Treatment planning for children with neuroblastoma requires accurate assessment of prognosis. The most recent Children's Oncology Group (COG) risk classification system used tumor stage as defined by ...the International Neuroblastoma Staging System. Here, we validate a revised classifier using the International Neuroblastoma Risk Group Staging System (INRGSS) and incorporate segmental chromosome aberrations (SCA) as an additional genomic biomarker.
Newly diagnosed patients enrolled on the COG neuroblastoma biology study ANBL00B1 between 2007 and 2017 with known age, International Neuroblastoma Staging System, and INRGSS stage were identified (N = 4,832). Tumor
status, ploidy, SCA status (1p and 11q), and International Neuroblastoma Pathology Classification histology were determined centrally. Survival analyses were performed for combinations of prognostic factors used in COG risk classification according to the prior version 1, and to validate a revised algorithm (version 2).
Most patients with locoregional tumors had excellent outcomes except for those with image-defined risk factors (INRGSS L2) with
amplification (5-year event-free survival and overall survival: 76.3% ± 5.8% and 79.9% ± 5.5%, respectively) or patients age ≥ 18 months with L2
nonamplified tumors with unfavorable International Neuroblastoma Pathology Classification histology (72.7% ± 5.4% and 82.4% ± 4.6%), which includes the majority of L2 patients with SCA. For patients with stage M (metastatic) and MS (metastatic, special) disease, genomic biomarkers affected risk group assignment for those < 12 months (
) or 12-18 months (
, histology, ploidy, and SCA) of age. In a retrospective analysis of patient outcome, the 5-year event-free survival and overall survival using COG version 1 were low-risk: 89.4% ± 1.1% and 97.9% ± 0.5%; intermediate-risk: 86.1% ± 1.3% and 94.9% ± 0.8%; high-risk: 50.8% ± 1.4% and 61.9% ± 1.3%; and using COG version 2 were low-risk: 90.7% ± 1.1% and 97.9% ± 0.5%; intermediate-risk: 85.1% ± 1.4% and 95.8% ± 0.8%; high-risk: 51.2% ± 1.4% and 62.5% ± 1.3%, respectively.
A revised 2021 COG neuroblastoma risk classifier (version 2) that uses the INRGSS and incorporates SCAs has been adopted to prospectively define COG clinical trial eligibility and treatment assignment.
Coronavirus disease 2019 (COVID-19) pandemic is a major public health concern all over the world. Little is known about the impact of COVID-19 pandemic on mental health in the general population. ...This study aimed to assess the mental health problems and associated factors among a large sample of college students during the COVID-19 outbreak in China.
This cross-sectional and nation-wide survey of college students was conducted in China from 3 to 10 February 2020. A self-administered questionnaire was used to assess psychosocial factors, COVID-19 epidemic related factors and mental health problems. Acute stress, depressive and anxiety symptoms were measured by the Chinese versions of the impact of event scale-6, Patient Health Questionnaire-9 and Generalized Anxiety Disorder-7, respectively. Univariate and hierarchical logistic regression analyses were performed to examine factors associated with mental health problems.
Among 821 218 students who participated in the survey, 746 217 (90.9%) were included for the analysis. In total, 414 604 (55.6%) of the students were female. About 45% of the participants had mental health problems. The prevalence rates of probable acute stress, depressive and anxiety symptoms were 34.9%, 21.1% and 11.0%, respectively. COVID-19 epidemic factors that were associated with increased risk of mental health problems were having relatives or friends being infected (adjusted odds ratio = 1.72-2.33). Students with exposure to media coverage of the COVID-19 ≥3 h/day were 2.13 times more likely than students with media exposure <1 h/day to have acute stress symptoms. Individuals with low perceived social support were 4.84-5.98 times more likely than individuals with high perceived social support to have anxiety and depressive symptoms. In addition, senior year and prior mental health problems were also significantly associated with anxiety or/and depressive symptoms.
In this large-scale survey of college students in China, acute stress, anxiety and depressive symptoms are prevalent during the COVID-19 pandemic. Multiple epidemic and psychosocial factors, such as family members being infected, massive media exposure, low social support, senior year and prior mental health problems were associated with increased risk of mental health problems. Psychosocial support and mental health services should be provided to those students at risk.
Aim
Gastroparesis is a common non‐motor system symptom of Parkinson's disease (PD). However, the mechanism responsible for the gastric motor abnormality is not clear. We previously reported on the ...impaired gastric motility in 6‐hydroxydopamine (6‐OHDA) rats, which were treated with a bilateral microinjection of 6‐OHDA in the substantia nigra (SN). We hypothesize that the enhanced dopamine system and reduced acetylcholine (Ach) in gastric tissues might contribute to the delayed gastric emptying observed in PD.
Methods
A strain gauge force transducer, digital X‐ray imaging system, Western blot, immunofluorescence and Radio Immunoassay were used in this study.
Results
Dopaminergic neurones in the SN were greatly reduced following the bilateral microinjection of 6‐OHDA. 6‐OHDA rats exhibited impaired gastric motility and delayed gastric emptying, accompanied by increased dopamine content and the overexpression of D2 receptors in the stomach. The administration of the D2 receptor antagonist domperidone relieved gastric dysmotility in 6‐OHDA rats, but the D1 receptor antagonist SCH23390 failed to do so. Subdiaphragmatic vagotomy prevented the increase in the gastric dopamine content and D2 receptor expression and improved gastric dysmotility in 6‐OHDA rats.
Conclusion
Dopaminergic deficiency in the SN results in impaired gastric motility, possibly as a result of the enhanced activity of dopamine system and reduced Ach in gastric tissue. The vagus nerve plays an important role in peripheral gastric motility disorder.
With first-principles density functional theory calculations, we demonstrate that quantum capacitance of graphene-based electrodes can be improved by the N-doping, vacancy defects, and adsorbed ...transition-metal atoms. The enhancement of the quantum capacitance can be contributed to the formation of localized states near Dirac point and/or shift of Fermi level induced by the defects and doping. In addition, the quantum capacitance is found to increase monotonically following the increase of defect concentrations. It is also found that the localized states near Fermi level results in the spin-polarization effect.
A model is developed to study the stress generation in a spherical particle subjected to lithium insertion. The model accounts for both the plastic deformation and the coexistence of lithium-poor and ...lithium-rich phases with a sharp and curved phase boundary. Such two-phase and inelastic deformation characteristics often arise during lithiation of crystalline particles with high capacity. A flexible sigmoid function is used to create the lithium profile with a step-like change in lithium concentration, mimicking a sharp phase boundary that separates a pristine core and a lithiated shell in the particle. The mechanics results, obtained by an analytic formulation and finite difference calculations, show the development of tensile hoop stress in the surface layer of the lithiated shell. This hoop tension provides the driving force of surface cracking, as observed by in situ transmission electron microscopy. The two-phase lithiation model is further compared with the single-phase one, which assumes a gradual and smooth variation in radial lithium distributions, and thus predicts only hoop compression in the surface layer of the particle. Furthermore, the effect of dilatational vs. unidirectional lithiation strains in the two-phase model is studied, thereby underscoring the critical role of anisotropy of lithiation strain in controlling stress generation in high-capacity electrodes for lithium ion batteries.
Abstract Background The preoperative predictors of microvascular invasion (MVI) in multinodular hepatocellular carcinoma (HCC) are currently unclear. Methods We retrospectively analyzed 266 patients ...who underwent potentially curative resection of multinodular HCC. MVI was diagnosed on pathological examination in 64 patients. Preoperative risk factors for MVI were identified and survival curves were analyzed. Results Patients with MVI had significantly lower overall and recurrence-free survival rates than those without MVI (overall survival, 1 year: 86% vs. 71%, 3 years: 58% vs. 16%; recurrence-free survival, 1 year: 69% vs. 12%; 3 years: 48% vs. 12%; both P < 0.001). Multivariate analysis showed that serum alpha-fetoprotein (AFP) level >400 μg/L (odds ratio OR = 3.732, P = 0.016), serum gamma-glutamyltransferase (GGT) level >130 U/L (OR = 19.779, P < 0.001), total tumor diameter >8 cm (OR = 5.545, P = 0.010), and tumor number >3 (OR = 11.566, P = 0.007) were independent predictors of MVI. A scoring system was constructed, and the MVI rate was significantly higher in patients with a score of ≥3 than those with a score of <3 (64.1% vs. 10.9%, P < 0.001). Overall and recurrence-free survival rates were significantly lower in patients with a score of ≥3 (both P < 0.001). Conclusions Serum AFP level >400 μg/L, serum GGT level >130 U/L, total tumor diameter >8 cm, and tumor number >3 were preoperative predictors of MVI in patients with multinodular HCC. In patients with a high risk of MVI and well-preserved liver function, anatomic resection may be worth considering.
On the basis of the existing performance evaluation criteria analysis and four assumptions, a performance evaluation plot has been proposed in this paper. This plot takes the ratios of heat transfer ...enhancement and friction factor increase as its two coordinates. The quadrant of the coordinate where both (
Nu
e/
Nu
0), (
f
e/
f
0) are greater than 1.0 can be divided into four regions. In Region 1 heat transfer is actually deteriorated based on identical pumping power, in Region 2 heat transfer is enhanced based on identical pumping power but deteriorated based on identical pressure drop, in Region 3 heat transfer is enhanced based on identical pressure drop but the increase in friction factor is larger than the enhancement of heat transfer at identical flow rate, and in Region 4 heat transfer enhancement ratio is larger than friction factor increase ratio based on identical flow rate. For some techniques which lead to the reduction of both heat transfer rate and friction factor, the proposed plot is still applicable. Different enhanced techniques for the same reference one can be easily and clearly compared for their effectiveness when enhancement study is based on energy-saving. Five practical examples are provided to show the functions of the plot.
In 2006, Children's Oncology Group (COG) reclassified subgroups of toddlers diagnosed with neuroblastoma from high-risk to intermediate-risk, when the age cutoff for high-risk assignment was raised ...from 365 days (12 months) to 547 days (18 months). The primary aim of this retrospective study was to determine if excellent outcome was maintained after assigned reduction of therapy.
Children <3 years old at diagnosis, enrolled on a COG biology study from 1990 to 2018, were eligible (n = 9,189). Assigned therapy was reduced for two cohorts of interest on the basis of the age cutoff change: 365-546 days old with International Neuroblastoma Staging System (INSS) stage 4,
not amplified (
), favorable International Neuroblastoma Pathology Classification (INPC), hyperdiploid tumors (12-18mo/Stage4/FavBiology), and 365-546 days old with INSS stage 3,
and unfavorable INPC tumors (12-18mo/Stage3/
/Unfav). Log-rank tests compared event-free survival (EFS) and overall survival (OS) curves.
For 12-18mo/Stage4/FavBiology, 5-year EFS/OS (± SE) before (≤2006; n = 40) versus after (>2006; n = 55) assigned reduction in therapy was similar: 89% ± 5.1%/89% ± 5.1% versus 87% ± 4.6%/94% ± 3.2% (
= .7;
= .4, respectively). For 12-18mo/Stage3/
/Unfav, the 5-year EFS and OS were both 100%, before (n = 6) and after (n = 4) 2006. The 12-18mo/Stage4/FavBiology plus 12-18mo/Stage3/
/Unfav classified as high-risk ≤2006 had an EFS/OS of 91% ± 4.4%/91% ± 4.5% versus 38% ± 1.3%/43% ± 1.3% for all other high-risk patients <3 years old (
< .0001;
< .0001, respectively). The 12-18mo/Stage4/FavBiology plus 12-18mo/Stage3/
/Unfav classified as intermediate-risk >2006 had an EFS/OS of 88% ± 4.3%/95% ± 2.9% versus 88% ± 0.9%/95% ± 0.6% for all other intermediate-risk patients <3 years old (
= .87;
= .85, respectively).
Excellent outcome was maintained among subsets of toddlers with neuroblastoma assigned to reduced treatment after reclassification of risk group from high to intermediate on the basis of new age cutoffs. Importantly, as documented in prior trials, intermediate-risk therapy is not associated with the degree of acute toxicity and late effects commonly observed with high-risk regimens.
The combination of irinotecan, temozolomide, dintuximab, and granulocyte-macrophage colony-stimulating factor (I/T/DIN/GM-CSF) demonstrated activity in patients with relapsed/refractory neuroblastoma ...in the randomized Children's Oncology Group ANBL1221 trial. To more accurately assess response rate and toxicity, an expanded cohort was nonrandomly assigned to I/T/DIN/GM-CSF.
Patients were eligible at first relapse or first designation of refractory disease. Oral T and intravenous (IV) irinotecan were administered on days 1 to 5 of 21-day cycles. DIN was administered IV (days 2-5), and GM-CSF was administered subcutaneously (days 6-12). The primary end point was objective response, analyzed on an intent-to-treat basis per the International Neuroblastoma Response Criteria.
Seventeen eligible patients were randomly assigned to I/T/DIN/GM-CSF (February 2013 to March 2015); 36 additional patients were nonrandomly assigned to I/T/DIN/GM-CSF (August 2016 to May 2017). Objective (complete or partial) responses were observed in nine (52.9%) of 17 randomly assigned patients (95% CI, 29.2% to 76.7%) and 13 (36.1%) of 36 expansion patients (95% CI, 20.4% to 51.8%). Objective responses were seen in 22 (41.5%) of 53 patients overall (95% CI, 28.2% to 54.8%); stable disease was also observed in 22 of 53. One-year progression-free and overall survival for all patients receiving I/T/DIN/GM-CSF were 67.9% ± 6.4% (95% CI, 55.4% to 80.5%) and 84.9% ± 4.9% (95% CI, 75.3% to 94.6%), respectively. Two patients did not receive protocol therapy and were evaluable for response but not toxicity. Common grade ≥ 3 toxicities were fever/infection (18 35.3% of 51), neutropenia (17 33.3% of 51), pain (15 29.4% of 51), and diarrhea (10 19.6% of 51). One patient met protocol-defined criteria for unacceptable toxicity (grade 4 hypoxia). Higher DIN trough levels were associated with response.
I/T/DIN/GM-CSF has significant antitumor activity in patients with relapsed/refractory neuroblastoma. Study of chemoimmunotherapy in the frontline setting is indicated, as is further evaluation of predictive biomarkers.
Background
Hepatic vein tumour thrombus (HVTT) is a major determinant of survival outcomes for patients with hepatocellular carcinoma (HCC). An Eastern Hepatobiliary Surgery Hospital (EHBH)‐HVTT ...model was established to predict the prognosis of patients with HCC and HVTT after liver resection, in order to identify optimal candidates for liver resection.
Methods
Patients with HCC and HVTT from 15 hospitals in China were included. The EHBH‐HVTT model with contour plot was developed using a non‐linear model in the training cohort, and subsequently validated in internal and external cohorts.
Results
Of 850 patients who met the inclusion criteria, there were 292 patients who had liver resection and 198 who did not in the training cohort, and 124 and 236 in the internal and external validation cohorts respectively. Contour plots for the EHBH‐HVTT model were established to predict overall survival (OS) rates of patients visually, based on tumour diameter, number of tumours and portal vein tumour thrombus. This differentiated patients into low‐ and high‐risk groups with distinct long‐term prognoses in the liver resection cohort (median OS 34·7 versus 12·0 months; P < 0·001), internal validation cohort (32·8 versus 10·4 months; P = 0·002) and external validation cohort (15·2 versus 6·5 months; P = 0·006). On subgroup analysis, the model showed the same efficacy in differentiating patients with HVTT in peripheral and major hepatic veins, the inferior vena cava, or in patients with coexisting portal vein tumour thrombus.
Conclusion
The EHBH‐HVTT model was accurate in predicting prognosis in patients with HCC and HVTT after liver resection. It identified optimal candidates for liver resection among patients with HCC and HVTT, including tumour thrombus in the inferior vena cava, or coexisting portal vein tumour thrombus.
Antecedentes
La trombosis tumoral de la vena hepática (hepatic vein tumour thrombus, HVTT) es un determinante importante de los resultados de supervivencia en pacientes con carcinoma hepatocelular (hepatocellular carcinoma, HCC). Se desarrolló el modelo llamado Eastern Hepatobiliary Surgery Hospital (EHBH)‐HVTT para predecir el pronóstico de los pacientes con HCC y HVTT después de la resección hepática (liver resection, LR), con el fin de identificar los candidatos óptimos para LR entre estos pacientes.
Métodos
Se incluyeron pacientes con HCC y HVTT de 15 hospitales en China. El modelo EHBH‐HVTT con gráfico de contorno se desarrolló utilizando un modelo no lineal en la cohorte de entrenamiento, siendo posteriormente validado en cohortes internas y externas.
Resultados
De 850 pacientes que cumplieron con los criterios de inclusión, hubo 292 pacientes en el grupo LR y 198 pacientes en el grupo no LR en la cohorte de entrenamiento, y 124 y 236 en las cohortes de validación interna y externa. Los gráficos de contorno del modelo EHBH‐HVTT se establecieron para predecir visualmente las tasas de supervivencia global (overall survival, OS) de los pacientes, en función del diámetro del tumor, número de tumores y del trombo tumoral de la vena porta (portal vein tumour thrombus, PVTT). Esto diferenciaba a los pacientes en los grupos de alto y bajo riesgo, con distinto pronóstico a largo plazo en las 3 cohortes (34,7 versus 12,0 meses, 32,8 versus 10,4 meses y 15,2 versus 6,5 meses, P < 0,001). En el análisis de subgrupos, el modelo mostró la misma eficacia en la diferenciación de pacientes con HVTT, con trombo tumoral en la vena cava inferior (inferior vena cava tumour thrombus, IVCTT) o en pacientes con PVTT coexistente.
Conclusión
El modelo EHBH‐HVTT fue preciso para la predicción del pronóstico en pacientes con HCC y HVTT después de la LR. Identificó candidatos óptimos para LR en pacientes con HCC y HVTT, incluyendo IVCTT o PVTT coexistente.
The Eastern Hepatobiliary Surgery Hospital–hepatic vein tumour thrombus (EHBH‐HVTT) model was accurate in predicting prognosis in patients with hepatocellular carcinoma (HCC) and HVTT after liver resection. It identified optimal candidates for liver resection among patients with HCC and HVTT, including inferior vena cava tumour thrombus, or coexisting portal vein tumour thrombus (PVTT).
predicts prognosis
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