Relationship between age and the histopathological features to chemotherapy response in colorectal cancer patients: a prospective observational study

Introduction: Chemotherapy response in early age-onset colorectal cancer patients is still controversial, and the results of chemotherapy response are unknown. Therefore, the purpose of this study is to determine the relationship between the age of colorectal cancer patients and histopathological features and chemotherapy response. Methods: This is a prospective observational study. The subjects in this study were colorectal cancer patients in the Digestive Surgery division at Tertiary Hospital in West Java from September 2021 to September 2022. Results: There were 86 subjects who underwent chemotherapy in accordance with the inclusion and exclusion criteria. Consisting of 39 patients of early age onset and 44 female patients. The most common histopathological feature in early age onset (EAO) and late age onset (LAO) was adenocarcinoma (25% and 46%, respectively). Stage III colorectal cancer affected 38 patients, while stage IV affected 48 patients. There was a significant relationship between early age onset and late age onset with histological features (p < 0.001). The patients with the highest chemotherapy response had stable diseases in EAO (17 patients) and LAO (20 patients). There was no statistically significant relationship between age, histological features, and stage of colorectal cancer and chemotherapy response (p > 0.05). The results of the ordinal logistic regression test showed no systematic relationship between chemotherapy response and age, histopathological features, gender, or cancer stage (p > 0.05). Conclusion: There was no association between age and histopathologic features with chemotherapy response and there is no difference in chemotherapy response between early and late age onset. (AU)

Identification of KRAS mutation and HER2 expression in Indonesian colorectal cancer population: a cross-sectional study.

In Indonesia, colorectal cancer is the third most common type. In 2008, Indonesia ranked fourth in the Association of Southeast Asian Nations (ASEAN) countries, with an incidence rate of 17.2 per 100 000 population. This figure is predicted to continue to increase from year to year. In 30% of colorectal cancer patients diagnosed after metastases, some patients will develop metastases after undergoing surgical resection of the primary tumor. The survival of metastatic colorectal cancer patients has improved significantly in the last 20 years with the introduction of target-oriented drugs, anti-epidermal growth factor receptor (EGFR), and anti-human epidermal growth factor receptor-2 (HER2). This study aims to assess the relationship between Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation and HER2 expression for targeted therapy implementation. Patients and methods: This research is a cross-sectional study. The research subjects in this study were colorectal cancer patients in the digestive surgery division. There were 58 study subjects. Examination of KRAS mutations was carried out by PCR on fresh tumor tissue obtained from surgery or colonoscopy. Meanwhile, the HER2 examination used the immunohistochemistry method of paraffin blocks for anatomical pathology examination. Results: Examination of KRAS mutations showed 28/58 (43.8%) patients with colorectal cancer, while HER2 overexpression was found in 6/58 (10.3%) patients with colorectal cancer. Univariate analysis of KRAS mutations and HER2 expression showed that four subjects with KRAS mutations had excess HER2 expression (P=0.341). Conclusion: There is no association between KRAS mutations and HER2 overexpression in colorectal cancer patients.

Different Clinicopathological Characteristics in Indonesian Colorectal Patients with NRAS Mutations and HER2 Over-Expression.

OBJECTIVE: This study aims to assess the association of subject characteristics and NRAS mutations with HER2 expression in CRC. METHODS: This research is a cross-sectional study. The research subjects in this study were colorectal cancer patients in the Digestive Surgery division at Dr. Hasan Sadikin Hospital. There were 58 study subjects. Examination of NRAS mutations was carried out by Polymerase Chain Reaction (PCR) from fresh tumour tissue obtained from surgery or colonoscopy. Meanwhile, HER2 examination used the Immunohistochemistry (IHC) method of paraffin blocks for anatomical pathology examination of the same patients. RESULT: HER2 overexpression was found in 6/58 (10.3%) patients with CRC, and from 8 subjects with NRAS mutations, only 1 subject (1.7%) showed overexpression of HER2. Univariate analysis of HER2 expression showed no significant associations to age, sex, histologic feature, tumor location, and NRAS mutations. A significant association was found between HER2 expression and stage of the CRC with p=0.001. CONCLUSION: There is no association between NRAS mutations and HER2 overexpression in colorectal cancer patients.

The Omicron variant of concern: The genomics, diagnostics, and clinical characteristics in children.

Since WHO announced the COVID-19 pandemic in March 2020, SARS-CoV-2 has undergone several mutations, with the most recent variant first identified in South Africa in November 2021, the SARS-CoV-2 variant of concern (VOC B.1.1.529) named by WHO as Omicron. To date, it has undergone more mutations compared to previous SARS-CoV-2 variants, particularly, in the S gene that encodes the spike protein, which can cause S gene target failure in some PCR kits. Since its discovery, the Omicron variant has caused a sharp rise in COVID-19 cases worldwide and was responsible for a record of 15 million new COVID-19 cases reported globally in a single week, although this may be an underestimate. Since January 2022, Omicron subvariants with variable genetic characteristics, BA.1, BA.1.1, BA.2, BA.3, BA.4, BA.5, and BA.2.12.2 have been identified, with several countries reporting BA.1.1 was the major subvariant (27.42%), followed by BA.2 (25.19%). At the begining of May 2022, BA.2.12.1 mostly (42%) was detected in the United States. Like adults, the clinical manifestations of the Omicron variant in children are similar to the previous variants consisting of fever, cough, vomiting, breathing difficulties, and diarrhea, with some reports on croup-like symptoms and seizures. Though it presents apparently milder disease than the Delta variant, it is significantly more contagious and has caused more hospitalizations, especially in unvaccinated children younger than 5 years and unvaccinated or incompletely vaccinated adults. However, there is insufficient evidence yet to distinguish the Omicron variant from the other variants based solely on the clinical manifestations, therefore, this review presents a brief literature review of the most current evidence and data related to Omicron.

Brain MRI Volumetry Analysis in an Indonesian Family of SCA 3 Patients: A Case-Based Study.

Introduction: Spinocerebellar ataxia type-3 (SCA3) is an adult-onset autosomal dominant neurodegenerative disease. It is caused by expanding of CAG repeat in ATXN3 gene that later on would affect brain structures. This brain changes could be evaluated using brain MRI volumetric. However, findings across published brain volumetric studies have been inconsistent. Here, we report MRI brain volumetric analysis in a family of SCA 3 patients, which included pre-symptomatic and symptomatic patients. Methodology: The study included affected and unaffected members from a large six-generation family of SCA 3, genetically confirmed using PolyQ/CAG repeat expansion analysis, Sanger sequencing, and PCR. Clinical evaluation was performed using Scale for the Assessment and Rating of Ataxia (SARA). Subjects' brains were scanned using 3.0-T MRI with a 3D T1 BRAVO sequence. Evaluations were performed by 2 independent neuroradiologists. An automated volumetric analysis was performed using FreeSurfer and CERES (for the cerebellum). Result: We evaluated 7 subjects from this SCA3 family, including 3 subjects with SCA3 and 4 unaffected subjects. The volumetric evaluation revealed smaller brain volumes (p < 0.05) in the corpus callosum, cerebellar volume of lobules I-II, lobule IV, lobule VIIB and lobule IX; and in cerebellar gray matter volume of lobule IV, and VIIIA; in the pathologic/expanded CAG repeat group (SCA3). Conclusion: Brain MRI volumetry of SCA3 subjects showed smaller brain volumes in multiple brain regions including the corpus callosum and gray matter volumes of several cerebellar lobules.

The incidence and mortality of childhood acute lymphoblastic leukemia in Indonesia: A systematic review and meta-analysis.

BACKGROUND: The incidence of childhood ALL in Indonesia is still largely unknown. The widely mentioned statistics from other countries turn out to be only estimated figures. Other data do not specify the types of leukemia and are not specifically focused on children. Therefore, this study aims to pool incidence and mortality statistics from available studies in Indonesia. METHODS: We searched five different academic databases, including Pubmed, MEDLINE, Cochrane Library, Science Direct, and Google Scholar. Three Indonesian databases, such as the Indonesian Scientific Journal Database (ISJD), Neliti, and Indonesia One Search, were also utilized. Incidence was expressed as per 100,000 children. We used the Newcastle-Ottawa scale (NOS) to assess the quality of cohort studies. The inclusion criteria are cohort studies published in the languages of English or Indonesian. For this analysis, we define children as 0-18 years old. FINDINGS: The incidence rate for childhood ALL was found to be 4.32 per 100,000 children (95% CI 2.65-5.99) with a prediction interval of 1.98 to 9.42 per 100,000 children. The incidence rate is higher in males, with 2.45 per 100,000 children (95% CI 1.98-2.91) and a prediction interval of 1.90 to 3.16 per 100,000 children. As for females, the incidence rate is 2.05 per 100,000 children (95% CI 1.52-2.77) with a prediction interval of 1.52 to 2.77 per 100,000 children. The mortality of childhood ALL ranges from 0.44 to 5.3 deaths per 100,000 children, while the CFR is 3.58% with varying true effect sizes of 2.84% to 4.52%. INTERPRETATION: With 79.5 million children living in Indonesia in 2018, this means that there were roughly 3,434 new cases of childhood ALL. An organized effort between multiple sectors is needed to improve the registries of childhood ALL in Indonesia.

Polymorphisms of SLCO1B1 Gene in Sundanese Ethnic Population of Tuberculosis Patients in Indonesia.

BACKGROUND: The blood level of rifampicin, one of the tuberculosis (TB) drugs, depends on the organic anion transporting polypeptide 1B1 (OATP1B1) in hepatocytes. This protein is encoded by the solute carrier organic anion 1B1 (SLCO1B1) gene. Its genetic variation has been reported to have an impact on clinical outcomes and drug efficacy. However, the polymorphism in the SLCO1B1 gene has not been examined in Indonesia yet. We aimed to identify the frequency of polymorphism in SLCO1B1 gene among pulmonary TB patients in Bandung, Indonesia. METHODS: Cross-sectional study was conducted in West Java. 145 pulmonary TB patients who were treated with first-line drugs treatment (including rifampicin 450 mg daily) were analyzed for polymorphism in SLCO1B1 gene. Patients aged between 18-64 years old and mainly came from Sundanese ethnic group (92.4%). Genetic variants were detected using Polymerase Chain Reaction (PCR) and Sanger sequencing. RESULTS: Polymorphism of c.463C>A(rs11045819) was not identified, while heterozygous and homozygous polymorphism of c.85-7793C>T(rs4149032) were identified in 74 (51.0%) and 56 (38.6%) patients, respectively. The minor allele frequency (MAF) of T (mutant) allele of c.85-7793C>T(rs4149032) was 64.13% (186/209), higher than in the general population, which the MAF of rs4149032 is 53.6% based on 1000 genome database. CONCLUSION: This study highlights the presence of different allele frequencies of polymorphisms within the population, which might affect treatment outcomes.

Extended family thalassemia screening as a feasible alternative method to be implemented in identifying carriers in West Java, Indonesia.

The thalassemia screening program in Indonesia mostly conducted sporadically. Ideal prospective screening is still limited. This study aimed to compare thalassemia screening methods using the extended family approach with and without a history of severe thalassemia and the feasibility of implementing extended family screening method. A case control study was conducted in Dr. Hasan Sadikin General Hospital Bandung with 3 generations of extended families. Data were collected from 150 subjects of 8 extended families with severe thalassemia as an index case entry and 151 subjects of 12 families with no history of thalassemia. All subjects were examined for Hb, MCV, MCH, and peripheral blood smear (PBS) as initial laboratory examinations. Subjects with MCV < 80 fL, MCH < 27 pg, and suggestive findings on PBS continued hemoglobin analysis. Carrier status was determined by definition. All subjects consented to undergo screening and voluntarily participated. The proportion of thalassemia carriers and the participation rate between the 2 groups were compared. Sixty-four of 150 (42.7%) and 16 of 151 (10.6%) carriers were identified in both the case and control group (p < 0.001). The participation rate was 42-88 vs. 23-100% (p = 0.244). The mean age was 31.9 ± 21.2 vs. 31.1 ± 20.8 years (p = 0.782). The median family size was 28.5 vs. 20 subjects per family (p = 0.245). The types of identified thalassemia carrier in both groups consisted of ß-thalassemia, ß-thalassemia/HbE, suspected α-thalassemia, and ß-thalassemia Hb variant. All carriers continued the counseling process. The extended family method seems feasible to be implemented for thalassemia screening in West Java, Indonesia.

The Somatic Mutation Paradigm in Congenital Malformations: Hirschsprung Disease as a Model.

Patients with Hirschsprung disease (HSCR) do not always receive a genetic diagnosis after routine screening in clinical practice. One of the reasons for this could be that the causal mutation is not present in the cell types that are usually tested-whole blood, dermal fibroblasts or saliva-but is only in the affected tissue. Such mutations are called somatic, and can occur in a given cell at any stage of development after conception. They will then be present in all subsequent daughter cells. Here, we investigated the presence of somatic mutations in HSCR patients. For this, whole-exome sequencing and copy number analysis were performed in DNA isolated from purified enteric neural crest cells (ENCCs) and blood or fibroblasts of the same patient. Variants identified were subsequently validated by Sanger sequencing. Several somatic variants were identified in all patients, but causative mutations for HSCR were not specifically identified in the ENCCs of these patients. Larger copy number variants were also not found to be specific to ENCCs. Therefore, we believe that somatic mutations are unlikely to be identified, if causative for HSCR. Here, we postulate various modes of development following the occurrence of a somatic mutation, to describe the challenges in detecting such mutations, and hypothesize how somatic mutations may contribute to 'missing heritability' in developmental defects.

Serum TNF-α Level as a Possible Predictor of Inhibitor Levels in Severe Hemophilia A.

BACKGROUND: The development of factor VIII (FVIII) inhibitor in patients with hemophilia A (PWHA) is a great challenge for hemophilia care. Both genetic and environmental factors led to complications in PWHA. The development of inhibitory antibodies is usually induced by the immune response. Tumor necrosis factor α (TNF-α), one of the cytokines, might contribute to its polymorphism. In this study, we investigated the clinical factors, level of serum TNF-α, and polymorphism of c.-308G > A TNF - α gene in inhibitor development in severe PWHA. METHODS: A cross-sectional study was conducted among all PWHA in West Java province. The clinical parameters, FVIII, FVIII inhibitor, and serum TNF-α level were assessed. The genotyping of -380G > A TNF-α gene polymorphism was performed using polymerase chain reaction and Sanger sequencing. RESULTS: Among the 258 PWHA, 216 (83.7%) were identified as severe PWHA. The FVIII inhibitor was identified in 90/216 (41.6%) of severe PWHA, consisting of 45 high-titer inhibitors (HTI) and 45 low-titer inhibitors (LTI). There was a significant correlation between serum TNF-α level and the development of HTI (p = 0.043). The cutoff point of serum TNF-α level, which can be used to differentiate between HTI and LTI, was 11.45 pg/mL. The frequency of FVIII replacement therapy was significant only in HTI of severe PWHA regarding serum TNF-α level (p = 0.028). There is no correlation between polymorphisms of -380G > A TNF-α gene and inhibitor development (p = 0.645). CONCLUSIONS: The prevalence of FVIII inhibitor in severe PWHA in West Java, Indonesia, was 41.6%. The frequency of replacement therapy is a risk factor for inhibitor development. Serum TNF-α level might be used to differentiate between high and low inhibitor levels in severe hemophilia A, and this might support decision making regarding treatment options for inhibitor in severe hemophilia A.

Clinical and genetic profile in index patients with spinocerebellar ataxia type 3 in Indonesia: case report.

Spinocerebellar ataxia (SCA) is an autosomal dominant hereditary disease with progressive course, and no causal therapy. Diagnostics are still challenging, due to facility and protocols, and so as in Indonesia. As a national referral center, Dr. Hasan Sadikin Central General Hospital has received a lot of patients from all over Indonesia, particularly from Western Java. Study related to SCA (including clinical and genetic profile) is still limited in Indonesia. We identified index patients from three families with ataxia, hence intend to determine their clinical and genetic pattern. The hereditary pattern is autosomal dominant. Scale for the assessment and rating of ataxia (SARA) shows mild and moderate ataxia. Inventory of non-ataxia signs (INAS) scores of the patients were 3, 5 and 6. Montreal cognitive assessment-Indonesian version (MOCA-INA) shows only one patient has mild cognitive impairment, despite young age. Barthel index shows 1 subject has moderate dependency. Mutation in Ataxin3 polyQ repeats shows pathologically long CAG repeats, 72,10; 72,10; and 72,23 respectively in mutant and wild type allele. We diagnosed the index patients with spinocerebellar ataxia type 3. This study is the first case series study in Indonesia. The hereditary pattern is clearly shown as an autosomal dominant ataxia. The clinical and genetic profile was varied, and the symptom is progressive and deteriorates overtime, including wide based gait, speech problem, motor and sensor complaint, and cognitive decline complaint. Despite the same polyQ stretch length, the onset and clinical characteristics of patients are diverse.

Iron Status in Newly Diagnosed ß-Thalassemia Major: High Rate of Iron Status due to Erythropoiesis Drive.

BACKGROUND: Iron overload in severe ß-thalassemia is a serious complication that occurs during the course of the disease. Information about the iron status during initial illness with ß-thalassemia major seemed to be limited. This study is aimed at analyzing iron status, serum hepcidin, and growth differentiation factor 15 (GDF15) levels in newly diagnosed ß-thalassemia major. METHODS: A case-control study was performed at Dr. Hasan Sadikin General Hospital, which included 41 children with newly diagnosed ß-thalassemia major. Age- and sex-matched controls were enrolled. The subjects had no blood transfusion, had normal liver function, and had no sign of inflammation. The groups were compared in terms of the levels of hemoglobin (Hb), serum ferritin (SF), transferrin saturation (TS), serum hepcidin, and GDF15 as iron homeostasis parameters. RESULTS: Of the 41 newly diagnosed ß-thalassemia major patients, those who were less than 24 months old had significantly lower median Hb levels than controls (5.0 vs. 11.7 g/dL, P < 0.001). The median SF and TS levels were significantly higher than those in controls (315.0 vs. 29.0 ng/mL, P < 0.001; 70.6 vs. 16.5%, P < 0.001), and median hepcidin was at the normal limit, but the value was higher in patients (251.0 vs. 123.1 ng/mL, P < 0.001). The median GDF15 level was significantly higher in patients (2,095.3 vs. 342.4 pg/mL, P < 0.001). There was a positive correlation between SF-TS, SF-hepcidin, TS-hepcidin, SF-GDF15, TS-GDF15, and hepcidin-GDF15 (P < 0.001). CONCLUSION: In newly diagnosed ß-thalassemia major, an increase in iron status occurred. This may be caused by increased iron absorption due to massive erythropoietic activity, characterized by an increase in GDF15 levels, which does not cause hepcidin suppression. The iron homeostasis response seems to be physiologically indicated by a tendency to increase hepcidin levels.

The level of transforming growth factor-ß as a possible predictor of cyclophosphamide response in children with steroid-resistant nephrotic syndrome.

BACKGROUND: Steroid-resistant nephrotic syndrome (SRNS) is a burden in the country due to the progressive severity of chronic kidney disease (CKD). Calcineurin inhibitors (CNIs) or monoclonal antibodies are currently recommended for the treatment of this disease. In developing countries, steroid and cyclophosphamide (CPA) are available drugs used during the treatment. This study aims to provide a non-invasive modality that can be used to predict the response of SRNS children to CPA therapy. Subsequently, the proteinuria duration was shortened to reduce the risk of glomerular damage. The present study aims to determine whether there is a correlation between baseline serum TGFB and proteinuria in SRNS children six months after receiving CPA treatment. The author hypothesized that there would be a negative correlation between those variables. METHOD: A prospective-cohort-study was conducted at Hasan Sadikin General Hospital Bandung, Indonesia. A total of 88 SRNS children, aged 1 to 18 were accessed for serum TGF-ß level before receiving CPA therapy for six months, and clinical signs were observed. Furthermore, after six months of CPA treatment, the subjects were divided into CPA responder and non-responder based on the presence of proteinuria, then the data were analyzed using multiple logistic regression to adjust age and gender. RESULTS: There was a statistically significant relationship between TGF-ß and the risk of non-response to CPA therapy, after accounting for age, gender, baseline GFR, baseline ureum, and baseline urinary protein, the adjusted-OR was 1.051 (95% CI 1.007, 1.097, p = 0.022). CONCLUSION: The high level of serum TGF-ß obtained prior to CPA administration are reliable data for estimating adverse results on CPA therapy. Based on these results, a high baseline TGF-ß level correlates with the poor response of CPA therapy.

The association of rs187238, rs19465518 and rs1946519 IL-8 polymorphisms with acute kidney injury in preterm infants.

BACKGROUND: Interleukin 18 (IL-18) promoter polymorphisms (-656G > T, -607C > A, and -137G > C) affect serum IL- 18 (sIL-18) levels and are associated with renal injury. PURPOSE: This study aimed to determine the diagnostic utility of sIL-18 and urine IL-18 (uIL-18) as biomarkers for acute kidney injury (AKI) and analyse the association of IL-18 polymorphisms to AKI in preterm infants. METHODS: Blood and urine samples were collected from 56 preterm infants with AKI and 56 without AKI to measure serum creatinine (SCr), sIL-18, and uIL-18. Genotyping of polymorphisms was performed and analysed, with AUC-ROCs analysis used to evaluate the diagnostic utility of s-/uIL-18 levels. RESULTS: The median sIL-18 and uIL-18 levels were significantly higher than those without AKI. For a cutoff of >132 pg/mL, the sIL-18 expression had sensitivity and specificity of 80.36% and 60.71%, respectively, while for uIL-18, a cutoff of >900.7 pg/mL had sensitivity and specificity of 51.79% and 78.57%, respectively. The odds ratio of sIL-18 and uIL-18 to predict AKI in preterm infants was 5.89 (95%CI:2.31-15.02) and 4.15 (95%CI:1.58-10.89), respectively. The polymorphisms -137G > C and -656G > T were significantly associated with sIL-18 expression. CONCLUSION: Serum and urine IL-18 levels are risk factors for and a moderate predictor of AKI in preterm infants.

Potential role of ACE2-related microRNAs in COVID-19-associated nephropathy.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is responsible for coronavirus disease (COVID-19), potentially have severe kidney adverse effects. This organ expressed angiotensin-converting enzyme 2 (ACE2), the transmembrane protein which facilitate the entering of the virus into the cell. Therefore, early detection of the kidney manifestations of COVID-19 is crucial. Previous studies showed ACE2 role in various indications of this disease, especially in kidney effects. The MicroRNAs (miRNAs) in this organ affected ACE2 expression. Therefore, this review aims at summarizing the literature of a novel miRNA-based therapy and its potential applications in COVID-19-associated nephropathy. Furthermore, previous studies were analyzed for the kidney manifestations of COVID-19 and the miRNAs role that were published on the online databases, namely MEDLINE (PubMed) and Scopus. Several miRNAs, particularly miR-18 (which was upregulated in nephropathy), played a crucial role in ACE2 expression. Therefore, the antimiR-18 roles were summarized in various primate models that aided in developing the therapy for ACE2 related diseases.

Bi-allelic Variations of SMO in Humans Cause a Broad Spectrum of Developmental Anomalies Due to Abnormal Hedgehog Signaling.

The evolutionarily conserved hedgehog (Hh) pathway is essential for organogenesis and plays critical roles in postnatal tissue maintenance and renewal. A unique feature of the vertebrate Hh pathway is that signal transduction requires the primary cilium (PC) where major pathway components are dynamically enriched. These factors include smoothened (SMO) and patched, which constitute the core reception system for sonic hedgehog (SHH) as well as GLI transcription factors, the key mediators of the pathway. Here, we report bi-allelic loss-of-function variations in SMO in seven individuals from five independent families; these variations cause a wide phenotypic spectrum of developmental anomalies affecting the brain (hypothalamic hamartoma and microcephaly), heart (atrioventricular septal defect), skeleton (postaxial polydactyly, narrow chest, and shortening of long bones), and enteric nervous system (aganglionosis). Cells derived from affected individuals showed normal ciliogenesis but severely altered Hh-signal transduction as a result of either altered PC trafficking or abnormal activation of the pathway downstream of SMO. In addition, Hh-independent GLI2 accumulation at the PC tip in cells from the affected individuals suggests a potential function of SMO in regulating basal ciliary trafficking of GLI2 when the pathway is off. Thus, loss of SMO function results in abnormal PC dynamics of key components of the Hh signaling pathway and leads to a large continuum of malformations in humans.

Time to Start Delivering Iron Chelation Therapy in Newly Diagnosed Severe ß-Thalassemia.

BACKGROUND: Iron overload is still a major complication of severe ß-thalassemia. Indication to start iron chelation therapy is based on serum ferritin (SF) or transferrin saturation (TS) level or the amount of transfusion. The goal of this study is to analyse the pattern of iron status, the amount of transfusion regarding the time to start iron chelator, and serum hepcidin levels in newly diagnosed severe ß-thalassemia. METHODS: A prospective cohort study was performed at Hasan Sadikin General Hospital on newly diagnosed severe ß-thalassemia patients. Subjects had not received any blood transfusion with normal liver function test, CRP, and IL-6 levels who consumed normal diet according to age. The SF and TS levels indicate iron status, while hepcidin level indicates iron regulator status. Main indicator to start iron chelation therapy when SF level ≥1.000 ng/mL, TS level ≥70%, or after receiving transfusion at least 10 times. Statistical analysis used Mann-Whitney and Spearman. RESULTS: Forty-two newly severe ß-thalassemia, 30 (71.4%), were diagnosed before 1 year old, mean 9.9 ± 6.4 months, range 2-24 months. Range amount of transfusion until SF level reached ≥1,000 ng/mL were 4-12 times, mean 7 ± 2 times. Mean SF and TS level at diagnosis were 365.6 ± 194.9 ng/mL and 67.3 ± 22.5%, while hepcidin level was normal, mean 242.6 ± 58 ng/mL. 36/42 patients have reached SF >1000 ng/mL with amount of transfusion less than 10 times. There was no significant difference of SF, TS, and hepcidin levels when SF >1000 ng/mL in the group with amount of transfusion 7-12 and less than 7 (p = 0.454, p = 0.084, p = 0.765), respectively. A significant positive correlation between SF and amount of transfusion was observed (p < 0.001; r = 0.781). CONCLUSION: Iron overload in severe ß-thalassemia patients might occur earlier even before they received 10 times transfusion. Hepcidin serum level tends to increase when iron overload just started.

G6PD genetic variations in neonatal Hyperbilirubinemia in Indonesian Deutromalay population.

BACKGROUND: Neonatal jaundice is a common finding in newborns in Asia, including Indonesia. In some cases, the serum total bilirubin levels exceeds the 95th percentile for hours of life (neonatal hyperbilirubinemia). Severe neonatal hyperbilirubinemia (NH) could lead to kernicterus and neonatal death. Glucose-6-Phosphage Dehydrogenase (G6PD) genetic variations and deficiency have been reported in several studies to be associated with NH. This study aimed to analyze the G6PD genetic variations and its activity in neonates with and without hyperbilirubinemia in the Deutromalay Indonesian population. METHODS: Deoxyribose Nucleic Acid (DNA) was isolated from peripheral blood of 116 and 115 healthy term neonates with and without hyperbilirubinemia. All infants underwent the following laboratory examinations: routine hematologic evaluation, Coombs test, G6PD activity measurement using the Randox kit method, and serum total bilirubin level. All exons of the G6PD gene were targeted for deep sequencing using MiSeq (Illumina). An association study of G6PD polymorphisms with NH was performed using PLINK. RESULTS: The prevalence of G6PD deficiency in neonates with and without hyperbilirubinemia in Indonesian Deutromalay population were 1.72% (95% Confidence Interval (CI): 0.6-4.1%) and 1.74% (95% CI: 0.7-4.1%), respectively. The most common G6PD polymorphisms, i.e. rs1050757/c.* + 357A > G, rs2230037/c.1311C > T, and rs2071429/c.1365-13 T/IVS11, were identified. However, none of those polymorphisms and their haplotype were associated with NH (p > 0.05, Odds Ratio (OR) ~1.00). The prevalence of G6PD mutations in neonates with and without hyperbilirubinemia were 6.8% (95% CI: 2.3-11.5%) and 6.9% (95% CI: 2.3-11.6%), respectively. The most frequently identified G6PD mutation was the Viangchan variant (p.V291 M), which was followed by the Canton (p.R459L) and Vanua Lava (p.L128P) variants. Two novel mutations were identified both in case (p.V369A, p.I167F) and control (p.L474=, p.I36T) groups. CONCLUSION: The prevalence of G6PD deficiency is low in neonates with or without hyperbilirubinemia in Deutromalay Indonesian population. The majority of G6PD mutations identified among Indonesian Deutromalay population in this study are Viangchan, Canton and Vanua Lava variants.

Epidermal Growth Factor and Adenosine Triphosphate Induce Natrium Iodide Symporter Expression in Breast Cancer Cell Lines.

AIM: This study aims to investigate the effect of ATP, EGF and combination of those two to the Natrium Iodide Symporter (NIS) expression in MCF7, SKBR3 and HaCaT cell lines. METHODS: MCF7, SKBR3 and HaCaT cell lines were treated with ATP, EGF and combination of those two for 6, 12 and 24 hours. The expression of NIS mRNA was measured through quantitative-reverse transcription-polymerase chain reaction (qRT-PCR). The NIS protein expression was confirmed by immunocytofluorescence. RESULTS: NIS mRNA was expressed in SKBR3 and HaCaT cell lines but not in MCF7. The levels of NIS mRNA expression, after treatment by epidermal growth factor (EGF), adenosine Tri-Phosphate (ATP) or the combination of both for 6 and 12 hours were not significantly different from those of untreated cells. However, the treatment by a combination of ATP and EGF for 24 hours increases the level of NIS mRNA expression by 1.6 fold higher than that of the untreated cells (1.6241 ± 0.3, p < 0.05) and protein NIS expression increase significantly by the treatment than untreated cells (P < 0.05). CONCLUSION: The level of NIS expression varies among the different subtypes of breast cancer cell lines. MCF7 cell line is representing the luminal A subtype of breast cancer does not express NIS. Only SKBR3 cell line express NIS and this subtype might be suitable to receive radioiodine therapy as those cells expressing NIS. A combination treatment of EGF and ATP increases the expression of NIS mRNA and protein at the membrane in SKBR3 cells.

Association of first trimester maternal vitamin D, ferritin and hemoglobin level with third trimester fetal biometry: result from cohort study on vitamin D status and its impact during pregnancy and childhood in Indonesia.

INTRODUCTION: The role of vitamin D in placental functions and fetal growth had been addressed in many reports with conflicting results. However, such report is limited for Indonesian population. The aim of this study was to explore the association between maternal vitamin D level in the first trimester and fetal biometry in the later stage of pregnancy with adjusted OR for other determinants like hemoglobin and ferritin level. METHODS: From July 2016 a prospective cohort study of pregnant women had begun in four cities in West Java, Indonesia. Data on maternal vitamin D, ferritin, hemoglobin level, maternal demography and fetal biometry were analyzed with linear regression. RESULTS: Among 203 recruited women, 195 (96.06%) had hypovitaminosis D. One hundred fifty two (75%) were in deficient state and 43 women (21%) were in insufficient state. Women with insufficient vitamin D had the highest proportion of anemia, while women with normal vitamin D level had the highest proportion of low ferritin level. Maternal serum vitamin D showed significant associations with biparietal diameter (ß = 0.141, p = 0.042) and abdominal circumference (ß = 0.819, p = 0.001) after adjustment with maternal age, pre-pregnancy body mass index, parity, serum ferritin level, and hemoglobin level. CONCLUSION: Our study suggested that sufficient maternal vitamin D level was an important factor to improve fetal growth and development.