Role of cytogenetic profiles as prognostic factors for complete remission after induction phase in acute myeloblastic leukemia

Background Risk stratification for acute myeloid leukemia (AML) in children is a must in treatment strategy. This stratification is based on cytogenetic profiles, which are needed to determine proper management to gain better outcomes and reduce side effects of treatment. There is no such risk stratification available in Indonesia until now. Objective To evaluate the association between cytogenetic profiles of t(8,21) and inv(16) mutations with the complete response to induction phase of chemotherapy in pediatric AML. Methods A prospective study was conducted between year 2018 and 2020, involving children with AML from 4 pediatric oncology centers in Jakarta. Subjects were evaluated for cytogenetic profiles, especially t(8,21) and inv(16), as the favorable predictors for AML. Bone marrow remission was evaluated after 2 cycles of induction phase. The results were evaluated for remission rate and survival analysis. Results Karyotype data of 18 subjects were obtained. Translocation t(8;21) detected in 1 subject, and inv(16) mutation in 4 subjects. These two variables had no significant correlation with complete remission after induction phase. Nevertheless, favorable group had more tendencies to achieved remission than unfavorable group. Complete remission achieved in 61% subjects, 90% of theme had a relapse period with an average time 43 weeks. The relapse period in favorable group was shoter than in unfavorable group (34 weeks and 44 weeks, respectively). Conclusions This study shows that cytogenetic profiles of t(8;21) and inv(16) mutation can not be used as prognostic factors for complete remission after induction phase of chemotherapy in pediatric AML.

P.028 Surgical Treatment for Idiopathic Intracranial Hypertension – Strategy for the Better Management

Background: Idiopathic intracranial hypertension (IIH) is a condition of increased intracranial pressure in the absence of a space-occupying lesion. The goal of this study is to investigate which factors may influence outcomes in order to improve surgical strategy. We hypothesized diabetes, hypertension, smoking, and obesity influence patients prognosis. Methods: This retrospective chart review included patients diagnosed with IIH who underwent surgical intervention. All patients receiving surgery between 2008 and 2018 were included, and divided into 2 cohorts. Cohort 1 representing favorable course and cohort 2 representing unfavorable course. Favorable course was defined as requiring single surgery for management. Unfavorable course required multiple surgical revisions. Results: Overall, 35/48 (73%) comprised the favorable group. Thirteen patients (27%) comprised the unfavorable group. Of the unfavorable group, 54% had LP shunts, with the remaining receiving VP shunts. There was no association between type of shunt and outcome. Common issues the unfavorable group encountered were persisting symptoms, infections, obstruction of shunt and replacement of shunt. Smoking and frequent follow-up were associated with unfavorable course. Gender, BMI, age, comorbidities and shunt type were not associated with outcome. Conclusions: We found smoking and patient follow-up had a significant association with unfavorable outcome. Other factors had no association with patient outcome.

Genetic and epigenetic characterization of posterior pituitary tumors

Pituicytoma (PITUI), granular cell tumor (GCT), and spindle cell oncocytoma (SCO) are rare tumors of the posterior pituitary. Histologically, they may be challenging to distinguish and have been proposed to represent a histological spectrum of a single entity. We performed targeted next-generation sequencing, DNA methylation profiling, and copy number analysis on 47 tumors (14 PITUI; 12 GCT; 21 SCO) to investigate molecular features and explore possibilities of clinically meaningful tumor subclassification. We detected two main epigenomic subgroups by unsupervised clustering of DNA methylation data, though the overall methylation differences were subtle. The largest group (n = 23) contained most PITUIs and a subset of SCOs and was enriched for pathogenic mutations within genes in the MAPK/PI3K pathways (12/17 [71%] of sequenced tumors: FGFR1 (3), HRAS (3), BRAF (2), NF1 (2), CBL (1), MAP2K2 (1), PTEN (1)) and two with accompanying TERT promoter mutation. The second group (n = 16) contained most GCTs and a subset of SCOs, all of which mostly lacked identifiable genetic drivers. Outcome analysis demonstrated that the presence of chromosomal imbalances was significantly associated with reduced progression-free survival especially within the combined PITUI and SCO group (p = 0.031). In summary, we observed only subtle DNA methylation differences between posterior pituitary tumors, indicating that these tumors may be best classified as subtypes of a single entity. Nevertheless, our data indicate differences in mutation patterns and clinical outcome. For a clinically meaningful subclassification, we propose a combined histo-molecular approach into three subtypes: one subtype is defined by granular cell histology, scarcity of identifiable oncogenic mutations, and favorable outcome. The other two subtypes have either SCO or PITUI histology but are segregated by chromosomal copy number profile into a favorable group (no copy number changes) and a less favorable group (copy number imbalances present). Both of the latter groups have recurrent MAPK/PI3K genetic alterations that represent potential therapeutic targets.

The First 24 h Hemodynamic Management in NICU after Revascularization Surgery in Moyamoya Disease

Objective. To evaluate whether hemodynamic factors are risk factors for prognosis in moyamoya disease (MMD). Materials and Methods. The retrospective study reviewed a single-center MMD cohort in Huashan Hospital from August 2017 to January 2020. Stroke events in 30 days and follow-up modified Rankin Scale (mRS) grade were recorded. Systematic assessments with perioperative mean arterial pressure (MAP), red blood cell (RBC) parameters, and fluid management were also conducted. Logistic regressions were applied to evaluate the predictors of worse outcomes. Data was analyzed using SPSS 24.0. Results. Admission to neurological intensive care unit (NICU) totalled about 347 after revascularization surgery. The result showed that the higher the postoperative MAP level (favorable group 95.7 ± 11.4 mmHg vs. unfavorable group 103.6 ± 10.4 mmHg, p < 0.001 ) and the greater the MAP variability (favorable group 0.26 ± 13.2 vs. unfavorable group 7.2 ± 13.5 , p = 0.006 ) were, the higher the patient’s follow-up mRS grade was. What is more, a higher early postoperative Hb level also seemed to predict a worse long-term clinical outcome (favorable group 116.9 ± 17.1 g/L vs. unfavorable group 123.7 ± 13.0 g/L, p = 0.03 ), but the difference disappeared after adjusting sex and age. Logistic regression analyses showed that a higher level of postoperative MAP ( β = 0.024 , 95% CI (0.004, 0.044), and p = 0.02 ) within the first 24 h in NICU might be the short-term risk factor. For long-term outcome, a higher level ( β = 1.058 , 95% CI (1.022, 1.096), and p = 0.001 ) and a greater variability ( β = 30.982 , 95% CI (2.112, 454.414), and p = 0.01 ) of postoperative MAP might be the negative predictors of mRS grade. Conclusions. The early postoperative hemodynamic management might be extremely critical for patients with MMD. Both high postoperative MAP levels and large MAP variability might affect the prognosis. What is more, we also found that a higher postoperative Hb level might be related with a worse outcome.

DNA Hypomethylation of DOCK1 Leading to High Expression Correlates with Neurologic Deterioration and Poor Function Outcomes after Spontaneous Intracerebral Hemorrhage

Objective. Spontaneous intracerebral hemorrhage (ICH) is a blood clot arising in the brain parenchyma in the absence of trauma or surgery and accounts for 10% to 15% of all strokes, leading to higher rates of mortality and morbidity than either ischemic stroke or subarachnoid hemorrhage. We sought to investigate the potential association of DOCK1 with neurological deficits and outcomes in patients with spontaneous ICH. Methods. Identification of methylation-regulated differentially expressed genes (MeDEGs) between ICH patients and matched controls was performed by analyzing the raw data from the GSE179759 and GSE125512 datasets deposited in the Gene Expression Omnibus. A total of 114 patients who were admitted to our hospital for spontaneous ICH were retrospectively analyzed, with 108 healthy volunteers who had received physical examinations at the same period as controls. The mRNA expression of DOCK1 was determined by quantitative real-time polymerase chain reaction (qRT-PCR). The hematoma volume was calculated according to the Coniglobus formula. The severity of neurological deficits was evaluated using National Institutes of Health Stroke Scale (NIHSS) scores and function outcomes were evaluated by modified Rankin Scale (mRS) scores. Results. A total of 15 MeDEGs between ICH patients and matched controls were identified. The mRNA expression of DOCK1 was remarkably higher in the serum samples of patients with spontaneous ICH than in the healthy controls. According to hematoma volume after ICH attack, small (<10 mL), medium (10 to 30 mL), and large (>30 mL) groups were arranged. The proportions of male patients and patients aged ≥60 years were significantly higher in the large group than in the small and medium groups ( P < 0.05 ). The mRNA expression of DOCK1 was significantly higher in the large group than in the small and medium groups ( P < 0.05 ). According to NIHSS scores, mild (NIHSS scores ≤15), moderate (NIHSS scores from 16 to 30), and severe (NIHSS scores from 31 to 45) groups were classified. It was observed that the severe group had higher proportions of male patients and patients aged ≥60 years than the mild and moderate groups ( P < 0.05 ). The severe group exhibited a higher mRNA expression of DOCK1 than the mild and moderate groups ( P < 0.05 ). According to mRS scores, higher proportions of male patients and patients aged ≥60 years were observed in the unfavorable group than the favorable group ( P < 0.05 ). The patients in the unfavorable group showed an elevated DOCK1 mRNA expression compared to those in the favorable group ( P < 0.05 ). Conclusion. The study provided evidence that male gender, older age, and higher DOCK1 mRNA expression were related to higher admission hematoma volume, neurologic deterioration, and poor function outcomes in patients with spontaneous ICH.

Adverse Impact of DNA Methylation Regulatory Gene Mutations on the Prognosis of AML Patients in the 2017 ELN Favorable Risk Group, Particularly Those Defined by NPM1 Mutation

The 2017 ELN risk stratification has been widely adopted, but some studies have suggested the outcomes are heterogenous within the ELN risk groups and may be affected by other co-existing genetic mutations. This study evaluated the impact of DNA methylation regulatory gene (TET2, IDH1/2, DNMT3A, SETBP1) mutations (DMRGM) evaluated by NGS in the outcome of AML patients in each ELN risk group. A total of 114 patients were analyzed with a median follow-up of 12 months. Overall, 30.7% (35/114) of patients had DMRGM. DMRGM status had no impact on CR rate in each ELN risk group. The OS, however, was significantly shorter in patients with DMRGM compared to those without DMRGM (median OS: 12 vs. 33 months, p = 0.0053). Multivariate analysis showed DMRGM status was an independent unfavorable factor for OS (HR: 2.704, 95% CI: 1.451–5.041, p = 0.0017). The adverse OS impact of DMRGM was only observed in the ELN favorable group (7 months vs. not reached, p = 0.0001), but not in the intermediate or adverse group. Among the favorable group with DMRGM (n = 16), DMRGM occurred predominantly in cases with mutated NPM1 (15/16, or 93.8%). Our results suggest that DMRGM adversely impact the outcomes of ELN favorable group patients, particularly those with mutated NPM1. Further studies are warranted to confirm our observations.

Main Dependences between Gender, Financial Status and Indicators Predicting Purchase of Mobile Products and Services in Bulgaria

The present study was conducted in order to establish the main relationships between gender and financial status on indicators influencing the purchase of a mobile operator. Basic indicators for measuring consumer behavior are derived, applying analysis of variations, ANOVA, and correlation analyses to check the strength of indicators influence. According to the results of statistical data processing, two groups were identified: the most favorable group for influence – young women who are financially disadvantaged, and one on which it is difficult to achieve advertising impact of mobile operator. The practical applicability of the study is significant, as mobile operators in Bulgaria can have a much more successful impact on the group with a higher propensity to try new, specific products, as well as those who declare greater confidence in a mobile company, built through the influence of advertising.

Circulating Tumor Cells Predict Prognosis Following First-Generation EGFR-TKI Treatment in EGFR- and TP53-Mutant Non-Small Cell Lung Cancer

Background: First-generation EGFR-TKIs have become the first-line standard treatment for advanced non-small cell lung cancer (NSCLC) with EGFR mutations. This study isolates and quantifies circulating tumor cells (CTCs) and evaluates patient prognosis before and after first-line treatment with EGFR-TKIs in advanced NSCLC with EGFR and TP53 mutation.Methods: Patients with advanced NSCLC with EGFR and TP53 mutation were treated with a first-generation EGFR-TKI using a standard daily dose. Continuous blood samples were collected at baseline (CTCs-d0) and 28 days (CTCs-d28), and the isolation by size of tumor cells (ISET) method was used to detect CTCs.Results: The CTCs results were divided into favorable (< 5 CTCs) and unfavorable (≥ 5 CTCs) groups. The median progression-free survival (PFS) of patients in the favorable group was significantly longer at baseline compared to those in the unfavorable group (15 vs 7.5 months; p = 0.0055). After 28 days of treatment with first-generation EGFR-TKI, the PFS of patients in the favorable group was 12.5 months, which was significantly longer than the median PFS of 7 months in the unfavorable group (p = 0.0003). After treatment, the PFS of patients with reduced CTCs was significantly better than those with no significant change in CTCs (9 months vs 6 months, p = 0.014). In univariate and multivariate analysis, patients with CTCs-d0 ≥ 5 and CTCs-d28 ≥ 5 had significantly lower PFS when compared to those with CTCs-d0 < 5 and CTCs-d28 < 5, respectively.Conclusion: This study confirmed for the first time that CTC count is closely correlated with prognosis in EGFR- and TP53-mutant advanced NSCLC following first-line treatment with first-generation EGFR-TKIs.

Circulating Tumor Cells Predict Prognosis Following First-Generation EGFR-TKI Treatment in EGFR- and TP53-Mutant Non-Small Cell Lung Cancer

Purpose: First-generation EGFR-TKIs have become the first-line standard treatment for advanced non-small cell lung cancer (NSCLC) with EGFR mutations. This study isolates and quantifies circulating tumor cells (CTCs) and evaluates patient prognosis before and after first-line treatment with EGFR-TKIs in advanced NSCLC with EGFR and TP53 mutation.Methods: Patients with advanced NSCLC with EGFR and TP53 mutation were treated with a first-generation EGFR-TKI using a standard daily dose. Continuous blood samples were collected at baseline (CTCs-d0) and 28 days (CTCs-d28), and the isolation by size of tumor cells (ISET) method was used to detect CTCs.Results: The CTC results were divided into favorable (< 5 CTCs) and unfavorable (≥ 5 CTCs) groups. The median progression-free survival (PFS) of patients in the favorable group was significantly longer at baseline compared to those in the unfavorable group (15 vs 7.5 months; p = 0.0055). After 28 days of treatment with first-generation EGFR-TKI, the PFS of patients in the favorable group was 12.5 months, which was significantly longer than the median PFS of 7 months in the unfavorable group (p = 0.0003). After treatment, the PFS of patients with reduced CTCs was significantly better than those with no significant change in CTCs (9 months vs 6 months, p = 0.014). In univariate and multivariate analysis, patients with CTCs-d0 ≥ 5 and CTCs-d28 ≥ 5 had significantly lower PFS when compared to those with CTCs-d0 < 5 and CTCs-d28 < 5, respectively.Conclusion: This study confirmed for the first time that CTC count is closely correlated with prognosis in EGFR- and TP53-mutant advanced NSCLC following first-line treatment with first-generation EGFR-TKIs.

Assessing and decomposing inequality of opportunity in access to child health and nutrition in sub-Saharan Africa: evidence from three countries with low human development index

Background Inequality of opportunity in health and nutrition is a major public health issue in the developing regions. This study analyzed the patterns and extent of inequality of opportunity in health and nutrition among children under-five across three countries sub-Saharan Africa with low Human development index (HDI). Methods We used data from the Multiple Indicator Cluster Survey of the Democratic Republic of Congo (20,792 households, 21,756 women aged 15 to 49 and 21,456 children under five), Guinea Bissau (6601 households, 10,234 women aged 15–49 and 7573 children under five) and Mali (11,830 households, 18,409 women in 15–49 years and 16,468 children under five) to compute the human opportunity index (HOI) and the dissimilarity index (D-index). Secondly, the Shapley decomposition method was used to estimate the relative contribution of circumstances that are beyond the control of children under-five and affecting their development outcomes in later life stages. Results The study revealed that children belonging to the most favorable group had higher access rates for immunization (93.64%) and water and sanitation facilities (73.59%) in Guinea Bissau. In Congo DR, the access rate was high for immunization (93.9%) for children in the most favorable group. In Mali, access rates stood at 6.56% for children in the most favorable group. In Guinea Bissau, the inequality of opportunity was important in access to health services before and after delivery (43.85%). In Congo DR, the inequality of opportunity was only high for the immunization composite indicator (83.79%) while in Mali, inequality of opportunity was higher for access to health services before and after delivery (41.67%). Conclusion The results show that there are efforts in some places to promote access to health and nutrition services in order to make access equal without distinction linked to the socio-economic and demographic characteristics in which the children live. However, the inequalities of opportunity observed between the children of the most favorable group and those of the least favorable group, remain in general at significant levels and call on government of these countries to implement policies taking them into account.