Factors Associated with All-Cause 30-Day Mortality in Indonesian Inpatient COVID-19 Patients at Cipto Mangunkusumo National General Hospital.

Introduction: Indonesia, as a developing country, has limited data on the factors associated with 30-day mortality in COVID-19 patients in Indonesia. As a matter of fact, study analyzing factors associated with 30-day mortality of COVID-19 infection in Indonesia has never been conducted. This study aims to fill this gap in the literature by conducting a large-scale analysis of factors associated with 30-day mortality in COVID-19 patients in Indonesia. Method: This study employed a single-center retrospective cohort observational design, and was conducted at Cipto Mangunkusumo National General Hospital between the years 2022 and 2023. Sampling was conducted using the consecutive sampling method. The study included patients aged 18 years and above who had been confirmed to have COVID-19 infection. Survival analysis was conducted using Kaplan-Meier and multivariate Cox regression analysis. Result: Our study included a total of 644 patients, with 120 patients (18.6%) expiring within 30 days. In the multivariate analysis using the backward Wald method, severe COVID-19 (HR: 7.024; 95% CI: 3.971-12.744; p value: <0.0001), moderate COVID-19 infection (HR: 1.660; 95% CI: 1.048-2.629; p value: 0.031), liver cirrhosis (HR: 3.422; 95% CI: 1.208-9.691; p value: 0.021), female sex (HR: 1.738; 95% CI: 1.187-2.545; p value: 0.004), old age (HR: 2.139; 95% CI: 1.279-3.577; p value: 0.004), high leukocyte (HR: 11.502; 95% CI: 1.523-86.874; p value: 0.018), high NLR (HR: 1.720; 95% CI: 1.049-2.819; p value: 0.032), high CRP (HR: 1.906; 95% CI: 1.092-3.329; p value: 0.023), high procalcitonin (HR: 3.281; 95% CI: 1.780-6.049; p value: 0.001), and high creatinine (HR: 1.863; 95% CI: 1.240-2.800; p value: 0.003) were associated with 30-day mortality from COVID-19 infection. Subgroup analysis excluding cancer patients showed that age, D-Dimer, CRP, and PCT were associated with 30-day mortality in COVID-19 patients, while steroid therapy is protective. Conclusions: This study finds that COVID-19 severity, liver cirrhosis, sex, age, leukocyte, NLR, CRP, creatinine, and procalcitonin were associated with COVID-19 mortality within 30 days. These findings underscore the multifactorial nature of COVID-19 infection mortality. It is important, therefore, that patients which exhibit these factors should be treated more aggressively to prevent mortality.

Expert consensus on the management of chronic lymphocytic leukaemia in Asia.

In recent years, considerable progress has been made in the standard treatment for chronic lymphocytic leukaemia (CLL) due to the availability of new potent drugs. However, the majority of data on CLL were derived from Western populations, with limited studies and guidelines on the management of CLL from an Asian population perspective. This consensus guideline aims to understand treatment challenges and suggest appropriate management approaches for CLL in the Asian population and other countries with a similar socio-economic profile. The following recommendations are based on a consensus by experts and an extensive literature review and contribute towards uniform patient care in Asia.

Immune cells markers within local tumor microenvironment are associated with EBV oncoprotein in nasopharyngeal cancer.

INTRODUCTION: EBV infection in nasopharyngeal cancer ensued in latent infection mode. In this latent infection various EBV oncoproteins such as EBNA1 and LMP1 was expressed. EBV oncoproteins could theoretically recruit immune cells, which might help to control cancer. Therefore, this study was aimed to elucidate the association with EBV oncoproteins (EBNA1 and LMP1), immune markers (CD4, CD8, and FOXP3) from nasopharyngeal cancer microenvironment with tumor progression. METHOD: Nasopharyngeal biopsy was obtained from patients suspected to have nasopharyngeal cancer. Those samples with microscopically confirmed nasopharyngeal cancer were tested for EBNA1, LMP1, CD4, CD8, and FOXP3 concentration with ELISA, then verified with IHC. Each patient tumor volume was assessed for primary nasopharyngeal tumor volume (GTVp) and neck nodal metastases tumor volume (GTVn). Correlation test with Spearman correlation and scatterplot were carried out. RESULT: Total 23 samples with nasopharyngeal cancer were analyzed. There was moderate correlation (ρ = 0.45; p value = 0.032) between LMP1 and GTVp. There was strong correlation (ρ = 0.81; p value < 0.001) between CD8 and GTVp. There was also moderate correlation (ρ = 0.6; p value = 0.002) between FOXP3 and GTVp. The CD8 concentration has moderate correlation with both EBNA1 (ρ = 0.46; p value = 0.026) and LMP1 (ρ = 0.47; p value = 0.023). While FOXP3 has moderate correlation with only LMP1 (ρ = 0.58; p value = 0.004). No correlation was found between all the markers tested here with GTVn. DISCUSSION: We found larger primary nasopharyngeal tumor was associated with higher CD8 marker. This was thought due to the presence of abundance CD8 T cells in the nasopharynx, but those abundance CD8 T cells were suspected to be dysfunctional. The nasopharyngeal cancer was also known to upregulate chemokines that could recruit T regulatory FOXP3 cells. Furthermore, T regulatory FOXP3 cells differentiation was induced through several pathways which was triggered by EBNA1. The correlation found in this study could guide further study to understand nasopharyngeal carcinogenesis and the relationship with our immune system.

COVID-19 in Patients with Transfusion Dependent Thalassemia (TDT) in Indonesia: Characteristics of the Disease and Patients, and Comparison between Epidemiological Data for COVID-19 and Thalassemia in Indonesia and Southeast Asia.

BACKGROUND: People living with transfusion dependent thalassemia have a high risk of becoming infected with COVID-19. This can be caused by both internal factors, namely the formation of alloantibodies and autoimmune disorder, and external factors such as routine visits for blood transfusions. Chronic complications of thalassemia also render them more vulnerable to infectious diseases, including COVID-19. However, anecdotal data shows that thalassemia patients experience less incidence of COVID-19 compared to the general population. PURPOSE: This study aims to find the correlation between COVID-19 in thalassemia-dependent transfusion patients in Indonesia and Southeast Asia. PATIENTS AND METHODS: This study used a cross-sectional design. The study was conducted at the Division of Hematology and Medical Oncology of the Cipto Mangunkusumo Hospital in Jakarta from May 2020-August 2021. The total sampling method was used involving all thalassemia major patients who had been infected with COVID-19 (obtained directly from medical record and through the thalassemia patients-parents foundation). RESULTS: From 10,397 patients with thalassemia, 67 (0.64%) people were infected by COVID-19 and 2 (2.9%) were deceased. Meanwhile, the incidence of COVID-19 in the general population of Indonesia was 0.87% (more than in the thalassemia population). This means that thalassemia might provide additional protection against COVID-19 due to several mechanisms. This phenomenon has also been seen in other countries with a high prevalence of thalassemia, wherein there are less COVID-19 cases despite the pandemic. On the contrary, countries with low rates of thalassemia had experienced deadly surges of the pandemic. CONCLUSION: Indonesia and other countries with a high prevalence of thalassemia have lower COVID-19 incidence than countries with low prevalence of thalassemia. Thalassemia might provide additional protection against COVID-19. Well-designed studies are needed to provide better evidence on the protective effect of thalassemia on COVID-19.

Achievement of Pre- and Post-Transfusion Hemoglobin Levels in Adult Transfusion-Dependent Beta Thalassemia: Associated Factors and Relationship to Reduction of Spleen Enlargement.

INTRODUCTION: The achievement of blood transfusion hemoglobin targets in transfusion-dependent beta-thalassemia patients is influenced by several factors such as genotype, hypersplenism, blood compatibility, donor blood adequacy, and transfusion interval. Failure to achieve these targets leads to an increase in the size of the spleen. Meanwhile, the post-transfusion hemoglobin of thalassemia patients that is not regularly evaluated has made it difficult to determine donor adequacy. Therefore, this study aims to determine the proportion of patients who achieve optimal pre- and post-transfusion hemoglobin levels, determine the factors involved, and the relationship between achieving hemoglobin levels with spleen enlargement in adult transfusion-dependent beta-thalassemia patients. METHODS: This retrospective cohort study was conducted using total sampling of adult thalassemia transfusion-dependent patients at Cipto Mangunkusumo Hospital. Data were obtained through medical records. RESULTS: A hundred and ten study subjects fulfilled inclusion criteria. The results showed that the blood transfusion deficit <30 mL/kg/year was associated with achieving pre- and post-transfusion hemoglobin targets (p = 0.008). Furthermore, there were significant differences between the groups that achieved the pre- and post-transfusion target hemoglobin levels on the reduction of spleen enlargement in centimeters (p < 0.001). However, thalassemia genotype, blood compatibility, and transfusion interval did not correlate with the achievement of pre- and post-transfusion hemoglobin. CONCLUSION: The achievement of pre- and post-transfusion hemoglobin levels in adult transfusion-dependent beta-thalassemia patients significantly reduced spleen enlargement and contributed to better patient outcomes.

Oxidative Stress (Malondialdehyde) in Adults Beta-Thalassemia Major and Intermedia: Comparison Between Before and After Blood Transfusion and Its Correlation with Iron Overload.

BACKGROUND: Iron overload is a major problem in both transfusion-dependent (TDT) and non-transfusion-dependent thalassemia (NTDT). It has been known to increase oxidative stress. Meanwhile, blood transfusion as main therapy for thalassemia increases iron overload. One of the markers of oxidative stress is malondialdehyde (MDA). This study aims to provide data on MDA levels in adult thalassemia patients, and to compare the levels before and after transfusion in patients with TDT and NTDT. METHODS: This is a cross-sectional, pre-post study in adult patients with thalassemia major and intermedia that received blood transfusion with or without iron-chelating agents in Cipto Mangunkusumo Hospital. Blood samples were taken immediately before the transfusion and one day after. Serum ferritin (SF) assays were conducted by electrochemiluminescence immunoassay method, while transferrin saturation (TS) was calculated by dividing serum iron by the binding capacity. Subsequently, plasma MDA levels assays were performed using the Wills method, and data analysis was conducted using the t-test/Mann-Whitney and Pearson/Spearman correlation test, depending on the data distribution. RESULTS: The 63 respondents recruited consist of 51 TDT and 12 NTDT patients, and their median plasma MDA level before and after transfusion was 0.49 µmol/L and 0.45 µmol/L, respectively. Before transfusion, there was no correlation between SF and MDA, and TS and MDA levels. After the transfusion, there was no correlation between, SF and MDA, or TS and MDA levels. CONCLUSION: There is no significant difference in MDA levels before and after transfusion. Although blood transfusion increases the iron load in thalassemia patients, there was no increase in median MDA level after transfusion. Meanwhile, there was no correlation between markers of iron overload and MDA level in thalassemia patients both before and after transfusion.

Correlation of Serum Ferritin and Cardiac Iron Toxicity with Cardiac Function in Transfusion Dependent Beta-Thalassemia Major Patients.

BACKGROUND: Cardiac iron toxicity is a major cause of mortality in transfusion-dependent beta-thalassemia major patients. The main modality for detecting cardiac iron toxicity is MRI T2* with limited availability. This study aims to obtain iron toxicity profiles in transfusion-dependent beta-thalassemia patients; to see a correlation between iron toxicity and cardiac function. METHODS: We conducted a cross-sectional study at the Adult Thalassemia Polyclinic of Cipto Mangunkusumo Hospital, Indonesia from December 2017 to March 2018. We performed the statistical analysis using Pearson/Spearman Test comparing MRI T2* values with ejection fraction and E/A ratio. RESULTS: The median of 4-months mean of ferritin levels was 5130 ng/mL. The mean for cardiac T2* was 24.96 ms. Severe cardiac hemosiderosis (mean cardiac MRI T2* < 10 ms)  occurred in 11.3% of the subjects.  There was weak correlation between serum ferritin with cardiac iron toxicity (r=-0.272, p=0.032) and ejection fraction (r=-0.281, p=0.013). But, there was no correlation between cardiac iron toxicity with ejection fraction and E/A ratio. CONCLUSION: Serum ferritin correlated weakly with cardiac iron toxicity and cardiac systolic function. Meanwhile, there was no correlation between cardiac iron toxicity with cardiac systolic and diastolic function.

Correlation of Transferrin Saturation and Serum Ferritin with Bone Mass Density in Adult Transfusion Dependent Beta-Thalassemia Patients.

BACKGROUND: The use of regular blood transfusions and iron chelation therapy to treat thalassemia has improved survival and increased the incidence of osteoporosis. Moreover, iron toxicity is one of the contributing factors that reduce bone mass density in adult transfusion-dependent beta-thalassemia patients. Therefore, this study aims to determine the proportion of low bone mass density in adult thalassemia patients and transferrin saturation, as well as serum ferritin, which correlates to the skeletal condition. METHODS: This is a cross-sectional study conducted in Thalassemia and Hematology Medical Oncology Clinics of Cipto Mangunkusumo Hospital in March 2016. The anthropometric data and hemoglobin levels were obtained before transfusion. Subsequently, the average ferritin levels, bone mineral density, and radiographic results were obtained. RESULTS: The percentage of adult thalassemia major and intermedia patients with low bone mass density was 68%. Also, there was a weak inverse correlation between bone mass density and transferrin saturation (r = -0.329, p = 0.01), while no correlation was shown between bone mass density and ferritin (r = -0.088, p = 0.504). The transferrin saturation cutoff point value used to distinguish the incidence of low and normal bone density in patients with transfusion-dependent beta-thalassemia was 89.5%. In addition, there was weak correlation between Singh index and bone mass density (r = 0.273, p = 0.038). CONCLUSION: Among the transfusion-dependent beta-thalassemia patients, 68% had low bone mass density, which inversely correlated to transferrin saturation. Furthermore, the cutoff value of transferrin saturation to differentiate the incidence of low and normal bone density in thalassemia major compared to thalassemia intermedia was 89.5%. Singh Index correlates weakly with bone mass density and might be used to detect low bone mass density in remote healthcare facilities.

The Correlation Between Iron Overload and Endocrine Function in Adult Transfusion-Dependent Beta-Thalassemia Patients with Growth Retardation.

BACKGROUND: Iron overload is a major problem in patients with transfusion-dependent beta-thalassemia (TDT). Reports on the correlation between iron overload and endocrine function with growth retardation in such a population in Indonesia have not been established. Therefore, this study aims to obtain a profile of iron load and endocrine function of adult transfusion dependent beta-thalassemia patients and their correlation with growth retardation. METHODS: A cross-sectional study was performed, involving adult homozygous and HbE beta-thalassemia patients receiving blood transfusions at the Cipto Mangunkusumo Hospital, Jakarta. Iron overload was represented by serum ferritin (FS) and transferrin saturation (TS), while the endocrine function was examined by the Thyroid Stimulating Hormone-sensitive (TSHs), free T4 (fT4), and insulin-like growth factor-1 (IGF-1). The results were analyzed using bivariate analysis plus Pearson and Spearman correlation tests. RESULTS: In general, 58 subjects were selected from 224 adult transfusion dependent beta- thalassemia patients, consisting of 31 males (53.4%) and 27 females (46.6%). Furthermore, their median age was 21 (18-24) years, while the subclinical hypothyroid proportion was 32.7% and low IGF-1 levels were detected in 79.3% of the total population. There was a weak negative correlation between FS and fT4 (Spearman rho=-0.361; p=0.003), as well as IGF-1 (Spearman rho=-0.313; p=0.008), but FS and TSHs had no correlation (Spearman rho=0.074; p=0.29). Also, there was no correlation between ST with TSHs (Spearman rho=0.003; p=0.492), fT4 (Spearman rho=0.018; p=0.448), and IGF-1 (Spearman rho=-0.142; p=0.143). CONCLUSION: Based on serum ferritin, iron overload is discovered to have a negative correlation with free T4 and insulin-like growth factor-1.

Correlations between Iron Load and CD4 in Adult Transfusion-Dependent Beta Thalassemia.

BACKGROUND: Thalassemia is a hereditary disease, and severe anemia is the main phenotype of major thalassemia. Furthermore, the most important method in the management of this disease is red blood cell transfusion. Regular transfusions administered 1 or 2 times every month improve prognosis and survival. However, there is higher risk of infections and iron overload, especially in transfusion-dependent thalassemia (TDT). Infections are the second leading cause of death in adult TDT, after heart failure. Higher risk of infection is also influenced by multiple blood transfusions which causes alteration in immune response due to alloimmunization, transfusion-related infections, and iron overload. Meanwhile, iron overload in TDT alters both innate and specific immune responses. Furthermore, previous studies have shown the correlation between ferritin with CD4, but this has not been carried out in Indonesia. Therefore, this study aims to determine the correlations between iron overload (serum ferritin and transferrin saturation) and specific immune cells (CD4). METHODS: This is a cross-sectional study, and a total number of 64 subjects were examined consecutively. Chest X-ray and blood sera were obtained. The total number of subjects was 64. The seromarkers HBsAg, anti-HCV, and anti-HIV were tested using the ELISA method. Serum ferritin and transferrin saturation was tested using ECLIA, and lymphocyte subsets were analyzed using flowcytometry. Meanwhile, the correlation between variables was determined using Spearman's test. RESULTS: The results showed that 4.9% subjects were HBsAg positive, 10.7% were anti-HCV positive, and none were anti-HIV positive. There were 4 subjects with lung tuberculosis based on the 41 chest X-ray. Meanwhile, there was a weak negative and insignificant correlation between serum ferritin with CD4 (p=0.75; r = -0.04) and a weak positive and insignificant correlation between transferrin saturation with CD4 (p=0.133; r = 0.19). CONCLUSION: There were no correlations between iron overload (ferritin) and cellular immunity (CD4) in adult transfusion-dependent thalassemia.

Correlation of Serum Ferritin and Liver Iron Concentration with Transient Liver Elastography in Adult Thalassemia Intermedia Patients with Blood Transfusion.

INTRODUCTION: Iron overload is a common feature of thalassemia intermedia due to regular blood transfusion and increased gastrointestinal iron absorption. Early detection and adequate iron chelator can decrease morbidity and mortality from iron overload. Liver iron concentration (LIC) by MRI T2* is the best non-invasive way to measure body iron stores. However, this method is expensive and not available nationwide in Indonesia. The aim of this study was to identify liver iron overload and correlation of transferrin saturation, serum ferritin, liver MRI T2* and LIC with transient liver elastography in adult thalassemia intermedia patients. METHODS: This is a cross-sectional study of 45 patients with thalassemia intermedia with blood transfusion and with and without iron chelator therapy. The study was conducted at Cipto Mangunkusumo Hospital from August through October 2016. We performed measurements of transferrin saturation, serum ferritin level, transient liver elastography and liver MRI T2*. Pearson and Spearman correlation tests were used to evaluate the correlation between transient liver elastography with transferrin saturation, serum ferritin, liver MRI T2*and LIC. RESULTS AND DISCUSSION: This study showed that 64.4% of study subjects are ß-Hb E thalassemia intermedia. Furthermore, 84.4% of study subjects have regular transfusion. Based on liver MRI T2*all subjects suffered from liver iron overload, 48.9% had severe degree. Median value of liver MRI T2* was 1.6 ms. Mean serum ferritin was 2831 ng/mL, with median transferrin saturation of 66%. Mean of LIC corresponding to liver MRI T2* and mean liver stiffness measurement was 15.36±7.37 mg Fe/gr dry weight and 7.7±3.8 kPa, respectively. Liver stiffness correlated with serum ferritin (r=0.651; p=0.000), liver MRI T2* (r=-0.357; p=0.016), and LIC (r=0.433; p=0.003). No correlation was found between liver elastography and transferrin saturation (r=0.204; p=0.178). CONCLUSION: Serum ferritin, liver MRI T2*and LIC correlated with liver elastography. No correlation was found between transferrin saturation and liver elastography.

Patterns of Care and Outcome Analysis of Nasopharyngeal Carcinoma: An Indonesian Single Institution Study.

BACKGROUND: Nasopharyngeal cancer is endemic to Southeast Asia. However, there is limited clinical evidence of nasopharyngeal cancer in Indonesia, which has the largest population in Southeast Asia. METHODS: Patterns of care and treatment outcomes in 428 patients with newly-diagnosed and pathologically-confirmed nasopharyngeal cancer were retrospectively analyzed. RESULTS: Concurrent chemo-radiotherapy (CCRT) was the first-line treatment for stages I-IVB diseases. The 2-year overall survival (OS) of all patients were 100.0%, 100.0%, 93.8%, 86.2%, 82.9%, and 62.4% for stages I, II, III, IVA, IVB, and IVC, respectively. The 2-year OS of CCRT-treated patients were 100.0%, 100.0%, 92.6%, 82.4%, and 78.3% for stages I, II, III, IVA, and IVB, respectively. CONCLUSION: The patterns of care and treatment outcomes were potentially consistent with world standards, needing future validation. This is the largest study of newly diagnosed nasopharyngeal cancer in Indonesia, a huge disease burden, providing an important basis for the clinical management of this disease.

Validity and Reliability of the Indonesian Version of the Brief Fatigue Inventory in Cancer Patients.

CONTEXT: Cancer-related fatigue is one of the most commonly reported symptoms in cancer patients. Short but good assessment is essential to detect and manage this symptom. Brief Fatigue Inventory (BFI) is a valid and reliable short instrument to assess cancer-related fatigue. OBJECTIVE: To examine the validity and reliability of the Indonesian BFI. METHODS: Forward and backward translation approach, followed by cognitive debriefing process, was done to develop Indonesian BFI. One hundred twenty-one consecutive adult outpatients with cancer who are willing to participate in this study filled in Indonesian BFI along with the Medical Outcome Study Quality of Life Short Form 36 (MOS SF-36). Demographic and health data were collected. RESULTS: The Indonesian BFI had an overall Cronbach's alpha for the nine items of 0.956. The results of the factor analysis suggested a one-factor solution, supporting the hypothesis of unidimensionality of the Indonesian BFI. The Indonesian BFI score was compared with MOS SF-36 subscale to evaluate convergent validity. An expected inverse correlation between Indonesian BFI and all domains of MOS SF-36 was observed (r = -0.388 to -0.676; P < 0.0000). Discriminant validity analysis showed that the Indonesian BFI mean score significantly increased with increasing Eastern Cooperative Oncology Group Performance Status values (P = 0.000). CONCLUSION: Indonesian BFI is a reliable and valid instrument for Indonesian cancer patients.