The Impact on Working Conditions and Income Amongst Internists in Indonesia: Lesson Learned from the COVID-19 Pandemic.

Internists are at the forefront of providing care for COVID-19 patients. This situation adds more strain on already overburdened internists, particularly in Indonesia, where resources are scarce and unevenly distributed. The pandemic altered working conditions due to restrictions and regulatory changes. Multiple evidence exists for the effect of the COVID-19 pandemic on physicians' well-being, but less is known about its impact on their work dynamics and livelihoods. This study provides some lessons learned during the COVID-19 pandemic regarding the changes in working conditions and earnings experienced by Indonesian internists. There were 3,115 and 1,772 participants in the first and second survey, respectively. After one year, the proportion of internists handling COVID-19 cases, including critical COVID-19 cases, increased; with fewer internists over 60 years old involved. Working hours, number of patients, and monthly earnings decreased for the majority of internists. The increased workload was experienced by most participants one year of the pandemic, predominantly reported by female internists. The COVID-19 pandemic caused a considerable impact on working conditions and income amongst internists in Indonesia. These findings may provide information to institutions in formulating strategies and tools to improve the working conditions and livelihoods of internists in Indonesia amidst the pandemic and potential public health emergencies in the future.

Gene expression profiling of vitamin D metabolism enzymes in leukemia and lymphoma patients: molecular aspect interplay of VDR, CYP2R1, and CYP24A1.

BACKGROUND: Vitamin D deficiency is prevalent among the Indonesian population, particularly in individuals diagnosed with leukemia-lymphoma. The regulation of vitamin D metabolism is influenced by the expression of several enzymes, such as CYP2R1, CYP24A1, and the vitamin D receptor (VDR). This study aimed to scrutinize the gene expression profiles in both mRNA and protein levels of VDR, CYP2R1, and CYP24A1 in leukemia and lymphoma patients. METHOD: The research was a cross-sectional study conducted at Cipto Mangunkusumo Hospital (RSCM) in Jakarta, Indonesia. The study included a total of 45 patients aged over 18 years old who have received a diagnosis of lymphoma or leukemia. Vitamin D status was measured by examining serum 25 (OH) D levels. The analysis of VDR, CYP2R1, and CYP24A1 mRNA expression utilized the qRT-PCR method, while protein levels were measured through the ELISA method. CONCLUSION: The study revealed a noteworthy difference in VDR protein levels between men and women. The highest mean CYP24A1 protein levels were observed in the age group > 60 years. This study found a significant, moderately positive correlation between VDR protein levels and CYP24A1 protein levels in the male and vitamin D sufficiency groups. In addition, a significant positive correlation was found between VDR mRNA levels and CYP2R1 mRNA levels, VDR mRNA levels and CYP2R1 mRNA levels, and CYP2R1 mRNA levels and CYP24A1 mRNA levels. However, the expression of these genes does not correlate with the protein levels of its mRNA translation products in blood circulation.

The relationship between high ratios of CD4/FOXP3 and CD8/CD163 and the improved survivability of metastatic triple-negative breast cancer patients: a multicenter cohort study.

BACKGROUND: Triple-negative breast cancer (TNBC) has been documented as the most aggressive subtype of breast cancer. This study aimed to analyze antitumor and protumor immune activities, and their ratios as significant prognostic biomarkers in metastatic TNBC (mTNBC). METHODS: A multicenter cohort study was conducted among 103 de novo mTNBC patients. The expression of CD8 and CD163 was evaluated using immunohistochemistry staining, CD4 and FOXP3 using double-staining immunohistochemistry, and PD-L1 using immunohistochemistry and RT-PCR. RESULTS: Multivariate analysis revealed that high CD4/FOXP3 (HR 1.857; 95% CI 1.049-3.288; p = 0.034) and the CD8/CD163 ratio (HR 2.089; 95% CI 1.174-3.717; p = 0.012) yield significantly improved 1 year overall survival (OS). Kaplan-Meier analysis showed that high levels of CD4 (p = 0.023), CD8 (p = 0.043), CD4/FOXP3 (p = 0.016), CD8/FOXP3 (p = 0.005), CD8/CD163 (p = 0.005) ratios were significantly associated with higher rate of 1 year OS. Furthermore, 1 year OS was directly correlated with antitumor CD4 (R = 0.233; p = 0.018) and CD8 (R = 0.219; p = 0.026) and was indirectly correlated with protumor CD163 and FOXP3 through CD4/FOXP3 (R = 0.282; p = 0.006), CD4/CD163 (R = 0.239; p = 0.015), CD8/FOXP3 (R = 0.260; p = 0.008), and CD8/CD163 (R = 0.258; p = 0.009). CONCLUSION: This is the first study to demonstrate that high levels of CD4/FOXP3 and CD8/CD163 significantly improved the 1 year OS in de novo mTNBC patients. Thus, we recommend the application of these markers as prognosis determination and individual treatment decision.

Combining Nimotuzumab With Chemotherapy for Patients With Locally Advanced and Intermediate-Stage Nasopharyngeal Cancer: A Retrospective Comparison Study Using Five-Year, Real-World Survival Data.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is the most prevalent geographically-specific head and neck cancer. Its incidence was high in the Asian population, especially in certain parts such as Southern China and South East Asia. Most patients with NPC are presented with intermediate-stage or locally advanced disease requiring chemoradiation as the primary treatment of choice. Epidermal Growth Factor Receptor (EGFR) was found overexpressed in most patients with NPC associated with poor prognosis making its inhibitor one of the most plausible treatment options in addition to chemoradiation. In EGFR-positive NPC patients, nimotuzumab, a humanized anti-EGFR monoclonal antibody will bind the extracellular domain of EGFR leading to tumor growth suppressions. This study's objective was to assess the real-world clinical efficacy of nimotuzumab for patients with intermediate-stage and locally advanced NPC when in combination with concurrent chemoradiation. METHODS: This retrospective real-world study examined a sample of intermediate-stage and locally advanced NPC patients who were treated with or without adding nimotuzumab to concurrent chemoradiation at Dr. Cipto Mangunkusumo General Hospital in Indonesia from January 2009 to December 2017. The outcomes were patients' real-world five-year overall survival (rwOS) and progression-free survival (rwPFS) compared using Kaplan-Meier analysis and Cox proportional hazard models adjusting for age, gender, comorbidities, clinical staging, staging based on Tumor status (T), staging based on Nodes status (N), and types of radiotherapy.  Results: A total of 407 patients were included in the analysis, 61 patients receiving concurrent nimotuzumab and chemoradiation and 346 patients receiving chemoradiation alone. Patients receiving concurrent nimotuzumab and chemoradiation tended to have less aggressive NPC than patients receiving chemoradiation alone. Multivariate-adjusted Cox models revealed that combining nimotuzumab with chemoradiation was associated with a statistically significant longer rwOS gain (hazard ratio (HR)=0.46 (95% CI: 0.26-0.82, p=0.008)) and a trend of longer rwPFS (hazard ratio (HR)=0.67 (95% CI: 0.41-1.09, p=0.109)) in comparison to chemoradiation alone.  Conclusion: In this retrospective real-world study, concurrent nimotuzumab and chemoradiation usage was associated with a significant overall survival benefit than chemoradiation alone for intermediate-stage and locally advanced NPC patients. Hence, adding nimotuzumab to patients' chemoradiation should be considered in patients with intermediate-stage and locally advanced NPC.

TNFα induces Caspase-3 activity in hematopoietic progenitor cells CD34+, CD33+, and CD41 + of myelodysplastic syndromes.

BACKGROUND: Cytopenia is the primary feature of Myelodysplastic Syndrome, even in the presence of hypercellular bone marrow. TNFα is recognized as both a proinflammatory, and proapoptotic cytokine with a well established role in promoting apoptosis in MDS. Therefore, TNFα has the potential to be a valuable biomarker for predicting the progression of cytopenia in MDS. This study aims to establish the role of TNFα exposure in triggering apoptosis through caspase-3 activity in CD34+, CD33+, and CD41 + cells in MDS. METHODS: This study is an in vitro comparative experimental research. Bone marrow mononuclear cells were isolated as the source of hematopoietic progenitor cells. Subsequently, CD34+, CD33+, and CD41 + cells were exposed to rhTNFα, and the caspase-3 activity was measured using flowcytometry. RESULTS: In MDS CD33 + and CD41 + caspase-3 activity of rhTNFα exposed cells was significantly higher than without exposed cells. The opposite result was found in CD34 + cells, where the caspase-3 activity without rhTNFα exposed cells was significantly higher than rhTNFα exposed cells. CONCLUSION: rhTNFα exposure led to an elevation in caspase-3 activity in MDS progenitor cells, especially in those that had differentiated into myeloid cell CD33 + and megakaryocyte cell CD41+, as opposed to the early progenitor cells CD34+.

Metabolic Profile and Negatively Association Between Insulin Resistance and Metastatic Incidence in Indonesian Primary Invasive Breast Cancer: A Cross-Sectional Study.

Introduction: Metastatic breast cancer was associated with high morbidity and mortality. Insulin resistance was hypothesized to be related to the incidence of advanced breast cancer. Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) and Triglyceride/Glucose Index (TyG Index) are two metrics used to measure the degree of insulin resistance. This study aims to assess the relationship between the incidence of metastatic breast cancer and insulin resistance as reflected by both metrics. Material and Methods: This study is a cross-sectional study involving 150 primary invasive breast cancer patients recruited from two hospitals of different sectors from August 2019 to April 2020. Patients with double cancer and autoimmune disorder were excluded from this study. Data obtained from the patients include age, body mass index (BMI), type 2 diabetes mellitus (T2DM) status and treatment, and low-density lipoprotein (LDL) cholesterol. The electronic medical records (EMR) was consulted to find histopathology examination result, cancer staging, and any missing data. The association between HOMA-IR and TyG with metastatic incidence was analyzed using either the Mann-Whitney test (for non-normally distributed data) or the independent-sample t-test (for normally distributed data). Results: The mean of the TyG index is 8.60, and the median of HOMA-IR is 1.22. We found no significant correlation between both variables and the incidence of metastases. Conclusion: Insulin resistance was not associated with metastatic breast cancer.

A comparative study of the COVID-19 vaccine efficacy among cancer patients: mRNA versus non-mRNA.

BACKGROUND: Cancer patients have an increased risk of a severe COVID-19 infection with higher mortality rate. This study aimed to analyze the levels of anti-SARS-CoV-2 S-RBD IgG and NAB among cancer patients who were vaccinated with COVID-19 vaccines, either with BNT162b2, mRNA-1273, AZD1222/ChAdOx1nCoV-19, or Coronavac/BBIBP-CorV vaccines. METHOD: A cross-sectional study was conducted among subjects with either solid or hematological cancers who had received two doses of either mRNA or non-mRNA vaccines within 6 months. The levels of anti-SARS-CoV-2 S-RBD IgG and NAb were analyzed using the Mindray Immunoassay Analyzer CL-900i. Statistical analysis was conducted using mean comparison and regression analysis. RESULT: The mRNA-1273 vaccine had the highest median levels of S-RBD IgG and NAb, followed by BNT162b, ChAdOx1nCoV-19, and BBIBP-CorV/Coronavac. The levels of S-RBD IgG and NAb in subjects vaccinated with mRNA vaccines were significantly higher than those of non-mRNA vaccines when grouped based on their characteristics, including age, type of cancer, chemotherapy regimen, and comorbidity (p<0.05). Furthermore, the S-RBD IgG and NAb levels between the subjects vaccinated with non-mRNA vaccines and the subjects vaccinated with mRNA vaccines were significantly different (p<0.05). However, there was no significant difference between the same types of vaccines. This study demonstrated a very strong correlation between the level of S-RBD IgG and the level of NAb (R = 0.962; p<0.001). The level of anti-SARS-CoV-2 S-RBD IgG was consistently higher compared to the level of NAb. CONCLUSIONS: Generally, mRNA vaccines produced significantly higher anti-SARS-CoV-2 S-RBD IgG and NAb levels than non-mRNA vaccines in cancer subjects.

The association between vitamin D deficiency and the clinical outcomes of hospitalized COVID-19 patients.

Background: Vitamin D deficiency is an emerging public health problem that affects more than one billion people worldwide. Vitamin D has been shown to be effective in preventing and reducing the severity of viral respiratory diseases, including influenza. However, the role of vitamin D in COVID-19 infection remains controversial. This study aimed to analyze the association of vitamin D deficiency on the clinical outcome of hospitalized COVID-19 patients. Methods: A prospective cohort study was conducted among hospitalized COVID-19 patients at two COVID-19 referral hospitals in Indonesia from October 2021 until February 2022. Results: The median serum 25(OH)D level in 191 hospitalized COVID-19 patients was 13.6 [IQR=10.98] ng/mL. The serum 25(OH)D levels were significantly lower among COVID-19 patients with vitamin D deficiency who had cardiovascular disease (p-value=0.04), the use of a ventilator (p-value=0.004), more severe COVID-19 cases (p-value=0.047), and mortality (p-value=0.002). Furthermore, serum 25(OH)D levels were significantly different between patients with mild and severe COVID-19 cases (p-value=0.019). Serum 25(OH)D levels in moderate and severe COVID-19 cases were significantly different (p-value=0.031). Lower serum 25(OH)D levels were significantly associated with an increased number of comorbidities (p-value=0.03), the severity of COVID-19 (p-value=0.002), and the use of mechanical ventilation (p-value=0.032). Mortality was found in 7.3% of patients with deficient vitamin D levels. However, patients with either sufficient or insufficient vitamin D levels did not develop mortality. Conclusions: COVID-19 patients with vitamin D deficiency were significantly associated with having cardiovascular disease, mortality, more severe COVID-19 cases, and the used of mechanical ventilation. Lower serum 25(OH)D levels were associated with an increased number of comorbidities, COVID-19 severity, and the use of mechanical-ventilation. Thus, we suggest hospitalized COVID-19 patients to reach a sufficient vitamin D status to improve the clinical outcome of the disease.

The Association of Immune Cell Infiltration with Metastasis Location in De Novo Metastatic Triple Negative Breast Cancer: A Multicenter Cross-Sectional Study in Indonesia.

BACKGROUND: Triple-negative breast cancer (TNBC) is an aggressive cancer subtype, with limited treatments and a high metastasis risk. The varying location of metastasis in TNBC patients often leads to in prognosis in breast cancer. Therefore, this study aimed to investigate the potential association between immune cells profiles in the tumor microenvironment and metastatic patterns. METHODS: We conducted a multicenter cross-sectional study in 2022 to examine formalin-fixed paraffin-embedded (FFPE) and medical record data from 2015 to 2020 in de novo metastatic TNBC patients. The medical records provided crucial information about the sites of metastasis. Immunohistochemistry (IHC) analysis was carried out on primary breast tumor tissues to evaluate the expressions of cluster of differentiation (CD)4 T-cells, CD8 T-cells, CD163, FOXP3 Tregs, and programmed death-ligand 1 (PD-L1), along with immune cells ratios showing antitumor-to-protumor activity (CD4/FOXP3, CD8/FOXP3, CD4/CD163, CD8/CD163). Metastatic locations were grouped into bone-only, visceral, lung, liver, and brain metastasis.  Results: A total of 120 metastatic TNBC patients were documented for their metastatic location and IHC report. The clinical and histopathological characteristics showed that the majority of the patients were within the 40-65 years old group, and 34.2% had standard body mass index (BMI). Furthermore, the majority (89.22%) of the patients showed No Special Type (NST), (56.7%) had histopathology grade III, high Ki-67 ≥20% (85.8%), and positive PD-L1 expression (30.8%), with visceral metastasis indicating the highest proportion of 75.8%. Patients with a high CD8/FOXP3 and CD4/FOXP3 ratio were significantly prone to have bone-only metastasis compared to visceral metastasis (p= 0.028 and p=0.024, respectively).  Conclusion: The ratio of antitumor to protumor T-lymphocytes had a significant relevance in the metastatic location patterns in TNBC.

The correlation between serum 25-hydroxy-vitamin D levels and anti-SARS-CoV-2 S-RBD IgG and neutralizing antibody levels among cancer patients receiving COVID-19 vaccines.

Introduction: During the coronavirus disease 2019 (COVID-19) pandemic, vitamin D has been established as an immune-modulator that reduces pro-inflammatory damage which effectively diminish the severity of COVID-19. Vitamin D also has a significant effect against influenza and dengue and increase the seroconversion following influenza vaccination. To date, the role of vitamin D in optimizing the efficacy of COVID-19 vaccines remains unclear. This study aimed to analyze the correlation between serum 25-hydroxy-cholecalciferol or 25(OH)D levels and anti-SARS-CoV-2 S-RBD IgG and neutralizing antibody levels among cancer patients. Methodology: A multicenter cross-sectional study was conducted among solid and hematologic cancer patients who were vaccinated with two doses of the same types of COVID-19 vaccines (either mRNA, non-replicating viral vector, or inactivated) within 6 months. Result: The median serum 25(OH)D level in 119 cancer patients was 36.36 [IQR = 30.30] ng/mL. The seropositivity of S-RBD IgG and NAb reached 93.3 and 94.1%, respectively. The S-RBD IgG level was significantly higher in the sufficient group (median = 414.07 [1,441.83] AU/mL) than in the deficient group (median = 91.56 [652.00] AU/mL) (p-value = 0.049). Among non-chemotherapy subjects, the anti-SARS-CoV-2 S-RBD IgG levels had a significant positive correlation with 25(OH)D levels (p-value = 0.03; R = 0.588). The NAb levels also showed significantly positive correlation with 25(OH)D level (p-value = 0.005; R = 0.561). The 25(OH)D levels were positively correlated with S-RBD IgG levels among subjects younger than 60 years old (p-value = 0.047; R = 0.136). However, serum 25 (OH)D levels showed no such correlation with S-RBD IgG levels among subjects older than 60 years old (p-value = 0.933; R = 0.136). Conclusion: Both anti-SARS-CoV-2 S-RBD IgG and NAb levels developed moderate correlation with 25(OH)D levels among subjects treated without chemotherapy. The S-RBD IgG levels also had positive correlation with 25(OH)D levels among subjects younger than 60 years old. Thus, we recommended cancer patients to maintain serum 25(OH)D levels above 30 ng/mL (75 nmol/L) to enhance the efficacy of COVID-19 vaccines.

A case of aseptic bilateral cavernous sinus thrombosis following a recent inactivated SARS-CoV-2 vaccination.

This case report aims to describe the first report of bilateral aseptic cavernous sinus thrombosis (CST) with a recent history of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. A 50-year-old woman presented with bilateral proptosis, decreased vision, and ophthalmoplegia 16 days following CoronaVac® vaccine. The visual acuity of the left eye was 20/150, while the right eye was no light perception with a hyperemic optic nerve head. She had a history of hyperthyroidism and currently on warfarin consumption. Laboratory results depicted elevated free T4, free T3, international normalized ratio, and low protein S and C. Magnetic resonance imaging showed bilateral CST, and high-dose methylprednisolone along with fondaparinux was given. The symptoms were significantly resolved, with the visual acuity of the left eye being improved to 20/20 but not the right eye. Bilateral CST has not been previously reported following inactivated SARS-CoV-2 vaccination. The underlying systemic conditions should be taken into consideration for the possibility of the inactivated SARS-CoV-2 vaccine-related event.

The Relationship Between fragmented QRS Complexes (fQRS) and the Severity of Coronary Artery Lesion in Coronary Artery Disease: A Cross-sectional Study.

BACKGROUND: The severity of coronary artery lesion is commonly used as a predictor of mortality, major adverse cardiovascular event, and revascularization in coronary artery disease (CAD). Fragmented QRS complex (fQRS) is used as a marker of myocardial ischemia in patients with CAD. The relationship between the two should be studied further. The objective of this study was to determine the relationship between fQRS and the severity of coronary lesion in patients with CAD. METHODS: A cross-sectional study was conducted at Cipto Mangunkusumo Hospital Jakarta. Secondary data were taken from 172 patients with CAD who underwent percutaneous coronary intervention (PCI) from January to June 2018 with total sampling. Patients were divided into two groups based on the existence of fQRS. Demographic, clinical, and corangiography characteristics (Gensini score, total vascular lesion, and vascular lesion significance) were studied. Data were analyzed using agreement test and chi-square. RESULTS: fQRS was present in 94 subjects (54.6%). Bivariate analysis showed a significant difference between fQRS with mild-moderate Gensini score as well as mild-severe Gensini score (kappa = 0.721 and 0.820; p<0.001), fQRS with significant CAD (kappa = 0.670; p<0.001), and fQRS with multivessel CAD (kappa = 0.787; p<0.001). CONCLUSION: There is a significant relationship between fQRS and the degree of severity of coronary lesion in CAD patients.

The effect of mannitol addition to hydration on acute kidney injury event after high dose cisplatin chemotherapy: an ambispective cohort study.

BACKGROUND: Saline hydration with addition of mannitol have commonly been the strategy to avoid cisplatin induced acute kidney injury (AKI). While the initial reports demonstrated that mannitol diuresis decreased cisplatin induced renal injury, others have shown renal injury to be worsened. OBJECTIVE: To compare the risk of AKI in cancer patients receiving high dose cisplatin with and without addition of mannitol. METHOD: This was an ambispective cohort study based on consecutive sampling at Cipto Mangunkusumo General Hospital (CMGH) and Mochtar Riady Comprehensive Cancer Centre (MRCCC) Siloam Hospitals. The data was obtained from September 2017 to February 2018. The choice of mannitol administration based on attending physician clinical judgement. The primary outcome was increase of serum creatinine more than 0.3 mg/dL or 1.5 times from baseline. Analysis was done by using univariate, bivariate and multivariate logistic regression to obtain crude risk ratio and adjusted risk ratio of cisplatin induced AKI probability caused by mannitol addition on top of usual saline hydration protocol. RESULT: Data from 110 patients (57.3% male) with a median age of 44.5 years (range 19 to 60 years) were collected; 63 received saline with the addition of mannitol and 47 received saline only. Incidence of AKI were higher in mannitol vs saline only group. Bivariate analysis showed higher probability of post chemotherapy AKI in mannitol group, however it was statistically insignificant (RR 2.168; 95% CI 0.839-5.6; p = 0.094). On multivariate analysis the age adjusted RR was 2.852 (95% CI 0.68-11.96; p = 0.152). CONCLUSION: The addition of mannitol to hydration did not reduce the risk of cisplatin induced AKI as compared with saline hydration only. It was also found that risk for acute kidney injury were higher in population ≥ 40 years old.

Factors that Influence 2-Year Progression-Free Survival Among Head and Neck Cancer Patients.

OBJECTIVES: The majority of patients with head and neck cancer (HNC) come to the hospital at advanced stages. This research was conducted to determine the mortality, 2-year progression-free survival (PFS) and factors that influenced PFS of HNC patients. METHODS: A retrospective cohort study was conducted among locally advanced HNC patients who underwent chemoradiation for the first time at RSCM from January 2015 to December 2017. Data were retrieved through medical records. Laboratory data were taken 2-4 weeks prior and 2-4 weeks after chemoradiation. PFS observation started from the first day of chemoradiation until disease progression or death. PFS data were recorded in two groups: ≤ 2 years and > 2 years. The Chi-square test was used for bivariate analysis with the Fischer-exact test as an alternative. Variables will be further tested using multivariate logistic regression tests. RESULTS: Among 216 subjects, there were 103 (47.69%) patients who did not reach overall survival (OS) > 2 years. There were 108 (50%) patients who had PFS > 2 years. Based on the results of multivariate analysis, it was found that smoking, hemoglobin level ≤ 12 g/dl, ECOG (Eastern Cooperative Oncology Group) 1-2, and negative therapeutic response were associated with poor PFS. Hazard ratio (HR) for 2-year PFS for Brinkman index > 250 was 1.36 (95% CI 0.93-2.00; p = 0.02); HR for Hb ≤ 12 g/dl was 1.65 (95% CI 1.13-2.42; p = 0.01); HR for ECOG 1-2 was 4.05 (95% CI 1.49-11.00; p < 0.01); and HR for negative therapeutic response was 2.37 (95% CI 1.43-3.94; p < 0.01). CONCLUSION: Mortality of HNC patients within 2 years is 47.69%, with a 2-year PFS reaching 50%. Cigarette smoking, low hemoglobin levels, poor performance status, and negative therapeutic response (non-responders) negatively affect the 2-year PFS.

Role of Pretreatment Hemoglobin-to-Platelet Ratio in Predicting Survival Outcome of Locally Advanced Nasopharyngeal Carcinoma Patients.

BACKGROUND: The three-year survival rate of locally advanced nasopharyngeal carcinoma (NPC) patients in Indonesia is lower than in other Asian countries. Calculation of hemoglobin-to-platelet ratio (HPR) may become a more practical predictor than the ratios using leukocyte cell components. Yet, no study has been conducted to investigate the potential of HPR in predicting survival outcomes in locally advanced nasopharyngeal cancer patients. OBJECTIVE: To determine the role of pretreatment hemoglobin-to-platelet ratio in predicting the three-year overall survival (OS) of locally advanced NPC. METHOD: A retrospective cohort study followed up on 289 locally advanced NPC patients who had undergone therapy at the Dr. Cipto Mangunkusumo National General Hospital between January 2012 and October 2016. HPR cut-off was determined using ROC. Subjects were classified into two groups according to the HPR value. Kaplan-Meier curve was utilized to illustrate patients' three-year survival, and Cox regression test analyzed confounding variables to yield an adjusted hazard ratio (HR). RESULTS: The optimal cut-off for HPR was 0.362 (AUC 0.6228, 95% CI: 0.56-0.69, sensitivity 61.27%, specificity 60.34%). Of the subjects, 48.44% had HPR ≤ 0.362, and they had a higher three-year mortality rate than those with HPR > 0.362 (50% vs. 31.54%). In bivariate analysis, HPR ≤ 0.362 and age ≥ 60 significantly showed a worse three-year OS (p value = 0.003 and 0.075, respectively). In multivariate analysis, we concluded that a pretreatment HPR ≤ 0.362 was an independent negative predictor of three-year OS in locally advanced NPC patients (adjusted HR 1.82; 95% CI: 1.25-2.65). CONCLUSION: Pretreatment HPR ≤ 0.362 was a negative predictor of three-year OS in locally advanced nasopharyngeal cancer patients.

Expression of mRNA TNFα and level of protein TNFα after exposure sCD40L in bone marrow mononuclear cells of myelodysplastic syndromes.

BACKGROUND: Cytopenia is the primary phenomenon in myelodysplastic syndrome (MDS) amidst hypercellular bone marrow. The soluble CD40 ligand (sCD40L) is considered as a cytokine that can trigger synthesis of tumor necrosis factor α (TNFα) that promotes apoptosis. The objective of this study is to prove that recombinant human sCD40L (rh-sCD40L) exposure on bone marrow mononuclear cells (BMMC) MDS increases TNFα expression at mRNA level and at protein level. METHODS: BMMC from MDS patients whom diagnosed and classified using the WHO 2008 criteria, were exposed to rh-sCD40L and antiCD40L. The expressions of TNFα mRNAs were quantified by qRT-PCR, level of TNFα were measured using the ELISA method. RESULTS: Exposure of rh-sCD40L significantly increased the expression of TNFα mRNA. The similar exposure also significantly increased the level of TNFα compared to controls. TNFα mRNA expression on BMMC in MDS samples exposed to rh-sCD40L is 3.32 times compared to TNFα mRNA expression without exposure. level of TNFα in supernatant media exposed to rh-sCD40L in MDS samples was higher than that of control samples which were 44.44 and 4.85 pg/mL, P=0.018. CONCLUSIONS: The sCD40L plays a role in increasing the synthesis of TNFα in mRNA level and protein level in BMMC MDS.

Correlation Between Higher Cumulative Dose of Cisplatin for Concurrent Chemoradiation and Acute Kidney Disease Incidence Among Nasopharyngeal Carcinoma Patients: A Comparative Study.

INTRODUCTION: Nasopharyngeal carcinoma (NPC) is the most malignant cancer in the head and neck area. According to the stage, the management of NPC includes radiation, chemotherapy, or a combination of both. The standard agent for radiosensitizing chemotherapy is cisplatin. Among the several effects of cisplatin administration, nephrotoxicity raises the most concern, especially in high doses. Acute kidney disease (AKD) is a condition in which an acute kidney injury occurs at >7 days but <90 days. This study aimed to assess whether there is a significant difference in the incidence of AKD between NPC patients who received a cumulative dose of cisplatin up to (≤) 200 mg/m2 and patients who received more than (>) 200 mg/m2. METHODS: This is a cohort retrospective study conducted in the radiotherapy unit of Cipto Mangunkusumo General Hospital. Medical records of 540 patients from January 2014 to December 2018 were collected and sorted. After sorting, 120 of the records were analyzed. RESULTS: The analysis showed that 38.4% of patients who received >200 mg/m2 cumulative dose of cisplatin experienced AKD, whereas 38.3% of the patients who received ≤200 mg/m2 cumulative dose of cisplatin experienced AKD. CONCLUSION: This study found that in patients with locally advanced NPC who received cisplatin chemoradiation, there was no significant difference in the incidence of AKD, recovery of renal function, or progression of chronic kidney disease between patients receiving a cumulative dose of cisplatin ≤200 mg/m2 and those receiving >200 mg/m2.

Association between serum homocysteine level and cognitive function in middle-aged type 2 diabetes mellitus patients.

Type-2 diabetes mellitus (T2DM) is strongly associated with various complications, including cognitive impairment. Diabetic complication is related with structural and functional changes of brain. Studies investigated that homocysteine as an independent risk factor of several organ complications. This marker might have a role in pathogenesis of cognitive impairment in T2DM patients. We aimed to know the association between serum homocysteine level and cognitive impairment in middle-aged T2DM populations. The study was a cross-sectional study involving 97 T2DM patients aged <60 years old. Cognitive assessment was based on validated Indonesian version of Montreal Cognitive Assessment (MoCA-INA) test. Besides, serum homocysteine level (Hcy) was measured based on standard laboratory assay. Filling out the questionnaire of MoCA-INA was conducted when patients came to take the blood sample. This study used independent t-test, chi-square and multivariate logistic regression model to analyze the data. There were 47 subjects (48.5%) with mild cognitive impairment (MCI). Delayed recall was the most impaired domain (94.8%). There was no significant mean difference of serum Hcy level in MCI and non-MCI group (11.99±3.27 µmol/L vs 12.36±4.07 µmol/L respectively, p = 0.62). Final model of logistic regression showed no association between serum Hcy and cognitive function after adjusting confounding variables (OR: 1.778; 95%CI: 0.69-4.54). Further investigation involving slight elderly T2DM patients with larger sample size should be conducted to confirm this finding.

Visceral fat thickness of erosive and non-erosive reflux disease subjects in Indonesia's tertiary referral hospital.

BACKGROUND: There has been an increasing number of reports regarding the correlation between obesity and gastroesophageal reflux disease (GERD). Visceral fat thickness is thought to be a risk factor for GERD and its severity. Several studies have conflicting results, so this study aimed to determine visceral fat thickness difference between erosive and non-erosive reflux disease. METHODS: A cross-sectional study of 56 adult subjects with GERD symptoms was held at Cipto Mangunkusumo National General Hospital between April and November 2018. Gastroesophageal Reflux Disease Questionnaires (GERDQ) were utilized to determine the presence of GERD. Ultrasonography was used to determine visceral fat thickness. Esophageal erosions were diagnosed using upper gastrointestinal endoscopy. The difference in visceral fat thickness between esophagitis and non-esophagitis group was analysed using T-test. RESULTS: From 56 total subjects, 55.4% have erosive reflux disease (ERD), in which were dominated by subjects with grade A esophagitis (64.5%) based on Los Angeles Classification of Esophagitis (LA classifications). There was no significant difference of visceral fat thickness between non-erosive reflux disease (NERD) and ERD (p = 0,831). There was, however, an increasing trend of visceral fat thickness with the advancing severity of esophagitis, although statistical significance was not reached. CONCLUSION: Visceral fat thickness as measured by ultrasonography has no significant difference between NERD and ERD.

Association of Peripheral Monocyte Count with Soluble P-Selectin and Advanced Stages in Nasopharyngeal Carcinoma.

INTRODUCTION: Inflammation is widely recognized to play an important role in cancer progression and is related to thrombosis. Soluble P-selectin (sP-selectin) is one of several biomarkers that may be predictive of thrombosis in cancer. This study aimed to investigate the correlation between monocyte count and sP-selectin in various stages of nasopharyngeal carcinoma. METHODS: Fifty-five patients with nasopharyngeal carcinoma were divided into three groups according to nodal and distant metastasis (group of stages I-IVA, IVB, and IVC). Monocyte count was calculated from routine peripheral blood examination, while sP-selectin level was measured using commercial ELISA kit. RESULTS: The monocyte count of subjects in groups IVB and IVC was significantly higher compared to group I-IVA (707/µL versus 528/µL, p = 0.022; 841/µL versus 528/µL, p = 0.005). Plasma levels of sP-selectin in group IVC were higher than group I-IVA (59.5 ng/mL versus 41.97 ng/mL, p = 0.001) and group IVB (59.5 ng/mL versus 45.53 ng/mL, p = 0.007). In subjects with high monocyte count (>665/µL), there was moderate correlation between monocyte count and sP-selectin (r = 0.436, p = 0.022). CONCLUSION: Advanced stages of nasopharyngeal carcinoma had higher levels of monocyte count and sP-selectin compared to earlier stages. Monocyte count was correlated with sP-selectin especially in high monocyte count subgroup.