tbuckley/cabot-search huggingface dataset:
Protecting children against Japanese encephalitis in Bali, Indonesia
Authors: Justin Im, Ruchita Balasubramanian, Ni Wayan Yastini, I Gusti Ngurah Suwarba, Ayu Rai Andayani, Vinod Bura, Hyon Jin Jeon, John D Clemens, Florian Marks
Journal: The Lancet (2018)
NSRG-10. SURGICAL MANAGEMENT OF SYMPTOMATIC PAEDIATRIC VERTEBRAL HAEMANGIOMAS PRESENTING WITH MYELOPATHY WITH LONG TERM FOLLOW UP
Authors: Pankaj Singh, P Sarat Chandra, Shashank Kale, Satish Verma, Dattaraj Sawarkar, Amandeep Kumar
Journal: Neuro-Oncology (2018)

Vertebral hemangiomas (VH) are very rare in pediatric age group. There is no published large series with long term follow up. The purpose of this study was to look for long term outcome of surgical management. All patients up to 18 years age of VH treated at our hospital from May 2003 to August 2014 were included with follow up till august 2016. All had features of myelopathy. Patients demography, clinical details and follow up and complications were retrieved from hospital records. Functional clinical outcomes were measured using ASIA score. Mean age was 14.57 years with range of 10 years to 18 years. Mean follow up was 54.79 months with range from 25 month to 90 months. There were 7 male and 7 female patients. All were located in dorsal spine with single level involvement. Upper dorsal spine involvement was more common (12 cases 85.71%) than lower dorsal spine involvement (2 case 14.29%). All patients had weakness of lower limbs with features of myelopathy, urinary bladder symptoms were present in five patients. One patient had local site pain also. All patients have improvement in power of both lower limbs. Local pain which was present in 1 patient resolved, bladder symptoms present in 5 patients also resolved. This is largest series on symptomatic pediatric VH with long term follow up. Good postoperative results can be achieved with minimal complications. Individualization of treatment for each patient should be done with avoidance of selecting more blood loss procedures like corpectomies.
68Ga-PSMA-HBED-CC–Avid Synchronous Urinary Bladder Paraganglioma in a Patient With Metastatic Prostate Carcinoma
Authors: Ashwin Singh Parihar, Shelvin Kumar Vadi, Bhagwant Rai Mittal, Rajender Kumar, Amanjit Bal, Shrawan Kumar Singh
Journal: Clinical Nuclear Medicine (2018)

Ga-PSMA-HBED-CC PET/CT has proven to be a useful modality in patients with prostate carcinoma, especially in those with suspected recurrence and in detection of locoregional and distant metastases. However, with expanding use of this tracer, several recent reports of in vivo expression of PSMA in nonprostatic benign and malignant entities have been published. We report a patient with PSMA-avid synchronous urinary bladder paraganglioma and metastatic prostate carcinoma.
Defens-IN! Human α-Defensin 5 Acts as an Unwitting Double Agent to Promote Shigella Infection
Authors: Alison G. Murphy, Kevin J. Maloy
Journal: Immunity (2018)

Shigella pathogenesis has confounded researchers for years because of its narrow host selectivity and extraordinary infectious capability. In this issue of Immunity, Xu et al. (2018) identify a cunning mechanism whereby Shigella hijacks human α-defensin 5 to enhance its adhesion and subsequent invasion.
NSRG-08. PEDIATRIC NEUROSURGEONS AS “TWO-WAY PLAYERS”
Authors: Akira Gomi, Takashi Yamaguchi, Hirofumi Oguma, Satsuki Miyata
Journal: Neuro-Oncology (2018)

To borrow a term from baseball, pediatric neurosurgeons should be “two-way players” like Shohei Ohtani in the treatment of low-grade glioma (LGG). In Japanese, a “two-way player” is called a “dual-sword player.” One sword is surgery, and the other is chemotherapy. Chemotherapy for pediatric brain tumor is managed by pediatric oncologists in many countries, but in Japan this task has traditionally fallen to neurosurgeons. Japanese neurosurgeons can choose between the two swords according to the situation. This system may be particularly effective in cases of LGG located in eloquent areas, as with optic pathway hypothalamic astrocytoma (OPHA) or cervicomedullary astrocytoma (CMA). Here, we clarified the effectiveness of “dual-sword” pediatric neurosurgeons. We retrospectively analyzed the cases of 25 pediatric LGG patients treated in our institute from 2004 to 2017. Ten cases were treated using surgery alone. Two cases were treated by surgery and radiotherapy. Five OHPAs, two CMAs and two spinal LGGs were treated by surgery and chemotherapy. The chemotherapeutic regimens used were a CBDCA/VCR regimen and a weekly VBL regimen. Although radiotherapy could only be used once after surgery, chemotherapy could be used repeatedly, and so could be alternated with surgical therapy depending on the situation. “Dual-sword” neurosurgeons deal with both surgery and chemotherapy, so the decision-making process is rapid and the transitions can be made smoothly. Because chemotherapy regimens for LGG are not complicated, unlike those for medulloblastoma, neurosurgeons familiar with chemotherapy can perform this task. Two-way pediatric neurosurgeons are important for the treatment of pediatric LGG.
Vitamin D and risk of pregnancy related hypertensive disorders: mendelian randomisation study
Authors: Maria C Magnus, Kozeta Miliku, Anna Bauer, Stephanie M Engel, Janine F Felix, Vincent W V Jaddoe, Debbie A Lawlor, Stephanie J London, Per Magnus, Ralph McGinnis, Wenche Nystad, Christian M Page, Fernando Rivadeneira, Lars C Stene, German Tapia, Nicholas Williams, Carolina Bonilla, Abigail Fraser
Journal: BMJ (2018)

<h3>Abstract</h3> <h3>Objective</h3> To use mendelian randomisation to investigate whether 25-hydroxyvitamin D concentration has a causal effect on gestational hypertension or pre-eclampsia. <h3>Design</h3> One and two sample mendelian randomisation analyses. <h3>Setting</h3> Two European pregnancy cohorts (Avon Longitudinal Study of Parents and Children, and Generation R Study), and two case-control studies (subgroup nested within the Norwegian Mother and Child Cohort Study, and the UK Genetics of Pre-eclampsia Study). <h3>Participants</h3> 7389 women in a one sample mendelian randomisation analysis (751 with gestational hypertension and 135 with pre-eclampsia), and 3388 pre-eclampsia cases and 6059 controls in a two sample mendelian randomisation analysis. <h3>Exposures</h3> Single nucleotide polymorphisms in genes associated with vitamin D synthesis (rs10741657 and rs12785878) and metabolism (rs6013897 and rs2282679) were used as instrumental variables. <h3>Main outcome measures</h3> Gestational hypertension and pre-eclampsia defined according to the International Society for the Study of Hypertension in Pregnancy. <h3>Results</h3> In the conventional multivariable analysis, the relative risk for pre-eclampsia was 1.03 (95% confidence interval 1.00 to 1.07) per 10% decrease in 25-hydroxyvitamin D level, and 2.04 (1.02 to 4.07) for 25-hydroxyvitamin D levels &lt;25 nmol/L compared with ≥75 nmol/L. No association was found for gestational hypertension. The one sample mendelian randomisation analysis using the total genetic risk score as an instrument did not provide strong evidence of a linear effect of 25-hydroxyvitamin D on the risk of gestational hypertension or pre-eclampsia: odds ratio 0.90 (95% confidence interval 0.78 to 1.03) and 1.19 (0.92 to 1.52) per 10% decrease, respectively. The two sample mendelian randomisation estimate gave an odds ratio for pre-eclampsia of 0.98 (0.89 to 1.07) per 10% decrease in 25-hydroxyvitamin D level, an odds ratio of 0.96 (0.80 to 1.15) per unit increase in the log(odds) of 25-hydroxyvitamin D level &lt;75 nmol/L, and an odds ratio of 0.93 (0.73 to 1.19) per unit increase in the log(odds) of 25-hydroxyvitamin D levels &lt;50 nmol/L. <h3>Conclusions</h3> No strong evidence was found to support a causal effect of vitamin D status on gestational hypertension or pre-eclampsia. Future mendelian randomisation studies with a larger number of women with pre-eclampsia or more genetic instruments that would increase the proportion of 25-hydroxyvitamin D levels explained by the instrument are needed.
The Fleischner Society 2017 and British Thoracic Society 2015 guidelines for managing pulmonary nodules: keep calm and carry on
Authors: Arjun Nair, Anand Devaraj, Matthew E J Callister, David R Baldwin
Journal: Thorax (2018)

Same recommendation for pure ground-glass and part-solid nodules.Single: 5 years.Multiple: dictated by the largest nodule.4 years Risk assessment* Applied to all nodule sizes.Modified ACCP guidance.► Low risk: <5%.► High risk: ≥5%.Assignment of risk primarily based on known risk factors (age, smoking history, family history, nodule morphology, spiculation, upper lobe location, emphysema, pulmonary fibrosis).No specific model-based quantification suggested.For solid nodules, risk assessment only suggested for large (>8 mm, >300 mm 3 ) nodules.Brock model.► Low risk: <10%.► High risk: ≥10%.Herder model following PET-CT.► Low risk: <10%.► Intermediate risk: ≥10%-70%.► High risk: >70%.*Denotes parameters where the guidelines differ, which are potentially most likely to create the greatest divergence in management recommendations.It should be noted that this is solely the view of the authors, in the absence of evidence comparing the two guidelines.
Pan-cancer adaptive immune resistance as defined by the Tumor Inflammation Signature (TIS): results from The Cancer Genome Atlas (TCGA)
Authors: Patrick Danaher, Sarah Warren, Rongze Lu, Josue Samayoa, Amy Sullivan, Irena Pekker, Brett Wallden, Francesco M. Marincola, Alessandra Cesano
Journal: Journal for ImmunoTherapy of Cancer (2018)

The Tumor Inflammation Signature (TIS) is an investigational use only (IUO) 18-gene signature that measures a pre-existing but suppressed adaptive immune response within tumors. The TIS has been shown to enrich for patients who respond to the anti-PD1 agent pembrolizumab. To explore this immune phenotype within and across tumor types, we applied the TIS algorithm to over 9000 tumor gene expression profiles downloaded from The Cancer Genome Atlas (TCGA). As expected based on prior evidence, tumors with known clinical sensitivity to anti-programmed cell death protein 1 (PD-1) blockade had higher average TIS scores. Furthermore, TIS scores were more variable within than between tumor types, and within each tumor type a subset of patients with elevated scores was identifiable although with different prevalence associated with each tumor type, the latter consistent with the observed clinical responsiveness to anti PD-1 blockade. Notably, TIS scores only minimally correlated with mutation load in most tumors and ranking tumors by median TIS score showed differing association to clinical sensitivity to PD-1/PD-1 ligand 1 (PD-L1) blockade than ranking of the same tumors by mutation load. The expression patterns of the TIS algorithm genes were conserved across tumor types yet appeared to be minimally prognostic in most cancers, consistent with the TIS score serving as a pan-cancer measurement of the inflamed tumor phenotype. Characterization of the prevalence and variability of TIS will lead to increased understanding of the immune status of untreated tumors and may lead to improved indication selection for testing immunotherapy agents.
NFM-11. PEDIATRIC MENINGIOMAS ARE MOLECULARLY DISTINCT FROM ADULT COUNTERPARTS
Authors: Elmar Kirches, Felix Sahm, Christina Blücher, Svenja Boekhoff, Ulrich Schüller, Jens Schittenhelm, Matija Snuderl, Matthias Karajannis, Arie Perry, Torsten Pietsch, Hermann Müller, Joshua Rubin, David Capper, Katja Beck, Matthias Schlesner, Siegfried Kropf, Priscilla Brastianos, Andrey Korshunov, Stefan Pfister, Christian Mawrin
Journal: Neuro-Oncology (2018)

In contrast to adulthood, meningiomas are rare among children and adolescents. Although recent papers have characterized the genomics of adult meningiomas, the molecular profiles of childhood meningiomas have not been elucidated in detail. We analyzed 41 tumor samples from 37 pediatric meningioma patients (female: 17, male: 20; age range: 1-21 years). Atypical meningioma WHO grade II was the most frequent histological subtype (N=14, 38%). Most tumors were located at the convexity (N=18) or the skull base (N=15). Lack of SMO, AKT, KLF4/TRAF7 mutations by Sanger sequencing (n=22) prompted whole genome sequencing of a subset (n=7). All seven cases exhibited bi-allelic inactivation of NF2 (combined large deletion and germline (5/7) or somatic (2/7) base exchanges/frameshifts). Subsequently, tumor samples from all 37 patients were subjected to 450K DNA methylation profiling and targeted DNA sequencing using brain tumor specific gene panel. Loss of chromosome 22 was frequent (N=28, 76%), followed by loss of chromosome 1 (N=12, 32%) and chromosome 18 (N=7, 19%). Moreover, separation into three groups was evident: One encompassing all clear-cell meningiomas with enrichment for SMARCE1 mutations, a second dominated by atypical meningiomas, and a third group composed of benign meningiomas, as well as rare subtypes such as rhabdoid meningiomas. When analyzed with 105 adult tumors, most of pediatric meningiomas (28/37) clustered into a separate methylation group both by unsupervised hierarchical clustering and t-stochastic nearest neighbor embedding (t-SNE). Four recurrences were similar to the primary tumor. These data suggest that pediatric meningiomas are genetically distinct from adult counterparts.
Youthful systemic milieu alleviates renal ischemia-reperfusion injury in elderly mice
Authors: Dong Liu, Lide Lun, Qi Huang, Yichun Ning, Ying Zhang, Linna Wang, Zhiwei Yin, Yinping Zhang, Lihua Xia, Zhong Yin, Bo Fu, Guangyan Cai, Xuefeng Sun, Xiangmei Chen
Journal: Kidney International (2018)
Response to Comment on Gordin et al. Differential Association of Microvascular Attributions With Cardiovascular Disease in Patients With Long Duration of Type 1 Diabetes. Diabetes Care 2018;41:815–822
Authors: Daniel Gordin, George L. King
Journal: Diabetes Care (2018)

We thank Dr. Azar and colleagues for their interest in our article (1) on the low prevalence of cardiovascular disease (CVD) in patients with long duration of type 1 diabetes without proliferative diabetic retinopathy (PDR) but with diabetic kidney disease. Their results, presented in the accompanying letter (2), showed an association of the severity …
DIPG-27. GLIAL TUMOURS IN CHILDREN AND YOUNG ADULTS: ISOLATED ATRX ALTERATIONS, DO THEY REPRESENT DISTINCT SUBGROUP?
Authors: Sridhar Epari, Mamta Gurav, Vickky Pandit, Omshree Shetty, Vinayak Kadam, Ayushi Sahay, Girish Chinaswamy, JayantSastri Goda, Prakash Shetty, Aliasgar Moiyadi, Tejpal Gupta, Rakesh Jalali
Journal: Neuro-Oncology (2018)

This study is correlation of ATRX-loss with histone and IDH-mutations in astrocytic tumours of children and young adults. MATERIALS AND Study sample included: 1. High-grade (HGA) and all non-pilocytic astrocytomas, non-BRAF altered low-grade glial tumours (LGANOS) in ≤39 years, 2. EGFR non-amplified/IDH1/2 wild type midline located HGA with loss of ATRX in 40–55 years. ATRX by immunohistochemistry, H3.3, H3.1 and IDH1R132/IDH2R172 mutations by Sanger sequencing was done. Total cases: 365[1st group: 356 (HGA: 346; LGANOS: 10); 2nd group: 9]. 133 (37.4%), 54 (15.2%) and 51 (14.3%) of 1st group showed IDH-mutations, histone-alterations and isolated ATRX-loss respectively. Of the 2nd group, 2 and 3 cases showed histone-alterations and isolated ATRX-loss respectively. Overall 56 were histone gene-altered - H3.3 (K27M=41, K27E=2, G34R=8, G34V=1), H3.1 (HIST3BK27M=3) and frameshift mutation (n=1). Age-range of H3K27M/K27E (n=46): 1–46 years (0–3: 3, 4–6:2, 7–14: 16, 15–18:5, 19–25:8, 26–30:4, 31–39:6, >39: 2) and G34R/G34V: 7–26 years (7–14:4, 15–18:3, 19–25:1, 26–30:1). 11(24%) K27-mutant and 1 (11%) of G34-mutant were of superficial cerebral hemispheric (SCH) location. Four K27M-mutant were low-grade. 28 histone-altered cases [52%; K27M: 19 (43.2%), G34R/V:8 (89%), Frameshift:1] showed ATRX-loss. Interestingly, 54 (14.8%) cases showed isolated ATRX-loss with age-range 4–43 years (4–6:2, 7–14:11, 15–18:2, 19–25:13, 26–30:11, 31–39:12, >39:3). All were high-grade; 4 were midline while the rest were SCH. Isolated ATRX-loss, a distinct alteration in HGA of children and young adults. H3K27-mutations can be seen in adults; G34-mutations can be seen in young children and rarely both can be uncommon variants (K27E, G34V).
Therapeutic Targeting of Vascular Remodeling and Right Heart Failure in Pulmonary Arterial Hypertension with a HIF-2α Inhibitor
Authors: Zhiyu Dai, Maggie M. Zhu, Yi Peng, Narsa Machireddy, Colin E. Evans, Roberto Machado, Xianming Zhang, You-Yang Zhao
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

Pulmonary arterial hypertension (PAH) is a devastating disease characterized by progressive vasoconstriction and obliterative vascular remodeling that leads to right heart failure (RHF) and death. Current therapies do not target vascular remodeling and RHF, and result in only modest improvement of morbidity and mortality.
NSRG-24. OUTCOME OF SINGLE-TRAJECTORY ENDOSCOPIC THIRD VENTRICULOSTOMY AND BIOPSY IN THE MANAGEMENT ALGORITHM OF PINEAL REGION TUMORS: A CASE SERIES AND REVIEW OF THE LITERATURE
Authors: Mahmoud Abbassy, Khaled Aref, Ahmed Farhood, Anwar Hekal
Journal: Neuro-Oncology (2018)

Tumors within the pineal region represent 1.5 to 8.5% of the pediatric brain tumors and 1.2% of all brain tumors. A management algorithm has been proposed in several publications. The algorithm includes endoscopic third ventriculostomy (ETV) and biopsy in cases presenting with hydrocephalus. In this series we are presenting the efficacy of a single-trajectory approach for both ETV and biopsy. Thirteen cases were admitted to Alexandria main university hospital from 2013 to 2016 presenting with pineal region tumors and hydrocephalus. Mean age of at diagnosis 12 years (1 - 24 years). All cases had ETV and biopsy using rigid ventriculoscope through a single-trajectory from a burr-hole planned on preoperative imaging. Follow-up period was 7 - 59 months. All 13 cases presented with hydrocephalus and increased intracranial pressure manifestations. Histopathological diagnosis was successful in 10 out of 13 cases (76.9%). Three cases were germ-cell tumors, 2 cases were pineoblastomas, 1 parenchymal tumor with intermediate differentiation, two cases were pilocytic astrocytomas and two cases were grade 2 tectal gliomas. Five of the ETV cases (38.4%) failed and required VPS later on. Other complications of ETV included 1 case of intraventricular hemorrhage and a case with tumor disseminated to the basal cisterns. In our series we were able to achieve ETV and biopsy through a single trajectory and a rigid endoscope with results comparable to other studies in the literature.
Prone vs supine position in patients with rectal cancer treated with volumetric arc therapy and concurrent chemotherapy
Authors: L. Diaz Gomez, A. Seguro Fernandez, P. Ramirez Daffos, J. Tisaire, J. Jaen Olasolo
Journal: Annals of Oncology (2018)

Introduction: Patients undergoing radiotherapy often are treated in prone position using a belly board as immobilization system with a full bladder protocol. Doing this, we reduce doses to organ at risk, but the position is difficult to maintain and hardly reproducible. This fact served for previous techniques of radiotherapy, but with the current ones we must suspect that the protection of normal tissues is assured regardless of the position. The objective of our study is to compare both positions and verify the protection of organ at risk, without loss of coverage of the treatment volume, using volumetric arc radiotherapy (VMAT) and concomitant chemotherapy. Methods: 12 patients were eligible for the study. We did CT scanning for VMAT planning first in prone position and immediately in supine, with full bladder protocol and using the corresponding immobilizers for each case. At the end of the test, we asked the patient's choice. Planning target volume (PTV) was delimited in both CT by the same facultative as the organ at risk (bladder and small bowel) We considered 2 PTVs, pelvis with a total dose of 45Gy, 1,8Gy/fraction and simultaneous integrated boost for tumour to 54Gy, 2.16Gy/fraction, all in 25 fractions. Radiotherapy was planned with double-arc VMAT, 6-MV photons, with a maximum variable dose rate of 600 MU/min. These two arcs were delivered with opposite rotation (clock and counter-clock) and two coplanars arcs of 360° sharing the same isocentre and optimised independently. Chemotherapy was capecitabine 825mg/m2 twice a day or 5-FU continuous infusion through an indwelling central venous catheter with ambulatory pump. Results: In terms of coverage for treatment volume, both positions were similar, without significant differences in homogeneity or median dose. At high doses, a significant volume of small bowel was irradiated in prone position (median 1,23% supine to 14,4% prone at 40Gy) being not significant for bladder (7,2% supine to 5,7% prone at 40Gy) As the patient's choice, most of them preferred the supine position, moreover the carriers of infusion pumps Conclusion: As a patient´s choice and with better dose-volume histograms for organ at risk, with VMAT radiotherapy we recommend supine position for rectal cancer treatment.
EPID-13. ISOLATED PITUITARY STALK THICKENING (IPST) IN CHILDREN: NATURAL HISTORY AND PREDICTORS OF NEOPLASTIC DISEASE
Authors: Maggie Skrypek, Anastasia Brown, Julie Pape-Blabolil, Charles Bendelsmith, Sachin Patel, Richard Patterson, M Jennifer Abuzzahab, Katherine Ingram, Amy Linabery, Anne Bendel
Journal: Neuro-Oncology (2018)

Isolated pituitary stalk thickening (IPST) is rare, frequently discovered while evaluating diabetes insipidus (DI), and has a broad differential diagnosis including malignancy. A retrospective chart review was performed to characterize the outcome of IPST. We reviewed the medical records of 365 patients <21 years of age with a diagnosis of DI seen at Children’s Minnesota between 11/2003 and 1/2018. Patients were eligible if brain MRI showed IPST, with “pituitary stalk thickening” defined as a pituitary stalk diameter >3 mm and “isolated” defined as a negative initial workup for pituitary thickening. Ten children were identified with IPST, with a male:female ratio of 6:4 and median age at diagnosis of 8.3 years (range: 3 days-19 years). Median follow-up was 5.1 years (range 0.5-9.6 years). At diagnosis, maximum pituitary stalk diameters (MPSD) ranged from 3.1-6.0 mm. During follow-up, 5 patients had resolution of IPST between 0.5-4.2 years from diagnosis (MPSD ranged from 3.3-12.0 mm), 3 remained minimally changed between 1.0-7.7 years from diagnosis (MPSD: 0.5-8.0 mm), and 2 showed asymptomatic progression of IPST between 6-8 months from diagnosis (MPSD: 7.0-17.0 mm). The 2 patients with progressive IPST underwent biopsy of the pituitary stalk and were diagnosed with a germinoma and craniopharyngioma. In conclusion, IPST typically remains stable or improves over time, but 20% of IPST may harbor a malignancy. Follow-up brain MRI is indicated, and progressive growth warrants further workup and potential biopsy to rule out malignancy. A detailed workup and follow-up algorithm for IPST will be discussed in the presentation.