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.

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.

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.

Summary of Known Genetic and Epigenetic Modification Contributed to Hypertension.

Hypertension is a multifactorial disease due to a complex interaction among genetic, epigenetic, and environmental factors. Characterized by raised blood pressure (BP), it is responsible for more than 7 million deaths per annum by acting as a leading preventable risk factor for cardiovascular disease. Reports suggest that genetic factors are estimated to be involved in approximately 30 to 50% of BP variation, and epigenetic marks are known to contribute to the initiation of the disease by influencing gene expression. Consequently, elucidating the genetic and epigenetic mediators associated with hypertension is essential for better discernment of its pathophysiology. By deciphering the unprecedented molecular hypertension basis, it could help to unravel an individual's inclination towards hypertension which eventually could result in an arrangement of potential strategies for prevention and therapy. In the present review, we discuss known genetic and epigenetic drivers that contributed to the hypertension development and summarize the novel variants that have currently been identified. The effect of these molecular alterations on endothelial function was also presented.

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.

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.

Effect of primary balloon angioplasty on draining vein diameter and volume flow in patients with arteriovenous fistula: A cohort study.

Background: Chronic kidney disease (CKD) and end-stage kidney disease (ESKD) cause major morbidity and mortality in 10% of the global population with CKD. The most common renal replacement therapy is hemodialysis with arteriovenous fistula (AVF) access. AVF often undergoes maturation failure due to feeding artery and draining vein inadequacy. Mechanical dilatation, such as primary balloon angioplasty (PBA), can overcome AVF maturation failure. The volume flow (VF) and diameter of the draining veins in AVF patients must be known to evaluate the effect of PBA on AVF maturation. This study aims to analyze the impact of PBA on VF and draining vein diameter in ESKD patients undergoing AVF surgery. Methods: A retrospective cohort clinical trial was conducted at our institution. A total of 75 participants had AVF with an arterial diameter >1.5 mm or vein diameter at the AVF creation site of 2-4 mm. The subjects were divided into 2 groups: the intervention group undergoing PBA (n = 36) and the control group, without PBA (n = 39). PBA was performed using a Mustang ballon (3-6 mm, Medtronic). Follow-ups were conducted at 1 week, 2 weeks, and 6 weeks after AVF creation. Results: Based on the data, the diameter and VF of the draining veins were significantly larger in the intervention group than in the control group (p < 0.001). Furthermore, we found significant differences in the mean diameter and VF of the draining veins between the control and intervention groups at all stages of examination, from preoperatively to 6 weeks postoperatively (p < 0.001). The strength of the analysis was more than 80%. Conclusion: PBA can increase the diameter and VF of the draining veins in patients with AVF.

The role of Tei index added to the GRACE risk score for prediction of in-hospital MACE after acute myocardial infarction.

Introduction: The Global Registry of Acute Coronary Events (GRACE) risk score is widely recommended for risk assessment in patients with acute myocardial infarction (AMI). Variable degrees of impairment in left ventricular (LV) systolic and diastolic function might be found after AMI. Tei index is an echocardiography parameter that represents both systolic and diastolic LV performance. Previous studies demonstrate Tei index as an independent predictor of Major Adverse Cardiovascular Events (MACE) after AMI. This study investigates whether the addition of Tei index could improve the GRACE risk score performance to predict inhospital MACE after AMI. Methods: A prospective cohort study was conducted on 75 patients who presented with AMI. Total GRACE score was calculated on patient admission and echocardiography was conducted within 72 hours of hospitalization for measurement of MPI. All patients were observed for the incidence of MACE during hospitalization. The incremental predictive value of the GRACE risk score alone and combined with Tei index was assessed by the change in area under the curve (AUC) by DeLong's method, likelihood ratio test (LRT), and continuous net reclassification improvement (cNRI). Results: The addition of Tei index to the GRACE risk score significantly improves the predictive value of the GRACE risk score (increase in AUC from 0.753 for the GRACE risk score to 0.801 for the GRACE score combine with Tei index, p=0.354; LRT=4.65, p=0.030; cNRI=0.515, p=0.046). Conclusions: Adjustment of Tei index to GRACE risk score might improve risk prediction of in-hospital MACE after AMI.

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.

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.

Usefulness of the CODE ST-Segment Elevation Myocardial Infarction Program to Improve Quality Assurance in Patients With ST-Segment Elevation Myocardial Infarction.

The highest mortality rate associated with acute coronary syndrome is observed in patients with ST-segment elevation myocardial infarction (STEMI). Quality care in STEMI management depends on timely reperfusion of the ischemic coronary artery. The CODE STEMI program has been developed to reduce delays and serves as a method to improve quality care in patients with STEMI. Our study aimed to investigate the effects of implementing the CODE STEMI program on quality care and hospital marketing strategy. Our research was a descriptive study with mixed evaluation methods. We enrolled 207 patients with STEMI who underwent primary percutaneous coronary intervention from 2015 to 2018. We used quantitative methods by tracking medical records and administrative documents, as well as qualitative methods by observation and in-depth interviews. Statistical analysis was done using Mann-Whitney and chi-square tests. Our study demonstrated reduced door-to-balloon time, total cost, and length of stay of patients with STEMI who were treated with the CODE STEMI program (p <0.001, p <0.001, and p = 0.009, respectively). In addition, there was a likely decrease in major adverse cardiac event incidence and mortality rate after the implementation of CODE STEMI. The hospital and patients expressed their satisfaction with the CODE STEMI program. The program proved to have good efficacy, effectiveness, optimality, acceptability, legitimation, and equity. It also met the marketing mix principles, which included increasing the total number of patients with cardiovascular diseases as well as increasing levels of public trust in STEMI management. In conclusion, the CODE STEMI program has a positive impact on quality care and hospital marketing strategy.

The role of clopidogrel resistance-related genetic and epigenetic factors in major adverse cardiovascular events among patients with acute coronary syndrome after percutaneous coronary intervention.

Despite patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) and receiving clopidogrel therapy, some patients still experience major adverse cardiovascular events (MACEs). Clopidogrel resistance, which may be regulated by genetic and epigenetic factors, may play a role in MACEs. This study aimed to determine the association between genetic (CYP2C19 and P2Y12 polymorphisms) and epigenetic (DNA methylation of CYP2C19 and P2Y12 and miRNA-26a expression) factors and their effects on MACEs among post-PCI patients. Post-PCI patients who received a standard dosage of clopidogrel at Harapan Kita Hospital between September 2018 and June 2020 were included in this study. MACEs were observed in patients within 1 year after PCI. Platelet aggregation was assessed using light transmission aggregometry (LTA). DNA methylation of CYP2C19 and P2Y12 was assessed using the bisulfite conversion method. CYP2C19 and P2Y12 polymorphisms and miRNA-26a expression were evaluated using quantitative real-time polymerase chain reaction (qRT-PCR). Among a total of 201 subjects, 49.8% were clopidogrel-resistant, and 14.9% experienced MACEs within 1 year after PCI (death was 7.5%). Hypomethylation of CYP2C19 (p = 0.037) and miRNA-26a upregulation (p = 0.020) were associated with clopidogrel resistance. CYP2C19*2/*3 polymorphisms (p = 0.047) were associated with MACEs in 1 year. This study demonstrated that hypomethylation of CYP2C19 and miRNA-26a upregulation increased the risk of clopidogrel resistance in post-PCI patients, but there was no correlation between clopidogrel resistance and MACEs. However, CYP2C19*2/*3 polymorphisms were the factors that predicted MACEs within 1 year.

Effects of the COVID-19 pandemic on the management of ST-Segment elevation myocardial infarction in Indonesia: a cohort study.

Background: ST-segment elevation myocardial infarction (STEMI) is a form of acute coronary syndrome with high mortality rate. Management of STEMI should be performed as soon as possible to prevent further damage. With the emergence of coronavirus disease 2019 (COVID-19), it may face obstacles. To overcome those problems, some changes in policy focusing on fibrinolytic therapy in STEMI patients have been applied. This study aimed to identify the effects of COVID-19 in management of STEMI patients in Indonesia. Methods: This retrospective study was conducted in Dr. Cipto Mangunkusumo Hospital (CMH), the national referral center in Indonesia. We compared data between 2018 to 2019 and 2020 to 2021 as before and during COVID-19 pandemic period, respectively. We analyzed the effects of COVID-19 on STEMI patients' visits to hospital i.e., monthly hospital admission and symptoms-to-hospital, management of STEMI i.e., the strategies and time of reperfusion, and clinical outcomes of STEMI patients i.e., major adverse coronary event and mortality. Results: There was a significant statistically reduced mean of monthly hospital admissions from 11 to 7 (p = 0.002) and prolonged duration of symptoms-to-hospital during COVID-19 from 8 to 12 hours (p = 0.005). There was also a decrease in primary percutaneous coronary intervention (PPCI) procedures during COVID-19 (65.2% vs. 27.8%, p<0.001), which was accompanied by an increased number of fibrinolytic (1.5% vs. 9.5%, p<0.001) and conservative therapy (28.5% vs. 55.6%, p <0.01). Moreover, there was also a prolonged duration of diagnosis-to-wire-crossing time (160 vs. 186 minutes, p = 0.005), meanwhile, percentage of urgent PCI, door-to-needle time, and clinical outcomes were not statistically significant. Conclusions: During COVID-19 pandemic, the number STEMI patients declined in monthly hospital admission, delays in symptoms-to-hospital time, changes in type of reperfusion strategy, and delays in PPCI procedures in CMH. Meanwhile, fibrinolytic time and clinical outcomes were not affected.

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.

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.

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 role of VEGF, PDGF and IL-6 on diabetic foot ulcer after Platelet Rich Fibrin + hyaluronic therapy.

BACKGROUND: Current standard management of diabetic foot ulcers (DFUs) consists of surgical debridement followed by soak NaCl 0.9% gauzes tight infection and glycaemic control. Nowadays the use of advanced platelet-rich fibrin (A-PRF) has emerged as an adjunctive method for treating DFUs. This study was conducted to demonstrate the ability of combine A-PRF + HA as a complementary therapy in DFUs healing related with angiogenesis,inflammation and granulation index process. METHODS: This open label randomized controlled trial was conducted in Koja District Hospital and Gatot Soebroto Hospital Jakarta, Indonesia on July 2019-April 2020. DFUs patients with wound duration of three months, Wagner-2, with size of ulcer less than 40 cm2 were included in the study. The number of subjects was calculated based on the rule of thumb and allocated randomly into three groups, namely topical A-PRF + HA, A-PRF and Sodium Chloride 0.9% as a control, for each of 10 subjects. A-PRF made by 10 mL venous blood, centrifuge 200 G in 10 min, meanwhile A-PRF + HA though mix both them with vertex machine around 5 min. Biomarker such as VEGF, PDGF and IL-6 examined from DFU taken by cotton swab and analysis using ELISA. Granulation Index was measured using ImageJ. Biomarkers and granulation index were evaluated on day 0, 3, 7 and 14. Data were analysed using SPSS version 20 with Anova and Kruskal Wallis test to compare the angiogenesis and inflammation effect between the three groups. RESULT: In topical dressing A-PRF + HA, there is an increase in delta VEGF on day-3 (43.1 pg/mg protein) and day-7 (275,8 pg/mg protein) compared to A-PRF on day-3 (1.8 pg/mg protein) and day-7 (104.7 pg/mg protein), also NaCl (control) on day-3 (-4.9 pg/mg protein) and day-7 (28.3 pg/mg protein). So that the delta VEGF of A-PRF + HA group increase significantly compared with others on day-3 (p = 0.003) and day- 7 (p < 0.001). Meanwhile A-PRF + AH group, there is also a decrease in delta IL-6 after therapy on day-3 (-10.9 pg/mg protein) and day-7 (-18.3 pg/mg protein) compared to A-PRF in delta IL-6 on day- 3 (-3.7 pg/mg protein) and on day-7 (-7.8 pg/mg protein). In NaCl (control) group there is a increase delta IL-6 on day-3 (4.3 pg/mg protein) and on day-7 (35.5 pg/mg protein). So that the delta IL-6 of A-PRF + HA group decrease significantly compared with others only on day- 7 (p = 0.015). In PDGF le level analysis, A-PRF + HA group increase significantly (p = 0.012) only in day -7 compare with other group (5.5 pg/mg protein). CONCLUSION: The study shows the superior role of combined A-PRF + HA in the treatment DFU though increase angiogenesis and decrease inflammation pathway. The advantage of using A-PRF + HA is that it accelerates wound healing by increasing granulation tissue compared to A-PRF alone.

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.

Visceral adiposity, subcutaneous adiposity, and severe coronavirus disease-2019 (COVID-19): Systematic review and meta-analysis.

BACKGROUND AND AIMS: Body mass index (BMI) has previously been shown to increase mortality and disease severity in patients with COVID-19, but the pooled effect estimate was heterogeneous. Although BMI is widely used as an indicator, it cannot distinguish visceral from subcutaneous fat. This systematic review and meta-analysis aimed to investigate the association between visceral adiposity, subcutaneous fat, and severe COVID-19. METHODS: We performed a systematic literature search using the databases: PubMed, Embase, and EuropePMC. Data on visceral fat area (VTA), subcutaneous fat area (SFA), and total fat area (TFA) were collected. The outcome of interest was severe COVID-19. We used a REML random-effects model to pool the mean differences and odds ratio (OR). RESULTS: There were 5 studies comprising of 539 patients. Patients with severe COVID-19 have a higher VTA (mean difference 41.7 cm2 [27.0, 56.4], p < 0.001; I2: 0%) and TFA (mean difference 64.6 cm2 [26.2, 103.1], p = 0.001; I2: 0%). There was no significant difference in terms of SFA between patients with severe and non-severe COVID-19 (mean difference 9.3 cm2 [-4.9, 23.4], p = 0.199; I2: 1.2%). Pooled ORs showed that VTA was associated with severe COVID-19 (OR 1.9 [1.1, 2.2], p = 0.002; I2: 49.3%). CONCLUSION: Visceral adiposity was associated with increased COVID-19 severity, while subcutaneous adiposity was not. PROSPERO ID: CRD42020215876.