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.

Platelet-lymphocyte ratio and sepsis outcome in children

Background Sepsis is the most common cause of death in infants and children worldwide. Identification of patients with a high risk of death and accurately anticipating outcomes in the early phase is very important in order to provide adequate intervention to the patient. Predictors and scoring systems have been used to determine the prognosis of sepsis n children. The platelet-lymphocyte ratio (PLR), a newly-used marker for inflammation, has received recent attention, as it can act as an indicator in a variety of diseases, including sepsis. Objective o investigate the relationship between PLR and clinical outcomes in pediatric patients with sepsis. Methods This study was conducted using an analytic, observational method with a prospective cohort approach in children with sepsis in the Pediatric Intensive Care Unit (PICU) of Prof. Dr. R. D. Kandou Central General Hospital, Manado, North Sulawesi, from February to August 2020. We analyzed patients’ platelet-lymphocyteratio (PLR), mortality rate, and length of stay using SPSS software. The PLR were recorded once within the first 24 hours of PICU admission. Results Of 96 PICU patients, 87 patients were eligible for this study. In total, 50 patients (57.47%) died. Mean PLR was 77.53 among sepsis survivors and 157.2 among non-survivors (rpb=0.566, P<0.0001) indicating a strong relationship between PLR and mortality. We also found a strong positive linear relationship between PLR and PICU length of stay. Conclusion Platelet-lymphocyte ratio is a predictor of sepsis outcomes that can be easily and inexpensively checked. Thus, it can be used in regions with limited health facilities.

Predictors of transcatheter closure cancellation in children with ventricular septal defect

Background Ventricle septal defect (VSD) is the most common type of congenital heart disease in children. If definitive therapy delayed, failure to thrive and developmental delays can lead to decreased quality of life. The options for VSD closure include surgical and minimally invasive procedures with transcatheterization. Although transcatheterization is considered to be the safest therapy, the risk of complications can lead to cancellation of procedure. Objective To determine whether nutritional status, body height, VSD type and size, and type of device used were predictors of cancellation of transcatheter closure of VSD. Methods A retrospective cohort study using medical records was performed for all children who underwent transcatheter closure of VSD at Dr. Sardjito Hospital, Yogyakarta, Central Java, between January 2017 to March 2020. Cancellation of closure was defined as complications occurring during the procedure, such as cardiac conduction problems, valve regurgitation, and device embolization. Multivariate logistic regression analysis was done to determine independent predictors of closure cancellation. Results One hundred thirty-four children were enrolled. Independent variables that were significant predictors were doubly committed subarterial (DCSA) VSD type (OR 5.98; 95%CI 1.52 to 23.61; P=0.045), moderate VSD size (OR 15.59; 95%CI 4.67 to 52.06; P=0.001), and types of devices used: symmetric (OR 27.06; 95%CI 2.75 to 266.17; P=0.001), asymmetric (OR 16.46; 95%CI 2.15 to 210.0; P=0.001), and coil (OR 21.26; 95%CI 2.15 to 210.0; P=0.001). Taller body height was a protective factor against cancellation of the procedure (OR 0.98; 95%CI 0.96 to 1.00; P=0.008). Conclusion Significant predictors of cancellation of transcatheter VSD closure are DCSA VSD, moderate VSD size, as well as coil, symmetric, and asymmetric devices, and increased body height.

Analytical study of inflammatory cytokines and immunoglobulin expression following dust mite allergen exposure in pregnant mice

Background Allergen tolerability due to allergic immune reactions could be transferred through the placenta from maternal to fetal circulation. Hence, a further investigation regarding the tolerability following mite allergen exposures is desirable. Objective To evaluate various doses of mite allergens and cytokines associated with Th1, Th2, and Treg cells with regards to possible allergic tolerance in neonatal mice. Methods This study used an experimental design with a post-test only control group, to assess the effect of mite allergens on pregnant BALB/C mice and their newborns. In this study female BALB/C mice aged 10 weeks were mated with male mice, then pregnant BALB/C mice were exposed to allergens at 4 weeks gestation. During pregnancy, pregnant females’ blood specimens were taken to measure cytokines and immunoglobulins. Meanwhile, neonatal blood specimens were taken at 2 weeks postnatally to measure cytokines and immunoglobulins. Blood specimens from pregnant BALB/C mice and their newborns were evaluated using ELISA kits for the following cytokines: interleukin (IL)-2, interferon (IFN)-γ, interleukin (IL)-4, IL-5, IL-10, TGF-β1, as well as immunoglobulins (Ig)G-1, IgG-2a, IgG-2b, IgG3 subclass, IgM, IgA, and IgE. The case group was the group that received high and low doses of exposure, while the control group did not get exposure. Results In response to low dose mite allergen exposure, there were significant increases of IL-2, IFN-y, and IL-4, IL-5, and TGF-β1 in mothers and neonates. Pregnant mices that received high doses of allergens, however, had significant increases in IL-5 and TGF-B1; results were likewise for their offspring. Mothers and neonates, had significantly increased expression of IgG subclasses after a low dose of dust mite allergen. Following a ten-fold increase in allergen dose, the mothers showed significant increases in IgA, IgM, IgE, and IgG subclasses, whereas in neonatal mice, those immunoglobulin levels were not significantly different from control mice. Conclusion Exposure to mite allergens can trigger regulatory functions of Th1, Th2, and Tregs cells to activate their cytokines, except IL-10. The regulatory function of Tregs is dominated by TGFβ in maternal and neonatal mice, at low and high doses. Th1 cytokines express cytokines during exposure only to low-dose allergens and Th2 cells regulate IL-5 levels to both low- and high-dose allergens.

Atypical presentations of hepatitis A infection in children

Background Hepatitis A is the most common cause of acute viral hepatitis, with a typical simple, self-limiting course. But it is not free from complications. Atypical presentations, such as in the form of prolonged cholestasis, ascites, pleural effusion, relapsing hepatitis, or fulminant hepatic failure, pose challenges to disease management. Knowledge about varying presentations and identification of factors associated with atypical presentations will help to early diagnosis of atypical courses of disease. Objective To describe various atypical clinical presentations, biochemical findings of hepatitis A infection, and possible related factors. Methods Ninety-five children aged 1 to 18 years, diagnosed with hepatitis A infection, and admitted to the Department of Pediatric Gastroenterology & Nutrition, BSMMU, Dhaka, Bangladesh from January 2015 to May 2018 were studied retrospectively. Results Atypical presentations were manifested in 19 (20%) out of 95 children with hepatitis A virus (HAV) infection. The mean age of atypical patients [6.32 (SD 3.45) years] was significantly lower than that of typical patients [8.22 (SD 3.58) years] (P=0.0041). The most common atypical manifestation was ascites (11/19), followed by hepatic encephalopathy (9/19), acute liver failure (719), thrombocytopenia (2/19), pleural effusion (2/19), and cholestasis (1; 1.1%). Children with atypical features had significantly higher international normalized ratio (INR) and serum bilirubin, as well as lower hemoglobin level than the typical group. Children of atypical group had significantly higher number of organomegaly and coagulopathy. Conclusion Ascites, hepatic encephalopathy, acute liver failure, thrombocytopenia, pleural effusion, and prolonged cholestasis were common forms of atypical presentation. Younger age, organomegaly, higher bilirubin level, prolonged PT, and decreased hemoglobin level could be predictive of an atypical presentation of HAV in children.

Soluble vascular cell adhesion molecule-1 levels and severity of dengue hemorrhagic fever in children

Background The clinical manifestations of dengue infection vary widely, ranging from asymptomatic to severe forms that can cause death. In severe infections, the expression of soluble vascular cell adhesion molecule-1 (sVCAM-1) in endothelial cells is reportedly excessive, causing endothelial cell gaps through VE-cadherin and plasma leakage, which is the basic mechanism for shock in dengue hemorrhagic fever (DHF). Objective To determine the association between sVCAM-1 levels and severity of dengue hemorrhagic fever in children. Methods This cross-sectional study was done in children with DHF at Dr. M. Djamil Hospital, Padang, West Sumatera. Subjects were diagnosed according to the 2011 WHO criteria and selected by consecutive sampling. They were grouped as DHF with or without shock. Examination of sVCAM-1 levels was done by ELISA method. Mann-Whitney test with a significance of P<0.05 was used for statistical analysis. Results A total of 66 patients were collected from January 2018 to December 2019, but 2 patients were excluded. The 64 subjects who met the inclusion criteria consisted of 32 (50%) DHF without shock and 32 (50%) DHF with shock. Median sVCAM-1 was significantly higher in the DHF with shock group (840 ng/mL) than in DHF without shock group (598 ng/mL) (P<0.05). Conclusion There was a significant association between higher sVCAM-1 levels and greater severity of dengue hemorrhagic fever in children.

Ethical aspects of gender assignment in ambiguous genitalia - congenital adrenal hyperplasia: a case report

Congenital adrenal hyperplasia (CAH) is an autosomal recessive disorder commonly caused by mutation of the CYP21A2 gene, resulting in deficiency of an enzyme required for cortisol synthesis in the adrenal cortex. In 90-95% of cases, the deficient enzyme is 21-hydroxylase (21-OH), with an incidence ranging from 1 in 5,000 to 15,000 live births across various ethnic and racial backgrounds. In classical 21-OH deficiency (21-OHD) CAH, excessive androgen exposure in the fetus results in virilization at birth.1 The management of ambiguous genitalia in children with CAH presents a unique and ethically challenging decision-making dilemma for the medical team. Insensitive and poorly informed statements made in the delivery room may cause long-term psychological problems for the families. It is important to refrain from assigning gender until sufficient diagnostic information can be gathered. Parents, as guardians, and the supporting medical team must make decisions on behalf of the child, with the goal of enabling the child to grow into a healthy and happy adult with his or her assigned gender.2,3 We report a case of a child with CAH, focusing on the ethical challenges in management of ambiguous genitalia.

Parental consanguinity and congenital heart defects in Afghan children with Down’s syndrome

Background: It seems that parents’ consanguinity status effects the pattern of congenital heart defects (CHDs). In this study the CHD pattern in children with Down’s syndrome (DS) was determined in Afghanistan’s children population with a high consanguineous marriage rate and compared with historical cohorts from populations with low prevalence of parental consanguinity. Objective: This analytic cross sectional study aimed to determine the frequency and distribution of CHDs in Afghanistan children with Down’s Syndrome as a group in a community with a high consanguineous marriage rate and comparing these with different global studies and populations with low prevalence of consanguinity. Methods: This analytic cross sectional study was conducted in a pediatric teaching hospital in Kabul city - Afghanistan, named Maiwand Hospital. The subjects were all children with DS proven by clinical and cytogenetic study and referred to the pediatric cardiology service from September 2018–September 2020. Parents’ consanguinity was documented and 2D echocardiography and Doppler studies were performed by two experienced pediatric cardiologists after physical examination, ECG, and chest X-ray for each patient. Results: During the two-year study period, 120 DS patients were identified, 78 (65%) of whom had CHDs. The prevalence of isolated and multiple CHD in the 78 children with DS were 35% (42 patients) and 30% (36 patients), respectively. Ventricular septal defect (20.5%) and atrial septal defect (15.3%) were the most common isolated defects. The combination of VSD and PDA (20.5%) were the most frequent multiple CHDs. The most com­mon associations of CHD were VSD + PDA (20.5%) and VSD + ASD (10.2%). Consanguinity was found in 69.2 % of all parents. Conclusions: A higher frequency of CHD was documented in DS children from this population with a high consanguineous marriage rate. The frequencies of specific lesions were almost similar to those reported locally and internationally; VSD was the most frequently detected in this study. Interesting was the predominance of left-right shunt lesions and the relative rarity of cyanotic and complex CHD in this DS population. key words: congenital heart disease, atrioventricular septal defect, Down’s syndrome, trisomy 21, Afghanistan

Neonatal hemochromatosis attributed to gestational alloimmune liver disease treated with intravenous immunoglobulin and exchange transfusion therapy: an evidence-based case report

Neonatal hemochromatosis (NH) is a rare fatal liver disease accompanied by hepatic and extrahepatic iron overload.1-3 Gestational alloimmune liver disease (GALD) is a materno-fetal alloimmune disorder and leading cause of NH.2,4,5 This condition allows an interplay between the maternal adaptive immune system and the fetus, resulting in an allograft to the mother. The mother becomes sensitized to an alloantigen expressed by the fetus and forms specific reactive antibodies. Immunoglobulin G (IgG) is transported through the placenta and attacks the fetal hepatocytes, resulting in severe loss of hepatocytes and fetal iron overload.3,6 Liver transplantation has been the only definitive treatment for NH for many years, with a survival rate of ±35%. Conventional therapy containing antioxidants and chelation agents reportedly have very poor success, with survival rate of only 10-20%. A new treatment paradigm involving intravenous immunoglobulin (IVIG) and exchange transfusion (ET) therapy has shown significant success in survival rate in NH, decreasing the need for liver transplantation.3,7,8 Here we present a case of NH caused by GALD and treated successfully with a combination of IVIG therapy and ET. We also aimed to evaluate the efficacy of IVIG and ET therapy for NH.

Prevalence and risk factors of irritable bowel syndrome in adolescents

Background Irritable bowel syndrome (IBS) is a common gastrointestinal disorder in children and adults. The IBS is diagnosed by symptoms that fulfill the Rome IV criteria. This condition can impact quality of life, especially in adolescents. Objectives To investigate the prevalence of IBS in high school students and analyze its risk factors. Methods This cross-sectional study was done with e-questionnaires from Rome IV Diagnostic Questionnaire on Pediatric Functional Gastrointestinal Disorders (R4PDQ). Students from high school and occupational schools age 14 to 18-years-old in Jakarta were included in this study. Possible risk factors for IBS were analyzed using Fisher’s exact test for bivariate analysis and logistic regression for multivariate analysis. Results Of 210 subjects, 10 (4.8%) had IBS. The IBS-M and IBS-C subtypes were more common than IBS-D. Gastrointestinal infection history was significantly associated with IBS (OR 7.1; 95%CI 1.7 to 29.3; P=0.013). Other factors such as gender, corporal punishment, asthma, spicy and fatty food consumption, as well as socioeconomic status were not significantly associated with IBS (P>0.05). Conclusion The prevalence of IBS in adolescents is 4.8%. History of gastrointestinal infection is a risk factor for IBS.