Correlation between circulating fibrosis biomarkers with left atrial function and left atrial volume index in rheumatic mitral stenosis.

Mitral stenosis is the most common rheumatic heart disease (RHD) disorder worldwide, including in Indonesia. This pathological condition causes left atrial pressure, leading to left atrial fibrosis that affects the structure and function of the left atrial as well as the clinical condition. The aim of this study was to assess the correlation between circulating fibrosis biomarkers with net atrioventricular compliance (Cn) as a parameter of left atrial function, and left atrial volume index (LAVI) as a parameter left atrium structure of changes. A cross-sectional study was conducted at Panti Rahayu Hospital and Permata Bunda Hospital, Purwodadi, Central Java, with a total of 40 RHD patients with severe mitral stenosis. The ELISA was used to measure the levels of carboxy-terminal propeptide of type I procollagen (PICP), matrix metalloproteinase I (MMP-1), tissue inhibitor matrix metalloproteinase 1 (TIMP-1), and transforming growth factor-ß1 (TGF-ß1). The left atrial function was assessed by measuring Cn, and the LAVI parameters were measured to assess left atrium structure/size. The mean levels of circulating fibrosis biomarkers were as follows: PICP 153.96±89.12 ng/mL; MMP-1 1.44±2.12 ng/mL; MMP-1/TIMP-1 ratio 0.38±0.54 and TGF-ß1 2.66±1.96 pg/mL. From the echocardiographic evaluation, the mean Cn was 5.24±1.93 mL/mmHg and the mean LAVI was 152.55±79.36 mL/m2. There were significant correlation between MMP-1 and MMP-1/TIMP-1 ratio with Cn (r=0.345 and r=0.333, respectively; both had p<0.05). PICP and TGF-ß1 biomarkers did not significantly correlate with Cn (p>0.05). Meanwhile, none of the biomarkers had a significant correlation with LAVI (p>0.05). This study highlights that MMP-1 and MMP-1/TIMP-1 ratio are potentially to be used as markers to determine the Cn in RHD patients with severe mitral stenosis. However, further studies with a higher sample size are needed to confirm this finding.

Effect of Dapagliflozin on Patients with Rheumatic Heart Disease Mitral Stenosis.

(1) Background: Mitral stenosis is the most common rheumatic heart disease (RHD). Inflammation and fibrosis are the primary pathophysiology, resulting in left atrial stress and dysfunction. Dapagliflozin is a new heart failure treatment with anti-inflammation and anti-fibrosis effects from previous studies. However, the specific role of dapagliflozin in RHD mitral stenosis is unknown. This study aims to investigate (i) the effect of dapagliflozin on biomarkers of fibrosis, NT-pro BNP levels and left atrial function; (ii) the relationship between the changes in fibrosis biomarkers with left atrial function and NT-pro BNP levels. (2) Methods: An open-label randomized study was conducted on 33 RHD mitral stenosis patients divided into a dapagliflozin group which received 10 mg dapagliflozin and standard therapy, and a control group which only received standard therapy. All patients were examined for levels of PICP, MMP-1/TIMP-1 ratio, TGF-ß1, NT-proBNP, mitral valve mean pressure gradient (MPG), and net atrioventricular compliance (Cn) pre- and post-intervention. (3) Results: This study found a significant increase in PICP and TGF-ß1 and a reduction in the MMP-1/TIMP-1 ratio in the dapagliflozin group and the control group (p < 0.05). In the dapagliflozin group, the levels of NT-pro BNP decreased significantly (p = 0.000), with a delta of decreased NT-pro BNP levels also significantly greater in the dapagliflozin group compared to the control (p = 0.034). There was a significant increase in Cn values in the dapagliflozin group (p = 0.017), whereas there was a decrease in the control group (p = 0.379). Delta of changes in Cn values between the dapagliflozin and control groups also showed a significant value (p = 0.049). The decreased MPG values of the mitral valve were found in both the dapagliflozin and control groups, with the decrease in MPG significantly greater in the dapagliflozin group (p = 0.031). There was no significant correlation between changes in the value of fibrosis biomarkers with Cn and NT-pro BNP (p > 0.05). (4) Conclusions: This study implies that the addition of dapagliflozin to standard therapy for RHD mitral stenosis patients provides benefits, as evidenced by an increase in net atrioventricular compliance and decreases in the MPG value of the mitral valve and NT-pro BNP levels (p < 0.05). This improvement was not directly related to changes in fibrosis biomarkers, as these biomarkers showed ongoing fibrosis even with dapagliflozin administration.

Effectiveness of Zingiber officinale to reduce inflammation markers and the length of stay of patients with community-acquired pneumonia: An open-label clinical trial.

Examination of the interleukin 6 (IL-6) and procalcitonin levels, and neutrophil-lymphocyte ratio (NLR) might could help to diagnosis and predict the duration of therapy and prognosis of pneumonia cases. Zingiber officinale var rubrum could be used as an adjunct therapy in infectious diseases as it has anti-inflammatory activity. The aim of study was to assess the effect of Z. officinale on levels of IL-6 dan procalcitonin, NLR, and the length of hospitalization of patients with community-acquired pneumonia (CAP). An open-label clinical trial was conducted among CAP cases regardless of the etiology at Dr Moewardi Hospital and Universitas Sebelas Maret Hospital, Surakarta, Indonesia from July to September 2022. A total of 30 inpatient CAP cases were recruited and were randomly divided into two groups: (1) received Z. officinale capsule 300 mg daily for five days in addition to CAP standard therapy; and (2) received CAP standard therapy only, as control group. The data were compared using a paired Student t-test, Chi-squared test, Mann-Whitney test and Wilcoxon signed-rank test as appropriate. In Z. officinale group, the mean difference between post-and pre-treatment as follow: IL-6 level was 9.93 pg/mL, procalcitonin level -471.31 ng/mL, and NLR value -4.01. In control group, the difference was 18.94 pg/mL for IL-6, 339.39 ng/mL for procalcitonin, and 1.56 for NLR. The change of IL-6 was not statistically significant between treatment and control groups with p=0.917. The changes of procalcitonin level and NLR were significant between treatment and control group with p=0.024 and p=0.007, respectively, of which the treatment had better improvement. In addition, our data indicated that the length of stay was not statistically significant between the treatment and control groups (4.13 vs 4.47 days, p=0.361). In conclusion, Z. officinale could reduce serum inflammatory markers such as procalcitonin and NLR but it has little impact in reducing IL-16 level and the length of hospitalization of CAP patients.

Effects of secretome supplementation on interleukin-6, tumor necrosis factor-α, procalcitonin, and the length of stay in acute exacerbation COPD patients.

Acute exacerbation chronic obstructive pulmonary disease (AECOPD) is associated with significant poor survival. Mesenchymal stem cells (MSC) therapy has been a promising treatment for COPD; therefore, it has the potential to be an additional therapy for AECOPD. Its potential is associated with its secretome since it has anti-inflammatory and immunomodulator activities. The aim of this study was to determine the effect of the secretome as an adjuvant therapy in reducing the levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), procalcitonin, and the length of stay in AECOPD patients. A clinical control trial study was conducted among 28 moderate and severe AECOPD patients who were hospitalized from January to February 2023. The control group (n=14) received standard therapy of AECOPD while the treatment group (n=14) received standard therapy plus secretome 1 ml twice daily for three days. The levels of IL-6, TNF-α, and procalcitonin were measured at admission and on the fourth day of treatment. The length of stay was calculated from the time the patient was admitted until the patient was discharged from hospital. The data were compared using a paired Student t-test, chi-squared test and Mann-Whitney test as appropriate. In the treatment group, the levels of IL-6, TNF-α and procalcitonin after the treatment reduced 13.09 pg/mL, 5.00 pg/mL and 751.26 pg/mL, respectively compared to pre-treatment. In contrast, the levels of IL-6, TNF-α and procalcitonin increased 48.56 pg/mL, 44.48 pg/mL and 346.96 pg/mL, respectively after four days of treatment. There was a significant reduction of IL-6, TNF-α and procalcitonin in treatment group compared to the control group with p=0.022, p=0.009 and p=0.001, respectively. However, there was no significant reduction of the length of stay (p=0.072). In conclusion, administration of secretome to AECOPD patients could reduce the levels of IL-6, TNF-α and procalcitonin.

Cytokines dynamics in a wistar rat model infected with Mycobacterium Tuberculosis strain H37Rv.

Background: The immunology characteristics of the rat model of tuberculosis (TB) infection are still unclear. This study aimed to evaluate the dynamics of pathology and cytokines in a rat model infected with Mycobacterium TB (MTB). Methods: Sixty male Wistar rats were divided into four groups, namely the control group (without MTB infection) and the MTB -induced group (observations at week-3, week-6, and week-12 postinfection). Granuloma formation was analyzed by histology procedure. Analysis of the levels of tumor necrosis factor-a (TNF-α), interleukin-6 (IL-6), IL-17, IL-2, IL-4, and IL-12 was performed using an enzyme-linked immunosorbent assay technique. Results: The number and size of the ganulomas increased proportionally between weeks 6 and 12 postinfection. Several cytokines, namely IL-6, IL-17, IL-2, IL-4, and IL-12 significantly increased in the 6th week compared to the 3rd week after infection (P < 0.05). These cytokines decreased significantly at the 12th week compared to the 6th week (P < 0.05). TNF-α was found to be stable at the third and 6th weeks and then decreased at the twelfth postinfection week. For IL-12, the longer the infection time, the higher the level. Conclusions: It was concluded that there was a typical pattern of TB infection in Wistar rats, namely certain cytokines that peaked at week 6 of infection. Thus, TB infection in rats can be a model for early-phase TB study.

Kinetics of Granuloma, IFN-γ and IP-10 in a Wistar Rat Model Infected with Mycobacterium Tuberculosis.

Background: Improved access and treatment are critical to controlling the problem. Molecular diagnostic tests, although available, are not feasible in developing countries. Where available, these tests require state-of-the-art laboratories and are not cheap. One alternative to molecular diagnostics is the use of acute phase protein values. This protein is a protein whose levels will increase or decrease in plasma in response to injury or inflammation. Objective: This study aimed to analyze the kinetics of granulomas and the role of IFN-γ and IP-10 in the pathology of tuberculosis in a rat model. Methods: Sixty Wistar rats were divided into four groups, namely the control group (without MTB induction) and the MTB-induced group (observations at week-3, week-6, and week-12 post infection). Induce tuberculosis with bacterial strain H37Rv ATCC 27294. Results: The number and size of the granuloma increased to a peak at week 6 and was consistent for weeks 6 and 12 post-infection. The kinetics of granulomas were consistent with IFN-γ and IP-10 levels. Conclusion: It was concluded that the model of tuberculosis infection by the H37Rv ATCC 27294 strain in Wistar rat found granuloma characteristics and IFN-γ and IP-10 patterns in similar kinetics, so that there was involvement of these molecules in TB pathology. Thus, tuberculosis infection of the H37Rv ATCC 27294 strain in rats can serve as a model for rapid tuberculosis study and display a complete pathological phase.

Good Agreement between an Interferon Gamma Release Assay and Tuberculin Skin Tests in Testing for Latent Tuberculosis Infection among HIV-Infected Patients in Indonesia.

BACKGROUND: Latent tuberculosis infection is a condition where there is a persistent immune response to Mycobacterium tuberculosis without clinical manifestations of tuberculosis. Currently, there is no gold standard to diagnose latent tuberculosis infection. The tuberculin skin test and interferon-gamma release assay are currently used to diagnose latent tuberculosis infection. However, studies have shown inconsistencies regarding the level of agreement between these tests in different settings. In this study, we aimed to evaluate the agreement between these two tests for diagnosing latent tuberculosis infection in human immunodeficiency virus (HIV)-infected individuals. METHODS: We screened HIV patients with no clinical symptoms of tuberculosis, a normal chest X-ray, and no history of tuberculosis or use of antituberculous drugs. Participants were tested with tuberculin skin test (TST) and T-SPOT.TB (an interferon gamma release assay) simultaneously. Participants' HIV stage was determined by measuring the level of CD4+ T-lymphocytes. Tuberculosis status was confirmed by sputum examination using GeneXpert. The level of agreement between the TST and T-SPOT.TB results was measured using Cohen's κ coefficient. RESULTS: Of the 112 participants, 20 had a positive T-SPOT.TB test result, and 21 had a positive TST result. The TST and T-SPOT.TB test results showed a high level of agreement (κ = 0.648, P < 0.001). Performance of the tests did not vary with CD4+ level. However, in participants with CD4+ < 200 cells/mm³, T-SPOT.TB detected more latent tuberculosis infections than the TST. CONCLUSION: There was good agreement between the TST and T-SPOT.TB results of latent tuberculosis infection in participants. TST is the preferred test for diagnosing latent tuberculosis infection in HIV-infected patients, especially in resource-limited settings, because it is simple and cost-effective. However, T-SPOT.TB may be useful to rule out latent tuberculosis infection in patients with severe immunodeficiency.

Good Agreement between an Interferon Gamma Release Assay and Tuberculin Skin Tests in Testing for Latent Tuberculosis Infection among HIV-Infected Patients in Indonesia

BACKGROUND: Latent tuberculosis infection is a condition where there is a persistent immune response to Mycobacterium tuberculosis without clinical manifestations of tuberculosis. Currently, there is no gold standard to diagnose latent tuberculosis infection. The tuberculin skin test and interferon-gamma release assay are currently used to diagnose latent tuberculosis infection. However, studies have shown inconsistencies regarding the level of agreement between these tests in different settings. In this study, we aimed to evaluate the agreement between these two tests for diagnosing latent tuberculosis infection in human immunodeficiency virus (HIV)-infected individuals. METHODS: We screened HIV patients with no clinical symptoms of tuberculosis, a normal chest X-ray, and no history of tuberculosis or use of antituberculous drugs. Participants were tested with tuberculin skin test (TST) and T-SPOT.TB (an interferon gamma release assay) simultaneously. Participants' HIV stage was determined by measuring the level of CD4+ T-lymphocytes. Tuberculosis status was confirmed by sputum examination using GeneXpert. The level of agreement between the TST and T-SPOT.TB results was measured using Cohen's κ coefficient. RESULTS: Of the 112 participants, 20 had a positive T-SPOT.TB test result, and 21 had a positive TST result. The TST and T-SPOT.TB test results showed a high level of agreement (κ = 0.648, P < 0.001). Performance of the tests did not vary with CD4+ level. However, in participants with CD4+ < 200 cells/mm³, T-SPOT.TB detected more latent tuberculosis infections than the TST. CONCLUSION: There was good agreement between the TST and T-SPOT.TB results of latent tuberculosis infection in participants. TST is the preferred test for diagnosing latent tuberculosis infection in HIV-infected patients, especially in resource-limited settings, because it is simple and cost-effective. However, T-SPOT.TB may be useful to rule out latent tuberculosis infection in patients with severe immunodeficiency.

Influence social and healthcare support on psychiatric adverse events in MDR-TB patient.

INTRODUCTION: Multidrug resistance tuberculosis (MDR-TB) is a continuing threat because the treatment is rather toxic. One of the causes of poor treatment outcome is due to the adverse events, especially the occurrence of psychiatric adverse events. METHODOLOGY: The two cases presented in this paper are MDR-TB patients with psychiatric adverse events related to depression spectrum. The diagnosis of psychiatric adverse events was done by psychiatrist in the referral hospital. RESULTS: The treatment of MDR-TB and psychiatric adverse event was carried out simultaneously. One of the patients was able to manage the adverse events, but the other was not. The management of psychiatric adverse events need to be performed carefully. Social support of family and friends was received by the successful patient, while the other was not fully supported, thus failed the treatment. CONCLUSION: The social support provided by the family and friends are precious for the successful treatment of MDR-TB psychiatric adverse events. The availability of healthcare personnel who is able to recognize the symptoms early is needed in the community healthcare service in order to properly detect and manage the psychiatric adverse events on MDR-TB patients.

The dynamic of tuberculosis case finding in the era of the public-private mix strategy for tuberculosis control in Central Java, Indonesia.

BACKGROUND: The public-private mix (PPM) strategy has strengthened tuberculosis care and control in many countries. Indonesia, a country with a high tuberculosis burden, has a low tuberculosis case detection rate (CDR), despite PPM implementation in 2003. The PPM in Indonesia involves primary healthcare centers, hospitals, and specialized chest clinics. The long-term impact of the strategy is unknown. OBJECTIVE: We aimed to explore the case detection achievements of the tuberculosis program since PPM implementation in Central Java in 2003. METHODS: This retrospective cohort study covered the period 1 January 2000 to 31 December 2014. The data from tuberculosis patients treated in all health facilities in Central Java implementing directly observed treatment short-course, recorded via a standardized form, were analyzed after being validated by the Office of Health of Central Java Province. We evaluated the CDR, case notification rate, and total number of cases, using linear regression to analyze the temporal trends of those indicators in the phases of PPM implementation. RESULTS: The CDR increased during the initial phase (2000-2005), decreased during the mid-phase (2006-2009), and increased slightly during the late phase (2010-2014), ranging from 13 to 61.72. These trends were observed despite a steady increase in the number of participating healthcare facilities. The regression analysis showed that the CDR of referral institutions contributed the most to the total CDR of Central Java Province. Many of the smear-negative tuberculosis cases recorded at primary healthcare centers may have been smear positive; this probable misclassification could have been partially avoided if more specific and sensitive diagnostic tools were available. CONCLUSIONS: The CDR remains below the national target (70%). Early awareness of a negative trend in certain program indicators is important to ensure program sustainability. Careful observation of the indicator pattern will secure the long-term success of the program.