Abstract
Recently,
telomerase reverse transcriptase
(
TERT
) gene rearrangements have been identified in neuroblastoma (NB), the typical pathological type of neuroblastic tumours (NTs); however, the ...prevalence of
TERT
rearrangements in other types of NT remains unknown. This study aimed to develop a practical method for detecting
TERT
defects and to evaluate the clinical relevance of
TERT
rearrangements as a biomarker for NT prognosis. A
TERT
break‐apart probe for fluorescence
in situ
hybridisation (FISH) was designed, optimised, and applied to assess the genomic status of
TERT
in Chinese children with NTs at the Beijing Children's Hospital from 2016 to 2019. Clinical, histological, and genetic characteristics of
TERT
‐rearranged NTs were further addressed. Genomic
TERT
rearrangements could be effectively detected by FISH and were mutually exclusive with
MYCN
amplification.
TERT
rearrangements were identified in 6.0% (38/633) of NTs overall, but 12.4% (31/250) in high‐risk patients.
TERT
rearrangements identified a subtype of aggressive NTs with the characteristics of Stage 3/4, high‐risk category, over 18 months old, and presenting all histological subtypes of NB and ganglioneuroblastoma nodular. Moreover,
TERT
rearrangements were significantly associated with elevated
TERT
expression levels and decreased survival chances. Multivariable analysis confirmed that it was an independent prognostic marker for NTs. FISH is an easily applicable method for evaluating
TERT
defects, which define a subgroup of NTs with unfavourable prognosis.
TERT
rearrangements would contribute to characterising NT molecular signatures in clinical practice.
In adults, the presence of the BRAF
mutation in papillary thyroid cancer (PTC) has been demonstrated to be strongly associated with aggressive cancer-cell characteristics and poor patient prognosis. ...In contrast, the frequency of this mutation in pediatric PTC has undergone limited study, and the few available estimates range from 0 to 63%. Furthermore, the role of the BRAF
mutation in pediatric PTC is controversial; thus, the present study aimed to investigate the prevalence and role of the BRAF
mutation in 48 pediatric patients with PTC, aged 3-13 years. Of these patients, 41 were diagnosed with classic PTC, five were found to have a follicular variant of PTC, and two to exhibit a diffuse sclerosing PTC variant. The BRAF
mutation was identified to be present in 35.4% of the 48 analyzed patients, and in 41.5% of the patients diagnosed with classical PTC. Furthermore, the presence of the BRAF
mutation was found to be associated with a patient age at diagnosis of less than ten years (P=0.011), the performance of a thyroidectomy (P=0.03), exhibited tumor multifocality (P=0.02) and/or extra-thyroidal invasion (P=0.003), and both a low MACIS (Metastases, Age, Completeness of resection, Invasion, Size)(P=0.036) and AMES (Age, Metastasis, Extent of tumor, Size)(P=0.001) score. Together, these data suggest that the presence of the BRAF
mutation may be negatively correlated with partial aggressive clinicopathological features of pediatric PTC.
To describe the characteristics, treatments, and prognosis of pediatric gastric perforation patients beyond neonatal period.
Twenty pediatric patients beyond neonatal period were included in this ...study. Medical records were reviewed and clinical characteristics were analyzed. According to the outcomes, patients were divided into the survival group and the death group. Death time was documented, and survival patients were followed up. The degree of severity was calculated using pediatric critical illness score (PCIS). Differences between the two groups were analyzed by the Student's t-test, Mann-Whitney test and Chi-square test appropriately.
Gastric perforation was diagnosed in 20 pediatric patients beyond neonatal period, including 6 males (30%) and 14 females (70%), with the age of 37.18 (15.90, 107.12) months, and the range was from 4.30 months to 14.17 years old. They had different manifestations, etiologies, sites of perforation and surgery procedures. Among the 20 cases, 14 (70%) survived and 6 (30%) died. Age, gender, length and number of perforation had no statistically difference between the two groups. However, PCIS, ischemia of gastrointestinal wall, and transmural necrosis of gastric wall were statistically different. For the survival group, during a follow-up period of 50 (36, 68) months, ranging from 2 months to 8 years and 7 months, one patient had a second-time perforation, another 3 patients had brain injury symptoms, and the rest 10 patients had good quality of lives.
Gastric perforation of pediatric patients beyond neonatal period causes a mortality of 30% on this study. Spontaneous great curvature of gastric wall perforation has the highest morbidity. Low PCIS predicts for unfavorable prognosis. Most of the survival patients have satisfactory living quality after operation.
Objective:
To investigate the clinical characteristics, treatment, and prognosis of children with systemic juvenile xanthogranuloma (JXG).
Methods:
Clinical data of children with JXG who were ...hospitalized in Beijing Children's Hospital, Capital Medical University, from January 2012 to December 2019 were retrospectively analyzed, including clinical manifestations, laboratory determinations, treatment, and prognosis of the children. Patients were treated with vindesine + prednisone as the first-line treatment and cytarabine + vindesine + dexamethasone ± cladribine as the second-line treatment.
Results:
Ten patients, including 8 males and 2 females, with a median of onset age of 1.95 (0.80–7.30) years, exhibited multi-system dysfunction. The median age of diagnosis was 2.45 (1.30–12.10) years. The most common location of extracutaneous lesions was the central nervous system (6 cases), followed by the lung (5 cases) and bone (4 cases). Nine patients underwent first-line chemotherapy, and 6 patients underwent second-line chemotherapy, including 5 patients with poorly controlled disease after first-line treatment. The median observation time was 29 (3–115) months. Nine patients survived, whereas one patient died of respiratory failure caused by pulmonary infection. At the end of follow-up, 7 patients were in active disease (AD)/regression state (AD-better), and 2 patients were in an AD/stable state (AD-stable). Three patients had permanent sequelae, mainly central diabetes insipidus. The rates of response to the first-line treatment and the second-line treatment were 40.0 and 66.7% respectively.
Conclusion:
The chemotherapy protocol for Langerhans cell histiocytosis (LCH) may be effective for patients with systemic JXG. Central nervous system involvement may not impact overall survival, but serious permanent sequelae may occur.
Prognostic effects of Mitosis-Karyorrhexis Index (MKI) used in the International Neuroblastoma Pathology Classification (INPC) are age-dependent. A total of 4,282 neuroblastomas reviewed at the ...Children's Oncology Group Neuroblastoma Pathology Reference Laboratory (8/1/2001–3/31/2012) included 2,365 low-MKI (L-MKI), 1,068 intermediate-MKI (I-MKI), and 849 high-MKI (H-MKI) tumors. Cox proportional hazards models were fit to determine age cut-offs at which the relative risk of event/death was maximized in each MKI class. Backward-selected Cox models were fit to determine the prognostic strength of the age cut-offs for survival in the presence of other prognostic factors. The age cut-offs used in the INPC for L-MKI tumors (<60 months, n = 2,710, 84.0% ± 1.0% event-free survival EFS, 93.8 ± 0.7% overall survival OS vs ≥60 months, n = 195, 49.8% ± 4.6% EFS, 71.7% ± 4.1% OS; P < 0.0001) and I-MKI tumors (<18 months, n = 568, 83.8% ± 2% EFS, 93.7% ± 1.3% OS vs ≥18 months, n = 500, 51.4% ± 2.9% EFS, 66.7% ± 2.7% OS; P < 0.0001) were within the effective range for distinguishing prognostic groups. As for H-MKI tumors (no cut-off age in the INPC, 51.0% ± 2.2% EFS, 64.4% ± 2.1% OS), a new cut-off of 3–4 months was suggested (<4 months, n = 38, 82.3% ± 8.4% EFS, 81.8% ± 8.5% OS vs ≥4 months, n = 811, 49.6% ± 2.2% EFS, 63.7% ± 2.1% OS, P = 0.0034 and 0.0437, respectively). Multivariate analyses revealed that cut-offs of 60 and 18 months for L-MKI and I-MKI tumors, respectively, were independently prognostic. However, the cut-off of 4 months for H-MKI tumors did not reach statistical significance in the presence of other factors. The age cut-offs for MKI classes (60 months for L-MKI, 18 months for I-MKI, no cut-off for H-MKI) in the current INPC are reasonable and effective for distinguishing prognostic groups with increased risk of event/death for older patients.
ABSTRACT
Importance
Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children. More than 90% of cases are classified as embryonic RMS (ERMS) or alveolar RMS (ARMS). ERMS has a worse ...prognosis than ARMS. Early differential diagnosis is of paramount importance for optimization of treatment.
Objective
To identify genes that are differentially expressed between ARMS and ERMS, which can be used for accurate rhabdomyosarcoma classification.
Methods
Three Gene Expression Omnibus datasets composed of ARMS and ERMS samples were screened and 35 differentially expressed genes (DEGs) were identified. Receiver operating characteristic curve analysis and area under the curve analysis was performed for these 35 DEGs and seven candidate genes with the best differential expression scores between ARMS and ERMS were determined. The expression of these seven candidate genes was validated by immunohistochemical analysis of pre‐chemotherapy ARMS and ERMS specimens.
Results
The levels of DCX and CRABP2 were confirmed to be remarkably different between paraffin‐embedded ARMS and ERMS tissues, while EGFR abundance was only marginally different between these two RMS subtypes.
Interpretation
DCX and CRABP2 are potential biomarkers for distinguishing ARMS from ERMS in pre‐chemotherapy pediatric patients.
Introduction
There is a known association between primary mediastinal germ cell tumor (PMGCT) and hematologic malignancy that is not linked to treatment. They are exceptionally rare entities with a ...low morbidity and a poor prognosis.
Case presentation
An 11‐year‐old boy presented with an anterior mediastinal mass diagnosed as a malignant germ cell tumor on the basis of an excisional biopsy. He was found to have acute myeloid leukemia (AML) two years after the chemotherapy for his germ cell tumor. The clinical course was very aggressive with a survival time of only 1 week after diagnosis of AML associated with PMGCT.
Conclusion
AML associated with PMGCT needs to be diagnosed correctly. Relevant examinations should be carried out in patients with PMGCTs during and after chemotherapy, and long‐term follow‐up is still necessary to reduce the risk of morbidity and mortality.
The morphologies of alveolar rhabdomyosarcoma (ARMS) are various. Some cases entirely lack an alveolar pattern and instead display a histological pattern that overlaps with embryonal rhabdomyosarcoma ...(ERMS). The method of pathological diagnosis of ARMS and ERMS has been updated in the 4th edition of the World Health Organization's guidelines for classification of skeletal muscle tumors. Under the new guidelines, there is still no molecular test to distinguish between these two subtypes of rhabdomyosarcoma (RMS). In the present study, we applied fluorescent in situ hybridization (FISH) and found that the Forkhead box O1 (FOXO1) gene broke apart, amplified, and displayed an aneuploid signal that was related to the RMS pathological subtype. Aside from the fact that FOXO1 break-apart and its amplification were correlated with atypical ARMS, aneuploidies were usually found in atypical ERMS. In conclusion, our results detail a potential biomarker to improve the accuracy of pathological diagnosis by discriminating between atypical ARMS and atypical ERMS.
Environmental concerns have been raised on the adverse health effects of vehicle emissions in micro-scale traffic-crowded street canyons, especially for pedestrians and residents living in near-road ...buildings. Viaduct design is sometimes used to improve transportation efficiency but possibly affects urban airflow and the resultant exposure risk, which have been rarely investigated so far. The personal intake fraction (P_IF) is defined as the average fraction of total emissions that is inhaled by each person of a population (1 ppm = 1 × 10−6), and the daily carbon monoxide (CO) pollutant exposure (Et) is estimated by multiplying the average concentration of a specific micro-environment within one day. As a novelty, by considering time activity patterns and breathing rates in various micro-environments for three age groups, this paper introduces IF and Et into computational fluid dynamic (CFD) simulation to quantify the impacts of street layouts (street width/building height W/H = 1, 1.5, 2), source location, viaduct settings and noise barriers on the source-exposure correlation when realistic CO sources are defined. Narrower streets experience larger P_IF (1.51–5.21 ppm) and CO exposure, and leeward-side buildings always attain higher vehicular pollutant exposure than windward-side. Cases with a viaduct experience smaller P_IF (3.25–1.46 ppm) than cases without a viaduct (P_IF = 5.21–2.23 ppm) if the single ground-level CO source is elevated onto the viaduct. With two CO sources (both ground-level and viaduct-level), daily CO exposure rises 2.80–3.33 times but P_IF only change slightly. Noise barriers above a viaduct raise concentration between barriers, but slightly reduce vehicular exposure in near-road buildings. Because people spend most of their time indoors, vehicular pollutant exposure within near-road buildings can be 6–9 times that at pedestrian level. Although further studies are still required to provide practical guidelines, this paper provides effective methodologies to quantify the impacts of street/viaduct configurations on human exposure for urban design purpose.
Display omitted
•Intake fraction (IF) and daily CO exposure are adopted to assess human exposure.•Effects of street layouts, viaduct/noise barriers and source locations are studied.•Viaducts attain smaller human exposure if single source is elevated onto viaduct.•Noise barriers raise CO concentration above a viaduct, but reduce indoor exposure.•Indoor exposure to traffic emissions is much greater than that at pedestrian level.
Wider street and urban viaduct with a single elevated source could alleviate indoor exposure and building intake fraction. Adding noise barriers has no significant impact.
Vehicular pollutant exposure of residents and pedestrians in high-rise deep street canyons with viaducts and noise barriers requires special concerns because the ventilation capacity is weak and the ...literature reported inconsistent findings on flow patterns as aspect ratios (building height/street width, H/W) are larger than 2. By conducting computational fluid dynamics (CFD) simulations coupled with the intake fraction iF and the daily pollutant exposure Et, this paper investigates the impact of street aspect ratios, viaducts and noise barriers on the flow and vehicular passive pollutant exposure in full-scale street canyons (H/W=1–6, W=24m). iF represents the fraction of total emissions inhaled by a population (1ppm=10−6), while Et means the extent of human beings’ contact with pollutants within one day. CFD methodologies of passive pollutant dispersion modeling are successfully validated by wind tunnel data in Meroney et al. (1996).
As a novelty, the two-main-vortex pattern start appearing in full-scale street canyons as H/W changes from 4 to 5, however previous studies using wind-tunnel-scale models (H=6cm) reported two to five vortexes as H/W=2–5. This finding is validated by both smoke visualization in scale-model outdoor field experiments (H=1.2m, W=0.6m) and CFD simulations of Reynolds number independence. Cases with two main vortexes (H/W=5–6) experience much larger daily pollutant exposure (~103–104mg/m3/day) than those with single main vortex as H/W=1–4 (~101–102mg/m3/day). Moreover leeward-side pollutant exposures are much larger than windward-side as H/W=1–4 while oppositely as H/W=5–6. Assuming a general population density, the total iF is 485–803ppm as H/W=1, 2020–12051ppm as H/W=2–4, and 51112–794026ppm as H/W=5–6. With a single elevated pollutant source, cases with viaducts experience significantly smaller pollutant exposures than cases without viaducts. Road barriers slightly increase pollutant exposure in near-road buildings with H/W=1 while reduce a little as H/W=3 and 5. Two-source cases can experience 2.60–5.52 times pollutant exposure as great as single-source cases.
•Intake fraction (iF) and daily CO exposure (Et) are used for exposure assessment.•Effects of aspect ratios (H/W=1–6), viaduct/noise barriers are studied by CFD.•iF=102–104ppm as H/W=1–4 (one vortex) but iF=105–106ppm as H/W=5–6 (two vortexes).•Viaducts produce less CO exposure if only a viaduct-level CO source is fixed.•Noise barriers slightly reduce vehicular indoor CO exposure as H/W=3–6.
PDF
