A retrospective study on the investigation of potential dosimetric benefits of online adaptive proton therapy for head and neck cancer.

PURPOSE: Proton therapy is sensitive to anatomical changes, often occurring in head-and-neck (HN) cancer patients. Although multiple studies have proposed online adaptive proton therapy (APT), there is still a concern in the radiotherapy community about the necessity of online APT. We have performed a retrospective study to investigate the potential dosimetric benefits of online APT for HN patients relative to the current offline APT. METHODS: Our retrospective study has a patient cohort of 10 cases. To mimic online APT, we re-evaluated the dose of the in-use treatment plan on patients' actual treatment anatomy captured by cone-beam CT (CBCT) for each fraction and performed a templated-based automatic replanning if needed, assuming that these were performed online before treatment delivery. Cumulative dose of the simulated online APT course was calculated and compared with that of the actual offline APT course and the designed plan dose of the initial treatment plan (referred to as nominal plan). The ProKnow scoring system was employed and adapted for our study to quantify the actual quality of both courses against our planning goals. RESULTS: The average score of the nominal plans over the 10 cases is 41.0, while those of the actual offline APT course and our simulated online course is 25.8 and 37.5, respectively. Compared to the offline APT course, our online course improved dose quality for all cases, with the score improvement ranging from 0.4 to 26.9 and an average improvement of 11.7. CONCLUSION: The results of our retrospective study have demonstrated that online APT can better address anatomical changes for HN cancer patients than the current offline replanning practice. The advanced artificial intelligence based automatic replanning technology presents a promising avenue for extending potential benefits of online APT.

Active control of equilibrium, near-equilibrium, and far-from-equilibrium colloidal systems.

The development of top-down active control over bottom-up colloidal assembly processes has the potential to produce materials, surfaces, and objects with applications in a wide range of fields spanning from computing to materials science to biomedical engineering. In this review, we summarize recent progress in the field using a taxonomy based on how active control is used to guide assembly. We find there are three distinct scenarios: (1) navigating kinetic pathways to reach a desirable equilibrium state, (2) the creation of a desirable metastable, kinetically trapped, or kinetically arrested state, and (3) the creation of a desirable far-from-equilibrium state through continuous energy input. We review seminal works within this framework, provide a summary of important application areas, and present a brief introduction to the fundamental concepts of control theory that are necessary for the soft materials community to understand this literature. In addition, we outline current and potential future applications of actively-controlled colloidal systems, and we highlight important open questions and future directions.

A component method to delineate surgical spine implants for proton Monte Carlo dose calculation.

PURPOSE: Metallic implants have been correlated to local control failure for spinal sarcoma and chordoma patients due to the uncertainty of implant delineation from computed tomography (CT). Such uncertainty can compromise the proton Monte Carlo dose calculation (MCDC) accuracy. A component method is proposed to determine the dimension and volume of the implants from CT images. METHODS: The proposed component method leverages the knowledge of surgical implants from medical supply vendors to predefine accurate contours for each implant component, including tulips, screw bodies, lockers, and rods. A retrospective patient study was conducted to demonstrate the feasibility of the method. The reference implant materials and samples were collected from patient medical records and vendors, Medtronic and NuVasive. Additional CT images with extensive features, such as extended Hounsfield units and various reconstruction diameters, were used to quantify the uncertainty of implant contours. RESULTS: For in vivo patient implant estimation, the reference and the component method differences were 0.35, 0.17, and 0.04 cm3 for tulips, screw bodies, and rods, respectively. The discrepancies by a conventional threshold method were 5.46, 0.76, and 0.05 cm3 , respectively. The mischaracterization of implant materials and dimensions can underdose the clinical target volume coverage by 20 cm3 for a patient with eight lumbar implants. The tulip dominates the dosimetry uncertainty as it can be made from titanium or cobalt-chromium alloys by different vendors. CONCLUSIONS: A component method was developed and demonstrated using phantom and patient studies with implants. The proposed method provides more accurate implant characterization for proton MCDC and can potentially enhance the treatment quality for proton therapy. The current proof-of-concept study is limited to the implant characterization for lumbar spine. Future investigations could be extended to cervical spine and dental implants for head-and-neck patients where tight margins are required to spare organs at risk.

Comparing Deceased Organ Donation Performance in Two Countries that Use Different Metrics: Comparing Apples With Apples.

Organ donation networks audit and report on national or regional organ donation performance, however there are inconsistencies in the metrics and definitions used, rendering comparisons difficult or inappropriate. This is despite multiple attempts exploring the possibility for convergently evolving audits so that collectives of donation networks might transparently share data and practice and then target system interventions. This paper represents a collaboration between the United Kingdom and Australian organ donation organisations which aimed to understand the intricacies of our respective auditing systems, compare the metrics and definitions they employ and ultimately assess their level of comparability. This point of view outlines the historical context underlying the development of the auditing tools, demonstrates their differences to the Critical Pathway proposed as a common tool a decade ago and presents a side-by-side comparison of donation definitions, metrics and data for the 2019 calendar year. There were significant differences in donation definition terminology, metrics and overall structure of the audits. Fitting the audits to a tiered scaffold allowed for reasonable comparisons however this required substantial effort and understanding of nuance. Direct comparison of international and inter-regional donation performance is challenging and would benefit from consistent auditing processes across organisations.

Onboard cone-beam CT-based replan evaluation for head and neck proton therapy.

PURPOSE: Quality assurance computed tomography (QACT) is the current clinical practice in proton therapy to evaluate the needs for replan. QACT could falsely indicate replan because of setup issues that would be solved on the treatment machine. Deforming the treatment planning CT (TPCT) to the pretreatment CBCT may eliminate this issue. We investigated the performance of replan evaluation based on deformed TPCT (TPCTdir) for proton head and neck (H&N) therapy. METHODS AND MATERIALS: Twenty-eight H&N datasets along with pretreatment CBCT and QACT were used to validate the method. The changes in body volume were analyzed between the no-replan and replan groups. The dose on the TPCTdir, the deformed QACT (QACTdir), and the QACT were calculated by applying the clinical plans to these image sets. Dosimetric parameters' changes, including ΔD95, ΔDmean, and ΔD1 for the clinical target volumes (CTVs) were calculated. Receiver operating characteristic curves for replan evaluation based on ΔD95 on QACT and TPCTdir were calculated, using ΔD95 on QACTdir as the reference. A threshold for replan based on ΔD95 on TPCTdir is proposed. The specificities for the proposed method were calculated. RESULTS: The changes in the body contour were 95.8 ± 83.8 cc versus 305.0 ± 235.0 cc (p < 0.01) for the no-replan and replan groups, respectively. The ΔD95, ΔDmean, and ΔD1 are all comparable for all the evaluations. The differences between TPCTdir and QACTdir evaluations were 0.30% ± 0.86%, 0.00 ± 0.22 Gy, and -0.17 ± 0.61 Gy for CTV ΔD95, ΔDmean, and ΔD1, respectively. The corresponding differences between the QACT and QACTdir were 0.12% ± 1.1%, 0.02 ± 0.32 Gy, and -0.01 ± 0.71 Gy. CTV ΔD95 > 2.6% in TPCTdir was chosen as the threshold to trigger QACT/replan. The corresponding specificity was 94% and 98% for the clinical practice and the proposed method, respectively. CONCLUSIONS: The replan evaluation based on TPCTdir provides better specificity than that based on the QACT.

Telestroke: Maintaining Quality Acute Stroke Care During the COVID-19 Pandemic.

Introduction: The coronavirus disease 2019 (COVID-19) pandemic has significantly impacted acute stroke care globally. Decreased stroke presentations and concern for delays in acute stroke care have been identified. This study evaluated the impact of COVID-19 on the timely treatment of patients with thrombolytics at hospitals utilizing telestroke acute stroke services. Methods: Acute stroke consultations seen in 171 hospitals (19 states) via telestroke from December 1, 2019, to June 27, 2020, were extracted from the TeleCare™ database. The consults were divided into pre-COVID and COVID groups (March 15, 2020, start of COVID group). The consults were reviewed for age, sex, hospital, state, date seen, last known normal, arrival time, consult call time, needle time, thrombolytic candidate, and National Institutes of Health Stroke Scale (NIHSS) score. The total number of consults, median door to needle (DTN) time for emergency department (ED) patients, and call to needle (CTN) time for inpatients were calculated. Results: Pre-COVID, 15,226 stroke consults were evaluated compared with 11,105 in the COVID group, a 27% decrease. Pre-COVID, 1,071 ED patients (7.9%) received thrombolytics and 66 inpatients (4.0%), while COVID, 813 ED patients (8.2%) and 70 inpatients (5.7%). The median DTN time for ED patients pre-COVID was 42 (32, 55) versus 40 (31, 52) in the COVID group, with no statistically significant difference between groups. CTN time pre-COVID was 53 (35, 67) versus 46 (35, 61) in the COVID group, with no statistically significant difference between groups. Conclusions: Telestroke assessments allowed for uninterrupted acute stroke care and treatment stability despite nursing and other resource realignments triggered by the COVID-19 pandemic.

An Audit of Lung Donor Pool: Optimal Current Donation Strategies and the Potential of Novel Time-Extended Donation After Circulatory Death Donation.

BACKGROUND: In Australia, increased organ donation and subsequent lung transplantation (LTx) rates have followed enhanced donor identification, referral and management, as well as the introduction of a donation after circulatory death (DCD) pathway. However, the number of patients waiting for LTx still continues to exceed the number of lung donors and the search for further suitable donors is critical. METHODS: All 2014-2018 Victorian DonateLife hospital deaths after intensive care unit (ICU) admission were analysed retrospectively to quantify unrecognised lung donors using current criteria, as well as novel time-extended (90 mins-24 hrs post-withdrawal) DCD lung donors. RESULTS: Using standard lung donor eligibility criteria, we identified 473 potential lung donors and a further 122 time-extended DCD potential lung donors among 3,538 patients meeting general eligibility criteria. Detailed review of end-of-life discussions with patient families and the reasons why they were not offered donation revealed several categories of additional lung donors-traditional lung donors missed in current practice (n=2); hepatitis C infected lung donors potentially treatable with direct-acting antivirals (n=14), time-extended DCD lung donors (n=60); donor lungs potentially suitable for transplant with use of ex-vivo lung perfusion (EVLP) (n=7). CONCLUSION: While the number of lung donor opportunities missed under existing DonateLife donor identification and management processes was limited, a time-extended DCD lung donation pathway could substantially expand the lung donor pool. The use of hepatitis C infected donors, and the possibility of EVLP to solve donor graft assessment or logistic issues, could also provide small additional lung donor opportunities.

Improving the predictability of time to death in controlled donation after circulatory death lung donors.

Although the use of donation after circulatory death (DCD) donors has increased lung transplant activity, 25-40% of intended DCD donors do not convert to actual donation because of no progression to asystole in the required time frame after withdrawal of cardiorespiratory support (WCRS). No studies have specifically focussed on DCD lung donor progression. This retrospective study reviewed intended DCD lung donors to make a prediction model of the likelihood of progression to death using logistic regression and classification and regression tree (CART). Between 2014 and 2018, 159 of 334 referred DCD donors were accepted, with 100 progressing to transplant, while 59 (37%) did not progress. In logistic regression, a length of ICU stay ≤ 5 days, severe infra-tentorial brain damage on imaging and use of vasopressin were related with the progression to actual donation. CART modelling of the likelihood of death within 90-minute post-WCRS provided prediction with a sensitivity of 1.00 and positive predictive value of 0.56 in the validation data set. In the nonprogressed DCD group, 26 died within 6 h post-WCRS. Referral received early after ICU admission, with nonspontaneous ventilatory mode, deep coma and severe infra-tentorial damage were relevant predictors. The CART model is useful to exclude DCD donor candidates with low probability of progression.

Survival outcomes in patients with gastric and gastroesophageal junction adenocarcinomas treated with perioperative chemotherapy with or without preoperative radiotherapy.

BACKGROUND: Perioperative chemotherapy (POC) is one standard approach for the treatment of resectable cancers of the stomach and gastroesophageal junction (GEJ), whereas there has been growing interest in preoperative therapies. The objective of the current study was to compare survival between patients treated with preoperative chemoradiotherapy and adjuvant chemotherapy (PCRT) with those receiving POC using a large database. METHODS: The National Cancer Data Base was queried for patients diagnosed between 2004 and 2013 with American Joint Committee on Cancer clinical group stage IB to stage IIIC (excluding T2N0 disease) adenocarcinoma of the stomach or GEJ. Patients treated with definitive surgery and POC with or without preoperative radiotherapy of 41 to 54 Gy were included. Overall survival (OS) was defined from the date of definitive surgery and estimated using the Kaplan-Meier method. A total of 14 patient and treatment variables were used for propensity score matching (PSM). RESULTS: A total of 1048 patients were analyzed: 53.2% received POC and 46.8% received PCRT. The primary tumor site was the GEJ in 69.1% of patients and stomach in 30.9% of patients. The median age of the patients was 60 years, and the median follow-up was 25.8 months. The use of PCRT was associated with a greater pathologic complete response rate of 13.1% versus 8.2% (P = .01). POC was associated with a decreased risk of death in unmatched groups (hazard ratio [HR], 0.83; P = .043). Using PSM cohorts, POC decreased the risk of death with a median OS of 45.1 months versus 31.4 months (HR, 0.70; P = .016). The 2-year OS rate was 72.9% versus 62.5% and the 5-year OS rate was 40.7% versus 33.1% for POC versus PCRT, respectively. Survival favored POC in PSM gastric (HR, 0.41; P = .07) and GEJ (HR, 0.77; P = .08) patient subgroups. CONCLUSIONS: The addition of preoperative radiotherapy to POC appears to be associated with an increased risk of death in patients with resectable gastric and GEJ cancers.

Dual Antiplatelet Therapy Is Associated With Coagulopathy Detectable by Thrombelastography in Acute Stroke.

BACKGROUND: Thrombelastography (TEG) provides a global, dynamic measure of coagulation. We examined the effect of antiplatelet (AP) medications on coagulation in patients with acute stroke as measured by TEG. METHODS: We reviewed prospectively collected data on patients presenting with acute ischemic stroke (AIS) and spontaneous intracerebral hemorrhage (ICH) between 2009 and 2014. Patient demographics and baseline TEG values were compared among 4 different drug use groups: aspirin only, clopidogrel only, both aspirin and clopidogrel, and no AP. Multivariable regression models were conducted to compare the differences in TEG components. RESULTS: A total of 202 patients were included, 139 with AIS and 63 with ICH. Forty-eight (24%) patients were taking aspirin alone, 12 (6%) were taking clopidogrel, 16 (8%) dual AP, and 126 (62%) no AP. Dual AP use was associated with prolonged mean R (time to initiate clotting) of 5.5 minutes as compared to no AP use (4.6 minutes, P = .04). Additionally, mean maximal amplitude (MA; final clot strength) and angle (rate of clot formation) were decreased in the dual AP group (MA = 59.3 mm, angle = 57.8°) as compared to the no AP group (MA = 64.5 mm, angle = 64.5°; P = .04 and P = .01, respectively). Patients on single AP therapy (either aspirin or clopidogrel) did not differ from those on no AP therapy in any TEG parameters measured. CONCLUSION: Dual AP therapy is associated with a detectable coagulopathy which may have implications in the management of patients with AIS and hemorrhagic stroke. The effects of single AP therapy may not be demonstrated by TEG.

Survival outcomes by high-risk human papillomavirus status in nonoropharyngeal head and neck squamous cell carcinomas: A propensity-scored analysis of the National Cancer Data Base.

BACKGROUND: The prognostic relevance of human papillomavirus (HPV) status in patients with nonoropharyngeal (OPX) squamous cell cancer (SCC) of the head and neck is controversial. In the current study, the authors evaluated the impact of high-risk HPV status on overall survival (OS) in patients with non-OPX SCC using a large database approach. METHODS: The National Cancer Data Base was queried to identify patients diagnosed from 2004 through 2014 with SCC of the OPX, hypopharynx (HPX), larynx, and oral cavity (OC) with known HPV status. Survival was estimated using Kaplan-Meier methods; distributions were compared using log-rank tests. Propensity score-matching and inverse probability of treatment weighing (IPTW) methods were used; cohorts were matched based on age, sex, Charlson-Deyo score, clinical American Joint Committee on Cancer (AJCC) group stage, treatments received, and anatomic subsite. Propensity analyses were stratified by group stage of disease. RESULTS: A total of 24,740 patients diagnosed from 2010 through 2013 were analyzed: 1085 patients with HPX, 4804 with laryngeal, 4,018 with OC, and 14,833 with OPX SCC. The percentages of HPV-positive cases by disease site were 17.7% for HPX, 11% for larynx, 10.6% for OC, and 62.9% for OPX. HPV status was found to be prognostic in multiple unadjusted and propensity-adjusted non-OPX populations. HPV positivity was associated with superior OS in patients with HPX SCC with a hazard ratio (HR) of 0.61 (P < .001 by IPTW), in patients with AJCC stage III to IVB laryngeal SCC (HR, 0.79; P = .019 by IPTW), and in patients with AJCC stage III to IVB OC SCC (HR, 0.78; P = .03 by IPTW). CONCLUSIONS: Positive high-risk HPV status appears to be associated with longer OS in multiple populations of patients with non-OPX head and neck disease (HPX, locally advanced larynx, and OC). If prospectively validated, these findings have implications for risk stratification.

Smoking, age, nodal disease, T stage, p16 status, and risk of distant metastases in patients with squamous cell cancer of the oropharynx.

BACKGROUND: With an expectation of excellent locoregional control, ongoing efforts to de-intensify therapy for patients with human papillomavirus-associated squamous cell oropharyngeal cancer necessitate a better understanding of the metastatic risk for patients with this disease. The objective of this study was to determine what factors affect the risk of metastases in patients with squamous cell cancers of the oropharynx. METHODS: Under a shared use agreement, 547 patients from Radiation Therapy Oncology Group 0129 and 0522 with nonmetastatic oropharyngeal squamous cell cancers who had a known p16 status and smoking status were analyzed to assess the association of clinical features with the development of distant metastases. The analyzed factors included the p16 status, sex, T stage, N stage, age, and smoking history. RESULTS: A multivariate analysis of 547 patients with a median follow-up of 4.8 years revealed that an age ≥ 50 years (hazard ratio [HR], 3.28; P = .003), smoking for more than 0 pack-years (HR, 3.09; P < .001), N3 disease (HR, 2.64; P < .001), T4 disease (HR, 1.63; P = .030), and a negative p16 status (HR, 1.60; P = .044) were all factors associated with an increased risk of distant disease. CONCLUSIONS: Age, smoking, N3 disease, T4 disease, and a negative p16 status were associated with the development of distant metastases in patients with squamous cell cancers of the oropharynx treated definitively with concurrent chemoradiation.

Small Cell and Squamous Cell Carcinomas of the Head and Neck: Comparing Incidence and Survival Trends Based on Surveillance, Epidemiology, and End Results (SEER) Data.

BACKGROUND: Small cell carcinomas of the head and neck (SmCCHNs) are rare neoplasms with an unfavorable prognosis. Population-based data describing survival and prognostic factors for SmCCHN are limited. METHODS: Data were obtained from the U.S. National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database for 1973-2013. Patient and tumor-related characteristics for SmCCHN were compared with those for squamous cell carcinoma of the head and neck (SCCHN). Survival was compared by constructing Kaplan-Meier curves and Cox proportional hazard models with and without propensity score matching. RESULTS: The data set included 609 SmCCHN and 227,943 SCCHN cases. Both histological subtypes were more common in men than women and more common in white patients. SmCCHN was most likely to originate in the larynx, glottis and hypopharynx, or salivary glands and to present with more advanced stage and grade. SCCHN was most likely to originate in the oral cavity and was found infrequently in the salivary glands. Overall 5- and 10-year survival estimates were 27% and 18% for SmCCHN and 46% and 31% for SCCHN, respectively. In multivariable survival analyses adjusting for age, sex, race, marital status, year of diagnosis, stage, grade, and receipt of radiation, the hazard ratio (HR) comparing SmCCHN with SCCHN was 1.53 with a 95% confidence interval (CI) from 1.39 to 1.68. Average 5-year survival varied widely between the histologic types when comparing tumor sites: 14.5% for SmCCHN versus 48.9% for SCCHN in the oropharynx. In propensity score matched analyses, the corresponding HR was 1.27 (95% CI, 1.15-1.40). CONCLUSION: Compared with SCCHN, SmCCHN carries a worse survival and is more likely to present with more advanced stage. IMPLICATIONS FOR PRACTICE: Small cell carcinoma of the head and neck (SmCCHN) is a rare subtype of head and neck cancer. In this Surveillance, Epidemiology, and End Results (SEER) data analysis, the characteristics and survival of SmCCHN are compared with those of the common squamous cell carcinoma of the head and neck. Results show that SmCCHN carries a worse prognosis and tends to present at a more advanced stage; SmCCHN also is ten times more likely to originate from the salivary glands. These findings may have implications for clinical practice, as location of the tumor may strongly associate with the pathologic diagnosis. If a SmCCHN is diagnosed, a disseminated disease is likely; hence vigilance in staging procedures is indicated.

Racial Disparities, Outcomes, and Surgical Utilization among Hispanics with Esophageal Cancer: A Surveillance, Epidemiology, and End Results Program Database Analysis.

BACKGROUND: Hispanic patients with esophageal cancer (EC) have racially disparate survival outcomes compared with white patients. OBJECTIVES: We explored the impact on survival of racial differences in socioeconomic factors, tumor characteristics, and rates of surgical utilization in patients with EC. METHOD: Using the SEER (Surveillance, Epidemiology, and End Results) registry, we identified 22,531 cases of EC in Hispanic and white patients between the ages of 18 and 65 years in 2003-2014. Of these, 6,250 cases had locoregional EC. Patients were categorized according to age, gender, education, tumor grade, histology, primary tumor site, and surgical status. Postdiagnosis survival was examined over time and compared by race and stratified by surgical status. RESULTS: Compared with whites, Hispanics with EC had significantly higher unadjusted mortality (hazard ratio [HR] 1.11; 95% confidence interval [CI] 1.06-1.17; p < 0.001) as did Hispanics with locoregional EC (HR 1.15; 95% CI 1.03-1.29; p = 0.01). In the multivariate analysis, several socioeconomic and tumor factors were found to be independently associated with survival by race, including county of residence income and prevalence of smoking, tumor grade, stage, and primary site, and surgical utilization. After adjusting for demographic and tumor characteristics, surgical utilization in patients with locoregional EC had a significant interaction with race on overall mortality (p = 0.01). Hispanics with locoregional EC were significantly less likely to receive surgery than whites (46 vs. 60%; p < 0.001) and not receiving surgery was associated with a significantly lower overall survival (HR 2.84; 95% CI 2.65-3.04; p < 0.001). CONCLUSIONS: A lower rate of surgery among Hispanics with potentially resectable esophageal cancer was associated with a decreased survival rate when compared to whites, even when adjusting for relevant socioeconomic and tumor factors. These data support the need to better address patient barriers to surgical treatment and the systemic biases present in medical care.

Acupuncture in Adult and Pediatric Headache: A Narrative Review.

Headaches in children and adolescents remain a very common problem with migraine being the most common headache disorder to present to medical attention. The approach to the treatment of migraine in children has consisted of treatment with acute and preventive medications, combined with lifestyle modification and behavioral interventions, such as cognitive behavioral therapy. With increasing frequency, complementary and alternative medicine (CAM) approaches, including acupuncture, are often recommended in the pediatric population to address significant disability with limited evidence-based treatment options. In this article, the authors conduct a review of acupuncture in pediatric headache, including neurobiological mechanisms, adult headache studies, pediatric headache studies, safety, and use of acupuncture in other conditions in children. This article aims to summarize the currently available evidence with which to recommend acupuncture in children for the adjunctive treatment of headache. Acupuncture appears to be safe and effective for the treatment of migraine in children.

A selective insecticidal protein from Pseudomonas mosselii for corn rootworm control.

The coleopteran insect western corn rootworm (WCR, Diabrotica virgifera virgifera) is an economically important pest in North America and Europe. Transgenic corn plants producing Bacillus thuringiensis (Bt) insecticidal proteins have been useful against this devastating pest, but evolution of resistance has reduced their efficacy. Here, we report the discovery of a novel insecticidal protein, PIP-47Aa, from an isolate of Pseudomonas mosselii. PIP-47Aa sequence shows no shared motifs, domains or signatures with other known proteins. Recombinant PIP-47Aa kills WCR, two other corn rootworm pests (Diabrotica barberi and Diabrotica undecimpunctata howardi) and two other beetle species (Diabrotica speciosa and Phyllotreta cruciferae), but it was not toxic to the spotted lady beetle (Coleomegilla maculata) or seven species of Lepidoptera and Hemiptera. Transgenic corn plants expressing PIP-47Aa show significant protection from root damage by WCR. PIP-47Aa kills a WCR strain resistant to mCry3A and does not share rootworm midgut binding sites with mCry3A or AfIP-1A/1B from Alcaligenes that acts like Cry34Ab1/Cry35Ab1. Our results indicate that PIP-47Aa is a novel insecticidal protein for controlling the corn rootworm pests.

Chemotherapy with or Without Definitive Radiation Therapy in Inoperable Pancreatic Cancer.

BACKGROUND: The LAP07 randomized trial calls into question the role of radiation therapy (RT) in the modern treatment of locally advanced pancreatic cancer (LAPC). However, advances in chemotherapy and RT limit application of the LAP07 results to current clinical practice. Here we utilize the National Cancer Database (NCDB) to evaluate the effects of RT in patients receiving chemotherapy for LAPC. METHODS: Using the NCDB, patients with American Joint Committee on Cancer (AJCC) clinical stage T2-4, N0-1, M0 adenocarcinoma of the pancreas from 2004 to 2014 were analyzed. Patients were stratified into chemotherapy only (CT) and chemoradiation (CRT) cohorts. Patients undergoing definitive RT, defined as at least 20 fractions or ≥ 5 Gy per fraction [i.e., stereotactic body radiation therapy (SBRT)] were included in the CRT cohort. Propensity-score matching (PSM) and landmark analysis were used to address selection bias and lead-time bias, respectively. RESULTS: 13,004 patients met inclusion criteria, of whom 7034 (54%) received CT and 5970 (46%) received CRT. After PSM, 5215 patients remained in each cohort. The CRT cohort demonstrated better overall survival (OS) compared with CT alone, with median and 1-year OS of 12 versus 10 months, and 50% and 41%, respectively (p < 0.001). On multivariable analysis, CRT was associated with superior OS with hazard ratio of 0.79 (95% confidence interval 0.76-0.83) compared with CT alone. CONCLUSIONS: In our series, addition of definitive radiotherapy to CT was associated with better OS when compared with CT alone in LAPC. Definitive radiotherapy should remain a treatment option for LAPC, but optimal selection criteria remain unclear.

Auricular Acupuncture for the Treatment of Pediatric Migraines in the Emergency Department.

OBJECTIVES: Headache remains a frequent complaint for children presenting to a pediatric emergency department (ED). Typical treatments include oral or intravenous medications, but do not always relieve pain. An alternative intervention is auricular acupuncture. It has been shown to be effective in the treatment of migraines in adults. The objective of this study was to evaluate the utility and adverse effects of auricular acupuncture in the treatment of pediatric migraines in the ED. METHODS: This was a prospective, interventional, cohort study of patients 8 to 18 years of age. Efficacious ear points were located by needle contact or electrical point finder with attention to 2 migraine lines on the ear. ASP gold semipermanent ear needles were placed in the efficacious points and patients were monitored for 15 minutes. The primary outcome was the change in preintervention and postintervention pain scores using a numerical self-reported pain visual analog scale (VAS). RESULTS: Nineteen patients elected to enroll in the study. The mean change in the VAS scores was both clinically and statistically significant at 7.03 (interquartile range, 6-8.5) with a P value of less than 0.001. Two patients elected to withdraw from the study secondary to incomplete resolution of migraine pain despite improvement in VAS scores. There were no known adverse events. CONCLUSIONS: With all subjects showing improvement or resolution of migraine headache, this pilot study introduces an alternative intervention to pediatric migraine management. Further studies are needed to evaluate the duration of symptom resolution and comparative effectiveness; auricular acupuncture seems to be a valid alternative.

Thrombelastography Suggests Hypercoagulability in Patients with Renal Dysfunction and Intracerebral Hemorrhage.

BACKGROUND: The objective of this study was to quantify coagulopathy using thrombelastography (TEG) in patients with renal dysfunction and intracerebral hemorrhage (ICH). METHODS: We reviewed patients admitted with spontaneous ICH between November 2009 and May 2015. TEG was performed at the time of admission. Creatinine clearance (CCr) was calculated using the Cockroft-Gault equation. Patients were divided into 2 groups based on normal (CCr ≥ 90) or reduced renal function (CCr < 90). Multivariable regression models were conducted to compare the differences of TEG components. RESULTS: A total of 120 patients were included in the analysis. The normal CCr group was younger (56.1 versus 62.3 years, P < .01), was more often male (73.6% versus 53.7%, P = .03), and had higher mean admission hemoglobin (14.2 versus 13.2 mEq/L, P < .01) than the reduced renal function group. The 2 groups were similar with respect to antiplatelet or anticoagulant use, coagulation studies, and baseline ICH volume. Following multivariate analysis, the reduced renal function group was found to have shorter K (1.5 versus 2.2 min, P = 004), increased angle (66 versus 62.2 degrees, P = .04), increased MA (67.3 versus 62.3, P = .02), and increased G (11.3 versus 9.9 dynes/cm2, P = .04) compared with the normal group. Mortality, poor functional outcome (modified Rankin Scale score 4-6), hematoma enlargement, hospital length of stay, and surgical interventions were not different between the 2 groups. CONCLUSIONS: Patients with ICH and reduced CCr display faster clotting rate and increased clot strength, suggesting that patients with renal dysfunction present with a relatively hypercoagulable state based on TEG parameters thought to reflect platelet activity.

Health care disparities among octogenarians and nonagenarians with stage II and III rectal cancer.

BACKGROUND: Octogenarians and nonagenarians with stage II/III rectal adenocarcinomas are underrepresented in the randomized trials that have established the standard-of-care therapy of preoperative chemoradiation followed by definitive resection (ie, chemoradiation and then surgery [CRT+S]). The purpose of this study was to evaluate the impact of therapies on overall survival (OS) for patients with stage II/III rectal cancers and determine predictors of therapy within the National Cancer Data Base (NCDB). METHODS: In the NCDB, patients who were 80 years old or older and had clinical stage II/III rectal adenocarcinoma from 2004 to 2013 were queried. Kaplan-Meier analysis, log-rank testing, logistic regression, Cox proportional hazards regression, interaction effect testing, and propensity score-matched analysis were conducted. RESULTS: The criteria were met by 2723 patients: 14.9% received no treatment, 29.7% had surgery alone, 5.0% underwent short-course radiation and then surgery (RT+S), 45.3% underwent CRT+S, and 5.1% underwent surgery and then chemoradiation (S+CRT). African American race and residence in a less educated county were associated with not receiving treatment. Male sex, older age, worsening comorbidities, and receiving no treatment or undergoing surgery alone were associated with worse OS. There was no statistical difference in OS between RT+S, S+CRT, and CRT+S. Interaction testing found that CRT+S improved OS independently of age, comorbidity status, sex, race, and tumor stage. In the propensity score-matched analysis, CRT+S was associated with improved OS in comparison with surgery alone. CONCLUSIONS: A significant portion of octogenarians and nonagenarians with stage II/III rectal adenocarcinomas do not receive treatment. African American race and living in a less educated community are associated with not receiving therapy. This series suggests that CRT+S is a reasonable strategy for elderly patients who can tolerate therapy. Cancer 2017;123:4325-36. © 2017 American Cancer Society.