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Abstract Background Due to their immunomodulatory properties, mesenchymal stem cells (MSCs) have been proposed to have therapeutic potential to improve clinical outcomes in COVID-19. However, the safety and efficacy profile of MSC infusion therapy in patients with non-severe COVID-19 infection has not been completely established; there is, in particular, a substantial void in the literature on dose-dependent studies of MSC infusion in patients with low clinical risk COVID-19 infection. Methods This phase 1 double-blind, placebo-controlled, randomized clinical trial examines the safety, feasibility, and tolerability of 2 doses (high and low) of DW-MSC in patients with low clinical risk COVID-19. A total of 9 patients were enrolled in this study and randomized into low-dose (TL), high-dose (TH), and placebo (C) groups. Subjects in the TL and TH groups received single intravenous infusions of 5.0 × 107 cells and 1.0 × 108 cells, respectively. The main outcome was the occurrence of treatment-emergent adverse events (TEAE) during the 28-day study period. Vital signs and various inflammatory markers were also monitored weekly during the observation period. Results There were no apparent differences in clinical characteristics between study groups (TL, TH, and C) at baseline. All patients did not show the progression of severity during the study period. During the course of the study, 6 episodes of TEAE were observed in 5 subjects; however, none of the TEAEs were severe. During the follow-up period, 8 subjects recovered and were discharged from the hospital without complications. A subject exhibited abnormal liver function biomarkers at the end of the study period. Changes in inflammatory markers throughout the clinical course were not vastly different across study groups. Conclusions Our clinical trial has provided reliable results regarding the safety of MSCs in low clinical risk COVID-19 subjects treated with MSCs. However, further confirmation of the therapeutic efficacy aspects of MSC will require large-scale randomized controlled trials in subjects with varying severity profiles for COVID-19. Trial registration ClinicalTrials.gov, NCT04535856. Registered 2 September 2020, https://clinicaltrials.gov/ct2/show/NCT04535856

[This corrects the article DOI: 10.1371/journal.pntd.0007927.].

Abstract Background The burden of leptospirosis in Indonesia is poorly understood. Data from an observational study conducted from 2013 to 2016 in seven cities across Indonesia was used to estimate the incidence of leptospirosis and document its clinical manifestations in patients requiring hospitalization. Methods Specimens from patients hospitalized with acute fever were collected at enrollment, 14–28 days, and 3 months. Demographic and clinical information were collected during study visits and/or retrieved from medical records and double-entered into clinical report forms. After initially screening for dengue virus and other pathogens, specimens were tested at a central Reference Laboratory for anti-Leptospira IgM using commercial ELISA kits and for Leptospira DNA using an in-house quantitative real-time PCR assay. Results Of 1464 patients enrolled, 45 (3.1%) confirmed cases (by PCR and/or sero-coversion or four-fold increase of IgM) and 6 (0.4%) probable cases (by high titer IgM) of leptospirosis were identified by the Reference Laboratory. Disease incidence at sites ranged from 0 (0%) cases in Denpasar to 17 (8.9%) cases in Semarang. The median age of patients was 41.2 years (range of 5.3 to 85.0 years), and 67% of patients were male. Twenty-two patients (43.1%) were accurately diagnosed at sites, and 29 patients (56.9%) were clinically misdiagnosed as having another infection, most commonly dengue fever (11, 37.9%). Clinically, 20 patients (39.2%) did not present with hyperbilirubinemia or increased creatinine levels. Two patients (3.9%) died, both from respiratory failure. Fifteen patients (29.4%) clinically diagnosed with leptospirosis at sites were negative based on IgM ELISA and/or PCR at the Reference Laboratory. Conclusions Leptospirosis remains an important cause of hospitalization in Indonesia. It can have diverse clinical presentations, making it difficult to differentiate from other common tropical infections. PCR combined with ELISA is a powerful alternative to the cumbersome gold-standard microscopic agglutination test, particularly in resource-limited settings.

The burden of antimicrobial-resistant (AMR) infections in low and middle-income countries (LMICs) is largely unknown. Here, we evaluate attributable mortality of AMR infections in Indonesia. We used routine databases of the microbiology laboratory and hospital admission at Dr. Wahidin Sudirohusodo Hospital, a tertiary-care hospital in South Sulawesi from 2015 to 2018. Of 77,752 hospitalized patients, 8,341 (10.7%) had at least one blood culture taken. Among patients with bacteriologically confirmed bloodstream infections (BSI), the proportions of patients with AMR BSI were 78% (81/104) for third-generation cephalosporin-resistant (3GCR) Escherichia coli, 4% (4/104) for 3GCR plus carbapenem-resistant E. coli, 56% (96/171) for 3GCR Klebsiella pneumoniae, 25% (43/171) for 3GCR plus carbapenem-resistant K. pneumoniae, 51% (124/245) for methicillin-resistant Staphylococcus aureus, 48% (82/171) for carbapenem-resistant Acinetobacter spp., and 19% (13/68) for carbapenem-resistant Pseudomonas aeruginosa. Observed in-hospital mortality of patients with AMR BSI was 49.7% (220/443). Compared with patients with antimicrobial-susceptible BSI and adjusted for potential confounders, the excess mortality attributable to AMR BSI was -0.01 (95% CI: -15.4, 15.4) percentage points. Compared with patients without a BSI with a target pathogen and adjusted for potential confounders, the excess mortality attributable to AMR BSI was 29.7 (95%CI: 26.1, 33.2) percentage points. This suggests that if all the AMR BSI were replaced by no infection, 130 (95%CI: 114, 145) deaths among 443 patients with AMR BSI might have been prevented. In conclusion, the burden of AMR infections in Indonesian hospitals is likely high. Similar large-scale evaluations should be performed across LMICs to inform interventions to mitigate AMR-associated mortality.

Blood culturing remains the "gold standard" for bloodstream infection (BSI) diagnosis, but the method is inaccessible to many developing countries due to high costs and insufficient resources. To better understand the utility of blood cultures among patients in Indonesia, a country where blood cultures are not routinely performed, we evaluated data from a previous cohort study that included blood cultures for all participants. An acute febrile illness study was conducted from July 2013 to June 2016 at eight major hospitals in seven provincial capitals in Indonesia. All participants presented with a fever, and two-sided aerobic blood cultures were performed within 48 hours of hospital admission. Positive cultures were further assessed for antimicrobial resistance (AMR) patterns. Specimens from participants with negative culture results were screened by advanced molecular and serological methods for evidence of causal pathogens. Blood cultures were performed for 1,459 of 1,464 participants, and the 70.6% (1,030) participants that were negative by dengue NS1 antigen test were included in further analysis. Bacteremia was observed in 8.9% (92) participants, with the most frequent pathogens being Salmonella enterica serovar Typhi (41) and Paratyphi A (10), Escherichia coli (14), and Staphylococcus aureus (10). Two S. Paratyphi A cases had evidence of AMR, and several E. coli cases were multidrug resistant (42.9%, 6/14) or monoresistant (14.3%, 2/14). Culture contamination was observed in 3.6% (37) cases. Molecular and serological assays identified etiological agents in participants having negative cultures, with 23.1% to 90% of cases being missed by blood cultures. Blood cultures are a valuable diagnostic tool for hospitalized patients presenting with fever. In Indonesia, pre-screening patients for the most common viral infections, such as dengue, influenza, and chikungunya viruses, would maximize the benefit to the patient while also conserving resources. Blood cultures should also be supplemented with advanced laboratory tests when available.

BACKGROUND:Chikungunya virus (CHIKV) is often overlooked as an etiology of fever in tropical and sub-tropical regions. Lack of diagnostic testing capacity in these areas combined with co-circulation of clinically similar pathogens such as dengue virus (DENV), hinders CHIKV diagnosis. To better address CHIKV in Indonesia, an improved understanding of epidemiology, clinical presentation, and diagnostic approaches is needed. METHODOLOGY/PRINCIPAL FINDINGS:Acutely hospitalized febrile patients ≥1-year-old were enrolled in a multi-site observational cohort study conducted in Indonesia from 2013 to 2016. Demographic and clinical data were collected at enrollment; blood specimens were collected at enrollment, once during days 14 to 28, and three months after enrollment. Plasma samples negative for DENV by serology and/or molecular assays were screened for evidence of acute CHIKV infection (ACI) by serology and molecular assays. To address the co-infection of DENV and CHIKV, DENV cases were selected randomly to be screened for evidence of ACI. ACI was confirmed in 40/1,089 (3.7%) screened subjects, all of whom were DENV negative. All 40 cases initially received other diagnoses, most commonly dengue fever, typhoid fever, and leptospirosis. ACI was found at five of the seven study cities, though evidence of prior CHIKV exposure was observed in 25.2% to 45.9% of subjects across sites. All subjects were assessed during hospitalization as mildly or moderately ill, consistent with the Asian genotype of CHIKV. Subjects with ACI had clinical presentations that overlapped with other common syndromes, atypical manifestations of disease, or persistent or false-positive IgM against Salmonella Typhi. Two of the 40 cases were possibly secondary ACI. CONCLUSIONS/SIGNIFICANCE:CHIKV remains an underdiagnosed acute febrile illness in Indonesia. Public health measures should support development of CHIKV diagnostic capacity. Improved access to point-of-care diagnostic tests and clinical training on presentations of ACI will facilitate appropriate case management such as avoiding unneccessary treatments or antibiotics, early response to control mosquito population and eventually reducing disease transmission.

BackgroundThe epidemiology of acute febrile illness, a common cause of hospitalization in Indonesia, has not been systematically studied.Methodology/principal findingsThis prospective observational study enrolled febrile patients (temperature ≥38°C) aged ≥1 year from July 2013 until June 2016 at eight government referral teaching hospitals in seven provincial capitals in Indonesia. Patients were managed according to the hospital standard-of-care (SOC), and blood samples were drawn for molecular and serological assays. Clinical data, laboratory results, and specimens for additional tests were collected at enrollment, days 14-28, and at three months. Regular follow-up visits were then scheduled for every three months either until symptoms resolved or until one year. In total, this study included 1,486 adult and pediatric patients presenting with multi-organ (768, 51.7%), gastrointestinal (497, 33.0%), respiratory (114, 7.7%), constitutional (62, 4.2%), skin and soft-tissue (24, 1.6%), central nervous system (17, 1.1%), or genitourinary (4, 0.3%) manifestations. Microbiological diagnoses were found in 1,003/1,486 (67.5%) participants, of which 351/1,003 (35.0%) were not diagnosed during hospitalization using SOC diagnostic tests. Missed diagnoses included all cases caused by Rickettsia spp., chikungunya, influenza, and Seoul virus. The most common etiologic agents identified were dengue virus (467, 46.6%), Salmonella spp. (103, 10.3%), and Rickettsia spp. (103, 10.3%). The overall mortality was 89 (5.9%).Conclusions/significanceFebrile illness in Indonesia has various microbiologic etiologies and substantial overall mortality. Diagnostic limitations and lack of epidemiologic data resulted in potentially treatable, and at times fatal, diseases being missed.

INTRODUCTION Blood urea nitrogen and creatinine levels are routine laboratory tests for evaluating renal function. Renal dysfunction has been related to worse prognosis of cardiovascular diseases. The purpose of this study was to determine the relationship between admission blood urea nitrogen and creatinine levels with in-hospital mortality in acute myocardial infarction patients. METHODS A cross-sectional study was performed using secondary data of 80 acute myocardial infarction patients hospitalized in Intensive Cardiac Care Unit of dr. Wahidin Sudirohusodo Hospital, Makassar, from June 2010 to July 2011. Admission blood urea nitrogen and creatinine levels were analyzed with Mann Whitney and Chi-Square tests. RESULTS Mortality risk in the patients with blood urea nitrogen levels >50 mg/dL was 3.58 higher compared with those with blood urea nitrogen levels 1.1 mg/dL was 3.0-fold higher compared to patients with creatinine levels

BACKGROUND: Not only hypertension, prehypertension has been reported to be linked with increased cardiovascular morbidity and mortality risks as well. Prehypertension has three-fold hypertension and two-fold cardiovascular risks. Pathomechanism that links hypertension with cardiovascular is related with endothelial dysfunction and insulin resistance. Endothelial dysfunction occurs when nitric oxide (NO) biological function was impaired, whereas shown by asymmetric dimethylarginine (ADMA). Subjects with prehypertension had higher insulin resistance events than normotension, whereas shown by homeostatic model assessment-estimated insulin resistance (HOMA-IR). This research was conducted to investigate the correlation of HOMA-IR with ADMA in prehyper- and normo-tension. METHODS: A cross-sectional comparative research was designed. Subjects were recruited and divided into prehyper- and normo-tensive groups. ADMA was measured using ELISA method, while HOMA-IR was calculated by the ratio of fasting insulin and glucose. Spearman 1-tail and Mann Whitney statistical analyses were performed. RESULTS: Comparing to normotensive group, elevated levels of HOMA-IR and ADMA in prehypertensive group were shown, but not significant. In prehypertensive group, we found significant correlation between HOMA-IR and ADMA. CONCLUSIONS: Insulin resistance and endothelial dysfunction was elevated in prehyper-compared to normotension. KEYWORDS: prehypertension, insulin resistance, endothelial dysfunction, HOMA-IR, ADMA.

INTRODUCTION Blood urea nitrogen and creatinine levels are routine laboratory tests for evaluating renal function. Renal dysfunction has been related to worse prognosis of cardiovascular diseases. The purpose of this study was to determine the relationship between admission blood urea nitrogen and creatinine levels with in-hospital mortality in acute myocardial infarction patients. METHODS A cross-sectional study was performed using secondary data of 80 acute myocardial infarction patients hospitalized in Intensive Cardiac Care Unit of dr. Wahidin Sudirohusodo Hospital, Makassar, from June 2010 to July 2011. Admission blood urea nitrogen and creatinine levels were analyzed with Mann Whitney and Chi-Square tests. RESULTS Mortality risk in the patients with blood urea nitrogen levels >50 mg/dL was 3.58 higher compared with those with blood urea nitrogen levels 1.1 mg/dL was 3.0-fold higher compared to patients with creatinine levels

BACKGROUND: Hyperglycemia in diabetic patients cause both chronic inflammation and extracellular matrix accumulation that can lead to progressive renal damage. Albumin, Gammaglutamytransferase (GGT) and clusterin in urine are markers to detect damage in glomerulus, cell of the tubules and proximal tubules, respectively. METHODS: This study aimed to evaluate the pathomechanism of haemoglobin A1c (HbA1c), albumin, GGT, clusterin, type IV collagen in urine, and high sensitivity C-reactive protein (hsCRP) in type 2 diabetes mellitus (DM) patients. The study was a cross sectional study involving 82 subjects consisting of 36 males and 46 females, 35-65 years old, divided into 3 groups: uncontrolled DM, controlled DM and non DM. Data were obtained from interviews, physical examinations (weight, height, blood pressure) and laboratory examinations (HbA1c, serum glutamic oxaloacetic (SGOT), serum glutamic pyruvic (SGPT), creatinine, hsCRP, urinary albumin, urinary GGT, urinary clusterin, and urinary type IV collagen). Statistical analysis was performed for correlation, difference and cross tabulation tests. RESULTS: The study results showed there were significant differences (p

BACKGROUND: There is a prevalence increase of overweight and obesity in Indonesia. Central obesity can lead a variety of chronic diseases through the inflammatory process. There are some markers for low-grade chronic inflammatory, such as cathepsin S, high sensitivity C-reactive protein (hs-CRP), interleukin-1- beta (IL-1β). To our current interest that central obesity can lead to various chronic diseases through the inflammatory process, we conducted a study to investigate correlation of Cathepsin S, hs-CRP, IL-1β in men with central obesity. METHODS: A cross-sectional study was conducted. Seventy-eight selected subjects were examined to collect anthropometric data and prepared for sample collection. Collected samples were processed for the following biochemical analyses: fasting glucose, high density lipoprotein (HDL)-cholesterol, triglyceride, serum glutamic oxaloacetic transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT), cathepsin S, hs-CRP, and IL-1β. Data distribution and variable correlation were then statistically analyzed. RESULTS: There were significant correlations between waist circumference (WC) and cathepsin S (p=0.030; r=0.214), hs-CRP and cathepsin S (p=0.007; r=0.276), triglyceride and IL-1β (p=0.019; r=-0.235), WC and systolic blood pressure (SBP) (p=0.003; r=-0.312), WC and fasting glucose (p=0.000; r=0.380), WC and body mass index (BMI) (p=0.000; r=0.708). CONCLUSIONS: Our study showed that cathepsin S was correlated with central obesity, suggesting that cathepsin S could be a potential inflammatory marker in central obesity in the future. KEYWORDS: obesity, inflammation, hs-CRP, cathepsin S, IL-1β, waist circumference.

BACKGROUND: Coffee is the most widely consumed beverage in the world and has been known to have effects on cardiovascular system. Many researchers have examined the effects of coffee consumption on blood pressure (BP) and risk of cardiovascular disease (CVD), but their results were inconsistent and still remain a subject of controversy. Oxidative stress, inflammation, and endothelial dysfunction have been known as risk factors of hypertension and CVD. Those factors are also known to be affected by coffee consumption. The aim of this study was to examine the relationship between the effects of habitual coffee consumption on BP and to examine the role of oxidative stress (F2 isoprostane), inflammation (high sensitive C-reactive protein (hsCRP)) and endothelial dysfunction (asymmetric dimethylarginine (ADMA)). METHODS: This was a cross-sectional study in which 47 healthy, non-smoking men aged 30-60 years with varying coffee-drinking habits were enrolled. BP and blood/urine analysis of biomarkers were measured in the morning before activity. Coffee consumption was assessed using a questionnaire. The differences among variables were analyzed using ANOVA and the correlations between variables were analyzed using Kendall’s Tau correlation analysis. RESULTS: Habitual coffee consumption did not correlate with systolic/diastolic BP (r=-0.02; p=0.856 and r=0.15; p=0.230, respectively). Concentrations of ADMA and hsCRP were also not correlated with coffee consumption (r=0.03; p=0.764 and r=0.04; p=0.701, respectively). Coffee consumption only showed significant correlation with F2 isoprostane (r=0.34; p=0.004). CONCLUSIONS: BP was not affected by coffee consumption although coffee consumption has a significant correlation with F2 isoprostane. These findings suggest that correlation between coffee consumption and BP might be explained by other factors that were not included in this study. KEYWORDS: coffee, caffeine, cardiovascular disease, blood pressure, oxidative stress, inflammation, endothelial dysfunction.

BACKGROUND: Adipose tissue expansion in obesity leads to abnormal adipocyte function, chronic low grade inflammation, primary reticulum stress, and mitochondrial stress. This induces mitochondrial unfolded protein response (UPRmt) that selectively upregulates mitochondrial chaperone protein. Heat shock Protein 60 (HSP60) is the primary chaperone in mitochondrial matrix. Inflammatory stress promotes HSP60 released from adipocytes and induces insulin resistance. In this study we attempted to investigate the correlation between exHSP60 and HOMA-IR in men with different ranges of waist circumference (WC). METHODS: This study was an observational cross sectional study carried out on 141 non diabetic men, aged 30-55 years old, who were divided into three groups based on WC; WC ≤90 cm, 90 cm < WC ≤ 100 cm and WC >100 cm. Fasting plasma glucose, triglyceride, HDL-C, hsCRP, HSP60 serum and anti-HSP60 antibody, serum IL-1β serum, insulin, were examined. For statistical analysis, Kolmogorov-Smirnov and Spearman’s correlation analysis were conducted. RESULTS: There were a significant correlation between exHSP60 and HOMA-IR (r=0.281; p=0.041) in WC ≤90 cm group; and a negative significant correlation between exHSP60 and HOMA-IR (r=-0.508; p=0.007) in WC >100 cm group. CONCLUSIONS: This study showed that there was a dynamic correlation between exHSP60 and HOMA-IR in WC ≤90 cm group compared with WC >100 cm group. We also found inverse correlation patterns between exHSP60 and HOMA-IR, and between anti-HSP60 antibody and HOMA-IR in non diabetic subjects. KEYWORDS: obesity, insulin resistance, mitochondrial stress, exHSP60, hsCRP, HOMA-IR.

BACKGROUND: Hypertension and central obesity are risk factors of cardiovascular disease. Epidemiology studies have shown that these two conditions are closely linked and often occur simultaneously. Inflammation is an underlying pathomechanism in hypertension and obesity. Vascular inflammation is related to coagulation pathway, whereby high level of inflammation increases the risk of atherothrombosis event. The aim of this study was to investigate the correlation between inflammation and fibrinolysis in hypertensive centrally obese subjects compared with hypertensive non obese subjects. METHODS: This was a cross sectional study conducted in October 2009-June 2010 involving 53 eligible subjects according to the following criteria: men or women aged 30-65 years, had neither diabetes (FPG

BACKGROUND: Recent studies have indicated that lead may affect activities on bone cells, but the mechanism is not yet clear. Therefore, we conducted a study to investigate correlation of chronic low-concentration lead exposure with bone turnover activity (ratio of C-telopeptide (CTx) and Procollagen Type 1 Amino-terminal Propeptide (P1NP) (CTx/P1NP)) and antioxidant (aminolevulinic acid (ALA) dehydratase (ALAD)) in a workers community. METHODS: An observational study with cross-sectional design was carried out. Fifty two subjects from a workers community in Jakarta, Indonesia, had provided informed consents and undergone medical history, physical and laboratory examinations. Hair lead concentration was measured by Inductively Coupled Plasma Mass Spectrometry (ICP-MS) method. Meanwhile, P1NP was measured by Enzyme-linked immunosorbent assay (ELISA) and CTx was measured by Electro-chemiluminescence Immunoassay (ELICA) method. RESULTS: The mean hair lead concentration was 4.85 ppm. Based on Mayo Clinic reference, 28.85% of investigated subjects had hair lead concentration of ≥5 ppm. Hair lead concentration was not correlated with ALAD, CTx, P1NP concentrations or CTx/P1NP. ALAD concentration was significantly correlated with CTx/P1NP (p

BACKGROUND: Ghrelin has many biological activities such as regulating energy homeostasis and recent studies have shown its effects in the cardiovascular system. Ghrelin concentration decreases in obese man that indicates relatioship between ghrelin and energy homeostasis. Ghrelin also improves endothelial function by increasing the bioavaibility of nitric oxide (NO). The bioavaibility of NO is also influenced by ADMA. ADMA is an endogenous competitive inhibitor of endothelial nitric oxide synthase (eNOS), which is significantly elevated during endothelial dysfuction. This study aimed to evaluate the relationship of ADMA and ghrelin with central obesity based on waist circumference and to evaluate the relationship of total ghrelin and ADMA in centrally obese men. METHODS: Total ghrelin and ADMA were measured in 20 non-obese men (waist circumference (WC) 78.85±4.40 cm) and 60 centrally obese men (WC 97.54±5.94 cm). Anthropometric measurements (height, weight, BM, waist circumference and blood pressure) were also recorded. Statistic were carried out by the Spearman and Pearson bivariate correlation analysis and independent sample T test. RESULTS: ADMA concentrations were significantly higher in centrally obese men than in normal weight controls (p-value 0.05). Ghrelin total concentrations were significantly lower in centrally obese men with metabolic syndrome than in normal weight controls (p-value

BACKGROUND: A large number of obesity in the community increases the incidence of Metabolic Syndrome (MetS) that can increase the risks of heart disease, diabetes, and stroke. One of the possible causes of stroke is atherosclerosis. Atherosclerosis is initiated by the incidence of inflammation and endothelial dysfuction. Atherosclerosis is involved in an ongoing inflammatory response. At the beginning of atherosclerosis, when the endothel become inflamed, it expresses adhesion molecules that attract monocytes. The monocytes then migrate into the intima due to endothelial dysfunction. Activation of macrophage occurs in the process of inflammation as the earliest type of lesion of atherosclerosis. In this study, monocyte/macrophage activation is marked by Neopterin. In other process of atherosclerosis, vascular nitric oxide (NO) activity has a role as a potent endogenous vasodilator. In regulating the vascular tone, NO has a role to suppress vascular smooth muscle proliferation, inhibit platelet adhesion and aggregation, and interferes with the leukocyte-endothelial cell interaction. In MetS, hypercholesterolemia decreases NO activity. Asymmetric Dimethylarginine (ADMA) has been characterized as an endogenous, competitive inhibitor of NO synthase. In this study, the incidence of endothelial dysfunction is marked by ADMA. The aim of this study was to discover the role of Neopterin in MetS patients by evaluating the correlation between Neopterin and ADMA in MetS through tumor necrosis factor (TNF)-α or direct line. METHODS: The study was cross sectional on 64 males with MetS aged 30-65 years. The measurements of TNF-α concentrations was done, respectively. RESULTS: Neopterin concentration correlated with Log TNF-α concentration (r=0.311, p=0.012). There is no significant correlation between Neopterin and ADMA (r=0.012, p=0.930); ADMA and Log TNF-α (r=0.029, p=0.821). CONCLUSIONS: There is no significant correlation between Neopterin and ADMA through TNF-α or direct line. KEYWORDS: MetS, Neopterin, ADMA, NO, TNF-α.

BACKGROUND: Inflammation in the vascular wall plays an important role in the pathogenesis of atherosclerosis. Current studies have shown that increase of systemic inflammatory marker like the acute phase component C-reactive protein (CRP) are associated with an unfavorable progression of disease and an increased risk for acute cardiovascular events. Recently, a close association of Metabolic Syndrome (MetS) with hemostatic abnormalities has been reported. Among hemostatic abnormalities, an increase in plasminogen activator inhibitor (PAI)-1, a strong inhibitor of fibrinolysis, is considered a core feature of MetS. High PAI-1 concentrations may be associated with thrombus formation, also causing cardiovascular events. Therefore, we investigated the association between markers for chronic inflammation (CRP) and the markers of fibrinolytic impairment (PAI-1, PAP, TAFI) in subjects with central obesity. METHODS: This was a cross-sectional study in 80 male Indonesian subjects, aged 30-60 years old with central obesity, conducted from January to March 2008 in Bandung. RESULTS: The study results showed that there was a difference of PAI-1 levels between MetS and Non-MetS group. There were significant correlations between hsCRP and PAI-1 (r=0.252, p=0.024), hsCRP and PAP (r=0.253, p=0.024), and also between PAI-1 and PAP (r=-0.239, p=0.033) respectively. But, no correlation found between hsCRP and TAFI. CONCLUSIONS: There was correlation between inflammation and fibrinolysis impairment on central obesity. Concentrations oh hsCRP, PAI-1 and TAFI were significantly higher in MetS. KEYWORDS: inflammation, fibrinolysis impairment, hsCRP, PAI-1, PAP, TAFI.

BACKGROUND: Several researches reported that inflammatory and immunological mechanism such as autoantibody to β2-glycoprotein I (anti β2GPI) appear as related factors in initiation and progress of atherosclerosis lesion in patient with autoimmune disease. Antibody to β2GPI titers are correlated with atherosclerosis and in vitro studies showed that they enhance oxidized low density lipoprotein (ox-LDL) uptake by macrophages. Immunization with auto-antigen β2GPI elicits an immune response to influence lesion progression that mostly happens in autoimmune subjects. The metabolic syndrome (MetS) is combination of several metabolic disorders such as obesity, dyslipidemia, Diabetes Mellitus (DM) and conditions due to inflammation and stress oxidative. The Correlation between inflammatory markers such as High sensitivity C-Reactive Protein (hsCRP) and anti-β2GPI antibody in MetS needs to be further investigated. METHODS: This was an observational study with cross sectional design on subject with MetS as determined by the International Diabetes Federation (IDF) 2005’s criteria. RESULTS: There was a positive and significant correlation between hsCRP and anti-β2GPI antibody in MetS group (r=0.406; p≤0.05) as compared to non-MetS group. We found that there was elevated level of anti-β2GPI antibody in hsCRP of 3-10 mg/L. CONCLUSIONS: Anti-β2GPI antibody may be elevated in subjects with MetS who have low grade of inflammation as shown by hsCRP. KEYWORDS: metabolic syndrome, inflammation, autoantigen, atherosclerosis, obesity.

BACKGROUND: Obesity is closely associated with atherosclerosis risk and cardiovascular disease. Novel cardiovascular risk biomarkers such as Urine Albumin/Creatinine Ratio (UACR), High Sensitivity C-Reactive Protein (hsCRP) and N-Terminal pro Brain Natriuretic Peptide (NT-proBNP) have been observed to predict cardiovascular disease in the general population. The aim of this study was to observe the correlation of UACR, hsCRP and NT-proBNP with atherosclerosis (OxLDL) in centrally obese men. METHODS: The study was observational with a cross sectional design done on 76 male subjects aged 30–50 years with central obesity and mean of age of 37 years. Urine albumin was determined by PEG enhanced immunoturbidimetric assay, urine creatinine by Jaffe without deproteinase, hsCRP by chemiluminescent immunometric assay, NT-proBNP by electrochemiluminescence (ECLIA) and OxLDL by ELISA. RESULTS: There was significant correlation between hsCRP and OxLDL (r=0.230, p=0.046). There was no significant correlation between UACR and OxLDL (r=-0.138, p=0.236), neither between Log NT-proBNP and OxLDL (r=-0.173, p=0.136). CONCLUSIONS: Atherosclerosis was significantly correlated with hsCRP (low grade inflammation). KEYWORDS: NT-proBNP, UACR, hsCRP, OxLDL, atherosclerosis.

BACKGROUND: Heart failure (HF) is associated with an increased expression of proinflammatory cytokines, especially soluble tumor necrosis factor receptor I (sTNFR I), but the underlying mechanism to the relationship between sTNFR I activation and the progression of HF is not yet fully understood. This study aims to see the association between sTNFR I, MMP-9, PICP, and NT-proBNP in the progression of HF. METHODS: This was a cross sectional study which recruited 45 subjects with HF confirmed by echocardiography and NT-proBNP. Concentration sTNFR I, MMP-9, and PICP were measured using ELISA method, whereas NT-proBNP concentration was measured using ECLIA method. Univariate linear regression analysis, path analysis and General Linear Model were used to determine which parameters played the most significant role in HF. RESULTS: Results of the univariate linear regression and path analysis showed there was a linear relationship between sTNFR I with MMP-9, with R square of 25.8% (p=0.00; r=0.508), R square sTNFRI and MMP-9 with PICP was 14.4% (p=0.038; r=0.379) and R square MMP-9 and PICP with NT-proBNP was 39.6% (p=0.00; r=0.629). From the General Linear Model we found that the important predictor for HF was through MMP-9 and PICP. CONCLUSIONS: sTNFR I as a proinflammatory factor is one of the factors involved in the heart failure as seen by NT-proBNP through activation of brosis (PICP) and remodeling factor (MMP-9). KEYWORDS: sTNFR I, MMP-9, PICP, NT-proBNP, heart failure.

BACKGROUND: Adult obesity is rapidly increasing in the world including Indonesia. Tumor necrosis factor α (TNF-α) was chronically elevated in obese adipose tissue. TNF-α, a pleiotropic cytokine and also a regulator of bone formation, may might represent an important link between obesity and vascular calcification. Elegant genetic studies in mice and human have highlighted the important roles for Matrix Gla Protein (MGP) as an inhibitor of vascular calcification. The aim of this study was to examine the correlation between circulating levels of pro-inflammatory cytokines TNF-α and vascular calcification inhibitor MGP in obese men. METHODS: This was an observational cross-sectional study including 40 central obese men (waist circumference ≥90 cm) aged 31-60 years old. Serum MGP and serum TNF-α concentrations were quantified by ELISA principle. Fasting plasma glucose was assessed using hexokinase methods, triglyceride by GPO-PAP methods, and creatinine by Jaffe methods. All assays were performed according to the manufacture instruction. Statistical analysis was performed with SPSS for windows ver 16. Univariate analysis were performed to analyze mean, maximum, minimum value and SD. Pearson correlation statistic were performed to determine the correlation between variables. Significance value were define as alpha level=0.05 based on two-tailed tests. RESULTS: The cross-sectional study (n=40) showed that the advancing age was correlated with plasma TNF-α concentration (r = 0.348; p = 0.028). The mean concentration of TNF-α and MGP were 8.323 and 8.368, respectively. We found a significant negative correlation between TNF-α with MGP (r=-0.425; p=0.006) and a significant correlation between TNF-α and triglyceride (r=0.375; p=0.017). CONCLUSIONS: Circulating level of TNF-α was inversely correlated with MGP concentration in obese men. This finding suggested that high level TNF-α leads to low MGP concentration obese men, hence, limits inhibitory capacity in vascular calcification. KEYWORDS: hypertension, obesity, vascular calcification, MGP, TNF-α.

BACKGROUND: The low inflammatory state that accompanies the Metabolic Syndrome (MetS) associates with the overexpression of oxidative stress. Ferritin and Transferrin serum are often used to measure iron status and their concentrations are altered in several metabolic conditions. We hypothesized that concentration of Ferritin and Transferrin serum increase in Metabolic Syndrome (MetS) and correlate with the inflammation and oxidative stress. METHODS: We studied 65 male MetS patients, aged 43.26±7.16 years. Iron metabolism was measured by concentration of Ferritin and Transferrin serums, while inflammatory and oxidative stress by high sensitivity C-reactive Protein (hsCRP) and F2-Isoprostane. RESULTS: Concentration of Ferritin 315.70±188.63 ng/L and Transferrin 2.36±0.31 g/L increased along with increasing components of MetS. Concentration of Ferritin serum had a positive correlation with hsCRP (r=0.220) and F2-Isoprostane (r=0.023). CONCLUSIONS: Serum concentration of Ferritin increased in the MetS and correlates with hsCRP and F2-Isoprostane. KEYWORDS: metabolic syndrome, ferritin, transferrin, hsCRP, F2-isoprostane.

A recent modeling study estimated that there could be as many as 20,000 human melioidosis cases per year in Indonesia, with around 10,000 potential deaths annually. Nonetheless, the true burden of melioidosis in Indonesia is still unknown. The Indonesia Melioidosis Network was formed during the first melioidosis workshop in 2017. Here, we reviewed 101 melioidosis cases (99 human and two animal cases) previously reported and described an additional 45 human melioidosis cases. All 146 culture-confirmed cases were found in Sumatra (n = 15), Java (n = 104), Kalimantan (n = 15), Sulawesi (n = 11) and Nusa Tenggara (n = 1). Misidentification of Burkholderia pseudomallei was not uncommon, and most cases were only recently identified. We also evaluated clinical manifestations and outcome of recent culture-confirmed cases between 2012 and 2017 (n = 42). Overall, 15 (36%) cases were children (age

von Willebrand's disease (vWD) is an autosomally inherited bleeding disorder caused by a deficiency or abnormality of von Willebrand factor (vWF). vWF is a multimeric adhesive protein that plays an important role in primary hemostasis by promoting platelet adhesion to the subendothelium at the sites of vascular injury. It is also the carrier of factor VIII (FVIII), thus indirectly contributing to the coagulation process. Bleeding symptoms are usually mucocutaneous and postsurgical with varying severity. The diagnosis of vWD requires a personal and family history of bleeding and confirmation by laboratory analysis involving vWF antigen level, vWF ristocetin cofactor, FVIII activity, ristocetin-induced platelet aggregation, and vWF multimer analysis. KEYWORDS: von Willebrand's disease, von Willebrand factor.

BACKGROUND: Asymmetric dimethylarginine (ADMA) is a competitive inhibitor of nitric oxide synthase (NOS). ADMA reduces NO synthesis when its concentration elevates. ADMA is a novel risk factor for cardiovascular disease. Plasma ADMA accumulates in patients with endstage renal disease, due to reduced renal clearance. Hyperhomocysteinemia is often found in patients with chronic kidney disease (CKD). Homocysteine may cause ADMA to accumulate; however, the mechanism by which ADMA level elevates in hyperhomocysteinemia is still unclear. Objective of this study was to analyze the concentrations of homocysteine and ADMA and to assess the correlation between homocysteine and ADMA concentrations with the severity of chronic kidney disease. METHODS: This was a cross-sectional study on 75 patients with CKD, comprising men and women aged 40-70 years. Assessments were done on the concentrations of creatinine, homocysteine, ADMA, fasting blood glucose, cholesterol HDL and triglyceride. RESULTS: In later stage of CKD there was significantly higher tHcy concentration as compared with the earlier stage of CKD (p=0.0000). In CKD stage 2 to 4 there was a tendency for ADMA concentration to increase to a significant average (p=0.210), but ADMA concentration was lower at stage 5. There was increased ADMA along with increased tHcy concentration of around 20μ mol/L, and this then decreased. The inverse correlation between tHcy and ADMA concentrations started to appear in CKD stage 4, but this correlation was statistically insignificant (r2=0.19; p=0.499). CONCLUSIONS: This study showed there was a correlation between homocysteine and ADMA concentrations in patients with CKD stage 2 to 5, although statistically not significant. KEYWORDS: asymmetric dimethylarginine, homocysteine, chronic kidney disease.

BACKGROUND: Breast cancer is the most frequent cancer diagnosed among women. Many factors influence the carcinogenesis of breast cancer. The aim of this study to analyze the role of obesity (waist circumference and body mass index), serum Estradiol levels, TNF-α, and Adiponectin in the occurrence of breast cancer. METHODS: This was observational study with case control design. Eleven breast cancer patients as cases and twelve Fibroadenoma Mammae (FAM) patients as controls were analyzed. The serum Estrogen, TNF-α and Adiponectin were examined in their association with breast cancer risk. RESULTS: Women with breast tumor and waist circumference >80 cm have significantly higher breast cancer risk than women with breast tumor and waist circumference 2.30 pg/ml) have higher breast cancer risk (19.25 times) than women with breast tumor and have lower serum TNF-α levels (95% CI=1.77-209.55, p=0.015). Whereas, women with breast tumor and lower Adiponectin/TNF-α ratio (80 cm and low Adiponectin/TNF-α ratio in women with breast tumor are significantly associated with an increased risk for breast cancer. KEYWORDS: obesity, breast cancer, adiponectin/TNF-α ratio.