Navigating relapsed hepatoblastoma: Predictive factors and surgical treatment strategy.

OBJECTIVE: Hepatoblastoma (HB) is the most common primary hepatic malignancy in childhood. Relapse occurs in more than 50% of high-risk patients with a high mortality due to ineffective salvage therapies. The purpose of this study is to identify risk factors for relapsed HB and predictors of survival in a single tertiary referral center. METHODS: A retrospective chart review showed 129 surgically treated HB patients from October 2004 to July 2020. Of the cohort, 22 patients presented with relapsed HB. Relapse was defined as re-appearance of malignancy after 4 weeks of normalized AFP and disappearance of all tumors on imaging. RESULTS: Patients with relapsed HB had a 5-year overall survival (OS) of 45.4% compared to 93.1% in those without relapse (p = 0.001). When comparing PRETEXT IV, microvascular invasion, metastatic disease, and age on multivariate logistic regression, only PRETEXT IV was an independent risk factor for relapsed HB with an OR of 2.39 (95% CI: 1.16-4.96; p = 0.019). Mixed epithelial and mesenchymal HB (12/19, 63.2%) was the most common histology of primary tumors while pure epithelial HB (13/15, 86.6%) was the most common relapsed histology. Combination of surgical and medical therapy for relapsed disease was predictive of survival with an HR of 16.3 (95% CI: 1.783-149.091; p = 0.013) compared to only chemotherapy. CONCLUSIONS: This study demonstrates that PRETEXT IV staging is an independent predictor of relapsed disease. The most common relapsed histology was epithelial, suggesting a potential selection or resistance of this component. Surgical resection is a critical component of multimodal therapy for relapsed HB.

Germline genetic variants and pediatric rhabdomyosarcoma outcomes: a report from the Children's Oncology Group.

BACKGROUND: Relative to other pediatric cancers, survival for rhabdomyosarcoma (RMS) has not improved in recent decades, suggesting the need to enhance risk stratification. Therefore, we conducted a genome-wide association study for event-free survival (EFS) and overall survival (OS) to identify genetic variants associated with outcomes in individuals with RMS. METHODS: The study included 920 individuals with newly diagnosed RMS who were enrolled in Children's Oncology Group protocols. To assess the association of each single nucleotide polymorphism (SNP) with EFS and OS, we estimated hazard ratios (HRs) and 95% confidence intervals (CIs) using multivariable Cox proportional hazards models, adjusted for clinical covariates. All statistical tests were two sided. We also performed stratified analyses by histological subtype (alveolar and embryonal RMS) and carried out sensitivity analyses of statistically significant SNPs by PAX3/7-FOXO1 fusion status and genetic ancestry group. RESULTS: We identified that rs17321084 was associated with worse EFS (HR = 2.01, 95% CI = 1.59 to 2.53, P = 5.39 × 10-9) and rs10094840 was associated with worse OS (HR = 1.84, 95% CI = 1.48 to 2.27, P = 2.13 × 10-8). Using publicly available data, we found that rs17321084 lies in a binding region for transcription factors GATA2 and GATA3, and rs10094840 is associated with SPAG1 and RNF19A expression. We also identified that CTNNA3 rs2135732 (HR = 3.75, 95% CI = 2.34 to 5.99, P = 3.54 × 10-8) and MED31 rs74504320 (HR = 3.21, 95% CI = 2.12 to 4.86, P = 3.60 × 10-8) were associated with worse OS among individuals with alveolar RMS. CONCLUSIONS: We demonstrated that common germline variants are associated with EFS and OS among individuals with RMS. Additional replication and investigation of these SNP effects may further support their consideration in risk stratification protocols.

Admixture Mapping in African Americans Identifies New Risk Loci for HCV-Related Cirrhosis.

BACKGROUND & AIMS: Cirrhosis is the main predisposing condition for hepatocellular carcinoma. Host genetic risk factors have been reported for cirrhosis; however, whether there is a genetic contribution to racial disparities in cirrhosis requires further investigation. METHODS: We used an affected-only mapping by admixture linkage disequilibrium analysis to characterize the genetic risk of cirrhosis in 227 African American patients with cirrhosis genotyped at 19,804 ancestry-informative marker single nucleotide polymorphisms. We additionally performed analyses stratified by hepatitis C virus (HCV) infection status. To replicate our findings, we conducted a case-control analysis in an external study population (452 cases and 196 controls). RESULTS: The mean age of patients was 63.3 years and 98.2% were male. Risk factors for cirrhosis included HCV infection (83.7%) and alcohol abuse (56.4%). In the admixture mapping analysis, we found that European ancestry on chromosome 2q21.1 and African ancestry on chromosome 6p21.2 were associated with increased risk of cirrhosis in African Americans. In the fine-mapping analysis, we identified regions near POTEKP on 2q21.1 (P = .0001) and DNAH8 on 6p21.2 (P = .0017) that were associated with cirrhosis. As the admixture peaks in the HCV-positive patients were the same as those in the overall group, findings in the analysis are reflective of the HCV-positive group. In the replication analysis, the results on chromosome 2 were not significant after adjusting for multiple comparisons, and we could not replicate the results on chromosome 6. CONCLUSIONS: We used admixture mapping to identify novel genomic regions on 2q21.1 and 6p21.2 that may be associated with HCV-related cirrhosis risk in African Americans.

Comparative analysis of the remineralization potential of CPP-ACP with Fluoride, Tri-Calcium Phosphate and Nano Hydroxyapatite using SEM/EDX - An in vitro study.

BACKGROUND: In recent years, the non-invasive management of non cavitated caries lesions using remineralization systems to repair the enamel have received more attention from the scientific community. Aim: To quantitatively evaluate the remineralization potential of Casein phosphopeptide-amorphous calcium phosphate-fluoride(CPP-ACPF), Tri-calcium phosphate(TCP) & Nano-hydroxyapatite(nHAP) using Scanning Electron Microscopy(SEM) and Energy dispersive X-ray Analysis(EDX). MATERIAL AND METHODS: 40 enamel specimens were prepared, and immersed in demineralising solution at a pH of 4.4 for 96 hours at 37°C, to induce artificial carious lesions. Remineralization was carried out for a period of 30 days using CPP-ACPF, TCP, nHAP. The specimens were evaluated for calcium and phosphorus content using SEM-EDX. RESULTS: The Ca/P mass % after remineralization was significantly higher with CPP-ACP-F and TCP-F followed by nHAP. CONCLUSIONS: CPP-ACP-F and TCP can promote significant remineralization of incipient carious lesions. These are excellent delivery vehicles available in a slow release amorphous form to localize calcium, phosphate and fluoride at the tooth surface. Key words:Remineralization, in vitro; CPP-ACP fluoride, Nano-hydroxyapatite, Tri-calcium phosphate, SEM/ EDX.

Development of norms for executive functions in typically-developing Indian urban preschool children and its association with nutritional status.

Executive functions (EFs) are essential and important for achieving success in children's everyday lives and play a fundamental role in children's cognitive, academic, social, emotional and behavioral functioning. A cross-sectional study was carried out to develop age- and sex-specific norms for EFs using the Behavior Rating Inventory of Executive Function - Preschool Version (BRIEF-P) among 2- to 5-year-olds from urban Bangalore, India. In addition, the association between EFs and anthropometric measures, a marker of nutritional status, is also examined. Primary caregivers of 412 children, equally distributed by age and sex, participated. Raw scores for each domain and indices were converted to standard t-scores and percentiles were computed. A t-score at or above 63 corresponding to the 90th percentile was considered as the cutoff for executive dysfunction in this sample. The prevalence of executive dysfunction is 10% based on the Global Executive Composite score of the BRIEF-P. The cutoff score for identifying executive dysfunction using existing United States (US) norms is higher compared to the cutoff score obtained in the current study. Therefore, using US norms for Indian children could result in the prevalence of executive dysfunction been underestimated. Multiple linear regression analysis revealed that stunted and underweight children have significantly elevated EF scores after adjusting for age, sex and socioeconomic status (SES; p < .01). A greater understanding of EFs in preschool children is important for the early identification of executive dysfunction and implementing interventions to improve their future prospects. This study also shows that undernourished children are more likely to have executive dysfunction.

In vivo Evaluation of Two Thiazolidin-4-one Derivatives in High Sucrose Diet Fed Pre-diabetic Mice and Their Modulatory Effect on AMPK, Akt and p38 MAP Kinase in L6 Cells.

We had previously demonstrated the anti-diabetic potential and pancreatic protection of two thiazolidin-4-one derivatives containing nicotinamide moiety (NAT-1 and NAT-2) in STZ-induced diabetic mice. However, due to the limitations of the STZ model, we decided to undertake a detailed evaluation of anti-diabetic potential of the molecules on a high sucrose diet (HSD) fed diabetic mouse model. Further, in vitro mechanistic studies on the phosphorylation of AMPK, Akt and p38 MAP kinase in L6 myotubes and anti-inflammatory studies in RAW264.7 mouse monocyte macrophage cells were performed. 15 months of HSD induced fasting hyperglycaemia and impaired glucose tolerance in mice. Treatment with NAT-1 and NAT-2 (100 mg/kg) for 45 days significantly improved the glucose tolerance and lowered fasting blood glucose levels compared to untreated control. An improvement in the elevated triglycerides and total cholesterol levels, and favorable rise in HDL cholesterol were also observed with test drug treatment. Also, no major changes were observed in the liver (albumin, AST and ALT) and kidney (creatinine and urea) parameters. This was further confirmed in their respective histology profiles which revealed no gross morphological changes. In L6 cells, significant phosphorylation of Akt and p38 MAP kinase proteins were observed with 100 µM of NAT-1 and NAT-2 with no significant changes in phosphorylation of AMPK. The molecules failed to exhibit anti-inflammatory activity as observed by their effect on the generation of ROS and nitrite, and nuclear levels of NF-κB in LPS-stimulated RAW264.7 cells. In summary, the molecules activated Akt and p38 MAP kinase which could have partly contributed to their anti-hyperglycaemic and hypolipidemic activities in vivo.

Norms for developmental milestones using VABS-II and association with anthropometric measures among apparently healthy urban Indian preschool children.

Assessment of developmental milestones based on locally developed norms is critical for accurate estimate of overall development of a child's cognitive, behavioral, social, and emotional development. A cross-sectional study was done to develop age specific norms for developmental milestones using Vineland Adaptive Behavior Scales (VABS-II) (Sparrow, Cicchetti, & Balla, 2005) for apparently healthy children from 2 to 5 years from urban Bangalore, India, and to examine its association with anthropometric measures. Mothers (or caregivers) of 412 children participated in the study. Age-specific norms using inferential norming method and adaptive levels for all domains and subdomains were derived. Low adaptive level, also called delayed developmental milestone, was observed in 2.3% of the children, specifically 2.7% in motor and daily living skills and 2.4% in communication skills. When these children were assessed on the existing U.S. norms, there was a significant overestimation of delayed development in socialization and motor skills, whereas delay in communication and daily living skills were underestimated (all p < .01). Multiple linear regression revealed that stunted and underweight children had significantly lower developmental scores for communication and motor skills compared with normal children (ß coefficient ranges from 2.6-5.3; all p < .01). In the absence of Indian normative data for VABS-II in preschool children, the prevalence of developmental delay could either be under- or overestimated using Western norms. Thus, locally referenced norms are critical for reliable assessments of development in children. Stunted and underweight children are more likely to have poorer developmental scores compared with healthy children. (PsycINFO Database Record

Evaluation of the knowledge and attitude of expectant mothers about infant oral health and their oral hygiene practices.

BACKGROUND: Mothers play a crucial role in developing and maintaining their infants' oral hygiene. Maternal oral health, their knowledge and attitude toward infant oral health are strong indicators of their infant's oral health status. AIM: The aim of this study is to evaluate the knowledge and attitude of expectant mothers about infant oral health and their oral hygiene practices. SETTINGS AND DESIGN: This was a cross-sectional questionnaire-based survey conducted among expectant mothers in Mangalore city, India. MATERIALS AND METHODS: Three hundred expectant mothers fulfilling the inclusion and exclusion criteria were randomly selected based on convenience method over a period of 1 month. The data were collected using a self-administered questionnaire addressing the various aspects of expectant mothers' knowledge and attitude about infant oral health and their own oral hygiene practices. The analysis was done using SPSS version 16.0. RESULTS: The overall score revealed that majority of the expectant mothers had poor knowledge and attitude toward infant oral health and followed poor oral hygiene practices. Expectant mothers' educational qualification, trimester, and the number of pregnancy had a significant role in their knowledge, attitude, and oral hygiene practices. CONCLUSION: Implementation of educational programs to motivate expectant mothers and bring out awareness about the importance of oral health and their implications must be emphasized.

Variants for HDL-C, LDL-C, and triglycerides identified from admixture mapping and fine-mapping analysis in African American families.

BACKGROUND: Admixture mapping of lipids was followed-up by family-based association analysis to identify variants for cardiovascular disease in African Americans. METHODS AND RESULTS: The present study conducted admixture mapping analysis for total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides. The analysis was performed in 1905 unrelated African American subjects from the National Heart, Lung and Blood Institute's Family Blood Pressure Program (FBPP). Regions showing admixture evidence were followed-up with family-based association analysis in 3556 African American subjects from the FBPP. The admixture mapping and family-based association analyses were adjusted for age, age(2), sex, body mass index, and genome-wide mean ancestry to minimize the confounding caused by population stratification. Regions that were suggestive of local ancestry association evidence were found on chromosomes 7 (low-density lipoprotein cholesterol), 8 (high-density lipoprotein cholesterol), 14 (triglycerides), and 19 (total cholesterol and triglycerides). In the fine-mapping analysis, 52 939 single-nucleotide polymorphisms (SNPs) were tested and 11 SNPs (8 independent SNPs) showed nominal significant association with high-density lipoprotein cholesterol (2 SNPs), low-density lipoprotein cholesterol (4 SNPs), and triglycerides (5 SNPs). The family data were used in the fine-mapping to identify SNPs that showed novel associations with lipids and regions, including genes with known associations for cardiovascular disease. CONCLUSIONS: This study identified regions on chromosomes 7, 8, 14, and 19 and 11 SNPs from the fine-mapping analysis that were associated with high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides for further studies of cardiovascular disease in African Americans.

Making WHO recommendations more responsive.

Recent World Health Organization (WHO) guidelines not only advise countries on what treatment to give patients and when, but also how to roll this out in countries. Priya Shetty reports.

Diagnosis of temporomandibular joint (TMJ) ankylosis in children.

Temporomandibular joint (TMJ) ankylosis involves fusion of the mandibular condyle with the base of the skull. It results in functional, esthetic, and psychosocial limitations, if it affects children at an early age. Hence, it is important to recognize and diagnose the pathology and provide immediate treatment alternatives to improve the patient condition. In this case report, we highlight the diagnostic perspective of TMJ ankylosis in children, and the use of 3D computed tomography as an effective diagnostic aid.

More midwives needed to improve maternal and newborn survival.

Retention of midwives, especially in rural areas, is a major challenge for many countries, one that threatens to negate all the hard work and resources invested in their training. Priya Shetty reports.