating scale score ranging from 0 [no pain] to 10 [worst pain possible]), and location (using anatomical chart) of back pain immediately after the procedure. The primary endpoint was the proportion of patients with moderate to severe pain (score of ≥3). Results A total of 100 (41.3%) of 242 patients reported intraprocedural back pain with a median severity of 5/10 (range 1-10). The mean age was 58.7 ± 16.2 years. The mean duration of the procedure was 82.3 minutes (range 15-410 minutes). The pain was classified as moderate to severe in 86 of 100 patients. The locations of pain were identified in lumbar (n = 77), thoracic (n = 6), cervical (n = 7), cervical and lumbar (n = 8), and cervical with thoracolumbar (n = 2) regions. There was a significant relationship between patients' history of the previous neck and/or back surgery and frequency of moderate to severe back pain (P = .02). No significant relationship was observed between frequency of none to mild and moderate to severe back pain among the strata by patients' age, body mass index, or duration of procedures. Conclusions The relatively high prevalence of intraprocedural back pain in patients undergoing neuroendovascular procedures in awake state must be recognized, and strategies to reduce the occurrence need to be identified.

BACKGROUND: Cisplatin is widely used to treat adult and pediatric cancers. It is the most ototoxic drug in clinical use, resulting in permanent hearing loss in approximately 50% of treated patients. There is a major need for therapies that prevent cisplatin-induced hearing loss. Studies in mice suggest that concurrent use of statins reduces cisplatin-induced hearing loss. METHODS: We examined hearing thresholds from 277 adults treated with cisplatin for head and neck cancer. Pretreatment and posttreatment audiograms were collected within 90 days of initiation and completion of cisplatin therapy. The primary outcome measure was a change in hearing as defined by the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE). RESULTS: Among patients on concurrent atorvastatin, 9.7% experienced a CTCAE grade 2 or higher cisplatin-induced hearing loss compared with 29.4% in nonstatin users (P < 0.0001). A mixed-effect model analysis showed that atorvastatin use was significantly associated with reduced cisplatin-induced hearing loss (P ≤ 0.01). An adjusted odds ratio (OR) analysis indicated that an atorvastatin user is 53% less likely to acquire a cisplatin-induced hearing loss than a nonstatin user (OR = 0.47; 95% CI, 0.30–0.78). Three-year survival rates were not different between atorvastatin users and nonstatin users (P > 0.05). CONCLUSIONS: Our data indicate that atorvastatin use is associated with reduced incidence and severity of cisplatin-induced hearing loss in adults being treated for head and neck cancer. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT03225157. FUNDING: Funding was provided by the Division of Intramural Research at the National Institute on Deafness and Other Communication Disorders (1 ZIA DC000079, ZIA DC000090).

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.

BACKGROUND AND PURPOSE Acute stroke patients may have undiagnosed coronavirus disease 2019 (COVID‐19) infection, transmissible to medical professionals involved in their care. Our aim was to determine the value of incorporating a chest computed tomography (CT) scan during acute stroke imaging, and the factors that influence this decision. METHODS We constructed a probabilistic decision tree of the value of acquiring a chest CT scan or not, expressed in quality‐adjusted life months (QALM) of patients and medical professionals. The model was based on the chance of detecting infection by chest CT scan, the case fatality rates of COVID‐19 infection, the risk of COVID‐19 infection after exposure, the expected proportion of medical professionals exposed, and the exposure reduction derived from early disease detection. RESULTS The decision to incorporate the chest CT scan was superior to not doing so (12.00 QALM vs 11.99 QALM, respectively), when the probability of patients having undetected COVID‐19 infection is 3.5%, potentially exposing 100% of medical professionals, and if early detection reduces exposure by 50%. The risk of developing symptomatic COVID‐19 infection following exposure casts uncertainty on the results, but this is offset by the potential for reducing exposure. CONCLUSIONS We identified a measurable benefit of incorporating a chest CT into the urgent imaging protocol of acute stroke patients in reducing exposure of medical professionals without appropriate precautions. The clinical impact of this benefit, however, may not be materially significant.

Suboptimal platelet inhibition by clopidogrel (clopidogrel resistance) may be associated with high rates of stent thrombosis and ischemic events. Our objective was to determine if ticagrelor, a P2YA thromboelastography-platelet mapping assay was used in all patients undergoing neuroendovascular procedures requiring oral clopidogrel. In patients with suboptimal platelet inhibition (60%) on clopidogrel, ticagrelor was imitated after an oral bolus of 180 mg followed by 90 mg twice daily and the platelet mapping assay was repeated. The primary endpoint was hemorrhagic complications classified as major (hemoglobin decrease5 g/dL or intracranial hemorrhage with deficits), minor (hemoglobin decrease 3-5 g/dL or intracranial hemorrhage without residual deficits), or insignificant.Suboptimal platelet inhibition on clopidogrel was seen in 70 of 106 patients undergoing neuroendovascular procedures. There was a significantly higher magnitude of platelet inhibition with ticagrelor compared with clopidogrel in patients with clopidogrel resistance (mean ± SD: 85.90 ± 10.74% vs. 29.26 ± 17.71%; P .001); 50 of 70 patients showed optimal inhibition. Two patients had major (fatal) hemorrhagic events (both received either intravenous thrombolytics and/or eptifibatide infusion). Three patients had minor hemorrhagic events, and two patients had insignificant hemorrhagic events. Four of seven hemorrhagic events occurred in patients with optimal response to clopidogrel, two occurred in patients with suboptimal response to ticagrelor, and one occurred in a patient with optimal response to ticagrelor.Oral ticagrelor can augment platelet inhibition in patients who have clopidogrel resistance.

The Functional Assessment of Cancer Therapy (FACT) instrument is comprised of a group of related and overlapping quality of life (QoL) questionnaires including a core general form, head and neck cancer (HNC)-specific items, and an expert-selected index (FACT-HNSI). Understanding how these relate to more HNC-specific instruments such as the MD Anderson Dysphagia Inventory (MDADI) and Sydney Swallow Questionnaire (SSQ) is vital for guiding their use in clinical trials.HNC patients concurrently completed MDADI, SSQ, and FACT questionnaires at radiation oncology clinic visits (2015-2016). Spearman correlation coefficients were calculated between each FACT instrument and MDADI or SSQ. Unsupervised k-means cluster analyses were performed to identify clusters of similar QoL responses. Principal component analysis (PCA) identified the degree of variability explained by each instrument.We identified 631 instances (363 patients) where the questionnaires were completed concurrently. Correlations between the various FACT measures and SSQ or MDADI were all significant (p 0.001), but FACT HNC-specific subscale and FACT-HNSI showed the strongest correlation with MDADI and SSQ. Clustering identified 3 distinct groups of responses when combining instruments either pairwise or three-way. PCA revealed that MDADI and FACT HNC-specific subscale provide similar and likely redundant information.FACT HNC-subscale and FACT-HNSI may be preferable over other FACT measures for use in clinical trials where patient-reported swallow function is evaluated. MDADI and FACT provide similar insights into HNC patient QoL while SSQ provides additional, complementary information which could serve to better stratify patients into groups with high, medium, and low QoL outcomes.

Introduction: Radiation-associated soft tissue sarcomas of the neck (RASN) constitute a rare and aggressive tumor type. Methods: A retrospective chart review at the authors’ institution revealed 3 patients with RASN. A systematic review of the literature was also conducted using MEDLINE, Ovid, the Cochrane Library, and Embase. Results: Patients within the authors’ institutional chart review presented from 6 to 26 years after neck radiation with neck masses. All patients underwent surgical resection with clear margins, and adjuvant radiation was offered when feasible. Patients had no evidence of disease at most recent follow-up. A total of 867 articles were screened for systematic review, revealing 9 articles detailing outcomes of RASN. Studies were small and heterogeneous, precluding pooled data. The importance of complete surgical extirpation was noted. Conclusions: Complete surgical resection appears to be the mainstay of therapy, but there are limited data on management and outcomes of patients with RASN.

Background Chronic obstructive pulmonary disease (COPD) is the most common smoking-related illness. COPD often is underemphasized as a comorbidity except when considering issues surrounding surgical treatment options. Objectives This article aims to provide nurses with an overview of the pharmacologic and nonpharmacologic treatment implications of COPD. Methods Definitions, differentials, and treatment considerations are provided, and clinical implications and resources are described. Findings The added burden of dyspnea, fatigue, and psychological distress related to COPD may affect the overall outcome and quality of life (QOL) of patients with lung cancer. Attention to the prevention, assessment, and treatment of lung cancer and COPD and related symptomatology will help maximize patients' QOL.

Xerostomia is the most common late toxicity after head and neck radiation. We demonstrate injection of a hydrogel spacer anteriorly displacing the submandibular gland. This procedure enables reduced dose to the displaced submandibular gland in cadaveric models of oropharynx cancer treated with IMRT, with potential implications in reducing xerostomia risk.

BackgroundThe benefit of immune checkpoint inhibitors (ICIs) in patients with leptomeningeal metastases (LMM) is unknown.MethodsWe undertook a phase II trial of pembrolizumab in patients with LMM from solid tumors. Eligible patients had radiologic/cytologic LMM and Eastern Cooperative Oncology Group performance status 0–1. Pembrolizumab was administered intravenously at 200 mg q3W until disease progression/unacceptable toxicity. The primary endpoint was central nervous system (CNS) response after four cycles, defined radiologically/cytologically/clinically. Serial cerebrospinal fluid (CSF) was assessed for tumor-derived DNA (t-DNA) aneuploidy and cytokines.ResultsThirteen of a planned 16 patients were treated between April 2017 and December 2019. The study closed early for poor accrual. Median age was 57 years (range: 22–79). Sixty-two percent of patients had tumors not traditionally ICI-responsive (hormone-receptor (HR)-positive breast carcinoma=39%; high-grade glioma=23%), while 38% had ICI-responsive tumors (non-small cell lung cancer (NSCLC)=23%, head and neck carcinoma=8%, cutaneous squamous carcinoma (CSC)=8%). CNS response was observed in 38% of patients at 12 weeks (95% CI 13.9% to 68.4%) by pre-defined criteria and LM-RANO, and 2 achieved durable complete responses (CSC=1, overall survival (OS) 3+ years; NSCLC=1, OS 9 months). Median CNS progression-free survival and OS was 2.9 months (95% CI 1.3 to NR) and 4.9 months (95% CI 3.7 to NR), respectively. Grade 3+ treatment-related adverse events occurred in 15% of patients. Sensitivity for LMM detection by t-DNA and cytopathology was 84.6% (95% CI 54.6% to 98.1%) and 53.9% (95% CI 25.1% to 80.8%), respectively. Pre-therapy and on-therapy CSF cytokine analysis demonstrated complete responders clustered together.ConclusionsPembrolizumab conferred a 38% CNS response rate in patients with LMM, a tolerable safety profile, and deep responses in selected patients with ICI-responsive tumors. CSF t-DNA may be sensitive for LMM detection, and immunologic subsets of CNS response warrant further study.Trial registration numberNCT03091478

Purpose Prior studies suggest a high incidence of leptomeningeal failure (LMF) in breast cancer metastatic to brain. This study examines breast cancer-specific variables affecting development of LMF and survival after Gamma-Knife Radiosurgery (GKS). Methods Between 2000–2010, 149 (breast) and 658 other-histology patients were treated with GKS. Hormone/HER2, age, local/distant brain failure, prior craniotomy, and prior whole-brain radiotherapy (WBRT) were assessed. Median follow-up was 54 months (range, 0–106). Serial MRI determined local and distant-brain failure and LMF. Statistical analysis with categorical/continuous data comparisons were done with Fisher’s-exact, Wilcoxon rank-sum, log-rank tests, and Cox-Proportional Hazard models. Results Of 149 patients, 21 (14%) developed LMF (median time of 11.9 months). None of the following predicted for LMF: Her2-status (HR = 0.49, p = 0.16), hormone-receptor status (HR = 1.15, p = 0.79), prior craniotomy (HR = 1.58, p = 0.42), prior WBRT (HR = 1.36, p = 0.55). Non-significant factors between patients that did (n = 21) and did not (n = 106) develop LMF included neurologic death (p = 0.34) and median survival (8.6 vs 14.2 months, respectively). Breast patients who had distant-failure after GKS (65/149; 43.6%) were more likely to later develop LMF (HR 4.2, p = 0.005); including 15/65 (23%) patients who had distant-failure and developed LMF. Median time-to-death for patients experiencing LMF was 6.1 months (IQR 3.4–7.8) from onset of LMF. Median survival from LMF to death was much longer in breast (6.1 months) than in other (1.7 months) histologies Conclusion Breast cancer patients had a longer survival after diagnosis of LMF versus other histologies. Neither ER/PR/HER2 status, nor prior surgery or prior WBRT predicted for development of LMF in breast 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 counseling of head and neck cancer patients.

We evaluated the toxicity associated with stereotactic radiosurgery (SRS) and whole brain radiation therapy (WBRT) in elderly and very elderly patients with brain metastases, as the role of SRS in geriatric patients who would traditionally receive WBRT is unclear.We conducted a retrospective review of elderly patients (aged 70-79 years) and very elderly patients (aged ≥80 years) with brain metastases who underwent RT from 2010 to 2015 at Johns Hopkins Hospital. Patients received either upfront WBRT or SRS for metastatic solid malignancies, excluding small cell lung cancer. Acute central nervous system toxicity within 3 months of RT was graded using the Radiation Therapy Oncology Group acute radiation central nervous system morbidity scale. The toxicity data between age groups and treatment modalities were analyzed using Fisher's exact test and multivariate logistic regression analysis. Kaplan-Meier curves were used to estimate the median overall survival, and the Cox proportion hazard model was used for multivariate analysis.A total of 811 brain metastases received RT in 119 geriatric patients. The median overall survival from the diagnosis of brain metastases was 4.3 months for the patients undergoing WBRT and 14.4 months for the patients undergoing SRS. On multivariate analysis, WBRT was associated with worse overall survival in this cohort of geriatric patients (odds ratio [OR] 3.7, 95% confidence interval [CI] 1.9-7.0, P.0001) and age ≥80 years was not. WBRT was associated with significantly greater rates of any grade 1 to 4 toxicity (OR 7.5, 95% CI 1.6-33.3, P=.009) and grade 2 to 4 toxicity (OR 2.8, 95% CI 1.0-8.1, P=.047) on multivariate analysis. Elderly and very elderly patients did not have significantly different statistically acute toxicity rates when stratified by age.WBRT was associated with increased toxicity compared with SRS in elderly and very elderly patients with brain metastases. SRS, rather than WBRT, should be prospectively evaluated in geriatric patients with the goal of minimizing treatment-related toxicity.

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.

PURPOSE To evaluate the utility of a clinical decision support system (CDSS) using a weight loss prediction model. METHODS A prediction model for significant weight loss (loss of greater than or equal to 7.5% of body mass at 3-month post radiotherapy) was created with clinical, dosimetric, and radiomics predictors from 63 patients in an independent training data set (accuracy, 0.78; area under the curve [AUC], 0.81) using least absolute shrinkage and selection operator logistic regression. Four physicians with varying experience levels were then recruited to evaluate 100 patients in an independent validation data set of head and neck cancer twice (ie, a pre-post design): first without and then with the aid of a CDSS derived from the prediction model. At both evaluations, physicians were asked to predict the development (yes/no) and probability of significant weight loss for each patient on the basis of patient characteristics, including pretreatment dysphagia and weight loss and information from the treatment plan. At the second evaluation, physicians were also provided with the prediction model’s results for weight loss probability. Physicians’ predictions were compared with actual weight loss, and accuracy and AUC were investigated between the two evaluations. RESULTS The mean accuracy of the physicians’ ability to identify patients who will experience significant weight loss (yes/no) increased from 0.58 (range, 0.47 to 0.63) to 0.63 (range, 0.58 to 0.72) with the CDSS ( P = .06). The AUC of weight loss probability predicted by physicians significantly increased from 0.56 (range, 0.46 to 0.64) to 0.69 (range, 0.63 to 0.73) with the aid of the CDSS ( P < .05). Specifically, more improvement was observed among less-experienced physicians ( P < .01). CONCLUSION Our preliminary results demonstrate that physicians’ decisions may be improved by a weight loss CDSS model, especially among less-experienced physicians. Additional study with a larger cohort of patients and more participating physicians is thus warranted for understanding the usefulness of CDSSs.

Xerostomia is a common consequence of radiotherapy in head and neck cancer. The objective was to compare the regional radiation dose distribution in patients that developed xerostomia within 6 months of radiotherapy and those recovered from xerostomia within 18 months post-radiotherapy. We developed a feature generation pipeline to extract dose volume histogram features from geometrically defined ipsilateral/contralateral parotid glands, submandibular glands, and oral cavity surrogates for each patient. Permutation tests with multiple comparisons were performed to assess the dose difference between injury vs. non-injury and recovery vs. non-recovery. Ridge logistic regression models were applied to predict injury and recovery using clinical features along with dose features (D10-D90) of the subvolumes extracted from oral cavity and salivary gland contours + 3 mm peripheral shell. Model performances were assessed by the area under the receiver operating characteristic curve (AUC) using nested cross-validation. We found that different regional dose/volume metrics patterns exist for injury vs. recovery. Compared to injury, recovery has increased importance to the subvolumes receiving lower dose. Within the subvolumes, injury tends to have increased importance towards D10 from D90. This suggests that different threshold for xerostomia injury and recovery. Injury is induced by the subvolumes receiving higher dose, and the ability to recover can be preserved by further reducing the dose to subvolumes receiving lower dose.

Static stretching (SS) has been used for inducing acute and long-term increases in range of motion (ROM). Foam rolling (FR) has recently gained popularity for acutely increasing ROM. However, the long-term effects of FR on ROM have not been thoroughly evaluated. Therefore, the purpose of this study was to investigate the acute and long-term changes in dorsiflexion ROM as a result of 6 wk of FR, SS, and FR followed by SS (FR + SS).Participants (n = 44) were randomly assigned to FR, SS, and FR + SS groups. The FR group foam rolled the triceps surae. The SS group performed a wall stretch for both legs. The FR + SS group performed FR immediately followed by SS. All groups completed 12 training sessions in 6 wk. Dorsiflexion ROM was assessed before and after the first training session, before the second session of week 3, before and after the last session in week 6, and at week 7.There was a 4.0% acute increase in ROM at week 6 (P = 0.004) for all three groups. ROM increased 8.4% from week 3 to week 7 for all three groups (P0.001). When comparing week 1 baseline to week 7, ROM increased 18.3% for all three groups (P = 0.003).SS and FR seem to be comparable in terms of increasing dorsiflexion ROM acutely as well as after 6 wk of training for healthy, university-age participants. FR combined with SS does not seem to provide a synergistic effect on improving dorsiflexion ROM.

Importance Despite progress in narrowing gender-based salary gaps, notable disparities persist in the scientific community. The significance of pay difference may be underestimated, with little data evaluating its effect on lifetime wealth after accounting for factors like time to promotion and savings. Objectives To characterize gender disparities in salary and assess the outcomes associated with a gender equity initiative (GEI). Design, Setting, and Participants Quality improvement study with simulations of salary and additional accumulated wealth (AAW) using retrospectively reviewed Johns Hopkins University School of Medicine annual salary and promotion data. All academic faculty were included in the faculty salary analysis from 2005 (n = 1481) and 2016 (n = 1885). Main Outcomes and Measures Salary and longitudinal promotion data from 2005 to 2016 were used to estimate gender-based differences in salary and time to promotion. The effect of these differences on total salary and AAW, including retirement and salary-based investments, was simulated for a representative male and female faculty member over a 30-year career in 3 scenarios: (1) pre-GEI, (2) post-GEI, and (3) in real time for GEI, beginning with and progressing through these initiatives. Results Analyses of salaries of 1481 faculty (432 women) in 2005 and 1885 faculty (742 women) in 2016 revealed that a decade after GEI implementation, the overall mean (SE) salary gap by gender decreased from −2.6% (1.2%) (95% CI, −5.6% to −0.3%) to −1.9% (1.1%) (95% CI, −4.1% to 0.3%). Simulation of pre-GEI disparities correlated with male faculty collecting an average lifetime AAW of $501 416 more than the equivalent woman, with disparities persisting past retirement. The AAW gap decreased to $210 829 in the real-time GEI simulation and to $66 104 using post-GEI conditions, reflecting success of GEI efforts. Conclusions and Relevance Even small gender-based salary gaps are associated with substantial differences in lifetime wealth, but an institutional commitment to achieving equitable promotion and compensation for women can appreciably reduce these disparities. The findings of this study support broad implementation of similar initiatives without delay, as results may take more than a decade to emerge. A modifiable version of the simulation is provided so that external users may assess the potential disparities present within their own institutions.

Stereotactic radiosurgery (SRS) has become a widely available treatment option for patients with brain metastases. Recent clinical trials suggest that SRS can be used without upfront whole brain radiotherapy (WBRT), resulting in several clinical dilemmas in the current daily practice of SRS. The proper patient selection for SRS or WBRT continues to evolve. Statistical models to predict when new brain metastases will occur as well as who will experience neurologic death have been developed. The optimization of imaging continues for both detection of brain metastases and response assessment. Larger brain metastases continue to pose a challenge to practitioners to find options to optimize the therapeutic ratio. The current review addresses the current state of the scientific literature for these clinical dilemmas.

The purpose of this study was to explore airway clearance practices for the preterm newborn in the neonatal intensive care unit (NICU).This descriptive, retrospective medical record review analyzed airway clearance practices in a level III regional NICU from 2016 to 2017 in preterm newborns ranging from 32 weeks to 36 weeks and 6 days. There were 87 preterm newborns and 384 suctioning events reviewed during the entire length of stay. Practices reviewed include device used, frequency, color, consistency, and tolerance of airway clearance. Method of nursing documentation for these practices was also reviewed.Babies born via cesarean required more suctioning (65.5%). Males (60.9%) required more airway clearance events than females (39.1%). After suction events, nurses reported no distress (74%), equal bilateral breath sounds (30%), desaturation (6%), and collectively color change, apnea, or bradycardia (1%). The most common discharge diagnosis was respiratory distress syndrome (90%). Preterm newborns were suctioned with the blue bulb syringe (15.6%), oral/nasal-pharyngeal suction device (42.7%), and endotracheal suction devices (41.7%).Electronic medical records promote less detailed, narrative documentation and more point and click documentation. If electronic medical record systems are not designed to gather airway clearance indications, specifics about the procedure and the preterm newborn response to the procedure, evidence-based practice cannot be measured. More studies are needed to evaluate suction practices applied in the NICU setting.

INTRODUCTION: Radiation-induced cognitive decline (RICD) is a late effect of radiotherapy (RT) occurring in 30–50% of irradiated brain tumor survivors. In preclinical models, pioglitazone prevents RICD but there are little safety data on its use in non-diabetic patients. We conducted a dose-escalation trial to determine the safety of pioglitazone taken during and after brain irradiation. METHODS: We enrolled patients > 18 years old with primary or metastatic brain tumors slated to receive at least 10 treatments of RT (≤ 3 Gy per fraction). We evaluated the safety of pioglitazone at 22.5 mg and 45 mg with a dose-escalation phase and dose-expansion phase. Pioglitazone was taken daily during RT and for 6 months after. RESULTS: 18 patients with a mean age of 54 were enrolled between 2010 and 2014. 14 patients had metastatic brain tumors and were treated with whole brain RT. Four patients had primary brain tumors and received partial brain RT and concurrent chemotherapy. No DLTs were identified. In the dose-escalation phase, there were only three instances of grade ≥ 3 toxicity: one instance of neuropathy in a patient receiving 22.5 mg, one instance of fatigue in a patient receiving 22.5 mg and one instance of dizziness in a patient receiving 45 mg. The attribution in each of these cases was considered “possible.” In the dose-expansion phase, nine patients received 45 mg and there was only one grade 3 toxicity (fatigue) possibly attributable to pioglitazone. CONCLUSION: Pioglitazone was well tolerated by brain tumor patients undergoing RT. 45 mg is a safe dose to use in future efficacy trials.

Background The management of potentially resectable stage III non-small cell lung carcinoma (NSCLC) is controversial. Options include induction chemotherapy or induction chemoradiation followed by resection, or chemoradiation without surgery. No trial has compared the outcomes of induction chemoradiation using different radiation doses. We reviewed our experience involving patients with clinical stage III disease treated with trimodality therapy involving two radiation strategies to determine the response rates, operative results, recurrence patterns, and long-term survival. Methods A retrospective review was made of consecutive stage III NSCLC patients treated from 2004 to 2011. Results Fifty-two patients with clinical stage IIIa NSCLC were treated with trimodality therapy. Eighteen patients were treated to doses of 60 Gy or higher, and 34 to lower doses (45, 50, or 54 Gy). There were significantly more postoperative complications in the higher radiation group ( p p = 0.016) and mediastinal nodal clearance (75% versus 42%, p = 0.254) rates were also higher in the high-dose group. That did not, however, translate into better disease-free and overall survival rates. Importantly, long-term noncancer mortality was significantly higher after higher dose preoperative radiation therapy. Conclusions In this series of patients with clinical stage IIIa NSCLC treated with trimodality therapy, a higher dose of preoperative radiation therapy resulted in better response rates but that did not translate to better cancer-specific survival. Of significance, we observed a notably higher delayed noncancer mortality in the high-dose group.

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

Purpose To test the hypothesis that quantifying swallow function with multiple patient-reported outcome (PRO) instruments is an important strategy to yield insights in the development of personalized deintensified therapies seeking to reduce the risk of head and neck cancer (HNC) treatment–related dysphagia (HNCTD). Methods and Materials Irradiated HNC subjects seen in follow-up care (April 2015 to December 2015) who prospectively completed the Sydney Swallow Questionnaire (SSQ) and the MD Anderson Dysphagia Inventory (MDADI) concurrently on the web interface to our Oncospace database were evaluated. A correlation matrix quantified the relationship between the SSQ and MDADI. Machine-learning unsupervised cluster analysis using the elbow criterion and CLUSPLOT analysis to establish its validity was performed. Results We identified 89 subjects. The MDADI and SSQ scores were moderately but significantly correlated (correlation coefficient −0.69). K-means cluster analysis demonstrated that 3 unique statistical cohorts (elbow criterion) could be identified with CLUSPLOT analysis, confirming that 100% of variances were accounted for. Correlation coefficients between the individual items in the SSQ and the MDADI demonstrated weak to moderate negative correlation, except for SSQ17 (quality of life question). Conclusions Pilot analysis demonstrates that the MDADI and SSQ are complementary. Three unique clusters of patients can be defined, suggesting that a unique dysphagia signature for HNCTD may be definable. Longitudinal studies relying on only a single PRO, such as MDADI, may be inadequate for classifying HNCTD.

Our objective was to explore the hypothesis that the risk of leptomeningeal dissemination (LMD) in patients who underwent stereotactic radiosurgery (SRS) for brain metastases is influenced by the site of the primary cancer, the addition of whole brain radiation therapy (WBRT), surgical resection, and control over their sys- temic disease. We conducted a retrospective cohort ana- lysis of 805 patients who were treated with SRS for brain metastases between 1999 and 2012 at the Wake Forest Baptist Medical Center, and excluded all patients with evidence of LMD before SRS. The primary outcome was LMD. Forty-nine of 795 patients developed LMD with a cumulative incidence of 6.2 % (95 % Confidence Interval (CI), 4.7-8.0). Median time from SRS to LMD was 7.4 months (Interquartile Range (IQR), 3.3-15.4). A colorectal primary site (Hazard Ratio (HR), 4.5; 95 % CI 2.5-8.0; p \ 0.0001), distant brain failure (HR, 2.0; 95 % CI 1.2-3.2; p = 0.007), breast primary site (HR, 1.6; 95 % CI 1.0-2.7; p = 0.05), the number of intracranial metas- tases at time of initial SRS (HR, 1.1; 95 % CI 1.0-1.2; p = 0.02), and age (by 5-year interval) (HR, 0.9; 95 % CI 0.8, 0.9; p = 0.0006) were independent factors associated with LMD. There was no evidence that surgical resection before SRS altered the risk of LMD (HR, 1.1; 95 % CI 0.6-2.0, p = 0.78). In patients who underwent SRS for brain metastases, a colorectal or breast primary site, distant brain failure, younger age, and an increased number of intracranial metastases were independently associated with LMD. Given its relative rarity as an outcome, multi-insti- tutional prospective studies will likely be necessary to validate and quantify these relationships.

The international growth of cancer and lack of available treatment is en route to become a global crisis. With >60% of cancer patients needing radiation therapy at some point during their treatment course, the lack of available facilities and treatment programs worldwide is extremely problematic. The number of deaths from treatable cancers is projected to increase to 11.5 million deaths in 2030 because the international population is aging and growing. In this review, we present how best to answer the need for radiation therapy facilities from a technical standpoint. Specifically, we examine whether cobalt teletherapy machines or megavoltage linear accelerator machines are best equipped to handle the multitudes in need of radiation therapy treatment in the developing world.

CMX001, a lipophilic nucleotide analog formed by covalently linking 3-(hexdecyloxy)propan-1-ol to cidofovir (CDV), is being developed as a treatment for smallpox. In the absence of human cases of smallpox, new treatments must be tested for efficacy in animal models. Previously, we demonstrated the efficacy of CMX001 in protecting New Zealand White rabbits from mortality following intradermal infection with rabbitpox virus as a model for smallpox, monkeypox and for treatment of adverse reactions to smallpox vaccination. Here we extend these studies by exploring different dosing regimens and performing randomized, blinded, placebo-controlled studies. In addition, because rabbitpox virus can be transmitted via naturally generated aerosols (animal to animal transmission), we report on studies to test the efficacy of CMX001 in protecting rabbits from lethal rabbitpox virus disease when infection occurs by animal to animal transmission. In all cases, CMX001 treatment was initiated at the onset of observable lesions in the ears to model the use of CMX001 as a treatment for symptomatic smallpox. The results demonstrate that CMX001 is an effective treatment for symptomatic rabbitpox virus infection. The rabbitpox model has key similarities to human smallpox including an incubation period, generalized systemic disease, the occurrence of lesions which may be used as a trigger for initiating therapy, and natural animal to animal spread, making it an appropriate model.

Spongiform degeneration is characterized by vacuolation in nervous tissue accompanied by neuronal death and gliosis. Although spongiform degeneration is a hallmark of prion diseases, this pathology is also present in the brains of patients suffering from Alzheimer’s disease, diffuse Lewy body disease, human immunodeficiency virus (HIV) infection, and Canavan’s spongiform leukodystrophy. The shared outcome of spongiform degeneration in these diverse diseases suggests that common cellular mechanisms must underlie the processes of spongiform change and neurodegeneration in the central nervous system. Immunohistochemical analysis of brain tissues reveals increased ubiquitin immunoreactivity in and around areas of spongiform change, suggesting the involvement of ubiquitin–proteasome system dysfunction in the pathogenesis of spongiform neurodegeneration. The link between aberrant ubiquitination and spongiform neurodegeneration has been strengthened by the discovery that a null mutation in the E3 ubiquitin–protein ligase mahogunin ring finger-1 (Mgrn1) causes an autosomal recessively inherited form of spongiform neurodegeneration in animals. Recent studies have begun to suggest that abnormal ubiquitination may alter intracellular signaling and cell functions via proteasome-dependent and proteasome-independent mechanisms, leading to spongiform degeneration and neuronal cell death. Further elucidation of the pathogenic pathways involved in spongiform neurodegeneration should facilitate the development of novel rational therapies for treating prion diseases, HIV infection, and other spongiform degenerative disorders.

BACKGROUND AND OBJECTIVE:Central venous catheters in the NICU are associated with significant morbidity and mortality because of the risk of central line–associated bloodstream infections (CLABSIs). The purpose of this study was to determine the effect of catheter dwell time on risk of CLABSI.METHODS:Retrospective cohort study of 13 327 infants with 15 567 catheters (93% peripherally inserted central catheters [PICCs], 7% tunneled catheters) and 256 088 catheter days cared for in 141 NICUs. CLABSI was defined using National Health Surveillance Network criteria. We defined dwell time as the number of days from line insertion until either line removal or day of CLABSI. We generated survival curves for each week of dwell time and estimated hazard ratios for CLABSI at each week by using a Cox proportional hazards frailty model. We controlled for postmenstrual age and year, included facility as a random effect, and generated separate models by line type.RESULTS:Median postmenstrual age was 29 weeks (interquartile range 26–33). The overall incidence of CLABSI was 0.93 per 1000 catheter days. Increased dwell time was not associated with increased risk of CLABSI for PICCs. For tunneled catheters, infection incidence was significantly higher in weeks 7 and 9 compared with week 1.CONCLUSIONS:Clinicians should not routinely replace uninfected PICCs for fear of infection but should consider removing tunneled catheters before week 7 if no longer needed. Additional studies are needed to determine what daily maintenance practices may be associated with decreased risk of infection, especially for tunneled catheters.