Citations

580 Background: Though studies indicate that the genomic profiles of ICC and ECC are distinct, the clinical features that differentiate them still remain to be well characterized. The purpose of this study was to further analyze these differences and patient treatment patterns in a multi-center cohort. Methods: A retrospective chart review was performed at 8 institutions on patients (pts) with ICC or ECC diagnosed after June 2009. Data on demographics, risk factors, treatments, pathology and overall survival (OS) were collected. Tumor genotyping results from CLIA-certified tissue assays were analyzed. Fisher’s exact, Wilcoxon rank sum and log-rank tests were used to compare sub-groups. Results: In a database of 737 pts with cholangiocarcinoma, 538(73%) had ICC and 199(27%) had ECC. Pts with ICC more often presented in later stages, had tumors > 5cm at resection (p < 0.0001) and had metastases to the liver, lymph nodes, lung and/or bone (p < 0.01). Pts with ICC more often received liver directed therapy, targeted therapy and multiple lines of systemic therapy and they more often enrolled in a clinical trial (all p < 0.01). Pts with ECC were more likely to be male, undergo surgery, receive adjuvant chemotherapy and/or chemoradiation (all p < 0.05). Mutation profiling performed in 381 (52%) pts (ICC/ECC = 301/80) showed that pts with ICC were more likely to have IDH1 mutations and FGFR2 fusions, whereas pts with ECC were more likely to have KRAS, APC, SMAD4, WNT, TGFb and TP53 mutations (all < 0.05). Factors that did not differ significantly between pts with ICC and ECC include race, rates of primary sclerosing cholangitis, median diagnosis CA19-9 levels and R1 resection rate. Median OS from diagnosis was 18.9 months in ICC and 17.3 months in ECC (p = 0.8471). Conclusions: While pts with ICC and ECC have some similarities in their clinical features, differences in metastases patterns and molecular profiling significantly impact their management such that pts with ICC receive more liver-directed therapy, targeted therapy and more lines of systemic therapy. Further prospective studies are needed as referral patterns to tertiary care centers may have impacted these results.

Introduction. Post-operative meningitis (POM) is a life-threatening complication of neurosurgery. Diagnosis is often difficult due to pre-existing inflammation and antecedent antimicrobial use. Bacterial cerebrospinal fluid (CSF) cultures may reveal no growth, but empiric antibiotics are typically given due to the high morbidity and mortality associated with POM. 16S rRNA gene PCR/sequencing is a molecular methodology that can identify the presence of bacteria regardless of viability for culture. Case Presentation. A patient presented with a rapid onset of fever associated with headache, neck pain, nausea and altered mental status 11 days after undergoing laser interstitial thermal therapy for treatment of recurrent astrocytoma at another hospital. Based on clinical presentation and imaging, POM was suspected, and empiric antibacterial therapy was started. Microbiological stains and cultures of CSF were negative. Due to persistent fevers, 16S rRNA gene PCR/sequencing was done on CSF; it detected a member of the order Enterobacteriales most closely resembling Serratia species. All antimicrobials were stopped except for cefepime, which was given for 2 weeks. The patient’s mental status fully recovered. Conclusion. The application of 16S rRNA gene PCR/sequencing in the setting of POM is of value by improving the quality of patient care and decreasing costs by antimicrobial de-escalation. Further studies regarding the positive and negative predictive values of this test are required.

AbstractBackgroundPlasma ammonia is commonly measured in the diagnostic evaluation of hospitalized newborns, but reference values are not well defined.MethodsWe prospectively enrolled newborns admitted to the level III/IV neonatal intensive care unit and level II intermediate special care nursery from January 2017 to January 2018. Infants with inborn errors of metabolism or liver disease were excluded. Plasma ammonia concentrations were measured once within the first week of life and evaluated by sex, gestational age, timing of the draw, blood collection method, and type of nutrition. Reference intervals were calculated.Results127 neonates were included; one third (34%) were term infants born at ≥37 weeks gestation, and two thirds (66%) were born preterm at &lt;37 weeks gestation. Median plasma ammonia concentrations were 32 μmol/L (range &lt;10 to 86 μmol/L). Median ammonia concentrations were higher among preterm compared to term infants (35 vs. 28 μmol/L, p = 0.0119), and term female compared to term male infants (34 vs. 26 μmol/L, p = 0.0228). There was no difference in median ammonia concentrations between female and male preterm infants, based on gestational age within the preterm group, timing of the blood draw, presence of hyperbilirubinemia, blood collection method, or type of nutritional intake.ConclusionsPlasma ammonia concentrations among newborns are higher than the expected adult concentrations and may vary by gestational age and sex. Blood collection method, type of nutrition, hyperbilirubinemia, and timing of the draw do not impact concentrations. We propose a reference limit of ≤82 μmol/L for newborns less than one week of age.

The antibiofilm activity of a hydrogen peroxide-generating electrochemical scaffold (e-scaffold) was determined against mono- and trispecies biofilms of methicillin-resistant Staphylococcus aureus , multidrug-resistant Pseudomonas aeruginosa , and Candida albicans . Significant time-dependent decreases were found in the overall CFU of biofilms of all three monospecies and the trispecies forms. Confocal laser scanning microscopy showed dramatic reductions in fluorescence intensities of biofilm matrix protein and polysaccharide components of e-scaffold-treated biofilms.

AbstractIntroductionBehavioral variant frontotemporal dementia (bvFTD) may present sporadically or due to an autosomal dominant mutation. Characterization of both forms will improve understanding of the generalizability of assessments and treatments.MethodsA total of 135 sporadic (s‐bvFTD; mean age 63.3 years; 34% female) and 99 familial (f‐bvFTD; mean age 59.9; 48% female) bvFTD participants were identified. f‐bvFTD cases included 43 with known or presumed chromosome 9 open reading frame 72 (C9orf72) gene expansions, 28 with known or presumed microtubule‐associated protein tau (MAPT) mutations, 14 with known progranulin (GRN) mutations, and 14 with a strong family history of FTD but no identified mutation.ResultsParticipants with f‐bvFTD were younger and had earlier age at onset. s‐bvFTD had higher total Neuropsychiatric Inventory Questionnaire (NPI‐Q) scores due to more frequent endorsement of depression and irritability.Discussionf‐bvFTD and s‐bvFTD cases are clinically similar, suggesting the generalizability of novel biomarkers, therapies, and clinical tools developed in either form to the other.

AbstractIntroductionWe created global rating scoring rules for the CDR® plus NACC FTLD to detect and track early frontotemporal lobar degeneration (FTLD) and to conduct clinical trials in FTLD.MethodsThe CDR plus NACC FTLD rating was applied to 970 sporadic and familial participants from the baseline visit of Advancing Research and Treatment in Frontotemporal Lobar Degeneration (ARTFL)/Longitudinal Evaluation of Familial Frontotemporal Dementia Subjects (LEFFTDS). Each of the eight domains of the CDR plus NACC FTLD was equally weighed in determining the global score. An interrater reliability study was completed for 40 participants.ResultsThe CDR plus NACC FTLD showed very good interrater reliability. It was especially useful in detecting clinical features of mild non‐fluent/agrammatic variant primary progressive aphasia participants.DiscussionThe global CDR plus NACC FTLD score could be an attractive outcome measure for clinical trials in symptomatic FTLD, and may be useful in natural history studies and clinical trials in FTLD spectrum disorders.

AbstractIntroductionThe Advancing Research and Treatment for Frontotemporal Lobar Degeneration (ARTFL) and Longitudinal Evaluation of Familial Frontotemporal Dementia Subjects (LEFFTDS) consortia are two closely connected studies, involving multiple North American centers that evaluate both sporadic and familial frontotemporal dementia (FTD) participants and study longitudinal changes.MethodsWe screened the major dementia‐associated genes in 302 sporadic and 390 familial (symptomatic or at‐risk) participants enrolled in these studies.ResultsAmong the sporadic patients, 16 (5.3%) carried chromosome 9 open reading frame 72 (C9orf72), microtubule‐associated protein tau (MAPT), and progranulin (GRN) pathogenic variants, whereas in the familial series we identified 207 carriers from 146 families. Of interest, one patient was found to carry a homozygous C9orf72 expansion, while another carried both a C9orf72 expansion and a GRN pathogenic variant. We also identified likely pathogenic variants in the TAR DNA binding protein (TARDBP), presenilin 1 (PSEN1), and valosin containing protein (VCP) genes, and a subset of variants of unknown significance in other rare FTD genes.DiscussionOur study reports the genetic characterization of a large FTD series and supports an unbiased sequencing screen, irrespective of clinical presentation or family history.

AbstractIntroductionLeisure activities impact brain aging and may be prevention targets. We characterized how physical and cognitive activities relate to brain health for the first time in autosomal dominant frontotemporal lobar degeneration (FTLD).MethodsA total of 105 mutation carriers (C9orf72/MAPT/GRN) and 69 non‐carriers reported current physical and cognitive activities at baseline, and completed longitudinal neurobehavioral assessments and brain magnetic resonance imaging (MRI) scans.ResultsGreater physical and cognitive activities were each associated with an estimated >55% slower clinical decline per year among dominant gene carriers. There was also an interaction between leisure activities and frontotemporal atrophy on cognition in mutation carriers. High‐activity carriers with frontotemporal atrophy (−1 standard deviation/year) demonstrated >two‐fold better cognitive performances per year compared to their less active peers with comparable atrophy rates.DiscussionActive lifestyles were associated with less functional decline and moderated brain‐to‐behavior relationships longitudinally. More active carriers “outperformed” brain volume, commensurate with a cognitive reserve hypothesis. Lifestyle may confer clinical resilience, even in autosomal dominant FTLD.

Introduction Globally, the use of telestroke programmes for acute care is expanding. Currently, a standardised set of variables for enabling reliable international comparisons of telestroke programmes does not exist. The aim of the study was to establish a consensus-based, minimum dataset for acute telestroke to enable the reliable comparison of programmes, clinical management and patient outcomes. Methods An initial scoping review of variables was conducted, supplemented by reaching out to colleagues leading some of these programmes in different countries. An international expert panel of clinicians, researchers and managers ( n = 20) from the Australasia Pacific region, USA, UK and Europe was convened. A modified-Delphi technique was used to achieve consensus via online questionnaires, teleconferences and email. Results Overall, 533 variables were initially identified and harmonised into 159 variables for the expert panel to review. The final dataset included 110 variables covering three themes (service configuration, consultations, patient information) and 12 categories: (1) details about telestroke network/programme ( n = 12), (2) details about initiating hospital ( n = 10), (3) telestroke consultation ( n = 17), (4) patient characteristics ( n = 7), (5) presentation to hospital ( n = 5), (6) general clinical care within first 24 hours ( n = 10), (7) thrombolysis treatment ( n = 10), (8) endovascular treatment ( n = 13), (9) neurosurgery treatment ( n = 8), (10) processes of care beyond 24 hours ( n = 7), (11) discharge information ( n = 5), (12) post-discharge and follow-up data ( n = 6). Discussion The acute telestroke minimum dataset provides a recommended set of variables to systematically evaluate acute telestroke programmes in different countries. Adoption is recommended for new and existing services.

Abstract Purpose: With increasing incidence of renal mass, it is important to make a pretreatment differentiation between benign renal mass and malignant tumor. We aimed to develop a deep learning model that distinguishes benign renal tumors from renal cell carcinoma (RCC) by applying a residual convolutional neural network (ResNet) on routine MR imaging. Experimental Design: Preoperative MR images (T2-weighted and T1-postcontrast sequences) of 1,162 renal lesions definitely diagnosed on pathology or imaging in a multicenter cohort were divided into training, validation, and test sets (70:20:10 split). An ensemble model based on ResNet was built combining clinical variables and T1C and T2WI MR images using a bagging classifier to predict renal tumor pathology. Final model performance was compared with expert interpretation and the most optimized radiomics model. Results: Among the 1,162 renal lesions, 655 were malignant and 507 were benign. Compared with a baseline zero rule algorithm, the ensemble deep learning model had a statistically significant higher test accuracy (0.70 vs. 0.56, P = 0.004). Compared with all experts averaged, the ensemble deep learning model had higher test accuracy (0.70 vs. 0.60, P = 0.053), sensitivity (0.92 vs. 0.80, P = 0.017), and specificity (0.41 vs. 0.35, P = 0.450). Compared with the radiomics model, the ensemble deep learning model had higher test accuracy (0.70 vs. 0.62, P = 0.081), sensitivity (0.92 vs. 0.79, P = 0.012), and specificity (0.41 vs. 0.39, P = 0.770). Conclusions: Deep learning can noninvasively distinguish benign renal tumors from RCC using conventional MR imaging in a multi-institutional dataset with good accuracy, sensitivity, and specificity comparable with experts and radiomics.