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• The endoscopic endonasal approach (EEA) to olfactory groove meningioma (OGM) resection provides a high gross total resection rate, comparable to that of open resection. • Rates of cerebrospinal fluid leakage following EEA resection have significantly decreased and no longer favor open resection. • Although rates of post-operative anosmia with EEA remain high, smell preservation is a possibility with select cases. • Lack of tumor extension beyond the mid-orbit and the presence of significant peri -tumoral edema may favor resection via EEA. Though the endoscopic endonasal approach (EEA) is a widely accepted treatment for skull base tumors, the specific use of EEA for olfactory groove meningiomas (OGMs) is debated, with variable outcomes reported in the literature. We review the surgical results of OGM resections for one surgeon including the operative approach, surgical nuances, and outcomes, with a focus on factors relating to patient selection which favor EEA over transcranial approaches. We retrospectively reviewed thirteen cases of endoscopic endonasal resection of olfactory groove meningiomas. Patient characteristics, clinical characteristics, surgical outcomes, and complications were analyzed. Extent of resection was determined based on volumetric analysis of pre- and postoperative MRI. Anatomic characteristics that render a tumor difficult to access fully are lateral extension beyond the mid-orbit and anterior extension to the falx. Simpson Grade I resection was achieved in 11/13 (84.6 %) cases. Mean pre-operative tumor volume was 8.99 cm3 (range 2.19–16.79 cm3), and 92 % of tumors were WHO grade I. We demonstrate 2 cases of smell preservation, possible with small unilateral tumors and tumors that are confined to either the anterior or posterior portion of the cribriform plate. The post-operative CSF leak rate was 7.7 %, without prophylactic lumbar CSF drainage. The mortality rate was 7.7 % (n = 1) after infectious complications following CSF leak. Endoscopic endonasal resection of olfactory groove meningiomas is an effective and safe operative method with outcomes and complication rates comparable to transcranial approaches. Key considerations include careful patient selection and familiarity with technical nuances of endoscopic endonasal approach for this specific tumor type. [ABSTRACT FROM AUTHOR]

Prediction models of post-liver transplant mortality are crucial so that donor organs are not allocated to recipients with unreasonably high probabilities of mortality. Machine learning algorithms, particularly deep neural networks (DNNs), can often achieve higher predictive performance than conventional models. In this study, we trained a DNN to predict 90-day post-transplant mortality using preoperative variables and compared the performance to that of the Survival Outcomes Following Liver Transplantation (SOFT) and Balance of Risk (BAR) scores, using United Network of Organ Sharing data on adult patients who received a deceased donor liver transplant between 2005 and 2015 (n = 57,544). The DNN was trained using 202 features, and the best DNN's architecture consisted of 5 hidden layers with 110 neurons each. The area under the receiver operating characteristics curve (AUC) of the best DNN model was 0.703 (95% CI: 0.682-0.726) as compared to 0.655 (95% CI: 0.633-0.678) and 0.688 (95% CI: 0.667-0.711) for the BAR score and SOFT score, respectively. In conclusion, despite the complexity of DNN, it did not achieve a significantly higher discriminative performance than the SOFT score. Future risk models will likely benefit from the inclusion of other data sources, including high-resolution clinical features for which DNNs are particularly apt to outperform conventional statistical methods. • Liver transplant mortality can be predicted by using deep neural networks that use UNOS data. • Deep neural networks outperformed the BAR score in predicting mortality. • Deep neural networks did not significantly outperform the SOFT score. • Deep learning using higher resolution features may achieve superior performance. [ABSTRACT FROM AUTHOR]

The purpose of this study was to evaluate the diagnostic utility of noninvasive Vibration-Controlled Transient Elastography (VCTE) for assessing liver fibrosis in pediatric intestinal failure (PIF) patients. Data from children with severe intestinal failure (≥ 90 days parenteral nutrition dependence) who underwent liver stiffness measurement (LSM), as measured by VCTE, at our institution between December 2015 and March 2018 were reviewed. LSM was compared to METAVIR fibrosis score (F0-F4) on liver biopsy performed within 1 year of VCTE. Seventy children underwent 75 LSM. Sixty-three patients (38% female) had at least one valid LSM, and 63% had a history of cholestasis (direct bilirubin ≥ 2 mg/dL). Median (IQR) age at first valid LSM was 4.5 years (2.6, 8.7). Sixteen patients had a liver biopsy. LSM differentiated between METAVIR F0-F1 (n = 6) and F2-F4 (n = 10) with an area under the receiver operating characteristic (AUROC) curve of 0.883 (95% CI: 0.686–0.999). The optimal cut-point derived to predict F2-F4 was an LSM ≥ 6 kPa (sensitivity 80%, specificity 100%). LSM as determined by VCTE can distinguish mild (F0-F1) from moderate/severe (F2-F4) liver fibrosis in PIF. VCTE could allow for serial noninvasive monitoring of liver injury, potentially facilitating timely modifications to hepatoprotective management. Type of Study: Study of Diagnostic Test. Level of Evidence: II. [ABSTRACT FROM AUTHOR]

Background Posterior fossa decompression surgeries for Chiari malformations are susceptible to postoperative complications such as pseudomeningocele, external cerebrospinal fluid (CSF) leak, and meningitis. Various dural substitutes have been used to improve surgical outcomes. Objective This study examined whether the collagen matrix dural substitute type correlated with the incidence of postoperative complications after posterior fossa decompression in adult patients with Chiari I malformations. Methods A retrospective cohort study was conducted of 81 adult patients who underwent an elective decompressive surgery for treatment of symptomatic Chiari I malformations, with duraplasty involving a dural substitute derived from either bovine or porcine collagen matrix. Demographics and treatment characteristics were correlated with surgical outcomes. Results A total of 81 patients were included in the study. Compared with bovine dural substitute, porcine dural substitute was associated with a significantly higher risk of pseudomeningocele occurrence (odds ratio, 5.78; 95% confidence interval, 1.65–27.15; P = 0.01) and a higher overall complication rate (odds ratio, 3.70; 95% confidence interval, 1.23–12.71; P = 0.03) by univariate analysis. There was no significant difference in the rate of meningitis, repeat operations, or overall complication rate between the 2 dural substitutes. In addition, estimated blood loss was a significant risk factor for meningitis ( P = 0.03). Multivariate analyses again showed that porcine dural substitute was associated with pseudomeningocele occurrence, although the association with higher overall complication rate did not reach significance. Conclusions Dural substitutes generated from porcine collagen, compared with those from bovine collagen, were associated with a higher likelihood of pseudomeningocele development in adult patients undergoing Chiari I malformation decompression and duraplasty. [ABSTRACT FROM AUTHOR]

Objective: To derive an optimal liver stiffness measurement cut point to discriminate METAVIR fibrosis stage F4 and to validate both METAVIR fibrosis stage F3-F4 and F4 cut points in a separate cohort.Study Design: Patients at Boston Children's Hospital with liver stiffness measurement from 2006 to 2016 and liver biopsy ≤12 months before screening were eligible. Patients enrolled 2006-2011 were used to calibrate liver stiffness measurement cut points and those enrolled 2011-2016 for validation. Diagnostic performance was assessed by receiver operating curve analysis.Results: In total, 267 subjects were enrolled (97 calibration, 170 validation). The cohorts were similar with 54% male, aged 0-29 years (median 13 years), and liver diseases including 21% autoimmune, 19% viral, 11% nonalcoholic fatty liver, 9% cholestatic, and 9% primary sclerosing cholangitis. Cut points to discriminate F3-F4 and F4 were >8.6 kPa and >11.5 kPa with 81% and 84% accuracy, respectively. Applied to the validation cohort, accuracy was 67% and 75%, respectively. In 44 fasted subjects, the accuracy was 73% and 80%, respectively.Conclusion: This study validates previously determined liver stiffness measurement cut points of 8.6 kPa and 11.5 kPa to predict METAVIR F3-F4 and F4 fibrosis in children and young adults in separate cohorts. With increasing data on the utility and validity of liver stiffness measurement in children, transient elastography may help identify patients with greater risk of advanced fibrosis and those who need liver biopsy assessment and/or surveillance for the complications of cirrhosis in a variety of liver disorders. [ABSTRACT FROM AUTHOR]

A subset of patients with IDH-mutant glioma respond to inhibitors of mutant IDH (IDHi), yet the molecular underpinnings of such responses are not understood. Here, we profiled by single-cell or single-nucleus RNA-sequencing three IDH-mutant oligodendrogliomas from patients who derived clinical benefit from IDHi. Importantly, the tissues were sampled on-drug, four weeks from treatment initiation. We further integrate our findings with analysis of single-cell and bulk transcriptomes from independent cohorts and experimental models. We find that IDHi treatment induces a robust differentiation toward the astrocytic lineage, accompanied by a depletion of stem-like cells and a reduction of cell proliferation. Furthermore, mutations in NOTCH1 are associated with decreased astrocytic differentiation and may limit the response to IDHi. Our study highlights the differentiating potential of IDHi on the cellular hierarchies that drive oligodendrogliomas and suggests a genetic modifier that may improve patient stratification. [Display omitted] • Single-cell analysis of on-treatment gliomas reveals cellular basis of drug responses • In responders, mutant IDH inhibitors induce lineage differentiation • The differentiation favors astrocytic-like over stem/progenitor-like states • NOTCH1 mutations modify the response and may serve to stratify patients The molecular response of IDH-mutant glioma to mutant IDH inhibitors is poorly understood. Spitzer et al. show that, in patients with clinical response, mutant IDH inhibitors induce lineage differentiation of cancer cells and deplete cells in a stem/progenitor-like state. They further highlight potential modifiers of such differentiation response in glioma. [ABSTRACT FROM AUTHOR]