Treatment Strategy for Rifampin-Susceptible Tuberculosis.

BACKGROUND: Tuberculosis is usually treated with a 6-month rifampin-based regimen. Whether a strategy involving shorter initial treatment may lead to similar outcomes is unclear. METHODS: In this adaptive, open-label, noninferiority trial, we randomly assigned participants with rifampin-susceptible pulmonary tuberculosis to undergo either standard treatment (rifampin and isoniazid for 24 weeks with pyrazinamide and ethambutol for the first 8 weeks) or a strategy involving initial treatment with an 8-week regimen, extended treatment for persistent clinical disease, monitoring after treatment, and retreatment for relapse. There were four strategy groups with different initial regimens; noninferiority was assessed in the two strategy groups with complete enrollment, which had initial regimens of high-dose rifampin-linezolid and bedaquiline-linezolid (each with isoniazid, pyrazinamide, and ethambutol). The primary outcome was a composite of death, ongoing treatment, or active disease at week 96. The noninferiority margin was 12 percentage points. RESULTS: Of the 674 participants in the intention-to-treat population, 4 (0.6%) withdrew consent or were lost to follow-up. A primary-outcome event occurred in 7 of the 181 participants (3.9%) in the standard-treatment group, as compared with 21 of the 184 participants (11.4%) in the strategy group with an initial rifampin-linezolid regimen (adjusted difference, 7.4 percentage points; 97.5% confidence interval [CI], 1.7 to 13.2; noninferiority not met) and 11 of the 189 participants (5.8%) in the strategy group with an initial bedaquiline-linezolid regimen (adjusted difference, 0.8 percentage points; 97.5% CI, -3.4 to 5.1; noninferiority met). The mean total duration of treatment was 180 days in the standard-treatment group, 106 days in the rifampin-linezolid strategy group, and 85 days in the bedaquiline-linezolid strategy group. The incidences of grade 3 or 4 adverse events and serious adverse events were similar in the three groups. CONCLUSIONS: A strategy involving initial treatment with an 8-week bedaquiline-linezolid regimen was noninferior to standard treatment for tuberculosis with respect to clinical outcomes. The strategy was associated with a shorter total duration of treatment and with no evident safety concerns. (Funded by the Singapore National Medical Research Council and others; TRUNCATE-TB ClinicalTrials.gov number, NCT03474198.).

Correlation of CD 133 Biomarker with Outcomes and Therapy Response in Advanced-Stage Non-Small Cell Lung Carcinoma.

OBJECTIVE: This study aimed to analyze CD 133 stem cell biomarker levels in serum and bronchial lavage, as well as correlate these levels with treatment responses and outcomes in patients with advanced-stage NSCLC. METHODS: This is a cross-sectional, observational, and analytical study that analyzed data from NSCLC patients and control at Dr. Wahidin Sudirohusodo Hospital, Makassar. CD 133 levels in serum and bronchial lavages were quantified using ELISA and correlated with treatment responses assessed by RECIST 1.1 criteria. RESULT: A total of 118 participants were used, with 66 being NSCLC patients and 52 as the control. The results showed significant differences in CD 133 serum and bronchial lavage levels (p<0.05). Moreover, NSCLC patients with advanced tumors (T4) had higher CD 133 levels in bronchial wash (p<0.05). The bronchial wash CD 133 test showed higher sensitivity (83.6%) and specificity (79.2%) compared to serum CD 133. Even though CD 133 levels were not significantly correlated with treatment response, they were higher in patients with advanced tumor stages. CONCLUSION: CD 133 levels were significantly higher in bronchial wash samples from NSCLC patients with advanced tumors (T4). Also, there was a positive correlation between CD 133 levels in bronchial wash and serum. These results emphasized the potential of CD 133, particularly in bronchial wash, as a valuable diagnostic tool for NSCLC.

Exploring the link between cardiovascular risk factors and manifestations in latent tuberculosis infection: a comprehensive literature review.

BACKGROUND: The global burden of tuberculosis (TB) and cardiovascular disease (CVD) is overt, and the prevalence of this double burden disease remains steadily rising, particularly in low- and middle-income countries. This review aims to explore the association between latent tuberculosis infection (LTBI) and the development of cardiovascular diseases and risk factors. Furthermore, we elucidated the underlying pathophysiological mechanisms that contribute to this relationship. MAIN BODY: Approximately 25% of the global population carries a dormant form of tuberculosis (TB) infection. During this latent stage, certain subsets of mycobacteria actively reproduce, and recent research suggests that latent TB infection (LTBI) is connected to persistent, long-term low-grade inflammation that can potentially contribute to the development of atherosclerosis and cardiovascular disease (CVD). The presence of LTBI can be confirmed through a positive result on either a tuberculin skin test (TST) or an interferon-gamma release assay (IGRA). Several plausible explanations for the association between LTBI and CVD include increased inflammation, autoimmunity related to heat shock proteins (HSP), and the presence of pathogens within the developing atherosclerotic plaque. The most commonly observed cardiovascular events and risk factors associated with LTBI are acute myocardial infarction, coronary artery stenosis, diabetes mellitus, and hypertension. CONCLUSIONS: This article highlights the critical role of LTBI in perpetuating the tuberculosis disease cycle and its association with cardiovascular risk factors. Chronic and persistent low inflammation underlined the association. Identifying high-risk LTBI patients and providing targeted preventive medication are crucial strategies for global TB eradication and interrupting transmission chains.

Factors Influencing the Implementation of Interprofessional Collaborative Practice in Teaching Hospital Setting: A Mixed-Method Study.

Introduction: Health service in the current global era requires health workers to provide qualified service, this also applies to teaching hospitals. Collaboration between several professions involved (doctors, nurses, and pharmacists) in an interprofessional collaboration system is needed in providing such service. Factors influencing interprofessional collaboration is unique to each health care center. The purpose of this study was to determine the factors that influence the implementation of interprofessional collaborative practice among health workers in Dr. Wahidin Sudirohusodo General Hospital. Methods: This is a mixed-method explanatory sequential design study, utilizing quantitative and qualitative data. Quantitative data were obtained from the Indonesian-validated Collaborative Practice Assessment Tool (CPAT) questionnaire. CPAT in Indonesian language has been validated in previous research by Findyartini, et al. in 2019 in Indonesian population. The questionnaire was internally validated with the study population with Cronbach alpha of 0.812. All health care professionals meeting the selection criteria were enrolled for the quantitative study. The questionnaire was given to 152 health professionals enrolled as research subjects, including nutritionists, nurses, doctors, pharmacists, and medical rehabilitation specialists serving in Dr. Wahidin Sudirohusodo Hospital for >3 years. Five participants with highest and lowest CPAT score from each profession were invited for FGD entitled "Exploring factors involved in interprofessional collaboration in Wahidin Sudirohusodo General Hospital" and divided into 2 groups according to the CPAT score. The score from each subscale in the questionnaire is obtained for each research subjects and the median is compared among each profession group using Kruskall-Wallis test significant to a p value of <0.05. Qualitative data as recording transcript is acquired from FGD; the transcript was then coded into several general themes by 2 of the authors and was discussed using thematic analysis using MaxQDA. Results: Research subjects were predominantly women (121 respondents (79.6%)), 32.9% were nurses, and most of the healthcare professional (81 subjects (55.1%)) have been working for >10 years. Among profession groups (Doctors, Pharmacists, Medical Rehabilitation Specialists, Nutritionists, and Nurses), difference in score distribution (p<0.05) was found in relationships among team members (40 vs 39 vs 39.5 vs 36 vs 42, p<0.001), barriers to team collaboration (10 vs 18.5 vs 14 vs 18 vs 10, p<0.001), and leadership (20 vs 20 vs 23 vs 20 vs 20, p 0.045). From the FGD, factors influencing interpersonal collaborative practice are leadership factors, system/rule factors, and personal factors. Conclusion: This research showed that personal, system/organizational and leadership factors influence the implementation of interprofessional collaboration. In this study, there is a different perception regarding relationships among team members, barriers to team collaboration, and leadership among profession group.

Correlation expression Toll-like receptor 4 with multidrugs resistant tuberculosis in diabetes mellitus condition.

BACKGROUND: Toll-like receptor (TLR) are ligand homologous protein in the APC cell membrane that has functions as a receptor to triger leukocytes and innate immune responses. When there is a Microbacterium tuberculosis (MTB) infection enters from droplets to the lungs, the alveolar macrophages perform a phagocytic function. The interaction between M. tuberculosis and the TLR macrophage receptors produces chemokines which induce migration of monocytes and dendrite cells for destruction. Diabetes militus (DM) has become risk factor for developing tuberculosis. DM condition will reduce immunity and the ability of immune cell phagocytes bactery and triger severe infections. The consequences of more severe infection and metabolic disorders that occur make a person more likely to experience Multidrugs resistant MTB. Not much data that reports on the expression of TLR4 as a ligand that triggers an immune response in conditions of MDR and DM. We try to find out correlation between TLR-4 in MDR MTB, diabetes and level of MTB bacteria in experimental animals. METHODS: We conducted an experimental study on 30 experimental mice weighing 25 grams consisting of negative control grub, infected with MTB, infected with MDR MTB, negative control diabetes, MTB DM, MDR MTB DM. DM animals were induced by streptozosin to experience DM, then in the treatment of infection, intraperitoneal MTB and MDR MTB bacterial injections were given. Termination was carried out on day 14. We count number of bacteria level in the lungs and perform evaluation TLR4 from blood sampel. RESULTS: The negative control group had mean TLR value of 1.47 (± 0.46) while the MTB group showed an increase in TLR 9.22 (± 0.39) followed by MDR MTB 9.50 (± 0.29), DM negative control 9, 21 (± 0.24) and more increasing in conditions of DM MTB 13.36 (± 0.32) and DM MDR MTB 13.35 (± 0.34). ANOVA analysis showed a significant difference (P = 0.00). pearson correlation analysis find strong correlation TLR4 in MTB and MDR MTB with diabetes. CONCLUSION: there were a significant difference level TLR4 between MTB and MDR TB infection with diabetes. higher TLR4 level higher in DM MTB, DM MDR MTB. TLR 4 strong correlates with an increase in the number of MTB bacteria.

Serum iron levels in tuberculosis patients and household contacts and its association with natural resistance-associated macrophage protein 1 polymorphism and expression.

BACKGROUND: Iron deficiency can impair immune function, increasing tuberculosis (TB) susceptibility and severity. The research aimed to investigate iron deficiency anemia in TB patients and household contacts and its association with natural resistance-associated macrophage protein 1 (NRAMP1) polymorphism and expression. METHODS: The levels of iron, ferritin, and transferrin were measured in the serum by ELISA (Enzyme-Linked Immunosorbent Assay). NRAMP1 polymorphisms were determined by polymerase chain reaction (PCR) and sequencing. NRAMP1 gene expression was measured by real-time PCR. Interferon-gamma release assay (IGRA) checked on household contacts to screen household contacts with positive IGRA as the control. RESULTS: This study involved 35 TB cases and 35 TB contacts. The results showed that the serum Fe levels were found to be lower in the TB case group (median 149.6 µmol/L) than in the positive IGRA household contacts group (median 628.53 µmol/L) with a p-value <0.001. Meanwhile, ferritin levels in TB cases tended to be higher, in contrast to transferrin, which was found to tend to be lower in TB cases than household contacts but did not show a significant difference. This study found no association between the polymorphism of exon 15 D543 and active TB. However, NRAMP1 gene expression was lower in TB cases than in positive IGRA household contacts (p = 0.011). Besides, there was a positive correlation between NRAMP1 gene expression and serum Fe levels (r = 0.367, p = 0.006). TB was associated with decreased NRAMP1 gene expression (OR 0.086 95% CI 0.02-0.366, p = 0.001). Besides, TB was associated with low Fe levels (OR 0.533 95% CI 0.453-0.629, p < 0.001). CONCLUSION: Comparing the TB case to the household contacts group, decreased serum Fe levels were discovered in the TB case group. This study also shows a correlation of NRAMP1 gene expression to Fe levels in TB patients and household contacts and describes that TB may lead to decreased Fe levels by downregulating NRAMP1 expression.

Comparison between Neutralization Capacity of Antibodies Elicited by COVID-19 Natural Infection and Vaccination in Indonesia: A Prospective Cohort.

BACKGROUND: To fight the COVID-19 pandemic, immunity against SARS-CoV-2 should be achieved not only through natural infection but also by vaccination. The effect of COVID-19 vaccination on previously infected persons is debatable. METHODS: A prospective cohort was undergone to collect sera from unvaccinated survivors and vaccinated persons-with and without COVID-19 pre-infection. The sera were analyzed for the anti-receptor binding domain (RBD) titers by ELISA and for the capacity to neutralize the pseudovirus of the Wuhan-Hu-1 strain by luciferase assays. RESULTS: Neither the antibody titers nor the neutralization capacity was significantly different between the three groups. However, the correlation between the antibody titers and the percentage of viral neutralization derived from sera of unvaccinated survivors was higher than that from vaccinated persons with pre-infection and vaccinated naïve individuals (Spearman correlation coefficient (r) = -0.8558; 95% CI, -0.9259 to -0.7288), p < 0.0001 vs. -0.7855; 95% CI, -0.8877 to -0.6096, p < 0.0001 and -0.581; 95% CI, -0.7679 to -0.3028, p = 0.0002, respectively), indicating the capacity to neutralize the virus is most superior by infection alone. CONCLUSIONS: Vaccines induce anti-RBD titers as high as the natural infection with lower neutralization capacity, and it does not boost immunity in pre-infected persons.

Plasma Macrophage Migration Inhibitory Factor Concentration at Each Spectrum of Tuberculosis.

Macrophage migration inhibitory factor (MIF) is an inflammatory mediator in several diseases, including tuberculosis (TB). However, the role of MIF in each stage of TB remains to be further elucidated. Thus, this study aimed to analyze the differences in plasma MIF protein levels in patients with active pulmonary TB, positive and negative interferon-gamma release assay (IGRA) household contacts (HHCs), and healthy controls (HCs). Plasma MIF concentration was significantly higher in patients with active-new pulmonary tuberculosis (ATB) and HHCs compared with HCs (mean ± standard deviation: 17.32 ± 16.85, 16.29 ± 14.21, and 7.29 ± 5.39 ng/mL, respectively; P = 0.002). The plasma MIF concentration was not statistically different when compared between patients with ATB, IGRA-positive HHCs (17.44 ± 16.6 ng/mL), and IGRA-negative HHCs (14.34 ± 8.7 ng/mL) (P = 0.897). In conclusion, ATB patients, IGRA-positive HHCs, and IGRA-negative HHCs have a higher MIF concentration than HCs. This shows the involvement of MIF in each stage of TB, starting from TB exposure and infection, but not symptomatic, to the active stage.

Hematology profile analysis in coronavirus disease 2019 (COVID-19) patients.

Objectives: Some hematological parameters were reported as markers to assess severity of COVID-19 patients. Comorbidities were risk factors for severe COVID-19. Differences in hematology profile based on severity and comorbidity, and correlation between hematology profile and Ct value were never studied at Makassar, Indonesia. The aim of this study were to know the differences of hematology profile based on severity and comorbidity, and the correlation between hematology profile and Ct value in COVID-19 patients. Methods: This study was retrospective, cross-sectional of confirmed COVID-19 patients who had been hospitalized at Dr. Wahidin Sudirohusodo hospital, Makassar, since June to August 2020. Hematology profile, Ct value, comorbidity, and severity of COVID-19 patients were obtained from Hospital Information System Data. Results: From 217 patients, subjects were 102 (47%) male dan 115 (53%) female, 127 mild-moderate patients (58.5%) and 90 severe patients (41.5%), 143 patients (65%) without comorbidity, 74 patients (35%) with comorbidity. White blood cells (WBC), red cell distribution width (RDW), neutrophil and monocyte count, and neutrophil lymphocyte ratio (NLR) were significantly higher in severe patients than mild-moderate patients (p<0.05), besides RBC, hemoglobin, hematocrit, lymphocyte and thrombocyte count were significantly lower in severe patients than mild-moderate patients (p<0.05). Hematology profile was not different significantly based on comorbidity and was not correlated significantly with Ct value, except eosinophil count (r=0.161; p=0.018). Conclusions: We suggest that hematology profile could predict the severity of COVID-19 patients. Moreover, eosinophil count could be considered to predict the infectivity of patient with COVID-19.

Expression of miRNA-29a-3p and IFN-γ as biomarkers in active and latent pulmonary tuberculosis.

Background: Diagnosis and management of latent tuberculosis (TB) infections are one of the challenges of eradicating pulmonary TB. A critical aspect of controlling pulmonary TB spread is early diagnosis. One TB biological marker type under evaluation is microRNAs (miRNAs). Mycobacterium tuberculosis infection causes epigenetic changes. The upregulation of miRNA-29a-3p suppresses the immune response by post-transcriptionally inhibiting interferon (INF)-γ expression in T cells, increasing susceptibility to pulmonary TB. This study aimed to assess miRNA-29a-3p expression as a biomarker of active and latent pulmonary TB infection. Methods: This case-control study included 50 individuals with active TB, 33 household contacts with a positive IFN-γ release assay (IGRA), and 30 healthy controls. An enzyme-linked immunosorbent assay-based IGRA was used to determine latent pulmonary TB infection in household contacts. Quantitative real-time PCR was used to quantify miRNA-29a-3p expression. Data analysis used analyses of variance and receiver operating characteristic (ROC) curves. Results: miRNA-29a-3p expression differed significantly between active TB, latent TB, and healthy participants (controls; p = <0.001. ROC curve analysis showed that miRNA-29a-3p expression had 86% sensitivity and 73% specificity with an area under the ROC curve (AUC) of 0.763 (95% confidence interval [CI]: 0.668-0.858). The miRNA-29a-3p ROC curve had 84.8% sensitivity and 70% specificity with an AUC of 0.808 (95% CI: 0.698-0.919) for latent TB. Additionally, miRNA-29a-3p expression was significantly correlated with active (p < 0.0001) and latent (p < 0.0001) pulmonary TB. However, miRNA-29a-3p expression was not significantly correlated with INF-γ levels in patients with active (R = 0.005; p = 0.62) and latent (R = 0.010; p = 0.38) pulmonary TB or healthy controls (R = 0.060; p = 0.19). Conclusion: miRNA-29a-3p expression was increased in patients with active and latent pulmonary TB. Therefore, miRNA-29a-3p represents a potential biomarker for latent and active pulmonary TB. However, IFN-γ levels were not correlated with miR-29a-3p expression.

Excess mortality attributable to antimicrobial-resistant bacterial bloodstream infection at a tertiary-care hospital in Indonesia.

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.

Safety of DW-MSC infusion in patients with low clinical risk COVID-19 infection: a randomized, double-blind, placebo-controlled trial.

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.

Characteristics of Drug-sensitive and Drug-resistant Tuberculosis Cases among Adults at Tuberculosis Referral Hospitals in Indonesia.

As Indonesia's rifampin resistance testing rates are lower than global testing rates per the 2020 WHO global tuberculosis (TB) report, prevalence of multidrug-resistant TB may be underestimated. Our study aimed to evaluate prevalence and patterns of TB drug resistance (DR) within Indonesia. We conducted a cross-sectional analysis of baseline data collected from 2017-2018 as part of a cohort study of adults with presumed pulmonary TB at 7 DR-TB referral hospitals in Indonesia. Bacteriological examinations (acid-fast bacilli, GeneXpert, sputum culture) and drug-susceptibility testing were performed following the guidelines of the National TB Program. Of 447 participants with complete bacteriological examinations, 312 (69.8%) had positive sputum cultures for Mycobacterium tuberculosis. The proportion of MDR and pre-extensively drug-resistant was higher in previously treated compared with newly diagnosed participants (52.5% [73/139] versus 15% [26/173]). Compared with drug-sensitive case, drug-resistant TB was associated with cavities. Given the difference between rates of DR in TB referral hospitals from our study compared with the WHO survey in 2019 that showed 17.7% and 3.3% DR among previously treated and newly diagnosed participants globally, further characterization of Indonesia's TB epidemiology in the general population is needed. Strategies, including public policies to optimize case finding, strengthen capacity for resistance testing, and prevent loss to follow-up will be critical to reduce the burden of TB in Indonesia.

Comorbidities and mortality in COVID-19 patients.

BACKGROUND: The high mortality rate in Coronavirus Disease (COVID-19) patients is associated with their comorbid conditions. Therefore, it is important to identify risk factors associated with poor outcomes among COVID-19 patients. The aims of this study were to find out the comorbidities in case of death due to COVID-19. METHODS: The design of this study was a retrospective descriptive method with a confirmed COVID-19 patient on hospitalized at Dr. Wahidin Sudirohusodo Hospital from March to September 2020. Ethics Council recommendation number: 357/UN4.6.4.5.31/PP36/2020. RESULTS: A total of 454 patients were included of this study. 78 (17.18%) patients death due to COVID-19, consisting of 52 (66.67%) male and 26 (33.33%) female. Range of ages between 18 and 85 years. The highest mortality rate occurred in the age group ≥60 years (35; 51.47%), followed by the age group of 45-59 years (33; 48.53%), and the age group of <45 years (10; 12%). The prevalent comorbidity was hypertension (42.31%), cardiovascular disease (30.77%), diabetes (28.21%), chronic kidney disease (23.08%), malignancy (15.38%), obesity (15.38%), chronic liver disease (7.69%), chronic respiratory disease (6.41%), immune related disease (3.85%), and non-traumatic cerebral infarction (3.85%). 41 (52.56%) patients reported having two or more comorbidities, and 37 (47.44%) only has one comorbidity. Elevated neutrophil-to-lymphocyte ratio (NLR) ≥3.13 was seen in the majority of patients (68; 87.18%). The mean value of NLR was 20.94. CONCLUSIONS: Hypertension, cardiovascular disease, and diabetes were the most common comorbidity in patients death due to COVID-19. More than half of the patients had two or more comorbidities.

Serum vitamin D receptor and High Mobility Group Box-1 (HMGB1) levels in HIV-infected patients with different immunodeficiency status: A cross-sectional study.

BACKGROUND: HIV-AIDS patients typically have hypovitaminosis D. Vitamin D is a key mediator in inflammatory and infectious diseases, which VDR mediates its biological effect. High-mobility group box 1 protein (HMGB1) modulates HIV-1 replication in vitro. Vitamin D played a role in inhibiting HMGB1 secretion in the animal study. OBJECTIVES: This study aimed to examine differences and correlation of vitamin D receptor and HMGB1 protein levels in HIV patients with mild and severe immunodeficiency and healthy control participants. METHODS: This study using a cross-sectional design conducted at Volunteer Counseling and Testing (VCT) Clinic in Mataram, West Nusa Tenggara, Indonesia, from January to June 2020. Three groups of study participants were classified as HIV patients with severe immune deficiency (SID), HIV patients with mild immune deficiency (MID), and healthy controls (HC). RESULTS: Mean level of vitamin D receptor in SID HIV group was 25.89 ± 3.95 ng/ml, lower than those in MID-HIV group; 33.72 ± 1.69 ng/ml and in HC group; 50.65 ± 3.64 ng/ml. Mean levels of HMGB1 protein in the SID HIV group were 3119.81 ± 292.38 pg/ml higher than those in the MID HIV group 1553.55 ± 231.08 pg/ml and HC 680.82 ± 365.51 pg/ml. There was a significant and strong negative correlation (r = -0.932) between vitamin D receptor and HMGB1 levels (p < 0.01). CONCLUSIONS: Strong negative correlation between VDR and HMGB1 in different immunodeficiency statuses suggesting an important role of vitamin D in inflammation control in HIV infection. However, it needs to be confirmed in a further prospective study.

COVID-19 concomitant with infective endocarditis: A case report and review of management.

Coronavirus disease 2019 (COVID-19) has emerged as a pandemic and public health crisis across the world. With its high infectivity and rapid spread, the severity of the disease is escalating in certain populations, especially in patients with pre-existing cardiovascular disease. In developing countries, infective endocarditis remains a problem in patients with rheumatic heart disease. We report the case of a patient with a diagnosis of infective endocarditis concomitant with COVID-19, including the diagnosis, management, and main outcomes.

Intestinal tuberculosis: Case series of three patients.

BACKGROUND: Intestinal tuberculosis (ITB) is a fraction of extrapulmonary TB, and its diagnosis often pose a significant challenge due to nonspecific presentation. Several methods have been utilized to diagnosed ITB, including findings of specific inflammatory process on histopathological examination. We hereby report three cases of ITB that manifested as caecal and adnexal mass. CASE REPORT: First case, a 22-year-old male, presenting with abdominal pain, underwent exploratory laparotomy, biopsy, right hemicolectomy, and anastomosis end-to-side to the transverse ileocolical region due to partial ileus obstruction from caecal tumor. The second and third cases, a 27-year-old and 39-year-old females, both presenting with abdominal pain and distension, underwent exploratory laparotomy, adhesiolysis and biopsy. Histopathological examination in all three cases showed chronic granulomatous inflammation caused by TB. All three patients were diagnosed as ITB and received 6 months of anti-tuberculosis drug (ATD). DISCUSSION: Intestinal TB most commonly affected region is the ileocaecal, accounts for 64% of the incidence of gastrointestinal TB. The main reasons for the predilection of ileocaecal region are due to relatively longer faecal static, the abundant of lymphoid tissue, a neutral pH environment and absorptive transport mechanisms that allow swallowed mycobacterium to be absorbed. Intestinal TB may pose similar symptoms as those found in pulmonary TB, yet patients most commonly presenting with abdominal pain. Bacteriological signs and histopathological findings are gold standard for ITB diagnosis. Therapy for ITB includes pharmacological ATD and surgical therapy.

Relationship between Vitamin D Level and Serum TNF-α Concentration on the Severity of Chronic Obstructive Pulmonary Disease.

BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is a chronic inflammatory disease and disturbed bacterial clearance. Vitamin D deficiency is sometimes observed in COPD patients and as significant roles in increasing inflammation of airway obstruction and systemic obstruction, increasing pro-inflammatory cytokine including TNF-α, reduction of bacterial clearance and increase exacerbation risk due to infection. Also, vitamin D plays significant roles in the metabolism of calcium and mineralisation of bones and regulation system of immune. TNF-α also has essential roles in pathogenesis and inflammation of COPD. Several studies that investigate the relationship between vitamin D level and serum TNF-α concentration in COPD patients are relatively uncommon, including in Indonesia. AIM: This study aimed to assess the relationship between vitamin D level and TNF-α concentration in patients on the severity of the chronic obstructive pulmonary disease. METHODS: This study was a hospital-based descriptive cross-sectional study. Total samples were 50 COPD patients with the average age of older than 60 years during their enrollments at the Department of Pulmonology and Respiratory Medicine of the Dr Wahidin Sudirohusodo General Hospital Makassar in September 2018-January 2019. All procedures of the present study were reviewed and approved by the Research Ethics Committee of Medicine Faculty of Hasanuddin University. The severity of COPD was assessed according to the combination of COPD assessment stages that referred to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) Guideline 2015 that consisted of the combination of scoring COPD Assessment Test (CAT), the modified Medical Research Council (mMRC) questionnaire and results of the spirometry measurement. Assessment of airway obstruction levels referred to the GOLD spirometry criteria. Determination of thoracic photographs was conducted to verify the COPD diagnosis of the severity of COPD. Determination of serum TNF-α concentration and vitamin D3 [1,25(OH)2D3] level used the ELISA method. RESULTS: The majority of COPD patients were observed in the category of older than 60 years old accounted for 34 COPD patients (68%), and the majority of COPD patients were males accounted for 47 males with COPD (94%). The majority of COPD patients were observed in the group of D (38%). All the study subjects observed in this study were smokers, and 82% of them were in the category of heavy smokers. 21 study subjects had higher concentration of serum TNF-α (tertile 3 = 0.21-1.83 pg/dl), 20 study subjects and lower level of vitamin D (tertile 1 = 182.1-364.5 pg/dl). The majority of the study subjects (38%) were in the category of severe COPD (category D of the severity of COPD at the tertile 3) according to the GOLD Combine Assessment. Given the relationship between vitamin D level and serum TNF-α concentration on the airway obstruction, there were significant positive correlations between the increase of vitamin D levels and the increase of serum TNF-α concentrations on airway obstruction. Given the relationship between vitamin D level and serum TNF-α concentration on the severity of COPD, there were significant positive correlations between the increase of vitamin D levels (tertiles 1, 2 and 3) and the increase of serum TNF-α concentrations on the severity of COPD at p-value < 0.05. Overall, there were non-linear relationships between vitamin D level and serum TNF-α concentration on the severity of COPD. CONCLUSIONS: Serum TNF-α concentration was positively associated with airway obstruction level and severity of COPD. Low level of vitamin D was negatively associated with airway obstruction level and severity of COPD. Vitamin D3 level (1,25(OH)2D) was negatively associated with serum TNF-α concentration and airway obstruction level and severity of COPD.

The Effects of 10,000 IU Vitamin D Supplementation on Improvement of Clinical Outcomes, Inflammatory and Coagulation Markers in Moderate COVID-19 Patients: A Randomized-Controlled Trial / Los efectos de la suplementación con 10 000 UI de vitamina D en la mejora de los resultados clínicos, los marcadores inflamatorios y de coagulación en pacientes con COVID-19 moderado: un ensayo controlado aleatorizado

Background & aims: Vitamin D supplementation as animmunomodulator has been identified as a potential strategy to prevent and treat Coronavirus disease 2019 (COVID-19). We aimed to analyze the effect of 10,000 IU vitamin D3supplementation on 25(OH)D levels on primary clinical outcomes (conversion length), inflammatory markers (TotalLymphocyte Count (TLC), Neutrophil-to-Lymphocyte Ratio(NLR), Platelet-to-Lymphocyte Ratio (PLR)) and coagulationmarker (D-Dimer) in moderate COVID-19 patients atWahidin Sudirohusodo Hospital, Makassar, Indonesia.Methods: We conducted a singleblind randomized-controlled trial on the confirmed moderate COVID-19 patientsabove 18 years old and low vitamin D status. Each of inter-vention and control groups were supplemented of 10,000 IUand 1000 IU cholecalciferol that taken daily for 2 weeks.Levels of 25(OH)D were analyzed for the primary endpoint(conversion length), then correlated to secondary endpoints(Length of Stay (LOS)), clinical manifestations improvement,and markers TLC, NLR, PLR, and D-Dimer serum, handgripstrength (HGS) as functional capacity measurement, after ad-justed to age, sex, nutritional status based on body mass in-dex (BMI) and Subjective Global Assessment (SGA) tool, co-morbidities, and anticoagulant administration. Medical nutri-tional therapy was given and presented as energy, protein,carbohydrate, and fat achievement, and vitamin D intake wasalso calculated.Results: A significant effects was found in 60 samples withpre-intervention vitamin D deficiency (61.7%) and insuffi-ciency (38.3%) status, and 10,000 IU of vitamin D3 supplementation could increase 25(OH)D levels within 2 weeks toreach sufficiency status (16.7%). The Vitamin D3 supplementation of 10,000 IU and 1000 IU could significantly increase25(OH)D levels compared to the control group of 1000 IU(4.61±5.43 vs. -0.29±2.72; P <0.0001) and it was correlatedto primary clinical outcome, which is length of conversion...(AU)

Energy regulation in newly diagnosed TB with chronic energy deficiency: free fatty acids and RBP4.

BACKGROUND AND OBJECTIVES: Energy metabolism may be dysfunctionally integral between host and infective agent in active tuberculosis, mediated by adipocytokines and free fatty acids (FFA) as the products of triglyceride lipolysis in fat, blood or other tissues. Retinol Binding Protein 4 (RBP4) and asymmetric dimethylarginine (ADMA) are candidate adipocytokines. The possibility of a deleterious metabolic nexus in chronic energy deficiency (CED) (BMI <18.5 kg/m2) is explored. METHODS AND DESIGN: Newly diagnosed patients with tuberculosis (n=63) were selected using consecutive random sampling at a Centre for the Care and Treatment of Lung Diseases in Makassar, Indonesia. Diagnosis of pulmonary TB required microscopy with Ziehl-Neelsen stain. Anthropometric measurements were taken. Venesection allowed glomerular filtration rate, FFA, serum glutamic oxaloacetic transaminase and glutamate-pyruvate transaminase to be assessed. RESULTS: CED was evident in 60.3%. For the well and lesser nourished, medians were, respectively, FFA 0.30 and 0.37 mmol/mL (p=0.960); RBP4 199730 ng/mL and 11721 ng/mL (p=0.009); GFR 106 ml/min and 113 ml/min (p=0.673); and ADMA 0.52 ng/mL and 0.51 ng/mL (p=0.172). BMI and serum RBP4 were correlated (ρ=0.52, p<0.001), with odds ratios (OR) 5.8 (CI 1.68-20.3). RBP4 in CED was lower than in better nourished patients. Serum FFA is not evidently associated with BMI in patients with active TB. CONCLUSIONS: RBP4 is some 6-fold lower when active TB patients have CED than when BMI >25 kg/m2. However, FFA was not associated with CED in these active TB patients which may be a type 2 error or represent an energy impasse where infection and the host's metabolic needs are in competition.