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Image guidance is used to improve the accuracy of radiation therapy delivery but results in increased dose to patients. This is of particular concern in children who need be treated per Pediatric Image Gently Protocols due to long-term risks from radiation exposure. The purpose of this study is to design a deep neural network architecture and loss function for improving soft-tissue contrast and preserving small anatomical features in ultra-low-dose cone-beam CTs (CBCT) of head and neck cancer (HNC) imaging.A 2D compound U-Net architecture (modified U-Net++) with different depths was proposed to enhance the network capability of capturing small-volume structures. A mask weighted loss function (Mask-Loss) was applied to enhance soft-tissue contrast. Fifty-five paired CBCT and CT images of HNC patients were retrospectively collected for network training and testing. The output enhanced CBCT images from the present study were evaluated with quantitative metrics including mean absolute error (MAE), signal-to-noise ratio (SNR), and structural similarity (SSIM), and compared with those from the previously proposed network architectures (U-Net and wide U-Net) using MAE loss functions. A visual assessment of ten selected structures in the enhanced CBCT images of each patient was performed to evaluate image quality improvement, blindly scored by an experienced radiation oncologist specialized in HN cancer.All the enhanced CBCT images showed reduced artifactual distortion and image noise. U-Net++ outperformed the U-Net and wide U-Net in terms of MAE, contrast near structure boundaries, and small structures. The proposed Mask-Loss improved image contrast and accuracy of the soft-tissue regions. The enhanced CBCT images predicted by U-Net++ and Mask-Loss demonstrated improvement compared to the U-Net in terms of average MAE (52.41 vs 42.85 HU), SNR (14.14 vs 15.07 dB), and SSIM (0.84 vs 0.87), respectively (The proposed network architecture and loss function effectively improved image quality in soft-tissue contrast, organ boundary, and small structure preservation for ultra-low-dose CBCT following Image Gently Protocol. This method has potential to provide sufficient anatomical representation on the enhanced CBCT images for accurate treatment delivery and potentially fast online-adaptive re-planning for HN cancer patients.

BACKGROUND: Survivors of aneurysmal subarachnoid hemorrhage (SAH) face a protracted intensive care unit (ICU) course and are at risk for developing refractory hydrocephalus with the need for a permanent ventriculoperitoneal shunt (VPS). Management of the external ventricular drain (EVD) used to provide temporary cerebrospinal fluid diversion may influence the need for a VPS, ICU length of stay (LOS), and drain complications, but the optimal EVD management approach is unknown. Therefore, we sought to determine the effect of EVD discontinuation strategy on VPS rate. METHODS: This was a prospective multicenter observational study at six neurocritical care units in the United States. The target population included adults with suspected aneurysmal SAH who required an EVD. Patients were preassigned to rapid or gradual EVD weans based on their treating center. The primary outcome was the rate of VPS placement. Secondary outcomes were EVD duration, ICU LOS, hospital LOS, and drain complications. RESULTS: A rapid EVD wean protocol was associated with a lower rate of VPS placement, including a delayed post-hospitalization shunt, in an adjusted Cox proportional analysis (hazard ratio 0.52 [p = 0.041]) and adjusted logistic regression model (odds ratio 0.43 [95% confidence interval 0.18–1.03], p = 0.057). A rapid wean was also associated with 2.1 fewer EVD days (p = 0.007) and saved an estimated 2.5 ICU days (p = 0.049), as compared with a gradual wean protocol. There were fewer nonfunctioning EVDs in the rapid group (odds ratio 0.32 [95% confidence interval 0.11–0.92]). Furthermore, we found that the time to first wean and the number of weaning attempts were important independent covariates that affected the likelihood of receiving a VPS and the duration of ICU admission. CONCLUSIONS: A rapid EVD wean was associated with decreased rates of VPS placement, decreased ICU LOS, and decreased drain complications in survivors of aneurysmal SAH. These findings suggest that a randomized multicentered controlled study comparing rapid vs. gradual EVD weaning protocols is justified.

Christian Theology is a discipline that seeks to reflect and interpret God’s revelation in Jesus Christ and this interpretation is based on and for the faith community. In the early stages, the Christian theology in India had reflected the Hindu religious philosophies and practices. It is also translated Christian faith into the terminology of Hindu philosophical system which is based on Advaita, Dwaita and Visistadwaita, Bhakti and various Margas ideologies. Hence, the Indian Christian theology directly or indirectly fully influenced by these above philosophical ideologies and articulated accordingly. These approaches have been developed and continued up to the end of 1960s.[1] Since then Indian Christian Theology has been changing. One of the major tasks of theology is to interpret the person and work of Jesus Christ. The challenges for theology are to re-interpret the meaning of Jesus to the given context as a result, that the meaning of theology will impact the communities. Interpreting theology requires a committed encounter with the context because it is the context which becomes the locus of the theological reflection. The hallmark trends of today’s context are the awareness of one’s own identity and this awareness definitely shapes theology. Hence the present modern trends in Indian Christian theology are people-centered, praxis-oriented, contextual and liberative in natural.[2] Here in this article, I would like to bring out some important trends in Christian Theology in general and followed by trends and modern trends in Indian Christian Theology in particular. &nbsp

Purpose To examine associations between physiologic stress and delirium in the setting of a direct neurologic injury. Materials and methods We obtained initial neutrophil-to-lymphocyte ratio (NLR), glucose, and troponin in consecutive non-comatose patients with non-traumatic intracerebral hemorrhage (ICH) over 1 year, then used multivariable regression models to determine associations between each biomarker and incident delirium. Delirium diagnoses were established using DSM-5-based methods, with exploratory analyses further categorizing delirium as first occurring 24 h after presentation (“later-onset”). Results Of 284 patients, delirium occurred in 55% (early-onset: 39% [n = 111]; later-onset: 16% [n = 46]). Patients with delirium had higher NLR (mean 9.0 ± 10.4 vs. 6.4 ± 5.5; p = 0.01), glucose (mean 146.5 ± 59.6 vs. 129.9 ± 41.4 mg/dL; p = 0.008), and a higher frequency of elevated troponin (>0.05 ng/mL; 21% vs. 10%, p = 0.02). In adjusted models, elevated NLR (highest quartile: OR 3.4 [95% CI 1.5–7.8]), glucose (>180 mg/dL: OR 3.1 [95% CI 1.1–8.2]), and troponin (OR 3.0 [95% CI 1.2–7.2]) were each associated with delirium, but only initial NLR was specifically associated with later-onset delirium and with delirium in non-mechanically ventilated patients. Conclusions Stress-related biomarkers corresponding to multiple organ systems are associated with ICH-related delirium. Early NLR elevation may also predict delayed-onset delirium, potentially implicating systemic inflammation as a contributory delirium mechanism.

Background An increasing white blood cell (WBC) count in early course of aneurysmal subarachnoid hemorrhage (SAH) can indicate a systemic inflammatory state triggered by the initial insult. We sought to determine the significance of the early WBC trend as a potential predictor of outcomes. Methods We analyzed a cohort of consecutive patients with aneurysmal SAH. The WBC values in first 5 days of admission, plus relevant clinical and imaging data, and modified Rankin Scale (mRS) at 3 months after hospital discharge were retrieved and analyzed. Favorable outcome was defined as mRS 0–3. The association between WBC counts and outcomes including mRS and delayed cerebral ischemia (DCI) was determined using binary logistic regression models. We used receiver operating characteristic curve analysis to assess accuracy of WBC in predicting outcomes. Results We included 167 patients in final analysis. Mean age was 56.4 (standard deviation [SD] 14.8) years, and 65% (109) of patients were female. Peak WBC was greater in patients with poor functional outcome (mean 17 × 109 cells/L, SD 6.4 vs. 13.5 × 109 cells/L SD 4.7). Combining peak WBC with modified Fisher scale slightly increased accuracy in predicting DCI (area under the curve 0.670, 95% confidence interval 0.586–0.755) compared with each component alone. Conclusions WBC count in the early course of SAH may have prognostic values in predicting DCI and functional outcome. WBC count monitoring may be used in conjunction with other clinical and radiographic tools to stratify patients with SAH into high- and low-risk groups to tailor neuromonitoring and treatment strategies.

Traumatic brain injury (TBI) is of significant concern in the realm of high impact contact sports, including mixed martial arts (MMA). Extracellular vesicles (EVs) travel between the brain and oral cavity and may be isolated from salivary samples as a noninvasive biomarker of TBI. Salivary EVs may highlight acute neurocognitive or neuropathological changes, which may be particularly useful as a biomarker in high impact sports. Pre and post-fight samples of saliva were isolated from 8 MMA fighters and 7 from controls. Real-time PCR of salivary EVs was done using the TaqMan Human Inflammatory array. Gene expression profiles were compared pre-fight to post-fight as well as pre-fight to controls. Largest signals were noted for fighters sustaining a loss by technical knockout (higher impact mechanism of injury) or a full match culminating in referee decision (longer length of fight), while smaller signals were noted for fighters winning by joint or choke submission (lower impact mechanism as well as less time). A correlation was observed between absolute gene information signals and fight related markers of head injury severity. Gene expression was also significantly different in MMA fighters pre-fight compared to controls. Our findings suggest that salivary EVs as a potential biomarker in the acute period following head injury to identify injury severity and can help elucidate pathophysiological processes involved in TBI.

Purpose Megavoltage radiotherapy to irregular superficial targets is challenging due to the skin sparing effect. We developed a three-dimensional bolus (3DB) program to assess the clinical impact on dosimetric and patient outcomes. Materials and Methods Planar commercial bolus (PCB) and 3DB density, clarity, and net bolus effect were rigorously evaluated prior to clinical implementation. After IRB approval, patients with cutaneous or locally advanced malignancies deemed to require bolus for radiotherapy treatment were treated with custom 3DB. Results The mean density of 3DB and PCB was of 1.07 g/cm 3 and 1.12 g/cm3, respectively. 3DB optic clarity was superior versus PCB at any material thickness. Phantom measurements of superficial dose with 3DB and PCB showed excellent bolus effect for both materials. 3DB reduced air gaps compared with PCB - particularly in irregular areas such as the ear, nose, and orbit. A dosimetric comparison of 3DB and PCB plans showed equivalent superficial homogeneity for 3DB and PCB (3DB median HI 1.249, range 1.111–1.300 and PCB median HI 1.165, range 1.094–1.279), but better conformity with 3DB (3DB median CI 0.993, range 0.962–0.993) versus PCB (PCB median CI 0.977, range 0.601–0.991). Patient dose measurements using 3DB confirm the delivered superficial dose was within 1% of the intended prescription (95% CI 97–102%; P = 0.11). Conclusions 3DB improves radiotherapy plan conformity, reduces air gap volume in irregular superficial areas which could affect superficial dose delivery, and provides excellent dose coverage to irregular superficial targets.

Purpose The study aimed to use quantitative geometric and dosimetric metrics to assess the accuracy of atlas‐based auto‐segmentation of masticatory muscles (MMs) compared to manual drawn contours for head and neck cancer (HNC) radiotherapy (RT). Materials and methods Fifty‐eight patients with HNC treated with RT were analyzed. Paired MMs (masseter, temporalis, and medial and lateral pterygoids) were manually delineated on planning computed tomography (CT) images for all patients. Twenty‐nine patients were used to generate the MM atlas. Using this atlas, automatic segmentation of the MMs was performed for the remaining 29 patients without manual correction. Auto‐segmentation accuracy for MMs was compared using dice similarity coefficients (DSCs), Hausdorff distance (HD), HD95, and variation in the center of mass (∆COM). The dosimetric impact on MMs was calculated (∆dose) using dosimetric parameters (D99%, D95%, D50%, and D1%), and compared with the geometric indices to test correlation. Results DSCmean ranges from 0.79 ± 0.04 to 0.85 ± 0.04, HDmean from 0.43 ± 0.08 to 0.82 ± 0.26 cm, HD95mean from 0.32 ± 0.08 to 0.42 ± 0.16 cm, and ∆COMmean from 0.18 ± 0.11 to 0.33 ± 0.23 cm. The mean MM volume difference was

Background Alpha-1 antitrypsin (AAT) is a potent anti-protease enzyme which may play a role in arterial wall stability. A variant of its encoding gene has been recently linked to ischemic stroke due to large artery atherosclerosis (LAA). We sought to explore potential relationships between ischemic stroke mechanisms, atherosclerosis burden and serum AAT levels. Methods We performed a prospective observational study of consecutive patients with acute ischemic stroke who were admitted to an academic comprehensive stroke center over a three-month period. Blood samples were collected within 24 h of hospital admission, and stroke subtype classification was determined based on modified TOAST criteria. Modified Woodcock scoring system was used to quantify calcification of major cervico-cranial arteries as a surrogate for atherosclerosis burden. Linear regression analysis was used to assess the association between serum AAT levels and calcification scores, both as continuous variables. Results Among eighteen patients met our inclusion criteria and were enrolled in our study, 10 patients (56%) were men; mean age was 66 (SD 12.5); median NIH stroke scale was 4 (IQR 9.5); 8 patients (44%) had stroke due to LAA. The median serum level of AAT was 140 mg/dl (IQR 41.7) for patients with LAA-related stroke, and 148.5 mg/dl (IQR 37.7) for patients with other stroke mechanisms (p = 0.26). Higher serum AAT levels was associated with lower modified Woodcock calcification scores. (p-value = 0.038) Conclusions Measurement of AAT levels in patients with acute stroke is feasible, and there may be associations between AAT levels and stroke mechanism that warrant further study in larger samples.

OBJECTIVEThere is variability and uncertainty about the optimal approach to the management and discontinuation of an external ventricular drain (EVD) after subarachnoid hemorrhage (SAH). Evidence from single-center randomized trials suggests that intermittent CSF drainage and rapid EVD weans are safe and associated with shorter ICU length of stay (LOS) and fewer EVD complications. However, a recent survey revealed that most neurocritical care units across the United States employ continuous CSF drainage with a gradual wean strategy. Therefore, the authors sought to determine the optimal EVD management approach at their institution.METHODSThe authors reviewed records of 200 patients admitted to their institution from 2010 to 2016 with aneurysmal SAH requiring an EVD. In 2014, the neurocritical care unit of the authors’ institution revised the internal EVD management guidelines from a continuous CSF drainage with gradual wean approach (continuous/gradual) to an intermittent CSF drainage with rapid EVD wean approach (intermittent/rapid). The authors performed a retrospective multivariable analysis to compare outcomes before and after the guideline change.RESULTSThe authors observed a significant reduction in ventriculoperitoneal (VP) shunt rates after changing to an intermittent CSF drainage with rapid EVD wean approach (13% intermittent/rapid vs 35% continuous/gradual, OR 0.21, p = 0.001). There was no increase in delayed VP shunt placement at 3 months (9.3% vs 8.6%, univariate p = 0.41). The intermittent/rapid EVD approach was also associated with a shorter mean EVD duration (10.2 vs 15.6 days, p < 0.001), shorter ICU LOS (14.2 vs 16.9 days, p = 0.001), shorter hospital LOS (18.2 vs 23.7 days, p < 0.0001), and lower incidence of a nonfunctioning EVD (15% vs 30%, OR 0.29, p = 0.006). The authors found no significant differences in the rates of symptomatic vasospasm (24.6% vs 20.2%, p = 0.52) or ventriculostomy-associated infections (1.3% vs 8.8%, OR 0.30, p = 0.315) between the 2 groups.CONCLUSIONSAn intermittent CSF drainage with rapid EVD wean approach is associated with fewer VP shunt placements, fewer complications, and shorter LOS compared to a continuous CSF drainage with gradual EVD wean approach. There is a critical need for prospective multicenter studies to determine if the authors’ experience is generalizable to other centers.

Background: Dysphagia is a complication following radziation therapy (RT) for head and neck cancers (HNC). Radiologic findings of posterior pharyngeal wall thickening (PPWT) after RT has not been q...

Three different morphologies of CeO2 supports (NP, NC, and NR) were prepared by hydrothermal method and further Mn2O3 is impregnated on CeO2 supports using wet-impregnation methods, and their activity for NO reduction using NH3-SCR technique is analysed. The prepared catalysts and supports are further characterized through scanning electron microscopy (SEM), Energy-dispersive X-ray spectroscopy (EDX), X-ray diffraction (XRD), X-ray Photoelectron Spectroscopy (XPS), and transmission electron microscopy (TEM), and Brunauer–Emmett–Teller (BET). The catalytic performance of Mn2O3/CeO2-NP has shown the highest conversion (76.06 %) compared to the other two catalysts in the temperature range of 50 - 450°C.

IntroductionAtraumatic convexity subarachnoid hemorrhage is a subtype of spontaneous subarachnoid hemorrhage that often presents a diagnostic challenge. Common etiologies include cerebral amyloid angiopathy, vasculopathies, and coagulopathy; however, aneurysm is rare. Given the broad differential of causes of convexity subarachnoid hemorrhage, we assessed the diagnostic yield of common tests and propose a testing strategy.MethodsWe performed a single-center retrospective study on consecutive patients with atraumatic convexity subarachnoid hemorrhage over a 2-year period. We obtained and reviewed each patient’s imaging and characterized the frequency with which each test ultimately diagnosed the cause. Additionally, we discuss clinical features of patients with convexity subarachnoid hemorrhage with respect to the mechanism of hemorrhage.ResultsWe identified 70 patients over the study period (mean (SD) age 64.70 (16.9) years, 35.7% men), of whom 58 patients (82%) had a brain MRI, 57 (81%) had non-invasive vessel imaging, and 27 (38.5%) underwent catheter-based angiography. Diagnoses were made using only non-invasive imaging modalities in 40 patients (57%), while catheter-based angiography confirmed the diagnosis in nine patients (13%). Further clinical history and laboratory testing yielded a diagnosis in an additional 17 patients (24%), while the cause remained unknown in four patients (6%).ConclusionThe etiology of convexity subarachnoid hemorrhage may be diagnosed in most cases via non-invasive imaging and a thorough clinical history. However, catheter angiography should be strongly considered when non-invasive imaging fails to reveal the diagnosis or to better characterize a vascular malformation. Larger prospective studies are needed to validate this algorithm.

Background and Purpose: Patients with ischemic stroke of cardioembolic origin are at risk of visceral (renal or splenic) infarction. We hypothesized that serum troponin level at time of ischemic stroke would be associated with presence of visceral infarction. Methods: Data were abstracted from a single center prospective stroke database over 18 months and included all patients with ischemic stroke who underwent contrast-enhanced computerized tomography (CT) of the abdomen and pelvis for clinical purposes within 1 year of stroke. The primary predictor was troponin concentration ≥.1ng/mL. The primary outcome was visceral infarct (renal and/or splenic) on CT abdomen and pelvis. Univariate and multivariable logistic regression models were used to estimate the odds ratio and 95% confidence intervals (OR, 95% CI) for the association of troponin with visceral infarction. Results: Of 1233 patients with ischemic stroke, 259 patients had a qualifying visceral CT. Serum troponin level on admission was measured in 237 of 259 patients (93.3%) and 41 of 237 (17.3%) had positive troponin. There were 25 patients with visceral infarcts: 16 renal, 7 splenic, and 2 both. In univariate models, patients with a positive troponin level (versus negative) were more likely to have visceral infarcts (39.1% [9/23] versus 15.0% [32/214], P = .008) and this association persisted in multivariable models (adjusted OR 3.83; 95% CI 1.42-10.31, P = .006). Conclusions: In ischemic stroke patients, elevated serum troponin levels may help identify patients with visceral infarcts. This suggests that troponin in the acute stroke setting is a biomarker of embolic risk. Larger studies with systematic visceral imaging are needed to confirm our findings.

Objectives Opioids are frequently used for analgesia in patients with acute subarachnoid hemorrhage (SAH) due to a high prevalence of headache and neck pain. However, it is unclear if this practice may pose a risk for opioid dependence, as long-term opioid use in this population remains unknown. We sought to determine the prevalence of opioid use in SAH survivors, and to identify potential risk factors for opioid utilization. Methods We analyzed a cohort of consecutive patients admitted with non-traumatic and suspected aneurysmal SAH to an academic referral center. We included patients who survived hospitalization and excluded those who were not opioid-naive. Potential risk factors for opioid prescription at discharge, 3 and 12 months post-discharge were assessed. Results Of 240 SAH patients who met our inclusion criteria (mean age 58.4 years [SD 14.8], 58% women), 233 (97%) received opioids during hospitalization and 152 (63%) received opioid prescription at discharge. Twenty-eight patients (12%) still continued to use opioids at 3 months post-discharge, and 13 patients (6%) at 12-month follow up. Although patients with poor Hunt and Hess grades (odds ratio 0.19, 95% CI 0.06–0.57) and those with intraventricular hemorrhage (odds ratio 0.38, 95% CI 0.18–0.87) were less likely to receive opioid prescriptions at discharge, we did not find significant differences between patients who had long-term opioid use and those who did not. Conclusion Opioids are regularly used in both the acute SAH setting and immediately after discharge. A considerable number of patients also continue to use opioids in the long-term. Opioid-sparing pain control strategies should be explored in the future.

The development of the endovascular thrombectomy (EVT) technique has revolutionized acute stroke management for patients with large vessel occlusions (LVOs). The impact of successful recanalization using an EVT on autoregulatory profiles is unknown. A more complete understanding of cerebral autoregulation in the context of EVT may assist with post-procedure hemodynamic optimization to prevent complications. We examined cerebral autoregulation in 107 patients with an LVO in the anterior circulation (proximal middle cerebral artery (M1/2) and internal cerebral artery (ICA) terminus) who had been treated using an EVT. Dynamic cerebral autoregulation was assessed at multiple time points, ranging from less than 24 hours to 5 days following last seen well (LSW) time, using transcranial Doppler ultrasound recordings and transfer function analysis. Complete (Thrombolysis in Cerebral Infarction (TICI) 3) recanalization was associated with a more favorable autoregulation profile compared with TICI 2b or poorer recanalization (p < 0.05), which is an effect that was present after accounting for differences in the infarct volumes. Less effective autoregulation in the first 24 h following the LSW time was associated with increased rates of parenchymal hematoma types 1 and 2 hemorrhagic transformations (PH1–PH2). These data suggest that patients with incomplete recanalization and poor autoregulation (especially within the first 24 h post-LSW time) may warrant closer blood pressure monitoring and control in the first few days post ictus.

Tumor cure with conventional fractionated radiotherapy is 65%, dependent on tumor cell-autonomous gradual buildup of DNA double-strand break (DSB) misrepair. Here we report that single-dose radiotherapy (SDRT), a disruptive technique that ablates more than 90% of human cancers, operates a distinct dual-target mechanism, linking acid sphingomyelinase-mediated (ASMase-mediated) microvascular perfusion defects to DNA unrepair in tumor cells to confer tumor cell lethality. ASMase-mediated microcirculatory vasoconstriction after SDRT conferred an ischemic stress response within parenchymal tumor cells, with ROS triggering the evolutionarily conserved SUMO stress response, specifically depleting chromatin-associated free SUMO3. Whereas SUMO3, but not SUMO2, was indispensable for homology-directed repair (HDR) of DSBs, HDR loss of function after SDRT yielded DSB unrepair, chromosomal aberrations, and tumor clonogen demise. Vasoconstriction blockade with the endothelin-1 inhibitor BQ-123, or ROS scavenging after SDRT using peroxiredoxin-6 overexpression or the SOD mimetic tempol, prevented chromatin SUMO3 depletion, HDR loss of function, and SDRT tumor ablation. We also provide evidence of mouse-to-human translation of this biology in a randomized clinical trial, showing that 24 Gy SDRT, but not 3×9 Gy fractionation, coupled early tumor ischemia/reperfusion to human cancer ablation. The SDRT biology provides opportunities for mechanism-based selective tumor radiosensitization via accessing of SDRT/ASMase signaling, as current studies indicate that this pathway is tractable to pharmacologic intervention.

Hypertension is a known risk factor for intracerebral hemorrhage (ICH), but it is unclear whether blood pressure (BP) at hospital arrival can be used to distinguish hypertensive ICH from non-hypertensive etiologies.We performed a single-center cohort study using data from consecutive ICH patients over 12 months. ICH characteristics including etiology were prospectively adjudicated by two attending neurologists. Using adjusted linear regression models, we compared first recorded systolic BPs (SBP) and mean arterial pressures (MAP) in patients with hypertensive vs. other ICH etiologies. We then used area under the ROC curve (AUC) analysis to determine the accuracy of admission BP in differentiating between hypertensive and non-hypertensive ICH.Of 311 patients in our cohort (mean age 70.6 ± 15.6, 50% male, 83% white), the most frequent ICH etiologies were hypertension (50%) and cerebral amyloid angiopathy (CAA; 22%). Mean SBP and MAP for patients with hypertensive ICH was 175.1 ± 32.9 mmHg and 120.4 ± 22.9 mmHg, respectively, compared to 156.4 ± 28.0 mmHg and 109.6 ± 20.3 mmHg in non-hypertensive ICH (p .001). Adjusted models showed that hypertensive ICH patients had higher BPs than those with CAA (mean SBP difference 10.7 mmHg [95% CI 0.8-20.5]; mean MAP difference 8.1 mmHg [1.1-15.0]) and especially patients with other non-CAA causes (mean SBP difference 23.9 mmHg [15.3-32.4]; mean MAP difference 14.5 mmHg [8.5-20.6]). However, on a patient-level, arrival BP did not reliably discriminate between hypertensive and non-hypertensive etiologies (AUC 0.660 [0.599-0.720]).Arrival BP differs between hypertensive and non-hypertensive ICH but should not be used as a primary determinant of etiology, as hypertension may be implicated in various subtypes of ICH.

Head and neck squamous cell carcinomas (HNSCCs) are malignancies that originate in the mucosal lining of the upper aerodigestive tract. Despite advances in therapeutic interventions, survival rates among HNSCC patients have remained static for years. Cancer stem cells (CSCs) are tumor-initiating cells that are highly resistant to treatment, and are hypothesized to contribute to a significant fraction of tumor recurrences. Consequently, further investigations of how CSCs mediate recurrence may provide insights into novel druggable targets. A key element of recurrence involves the tumor's ability to evade immunosurveillance. Recent published reports suggest that CSCs possess immunosuppressive properties, however, the underlying mechanism have yet to be fully elucidated. To date, most groups have focused on the role of CSC-derived secretory proteins, such as cytokines and growth factors. Here, we review the established immunoregulatory role of exosomes derived from mixed tumor cell populations, and propose further study of CSC-derived exosomes may be warranted. Such studies may yield novel insights into new druggable targets, or lay the foundation for future exosome-based diagnostics.

Management of head and neck cancer in the elderly patient is particularly challenging given the high morbidity associated with treatment. Surgery, radiotherapy, and chemotherapy have all been demonstrated as effective in older patients; however, older patients are more susceptible to treatment-induced toxicity, which can limit the survival benefits of certain interventions. This susceptibility is better associated with the presence of multiple comorbidities and decreasing functional status than with age alone. Screening tools allow for risk stratification, treatment deintensification, and even treatment avoidance in patients who are deemed at high-risk of being harmed by standard therapy.

PurposeDespite the strong interest in combining stereotactic ablative radiation therapy (SAR) with immunotherapy, limited data characterizing the systemic immune response after SAR are available. We hypothesized that the systemic immune responseto SAR would differ by irradiated site owing to inherent differences in the microenvironment of various organs.Methods and materialsPatients receiving SAR to any organ underwent prospective blood banking before and 1 to 2weeks after SAR. Peripheral blood mononuclear cells (PBMCs) and serum were isolated. PBMCs were stained with fluorophore-conjugated antibodies against T and natural killer (NK) cell markers. Cells were interrogated by flow cytometry, and the results were analyzed using FlowJo software. Serum cytokine and chemokine levels were measured using Luminex. We analyzed the changes from before to after therapy using paired t tests or 1-way analysis of variance (ANOVA) with Bonferroni's post-test.ResultsA total of 31 patients had evaluable PBMCs for flow cytometry and 37 had evaluable serum samples for Luminex analysis. The total number of NK cells andcytotoxic (CD56dimCD16+) NK cells decreased (P=.02) and T-cell immunoglobulin- and mucin domain-containing molecule-3-positive (TIM3+) NK cells increased (P=.04) after SAR to parenchymal sites (lung and liver) but not tobone or brain. The total memory CD4+ T cells, activated inducible co-stimulator-positive and CD25+CD4+ memory T cells, and activated CD25+CD8+ memory Tcells increased after SAR to parenchymal sites but not bone or brain. The circulating levels of tumor necrosis factor-α (P=.04) and multiple chemokines, including RANTES (P=.04), decreased after SAR to parenchymal sites but not bone or brain.ConclusionsOur data suggest SAR to parenchymal sites induces systemic immune changes, including a decrease in total and cytotoxic NK cells, an increase in TIM3+ NK cells, and an increase in activated memory CD4+ and CD8+ T cells. SAR to nonparenchymal sites did not induce these changes. By comparing the immune response after radiation to different organs, our data suggest SAR induces systemic immunologic changes that are dependent on the irradiated site.

Purpose To analyze functional outcomes for patients treated on a phase 2 trial of de-escalated chemoradiation therapy for human papillomavirus–positive oropharyngeal cancer. Methods and Materials Patient eligibility included p16-positive, stage III or IV oropharyngeal squamous cell carcinoma and a Zubrod performance status of 0 to 1. Treatment was induction chemotherapy with paclitaxel, 175 mg/m2, and carboplatin, area under the curve (AUC) of 6 mg/ml/min, for 2 cycles every 21 days, followed by concurrent paclitaxel, 30 mg/m2, every 7 days with dose-reduced radiation therapy of 54 or 60 Gy. Trends in body weight and body mass index (BMI) were analyzed with gastrostomy tube and narcotic use rates. Functional outcomes were assessed using the University of Washington Quality of Life Scale and the Functional Assessment of Cancer Therapy–Head and Neck Scale. Results Forty-five patients were registered, of whom 40 were evaluable. Only 1 patient had a BMI deemed unhealthy at the completion of treatment. For the 15 patients (38%) with a normal BMI (18-25 kg/m2) before treatment, recovery back to baseline occurred at approximately 18 months (average BMI, 23.2 kg/m2 vs 22.3 kg/m2; P=.09). In 2 patients (5%), gastrostomy tubes were placed during treatment. No patient was enteral feeding tube-dependent at 6 months after treatment. Ninety-five percent of patients tolerated a normal regular diet at last follow-up. Conclusions De-escalated chemoradiation therapy may improve functional outcomes as indicated by the relatively low incidence of gastrostomy tube placement and long-term dysphagia. In patients with a normal BMI prior to chemoradiation therapy, BMI recovered to baseline levels.

Background The current study represents a subset analysis of quality-of-life (QOL) outcomes among patients treated on a phase 2 trial of de-escalated chemoradiation for human papillomavirus (HPV)-associated oropharyngeal cancer. Methods Eligibility included newly diagnosed, (American Joint Committee on Cancer, 7th edition) stage III or IV oropharyngeal squamous cell carcinoma, p16 positivity, age ≥ 18 years, and a Zubrod performance status of 0 to 1. Treatment was induction paclitaxel at a dose of 175 mg/m2 and carboplatin at an area under the curve of 6 for 2 cycles followed by response-adapted, dose-reduced radiation of 54 Gy or 60 Gy with weekly concurrent paclitaxel at a dose of 30 mg/m2 . The University of Washington Quality of Life (UW-QOL) and the Functional Assessment of Cancer Therapy-Head and Neck questionnaires were used to assess patient-reported QOL as a secondary endpoint. Results A total of 45 patients were registered, 40 of whom completed QOL surveys and were evaluable. Nadirs for overall UW-QOL and Functional Assessment of Cancer Therapy-Head and Neck scores were reached at 4 weeks after treatment but returned to baseline at 3 months. Nearly all functional indices returned to baseline levels by 6 to 9 months. The mean overall UW-QOL score was 71.6 at baseline compared with 70.8, 73.0, 83.3, and 81.1, respectively, at 3 months, 6 months, 1 year, and 2 years after therapy. The percentage of patients rating their overall QOL as "very good" or "outstanding" at 6 months, 1 year, and 2 years using the UW-QOL was 50%, 77%, and 84%, respectively. Conclusions This de-escalation regimen achieved QOL outcomes that were favorable compared with historical controls. These results serve as powerful evidence that ongoing de-escalation efforts lead to tangible gains in function and QOL. Cancer 2018;124:521-9. © 2017 American Cancer Society.

BACKGROUND: We conducted a phase II multi-center trial of induction chemotherapy followed by response-adapted, dose-reduced radiation therapy with radiosensitizing chemotherapy for patients with locally advanced, human papillomavirus (HPV)-associated squamous cell carcinoma of the oropharynx. The aim of this study was to determine the progression-free survival for patients treated using this de-escalated approach to determine its worthiness for further investigation in a phase III setting. METHODS: Eligible patients presented with newly diagnosed, biopsy-proven stage III or IV squamous cell carcinoma of the oropharynx, p16-positivity, and Zubrod performance status 0 to 1. Smoking history was not used as a criterion for eligibility. Treatment was induction paclitaxel 175 mg/m2 and carboplatin area under the concentration-time curve (AUC) 6 for two cycles every 21 days followed by dose-reduced radiation of 54 Gy or 60 Gy for responders and non-responders, respectively, with weekly paclitaxel 30 mg/m2. Intensity-modulated radiotherapy with daily image-guidance was required. The primary endpoint was 2-year progression-free survival as determined by per protocol analysis. This study is registered with ClinicalTrials.gov, numbers NCT02048020 and NCT01716195. FINDINGS: Between October 4, 2012 and March 3, 2015, forty-five patients (26 tonsil; 19 base of tongue) were registered, of which 44 were analyzable. Median age was 60 years old (IQR, 54 to 67). Sixty-nine percent of the patients were lifelong never smokers. Twenty-four patients (55%) exhibited a complete or partial response to induction chemotherapy; twenty patients (45%) had a less than partial response to induction chemotherapy. With a median follow up of 30 months (IQR, 26 to 37 months), three (7%) of 44 patients developed local-regional recurrence and another distant metastasis, yielding a 2-year progression-free survival of 92%. The most commonly observed grade 3+ toxicity was leukopenia (17 patients) with the most common grade 3+ non-hematologic toxicities being dysphagia (4 patients) and mucositis (4 patients). Seventeen (39%) of 44 patients and nine (20%) of 44 patients developed any grade 3+ and non-hematologic grade 3+ toxicity, respectively, during protocol therapy.. The proportion who were gastrostomy-tube dependent at 3- and 6-months post-therapy was 2% (1 of 44 patients) and 0%, respectively. INTERPRETATION: The rates of disease control demonstrated with this de-escalation regimen for patients with locally advanced, HPV-associated oropharyngeal carcinoma were comparable to those of historical controls treated by standard dose chemoradiotherapy regimens. Additionally, long-term side effects appeared to be reduced. By decreasing toxicity while maintaining cure rates, de-escalation of radiation dose has the potential to improve the therapeutic ratio and optimize long-term function for patients with a disease that is rapidly increasing in incidence.

Objective Cutaneous squamous cell carcinoma (CSCC) is one of the most common malignancies worldwide. With advanced CSCC of the head and neck, there is conflicting evidence on what constitutes high-risk disease. Our objective is to evaluate which factors are predictive of recurrence and nodal spread and survival. Study Design Case series with chart review. Setting Tertiary academic institution. Subjects and Methods Patients with advanced head and neck CSCC treated with primary resection identified by chart review. Results A total of 212 patients met inclusion criteria, with a mean age of 70.4 years; 87.3% were men. Mean tumor diameter was 3.65 cm, with an average depth of invasion of 1.38 cm. The mean follow-up time was 35 months (median, 21.5), and over that period 67 recurrences were recorded, 49 of which were local. The 5-year Kaplan-Meier estimate of disease-free survival for the cohort was 53.2%. On Cox multivariate analysis, recurrent disease, perineural invasion (PNI), and poorly differentiated histology were independent predictors of recurrence. On multinomial logistic regression, patients with primary tumors on the ear, cheek, temple, or lip, as well as those with PNI, were more likely to present with nodal metastasis. Conclusion For advanced CSCCs of the head and neck, patients with recurrent disease, PNI, and poorly differentiated tumors are at highest risk for local recurrence. Patients with tumors or the ear, cheek, temple, or lip, as well as those with PNI, are at increased risk of harboring nodal disease.

Introduction: Carotid web is a putative mechanism of cryptogenic ischemic stroke. We aimed to determine the prevalence of carotid web based on assigned stroke mechanism, and hypothesized that carotid webs would be found more frequently in younger cryptogenic stroke patients. Methods: We performed a single-center retrospective cohort study using institutional registry data from consecutive patients with confirmed anterior circulation ischemic stroke between July 2015-September 2017. We reviewed all available computed tomography angiogram (CTA) studies of the neck, and excluded patients who did not have a high-quality CTA of the neck performed. Carotid web was defined as a thin shelf of non-calcified tissue protruding into the lumen of the internal carotid artery immediately distal to the bifurcation, best visualized on sagittal oblique imaging and evident as a small septum on axial imaging. Stroke subtype was adjudicated a priori using validated methods, and we compared relevant risk factors in patients with cryptogenic stroke with and without carotid web. Results: We identified 882 patients with anterior circulation stroke who had a CTA neck available for review (49.3% male, 30% cryptogenic). A total of 7 patients (0.8%) were found to have carotid webs, of which 4 were ipsilateral to a patient’s stroke; all patients with ipsilateral carotid webs were adjudicated to have cryptogenic stroke. Patients with carotid web were younger than other patients in our cohort (age 49.0±14.6 vs. 72.2±14.9 years, p=0.003), and none of them had a history of hypertension (0% vs. 72%, p=0.04). In patients with cryptogenic stroke, overall prevalence of carotid webs was 1.5%, but the prevalence was significantly higher in younger cryptogenic stroke patients (age Discussion: Carotid web may represent an under-recognized occult mechanism of cryptogenic stroke, particularly amongst younger patients.

Background: Delays in medical care are known to be associated with worse outcomes in ischemic stroke, but outcomes in patients with intracerebral hemorrhage (ICH) and delayed presentation are unclear. We aimed to determine factors associated with prolonged delays from ICH symptom onset to hospital presentation and implications for long-term outcomes. Methods: We performed a single-center cohort study using data from consecutive ICH patients over 12 months. ICH characteristics and outcomes were prospectively collected, while time of symptom onset (or last-known-well) and emergency department arrival were retrospectively abstracted. We calculated time-to-arrival and defined prolonged delay as >24 hours. Using multivariable logistic regression, we determined factors associated with prolonged delays to presentation, then determined associations with unfavorable 3-month outcomes (modified Rankin Scale [mRS] 4-6) after adjusting for demographics and ICH severity. Results: Of 299 patients with out-of-hospital ICH, 21% (n=62) presented >24 hours from symptom onset; median time-to-arrival was 5.5 hours (IQR 1.2-17.8). There were not significant differences in age (mean 71.9±14.0 vs. 70.4±16.0, p=0.50), sex (48% vs. 50% male, p=0.80), race (89% vs. 82% white, p=0.22), or ICH size (mean 15.5±23.2 vs. 20.5±27.4cc, p=0.19) between patients presenting >24 hours and Conclusions: Outcomes in ICH patients with prolonged delays to presentation differ from those who present earlier. ICH severity in such patients may not be accurately captured by established predictors, and prognostication models should therefore account for inherent survivorship bias.

Background: Delirium occurs frequently in patients with intracerebral hemorrhage (ICH), though its pathogenesis may be multifactorial. Given the potential role of systemic stressors in delirium, we aimed to explore differences in commonly measured markers of physiologic stress between delirious and non-delirious ICH patients. Methods: We performed a single-center cohort study using data from consecutive non-comatose ICH patients over 12 months. ICH and patient characteristics were prospectively collected, and the presence of delirium at any point during hospitalization was diagnosed based on DSM-5 criteria. We retrospectively abstracted admission laboratory values and selected three common markers of physiologic stress for comparison: neutrophil-lymphocyte ratio (NLR), troponin, and glucose. Using multivariable models adjusted for demographics, relevant comorbidities, and ICH severity, we determined associations between delirium and the following: NLR, using linear regression; elevated troponin (>0.05 ng/mL), using binary logistic regression; and elevated glucose (categorized as 130-180 or >180 mg/dL), using ordered logistic regression. Results: Of 284 ICH patients in our cohort, 55% (n=157) had delirium. Patients with delirium were not significantly older than non-delirious patients (mean age 71.7±16.2 vs. 68.3±15.1, p=0.07), but had larger ICH volumes (mean 23.3±24.6 vs. 7.0±10.6 cc, p Conclusions: Delirium after ICH is independently associated with elevated serum markers of physiologic stress, suggesting that systemic factors may be implicated in delirium pathogenesis.

Introduction: Spontaneous intracerebral hemorrhage (ICH) most commonly arises due to primary etiologies such as hypertensive or cerebral amyloid angiopathy (CAA), but may also occur due to underlying secondary causes such as vascular malformations or intracranial neoplasms. However, focal mass effect may potentially obscure underlying lesions on neuroimaging performed during the acute phase of ICH, and follow-up imaging is often recommended. We sought to determine the yield of interval magnetic resonance imaging (MRI) in identifying cryptogenic ICH etiologies. Methods: We performed a single-center descriptive cohort study of consecutive patients enrolled in an institutional ICH registry over 12 months. ICH features including etiology and acute neuroimaging were prospectively adjudicated, while planned interval follow-up imaging was retrospectively reviewed. We determined the frequency of newly-discovered findings on interval MRI, and classified new findings according to whether or not they contributed meaningfully to patient management. Results: There were 241 ICH patients in our cohort who survived to discharge and did not have MRI-incompatible devices; 44 had planned follow-up imaging and 33 ultimately completed a follow-up MRI. Mean interval between initial and follow-up MRI was 61 (±34) days. New findings were identified in 33% of follow-up cases (11/33), with changes in patient management occurring in 12% (4/33). Age (59.4 vs. 61.5, p=0.74), sex (45% vs. 45% male, p>0.99), and secondary ICH score (median 3 [IQR 2-3] vs. 3 [1-4], p=0.87) were not significantly different between patients who had new findings and those who did not. New findings included cavernoma (n=4; 1 underwent resection), CAA-related changes (n=3), intracranial malignancy (n=2; 1 transitioned to hospice care, 1 led to cancer workup), new embolic stroke (n=1, underwent extended cardiac monitoring), and demyelination (n=1). Conclusions: Interval MRI aided in diagnosing ICH etiology in one-third of patients who received one, though few cases led to direct actionable changes in patient management.

Background: Intracerebral hemorrhage (ICH) often carries cardiac implications, and serum troponin has been suggested as a predictive biomarker for patients with ICH and other stroke subtypes. We aimed to determine whether previously described associations between troponin and worse outcomes in ICH patients varied based on the presence of atrial fibrillation (AF). Methods: We performed a single-center cohort study using data from consecutive ICH patients admitted over 12 months. ICH characteristics and 3-month outcomes were prospectively collected, while admission troponin levels were retrospectively abstracted. We performed ordinal and binary logistic regression to determine associations between elevated troponins (>0.05 ng/mL) and 3-month outcomes (using the modified Rankin Scale [mRS]), with multivariable models adjusted for relevant demographics, ICH severity, and comorbidities including AF, anticoagulation use, coronary artery disease (CAD), and chronic kidney disease (CKD). An interaction variable combining elevated troponin and AF was also included in our models. Results: Of 261 ICH patients with troponin measured on admission, 17% (n=44) had elevated troponins. Patients with elevated troponins were not significantly older than patients with normal troponin levels (mean age 74.8±13.6 vs. 70.4±15.4, p=0.08), but were more likely to have AF (36% vs. 21%, p=0.03), CAD (32% vs. 15%, p=0.007), and CKD (16% vs. 5%, p=0.006); ICH size, location, and other predictors were not significantly different between groups. In adjusted models, neither elevated troponin nor AF were independently associated with worse outcomes. However, the interaction between the two was significant (p=0.003), and the presence of elevated admission troponin in the context of AF was significantly associated with worse outcomes (ordinal: common OR 9.8 [95% CI 2.0-47.8]; binary (mRS 4-6): OR 14.4 [95% CI 1.9-106.4]). Conclusions: Troponin may be a useful predictive biomarker in ICH patients with underlying AF, potentially signaling higher levels of cardiac and systemic stress in patients with lower cardiac reserve.

Background: Headache and neck pain are common in patients with aneurysmal subarachnoid hemorrhage (aSAH) throughout their course. Because pain is often a sequela, these patients are at risk for opioid dependence. Long term opioid use has not been well studied in this population. Methods: We analyzed a cohort of consecutive patients who were admitted with diagnosis of aSAH to an academic referral center from 2015 to 2018. We excluded patients who died during hospitalization or were discharged to hospice or were previously taking any opioids. The following variables were collected: demographics, any opioid use during hospitalization, short-term low-dose steroid use (mostly for headache management but some cases for immediate post craniotomy for aneurysm clipping), opioid prescription at the time of discharge and 3-month or longer opioid use verified by pharmacy and any follow up out patient records. Results: Of 200 patients with aSAH, 144 patients (72%) met our inclusion criteria. Mean age was 58 years (SD 14.8); Ninety-four patients (65%) were women; All patients received opioids at some point during hospitalization but 66% (96/144) were discharged with opioid prescription. Of these, 31% (30/96) continued to use opioids at ≥3 months. The overall rate of chronic opioid use was 20% (30/144). The rate of opioid prescription at discharge was 72% (52/72) in patients who received short course steroids and 61% (44/72) in patients who did not receive steroids. (p=0.21; OR 2.6, 95% CI 0.82-3.3). Steroids did not prevent long term opioid use. (p=0.30; OR 0.6, 95% CI 0.26-1.3) Conclusion: Opioids are regularly used as the main treatment option for pain control in patients with aSAH. A noteworthy number of patients continue to use opioids beyond their initial hospitalization. Steroid use does not prevent long term opioid use in these patients. Non-opioid pain control strategies should be explored in the future.

ObjectiveTo determine the impact of delirium on withdrawal of life-sustaining treatment (WLST) after intracerebral hemorrhage (ICH) in the context of established predictors of poor outcome, using data from an institutional ICH registry.MethodsWe performed a single-center cohort study on consecutive patients with ICH admitted over 12 months. ICH features were prospectively adjudicated, and WLST and corresponding hospital day were recorded retrospectively. Patients were categorized using DSM-5 criteria as never delirious, ever delirious (either on admission or later during hospitalization), or persistently comatose. We determined the impact of delirium on WLST using Cox regression models adjusted for demographics and ICH predictors (including Glasgow Coma Scale score), then used logistic regression with receiver operating characteristic curve analysis to compare the accuracy of ICH score–based models with and without delirium category in predicting WLST.ResultsOf 311 patients (mean age 70.6 ± 15.6, median ICH score 1 [interquartile range 1–2]), 50% had delirium. WLST occurred in 26%, and median time to WLST was 1 day (0–6). WLST was more frequent in patients who developed delirium (adjusted hazard ratio 8.9 [95% confidence interval (CI) 2.1–37.6]), with high rates of WLST in both early (occurring ≤24 hours from admission) and later delirium groups. An ICH score-based model was strongly predictive of WLST (area under the curve [AUC] 0.902 [95% CI 0.863–0.941]), and the addition of delirium category further improved the model's accuracy (AUC 0.936 [95% CI 0.909–0.962], p = 0.004).ConclusionDelirium is associated with WLST after ICH regardless of when it occurs. Further study on the impact of delirium on clinician and surrogate decision-making is warranted.

Background and Aims: Many studies have conclusively proven that meditative techniques derived from the Indian systems of philosophy, meditation and ritual classified as “Tantra” can bring about sustained changes in the structure and function of the nervous system of practitioners. The aim of this study is to provide neuroscientists a framework through which to interpret Tantra, and thereby provide a foundation upon which future interdisciplinary study can be built. Methods: We juxtapose Tantric concepts such as the subtle body, nadis and mantras with relevant neuroscientific findings. Our premise is that through sustained internalization of attention, Tantric practitioners were able to identify and document subtle changes in their field of awareness, which usually do not cross the threshold to come into our perception. Results: The descriptions left by Tantric philosophers are often detailed and empirical, but they are about subjective phenomena, rather than external objects. They also focus on individual experiences, rather than the group-level analyses favored by modern medical science. Conclusion: Systematic exploration of Tantric texts can be of tremendous value in expanding our understanding of human beings' experiential reality, by enabling us to build bridges between first-person and third-person approaches to the nervous system. This may open up new avenues for cognitive enhancement and treating neurological diseases.

OBJECTIVES Poststroke delirium may be underdiagnosed due to the challenges of disentangling delirium symptoms from underlying neurologic deficits. We aimed to determine the prevalence of individual delirium features and the frequency with which they could not be assessed in patients with intracerebral hemorrhage. DESIGN Prospective observational cohort study. SETTING Neurocritical Care and Stroke Units at a university hospital. PATIENTS Consecutive patients with intracerebral hemorrhage from February 2018 to May 2018. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS An attending neurointensivist performed 257 total daily assessments for delirium on 60 patients (mean age 68.0 [SD 18.4], 62% male, median intracerebral hemorrhage score 1.5 [interquartile range 1-2], delirium prevalence 57% [n = 34]). Each assessment included the Confusion Assessment Method for the ICU, Intensive Care Delirium Screening Checklist, a focused bedside cognitive examination, chart review, and nurse interview. We characterized individual symptom prevalence and established delirium diagnoses using Diagnostic and Statistical Manual of Mental Disorders, fifth edition criteria, then compared performance of the Confusion Assessment Method for the ICU and Intensive Care Delirium Screening Checklist against reference-standard expert diagnosis. Symptom fluctuation (61% of all assessments), psychomotor changes (46%), sleep-wake disturbances (46%), and impaired arousal (37%) had the highest prevalence and were never rated "unable to assess," while inattention (36%), disorientation (27%), and disorganized thinking (18%) were also common but were often rated 'unable to assess' (32%, 43%, and 44% of assessments, respectively), most frequently due to aphasia (32% of patients). Including nonverbal assessments of attention decreased the frequency of 'unable to assess' ratings to 11%. Since the Intensive Care Delirium Screening Checklist may be positive without the presence of symptoms that require verbal assessment, it was more accurate (sensitivity = 77%, specificity = 97%, area under the receiver operating characteristic curve, 0.87) than the Confusion Assessment Method for the ICU (sensitivity = 41%, specificity = 88%, area under the receiver operating characteristic curve, 0.64). CONCLUSIONS Delirium is common after intracerebral hemorrhage, but severe neurologic deficits may confound its assessment and lead to underdiagnosis. The Intensive Care Delirium Screening Checklist's inclusion of nonverbal features may make it more accurate than the Confusion Assessment Method for the ICU in patients with neurologic deficits, but novel tools designed for such patients may be warranted.

Purpose In rectal cancer, the presence of extramesorectal/lateral pelvic lymph node (LPN) is associated with higher risk of locoregional and distant recurrences. LPNs are not typically resected during a standard total mesorectal excision (TME) procedure, and the optimal management for these patients is controversial. We assessed the safety and efficacy of adding a radiation therapy boost to clinically positive LPN during neoadjuvant chemoradiation therapy for rectal cancer. Methods and Materials We analyzed nonmetastatic, lymph node positive rectal adenocarcinoma patients treated with neoadjuvant chemoradiation therapy followed by TME between May 2011 and February 2018. Patients without LPN involvement received external beam radiation therapy (45 Gy in 25 fractions) to the primary tumor and regional draining lymph node basins followed by a boost (5.4 Gy in 3 fractions) to gross disease. Patients with clinically positive LPN that would not be removed during TME received an additional boost (up to a total dose between 54.0 and 59.4 Gy) to the involved LPNs. We compared locoregional control, overall survival, progression-free survival, and treatment-related toxicity between these 2 groups. Results Fifty-three patients were included in this analysis with median follow-up of 30.6 months for the LPN– group (n = 41) and 19.9 months for the LPN+ group (n = 12). There was no difference in 3-year overall survival (90.04% vs 83.33%, P = .890) and progression-free survival (80.12% vs 80.21%, P = .529) between the 2 groups. We did not observe any LPN recurrences. There were no differences in rates of acute grade 3+ or chronic toxicities. Conclusions Despite the well-documented negative prognostic effect of LPN metastasis, we observed promising outcomes for LPN+ patients treated with an additional radiation boost. Our results suggest that radiation therapy boost to clinically involved, unresected LPN is an effective treatment approach with limited toxicity. Additional studies are needed to optimize treatment strategies for this unique patient subset.

Identification of effective targeted therapies for recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) remains an unmet medical need. A patient with platinum‐refractory recurrent oral cavity HNSCC underwent comprehensive genomic profiling (CGP) that identified an activating MET mutation (R1004). The patient was treated with the oral MET tyrosine kinase inhibitor crizotinib with rapid response to treatment. Based on this index case, we determined the frequency of MET alterations in 1,637 HNSCC samples, which had been analyzed with hybrid capture‐based CGP performed in the routine course of clinical care. The specimens were sequenced to a median depth of >500× for all coding exons from 182 (version 1, n = 24), 236 (version 2, n = 326), or 315 (version 3, n = 1,287) cancer‐related genes, plus select introns from 14 (version 1), 19 (version 2), or 28 (version 3) genes frequently rearranged in cancer. We identified 13 HNSCC cases (0.79%) with MET alterations (4 point mutation events and 9 focal amplification events). MET‐mutant or amplified tumors represent a small but potentially actionable molecular subset of HNSCC. KEY POINTS. This case report is believed to be the first reported pan‐cancer case of a patient harboring a MET mutation at R1004 demonstrating a clinical response to crizotinib, in addition to the first documented case of head and neck squamous cell carcinoma (HNSCC) with any MET alteration responding to crizotinib. The positive response to MET inhibition in this patient highlights the significance of comprehensive genomic profiling in advanced metastatic HNSCC to identify actionable targetable molecular alterations as current treatment options are limited.

Background Treatment recommendations for advanced-stage laryngeal squamous cell carcinoma (SCC) have evolved significantly over the last 2 decades. Methods We retrospectively analyzed patients in the Surveillance, Epidemiology, and End Results (SEER) database with advanced-stage laryngeal SCC treated between 2004 and 2012. Results A total of 6797 patients were identified in the SEER database who met inclusion criteria, with 2051 patients undergoing primary surgery and 4746 patients undergoing primary radiotherapy (RT) or chemoradiotherapy (CRT). Disease-specific survival (DSS) and overall survival (OS) were significantly better for patients treated with primary surgery when compared using Kaplan–Meier curves and a Cox multivariate regression. When survival analysis was repeated for patients stratified by T classification, N classification, and subsite, OS and DSS benefits from primary surgery were observed for patients with T3 and T4a tumors, N0 neck disease, or supraglottic primaries. Conclusion Patients with advanced-stage laryngeal SCC with T3 and T4a tumors, N0 neck disease, or supraglottic primaries have the greatest chance of survival when treated with primary surgery. © 2016 Wiley Periodicals, Inc. Head Neck, 2016