Impact of Hemin on Interleukin-21 Levels and Plasma Cells in Transfusion-Dependent Thalassemia with Positive and Negative Allo-Autoantibody.

Introduction: Antibody formation in transfusion-dependent thalassemia is associated with chronic hemolysis and repeated transfusions. Hemolysis produces heme, which mediates B-cell differentiation into plasma cells and produces antibodies influenced by interleukin-21 (IL-21). Objective: This study aimed to compare IL-21 levels, plasma cell percentage, and red blood cell antibodies between positive and negative allo-autoantibody thalassemia before and after hemin administration. Materials and Methods: This research employed a quasi-experimental nonequivalent control group pre-test and post-test design performed from April to November 2021 at Soetomo Academic Hospital in Surabaya, Indonesia. Heparinized blood samples of 5 mL and 4 mL and EDTA blood samples of 3 mL were taken from positive (29 patients) and negative (28 patients) allo-autoantibody thalassemia participants. Hemin 20 µM was added to 5 mL of heparinized blood, incubated for 2 hours, prepared into peripheral blood mononuclear cells (PBMCs), and cultured for 3 days. The percentage of plasma cells (CD38+CD184+) of cultured and uncultured PBMCs was measured by BD FACSCalibur Flow Cytometer. IL-21 levels of plasma and supernatants were measured with Sandwich Enzyme-Linked Immunosorbent Assay by Elabscience. Red blood cell antibodies were detected by QWALYS 3 E.M. Technology. Autoantibodies were determined by the Grifols gel tube method. Results: IL-21 levels were significantly different in the positive and negative allo-autoantibody thalassemia groups after hemin administration. The percentage of plasma cells in the positive allo-autoantibody group increased significantly after the administration of hemin. The percentage of plasma cells between thalassemia groups was not significantly different before the hemin administration but increased significantly after it. Red blood cell antibodies after the administration of hemin were significantly different in the negative allo-autoantibody group but not significantly different in the positive allo-autoantibody group. Conclusion: Hemin administration affected IL-21 levels, plasma cell percentage, and antibody formation in positive and negative allo-auto antibody thalassemia.

Role of Hemin in the Immune Response of T Follicular Helper Lymphocytes Expressing T-Cell Immunoreceptor with Immunoglobulin and Immunoreceptor Tyrosine-Based Inhibitory Domains, Programmed Cell Death-1, and Interleukin-21 in Allo-Auto Positive and Negative Thalassemia.

Introduction: Repeated transfusions in thalassemia patients can cause several complications, including alloimmunization and autoimmunization. Purpose: This study compares the immune response of T follicular helper (Tfh) lymphocytes expressing T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory domains (TIGIT), programmed cell death-1 (PD-1), and interleukin-21 (IL-21) between patients with allo-auto positive and negative thalassemia before and after hemin administration. Materials and Methods: This study used a quasi-experimental pre- and post-test design and was performed between April and November 2021 at the Dr. Soetomo General Academic Hospital in Surabaya, Indonesia. It enrolled 29 patients with allo-auto positive thalassemia and 28 with allo-auto negative, and 9 mL of whole blood (WB) was drawn from each patient. Hemin solution (20 µM) was added to 5 mL of WB, incubated for two hours, processed into peripheral blood mononuclear cells (PBMCs) in RPMI media, and cultured with 5% CO2 for three days. The 4 mL WB sample was also processed into PBMCs. PBMC cells cultured and without cultured were examined by flow cytometry using a BD FACSCalibur after surface and intracellular staining. Differences in Tfh cells expressing TIGIT, PD-1, and IL-21 between thalassemia groups before and after hemin administration were compared using independent t-tests or Mann-Whitney U-tests (p < 0.05). Results: Tfh cell expression did not differ between groups before hemin administration and increased after hemin administration. The increase in Tfh cell expression was higher in the allo-auto positive group. TIGIT and PD-1 expression in Tfh cells did not differ between groups, but TIGIT decreased after hemin administration in contrast to PD-1 result. IL-21 expression in Tfh cells did not differ between groups and did not change after hemin administration. Conclusion: Hemin affected the expression of Tfh cells in both group thalassemia, but there was no difference of Tfh cell expression between the groups.

The incidence of and risk factors for hyperglycemia and hypoglycemia in preterm infants receiving early-aggressive parenteral nutrition.

Introduction: Optimizing nutritional support helps prevent extra uterine growth restriction and adverse long-term outcomes in preterm infants. Objectives: This study aimed to analyze the incidence of and risk factors for hyperglycemia and hypoglycemia in preterm infants receiving early-aggressive parenteral nutrition (PN). Methods: This prospective observational study included preterm infants receiving PN at the Neonatal Intensive Care Unit of Dr. Soetomo General Hospital between April 2018 and May 2019. Potential risk factors analyzed included asphyxia, sepsis, respiratory distress syndrome, multiple congenital anomalies, mortality, necrotizing enterocolitis, retinopathy of prematurity, the postoperative period, inotropic administration, glucose infusion rate (GIR) > 10-12 mg/kg/min, GIR 4-<5.5 mg/kg/min, and increase in GIR <1 mg/kg/min. Results: Of the 105 preterm infants included, hyperglycemia and hypoglycemia were found in 14 (13.3%) and 26 (24.8%) infants, respectively, with most incidents occurring in the first week (hyperglycemia: 85.7%; hypoglycemia: 88.5%). Sepsis was an independent risk factor for hyperglycemia (odds ratio [OR]: 8.743, 95% confidence interval [CI]: 2.392-31.959; P = 0.001). Hypoglycemia independent risk factors included the postoperative period (OR: 4.425, 95% CI: 1.218-16.073; P = 0.024) and use of GIR 4-<5.5 mg/kg/min (OR: 2.950, 95% CI: 1.035-8.405; P = 0.043). Conclusion: Hyperglycemia and hypoglycemia can occur in preterm infants receiving early-aggressive PN; most cases occur within the first week of life. Hypoglycemia correlated with low glucose intake, and hyperglycemia correlated with sepsis. Monitoring blood glucose levels in preterm infants receiving PN, especially in the first weeks of life, may decrease morbidity associated with hyperglycemia or hypoglycemia.

Relationship between serum ferritin and growth status of pediatric transfusion dependent thalassemia.

Background: Growth retardation is a long-term complication in pediatric transfusion-dependent thalassemias (TDTs), presented as short-stature and upper body segment shortening. The cause of this condition was chronic hypoxia, iron overload, endocrinopathy, inadequate transfusion, and iron chelation. We analyze the relationship between ferritin level and growth status of pediatric TDTs. Methods: This was a cross-sectional study on pediatric TDTs aged 2-18 years old at Dr. Soetomo General Academic Hospital Surabaya, Indonesia conducted in 2020. They required blood transfusion every 2-4 weeks. We evaluated the ratio of upper/lower body segments, weight for age Z-score (WAZ), height for age Z-score (HAZ), and body mass index (BMI) Z-score, based on CDC growth chart as growth status parameters. Serum ferritin was checked every three months to determine iron overload and iron chelation (deferiprone, deferasirox and deferoxamine). We used Spearman correlation and Mann-Whitney U test to analyze between variables (α=0.05). Results: We enrolled 15/29 males with median age 10.5 years. Serum Ferritin had negative correlation with the ratio of upper/lower body segments (rho=-0.552; P=0.002), but not for HAZ (rho=-0.078; P=0.694), WAZ (rho=-0.186; P=0.342), BMI Z-score (rho=-0.089; P=0.653) especially if serum ferritin was above 2500 µ/L. In deferiprone group (n=8), the WAZ (P=0.034) and BMI Z-score (P=0.031) were lower; but the ratio of upper/lower body segments was greater (P=0.039) than the deferasirox group. Conclusion: Growth retardation was more visible in pediatric TDTs with high ferritin and in deferiprone group. The height and the ratio of upper/lower body segments of the body were more affected.

Towards a prevention program for ß-thalassemia. The molecular spectrum in East Java, Indonesia.

Defining the spectrum of specific thalassemia mutations is an important issue when planning prevention programs in large multi ethnic countries as is Indonesia. In a first attempt to define the prevalence of the common mutations in East Java we selected a cohort of 17 transfusion-dependent patients attending the Dr. Soetomo Hospital, Surabaya, Indonesia. After basic diagnostics we performed direct DNA sequencing for all ß-globin genes. The results obtained on 34 independent chromosomes revealed the following prevalence rates: c.79 G>A p. Glu27Lys (Hb E) 47.0%; c.92+5G>C (IVS-I-5 G>C) 20.6%; c.109_110 delC p.Pro37Leu fs X7 [codon 35 (-C)] 17.6%; c.46del T p.Trp16Gly fsX4 [codon 15 (-T)] 5.9%; c.126_129delCTTT p. Phe42Leu fs X19 (codons 41/42) 2.9%; c.316-197 C>T [IVS-II-654 (C>T)] 2.9%; c*112 A>G (PolyA) 2.9%. Our preliminary results show that the distribution of the prevalent mutations in our cohort is quite homogeneous but with different forms than previously reported. This indicates that more studies on a larger scale and in different geographical areas are needed to refine our provisional results and to characterize the molecular background of the disease in the whole country.

Nigella sativa L. as immunomodulator and preventive effect on renal tissue damage of lupus mice induced by pristane.

Introduction: Nigella sativa L. is an herbal plant with Thimoquinone as the main therapeutic properties. This plants has been shown to cure for various diseases and affected the immune system by modulating cytokines and T regulatory cell (Treg) sot that able to prevent renal injury in several diseases, but studies on Systemic Lupus Erythematous are still rare. Objective: This study aimed to investigate immunomodulation and preventive effects of Nigella sativa L. on renal tissue damage in Pristane induced Lupus (PIL)-mice model. Methods: This true experimental study included 48 female Balb/C mice, 38 mice were injected pristane intraperitoneally and waited 16 weeks to become lupus model. Only 30 mice met the Systemic Lupus International Collaborating Clinics criteria. Ten healthy mice were used as control, 30 PIL mice model divided into 3 groups (placebo, steroid, Nigella sativa L.). At the end of 28 days of treatment, the mice were sacrificed to take a blood sample and kidney organ to evaluate the injury histopathologically. Results: The results showed that the cytokine expression Interleukin (IL) (IL-17, IL-6, IL-23) in the Nigella sativa L. group was the lowest. The highest absolute number of Tregs was the steroid group followed Nigella sativa L. group. Renal injury assessed histopathologically showed the Nigella sativa L. group was the lowest and almost close to normal. Conclusion: This study indicate that Nigella sativa L. has an immunomodulatory effect and can prevent kidney injury PIL-treated mice. We suggest that Nigella sativa L. may need to be considered for further research on its use as a complementary supplement in lupus patients.

Observational study on necrotizing enterocolitis in neonates born to SARS-CoV-2-positive mothers.

Background: The impact of the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) pandemic on expectant mother and their babies extends to many aspects of life. Necrotizing enterocolitis (NEC) has been recognized as a life-threatening gastrointestinal inflammatory process in neonates that has high rates of morbidity and mortality. Objective: To investigate factors associated with NEC in hospitalized neonates whose mothers were SARS-CoV-2-positive and their relationship to mortality. Method: This observational study was conducted from May 2020 to March 2021. All neonates who were hospitalized, after confirming that the mother was SARS-CoV-2-positive, were included in this study. The confirmation of positive SARS-CoV-2 was determined according to the reverse transcription-polymerase chain reaction (PCR) assay. The neonatal SARS-CoV-2 test was performed on the first day of birth. NEC was established based on a suggestive clinical presentation and abnormal abdominal radiographs. Results: Of the 125 neonates enrolled in this study, there were 5 neonates who developed NEC and only one survived. Significant associated factors with NEC included lower birth weight (p < 0.001), lower gestational age (p < 0.001), positive SARS-CoV-2 PCR results (OR = 15.333; 95% CI = 2.074-113.381, p = 0.007), asphyxia (OR = 13.143; 95% CI = 1.411-122.443, p = 0.024), and mortality (OR = 156.000; 95% CI = 13.157-1849.623; p < 0.001). Mortality was significantly associated with lower gestational age (p = 0.025), cesarean section delivery (p = 0.025), and asphyxia (p = 0.025). Conclusion: Significant associated factors with NEC in neonates born to SARS-CoV-2-positive mothers included positive SARS-CoV-2 PCR results, asphyxia, lower gestational age, and lower birth weight. In addition to caesarean section delivery, these factors were related to mortality in neonates in such conditions.

Relationship between Bax and Bcl-2 Protein Expression and Outcome of Induction Phase Chemotherapy in Pediatric Acute Lymphoblastic Leukemia.

BACKGROUND: Overexpression of the antiapoptotic protein Bcl-2 causes apoptosis to stop and conversely the increased expression of the proapoptotic protein Bax makes lymphoblasts easy to destroy. The Bax/Bcl-2 ratio plays a role in the balance of apoptosis, immortality, resistance, and outcome of chemotherapy. We analyzed the relationship between the Bax/BCl-2 ratio and the outcome of induction phase chemotherapy in pediatric Acute Lymphoblastic Leukemia (ALL). METHODS: This research was conducted with a prospective observational study on pediatric ALL aged 1-18 years who were newly diagnosed based on bone marrow aspiration (morphology and immunophenotyping) at Dr. Soetomo General Hospital, Surabaya on October 2020 to March 2021. Expression of Bcl-2, Bax, and Bax/Bcl-2 protein ratio was measured by the flow cytometry method from lymphoblast on bone marrow aspirate samples before and after induction phase chemotherapy according to the 2018 Childhood ALL Indonesian Protocol. The outcomes evaluated were survival and remission rate (lymphoblasts in the bone marrow less than 5%). We used the Mann-Whitney U test and Wilcoxon Signed Rank test to analyze the differences between protein expression with p<0.05 for a two-tailed test. RESULTS: We included 17/26 pediatric ALL, consisting of 88% male, 94% LLA-L1, 76% B cell ALL and 24% T cell ALL. Mean expression of Bax, Bcl-2, and Bax/Bcl-2 protein ratio before chemotherapy among pediatric ALL who alive (N=11) and dead (N=6) were not significantly different (p>0.05). All children who completed the induction phase of chemotherapy went into remission. Bax and Bcl-2 expression before and after chemotherapy showed no difference (p>0.05). The Bax/Bcl-2 ratio increased from 1.74(SD 1.846) to 6.17(4.139) with p=0.021. CONCLUSION: Expression of Bax, Bcl-2, and Bax/Bcl-2 protein ratio at the beginning of diagnosis did not affect the survival of pediatric ALL after the induction phase of chemotherapy. The Bax/Bcl-2 protein ratio increased 3.5 times in pediatric ALL with remission outcomes, indicating proapoptotic dominance.

Association between glial fibrillary acidic protein, glial-derived neurotrophic factor, and fatty acid-binding protein-2 at birth in the incidence of necrotizing enterocolitis in preterm infants.

Background: This study aimed to analyze the relationship between glial fibrillary acidic protein (GFAP), glial-derived neurotrophic factor (GDNF), and fatty acid-binding protein-2 (FABP-2) in preterm infants on the incidence of NEC. Methods: Preterm infants with a birth weight <1,500 g and gestational age <34 weeks were included in this study. Biomarker examination was performed using the umbilical vein blood at birth (first sample). Biomarker examination was repeated if the infant developed symptoms of NEC using peripheral vein blood (second sample). Infants were observed for 14 days. If NEC did not exist, a biomarker examination was performed at 14 days. Results: This study included 30 preterm infants, nine infants experienced NEC. The values of GFAP, GDNF, and FABP-2 (median and range) in the group with NEC were higher than those in the group without NEC in both the first samples {GFAP [1.40 (0.20-6.50) vs. 0.30 (0.10-1.30) P = 0.014], GDNF [2.84 (1.05-14.11) vs. 1.56 (1.07-3.48) P = 0.050], and FABP-2 [621.70 (278.40-2,207.00) vs. 294.20 (211.40-597.50) P = 0.002]} and second samples {GFAP [2.40 (0.30-3.10) vs. 0.30 (0.10-0.60) P = 0.003], GDNF [2.99 (0.56-10.30) vs. 1.46 (0.85-2.24) P = 0.019], and FABP-2 [646.8 (179.20-1,571.00) vs. 314.90 (184.70-521.60) P = 0.040]}. In infants with NEC, the median values of GFAP [2.40 (0.30-3.10) vs. 1.40 (0.20-6.50) P = 0.767], GDNF [2.99 (0.56-10.30) vs. 2.84 (1.05-14.11) P = 0.859], and FABP-2 [646.80 (179.20-1,571.00) vs. 621.70 (278.40-2,207.00) P = 0.953] in the second sample were higher than those in the first sample. Logistic regression demonstrated that GFAP at birth (Odds Ratio [OR] = 15.629, 95% Confidence Interval [CI] = 1.697-143.906, P = 0.015) and FABP-2 levels at birth (OR = 1.008, 95% CI = 1.001-1.015, P = 0.033) were significantly associated with an increased risk of NEC. Conclusion: Increased GFAP, GDNF, and FABP-2 at birth are associated with NEC occurrence within two weeks of birth. These findings suggest that early-onset NEC is associated with intestinal injury that occurs during the perinatal or even prenatal period.

Corrigendum on: Pediatric COVID-19: Report from Indonesian pediatric society data registry.

[This corrects the article DOI: 10.3389/fped.2021.716898.].

Hydration effect on kidney function and serum electrolyte in children with tumor lysis syndrome (TLS) and risk of TLS.

OBJECTIVES: Tumor lysis syndrome (TLS) is a life-threatening oncology emergency disorder, which may cause acute kidney injury (AKI), arrhythmias, seizures, and sudden death. Hydration is used to prevent TLS in medium-high risk patients, and treatment in TLS patients. According to the pediatric protocol in Dr. Soetomo District General and Teaching Hospital, close monitoring is required to prevent the progression of hematological malignancy towards TLS. The study aimed to analyze the hydration effect on potassium, calcium, and phosphate levels; serum creatinine (sCr); and blood urea nitrogen (BUN) level. METHODS: This was an observational and prospective study conducted at Dr. Soetomo District General and Teaching Hospital for four months on 15 pediatric hemato-oncology patients who got TLS and in risk of TLS. Laboratory parameters were observed in 11 days, pre and post hydration. RESULTS: Among the 15 patients who met the inclusion criteria, there were eight TLS patients and seven TLS risk patients. After hydration administration 67% of TLS patients achieved normal potassium level, 75% achieved normal phosphate level, 0% achieved normal calcium level, and 50% achieved normal sCr and BUN levels. Meanwhile, TLS risk patients reached normal level in all parameters. This difference in performance is caused by disease progression. CONCLUSIONS: Hydration can maintain serum electrolytes and renal function in a normal range, preventing TLS in TLS risk patients. In TLS patients, hydration only tends slow the progression of the disease.

RISK FACTORS OF VINCRISTINE-INDUCED PERIPHERAL NEUROPATHY IN ACUTE LYMPHOBLASTIC LEUKAEMIA CHILDREN.

Objective : This study analysed Vincristine-induced peripheral neuropathy (VIPN) risk factors in Acute Lymphoblastic Leukaemia (ALL) children. Method : This cross-sectional study design was performed at Dr. Soetomo Hospital, Surabaya, Indonesia, from August to October 2019. It included ALL children, aged 4-18 years, undergoing the 2013 or 2018 ALL Indonesian Protocol of Chemotherapy, with a cumulative vincristine dose ≥ 12 mg / m2. VIPN diagnosis is based on complaints, the Total Neuropathy Score Pediatric Vincristine (TNS-PV), and nerve conduction studies (NCS). The examined risk factors were sex, age, ALL classification, nutritional status, impaired liver function, and cumulative vincristine dose. Results : There were 52 ALL children : median age 7 years, 59.6% boys, 59.6% ALL standard risk, 44.2% experienced impaired liver function at initial ALL diagnosis. Based on a single parameter for diagnosis, 26.9% had VIPN based on complaints, 76.9% had it based on the TNS-PV, and 100% had it based on NCS. VIPN was diagnosed in 25% of children, with predominantly motor impairment and located in lower extremities. Impaired liver function is a risk factor for VIPN in ALL children (p = 0.046, prevalence ratio (PR) 2.84). Conclusion : Impaired liver function is a significant risk factor for VIPN in ALL children. J. Med. Invest. 68 : 232-237, August, 2021.

Psycho-Education on Knowledge of Oral Hygiene and Psychological Distress to the Parents with Leukemia Children.

OBJECTIVE: To analyze the effect of psycho-educational intervention on knowledge of oral hygiene and psychological distress to the parents of children suffering from leukemia. METHODS: Design of this study was a quasi-experimental pre-posttest control group design. The sample were 70 mothers who had children with leukemia (intervention group = 35 mothers; control group = 35 mothers). The independent variable was psycho-educational, while the dependent variables were oral hygiene knowledge and psychological distress. The instruments used were the knowledge questionnaire and the Depression-Anxiety-Stress Scale (DASS-21). Data were analyzed using the Wilcoxon signed rank test and the Mann Whitney U-test with the significance α =0.05. RESULTS: The knowledge most widely known by parents was about how to perform of oral care (37.3%). All parameters of knowledge about oral hygiene have increased after being given a psycho-educational intervention. Psycho-educational interventions had an effect on reducing psychological distress; depression (p=0.000), anxiety (p=0.001) and stress (p=0.000). CONCLUSION: Most parents whose children suffer from cancer experience psychological distress in the form of depression, anxiety and stress with a range of symptoms ranging from mild to moderate. Psycho-educational interventions can increase knowledge about oral hygiene and decrease psychological distress in parents. 
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The glucose infusion rate of parenteral nutrition in the first week of life in preterm infants: an observational study.

BACKGROUND: Most preterm infants require a continuous glucose infusion in the early postnatal period due to the interruption of the transplacental glucose supply after birth to promote better neurodevelopmental outcomes. AIMS: To investigate the glucose infusion rate (GIR) on parenteral nutrition (PN) in the first week of life administered in preterm infants and its effect on neonatal morbidity and mortality. METHODS: This study included 97 infants aged < 37 gestational weeks and weighed < 2500 g at birth. Infants recruited in this study were classified into 3 groups based on the GIR usage in parenteral nutrition as follows: GIR usage of 5- < 7 g/kg/day (Group I), GIR usage of 7-13 g/kg/day (Group II), and GIR usage of > 13-15 g/kg/day (Group III). Univariate and multivariate logistic regression analyzes were carried out to investigate whether the GIR usage in the three groups was associated with selected neonatal morbidities and mortality. Neonatal morbidities analyzed included respiratory distress syndrome (RDS), necrotizing enterocolitis, sepsis, retinopathy of prematurity, pulmonary hypertension, hypoglycemia, and hyperglycemia. RESULT: Of 97 preterm infants included, 51.5% infants had a gestational age of 34- < 37 weeks, and 54.6% infants had a birth weight of 1500- < 2500 g. The multivariate logistic regression analysis showed that the GIR usage of 5- < 7 g/kg/day was an independent variable that significantly increased the risk of hypoglycemia (Adjusted Odds Ratio [AOR] = 4.000, 95% Confidence Interval [CI] = 1.384-11.565, P = 0.010) and reduced the risk of sepsis (AOR = 0.096, 95% CI = 0.012-0.757, P = 0.026). The GIR usage in all three groups did not increase the risk of mortality. For neonatal morbidity analyzed in this study, RDS (AOR = 5.404, 95%CI = 1.421-20.548, P = 0.013) was an independent risk factor of mortality. CONCLUSION: The GIR usage of < 7 g/kg/day in PN in the first week of life administered to preterm infants was an independent variable in increasing hypoglycemia, but in contrast, reducing the risk of sepsis.

Associated neonatal and maternal factors of osteopenia of prematurity in low resource setting: A cross-sectional study.

OBJECTIVE: Determining neonatal and maternal factors that are associated with the incidence of OFP. METHODS: This study employed a cross-sectional design, in which the participants were identified for clinical variables (sex, gestational age, birth weight, etc.), neonatal morbidity (sepsis, necrotizing enterocolitis (NEC), etc.), and maternal risk factors (premature rupture of membranes, preeclampsia, etc.). The data were analyzed using Chi-square test, independent t-test, and logistic regression test with p < 0.05. RESULTS: The birth weight ranged from 800 to 1495 g (1219 ± 225 g), of which 5 newborns (17%) were <1000 g. The gestational age ranged from 27 to 32 weeks, with a mean of 29 ± 1.5 weeks. The signs of OFP were observed in 13 (43%) infants, of which 2 (15%) OFP infants had a birth weight <1000 g. There was significant difference in parenteral nutrition duration (p = 0.018), onset of vitamin D supplementation (p = 0.019), and ALP level (p = 0.012) of infants between the OFP group and the non-OFP group. The variables associated with the incidence of OFP were parenteral nutrition duration >15 days (OR = 5.4; 95% CI 1.120-26.044; p = 0.036), ALP level >500 U/L (OR = 2.889; 95% CI 1.703-4.900; p = 0.014), and PROM (OR = 5.4; 95% CI 1.039-28.533; p = 0.045). CONCLUSION: The lack of phosphate intake, prolonged parenteral nutrition, ALP level >500 U/L, onset of vitamin D supplementation, and premature rupture of membranes are associated with the incidence of OFP.

The incidence of osteopenia of prematurity in preterm infants without phosphate supplementation: A prospective, observational study.

ABSTRACT: To meet their requirements for bone mineralization, it is recommended that preterm infants receive nutritional support containing calcium and phosphate. There are no clear data on the incidence of osteopenia of prematurity (OFP) in preterm infants without phosphate supplementation.This study aimed to investigate the incidence of OFP in preterm infants without phosphate supplementation and its relationship with the duration of parenteral nutrition (PN).This was a prospective and observational study.This study included 30 infants aged <32 gestational weeks and weighed <1500 g at birth. All infants received PN according to a standard protocol, beginning on day 1 with calcium, without phosphate. Starting from the first day of life, all infants received human milk without fortifiers. Oral vitamin D (400 IU/d) was administered when enteral nutrition reached 100 mL/kg/d.The diagnosis of OFP was based on radiographs that were taken of both wrists. Serum alkaline phosphatase (ALP) was measured 3 times: at the start of PN (ALP 1), at the end of PN (ALP 2), and at discharge or the expected due date (ALP 3). Radiographs were obtained on the same day as ALP 3. The duration of PN was analyzed in the presence of OFP using receiver operating characteristic curve analysis.Among the 30 infants, 13 (43%) were diagnosed with OFP. The duration of PN was significantly longer in the OFP group than in the group without OFP (16 vs 12 days; P < .05). The provision of PN for >15 days significantly increased the risk of OFP (odds ratio, 5.40; 95% confidence interval, 1.12-26.04; P = .035).We found a high incidence of OFP in preterm infants without phosphate supplementation. An association was found between the duration of PN and the incidence of OFP. Further research is needed to prevent the development of osteopenia in preterm infants.

Hospital acquired pneumonia risk factors in children with Acute Lymphoblastic Leukemia on chemotherapy.

BACKGROUND: Over the past 10 years, infection has remained as the main cause of illness and mortality among children with Acute Lymphoblastic Leukemia on chemotherapy. The high incidence of Hospital-Acquired Pneumonia in children with Acute Lymphoblastic Leukemia on chemotherapy with risk factors should be intervened earlier. METHODS: An observational case control study of children with Acute Lymphoblastic Leukemia on chemotherapy. Patient with Hospital-Acquired Pneumonia considered as case and patient without Hospital-Acquired Pneumonia as control to analyze risk factors that affect the incidence of Hospital-Acquired Pneumonia in children with Acute Lymphoblastic Leukemia on chemotherapy from 2016 to 2018 was performed in the pediatric ward Dr. Soetomo General Academic Hospital with a total sampling technique. Nine risk factors were analyzed: age, gender, nutritional status, length of stay, risk stratification, chemotherapy phase, anemia, neutropenia, and thrombocytopenia. Bivariate and multivariate analysis using chi-square, continuity correction, and logistic regression was used for statistical analysis. RESULTS: 120 children enrolled the study. Analyzed of risk factors showed risk stratification (p = 0.009), chemotherapy phase (p < 0.001), and neutropenia (p < 0.001) was proven to significantly affect the incidence of Hospital-Acquired Pneumonia in children with Acute Lymphoblastic Leukemia on chemotherapy. Age, gender, nutritional status, length of stay, anemia, and thrombocytopenia were not proven to be a risk factor that affects the incidence of Hospital-Acquired Pneumonia in children with Acute Lymphoblastic Leukemia on chemotherapy. CONCLUSION: The incidence of Hospital-Acquired Pneumonia in children with Acute Lymphoblastic Leukemia on chemotherapy is significantly affected by the risk stratification, chemotherapy phase, and neutropenia.

Risk Factors of Daunorubicine Induced Early Cardiotoxicity in Childhood Acute Lymphoblastic Leukemia: A Retrospective Study.

BACKGROUND: Daunorubicine, a type of anthracycline, is a drug commonly used in cancer chemotherapy that increases survival rate but consequently compromises with cardiovascular outcomes in some patients. Thus, preventing the early progression of cardiotoxicity is important to improve the treatment outcome in childhood acute lymhoblastic leukemia (ALL). OBJECTIVE: The present study aimed to identify the risk factors in anthracycline-induced early cardiotoxicity in childhood ALL. METHODS: This retrospective study was conducted by observing ALL-diagnosed children from 2014 to 2019 in Dr. Soetomo General Hospital. There were 49 patients who met the inclusion criteria and were treated with chemotherapy using Indonesian Childhood ALL Protocol 2013. Echocardiography was performed by pediatric cardiologists to compare before and at any given time after anthracycline therapy. Early cardiotoxicity was defined as a decline of left ventricle ejection fraction (LVEF) greater than 10% with a final LVEF < 53% during the first year of anthracycline administration.  Risk factors such as sex, age, risk stratification group, and cumulative dose were identified by using multiple logistic regression. Diagnostic performance of cumulative anthracycline dose was evaluated by receiver operating characteristic (ROC) curve. RESULTS: Early anthracycline-induced cardiotoxicity was observed in 5 out of 49 patients. The median cumulative dose of anthracycline was 143.69±72.68 mg/m2. Thirty-three patients experienced a decreasing LVEF. The factors associated with early cardiomyopathy were age of ≥ 4 years (PR= 1.128; 95% CI: 1.015-1.254; p= 0.001), high risk group (PR= 1.135; 95% CI: 1.016-1.269; p= 0.001), and cumulative dose of ≥120 mg / m2 (CI= 1.161; 95% CI:1.019-1.332). CONCLUSION: Age of ≥ 4 years, risk group, and cumulative dose of ≥120 mg/m2 are significant risk factors for early cardiomyopathy in childhood ALL.

Pediatric COVID-19: Report From Indonesian Pediatric Society Data Registry.

Background: Indonesia has a high number of COVID-19 cases and mortalities relative to not only among the Asia Pacific region but the world. Children were thought to be less affected by the virus compared to adults. Most of the public data reported combined data between adults and children. The Indonesian Pediatric Society (IPS) was involved in the COVID-19 response, especially in the area of child health. One of IPS's activities is collecting data registries from each of their chapters to provide a better understanding of COVID-19 in children. Objective: The objective of this study was to share the data of suspected and confirmed COVID-19 cases in children from IPS's COVID-19 data registry. Method: This is a retrospective study from the IPS's COVID-19 registry data. We collected the data of COVID-19 in children during March to December 2020 from each of the IPS chapters. We analyzed the prevalence, case fatality rate (CFR), age groups, diagnosis, and comorbidities of the children diagnosed with COVID-19. Result: As of December 21, 2020, there were 35,506 suspected cases of children with COVID-19. In total, there were 522 deaths, with a case fatality ratio (CFR) of 1.4. There were 37,706 confirmed cases with 175 fatalities (CFR 0.46). The highest mortality in confirmed COVID-19 cases was from children ages 10-18 years (42 out of 159 cases: 26%). The most common comorbidity and diagnosis found were malignancy (17.3%) and respiratory failure (54.5%). Conclusion: The CFR of confirmed COVID-19 cases in children in Indonesia is high and should be a major public concern.

Comparison of two lipid emulsions on interleukin-1ß, interleukin-8 and fatty acid composition in infants post gastrointestinal surgery: a randomized trial.

Background: Nutritional support plays an essential role for recovery in infants who undergo gastrointestinal surgery. The current standard type of intravenous lipid emulsion (IVLE) used as parenteral nutrition is the mixture of medium-chain triglyceride (MCT) and long chain triglyceride (LCT) rich in ω-6. Studies showed that ω-6 is associated with higher level of proinflammatory cytokines, leading to increased mortality rate, morbidity rate, and postoperative recovery time. The latest generation of emulsion is a mixture of MCT, LCT, olive oil (OO), and fish oil (FO) which may optimize the ω6/ω3 ratio. This study aimed to compare the effect of MCT/LCT/OO/FO IVLE to standard IVLE on IL-1ß, IL-8 and serum fatty acids in infants who had undergone gastrointestinal surgery. Methods: A single-blind, randomised controlled, pretest-posttest design study was done in twelve subjects that were classified into two groups. Group 1 received standard IVLE, group 2 received MCT/LCT/OO/FO IVLE. The type of standard and MCT/LCT/OO/FO IVLE used in this study were Lipofundin 20% and SMOFlipid 20%, respectively, both administered for three consecutive days in 1-4 gram/kilogram/day. IL-1ß and IL-8 were examined using ELISA while fatty acids was analyzed using gas chromatography tandem mass spectrometry (GC-MS). Statistical analyses were performed using SPSS for Mac 23. Results: No statistical difference was found in age, gender, birth weight and diagnosis between both groups. Leukocyte was significantly lower in MCT/LCT/OO/FO group 3 days after surgery (p=0.025). CRP was lower in MCT/LCT/OO/FO group 3 days after surgery (p=0.01) and in changes within 3 days (p=0.016). There were no differences in IL-1ß, IL-8 and ω-3 but ω-6 was higher in standard IVFE group on third day after surgery (p=0,048) Conclusion: MCT/LCT/OO/FO IVLE can significantly lower leukocyte, CRP and ω-6 levels and is comparable with standard IVLE on IL-1ß, IL-8 and ω-3 levels in infants who had undergone gastrointestinal surgery.