A Prognostic Model Based on XRCC1 Gene Polymorphisms and Clinicopathological Factors to Predict One-Year Survival of Advanced Epithelial Ovarian Cancer Patients

Prognosis of advanced stage epithelial ovarian cancer (EOC) patients remains poor due to recurrence and disease progression after surgery and chemotherapy. Polymorphism in the genes involved in DNA repair, i.e. x-ray repair cross complementing protein-1 (XRCC1) and XRCC3 could alter function, diminish repair kinetics and may play a role in tumor resistance to therapy. This study was aimed to predict the prognosis of advanced stage EOC patients based on the polymorphism of XRCC1 and XRCC3 genes and the clinicopathology. This was an ambispective cohort study in EOC patients treated in Fatmawati General Central Hospital and its network hospitals in Jakarta between 2011 and 2016. Demographic data and clinicopathology was obtained from the medical record. Polymorphisms of XRCC1 and XRCC3 genes were detected by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Survival analyses were performed using the Kaplan-Meier curve and Cox proportional hazard test. Multivariate analyses were performed to obtain prediction model for 1-year survival. Scoring system was developed and tested using the receiver operating characteristic (ROC) curve analyses. A total of 129 eligible cases were included. Patients’ mean age was 49.6 years. Most patients (93.8%) were having stage III disease. Mortality at 1-year was associated with three independent variables, i.e. histopathology subtype, residual tumor > 1 cm, and XRCC1 gene Arg399Gln polymorphisms (Arg/Gln or Gln/Gln alleles). These prediction models gave 85.3% accuracy by ROC curve analysis and 82.7% posttest probability. Prognosis of advanced stage EOC patients can be predicted from several clinicopathological factors and XRCC1 gene polymorphisms. Validation study is needed to confirm these findings

Clinical features of patients with hemolytic anemia due to red blood cells membrane defect

Background Hemolytic anemia may result from corpuscular or extracorpuscular abnormalities. One of the types of corpuscular abnormalities is membrane defect. The diagnosis is sometimes difficult and it may need special hematologic investigations. There are no data yet on the clinical features of red blood cell membrane defect in Cipto Mangunkusumo Hospital. Objective To evaluate the clinical features and laboratory find- ings of patients with hemolytic anemia due to red blood cells mem- brane defect in Cipto Mangunkusumo Hospital. Methods This was a descriptive study on patients with red blood cells membrane defect who came to the Thalassemia Center at Cipto Mangunkusumo Hospital during 2002-2004. Results In 2002-2004, there were 241 new cases of hemolytic anemia consisted of 116 patients with beta-thalassemia, 109 with HbE-beta thalassemia, 3 with alpha-thalassemia, and 13 with red blood cells membrane defect. The red cells membrane defect pa- tients consisted of 4 males and 9 females, ranging in age from 1 months to 14 years. All subjects came to the hospital due to pale- ness as a chief compaint. Hepato-splenomegaly was found in 5 of 13 cases. Laboratory findings revealed hemoglobin level 6.4-13.1 g/dl (mean 9.4+2.1 g/dl), MCV 58.4-94.5 fl (mean 81.2+10.2 fl), MCHC 31.7-35.8 g/dl (mean 33.9+1.1g/dl), RDW 15.8-28.4% (mean 20.1+3.6%) and normal hemoglobin electrophoresis. Pe- ripheral blood smear showed anisocytosis, poikilocytosis, spherocytes, ovalocytes, stomatocytes, target cells, and fragmented cells. The most common diagnosis in this group was Southeast Asian Ovalocytosis (5/13). Conclusions In facing hemolytic anemia with normal Hb electro- phoresis or normal RBC enzyme level, the possibility of red cells membrane defect should be taken into consideration as a cause of this disorder. The clinical features and laboratory findings of red blood cells membrane defect patients are highly variable. Occa- sionally, hematologic investigations are necessar

Applicability of a clinical scoring criteria for disease severity of ß-thalassemia/hemoglobin E in Indonesia

Background: β-thalassemia/HbE presents with a variety of clinical symptoms, from asymptomatic to severe, requiring routine transfusion. However, there is currently no agreed classification system to stratify patients based on clinical severity of β-thalassemia/HbE in the Indonesian population. Thailand has already established a classification system, and this study aimed to identify the applicability of the Thailand clinical scoring criteria to determine the severity of β-thalassemia/HbE in the Indonesian population. Methods: This descriptive study was conducted by evaluating patients with β-thalassemia/HbE, who were classified into mild, moderate, or severe groups based on the Thailand clinical scoring criteria. Results: A total of 293 subjects with β-thalassemia/HbE were included. Based on this clinical scoring criteria, it was found that only 21.5% of patients were classified as mild, and the remaining 35.5% and 44% were classified as moderate and severe respectively. Approximately 68.2% of the subjects in the severe group received transfusion at <4 years old, while only 10% of those in the mild group were transfused at the same age. In the mild group, only 10% of the subjects underwent routine transfusion, compared to 98.4% of the subjects in the severe group. In addition, only 27% of the subjects in the mild group showed stunted growth, while that in the moderate and severe groups were 54.5% and 86.8%, respectively. Conclusion: Thailand clinical scoring criteria is able to determine the severity of Indonesia thalassemia patient which needs further management, i.e. transfusion and observation of stunted growth. This scoring system will help provide the provision of the most ideal management for the groups of patients based on their requirements

Phenotype and genotype characteristics of Indonesian 21-hydroxylase deficient patients

Background Congenital adrenal hyperplasia (CAH) is the most common cause of ambiguous genitalia in children and 90-95% cases show 21-hydroxylase deficiency. More than 100 mutations have been described and of these, four mutations have been frequently reported in Asia. Those mutations are deletion/large gene conversion (LGC), intron2 splice mutation (I2 splice), point mutations at codon 172 (I172N) and codon 356 (R356W). Genotyping is very valuable since close correlation observed between genotype and phenotype. Objective To identify phenotype and genotype characteristics of CAH due to 21-hydroxylase deficiency (CAH-21OH) and correlation between them. Methods From June to November 2006 we analyzed 37 confirmed CAH-21OH patients treated at the Department of Child Health, Cipto Mangunkusumo Hospital during the period of 1990-2006. Polymerase chain reaction (PCR) followed by restriction fragment length polymorphism (RFLP) analysis or amplification-created restriction site (ACRS) were performed. We first identified deletion/ LGC and I172N mutation that had been mostly reported in salt wasting (SW) and simple virilizing (SV) form patients respectively. Results There were 37 patients, consisted of 6 males and 31 females with the ratio 1:5.2. Of those, 25, 10, 2 patients were SW, SV and non-classic (NC) form, respectively. PCR-RFLP or ACRS was performed to detect two mutations in 32 patients (64 alleles). Deletion/LGC was found in 6 alleles while I172N mutations in two. All deletion alleles showed SW phenotype but I172 mutated alleles showed SW and SV phenotype. Conclusion There is a consistent close association between genotype and phenotype in our CAH-21OH patients

Iron Absorption in Iron-Deficient Women, Who Received 65 mg Fe with an Indonesian Breakfast, Is Much Better from NaFe(III)EDTA than from Fe(II)SO4, with an Acceptable Increase of Plasma NTBI. A Randomized Clinical Trial

Plasma non-transferrin-bound iron (NTBI) is potentially harmful due to the generation of free radicals that cause tissue damage in vascular and other diseases. Studies in iron-replete and iron-deficient subjects, receiving a single oral test dose of Fe(II)SO4 or NaFe(III)EDTA with water, revealed that FeSO4 was well absorbed when compared with NaFeEDTA, while only the Fe(II) compound showed a remarkable increase of NTBI. As NaFeEDTA is successfully used for food fortification, a double-blind randomized cross-over trial was conducted in 11 healthy women with uncomplicated iron deficiency. All subjects received a placebo, 6.5 mg FeSO4, 65 mg FeSO4, 6.5 mg NaFeEDTA, and 65 mg NaFeEDTA with a traditional Indonesian breakfast in one-week intervals. Blood tests were carried out every 60 min for five hours. NTBI detection was performed using the fluorescein-labeled apotransferrin method. Plasma iron values were highly increased after 65 mg NaFeEDTA, twice as high as after FeSO4. A similar pattern was seen for NTBI. After 6.5 mg of NaFeEDTA and FeSO4, NTBI was hardly detectable. NaFeEDTA was highly effective for the treatment of iron deficiency if given with a meal, inhibiting the formation of nonabsorbable Fe-complexes, while NTBI did not exceed the range of normal values for iron-replete subjects