Source:Practical Radiation Oncology
Author(s): Daniel G Petereit
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Very low-calorie ketogenic (VLCK) diets have been consistently shown to be an effective obesity treatment, but the current evidence for its acid-base safety is limited. The aim of the current work was to evaluate the acid-base status of obese patients during the course of a VLCK diet.
Twenty obese participants undertook a VLCK diet for 4 months. Anthropometric and biochemical parameters, and venous blood gases were obtained on four subsequent visits: visit C-1 (baseline); visit C-2, (1-2 months); maximum ketosis; visit C-3 (2-3 months), ketosis declining; and visit C-4 at 4 months, no ketosis. Results were compared with 51 patients that had an episode of diabetic ketoacidosis as well as with a group that underwent a similar VLCK diet in real life conditions of treatment.
Visit C1 blood pH (7.37 ± 0.03); plasma bicarbonate (24.7 ± 2.5 mmol/l); plasma glucose (96.0 ± 11.7 mg/l) as well as anion gap or osmolarity were not statistically modified at four months after a total weight reduction of 20.7 kg in average and were within the normal range throughout the study. Even at the point of maximum ketosis all variables measured were always far from the cut-off points established to diabetic ketoacidosis.
During the course of a VLCK diet there were no clinically or statistically significant changes in glucose, blood pH, anion gap and plasma bicarbonate. Hence the VLCK diet can be considered as a safe nutritional intervention for the treatment of obesity in terms of acid-base equilibrium.
Very low-calorie ketogenic (VLCK) diets have been consistently shown to be an effective obesity treatment, but the current evidence for its acid-base safety is limited. The aim of the current work was to evaluate the acid-base status of obese patients during the course of a VLCK diet.
Twenty obese participants undertook a VLCK diet for 4 months. Anthropometric and biochemical parameters, and venous blood gases were obtained on four subsequent visits: visit C-1 (baseline); visit C-2, (1-2 months); maximum ketosis; visit C-3 (2-3 months), ketosis declining; and visit C-4 at 4 months, no ketosis. Results were compared with 51 patients that had an episode of diabetic ketoacidosis as well as with a group that underwent a similar VLCK diet in real life conditions of treatment.
Visit C1 blood pH (7.37 ± 0.03); plasma bicarbonate (24.7 ± 2.5 mmol/l); plasma glucose (96.0 ± 11.7 mg/l) as well as anion gap or osmolarity were not statistically modified at four months after a total weight reduction of 20.7 kg in average and were within the normal range throughout the study. Even at the point of maximum ketosis all variables measured were always far from the cut-off points established to diabetic ketoacidosis.
During the course of a VLCK diet there were no clinically or statistically significant changes in glucose, blood pH, anion gap and plasma bicarbonate. Hence the VLCK diet can be considered as a safe nutritional intervention for the treatment of obesity in terms of acid-base equilibrium.
The different rheological properties of hyaluronic acid (HA) filler reflect their specific manufacturing processes and resultant physicochemical characteristics. However, there are few researches about the relationship between product differences and clinical outcome when HA fillers are used for nasolabial folds (NLFs).
This study sought to compare the rheological properties, efficacy and safety of a monophasic HA filler, and a well-studied biphasic HA filler, in the treatment of NLFs.
A total of 72 Korean subjects with moderate to severe NLFs were randomized to receive injections with monophasic HA or biphasic HA on the left or right side of the face. Efficacy was evaluated by the change in the Wrinkle Severity Rating Scale (WSRS) at 2, 10, 18, 26, and 52 weeks. Safety was assessed on the basis of all abnormal reactions during the clinical test period. To compare the rheological characteristics of two cross-linked HA fillers, viscoelastic analysis was performed.
At week 26, the mean WSRS was 2.26±0.56 for the monophasic HA side and 2.24±0.54 for the biphasic HA side. Both treatments were well tolerated. The adverse reactions were mild and transient. Monophasic HA filler had lower elasticity and higher viscosity than biphasic HA filler.
Despite a number of different rheological properties, monophasic HA is noninferior to biphasic HA in the treatment of moderate to severe NLFs for 52 weeks. Therefore, monophasic HA provides an alternative option for NLFs correction.
The different rheological properties of hyaluronic acid (HA) filler reflect their specific manufacturing processes and resultant physicochemical characteristics. However, there are few researches about the relationship between product differences and clinical outcome when HA fillers are used for nasolabial folds (NLFs).
This study sought to compare the rheological properties, efficacy and safety of a monophasic HA filler, and a well-studied biphasic HA filler, in the treatment of NLFs.
A total of 72 Korean subjects with moderate to severe NLFs were randomized to receive injections with monophasic HA or biphasic HA on the left or right side of the face. Efficacy was evaluated by the change in the Wrinkle Severity Rating Scale (WSRS) at 2, 10, 18, 26, and 52 weeks. Safety was assessed on the basis of all abnormal reactions during the clinical test period. To compare the rheological characteristics of two cross-linked HA fillers, viscoelastic analysis was performed.
At week 26, the mean WSRS was 2.26±0.56 for the monophasic HA side and 2.24±0.54 for the biphasic HA side. Both treatments were well tolerated. The adverse reactions were mild and transient. Monophasic HA filler had lower elasticity and higher viscosity than biphasic HA filler.
Despite a number of different rheological properties, monophasic HA is noninferior to biphasic HA in the treatment of moderate to severe NLFs for 52 weeks. Therefore, monophasic HA provides an alternative option for NLFs correction.
This article used novel non-magnetized and magnetized biochars prepared under a CO2 atmosphere returned to Cd-contaminated soil and compared these to the effects of conventional biochars prepared under a N2 atmosphere with regard to Cd-contaminated soil remediation. A pot experiment with lettuce (Lactuca sativa) was conducted to investigate the relative soil remediation effects of these biochars. The soil used for the pot experiment was spiked with 20 mg kg−1 Cd and amended with 5% of a biochar before sowing. Through these research works, some important results were obtained as follows: (1) applying biochar treated by pyrolysis under a CO2 atmosphere can obtain the best remediation effect of Cd-contaminated soil that the content of cadmium in the lettuce roots, stems, and leaves was reduced 67, 62, and 63%, respectively; (2) the magnetic biochar aggregation for the soil is weak, so the heavy metal cadmium in the soil could not be immobilized well by the magnetic biochar; (3) The remediation mechanism of novel biochars is that biochar includes a large number of organic functional groups (−C–OH, −C=O, COO−) that can act in a complexing reaction with heavy metal Cd(II) and the inorganic salt ions (Si, S, Cl, etc.) that can combine with cadmium and generate a stable combination.
Viral Immunology , Vol. 0, No. 0.
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Viral Immunology , Vol. 0, No. 0.
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Rejuvenation Research , Vol. 0, No. 0.
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Publication date: Available online 14 September 2017
Source:Allergology International
Author(s): Akira Igarashi, Yasuhiro Ebihara, Tomoaki Kumagai, Hiroyuki Hirai, Kinya Nagata, Kohichiro Tsuji
BackgroundSeveral methods have been developed to detect allergen-specific IgE in sera. The passive IgE sensitization assay using human IgE receptor-expressing rat cell line RBL-2H3 is a powerful tool to detect biologically active allergen-specific IgE in serum samples. However, one disadvantage is that RBL-2H3 cells are vulnerable to high concentrations of human sera. Only a few human cultured cell lines are easily applicable to the passive IgE sensitization assay. However, the use of human induced pluripotent stem cells (iPSCs) to generate human mast cells (MCs) has not yet been reported.MethodsThe nuclear factor-kappa B (NF-κB)-responsive luciferase reporter gene was stably introduced into a human iPSC line 201B7, and the transfectants were induced to differentiate into MCs (iPSC-MCs). The iPSC-MCs were sensitized overnight with sera from subjects who were allergic to cedar pollen, ragweed pollen, mites, or house dust, and then stimulated with an extract of corresponding allergens. Activation of iPSC-MCs was evaluated by β-hexosaminidase release, histamine release, or luciferase intensity.ResultsiPSCs-MCs stably expressed high-affinity IgE receptor and functionally responded to various allergens when sensitized with human sera from relevant allergic subjects. This passive IgE sensitization system, which we termed the induced mast cell activation test (iMAT), worked well even with undiluted human sera.ConclusionsiMAT may serve as a novel determining system for IgE/allergens in the clinical and research settings.
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Publication date: Available online 14 September 2017
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Kristine Bauer-Nilsen, Colin Hill, Daniel M. Trifiletti, Bruce Libby, Donna H. Lash, Melody Lain, Deborah Christodoulou, Constance Hodge, Timothy N. Showalter
PurposeThis study aims to evaluate the delivery costs, using time-driven activity-based costing (TDABC), and reimbursement for definitive radiation therapy for locally advanced cervical cancer.Methods and MaterialsProcess maps were created to represent each step of the radiation treatment process and included personnel, equipment, and consumable supplies used to deliver care. Personnel were interviewed to estimate time involved to deliver care. Salary data, equipment purchasing information and facilities costs were also obtained. We defined the capacity cost rate (CCR) for each resource, and then calculated the total cost of patient care based upon CCR and time for each resource. Costs were compared to 2016 Medicare reimbursement and relative value units (RVUs).ResultsThe total cost of radiation therapy for cervical cancer was $12,861.68, with personnel costs comprising 49.8%. Brachytherapy cost $8,610.68 (66.9% of total) and consumed 423 minutes of attending radiation oncologist time (80.0% of total). EBRT cost $4,055.01 in costs (31.5% of total). Personnel costs were higher for brachytherapy than for the sum of simulation and EBRT delivery ($4,798.73 vs. $1,404.72). A full radiation therapy course provides radiation oncologists 149.77 RVUs with IMRT or 135.90 RVUs with 3DCRT, with total reimbursement of $23,321.71 and $16,071.90 respectively. Attending time per RVU is approximately 4-fold higher for brachytherapy (5.68 minutes) than 3DCRT (1.63 minutes) or IMRT (1.32 minutes).ConclusionTDABC was used to calculate the total cost of definitive radiation therapy for cervical cancer, revealing that brachytherapy delivery and personnel resources comprised the majority of costs. However, current reimbursement policy does not reflect the increased attending physician effort and delivery costs of brachytherapy. We hypothesize that the significant discrepancy between treatment costs and physician effort versus reimbursement may be a potential driver of reported national trends towards poor compliance with brachytherapy and suggest re-evaluation of payment policies to incentivize quality care.
Publication date: Available online 14 September 2017
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Eli Sapir, Yebin Tao, Matthew J. Schipper, Latifa Bazzi, Paula M. Novelli, Paulina Devlin, Dawn Owen, Kyle C. Cuneo, Theodore S. Lawrence, Neehar D. Parikh, Mary Feng
BackgroundThere is little data to guide non-surgical treatment selection for patients with HCC. Therefore, we conducted a large, single institutional comparison of transarterial chemoembolization (TACE) and SBRT outcomes in similar groups of patients.MethodsFrom 2006 to 2014, 209 patients with 1-2 tumors underwent TACE (n=84) to 114 tumors or image-guided SBRT (n=125) to 173 tumors. Propensity score analysis with inverse probability of treatment weighting was used to compare outcomes between treatments while adjusting for imbalances in treatment assignment. Local control (LC), toxicity, and overall survival (OS) were retrospectively analyzed.ResultsTACE and SBRT groups were similar with respect to the number of tumors treated per patient, underlying liver disease and baseline liver function. Patients treated with SBRT were older (65 vs 61 yrs, p=0.01) and had smaller tumors (2.3 vs 2.9 cm, p < 0.001), and less frequently underwent liver transplantation (8% vs. 18%, p = 0.01). 1- and 2-yr LC favored SBRT: 97% and 91% for SBRT and 47% and 23%, for TACE (HR 66.5, p < 0.001). For patients treated with TACE, higher AFP (HR 1.11 per doubling, p =0.008) and segmental portal vein thrombosis (HR 9.9, p < 0.001) were associated with worse LC. Predictors associated with LC after SBRT were not identified. Grade 3+ toxicity occurred after 13% and 8% of TACE and SBRT treatments, respectively (p = 0.05). There was no difference in OS between patients treated with TACE or SBRT.ConclusionSBRT is a safe alternative to TACE for 1-2 tumors, and provides better LC, with no observed difference in OS. Prospective comparative trials of TACE and SBRT are warranted.
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Thyroid Sep 2017, Vol. 27, No. 9: 1128-1134.
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Thyroid Sep 2017, Vol. 27, No. 9: 1211-1211.
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Thyroid Sep 2017, Vol. 27, No. 9: 1201-1205.
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Thyroid Sep 2017, Vol. 27, No. 9: 1185-1193.
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Thyroid Sep 2017, Vol. 27, No. 9: 1128-1134.
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Thyroid Sep 2017, Vol. 27, No. 9: 1211-1211.
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Thyroid Sep 2017, Vol. 27, No. 9: 1201-1205.
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Thyroid Sep 2017, Vol. 27, No. 9: 1185-1193.
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Phyllodes tumor is a rare breast mass. Most phyllodes tumors are benign, but occasionally some show malignancy. Even if the tumors are benign, they can easily show recurrence.
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Publication date: Available online 14 September 2017
Source:Acta Biomaterialia
Author(s): Claudio Vergari, Jessica C. Mansfield, Daniel Chan, Andrew Clarke, Judith R. Meakin, Peter C. Winlove
Needle puncture of the intervertebral disc can initiate a mechanical and biochemical cascade leading to disc degeneration. Puncture's mechanical effects have been shown near the puncture site, mechanical effects should be observed far, relative to needle size, from the puncture site, given the disc-wide damage induced by the stab. The aim of this work was to quantify these far-field effects, and to observe the local structural damage provoked by the needle.Strips of cow tail annulus fibrosus underwent two consecutive mechanical loadings to 5% tensile strain; fifteen samples were punctured in a radial direction with a randomly assigned needle between the two loadings (needle gauges between 19 and 23). Ten samples (control group) were not punctured. During loading, the tissue strains were imaged using second harmonic generation microscopy in a <600x800µm region about 4.4mm from the puncture site. After mechanical testing, the puncture site was imaged in 3D.Puncture had no significant effect on annulus elastic modulus. Imaging showed a modest change in the shearing between fibre bundles however, the linear strain between bundles, intra-bundle shear and linear strain were not significantly affected. At the puncture site, detached lumps of tissue were present.These results suggest that the mechanical effects observed in intact discs are due to the depressurization of the disc, rather than the local damage to the annulus. Needle profiles could be designed, aiming at separating fibre bundles rather than cutting through them, to avoid leaving dying tissue behind.Statement of significanceNeedle puncture of the intervertebral disc can initiate a mechanical and biochemical cascade leading to disc degeneration, but the link between the local damage of the puncture and the disc-wide effects is not well understood. This work aimed at determining the micro–mechanical effects of the puncture far from its site, and to observe the damage induced by the puncture with high resolution imaging. Results show that the puncture had modest effect far from the puncture, but lumps of tissue were left by the needle, detached from the disc; these could cause further damage through friction and inflammation of the surrounding tissues. This suggests that the cascade leading to degeneration is probably driven by a biochemical response rather than disc-wide mechanical effects.
Publication date: 5 December 2017
Source:Materials & Design, Volume 135
Author(s): S. Pauly, C. Schricker, S. Scudino, L. Deng, U. Kühn
Compact specimens were produced by selective laser melting (SLM) from glass-forming Zr52.5Cu17.9Ni14.6Al10Ti5 powder. Below a critical energy density of Ecrit=15J/mm3 fully glassy samples were obtained. When the energy density is higher, the metastable big cube phase, stabilized by oxygen, precipitates next to other crystalline phases. We introduce density contour maps to identify the process window, which allows obtaining fully glassy samples with a high relative density of up to 98.5%. The systematic parameter variation illustrates the importance of laser power for obtaining dense SLM parts. Moreover, the distribution of pores in the present alloy is rather sensitive to the scanning strategy. The compressive strength of the SLM samples is comparable to values measured for as-cast glasses and even a distinct plastic strain is found. Finally, scaffolds were produced and high-energy X-ray diffraction proves that they are fully glassy irrespective of differences in the local cooling rates. Our experiments contribute to better understanding the behaviour of Zr52.5Cu17.9Ni14.6Al10Ti5 during SLM and for making glass-forming alloys progressively more accessible to laser-based additive manufacturing in order to overcome the intrinsic size limitation of bulk metallic glasses.
Publication date: 5 December 2017
Source:Materials & Design, Volume 135
Author(s): Esmat Sheydaeian, Kaveh Sarikhani, Pu Chen, Ehsan Toyserkani
This paper addresses a new methodology to fabricate cellular structures with embedded close pores distributed in controlled fashion. A hybrid additive manufacturing system integrating binder jetting and material extrusion was employed to selectively incorporate a sacrificial polymer into the structures followed by a post-processing step to decompose the polymer. Four different polymer compositions mixture of bisphenol-A ethoxylated diacrylate and cellulose acetate butyrate (CAB) were prepared. From determining the rheological and interfacial properties of the polymers, the composition with the highest CAB concentration (20wt%) demonstrated lowest permeation inside powder porous media (0.03m2/s). The significance of the results is in retaining the quality of green substrate via a decrease in influence of the polymer shrinkage stress due to a reduction in the polymer - powders interface. The effect of binder jetting and design parameters on the quality of green samples manufactured by embedding the optimized composition revealed the direct influence of binder saturation level, layer thickness, and the number of powder layers covering encapsulated polymers. In the heat treatment of the samples (up to 1400°C), a high level of accuracy (1% error margin) in morphology of cavities, resulted from the decomposition of polymers (400°C), was achieved.
Publication date: 5 December 2017
Source:Materials & Design, Volume 135
Author(s): Leonardo Santana, Jorge Lino Alves, Aurélio da Costa Sabino Netto
Open source projects have helped extrusion-based Additive Manufacturing processes gain popularity in recent years. While they allow the design and development of low cost machines, one of the main difficulties users have found is the parametric calibration. A study was proposed to understand the best practices for the setup of "input parameters", since in the open software chain there are many available for setup. Through experimental design methods, the dimensional accuracy of a cubic structure was analysed by varying factors such as: slicing software, layer thickness, infill density, first layer, infill and perimeter speeds, as well as extrusion temperature and multiplier. A Prusa I3 Hephestos printer and a Polylactic Acid (PLA) filament were used, and the parts were evaluated with contact measurement, 3D scanning and mass measurement procedures. Statistical analysis showed that the dimensional accuracy of the components was mostly affected by the infill density and the extrusion multiplier. Both parameters highlight the influence of the slicing software on the planning and quality of the models. Instabilities in the amount and flow of material, characterized by excess deposition, were responsible for the distortions along the three fundamental directions of the cubes.
Publication date: 5 December 2017
Source:Materials & Design, Volume 135
Author(s): Mohamed S. Selim, Feng Q. Wang, Hui Yang, Yong Huang, Shigenori Kuga
Engineering innovative nanomaterials with low volatile organic content (VOC) has awarded great interest to control air pollutant emissions. We designed a highly branched alkyd matrix suitable for surface coating from castor oil via polyesterification. A simple A2+B3 (di- and tri-functional monomers) methodology was used to prepare the hyperbranched polyester from natural multifunctional monomers. Magnetite-coated silica (Fe3O4@SiO2) particles with 60–70nm average diameter were prepared by in situ method that binds magnetite nanoparticles to silica nanospheres. The magnetite size and attaching efficiency were controlled by the concentration of chemicals and reflux duration. The nanocomposite coating was prepared by solution casting. The structure-property relationship was studied for different concentrations of nanofiller in the alkyd matrix. The surface and anticorrosive properties were studied via contact angle and salt spray tests. Mechanical performance and thermal stability were assessed by various methods. The highest improvement was achieved with nanofiller insertion up to 0.5% Fe3O4@SiO2 nanospheres.
Airflow during speech production is recorded using a pneumotachograph system wherein typically a mask is placed upon the face. Accurate measures of airflow require mask calibration and a complete seal of the mask rim to the face. Literature frequently cites mask rim leaks as causing flow measurement inaccuracies, but quantitative studies of the inaccuracies are needed.The purpose of this study was to determine the degree of inaccuracy of flow measurement using a Glottal Enterprises aerodynamic system for a variety of mask rim leak conditions.
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AbstractBackground.Obesity is a consideration in the pharmacologic intervention for estrogen receptor (ER) positive (ER+) breast cancer risk. Body mass index (BMI) and waist/hip ratio (WHR) have demonstrated different effects on breast cancer risk in relation to estrogen receptor (ER) status, but the results have been inconsistent. Furthermore, the situation in Chinese women remains unclear.Materials and Methods.We conducted a case‐control study including 1,439 breast cancer cases in Northern and Eastern China. Both ER and progesterone receptor (PR) statuses were available for 1,316 cases. Associations between body size‐related factors and breast cancer risk defined by receptor status were assessed by multiple polytomous unconditional logistic regression analysis.Results.Body mass index and WHR were positively associated with overall breast cancer risk. Body mass index was positively associated with both ER+/PR positive (PR+) and ER negative (ER−)/PR negative(PR−) subtype risks, although only significantly for ER+/PR+ subtype. Waist–hip ratio was only positively correlated with ER−/PR− subtype risk, although independent of BMI. Body mass index was positively associated with risk of ER+/PR+ and ER−/PR− subtypes in premenopausal women, whereas WHR was inversely correlated with ER+/PR− and positively with ER−/PR− subtype risks. Among postmenopausal women, WHR >0.85 was associated with increased risk of ER−/PR− subtype.Conclusions.Both general and central obesity contribute to breast cancer risk, with different effects on specific subtypes. General obesity, indicated by BMI, is more strongly associated with ER+/PR+ subtype, especially among premenopausal women, whereas central obesity, indicated by WHR, is more specific for ER−/PR− subtype, independent of menopausal status. These results suggest that different chemoprevention strategies may be appropriate in selected individuals.Implications for Practice.The results of this study suggest that general and central obesity may play different roles in different breast cancer subtypes, supporting the hypothesis that obesity affects breast carcinogenesis via complex molecular interconnections, beyond the impact of estrogens. The results also imply that different chemoprevention strategies may be appropriate for selected individuals, highlighting the need to be particularly aware of women with a high waist/hip ratio but normal body mass index. Given the lack of any proven pharmacologic intervention for estrogen receptor negative breast cancer, stricter weight‐control measures may be advised in these individuals.
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AbstractBackground.Pediatric brain tumors are the leading cause of death for children with cancer in the U.S. Incorporating next‐generation sequencing data for both pediatric low‐grade (pLGGs) and high‐grade gliomas (pHGGs) can inform diagnostic, prognostic, and therapeutic decision‐making.Materials and Methods.We performed comprehensive genomic profiling on 282 pediatric gliomas (157 pHGGs, 125 pLGGs), sequencing 315 cancer‐related genes and calculating the tumor mutational burden (TMB; mutations per megabase [Mb]).Results.In pLGGs, we detected genomic alterations (GA) in 95.2% (119/125) of tumors. BRAF was most frequently altered (48%; 60/125), and FGFR1 missense (17.6%; 22/125), NF1 loss of function (8.8%; 11/125), and TP53 (5.6%; 7/125) mutations were also detected. Rearrangements were identified in 35% of pLGGs, including KIAA1549‐BRAF, QKI‐RAF1, FGFR3‐TACC3, CEP85L‐ROS1, and GOPC‐ROS1 fusions. Among pHGGs, GA were identified in 96.8% (152/157). The genes most frequently mutated were TP53 (49%; 77/157), H3F3A (37.6%; 59/157), ATRX (24.2%; 38/157), NF1 (22.2%; 35/157), and PDGFRA (21.7%; 34/157). Interestingly, most H3F3A mutations (81.4%; 35/43) were the variant K28M. Midline tumor analysis revealed H3F3A mutations (40%; 40/100) consisted solely of the K28M variant. Pediatric high‐grade gliomas harbored oncogenic EML4‐ALK, DGKB‐ETV1, ATG7‐RAF1, and EWSR1‐PATZ1 fusions. Six percent (9/157) of pHGGs were hypermutated (TMB >20 mutations per Mb; range 43–581 mutations per Mb), harboring mutations deleterious for DNA repair in MSH6, MSH2, MLH1, PMS2, POLE, and POLD1 genes (78% of cases).Conclusion.Comprehensive genomic profiling of pediatric gliomas provides objective data that promote diagnostic accuracy and enhance clinical decision‐making. Additionally, TMB could be a biomarker to identify pediatric glioblastoma (GBM) patients who may benefit from immunotherapy.Implications for Practice.By providing objective data to support diagnostic, prognostic, and therapeutic decision‐making, comprehensive genomic profiling is necessary for advancing care for pediatric neuro‐oncology patients. We present the largest cohort of pediatric low‐ and high‐grade gliomas profiled by next‐generation sequencing. We detected reportable alterations in 95% of patients, including diagnostically relevant lesions as well as novel oncogenic fusions and mutations. Additionally, we report tumor mutational burden (TMB), which identifies a subpopulation of hypermutated glioblastomas that harbor deleterious mutations in DNA repair genes. This provides support for TMB as a potential biomarker to identify patients who may preferentially benefit from immune checkpoint inhibitors.
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