bluuebunny/crossref_metadata_2025 huggingface dataset:
PSXIV-28 Performance of lambs of sheep fed diets containing narasin
Authors: Assis Rhaissa Garcia de , Biava Janaina S , Eckermann Nathalia R , Sturion Thamires U , Souza Terezinha T de , Cerutti Maria Fernanda , Paula Matheus F F V de , Polizel Daniel M , Pires Alexandre Vaz , Ferreira Evandro M
Published: December 2019

The objective of this trial was to evaluate the effects of increasing levels of narasin in the diet of lactating ewes on dry matter intake (DMI) and average daily gain (ADG) of their lambs. Forty crossbred ewes Dorper x Santa Inês with their lambs were assigned to a randomized complete block design (10 blocks and 4 treatments). The treatments were defined by the inclusion of narasin to a base diet (16.8 ± 0.66 of CP) containing 50% of concentrate and 50% of Brachiaria brizanta hay, as follow: 0N - control diet; 13N - 13 mg of narasin/kg of DM; 20N - 20 mg of narasin/kg of DM; 27N - 27 mg of narasin/kg of DM. The experiment lasted from 14 to 70 days of lactation. From the second to the tenth week of age the lambs received initial concentrate (57.0% corn; 25.0% soybean meal; 1.5% limestone; 1.5% of mineral mix; 5.0% of sugarcane molasses and 10% of milk replacer; composition: DM=89.3%; CP = 21.1%; FDN = 8.9%; FDA=2.7%) (ad libitum) in a private feeder. All data were analyzed using the MIXED procedure of SAS. The lambs were weighed weekly after 5-hours fasting. The orts were quantified weekly to determine the DMI. There was no effect of the supply of narasin to the ewes on the DMI by the lambs (0N = 0.126; 13N = 0.088; 20N = 0.153; 27N = 0.145 kg/d; P > 0.05). However, the supply of narasin decreased the ADG (0N = 269.3; 13N = 259.60; 20N = 264.02; 27 = 228.01 g; P < 0.01) of lambs. In conclusion, the use of narasin for the ewes did not benefit lamb performance.
Effect of Different Fruit Developmental Stages and Biochemical Metabolites of Pomegranate (Ponicaceae) on Life History Parameters of Ectomyelois ceratoniae (Lepidoptera: Pyralidae)
Authors: Abedi Zahra , Golizadeh Ali , Soufbaf Mahmoud , Hassanpour Mahdi , Jafari-Nodoushan Ali , Akhavan Hamid-Reza
Published: December 2019

Plant–herbivore interactions can be influenced by plant developmental stages. Effects of four different developmental stages of pomegranate fruit (Hazelnut size, Walnut size, Juicy, and Ripe) were investigated on life table parameters, nutritional yield, and energy contents (protein, glycogen, and lipid) of Ectomyelois ceratoniae (Zeller) under controlled conditions in two pomegranate cultivars, namely Shahvare-Danesefid and Esfahani-Daneghermez as susceptible and resistant cultivars, respectively. Biochemical characteristics of the four developmental stages were determined, and a correlation was made with life-history and nutritional responses of E. ceratoniae. Significant differences were observed in developmental time and adult fecundity of E. ceratoniae across various tested stages in both pomegranate cultivars. The highest value of intrinsic rate of increase (rm) was found in Juicy and lowest in Hazelnut-size stage of Shahvare-Danesefid. The highest rm value was on Walnut-size and Juicy stages, and the lower rate was obtained from the feeding of E. ceratoniae on Ripe and Hazelnut-size stages in Esfahani-Daneghermez. A higher relative growth rate (RGR) was observed in Juicy (in Shahvare-Danesefid) and Walnut-size stages (in Esfahani-Daneghermez) when compared with other developmental stages tested. Life-history parameters of E. ceratoniae were correlated with biochemical qualities of pomegranate stages. Results indicated Juicy (Shahvare-Danesefid) and Walnut-size stages (Esfahani-Daneghermez) were relatively susceptible pomegranate stages, and Hazelnut-size and Ripe stages were unsuitable for feeding of E. ceratoniae in Shahvare-Danesefid and Esfahani-Daneghermez, respectively. Findings of this research could aid in the development of integrated management programs of E. ceratoniae in pomegranate orchards.
Influence of Substrate Age on Oviposition Behavior of a Specialist Carrion Colonizer, Cochliomyia macellaria (Diptera: Calliphoridae)
Authors: Kotzé Zanthé , Tomberlin Jeffery K
Published: December 2019

The location and consumption of carrion by arthropods is a process that can be potentially distinguished temporally based on the makeup of the associated community. In fact, succession on carrion is a continuum of different generalist and specialist arthropods entering and leaving the system. Blow flies commonly associated with vertebrate remains are considered specialists due to their reliance on carrion as a source of food for offspring and protein for females. However, this specialization may come at a price; increased competition for resources and greater risk of local extinction. The present study examined the effects of the presence or absence of intraspecific colonization, carcass age, and exposure time on the colonization and oviposition responses of the specialist, primary colonizer, the secondary screw worm, Cochliomyia macellaria (Fabricius) (Diptera: Calliphoridae). Carcass age, exposure time, and colonization status significantly influenced the ovipositional response of C. macellaria. This species exhibited an oviposition preference for aged carcasses, with a tendency for higher oviposition after 8-h exposure time, but no preference between previously colonized or uncolonized carcasses. Mean egg hatch rate was also shown to be influenced by the aforementioned factors, with mean hatch rates varying between 81.26 and 90.97% across various treatments. These results provide insight into mechanisms driving succession on carrion, as well as highlight the variation observed in successional studies for the targeted species. Investigators relying on arthropod succession to indicate a time of colonization should proceed with caution in relying solely on the assumption primary colonizers only arrive and colonize fresh carrion.
ATIM-33. INTERIM RESULTS OF A PHASE II MULTI-CENTER STUDY OF ONCOLYTIC ADENOVIRUS DNX-2401 WITH PEMBROLIZUMAB FOR RECURRENT GLIOBLASTOMA; CAPTIVE STUDY (KEYNOTE-192)
Authors: Aiken Robert , Chen Clark , Cloughesy Timothy , Colman Howard , Daras Mariza , Groves Morris , Khagi Simon , Kumthekar Priya , Lang Frederick , Nassiri Farshad , Ong Shirley , Ramakrishna Rohan , Sonabend Adam , Vogelbaum Michael , Zadeh Gelareh , Agensky Laura , Bidwell Carin , Watkins Barry , Tufaro Frank , Peterkin Joanna
Published: December 2019

BACKGROUND

DNX-2401 (tasadenoturev) is a replication-competent, tumor-selective, oncolytic adenovirus. Phase I studies in adults with recurrent glioblastoma (rGBM) have demonstrated safety and encouraging clinical activity. A Phase II open-label, dose-escalating multi-center study in rGBM was initiated to evaluate DNX-2401 with pembrolizumab. Planned enrollment of 48 subjects is complete.

METHODS

Subjects ≥ 18 years, with a single tumor, KPS ≥ 70% and adequate organ function were enrolled sequentially into 3 cohorts of DNX-2401 (5e8vp, 5e9vp, 5e10vp). A single intratumoral injection of DNX-2401 was administered followed 7 days later by pembrolizumab (200 mg IV). Thereafter, pembrolizumab was infused Q3wks up to 24 months until progression or toxicity. 5e10vp was determined as the optimal dose and this cohort was expanded. Safety monitoring, assessments of response and survival follow-up are ongoing.

RESULTS

Nine subjects were treated in the escalation phase; 42 subjects received 5e10vp. No dose-limiting toxicity or unexpected safety issues were identified by an independent review committee, and there were no treatment-related deaths. Adverse events were primarily consistent with underlying disease, effects of the neuro-procedure, expected effects of pembrolizumab, and concomitant use of steroids/anticonvulsants per the standard of care. The majority of events were mild to moderate, and unrelated to DNX-2401. Headache and manageable vasogenic edema were the most common events related to DNX-2401 with pembrolizumab. For the 48 subjects who received pembrolizumab (median 6 cycles), median OS from DNX-2401 administration was 12 months (95% CI, 10.6–14.7), OS6 was 91%, and 47% experienced clinical benefit (stable disease or better). Four subjects (5e10) had a partial response (two with > 94% regression of tumor), and three (5e8; 5e10[2]) are alive > 20 months. Updated safety and efficacy results will be presented.

CONCLUSIONS

The data continue to demonstrate that DNX-2401 administered with pembrolizumab has an acceptable safety profile. Long-term survival and clinical benefit remain compelling.
ATIM-35. THE ASSOCIATIONS BETWEEN TOTAL LYMPHOCYTE COUNTS AFTER CONCOMITANT CHEMORADIATION WITH OVERALL SURVIVAL IN PATIENTS WITH NEWLY DIAGNOSED GLIOBLASTOMA
Authors: Ahn Stephen , Park Jae-Sung , Kil Hong Yong , Ho Yang Seung , Jeun Sin-Soo
Published: December 2019

Several studies have been conducted to determine the relationship between post-treatment total lymphocyte count (TLC) and overall survival (OS) in patients with malignant tumors including glioblastomas (GBMs). In this retrospective study, whether patients with newly diagnosed GBM experience significant lymphopenia after concomitant chemoradiation (CCRT) was evaluated, and whether TLC after this treatment is associated with OS in the treated population was examined. Using electronic medical records, all patients newly diagnosed with GBM between 2008 and 2016 at Seoul St. Mary’s Hospital were retrospectively examined. The eligible criteria included the following: 1) craniotomy with surgical resection or biopsy, 2) completion of CCRT, 3) accessible baseline and/or follow-up complete blood count (CBC). Median TLC significantly decreased after completion of CCRT, compared to TLC at baseline (1,742 versus 1,319 cells/mm3, P-value < 0.001). Patients with TLC < 1,200 cells/mm3 at 4 weeks after the completion of CCRT showed shorter survival than those with TLC ≥ 1,200 cells/mm3 with median OS of 14.5 versus 21.0 months (P-value = 0.017). Also, in multivariate analysis for OS, TLC < 1,200 cells/mm3 at 4 weeks after the completion of CCRT (HR 1.97, 95% CI 1.61 – 2.25, P-value = 0.004) were significantly associated with shorter survival. The results from the present study indicate that treatment-related total lymphocyte counts after CCRT is associated with worse survival in patients with newly diagnosed GBM.
SURG-10. GRADE TWO GLIOMA SURGERY - A LARGE SINGLE CENTRE REVIEW OF CLINICAL, HISTOLOGICAL, GENETIC AND SURGICAL OUTCOMES
Authors: Richards Oliver , Kwon Churl-Su , Bolton William , Goodden John , Chumas Paul
Published: December 2019

We analysed the surgical outcomes in a large series of operated grade two glioma patients with emphasis on surgical resection volumes, histology, genetics and survival. All adult glioma patients (200) operated between 2009 and 2016 with histological confirmation of grade two glioma from a single United Kingdom unit were included. Baseline clinical data was obtained along with radiological assessment of the extent of tumour resection, histological diagnosis, mutation status and survival data. Univariate and multivariate statistical analysis was performed. Preliminary analysis of an initial 63 patients had an average follow up of 51 months. A mean tumour resection of 73.9% (Range 14.4–100%), with an average pre-operative tumour volume of 42.2cm3 was achieved. 48 patients underwent awake surgery. There was no significant difference between pre-operative Karnofsky score (93.0) and post-operative (91.6) function. IDH-mutant diffuse astrocytoma (55.5%), IDH-mutant 1p19q co-deleted oligodendroglioma (33.3%) and IDH wildtype diffuse astrocytoma (14.3%) were the commonest histological diagnoses. 32 patients underwent post-operative adjuvant oncology treatment, with 22 requiring repeat operation. Extent of resection in repeat surgeries was 58.6%. Preliminary statistical analysis on this initial sample has demonstrated that every additional year of age at diagnosis however is associated with a 0.5% reduction in resection (p=0.02) and a 0.2% decline in Karnofsky performance (p=< 0.01). Patients with 1p19q co-deletion had a significant increase in progression free survival (PFS) (p=0.04). No significant variables were found to predict the risk of second surgery. Patients with eloquent tumour locations were significantly less likely to suffer post-operative neurological deficits (p< 0.01) Provisional analysis of our case series demonstrates an excellent extent of resection for our cohort of grade two glioma patients. 1p19q co-deletion in this group was significantly associated with improved PFS. Full analysis of the entire patient cohort will be available in time for presenting.
SURG-14. DOES WAITING MATTER? HOW TIME FROM DIAGNOSTIC MRI TO SURGICAL RESECTION AFFECTS OUTCOMES IN NEWLY DIAGNOSED GLIOBLASTOMA
Authors: Young Jacob , Muster Rachel , Chandra Ankush , Morshed Ramin , Aghi Manish
Published: December 2019

Surgical resection is standard of care for patients with lesions concerning for high-grade glioma on MRI scan. There is no consensus on the urgency of the procedure for patients with good clinical performance status. Treatment history and functional outcomes were collected retrospectively from the electronic medical record for 105 consecutive patients with newly diagnosed WHO Grade IV gliomas who underwent surgical resection at the University of California, San Francisco in 2014 and 2015 (41% female, average age = 61.25). Median preoperative KPS score was 80. Median wait time to surgery was 11 days after the initial MRI scan (range: 0–213 days). Mean tumor volume at the time of initial MRI scan was 29.0 cm3 (SD = 26.1 cm3), which did not significantly differ from the mean pre-operative tumor volume of 31.2 cm3 (SD = 27.3 cm3). In this retrospective cohort, patients with larger glioblastomas were taken to surgery more quickly. Patients who presented to the emergency room were more likely to wait less than 7 days (p < 0.001). Patients who waited less than 7 days had a larger initial and pre-operative tumor volume compared to patients who waited between 7–21 days and patients who waited over 21 days (p=< 0.001, p=< 0.001). Tumor growth occurred in 10% of patients who waited one week or less, 26% of patients who waited one to three weeks, and 55% of patients who waited over 3 weeks. Overall survival was not significantly affected by wait time until tumor resection (p=0.52). Additionally, Tumor growth was not associated with postoperative outcomes including postoperative KPS score, postoperative deficits, 3-month follow up KPS score, overall survival, and survival after surgery. In conclusion, longer wait time to surgery does not impact overall survival, pre-, and post-operative KPS, but the tumor is likely to grow in the interim.
SCIDOT-29. EVALUATING THE FEASIBILITY OF INTRANASAL FLT DELIVERY FOR PET IMAGING OF PRIMARY BRAIN TUMORS
Authors: Carlisle Grant , Fowler Austin , Soma Joel , Drewes Lester , Friday Bret
Published: December 2019

INTRODUCTION

Glioblastoma (GBM) is an aggressive primary brain tumor with a dismal prognosis. Overall survival rates have been correlated to initial tumor resection making improved imaging techniques necessary for improved patient outcomes. Functional imaging with fluorothymidine (FLT) has been limited due to inefficient transfer through the blood-brain-barrier. In this experiment, we strived to test the efficacy of tritium-labeled-FLT (3H-FLT) delivery to brain tissue through intranasal (IN) versus intravenous (IV) administration in a rat model.

METHODS

Adult rats (Sprague Dawley, 180-200g) received 3H-FLT through either an IN or IV delivery method. At 5, 20, and 60 minutes, concentrations of 3H-FLT were measured in 16 brain regions as well as blood and non-target organs via isotope quantitation using scintillation detection. Pharmacokinetic parameters were calculated.

RESULTS

Intranasal olfactory bulb concentrations of 3H-FLT trended higher compared to IV olfactory bulb. All other brain region concentrations were insignificantly different. Kp (brain-blood ratio) values mimicked this trend. Secondary calculations were performed to evaluate intranasal CNS drug targeting. Initial trends showed a more effective IN drug penetration to the olfactory bulb, spinal cord, and hippocampus. Drug targeting efficiency (DTE%) was found to be highest in the olfactory bulb at 212%, but all other brain regions were greater than 100% suggesting more efficient drug targeting with intranasal administration. Nose-to-brain direct transport percentage (DTP%), and comparative brain bioavailability (B%) showed similar trends. Non-target tissues including heart, lung, adipose and skeletal muscle were collected in the 5- and 60-minute trials and found to be significantly higher than all brain concentrations.

CONCLUSION

Drug delivery calculations suggest increased efficacy with IN administration of FLT to all brain regions compared to IV administration. However, additional optimization is likely necessary to improve PET imaging of primary brain tumors using IN delivery due to the relatively small differences observed.
CBMT-37. OSMR CONTROLS CELLULAR RESPIRATION AND RESISTANCE TO THERAPY
Authors: Sharanek Ahmad , Burban Audrey , Jahani-Asl Arezu
Published: December 2019

Cytokines and their receptors play important roles in the regulation of cell fate, inflammation and immunity. The cytokine receptor for Oncostatin M (OSMR) drives brain tumor stem cell (BTSC) proliferation and tumorigenesis. Here, we report a novel role for OSMR in regulation of cellular respiration. Genetic knockdown of OSMR in BTSCs impairs mitochondrial biogenesis and oxidative phosphorylation. Importantly, blockade of OSMR signalling in BTSCs sensitizes them to ionizing radiation and Temozolomide in vitro and in vivo. This mechanism whereby OSMR regulates mitochondrial respiration and metabolism is conserved in post-mitotic neutrons. Thus, while OSMR is required for BTSC proliferation, OSMR confers resistance to therapy via enhancing mitochondrial respiration, independent of its role in proliferation. Our data suggest that therapeutic targeting of OSMR may be beneficial to eradicate quiescent tumour stem cells and tumour relapse.
PATH-50. ROUTINE MOLECULAR DIAGNOSIS OF GLIOMA PATIENTS USING A GLIOMA-SPECIFIC NGS PANEL
Authors: Yoshimoto Koji , Higa Nayuta , Yonezawa Hajime , Uchida Hiroyuki , Akahane Toshiaki , Tanimoto Akihide
Published: December 2019

AIM

The 2016 WHO classification requires molecular diagnosis in routine glioma diagnostics. However, analysis of key driver gene mutations and chromosome 1p/19q co-deletions cannot be performed in a single platform. In this study, we evaluated the feasibility of a glioma-specific NGS panel for molecular diagnosis of glioma patients.

MATERIALS AND METHODS

We developed a glioma-specific NGS panel consisting of 48 genes, including glioma-relevant key driver genes and 21 genes mapped to chromosome 1 and 19. DNA was extracted from formaldehyde fixed-paraffin embedded (FFPE) tumor tissues histologically identified by a pathologist, and from patient-derived blood as a control. In this system, we implemented a molecular barcodes method to enhance confidence in clinical samples and analyzed 80 glioma patients (Grade II: 17 cases, Grade III: 16 cases, Grade IV: 47 cases).

RESULTS

From these 80 cases, IDH1 and H3F3A mutations were detected in 23 cases (29%) and 2 cases (5%), respectively. The 1p/19q co-deletion was detected in 15 cases (19%), with all cases also containing IDH1 mutations. In Grade IV cases, EGFR, PDGFR, and FGFR mutations were detected in 6% (amp 19%), 9%, and 4% (amp 17%) of cases, respectively. PTEN, TP53, NF1, RB1, and CDKN2A mutations were detected in 37% (del 72%), 45% (del 13%), 21% (del 23%), 15% (del 60%), and 2% (del 53%) of cases, respectively.

CONCLUSION

Diagnosis of glioma patients with this glioma-specific NGS panel is feasible.
NCOG-03. COGNITIVE CONCERNS AND PERFORMANCE IN PATIENTS WITH METASTATIC NON-SMALL CELL LUNG CANCER (mNSCLC)
Authors: Eggen Annemarie , Richard Nadine , Shen Gerald , Shultz David , Leighl Natasha , Liu Geoffrey , Sun Alexander , Bosma Ingeborg , Reyners Anna , Jalving Mathilde , Rodin Gary , Edelstein Kim
Published: December 2019

INTRODUCTION

Cognitive concerns and objective cognitive impairment are both common in cancer patients, although the relationship between these variables is uncertain. Brain metastases have the potential to affect both outcomes. We examined the relationships between cognitive concerns, cognitive performance, and psychological disturbance in mNSCLC patients with and without brain metastases.

METHODS

mNSCLC patients completed standardized neuropsychological tests (HVLT-R, TMTA/B, COWA) and questionnaires measuring cognitive and neurobehavioral concerns, depression, demoralization, self-esteem, illness intrusiveness, and physical symptoms. Perceived cognitive impairment was defined as FACT-Cog scores ≤1.5 SD below the normative mean. Impaired cognitive performance was defined as ≥2 test scores ≤1.5 SD or one test score ≤2.0 SD below normative means. Multivariate analyses used the mean composite of neuropsychological test z-scores (COG-comp). Progressive disease (extra- and/or intracranial) was defined as radiological progression or clinical deterioration within one month before the study.

RESULTS

74 patients participated (53% female; median age 62 (37–82); 30% EGFR mutated). Time since mNSCLC diagnosis was 11 months (median; 0–89). 50% had brain metastases, 21 of whom received cranial radiation (11 SRS, 10 WBRT±SRS). 27% reported cognitive concerns and 42% were impaired on objective testing (HVLT-R:34%, TMT:27%, COWA:16%). Neither was more common in patients with brain metastases. COG-comp (mean±SD: –0.39±0.91) was unrelated to cognitive concerns. In multivariate analyses, less depression (p< 0.01) and illness intrusiveness (p=0.03), and absence of disease progression (p=0.03) were related to better perceived cognitive function. No significant associations were found between cognitive performance and demographic, disease, or psychological variables.

CONCLUSION

Cognitive impairment is common in mNSCLC patients with or without brain metastases, but is independent of cognitive concerns. Cognitive concerns which are linked to depression, illness intrusiveness and disease progression, may be more likely to reflect the impact of cognitive changes in daily life. Both merit further clinical and research attention.
NIMG-12. MULTICOLOURED-ASSISTED SURGERY FOR RESECTION OF HIGH GRADE GLIOMAS WITH 5-AMINOLEVULINACID
Authors: Charalampaki Cleopatra , Atanasopoulos Dimitrios
Published: December 2019

INTRODUCTION

Fluorescence guided surgery with the use of 5-aminolevulinacid (5 -ALA) is nowadays the state of the art treatment of high grade gliomas. However, intraoperative visualization of 5-ALA under dark blue light remains challenging, especially when leaking blood covers parts of the surgical field, where tumor fluorescence becomes invisible. To overcome this problem and combine the brightness of visible light with the information delivered by fluorescence we developed multispectral fluorescence, a technique able to project both information in real time to the surgeon’s eyes, and embedded it on a surgical microscope.

METHODS

We examined 40 patients with brain tumors who underwent surgery, using the MFL operative technique. The tumors involved comprised of 20 glioblastomas, 7 astrocytomas WHO III, 5 meningiomas and 8 metastatic tumors. The MFL technique with the real-time overlay of 5-ALA fluorescence and white light was intraoperatively compared to the classic blue filter detecting 5-ALA fluorescence.

RESULTS

The tumor was in all cases clearly visible and highlighted from the surrounding tissues. The pseudocolor we chose to visualize the tumor was green, representing 5-ALA fluorescence, with the surrounding brain tissueremained in its origin white color. In the cases where blood was covering the surgical field, orientation was easy to maintain, due to the additional information delivered from the white light image.

CONCLUSIONS

The MFL technique embedded on a surgical microscope opens the way for a precise and clear visualization of tumor 5-ALA fluorescence in real time under white light. It can be easily implemented in the resection of all tumors accumulating 5-ALA. Drawbacks of classic 5-ALA fluorescence such as hidden fluorescence because of overlying blood could be overcome with the presence of additional white light and the clear visualization of the exposed brain.
PDCT-03. CHEMOTHERAPY STRATEGIES FOR YOUNG CHILDREN NEWLY DIAGNOSED WITH MEDULLOBLASTOMA UP TO THE ERA OF MOLECULAR PROFILING – A COMPARATIVE OUTCOMES ANALYSIS
Authors: Finlay Jonathan , Mynarek Martin , Dhall Girish , Lafay-Cousin Lucie , Mazewski Claire , Ashley David , Leary Sarah , von Bueren Andre , Gerber Nicolas , Cohen Bruce , Robinson Giles , Russell Geyer J , Tait Diana , Stanek Joseph , Gajjar Amar , Rutkowski Stefan
Published: December 2019

BACKGROUND/OBJECTIVE

Survival had been poor in several multi-center/national studies since the 1980s attempting to delay, avoid or minimize brain irradiation in young children with medulloblastoma. The introduction of regimens in Germany incorporating both intravenous high-dose (HD-MTX) and intraventricular (IVENT-MTX) methotrexate, as well as regimens in North America incorporating marrow-ablative chemotherapy with autologous hematopoietic cell rescue (HDCx+AuHCR), have reported encouraging outcomes. The objective of this report is to perform a comparative outcomes analysis of these differing strategies.

METHODS

Data from 17 prospective multi-center trials published between 1990 and 2018 for children under six years old with medulloblastoma were reviewed; event-free (EFS) and overall survivals (OS) were compared.

RESULTS

Two trials using full-dose cranio-spinal irradiation with or without chemotherapy reported 5-year survivals of 32–38%. Three trials using standard chemotherapy with delayed irradiation reported 2-4-year EFS and OS of 23–34% and 31–46%. Two trials employing standard chemotherapy without irradiation reported 3-5-year EFS and OS of 22–33% and 34–43%. Four trials incorporating HD-MTX with or without IVENT-MTX reported 5-10-year EFS and OS of 56–59% and 67–80%, and 31% and 59% respectively; one trial with HD-MTX without IVENT-MTX for localized desmoplastic/nodular medulloblastoma (DN-MB) reported 2-year EFS and OS of 52% and 92%. Finally, five trials employing induction chemotherapy, with or without HD-MTX, followed by single or tandem HDCx+AuHCR have reported 3-5-year EFS and OS of 45–60% and 60–70%.

CONCLUSIONS

The best survivals are observed in trials including HD-MTX and IVENT-MTX or including HD-MTX during induction followed by HDCx+AuHCR. Because histology/biology (classic and large cell/anaplastic versus DN-MB; SHH versus non-SHH subtypes) have crucial prognostic roles, EFS and irradiation-free survival advantages require analysis in these settings. The benefit of these trials appears true for all young children with medulloblastoma. Risk-adapted treatment stratification for young children may be improved by molecular profiling of SHH- and non-SHH medulloblastoma.
PDCT-16. A PHASE I STUDY OF SUBEROYLANILIDE HYDROXAMIC ACID (SAHA) WITH TEMSIROLIMUS IN CHILDREN WITH NEWLY DIAGNOSED OR PROGRESSIVE DIFFUSE INTRINSIC PONTINE GLIOMA (DIPG)
Authors: Khatua Soumen , Chandra Joya , Gopalakrishnan Vidya , Ketonen Leena , Johnson Michael , Sandberg David , Fuller Greg , Morrell Miriam , Meador Heather , Bolton Krystal , Butterworth Ginger , Mukheef Farah , Sadighi Zsila , Zaky Wafik
Published: December 2019

Diffuse intrinsic pontine glioma (DIPG) in children remains essentially incurable with a median survival of 12 months. Radiation therapy is currently the standard treatment modality. To date chemotherapy or biologic agents have had no meaningful increase in survival. Data from biopsied DIPG showed the PI3K/AKT/mTOR pathway as a major oncogenic player. Thus targeting these pathways with mTOR inhibitors could hold promise. Genomic and epigenetic insights have shown the role of histone deacetylase (HDAC) in these tumors. Both temsirolimus (mTOR inhibitor) and SAHA (HDAC inhibitor) are well described in pediatric clinical trials with an established maximum tolerated dose (MTD) for phase II studies. This is the first ongoing phase I multi-targeted therapeutic study, in pediatric DIPG, using SAHA and temsirolimus in a combinatorial approach, targeting the key oncogenic pathway and molecules (NCT02420613 currently recruiting). Patients with a performance score of 50 or greater, with newly diagnosed (Stratum I), or progressive (stratum II) DIPG will be eligible. Biopsy is not mandatory. A standard 3 + 3 design is being used for this study. 1 dose escalation and 2 dose de-escalations are permitted beyond the starting dose level. In stratum I patients receive radiation therapy concurrently with vorinostat on the days of radiation, followed by adjuvant therapy with vorinostat and temsirolimus for 10 cycles if they do not have progressive disease. In stratum II patients receive vorinostat and temsirolimus for 12 cycles (28 day cycle), if they do not have progressive disease. Correlative studies evaluating histone acetylation, phosphorylated 70S6K and Akt are being performed. Currently 5 patients have been enrolled, and the study is at the dose escalation level with no dose limiting toxicity (DLT) seen so far. Safety, adverse effects, biological correlatives, and clinical outcomes will be reported once study is completed.
Adapting an evidence-based positive youth development intervention to prevent sexual and teen dating violence
Authors: Eisman Andria B , Hicks Megan , Kernsmith Poco D , Rupp Laney , Smith-Darden Joanne P , Zimmerman Marc A
Published: December 2019

Adapting evidence-based interventions (EBIs) guided by implementation science frameworks is a promising way to accelerate the translation of effective violence prevention in schools. School-based interventions offer an opportunity to reduce the risk of multiple forms of violence, including sexual violence (SV) and teen dating violence (TDV). EBIs in schools reach large populations of adolescents, including those underserved in other settings. Although specific SV/TDV prevention programs exist, evaluations indicate limited effectiveness over time. We adapted systematically the Youth Empowerment Solutions (YES) violence-prevention EBI using key adaptation steps described in implementation science frameworks to expand the scope of YES to integrate an SV/TDV focus and meet the needs of local youth. In the formative project year, the team adapted YES to integrate SV/TDV content informed by key steps outlined in frameworks including ADAPT-ITT, research-tested intervention programs, and map of the adaptation process. These steps include: (a) assess school and student needs, (b) identify, select an EBI, (c) consult with experts with knowledge in the new topic area (SV/TDV), (d) collaborate with community partners and stakeholders, (e) identify areas for adaptation while maintaining fidelity to core elements, (f) train staff, (g) pilot test adapted materials, (h) implement, and (i) evaluate. We developed the YES for Healthy Relationships (YES-HR), a school-based prevention program that retained core elements of YES, including content related to mastery, adult resources, leadership skills, and community engagement, while integrating SV/TDV-specific content (e.g., consent). Implementation science adaptation frameworks are useful in guiding the systematic adaptation of existing EBIs to meet the needs of youth.
The Cotton miR477-CBP60A Module Participates in Plant Defense Against Verticillium dahlia
Authors: Hu Guang , Hao Mengyan , Wang Le , Liu Jianfen , Zhang Zhennan , Tang Ye , Peng Qingzhong , Yang Zuoren , Wu Jiahe
Published: December 2019

Previous reports have shown that, when Verticillium dahliae localizes at the root surface, many microRNAs (miRNAs) were identified at the early induction stage. Here, we constructed two groups from two timepoints of small RNA (sRNA) in cotton root responses to V. dahliae at the later induction stage, pathogen localizing in the interior of root tissue. We identified 71 known and 378 novel miRNAs from six libraries of the pathogen-induced and the control sRNAs. Combined with degradome and sRNA sequencing, 178 corresponding miRNA target genes were identified, in which 40 target genes from differentially expressed miRNAs were primarily associated with oxidation-reduction and stress responses. More importantly, we characterized the cotton miR477-CBP60A module in the later response of the plant to V. dahliae infection. A β-glucuronidase fusion reporter and cleavage site analysis showed that ghr-miR477 directly cleaved the messenger RNA of GhCBP60A in the posttranscriptional process. The ghr-miR477-silencing decreased plant resistance to this fungus, while the knockdown of GhCBP60A increased plant resistance, which regulated GhICS1 expression to determine salicylic acid level. Our data documented that numerous later-inducible miRNAs in the plant response to V. dahliae, suggesting that these miRNAs play important roles in plant resistance to vascular disease.
Enhanced Recovery After Surgery (ERAS)
Authors: Echeverria-Villalobos Marco , Stoicea Nicoleta , Todeschini Alexandre B. , Fiorda-Diaz Juan , Uribe Alberto A. , Weaver Tristan , Bergese Sergio D.
Published: December 2019

Objectives:

The objective of this study was to review the current scientific evidence on the role of Enhanced Recovery After Surgery (ERAS) implementations in reducing postoperative opioid consumption and their potential association with the risk reduction for long-term opioid use, physical opioid dependency, and opioid addiction.

Methods:

A literature search was conducted using the following medical subject heading keywords: “postoperative pain,” “postoperative pain management,” “multimodal analgesia,” “ERAS,” “Enhanced Recovery,” “opioid-free analgesia,” or “opioid crisis.”

Discussion:

Identification and management of pre-existing psychosocial factors, comorbid pain entities, and chronic opioid use have a significant impact on the severity of postoperative pain. Different multimodal analgesia approaches have been associated with reduced postoperative pain scores and opioid consumption. Health care providers, patients, and family members should recognize the advantages of opioid-free analgesia techniques in postoperative pain management. As part of ERAS protocols, transitional pain services may consider current therapeutic alternatives for acute and long-term pain management that include minimizing perioperative opioid use and establishing adequate opioid prescription practices.
Hierarchical Models for International Comparisons
Authors: Disney George , Gurrin Lyle , Aitken Zoe , Emerson Eric , Milner Allison , Kavanagh Anne , Petrie Dennis
Published: December 2019

Background:

International comparisons of social inequalities in health outcomes and behaviors are challenging. Due to the level of disaggregation often required, data can be sparse and methods to make adequately powered comparisons are lacking. We aimed to illustrate the value of a hierarchical Bayesian approach that partially pools country-level estimates, reducing the influence of sampling variation and increasing the stability of estimates. We also illustrate a new way of simultaneously displaying the uncertainty of both relative and absolute inequality estimates.

Methods:

We used the 2014 European Social Survey to estimate smoking prevalence, absolute, and relative inequalities for men and women with and without disabilities in 21 European countries. We simultaneously display smoking prevalence for people without disabilities (x-axis), absolute (y-axis), and relative inequalities (contour lines), capturing the uncertainty of these estimates by plotting a 2-D normal approximation of the posterior distribution from the full probability (Bayesian) analysis.

Results:

Our study confirms that across Europe smoking prevalence is generally higher for people with disabilities than for those without. Our model shifts more extreme prevalence estimates that are based on fewer observations, toward the European mean.

Conclusions:

We demonstrate the utility of partial pooling to make adequately powered estimates of inequality, allowing estimates from countries with smaller sample sizes to benefit from the increased precision of the European average. Including uncertainty on our inequality plot provides a useful tool for evaluating both the geographical patterns of variation in, and strength of evidence for, differences in social inequalities in health.
Inhibition of TRPA1 Promotes Cardiac Repair in Mice After Myocardial Infarction
Authors: Li Ruoshui , Liu Rongchen , Yan Fangying , Zhuang Xinyu , Shi Haiming , Gao Xiufang
Published: December 2019

Recent studies have shown that TRPA1, a nonselective cation channel with high permeability to calcium, is expressed in many tissues of the cardiovascular system and is involved in the pathogenesis of many cardiovascular diseases. However, the role of TRPA1 in cardiac repair after myocardial infarction (MI) has not been clearly defined. The aim of this study was to confirm whether inhibition of TRPA1 could attenuate MI-induced cardiac ischemia injury. The C57BL/6 mice were subjected to ligation of the left anterior descending coronary artery and treated with TRPA1-specific inhibitor HC-030031 (HC) for 4 weeks. Echocardiography was performed to assess cardiac function. The results showed that HC significantly attenuated MI-induced cardiac dysfunction 4 weeks after MI. Similarly, HC reduced cardiac fibrosis and cell apoptosis after MI and significantly increased angiogenesis in the border zone of the infarct. In vitro, we found that HC promoted the proliferation and migration of human umbilical vein endothelial cells (HUVECs). Importantly, HC treatment decreased phosphatase and tensin homolog expression and augmented the expression of phosphorylated Akt in the myocardium post MI and HUVECs. However, treatment of HUVECs with a PI3K inhibitor, LY294002, before HC administration almost completely abolished HC-induced migration in HUVECs. In conclusion, we demonstrate that the inhibition of TRPA1 promotes angiogenesis after MI, thereby alleviating myocardial ischemia injury via mechanisms involving inhibition of phosphatase and tensin homolog expression and subsequent activation of the PI3K/Akt signaling.
Establishing a Protocol for Closed Treatment of Mandibular Condyle Fractures with Dynamic Elastic Therapy
Authors: Kamel George N. , De Ruiter Brandon J. , Baghdasarian Daniel , Mostafa Evan , Levin Avinoam , Davidson Edward H.
Published: December 2019

Treatment of mandibular condyle fractures is controversial. Open treatment achieves anatomic reduction with occlusal stability and faster functional recovery but risks facial nerve injury and jeopardizes joint capsule circulation which can lead to bone resorption. Traditional closed treatment avoids these issues but requires prolonged fixation and risks subsequent facial asymmetry, occlusal disturbance, and ankylosis. Rather than wires, closed treatment with elastics allows for customizable management of a healing fracture with ability to alter vector and degree of traction to restore vertical height and occlusion with less discomfort and decreased risk for ankylosis. In this protocol, unilateral condylar fractures were treated with class II elastics ipsilateral to injury and class I contralaterally. Class III elastics were used contralaterally if additional traction was required and Class II elastics were placed bilaterally for bilateral fractures. Patients were sequentially advanced from fixating to guiding to supportive elastics by titrating elastic vector to any dental midline incongruency or chin deviation. Six patients were treated with this protocol with six-month follow-up. Fracture patterns included displaced and dislocated fractures as well as intracapsular and extracapsular condylar fractures. All patients at completion of the protocol had objective centric occlusion with no subjective malocclusion, chin deviation, facial asymmetry, or temporomandibular joint pain. These early data demonstrate a safe and efficacious innovative protocol for closed treatment of mandibular condylar fractures with dynamic elastic therapy.
Comparing Dry Eye Disease After Small Incision Lenticule Extraction and Laser Subepithelial Keratomileusis
Authors: Chung Byunghoon , Choi Moonjung , Lee Keun Young , Kim Eung Kweon , Seo Kyoung Yul , Jun Ikhyun , Kim Kang Yoon , Kim Tae-im
Published: December 2019

Purpose:

To compare dry eye disease parameters between small incision lenticule extraction (SMILE) and laser subepithelial keratomileusis (LASEK).

Methods:

This prospective, nonrandomized study included 39 eyes of 39 patients who underwent SMILE (n = 19) and LASEK (n = 20). Dry eye disease parameters included Ocular Surface Disease Index (OSDI), tear breakup time, Schirmer I test (SIT) value, corneal esthesiometry result, tear meniscus area, meibomian gland evaluation result, lipid layer thickness, and blink rate. Evaluations were performed before surgery and at 1 and 6 months after surgery.

Results:

Compared with the LASEK group, the SMILE group showed lower corneal esthesiometry values at 1 month and higher OSDI scores and lower SIT values at 6 months after surgery. The SMILE group showed significantly higher OSDI scores at 1 and 6 months after surgery than before, but significantly lower OSDI scores at 6 months than at 1 month after surgery. Both groups showed significantly decreased corneal sensitivity at 1 month after surgery, which increased to the preoperative level 6 months after surgery. The change in OSDI scores at 1 month after surgery positively correlated with changes in the total and partial blink rates, whereas the change in corneal sensitivity at 1 month after surgery negatively correlated with the total and partial blink rates.

Conclusions:

Both SMILE and LASEK groups showed temporary decreases in corneal sensitivity, which recovered to baseline levels. Although subjective symptoms worsened after SMILE, SIT values improved after LASEK. Compared with SMILE, LASEK yielded better results regarding subjective symptoms, tear production, and corneal sensitivity.
Ultrasonic Aspiration for Debulking Infiltrative Masses of the Orbit
Authors: Sun Susan Y. , Stewart Krista , Lyford-Pike Sofia , Garrity James A. , Harrison Andrew R. , Mokhtarzadeh Ali
Published: December 2019

Purpose:

To demonstrate the utility of an ultrasonic aspirator (Sonopet, Stryker Corporation; Kalamazoo, MI) for debulking firm, soft tissue masses of the orbit.

Methods:

Case series. The ultrasonic aspirator was used to debulk firm, soft tissue masses in 3 cases. The initial patient had a large orbitofacial mass extending to the inferior and lateral orbital apex secondary to IgG4 disease. The second patient had a lacrimal sac adenocarcinoma extending to the medial orbital apex. The third patient had a large orbital mass extending to the apex secondary to granulomatosis with polyangiitis.

Results:

The ultrasonic aspirator facilitated debulking of infiltrative firm soft tissue masses of the orbit. The device’s ability to emulsify, irrigate, and aspirate, along with its small footprint, facilitated precise sculpting and debulking to an extent which would have been difficult otherwise due to location.

Conclusions:

The ultrasonic aspirator allows precise sculpting of infiltrative firm soft tissue masses in the orbit and is particularly useful in cases with challenging anatomical access.
Proptosis as a Primary Symptom of Brain Arteriovenous Malformation
Authors: Lee Jong Eun , Yoon Jin Sook , Park Keun Young
Published: December 2019

Proptosis is a common yet cardinal symptom that may indicate the development of a wide range of diseases. Causes of proptosis are usually classified into vascular, inflammatory, endocrine, and neoplastic. Herein, the authors describe a case where proptosis manifested as the primary and only symptom of a massive brain arteriovenous malformation. Deprived of any other conventional symptoms and signs of a brain arteriovenous malformation, such as headaches, nausea, vision loss, increased ocular pressure, and so on, brain imaging played a key role in confirming the diagnosis of this patient. This case proclaims how imperative it is for ophthalmologists to consider the potential of brain arteriovenous malformation as a cause of proptosis and actively engage in brain imaging for diagnosis.
Myoepithelioma of the Lower Eyelid
Authors: Chandrasekaran Subhashini , Mirani Neena , Langer Paul D.
Published: December 2019

A 59-year-old woman presented with a 4-year history of a progressively growing, subcutaneous, painless, left lower eyelid mass with associated swelling and discomfort. Excisional biopsy established the diagnosis of a myoepithelioma, a tumor which, to the authors’ knowledge, has not been previously reported in the lower eyelid.
Serous Ovarian Cancer Caused by Exposure to Asbestos and Fibrous Talc in Cosmetic Talc Powders—A Case Series
Authors: Steffen Joan E. , Tran Triet , Yimam Muna , Clancy Kate M. , Bird Tess B. , Rigler Mark , Longo William , Egilman David S.
Published: December 2019

Objective:

Asbestos is a known cause of ovarian cancer. We report 10 cases of serous ovarian cancer among users of Johnson & Johnson (J&J) asbestos-containing “cosmetic” talc products.

Methods:

We conducted an asbestos exposure assessment during talc application and analyzed surgical tissues and talc containers for asbestos and talc.

Results:

Talc was found in all cases and tremolite and/or anthophyllite asbestos was found in 8/10 cases. The asbestos fibers found in the “cosmetic” talc containers matched those found in tissues. We estimated inhaled asbestos dose ranged from 0.38 to 5.18 fiber years.

Conclusion:

We provide evidence that the inhaled dose of asbestos/fibrous talc from “cosmetic” talc use causes ovarian cancer. The unique combination of the types of asbestiform minerals detected in cancerous tissue and “cosmetic” talc is a fingerprint for exposure to asbestos-containing talc.
Using compression therapy in a primary care setting to treat complications of chronic venous insufficiency
Authors: Love Sherry , White Justin R. , Vestal Brittney
Published: December 2019

Background:

Patients with chronic venous insufficiency (CVI) are prone to developing complications such as slow-healing venous leg ulcers.

Local Problem:

Nurse practitioners can assess patients for complications of CVI during routine examinations. If found, they can implement compression therapy and possibly prevent the development of slow-healing venous leg ulcers.

Methods:

A retrospective chart review of patient occurrences with complications due to CVI between 2011 and 2018 was conducted to evaluate patient outcomes when treated with compression therapy by their primary care providers (PCPs). Patients were identified by the Unna boot's Current Procedural Technology code, the compression therapy used by the providers. Patients included in the review had the diagnosis of or symptoms of CVI. Patient outcomes were identified as improved, unchanged, or deteriorated.

Interventions:

The use of compression therapy for patients with documented complication of CVI. The Unna boot was the compression device used at this practice.

Results:

There were 60 occurrences distributed among 40 patients who met the inclusion criteria. Of the 60 occurrences, 54 or 90% of patient occurrences had an improvement of symptoms. According to the Wound Healing Society Guidelines, high compression therapy, such as the Unna boot, is classified as most supportive, for treatment of venous ulcers.

Conclusions:

The results of this study demonstrate the positive impact PCPs, including nurse practitioners, may have when initiating compression therapy for patients with complications of CVI.