Impacts of the COVID-19 Pandemic on the CODE ST-Segment Elevation Myocardial Infarction Program: A Quantitative and Qualitative Analysis.

BACKGROUND: The code ST-segment elevation myocardial infarction (STEMI) program is an operational standard of integrated service for STEMI patients carried out by Dr. Cipto Mangunkusumo Hospital. The emerging coronavirus disease 2019 (COVID-19) outbreak brought about many changes in the management of healthcare services, including the code STEMI program. This study aimed to evaluate the healthcare service quality of the Code STEMI program during the COVID-19 pandemic based on the Donabedian concept.  Methods: This was a mixed-methods study using quantitative and qualitative analyses. It was conducted at the Dr. Cipto Mangunkusumo Hospital, a national referral hospital in Indonesia. We compared the data of each patient, including response time, clinical outcomes, length of stay, and cost, from two years between 2018-2020 and 2020-2022 as the pre-COVID-19 code STEMI and COVID-19 Code STEMI periods, respectively. Interviews were conducted to determine the quality of services from the perspectives of stakeholders. RESULTS: A total of 195 patients participated in the study: 120 patients in pre-COVID-19 code STEMI and 75 patients in COVID-19 code STEMI. Our results showed that there was a significant increase in patient's length of stay during the COVID-19 pandemic (4 days vs. 6 days, p < 0.001). Meanwhile, MACE (13% vs. 11%, p = 0.581), the in-hospital mortality rate (8% vs. 5%, p = 0.706), door-to-wire crossing time (161 min vs. 173 min, p = 0.065), door-to-needle time (151 min vs. 143 min p = 0.953), and hospitalization cost (3,490 USD vs. 3,700 USD, p = 0.945) showed no significant changes. In terms of patient satisfaction, patients found code STEMI during COVID-19 to be responsive and excellent. CONCLUSION: The implementation of the code STEMI program during the COVID-19 pandemic revealed that modified pathways were required because of the COVID-19 screening process. According to the Donabedian model, during the pandemic, the code STEMI program's healthcare service quality decreased because of a reduction in efficacy, effectiveness, efficiency, and optimality. Despite these limitations attributed to the pandemic, the code STEMI program was able to provide good services for STEMI patients.

Aortic Valve Replacement with Single-Strip Autologous Pericardium.

BACKGROUND: Aortic valve replacement with mechanical valves is the standard treatment for aortic valve disease in Indonesia. Its usage is associated with high cost, risk of endocarditis and thromboembolic event, and lifetime consumption of anticoagulants. We performed a novel replacement technique of the aortic valve using an autologous pericardium and evaluated the short-term outcomes. METHODS: From April 2017 to April 2020, 16 patients underwent aortic valve replacement with a single-strip autologous pericardium. Outcomes of the left ventricular reverse remodeling (LVRR), 6-minute walk test (6MWT), and soluble suppression of tumorigenicity-2 (sST-2) were measured at 6 months postoperation. RESULTS: A total of 16 surgeries were performed using aortic valve replacement with single-strip pericardium without conversion to mechanical valve replacement. The patients included eight males and eight females, and the mean age was 49.63 ± 12.54 years. The most common diagnosis was mixed aortic valve stenosis and regurgitation (9 cases). Five patients underwent a concomitant coronary artery bypass graft (CABG) procedure and 12 patients underwent either mitral or tricuspid valve repair. The mean aortic cross-clamp time was 139.88 ± 23.21 minutes and cardiopulmonary bypass time was 174.37 ± 33.53 minutes. At 6 months postoperation, there was an increase in the distance walked at the 6MWT (p = 0.006) and a decrease of the sST-2 level (p = 0.098). Echocardiogram showed two patients had LVRR. Survival and freedom from reoperation are 100% at 1 year of follow-up. CONCLUSION: Aortic valve replacement with a single strip of pericardium is a good alternative to aortic valve replacement with a mechanical valve. Short-term evaluation at 6 months postoperation showed improvement in clinical status and echocardiographic parameters compared to baseline.

Harmonising Individual Patient Level Cardiac Registry Data Across the Asia Pacific Region-A Feasibility Study of In-Hospital Outcomes of STEMI Patients From the Asia Pacific Evaluation of Cardiovascular Therapies (ASPECT) Network.

OBJECTIVE: The Asia-Pacific Evaluation of Cardiovascular Therapies (ASPECT) collaboration was established to inform on percutaneous coronary intervention (PCI) in the Asia-Pacific Region. Our aims were to (i) determine the operational requirements to assemble an international individual patient dataset and validate the processes of governance, data quality and data security, and subsequently (ii) describe the characteristics and outcomes for ST-elevation myocardial infarction (STEMI) patients undergoing PCI in the ASPECT registry. METHODS: Seven (7) ASPECT members were approached to provide a harmonised anonymised dataset from their local registry. Patient characteristics were summarised and associations between the characteristics and in-hospital outcomes for STEMI patients were analysed. RESULTS: Six (6) participating sites (86%) provided governance approvals for the collation of individual anonymised patient data from 2015 to 2017. Five (5) sites (83%) provided >90% of agreed data elements and 68% of the collated elements had <10% missingness. From the registry (n=12,620), 84% were male. The mean age was 59.2±12.3 years. The Malaysian cohort had a high prevalence of previous myocardial infarction (34%), almost twice that of any other sites (p<0.001). Adverse in-hospital outcomes were the lowest in Hong Kong whilst in-hospital mortality varied from 2.7% in Vietnam to 7.9% in Singapore. CONCLUSIONS: Governance approvals for the collation of individual patient anonymised data was achieved with a high level of data alignment. Secure data transfer process and repository were established. Patient characteristics and presentation varied significantly across the Asia-Pacific region with this likely to be a major predictor of variations in the clinical outcomes observed across the region.

Validity and Reliability Studies of the Indonesian Version of Arrhythmia-Specific Questionnaire in Tachycardia and Arrhythmia (ASTA).

BACKGROUND: The Arrhythmia-Specific Questionnaire in Tachycardia and Arrhythmia (ASTA) was developed in Sweden using English which may pose cultural and language barriers for Indonesian patients. As such, we aimed to translate the original ASTA into Indonesian, then assess its validity and reliability. METHODS: Translation of the ASTA from English to Indonesian was done using forward and backward translation. The final version was then validated with the Short Form-36 (SF-36) questionnaire. Test-retest reliability study was done in a 7-14-day interval. RESULTS: The Indonesian version of ASTA was deemed acceptable by a panel of researchers with Cronbach's α of 0.816 and Intraclass Correlation Coefficient (ICC) ranging from 0.856-0.983. In a comparison to the SF-36, the medication utilization domain was poorly correlated with role limitations due to physical health (r:0.384; p<0.01) and pain (r:-0.317; p<0.05). The arrhythmia-specific symptoms domain was poorly correlated with role limitations due to emotional problems (r:0.271; p<0.05). In addition, the health-related quality of life (HRQOL) domain was poorly correlated with role limitations due to physical health (r:0.359; p<0.01) and emotional problems (r:0.348; p<0.01), also total SF-36 score (r:-0.367; p<0.01). The ASTA total score was poorly correlated with role limitations due to physical health (r:0.37; p<0.01), and emotional problems (r:0.376; p<0.01), also total SF-36 score (r:-0.331; p<0.01). CONCLUSION: The Indonesian version of ASTA has good internal and external validity as well as good reliability. Both the physical and mental domains of ASTA are correlated with role limitations due to emotional problems and SF-36 total score.

Transport viable heart tissue at physiological temperature yielded higher human cardiomyocytes compared to the conventional temperature.

This study investigated the optimum transport condition for heart tissue to recover single-cell cardiomyocytes for future in-vitro or in-vivo studies. The heart tissues were obtained from removing excessive myocardium discharged during the repair surgery of an excessive right atrial hypertrophy due to a congenital disease. The transportation temperature studied was the most used temperature (4 °C) or the conventional condition, compared to a physiological temperature(37 °C). The heart tissues were transported from the operating theatre to the lab maintained less than 30 min consistently. Single-cell isolation was enzymatically and mechanically performed using collagenase-V (160 U/mg) and proteinase-XXIV (7-14 U/mg) following the previously described protocol. The impact of temperature differences was observed by the density of cells harvested per mg tissue, cell viability, and the senescence signals, identified by the p21, p53 and caspase-9 mRNA expressions. Results the heart tissue transported at 37 °C yielded significantly higher viable cell density (p < 0.01) yielded viable cells significantly higher density (p < 0.01) than the 4 °C; 2,335 ± 849 cells per mg tissue, and 732 ± 425 cells per mg tissue, respectively. The percentage of viable cells in both groups showed no difference. Although the 37 °C group expressed the apoptosis genes such as p21, p53 and caspase9 by 2.5-, 5.41-, 5-fold respectively (p > 0.05). Nonetheless, the Nk×2.5 and MHC genes were expressed 1,7- and 3.56-fold higher than the 4 °C. and the c-Kit+ expression was 17.56-fold, however, statistically insignificant. Conclusion When needed for single-cell isolation, a heart tissue transported at 37 °C yielded higher cell density per mg tissue compared to at 4 °C, while other indicators of gene expressions for apoptosis, cardiac structural proteins, cardiac progenitor cells showed no difference. Further investigations of the isolated cells at different temperature conditions towards their proliferation and differentiation capacities in a 3-D scaffold would be essential.

Characterisation of the single-cell human cardiomyocytes taken from the excess heart tissue of the right ventricular outlet in congenital heart disease.

Cardiovascular disease is the second highest cause of death across the globe. Myocardial infarction is one of the heart diseases that cause permanent impairment of the heart wall leads to heart failure. Cellular therapy might give hope to regenerate the damaged myocardium. Single cells isolated from an excess heart tissue obtained from the correction of the right ventricular hypertrophy in patients with Tetralogy of Fallot for future heart study were investigated. METHODS: Once resected, the heart tissues were transported at 37 °C, in Dulbecco's Modified Eagle's medium/ DMEM (4.5 g.L-1, antibiotic-antimycotic 3x, PRP10% (v/v)), to reach the lab within 30 min, weighted and grouped into less than 500 mg and more than 1000 mg (n = 4). Each sample was digested with 250 U.mL-1 Collagenase type V and 4U.mL-1 Proteinase XXIV in the MACS™ C-tube (Milltenyi, Germany), then dissociated using the MACS™ Octo Dissociator with Heater (Milltenyi, Germany) for 60 min at 37 °C. RESULTS: All cells isolated were rod-shaped cells; viability was up to 90%. The cell density obtained from the 500 mg group were 4,867 ± 899 cells.mg-1 tissue weight, significantly higher compared to the 1,000 mg group; had 557 ± 490 cells.mg-1 tissue weight (mean of (n = 3) ± 95% C.l). The isolated cells were analyzed using FACs BD Flowcytometer, expressed cTnT + 13.38%, PECAM-1 + /VCAM-1- 32.25%, cKit + 7.85%, ICAM + 85.53%, indicating the cardiomyocyte progenitor cells. CONCLUSION: Cardiomyocytes taken from the wasted heart tissue might be a candidate of cardiomyocytes source to study interventions to the heart as it contained up to 13.38% cardiomyocytes, and 32.25% of cardiac progenitor cells. Moreover, perhaps when cardiac cell therapy needs autologous cardiomyocytes, less than 500 mg tissue weight can be considered as sufficient.

Supportive Psychotherapy for Healthcare Professionals in The Management of Acute Coronary Syndrome: The Use of Delphi Technique.

BACKGROUND: Supportive psychotherapy (SP) may increase the benefit of acute coronary syndrome (ACS) management, but there is no structured SP as a guideline for healthcare professionals. This study aimed to develop structured SP as a guideline for implementing psychotherapy in the management of ACS patients in intensive cardiac care unit (ICCU). METHODS:  This qualitative study used Delphi technique as a modified Delphi method to reach a consensus among experts of structured SP for healthcare professionals in the management of ACS during hospitalized in ICCU. This was developed using self-reflection, observation, and interview of SP implementation in daily psychosomatic practice, gathering literature reviews, doing focus group discussion (FGD) and interview with ACS survivors. During the Delphi rounds, we interviewed 50 informants as source people using valid questionnaires, to proceed a draft of the SP framework and the structured sessions. The SP framework draft and the structured sessions were evaluated and corrected by experts anonymously until the consensus was reached. The validity of the consensus was tested, using Likert psychometric scale to reach an agreement. Cronbach alpha test was used to assess construct validity with SPSS 20. RESULTS:  All of preparations conducted before the Delphi rounds showed that ACS patients had psychosomatic disorders during in ICCU, that required support. SP is very helpful to reduce the negative impact of this disorders.Off 50 informants answered a valid and reliable questionnaire which supports the above statement. The draft was made based on the above process. The development of SP for healthcare professionals of ACS managements was reached in a consensus of expert panelists in the second round of the Delphi with Cronbach alpha of 0.9. CONCLUSION: Supportive psychotherapy (SP) for healthcare professionals in the management of ACS in ICCU were developed and may be applied in clinical practice and research.

Learning Intelligent for Effective Sonography (LIFES) Model for Rapid Diagnosis of Heart Failure in Echocardiography.

BACKGROUND: The accuracy of an artificial intelligence model based on echocardiography video data in the diagnosis of heart failure (HF) called LIFES (Learning Intelligent for Effective Sonography) was investigated. METHODS: A cross-sectional diagnostic test was conducted using consecutive sampling of HF and normal patients' echocardiography data. The gold-standard comparison was HF diagnosis established by expert cardiologists based on clinical data and echocardiography. After pre-processing, the AI model is built based on Long-Short Term Memory (LSTM) using independent variable estimation and video classification techniques. The model will classify the echocardiography video data into normal and heart failure category. Statistical analysis was carried out to calculate the value of accuracy, area under the curve (AUC), sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and likelihood ratio (LR). RESULTS: A total of 138 patients with HF admitted to Harapan Kita National Heart Center from January 2020 to October 2021 were selected as research subjects. The first scenario yielded decent diagnostic performance for distinguishing between heart failure and normal patients. In this model, the overall diagnostic accuracy of A2C, A4C, PLAX-view were 92,96%, 90,62% and 88,28%, respectively. The automated ML-derived approach had the best overall performance using the 2AC view, with a misclassification rate of only 7,04%. CONCLUSION: The LIFES model was feasible, accurate, and quick in distinguishing between heart failure and normal patients through series of echocardiography images.

Thrombocytopenia as a prognostic marker in COVID-19 patients: diagnostic test accuracy meta-analysis.

This systematic review and meta-analysis aimed to evaluate thrombocytopenia as a prognostic biomarker in patients with coronavirus disease 2019 (COVID-19). We performed a systematic literature search using PubMed, Embase and EuropePMC. The main outcome was composite poor outcome, a composite of mortality, severity, need for intensive care unit care and invasive mechanical ventilation. There were 8963 patients from 23 studies. Thrombocytopenia occurred in 18% of the patients. Male gender (P = 0.037) significantly reduce the incidence. Thrombocytopenia was associated with composite poor outcome (RR 1.90 (1.43-2.52), P < 0.001; I2: 92.3%). Subgroup analysis showed that thrombocytopenia was associated with mortality (RR 2.34 (1.23-4.45), P < 0.001; I2: 96.8%) and severity (RR 1.61 (1.33-1.96), P < 0.001; I2: 62.4%). Subgroup analysis for cut-off <100 × 109/l showed RR of 1.93 (1.37-2.72), P < 0.001; I2: 83.2%). Thrombocytopenia had a sensitivity of 0.26 (0.18-0.36), specificity of 0.89 (0.84-0.92), positive likelihood ratio of 2.3 (1.6-3.2), negative likelihood ratio of 0.83 (0.75-0.93), diagnostic odds ratio of 3 (2, 4) and area under curve of 0.70 (0.66-0.74) for composite poor outcome. Meta-regression analysis showed that the association between thrombocytopenia and poor outcome did not vary significantly with age, male, lymphocyte, d-dimer, hypertension, diabetes and CKD. Fagan's nomogram showed that the posterior probability of poor outcome was 50% in patients with thrombocytopenia, and 26% in those without thrombocytopenia. The Deek's funnel plot was relatively symmetrical and the quantitative asymmetry test was non-significant (P = 0.14). This study indicates that thrombocytopenia was associated with poor outcome in patients with COVID-19.PROSPERO ID: CRD42020213974.

Cytomegalovirus may influence vascular endothelial health in Indonesian HIV-infected patients after 5 years on ART.

OBJECTIVES: Accelerated atherosclerosis in older HIV-infected patients has been attributed to persistent immune activation and high burden cytomegalovirus (CMV), as demonstrated in transplant recipients and the general population. Here we assess CMV and inflammatory markers linked with vascular health in young adult patients treated in Indonesia. STUDY DESIGN: HIV-infected adults (n = 32) were examined when they began antiretroviral therapy (ART) with < 200 CD4 T-cells/µl (V0) and after 60 months (V60). Age-matched healthy controls (HC, n = 32) were assessed once. METHODS: Flow Mediated Dilatation (FMD) was assessed by ultrasound on brachial arteries at V60 and in HC. Plasma markers of immune activation and endothelial activation, and CMV antibodies (lysate, gB, IE-1) were assessed in all samples. Results were assessed using bivariate (non-parametric) and multivariable analyses. RESULTS: Levels of inflammatory biomarkers and CMV antibodies declined on ART, but the antibodies remained higher than in HC. FMD values were similar in patients and HC at V60. In HIV patients, levels of CMV lysate antibody correlated inversely (r = - 0.37) with FMD. The optimal model predicting lower FMD values (adjusted R2 = 0.214, p = 0.012) included CMV lysate antibodies and chondroitin sulphate. In HC, levels of sTNFR correlated inversely with FMD (r = - 0.41) and remained as a risk factor in the optimal multivariable model, with CMV glycoprotein-B (gB) antibody predicting a healthier FMD (adjusted R2 = 0.248, p = 0.013). CONCLUSIONS: Higher levels CMV antibodies optimally predict vascular health measured by FMD in HIV patients. However in healthy controls, sTNFR marks risk and CMV gB antibody may be protective.

Effect of heart failure on the outcome of COVID-19 - A meta analysis and systematic review.

BACKGROUND: Several comorbidities have been associated with an increased risk of severity and mortality in coronavirus disease 2019 (COVID-19), including hypertension, diabetes, cerebrovascular disease, chronic kidney disease, and chronic obstructive pulmonary disease. PURPOSE: In this systematic review and meta-analysis, we attempted to investigate the association between heart failure (HF) and poor outcome in patients with COVID-19. METHODS: We performed a systematic literature search from PubMed, EuropePMC, SCOPUS, Cochrane Central Database, and medRxiv with the search terms, "Heart failure" and "COVID-19". The outcome of interest was mortality and poor prognosis (defined by incidence of severe COVID-19 infection, admission to ICU, and use of ventilator) in patients with preexisting heart failure with coronavirus disease. RESULTS: We identified 204 potential articles from our search, and 22 duplicates were removed. After screening of the titles and abstracts of the remaining 182 articles we identified 92 potentially relevant articles. We excluded 74 studies due to the following reasons: four studies were systematic reviews, two studies were meta-analyses, three articles were literature reviews, and 65 articles did not report on the outcome of interest. Finally, we included the remaining 18 studies in our qualitative synthesis and meta-analysis. There were 21,640 patients from 18 studies. HF was associated with hospitalization in COVID19 HR was 2.37 [1.48, 3.79; p < 0.001], high heterogeneity [I2, 82%; p < 0.001]. HF was associated with a poor outcome demonstrated by an OR of 2.86 [2.07; 3.95; p < 0.001] high heterogeneity [I2, 80%; p < 0.001]. Patient with preexisting HF was associated with higher mortality OR of 3.46 [2.52, 4.75; p < 0.001] moderately high heterogeneity [I2, 77%; p < 0.001]. CONCLUSION: Patients with heart failure are at increased risk for hospitalization, poor outcome, and death from COVID-19. A significant difference in mortality between patients with and without heart failure was observed, patients with heart failure having a higher mortality.

The Relationship between Folic Acid and Vitamin B12 Serum Levels with High Sensitivity C-reactive Protein and Homocysteine in Chronic Hemodialysis Patients: A Cross-sectional Study.

BACKGROUND: Folic acid (FA) and vitamin B12 treatment have been routinely prescribed to lower serum homocysteine levels and to reduce inflammation. However, no study has been conducted to determine serum folic acid (SFA) and vitamin B12 (B12) levels in patients who have twice-weekly hemodialysis. The aim of our study was to assess serum folate and B12  levels in chronic hemodialysis patients and their relationship with hsCRP and homocysteine levels. METHODS: Our study was a cross-sectional study involcing patients who had twice-weekly hemodialysis in Dr Cipto Mangunkusumo National Hospital Jakarta, Indonesia. Predialysis blood samples were taken to measure SFA, B12, homocysteine and hsCRP levels. Patients with medical conditions affecting the assays were excluded. Spearman correlation was used to compare variables. RESULTS: Eighty subjects enrolled in this study. Among those of non-given folic acid and vitamin B-12 supplementation, only 3.85% of subjects had low folic acid levels, and none had low vitamin B12 levels. A moderate negative correlation between serum folic acid and homocysteine level (p≤0.001; r=-0.42) and a weak correlation between serum vitamin B12 and homocysteine level (p=0.009; r=-0.29) was found. Among the high-risk cardiovascular group (CRP>3, n=49), there is a moderate negative correlation between serum folic acid and homocysteine level (p≤0.001; r=-0.561) and a weak negative correlation between vitamin B12 and homocysteine level (p=0.018; r=-0.338). CONCLUSION: There is a significant negative correlation between serum vitamin B12 and folic acid with homocysteine levels, especially in high-risk cardiovascular group.

The Association of ß2-Microglobulin and Fibroblast Growth Factor 23 with Major Adverse Cardiac Event in Acute Coronary Syndrome Patients with Chronic Kidney Disease.

BACKGROUND: chronic kidney disease (CKD) increases the severity and risk of mortality in acute coronary syndrome (ACS) patients. The role of ß2-M as a filtration and inflammation marker and FGF23 as a CKD-MBD process marker might be significant in the pathophysiology in ACS with CKD patients. This study aims to determine the association of ß2-M and FGF23 with major adverse cardiac event (MACE) in ACS patients with CKD. METHODS: we used cross sectional and retrospective cohort analysis for MACE. We collected ACS patients with CKD consecutively from January until October 2018 at Dr. Cipto Mangunkusumo General Hospital. Data were analyzed using logistic regression and Cox's Proportional Hazard Regression. RESULTS: a total of 117 patients were selected according to the study criteria. In bivariate analysis, ß2-M, FGF23, and stage of CKD had significant association with MACE (p = 0.014, p = 0.026, p = 0.014, respectively). In multivariate analysis, ß2-M - but not FGF 23- was significantly associated with MACE (adjusted HR 2.16; CI95% 1.15-4.05; p = 0.017). CONCLUSION: ß2-M was significantly associated with MACE, while FGF23 was not so. This finding supports the role of inflammation in cardiovascular outcomes in ACS with CKD patient through acute on chronic effect.

Wound Healing in Diabetic Foot Ulcer Patients Using Combined Use of Platelet Rich Fibrin and Hyaluronic Acid, Platelet Rich Fibrin and Placebo: An Open Label, Randomized Controlled Trial.

BACKGROUND: Autologous platelet-rich fibrin (A-PRF) is an adjunctive method for diabetic foot ulcer (DFU) in addition to glycaemic control and debridement. This study aimed to evaluate the role of A-PRF + hyaluronic acid (HA), A-PRF and sodium chloride 0.9% (control) in DFU wound healing. Nowaday, the use of  PRF autologous consider as adjuvant therapy in DFU treatment. METHODS: This open-label randomized controlled trial was conducted at Koja District Hospital and Gatot Soebroto Hospital from July 2019 to April 2020. DFU patients with wound duration of three months, Wagner-2, and ulcer size < 40 cm2 were recruited and randomly assigned into A-PRF + AH, A-PRF and control group. On day-0, day-3 and day -7, samples and photographs were taken. Samples were analysed with ELISA and photographs were analysed with ImageJ to calculate granulation index (GI). Statistical analysis was performed using SPSS version 20. RESULTS: Topical therapy with A-PRF + AH was associated with a significant increase in VEGF from day 0 (232.8 pg/mg) vs day 7 (544.5 pg/mg) compared to A-PRF on day 0 (185.7 pg/mg) vs day 7 (272.8 pg/mg), and the controls on day 0 (183.7 pg/mg) vs day 7 (167.4 pg/mg). On evaluation  of VEGF swab, there is increasing significantly in A-PRF+HA group compare others group in day -3 ( p=0.022) and day -7 (p= 0.001).In the A-PRF + AH group, there was a significant decrease in IL-6 from day 0 (106.4 pg/mg) vs day 7 (88.7 pg/mg) compared with PRF on day 0 (91.9 pg/mg) vs day 7 (48,8 pg/mg). IL-6 was increased in the control group from day 0 (125.3 pg/mg) vs day 7 (167.9 pg/mg). On evaluation  of IL-6 swab, there is decreasing significantly in A-PRF+HA group compare others group in day -7 (p= 0.041). CONCLUSION: The PRF + HA combination increased angiogenesis and reduced inflammation in DFUs and may represent a new DFU therapy.

Tocilizumab as a Treatment for 'Cytokine Storm Syndrome' in COVID-19: A Case Report.

Coronavirus disease 19 (COVID-19) which is caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), has been a problem worldwide, particularly due to the high rate of transmission and wide range of clinical manifestations. Acute respiratory distress syndrome (ARDS) and multiorgan failure are the most common events observed in severe cases and can be fatal. Cytokine storm syndrome emerges as one of the possibilities for the development of ARDS and multiorgan failure in severe cases of COVID-19. This case report describes a case of a 53-year-old male patient who has been diagnosed with COVID-19. Further evaluation in this patient showed that there was a marked increase in IL-6 level in blood accompanied with hyperferritinemia, which was in accordance with the characteristic of cytokine storm syndrome. Patient was treated with tocilizumab, a monoclonal antibody and is an antagonist to IL-6 receptor. The binding between tocilizumab and IL-6 receptors effectively inhibit and manage cytokine storm syndrome. Although this case report reported the efficacy of tocilizumab in managing cytokine storm syndrome, tocilizumab has several adverse effects requiring close monitoring. Further clinical randomized control trial is required to evaluate the efficacy and safety of tocilizumab administration in participants with various clinical characteristics and greater number of subjects.

The Role of Acute Hyperglycemia on the Risk of Malignant Arrhythmia in Acute Myocardial Infarction Patients: A Study of Myocardial Damage, Ion Channel Changes and Inflammatory Factors.

BACKGROUND: acute myocardial infarction (AMI) is often followed by hyperglycemia. To date, there is no study that examine the role of myocardial damage, ion channel changes and increased inflammatory response as a pathomechanism of malignant arrhythmias due to hyperglycemia in AMI patients. The aim of this study is to determine the effect of acute hyperglycemia on the occurence of malignant arrhythmias, troponin I, VLP, echocardiographic strain, ion channel changes (CaMKII) and hsCRP. This study also aims to assess the effect of troponin I, VLP, GLS, CaMKII and hsCRP on the occurence of malignant arrhythmias in AMI patients with acute hyperglycemia. METHODS: a cross-sectional study followed by a cohort study was conducted on AMI patients treated at ICCU Cipto Mangunkusumo Hospital Jakarta during November 2018 to May 2019 period. Patients with severe infections and who had experienced malignant arrhythmias at admission were excluded from the study. The occurence of malignant arrhythmias as the main outcome of this study and CaMKII level were assessed on the fifth day of treatment. Patients who died before the fifth day of treatment due to causes other than malignant arrhythmias were excluded from analysis. The association between acute hyperglycemia with VLP and the occurence of malignant arrhythmias was analyzed through a chi-square test, whereas the differences between troponin I, GLS, CaMKII and hsCRP, based on the hyperglycemia status of the patient, were analyzed by Mann-Whitney U test. RESULTS: a total of 110 patients were included in the study. Two patients died on the third day of observation due to malignant arrhythmias. No significant relationship was found between acute hyperglycemia in AMI and malignant arrhythmias (RR = 1,38, 95%CI 0.50-3.77). There were differences of CaMKII level on day-1 and day-5 between those who were experienced malignant arrhytmia and those who were not (p-value for differences are 0,03 and 0,01, respectively. In the acute hyperglycemia group, there was difference of CaMKII day-5 levels between positive and negative VLP (p = 0.03). CONCLUSION: it was concluded that the inititial stage of AMI causes more dominant myocardial damage, as compared to metabolic factors. In the next stage of AMI, acute hyperglycemia increases ROS and the activation of ion channel changes described by CaMKII. This change results in electrophysiological remodeling of the heart, as seen in the VLP image on SA-ECG.

Targeting Inflammation and Immune System in Acute Myocardial Infarction.

Over more than two decades, the concept of atherosclerosis has developed and lead to inflammatory hypothesis. Inflammation plays an important role on pathogenesis of atherothrombosis and coronary heart disease (CHD), including acute coronary syndrome (ACS). Although the management of ACS has been demonstrated to be beneficial for secondary prevention of coronary heart disease (such as using statin and aspirin) and also seemed to have positive effect on inflammation, the identification of effective management, specifically targeting inflammation, has been not been comprehensively understood.The Canakinumab Anti-inflammatory Thrombosis Outcomes Study (CANTOS) supported targeting inflammation as a potential effective treatment for chronic coronary heart disease. In the CANTOS study, canakinumab, a monoclonal antibody that inhibits interleukin-1ß, reduced the level of hsCRP and caused lower risk of composite endpoint of death due to cardiovascular diseases, myocardial infarct or stroke compared to placebo. However, non-specific anti-inflammatory treatment using methotrexate in the Cardiovascular Inflammation Reduction Trial (CIRT) study did not show any reduced hsCRP and demonstrated that there is no benefit associated with cardiovascular outcomes, which left us with a question whether direct intervention on inflammation could improve cardiovascular outcomes.

Validity and Reliability Studies of the Indonesian Version of the Minnesota Living with Heart Failure Questionnaire (MLHFQ): Quality of Life Questionnaire for Patients with Chronic Heart Failure.

BACKGROUND: Minnesota Living with Heart Failure Questionnaire (MLHFQ) is the most commonly used questionnaire and it has a good EMPRO (Evaluating the Measurement of Patient-Reported Outcomes) score. The MLHFQ has been adapted and used by various countries worldwide. However, to be utilized in Indonesia, it needs validity and reliability studies. This study aimed to obtain a valid and reliable Indonesian version of the Minnesota Living with Heart Failure Questionnaire (MLHFQ) so that it can be used in Indonesia. METHODS: the present study was a cross sectional study with 85 subjects (mean age 58 (SD 11) years; 55% subjects were male) who had chronic heart failure and was treated at the outpatient clinic of cardiology in Dr. Cipto Mangunkusumo Hospital, Jakarta. Validity of the MLHFQ was assessed by evaluating the construct validity using multitrait-multimethod analysis and external validity was evaluated by compairing  the MLHFQ with the SF-36 questionnaire.  Reliability was assessed using Cronbach's α and intraclass correlation coefficients (ICC). RESULTS: the Indonesian version of the MLHFQ had moderate-to-strong correlation between domains and items in questionnaire (r: 0.571-0.748; p<0.01) and it had moderate negative correlation with SF-36 questionnaire  (r -0.595; p<0.001). The Cronbach α of Indonesian version of MLHFQ was 0.887; while the ICCs was 0.918. CONCLUSION: the Indonesian version of MLHFQ has good validity and reliability to asses the quality of life of patients with chronic heart failure in Indonesia.

Validity and Reliability of the Indonesian Version of SF-36 Quality of Life Questionnaire on Patients with Permanent Pacemakers.

AIM: to construct and validate Indonesian version of SF-36. METHODS: this is a cross-sectional study, which consist of 2 stages process: 1) language and cultural adaption; and 2) validity and reliability evaluation. We evaluated 32 pacemaker patients during language and cultural adaptation stage and 20 pacemaker patients during validity and reliability evaluation stages from September 2014 to August 2015. We followed cross-cultural adaptation guideline to produce Indonesian version of the questionnaire. The final translated questionnaire was checked by assessing the correlation of SF-36 and 6-minutes walking test (6MWT) and NT pro-BNP result. RESULTS: Indonesian version of SF-36 showed positive correlation between 6MWT result and physical functioning (PF) (r=0.363; p=0.001) and negative correlation between NT pro-BNP score with general health (GH) (r=-0.269; p=0.020) and mental health (MH) (r=-0.271; p=0.019). The internal consistency of Indonesian version of SF-36 questionnaire, which measured by Cronbach's alpha, was good with value of >0.70. Repeatability between day 1 and day 8 was good, with strong positive correlation (r=0.626; p=0.003). CONCLUSION: the Indonesian version of SF-36 could be used as a general questionnaire to assess quality of life in patients with permanent pacemaker.

Factors Associated with In-stent Restenosis in Patients Following Percutaneous Coronary Intervention.

AIM: to determine factors associated with In-Stent Restenosis (ISR) in patients following Percutaneous Coronary Intervention (PCI). METHODS: a retrospective cross-sectional study was conducted using secondary information from medical records of post-PCI patients who underwent follow-up of angiography PCI between January 2009 and March 2014 at The Integrated Cardiovascular Service Unit, Cipto Mangunkusumo Hospital, Jakarta. Angiographic ISR was defined when the diameter of stenosis 50% at follow-up angiography including the diameter inside the stent and diameter with five-mm protrusion out of the proximal and distal ends of the stent. RESULTS: there were 289 subjects including 133 subjects with and 156 subjects without ISR. The incidence of ISR in patients using of bare-metal stent (BMS) and drug-eluting stent (DES) were 61.3% and 40.7%, respectively. Factors associated with ISR are stent-type (OR=4.83, 95% CI 2.51-9.30), stent length (OR=3.71, 95% CI 1.99-6.90), bifurcation lesions (OR=2.43, 95% CI 1.16-5.10), smoking (OR=2.30, 95% CI 1.33-3.99), vascular diameter (OR=2.18, 95% CI 1.2-3.73), hypertension (OR=2.16, 95% CI 1.16-4.04) and diabetes mellitus (OR=2.14, 95% CI 1.23-3.70). CONCLUSION: stent type, stent length, bifurcation lesions, smoking, vascular diameter, hypertension and DM are factors associated with ISR in patients following PCI.