The effect of 4 weeks of high-intensity interval training and 2 weeks of detraining on cardiovascular disease risk factors in male adolescents.

NEW FINDINGS: What is the central question of this study? What is the effect of 4 weeks of high-intensity interval training (HIIT) and 2 weeks of detraining on vascular function and traditional cardiovascular disease (CVD) risk factors in male adolescents? What is the main finding and its importance? Four weeks of HIIT improved macrovascular function in adolescents. However, this training period did not measurably change microvascular function, body composition or blood biomarkers. Following 2 weeks of detraining, the improvement in flow-mediated dilatation (FMD) was lost. This highlights the importance of the continuation of regular exercise for the primary prevention of CVD. ABSTRACT: High-intensity interval training (HIIT) represents an effective method to improve cardiometabolic health in adolescents. This study aimed to investigate the effect of 4 weeks of HIIT followed by 2 weeks of detraining on vascular function and traditional cardiovascular disease (CVD) risk factors in adolescent boys. Nineteen male adolescents (13.3 ± 0.5 years) were randomly allocated to either a training (TRAIN, n = 10) or control (CON, n = 9) group. Participants in TRAIN completed 4 weeks of HIIT running with three sessions per week. Macro- (flow-mediated dilatation, FMD) and microvascular (peak reactive hyperaemia, PRH) function, body composition (fat mass, fat free mass, body fat percentage) and blood biomarkers (glucose, insulin, total cholesterol, high- and low-density lipoprotein, triacylglycerol) were assessed pre-, 48 h post- and 2 weeks post-training for TRAIN and at equivalent time points for CON. Following training, FMD was significantly greater in TRAIN compared to CON (9.88 ± 2.40% and 8.64 ± 2.70%, respectively; P = 0.036) but this difference was lost 2 weeks after training cessation (8.22 ± 2.47% and 8.61 ± 1.99%, respectively; P = 0.062). No differences were detected between groups for PRH (P = 0.821), body composition (all P > 0.14) or blood biomarkers (all P > 0.18). In conclusion, 4 weeks of HIIT improved macrovascular function; however, this training period did not measurably change microvascular function, body composition or blood biomarkers. The reversal of the FMD improvement 2 weeks post-training highlights the importance of the continuation of regular exercise for the primary prevention of CVD.

NTRK2 gene fusions are uncommon in pilocytic astrocytoma.

BACKGROUND: Pilocytic astrocytoma is the most frequent pediatric glioma. Despite its overall good prognosis, complete surgical resection is sometimes unfeasible, especially for patients with deep-seated tumors. For these patients, the identification of targetable genetic alterations such as NTRK fusions, raised as a new hope for therapy. The presence of gene fusions involving NTRK2 has been rarely reported in pilocytic astrocytoma. The aim of the present study was to investigate the frequency of NTRK2 alterations in a series of Brazilian pilocytic astrocytomas. METHODS: Sixty-nine pilocytic astrocytomas, previously characterized for BRAF and FGFR1 alterations were evaluated. The analysis of NTRK2 alterations was performed using a dual color break apart fluorescence in situ hybridization (FISH) assay. RESULTS: NTRK2 fusions were successfully evaluated by FISH in 62 of the 69 cases. Neither evidence of NTRK2 gene rearrangements nor NTRK2 copy number alterations were found. CONCLUSIONS: NTRK2 alterations are uncommon genetic events in pilocytic astrocytomas, regardless of patients' clinicopathological and molecular features.

Effects of High-Intensity Interval Training on the Vascular and Autonomic Components of the Baroreflex at Rest in Adolescents.

PURPOSE: In a sample of healthy adolescents, the authors aimed to investigate the effects of high-intensity interval exercise (HIIE) training and detraining on baroreflex sensitivity (BRS) and it's vascular and autonomic components at rest. METHODS: Nineteen volunteers were randomly allocated to (1) 4 weeks HIIE training performed 3 times per week or (2) a control condition with no intervention for the same duration as HIIE training. PRE, POST, and following 2 weeks of detraining resting supine heart rate and blood pressure were measured, and a cross-spectral method (integrated gain [gain in low frequency]) was used to determine BRS gain. Arterial compliance (AC) was assessed as the BRS vascular component. LFgain divided by AC (LFgain/AC) was used as the autonomic determinant of BRS. RESULTS: The HIIE training was completed with 100% compliance. HIIE did not change resting gain in low frequency (LFgain) (P = .66; effect size = 0.21), AC (P = .44; effect size = 0.36), or LFgain/AC (P = .68; effect size = 0.19) compared to control. CONCLUSION: Four weeks of HIIE training does not change BRS and its autonomic and vascular determinant in a sample of healthy adolescents at rest.

The acute effect of high- and moderate-intensity interval exercise on vascular function before and after a glucose challenge in adolescents.

NEW FINDINGS: What is the central question of this study? What is the effect of high-intensity and moderate-intensity interval running on macro- and microvascular function in a fasted state and following a glucose challenge in adolescents? What is the main finding and its importance? Both macro- and microvascular function were improved after interval running independent of intensity. This finding shows that the intermittent exercise pattern and its associated effect on shear are important for vascular benefits. In adolescents, macrovascular function was enhanced after an acute glucose load. However, the effect of chronic glucose consumption on vascular function remains to be elucidated. ABSTRACT: Interventions targeting vascular function in youth are an important strategy for the primary prevention of cardiovascular diseases. This study examined, in adolescents, the effect of high-intensity interval running (HIIR) and moderate-intensity interval running (MIIR) on vascular function in a fasted state and postprandially after a glucose challenge. Fifteen adolescents (13 male, 13.9 ± 0.6 years) completed the following conditions on separate days in a counterbalanced order: (1) 8 × 1 min HIIR interspersed with 75 s recovery; (2) distance-matched amount of 1 min MIIR interspersed with 75 s recovery; and (3) rest (CON). Macro- (flow-mediated dilatation, FMD) and microvascular (peak reactive hyperaemia, PRH) function were assessed immediately before and 90 min after exercise/rest. Participants underwent an oral glucose tolerance test (OGTT) 2 h after exercise/rest before another assessment of vascular function 90 min after the OGTT. Following exercise, both HIIR and MIIR increased FMD (P = 0.02 and P = 0.03, respectively) and PRH (P = 0.04, and P = 0.01, respectively) with no change in CON (FMD: P = 0.51; PRH: P = 0.16) and no significant differences between exercise conditions. Following the OGTT, FMD increased in CON (P < 0.01) with no changes in HIIR and MIIR (both P > 0.59). There was no change in PRH after the OGTT (all P > 0.40). In conclusion, vascular function is improved after interval running independent of intensity in adolescents. Acute hyperglycaemia increased FMD, but prior exercise did not change vascular function after the OGTT in youth.

Associations of cardiometabolic risk factors with heart rate variability in 6- to 8-year-old children: The PANIC Study.

BACKGROUND: Associations of cardiometabolic risk factors with heart rate variability (HRV) in children are unclear. We examined associations of cardiometabolic risk score (CRS) and individual cardiometabolic risk factors with HRV variables in 6- to 8-year-olds. METHODS: The participants were a population-based sample of 443 children participating in baseline measurements of the Physical Activity and Nutrition in Children trial. Cardiometabolic risk factors included waist circumference (WC), insulin, glucose, triglycerides, HDL cholesterol, systolic blood pressure (SBP), and diastolic blood pressure (DBP). CRS was calculated as WC + insulin + glucose + triglycerides - HDL cholesterol + the mean of SBP and DBP. HRV variables (SDNN, RMSSD, HF, LF, LF/HF, Mean RR) were measured using 5-minute electrocardiography at rest and analyzed using the Kubios HRV software. In this cross-sectional study, associations of CRS and individual cardiometabolic risk factors with HRV were investigated using linear regression analyses adjusted for sex and peak height velocity. RESULTS: CRS was negatively associated with RMSSD, HF, Mean RR (P value < .05) and positively with LF/HF (P value = .005). Insulin was negatively associated with SDNN, RMSSD, HF, LF, and Mean RR (P value < .05) and positively with LF/HF (P value = .008). SBP was negatively associated with SDNN, RMSSD, HF, LF, and Mean RR (P value < .05). DBP was negatively associated with SDNN, RMSSD, and Mean RR (P value < .05). WC, glucose, triglycerides, or HDL cholesterol were not associated with HRV variables. CONCLUSIONS: Higher CRS, insulin, and blood pressure were associated with smaller HRV, mainly indicating lower parasympathetic activity, in young children. This knowledge may help improving the clinical management of metabolic syndrome and cardiovascular diseases since childhood.

Effects of exercise intensity on vascular and autonomic components of the baroreflex following glucose ingestion in adolescents.

PURPOSE: To investigate the effects of an oral glucose tolerance test (OGTT) on baroreflex sensitivity (BRS) in a sample of healthy adolescents, and how acute exercise bouts of different intensities alter the effects of the OGTT on BRS. METHODS: Thirteen male adolescents (14.0 ± 0.5 years) completed three conditions on separate days in a counterbalanced order: (1) high-intensity interval exercise (HIIE); (2) moderate-intensity interval exercise (MIIE); and (3) resting control (CON). At ~ 90 min following the conditions, participants performed an OGTT. Supine heart rate and blood pressure were monitored continuously at baseline, 60 min following the conditions, and 60 min following the OGTT. A cross-spectral method (LFgain) was used to determine BRS gain. Arterial compliance (AC) was assessed as the BRS vascular component. LFgain divided by AC (LFgain/AC) was used as the autonomic component. RESULTS: Although non-significant, LFgain moderately decreased post-OGTT when no exercise was performed (pre-OGTT = 24.4 ± 8.2 ms mmHg- 1; post-OGTT = 19.9 ± 5.6 ms mmHg- 1; ES = 0.64, P > 0.05). This was attributed to the decrease in LFgain/AC (pre-OGTT = 1.19 ± 0.5 ms µm- 1; post-OGTT = 0.92 ± 0.24 ms µm- 1; ES = 0.69, P > 0.05). Compared to CON (Δ = - 4.4 ± 8.7 ms mmHg- 1), there were no differences for the pre-post-OGTT delta changes in LF/gain for HIIE (Δ = - 3.5 ± 8.2 ms mmHg- 1) and MIIE (Δ = 1.3 ± 9.9 ms mmHg- 1) had no effects on BRS following the OGTT (all ES < 0.5). Similarly, compared to CON (Δ = - 0.23 ± 0.40 ms µm- 1) there were no differences for the pre-post-OGTT delta changes in LF/gain for HIIE (Δ = - 0.22 ± 0.49 ms µm- 1) and MIIE (Δ = 0.13 ± 0.36 ms µm- 1). CONCLUSION: A moderate non-significant decrease in BRS was observed in adolescents following a glucose challenge with no apparent effects of exercise.

Cardiac Autonomic Function, Cardiovascular Risk and Physical Activity in Adolescents.

The aims of this study were to investigate in adolescents: 1) the relationships of physical activity (PA) and cardiorespiratory fitness (CRF) to traditional CVD risk factors, rest and recovery autonomic function; and 2) whether autonomic function strengthens the associations between PA, CRF and CVD risk. Fifty-four (22 girls) adolescents had traditional CVD risk factors, rest and recovery autonomic function evaluated. CRF was measured using a steep ramp cycle test and PA was assessed with accelerometers. Resting HRV (and RMSSD30) and heart rate recovery (T30, HHRτ) were used. Clustered traditional (CVDRtrad) and autonomic (CVDRauto) risk scores were created and added to form a composite clustered CVD risk score (CVDRcom). PA and CRF were significantly and negatively associated with traditional CVD risk factors. Moderate (MPA) and vigorous (VPA) were positively related to resting RMSSD, and negatively related to T30 and HHRτ (all P<0.05). RMSSD30 recovered faster in the high compared to low median split for VPA. Stronger associations for CVDRcom compared to CVDRtrad were observed for MPA (CVDRcom: r2=0.32, P=<0.001; CVDRtrad: r2=0.17, P=0.002), and VPA (CVDRcom: r2=0.18, P=0.001; CVDRtrad: r2=0.06, P=0.08). These findings strengthen the proposed additional beneficial effects of PA on autonomic function above traditional CVD risk factors.

Expression of Methylthioadenosine Phosphorylase (MTAP) in Pilocytic Astrocytomas.

BACKGROUND/OBJECTIVES: Pilocytic astrocytomas (PAs) are the most frequent astrocytomas in children and adolescents. Methilthioadenosine phosphorylase(MTAP) is a tumor-suppressor gene, the loss of expression of which is associated with a poor prognosis and better response to specific chemotherapy in leukemia and non-small-cell lung cancer. The expression of MTAP in brain tumors remains largely unknown and its biological role in PA is still unexplored. Our aims were to describe the immunohistochemical MTAP expression in a series of PAs and relate it to the clinicopathological features of the patients. METHODS: We assessed MTAP expression on immunohistochemistry in 69 pediatric and adult patients with PA in a tissue microarray platform. RESULTS: Retained expression of MTAP was seen in >85% of the tumors compared to in the nonneoplastic adjacent tissue. Only 3 supratentorial tumors showed a complete loss of MTAP expression. No significant association with clinicopathological features or overall survival of the patients was found. CONCLUSIONS: MTAP expression is retained in PAs and is not an outcome predictor for these tumors. Nevertheless, a subset of patients with PAs exhibiting a loss of MTAP could potentially benefit from treatment with specific chemotherapy, especially when lesions are recurrent or surgical resection is not recommended.

The utility of the reperfusion rate of tissue oxygen saturation as a measure of vascular endothelial function in adolescents: reliability, validity and sensitivity.

Introduction: The near-infrared spectroscopy (NIRS)-derived reperfusion rate of tissue oxygen saturation (slope 2 StO2) may provide a surrogate measure of vascular function, however, this has yet to be examined in a paediatric population. This study investigated in adolescents: 1) the between-day reliability of NIRS-derived measurements; 2) the relationship between slope 2 StO2 and macro- (flow-mediated dilation, FMD) and microvascular (peak reactive hyperaemia, PRH) function; and 3) the effect of high-intensity interval exercise (HIIE) on slope 2 StO2, FMD, and PRH. Methods: Nineteen boys (13.3 ± 0.5 y) visited the laboratory on two occasions, separated by ∼ 1 week. On visit 1, participants underwent simultaneous assessment of brachial artery FMD and slope 2 StO2 and PRH on the internal face of the forearm. On visit 2, participants completed a bout of HIIE with slope 2 StO2, FMD and PRH measured pre-, immediately post- and 1.5 h post-exercise. Results: Slope 2 StO2 showed no mean bias (p = 0.18) and an intraclass correlation coefficient of 0.67 (p = 0.003) between visits. No significant correlation between slope 2 StO2 and FMD or PRH was observed on visit 1 (r = -0.04, p = 0.89 and r = -0.30, p = 0.23, respectively) or visit 2 pre-exercise (r = -0.28, p = 0.25 and r = -0.31, p = 0.20, respectively). Compared to pre-exercise, FMD decreased immediately post-exercise (p < 0.001) and then increased 1.5 h post-exercise (p < 0.001). No significant change was detected for slope 2 StO2 (p = 0.30) or PRH (p = 0.55) following HIIE. Conclusion: In adolescents, slope 2 StO2 can be measured reliably, however, it is not correlated with FMD or PRH and does not follow the acute time course of changes in FMD post-exercise. Hence, the use of slope 2 StO2 as a surrogate measure of vascular function in youth must be refuted.

Pediatric Skull Base Tumors: A Management Challenge.

CONTEXT: Skull base tumors are varied in children and are particularly challenging to pediatric neurosurgeons, with few papers in the literature describing the evolution, complications, and outcome. The authors evaluated long-term outcomes in children submitted to skull base tumor surgery and performed a literature review. AIMS: The aim of this study was to analyze surgical results, complications, and outcomes, on comparison with previous publications. MATERIALS AND METHODS: A retrospective analysis of children undergoing surgery at a single institution between 2000 and 2018 for lesions of the cranial base was carried out. In addition, a literature review was carried out describing a total of 115 children operated on for skull base tumors. STATISTICAL ANALYSIS: Chi-squared and Fisher's exact tests were performed to compare the distribution of categorical variables and a nonparametric Mann-Whitney U test was used to perform intergroup comparisons of continuous variables. RESULTS: Seventeen children ranging in age from 8 months to 17 years (mean, 10.9 years) underwent skull base approaches. Tumor types included schwannoma, meningioma, chondroid chordoma, mature teratoma, epidermoid cyst, hemangiopericytoma, rhabdomyosarcoma, myofibroblastic inflammatory tumor, fibromyxoid sarcoma, Crooke's cell adenoma, ossifying fibroma, osteoblastoma, nasopharyngeal angiofibroma and Ewing's sarcoma. Gross total resection was achieved in 6 patients (35.3%), 12 patients (70.6%) had benign histology, and 5 patients (29.4%) had a malignant tumor. Transient postoperative cerebrospinal fluid leak affected only one patient. Thirteen children (76.4%) had a residual neurological deficit at last follow-up evaluation. Three (17.6%) surviving patients received adjuvant therapy. The rate of recurrence or lesion progression was 17.6%. CONCLUSIONS: Skull base tumors in children present a therapeutic challenge because of their unique pathological composition and can lead to considerable morbidity and mortality in pediatric age.

Does motor coordination influence perceptual-cognitive and physical factors of agility in young soccer players in a sport-specific agility task?

This study aims to determine whether motor coordination influences the perception-decision time (perceptual-cognitive factor) and movement response time (physical factor) of young soccer players in a sport-specific agility task regardless of maturation. Eighty-seven young male soccer players were analysed. Anthropometric measurements were used to determine the maturity offset, while physical qualities including agility, change of direction speed (CODS) and motor coordination were also assessed. The following variables were obtained from these tests: Motor coordination score, perception-decision time, movement response time, agility time and CODS time. Motor coordination revealed a non-significant correlation with perception-decision time (r = 0.10, p = 0.34). However, motor coordination showed negative and significant correlations with CODS time (r = -0.47, p < 0.01), agility time (r = -0.52, p < 0.01) and movement response time (r = -0.62, p < 0.01). In addition, regression analysis showed that each increase in motor coordination score was associated with significant decreases in agility time (b = -0.023), movement response time (b = -0.021) and CODS time (b = -0.021) independent of maturity offset. The results of this study indicated that motor coordination was significantly related to the physical factors of agility in young soccer players.

Toxicity assessment and clearance of Brazilian microbial pest control agents in mice.

The environmental toxicology of chemical pesticides have increased interest in the development and use of microbial pest control agents. In the present study four new Brazilian strains of Bacillus and one fungus were tested to evaluate the acute oral toxicity and clearance of these microbials in C57BL6 mice. No mortality was observed after exposure for any of the microorganisms tested. Clearance was significant after 30 days but for one strain of B. thuringiensis and one of B. sphaericus this time was not enough to completely eliminate the spores.

Closed Depressed Skull Fracture in Childhood Reduced with Suction Cup Vacuum Method: Case Report and a Systematic Literature Review.

Depressed skull fracture, also referred to as a "ping-pong ball" or "pond" fracture in neonates, is a common sign of traumatic brain injury in paediatric patients. The main causes of depressed skull fractures include labour and obstetric trauma in newborns and direct head trauma in older children. Skull depression rarely resolves spontaneously, and the surgical options include open cranioplasty and percutaneous microscrew elevation, among others. The use of negative pressure as a technique for fracture reduction has been described in a few papers. Here, we present a case-based review along with an illustrative case of depressed skull fracture reduced using the suction cup method via negative pressure. In addition, a Systematic Literature Review was performed to evaluate the safety of applying this procedure. The suction cup method is a feasible method to reduce depressed skull fracture in children, with minimum complications and no apparent long-term impairments.

Reliability of autonomic and vascular components of baroreflex sensitivity in adolescents.

Improvements in the autonomic and vascular systems are implicated in cardiovascular disease risk reduction. Baroreflex sensitivity (BRS) is composed of vascular and autonomic components. This study aimed to investigate between- and within-day reliability of BRS and its autonomic and vascular determinants in adolescents. Thirteen male adolescents (14·1 ± 0·5 y) participated in this study. For between-day reliability, participants completed four experimental visits separated by a minimum of 48-h. For within-day reliability, participants repeated BRS assessments three times in the morning with one hour between the measures. BRS was evaluated using the cross-spectral gain (LFgain) between blood pressure and heart rate interval. BRS was further divided into: 1) vascular component using arterial compliance (AC); and 2) autonomic component measured as LFgain divided by AC (LFgain/AC). LFgain, AC and LFgain/AC presented between-day coefficient of variation (CV) of 20%, 17%, and 20%, respectively. Similarly, variables associated with blood pressure control, such as cardiac output, mean arterial pressure, heart rate and total peripheral resistance, presented CVs ranging from 6% to 15%. Within-day reliability was poorer compared to between-day for LFgain (25%), AC (25%), and LFgain/AC (31%), as well as all hemodynamic variables (CVs from 11% to 22%, except heart rate with presented CV of 6%). This study indicates suitable between- and within-reliability of BRS and its autonomic and vascular determinants, as well as hemodynamic variables associated with BRS, in adolescents.

Methods of assessment of the post-exercise cardiac autonomic recovery: A methodological review.

The analysis of post-exercise cardiac autonomic recovery is a practical clinical tool for the assessment of cardiovascular health. A reduced heart rate recovery - an indicator of autonomic dysfunction - has been found in a broad range of cardiovascular diseases and has been associated with increased risks of both cardiac and all-cause mortality. For this reason, over the last several years, non-invasive methods for the assessment of cardiac autonomic recovery after exercise - either based on heart rate recovery or heart rate variability indices - have been proposed. However, for the proper implementation of such methods in daily clinical practice, the discussion of their clinical validity, physiologic meaning, mathematical formulation and reproducibility should be better addressed. Therefore, the aim of this methodological review is to present some of the most employed methods of post-exercise cardiac autonomic recovery in the literature and comprehensively discuss their strengths and weaknesses.

[Giant internal carotid artery aneurysm simulating pituitary adenoma]. / Aneurisma gigante de carótida interna simulando macroadenoma de hipófise.

Giant aneurysm projected into the sellar region is a rare cause of hypopituitarism and is usually associated with atherosclerosis, fibromuscular dysplasia and pituitary radiation therapy. We report the case of a 78-year-old patient presenting a giant internal carotid artery aneurysm disclosed by clinical features of hypopituitarism and cranial nerves compression (optic and abducent). Computed tomographic scans, magnetic resonance images and cerebral angiography were performed and showed the aneurysm. Cerebral angiography confirmed concomitant atherosclerosis and fibromuscular dysplasia. After evaluation of risk/benefit, no surgical treatment was proposed. Replacement endocrine therapy with glucocorticoid and levothyroxine was initiated followed by a satisfactory clinical response.

Visceral leishmaniasis: historical series of hospitalized patients and correlation with climate in an endemic area in Minas Gerais, Brazil / Leishmaniose visceral: série histórica de pacientes hospitalizados e correlação com o clima em área endêmica de Minas Gerais, Brasil

RESUMEN Introducción La leishmaniasis visceral (LV) es una enfermedad infecciosa causada por protozoos del género Leishmania; predomina en las regiones tropicales, subtropicales y templadas. Objetivo Caracterizar una serie de casos de LV en pacientes mayores de 18 años atendidos en un hospital de referencia del norte de Minas Gerais, así como describir la ocurrencia de casos, según la caracterización climatológica, y correlacionar la distribución de los casos con la lluvia y la temperatura ambiente. Métodos El diseño del estudio fue una serie de casos recopilados entre 1999 y 2016. Los datos se extrajeron de historias clínicas seleccionadas cronológicamente. La información climática se recopiló en el Centro de estudios del Semiárido de la Universidad Federal de Montes Claros (Unimontes). Resultados Hubo un ligero predominio del sexo masculino (54,4%) y de edades comprendidas entre uno y cuatro años (42,9%). El tiempo de evolución de las manifestaciones clínicas hasta el momento de la hospitalización osciló entre cinco y 120 días, siendo la duración más frecuente entre 16 y 30 días (34,4%). Hepatomegalia, esplenomegalia, palidez cutánea y fiebre fueron manifestaciones presentes en más del 90% de los pacientes al ingreso. El diagnóstico se realizó por métodos serológicos en la mayoría de los casos (85,9%). La mayor parte de los ingresos duró entre 16 y 30 días (44%) y el alta hospitalaria con orientación para el control ambulatorio fue el resultado más frecuente de los ingresos. El porcentaje de muertes fue del 2%. Conclusión Las características predominantes son niños varones de 1 a 4 años, que acudió al servicio de salud con la clásica tríada LV: hepatoesplenomegalia, palidez y fiebre prolongada. En este estudio no hubo asociación estadísticamente significativa entre temperatura, precipitación y número de casos, sin embargo, existen matices en los factores ambientales que influyen en la dinámica de transmisión de LV, los cuales varían de región a otra.

KIAA1549: BRAF Gene Fusion and FGFR1 Hotspot Mutations Are Prognostic Factors in Pilocytic Astrocytomas.

Up to 20% of patients with pilocytic astrocytoma (PA) experience a poor outcome. BRAF alterations and Fibroblast growth factor receptor 1 (FGFR1) point mutations are key molecular alterations in Pas, but their clinical implications are not established. We aimed to determine the frequency and prognostic role of these alterations in a cohort of 69 patients with PAs. We assessed KIAA1549:BRAF fusion by fluorescence in situ hybridization and BRAF (exon 15) mutations by capillary sequencing. In addition, FGFR1 expression was analyzed using immunohistochemistry, and this was compared with gene amplification and hotspot mutations (exons 12 and 14) assessed by fluorescence in situ hybridization and capillary sequencing. KIAA1549:BRAF fusion was identified in almost 60% of cases. Two tumors harbored mutated BRAF. Despite high FGFR1 expression overall, no cases had FGFR1 amplifications. Three cases harbored a FGFR1 p.K656E point mutation. No correlation was observed between BRAF and FGFR1 alterations. The cases were predominantly pediatric (87%), and no statistical differences were observed in molecular alterations-related patient ages. In summary, we confirmed the high frequency of KIAA1549:BRAF fusion in PAs and its association with a better outcome. Oncogenic mutations of FGFR1, although rare, occurred in a subset of patients with worse outcome. These molecular alterations may constitute alternative targets for novel clinical approaches, when radical surgical resection is unachievable.

Metachronous occurrence of nonradiation-induced brain cavernous hemangioma and medulloblastoma in a child with neurofibromatosis type I phenotype.

Cavernous hemangioma (CH) is a sporadic vascular malformation occurring either as an autosomal dominant condition or as a well-known complication of radiation exposure. Medulloblastoma is a primitive neuroectodermal tumor common in children and currently treated with surgical resection, chemotherapy, and radiotherapy. Neurofibromatosis is the most common single-gene disorder of the central nervous system. Posterior fossa malignant tumors in the context of neurofibromatosis type I (NF1) are very infrequent. This is the first documented case of an unusual metachronous occurrence of non-radiation-induced CH and medulloblastoma in a child with NF1 phenotype. We report the case of a 13-month-old boy with café-au-lait skin lesions associated with NF1-like phenotype who underwent surgical resection of a single CH in the temporal lobe due to recurrent seizures. Four years later he presented with signs of raised intracranial pressure associated with a posterior fossa tumor and hydrocephalus, thus requiring gross total resection of the lesion. Histological analysis revealed a medulloblastoma. After being treated with radiotherapy and chemotherapy, he achieved total remission. Six years later a massive recurrence of the tumor was observed and the child eventually died. The interest in this case lies in the rarity of NF1-like phenotype associated with a non-radiation-induced brain CH and medulloblastoma in a child.