Proportion of Hypogonadism in Transfusion-Dependent Thalassemia Patients and Its Contributing Factors.

BACKGROUND: Beta thalassemia is a lifelong disease involving malformed red blood cells (RBC). One of the disease's complications is hypogonadism, in which adults tend to exhibit regression in sexual characteristics, experience sexual dysfunction, and therefore have a lower quality of life. Around 3-10% of the Indonesian population carries the beta-thalassemia gene. This study aimed to see the proportions of hypogonadism in transfusion-dependent thalassemia patients and its contributing factors. METHODS: This is a cross-sectional study involving 60 male patients admitted to three Indonesian general hospitals from July 2022 to July 2023. All patients were diagnosed with beta-thalassemia via chromatography hemoglobin analysis. We performed a single-time physical examination and laboratory examinations to determine FSH, LH, and free testosterone levels. The correlation between Hb and sexual hormone levels was analyzed using Spearman's rank correlation coefficient. ROC curve analysis was conducted afterward. All statistical analysis was done in SPSS version 29. RESULTS: 31 out of 60 thalassemia patients had hypogonadism. Pre-transfusion Hb count was found to be linearly correlated with FSH (r = 0.388, p = 0.049), LH (r = 0.338, p = 0.008), and free testosterone (r = 0.255, p = 0.049). ROC analysis indicated that pre-transfusion Hb was viable as a predictor for hypogonadism (AUC = 0.655, 65.5% sensitivity, 67.7% specificity). CONCLUSION: We confirmed the role of pre-transfusion Hb count as a potential predictor for hypogonadism due to the tissue hypoxia mechanism and transfusion-related iron overload in TDT patients. Decreased Hb is linearly correlated with FSH, LH, and testosterone levels. Decreased Hb also downregulates these factors.

Developing Models to Predict BRAFV600E and RAS Mutational Status in Papillary Thyroid Carcinoma Using Clinicopathological Features and pERK1/2 Immunohistochemistry Expression.

The Cancer Genome Atlas (TCGA) has classified papillary thyroid carcinoma (PTC) into indolent RAS-like and aggressive BRAF-like based on its distinct driver gene mutations. This retrospective study aimed to assess clinicopathology and pERK1/2 expression variations between BRAF-like and RAS-like PTCs and establish predictive models for BRAFV600E and RAS-mutated PTCs. A total of 222 PTCs underwent immunohistochemistry staining to assess pERK1/2 expression and Sanger sequencing to analyze the BRAF and RAS genes. Multivariate logistic regression was employed to develop prediction models. Independent predictors of the BRAFV600E mutation include a nuclear score of 3, the absence of capsules, an aggressive histology subtype, and pERK1/2 levels exceeding 10% (X2 = 0.128, p > 0.05, AUC = 0.734, p < 0.001). The RAS mutation predictive model includes follicular histology subtype and pERK1/2 expression > 10% (X2 = 0.174, p > 0.05, AUC = 0.8, p < 0.001). We propose using the prediction model concurrently with four potential combination group outcomes. PTC cases included in a combination of the low-BRAFV600E-scoring group and high-RAS-scoring group are categorized as RAS-like (adjOR = 4.857, p = 0.01, 95% CI = 1.470-16.049). PTCs included in a combination of the high-BRAFV600E-scoring group and low-RAS-scoring group are categorized as BRAF-like PTCs (adjOR = 3.091, p = 0.001, 95% CI = 1.594-5.995). The different prediction models indicate variations in biological behavior between BRAF-like and RAS-like PTCs.

Increased risk of poor clinical outcome in COVID-19 patients with diabetes mellitus and in-hospital mortality predictors: A retrospective cohort from a tertiary hospital in Indonesia.

AIM: To determine association between diabetes in confirmed cases of COVID-19 and intensive care admission and in-hospital mortality, evaluate several laboratory parameters as mortality predictor and develop predictors of in-hospital mortality among diabetics with COVID-19. METHODS: This retrospective cohort recruited all cases of COVID-19 hospitalized in Fatmawati General Hospital from March to October 2020. Inclusion criterion was RT-PCR confirmed cases of COVID-19 who aged 18 years and older while exclusion criteria were incomplete medical record or cannot be found and pregnant women. RESULTS: We enrolled 506 participants to this study with median age of 51 years (IQR:22), female (56.32%), and diabetes (28.46%). Diabetes increased intensive care admission (adjusted OR: 2.57; 95% CI: 3.52-10.43) and in-hospital mortality (adjusted OR: 2.50; 95% CI: 1.61-3.89). In predicting in-hospital mortality, ferritin and lactate dehydrogenase offered an acceptable discrimination, AUC: 0.71 (95% CI: 0.62-0.79) and AUC: 0.70 (95% CI: 0.61-0.78), respectively. The optimal cut-off of predicting mortality for ferritin was 786 g/mL and for LDH was 514.94 u/L. Factors include age above 70 years old, RBGs level on admission above 250 mg/dL or below 140 mg/dL, ferritin level above 786 ng/mL and presence of ARDS increased the odds of mortality among individuals with diabetes. CONCLUSIONS: Diabetes increases risk intensive care admission and in hospital mortality in COVID-19. Multivariate analysis showed that older age, RBG on admission, high ferritin level, presence of ARDS increased the odds of mortality among individuals with diabetes.

Prevalence and Factors Related to Hypovitaminosis D in Type 2 Diabetes Mellitus Patients with Depression.

BACKGROUND: The prevalence of hypovitaminosis D (hypoD) in patients with type 2 diabetes mellitus (T2DM) and depression has not been documented. In addition, the risk factors are unknown. This study aimed to identify the prevalence of and risk factors for hypoD in patients with T2DM who also have depression. METHODS: 118 patients with T2DM who visited the outpatient endocrinology clinics at Cipto Mangunkusumo National Hospital between December 2019-September 2022 provided the clinical and demographic data for this cross- sectional study, including body mass index, blood pressure, glycosylated haemoglobin (HbA1c), lipid profiles, therapy, gender, age, marital status, and educational background. We used The Beck Depression Inventory II (BDI II) to evaluate depression. We used enzyme-linked immunosorbent assay kit to assess the dependent variable: serum vitamin D. We characterized serum vitamin D levels into three groups (normal, 30 ng/mL; insufficient, 20-29 ng/mL; deficient, 20 ng/mL). We also used analyses of variance to examine the anthropometric, clinical, and biochemical factors between the three groups. RESULTS: 118 subjects with T2DM. Their median age was 56 years old (48, 75-60 years old), with a BDI II score of 17 (15-19), and a serum concentration of vitamin D. The D level was 18.3 ng/mL (9.17-29.46 ng/mL). Only 21.8% of patients with T2DM and depression had sufficient levels of vitamin D. We used multivariable analysis of variance model to examine the associations between age, BDI II score, HbA1c, and systolic and diastolic blood pressure with vitamin D level. Age and BDI II score both had a statistically significant effect on vitamin D levels. CONCLUSION: This cross-sectional study discovered that patients with T2DM and depression had a high prevalence (77.7%) of hypoD. Age and BDI II score both affected differences in vitamin D levels with statistical significance.

Profile of BRAFV600E, BRAFK601E, NRAS, HRAS, and KRAS Mutational Status, and Clinicopathological Characteristics of Papillary Thyroid Carcinoma in Indonesian National Referral Hospital.

Introduction: BRAFV600E and RAS mutations are the most common gene mutations in papillary thyroid carcinoma (PTC) that may be correlated with its biological behavior. There are still limited data about BRAFV600E and RAS mutations in Indonesia. This study aims to determine the prevalence of BRAFV600E and RAS mutations, and their association with clinicopathologic characteristics. Methods: Patients who had total thyroidectomy from 2019 to 2021 and those who met our study criteria underwent PCR and DNA sequencing analysis for BRAFV600E, BRAFK601E, exon 2 and 3 of NRAS, HRAS, and KRAS. Analyses were performed to determine the associations of BRAFV600E and RAS mutations with clinicopathologic characteristics. Results: Of 172 PTC patients, BRAFV600E mutation was observed in 37.8% of the patients and RAS mutations were found in 21.5%. One patient harbored BRAFK601E mutation. There was a significant association of BRAFV600E with a high-stage (p = 0.033, OR: 3.279; 95% CI: 1.048-10.259), tall-cell variants (p ≤0.001, OR: 41.143; 95% CI: 11.979-141.308), non-encapsulated (p = 0.001, OR: 4.176; 95% CI: 2.008-8.685), lymphovascular invasion (p = 0.043, OR: 1.912; 95% CI: 1.018-3.592), extrathyroidal extension (p = <0.001, OR: 3.983; 95% CI: 1.970-8.054), and lymph node metastasis (p = 0.009, OR: 2.301; 95% CI: 1.224-4.326). Follicular variant (p = 0.001, OR: 7.011; 95% CI: 2.690-18.268), encapsulated (p = 0.017, OR: 2.433; 95% CI: 1.161-5.100), and absent of extrathyroidal extension (p = 0.033, OR: 2.890; 95% CI: 1.052-7.940) were associated with RAS mutations. Conclusion: A significant association between BRAFV600E mutation and high clinical stage, tall-cell variants, non-encapsulated morphology, lymphovascular invasion, extrathyroidal extension, and lymph node metastasis in PTC was observed. RAS mutations were associated with the follicular variant, encapsulated tumor, and no extrathyroidal extension. HRAS-mutated PTC frequently exhibited tumor multifocality.

The determinants of thyroid function among vegetable farmers with primary exposure to chlorpyrifos: A cross-sectional study in Central Java, Indonesia.

Objectives: Occupational pesticide exposure, chlorpyrifos (CPF) in particular, may adversely affect the thyroid. The purpose of this study was to evaluate the determinants of thyroid function as indicated by the serum concentration of thyroid-stimulating hormone (TSH) among Indonesian vegetable farmers with primary exposure to CPF. Methods: A total of 151 vegetable farmers participated in this study. The sociodemographic and occupational characteristics of the participants were obtained using a structured interviewer-administered questionnaire. A validated quantitative method was used to estimate the cumulative exposure level (CEL). Serum TSH, thyroglobulin (Tg), free thyroxine (FT4), and urinary iodine excretion (UIE) were measured in the laboratory. The difference in TSH concentrations according to CEL and other characteristics were analysed using the Mann-Whitney U test. A multiple linear regression model was used to evaluate the potential determinants of TSH. Results: The mean age was 50 (SD 9.4) years. The median concentrations of TSH, FT4, and Tg/FT4 ratio were 1.46 mIU/L, 1.17 ng/dL, and 6.23 × 102, respectively. We observed that higher TSH concentrations were found among those with a higher Tg/FT4 ratio, were classified as high CEL, and had lower UIE or FT4. Conclusions: Our findings show that Tg/FT4 ratio, CEL, FT4, UIE concentrations, and post-spraying days were determinants of TSH concentrations among farmers with primary exposure to CPF. These results indicate that farmers are exposed to agents with thyroid-disrupting properties, thus supporting previous evidence showing the potential for thyroid disorders in agricultural populations exposed to pesticides.

Autologous intraarterial pancreatic bone-marrow mononuclear cells infusion in T2D patients: Changes on beta-cells function, insulin resistance, and inflammatory marker.

BACKGROUND: Type 2 diabetes (T2D) is a progressive disease. Many drugs currently being used for the management of T2D have minimal effect on pancreatic beta cells regeneration. Cell-based therapies might provide potential benefits in this aspect. METHODS: A pilot study in five T2D patients with 12 months follow-up was performed to evaluate the effect of autologous bone marrow mononuclear stem cells (BM-MNCs) infusion into pancreatic arteries on the insulin requirement, beta-cell function, insulin resistance, and systemic inflammatory marker (CRP). RESULTS: The primary endpoint, a 50 % reduction of total insulin doses from baseline, was not achieved in this study. However, a trend of increasing fasting C-peptide (p = 0.07) and C-peptide 60' (p = 0.07) and 90' (p = 0.07) after a mixed-meal tolerance test was observed 12 months post-infusion compared to baseline levels. A similar result was observed for the homeostatic model assessment of beta cell function (HOMA1-B), an index for beta cell function. No improvement was observed for insulin resistance measured by homeostasis model assessment of insulin resistance (HOMA1-IR) and systemic inflammatory parameter. CONCLUSION: Intraarterial pancreatic autologous BM-MNCs infusion might potentially improve beta cell function in T2D patients, although further study is needed to confirm this finding.

Case Report: Left atrial myxoma with confirmed Delta variant COVID-19 infection, "to treat or withhold".

Primary cardiac tumors (PCTs) are extremely rare entities. More than half of PCTs are benign, with myxoma being the most common tumor. Generally, simple tumor resection is the treatment of choice for benign PCTs since it has promising results that yield low complication and recurrence rates. However, in the COVID-19 pandemic era, the mitigation protocols and/or concurrent COVID-19 infection should be taken into account in patient management for the best overall outcome. To our knowledge, this is the first case report of a patient with a left atrial myxoma and systemic embolism complication in the form of an ischemic stroke, with a concurrent confirmed COVID-19 delta variant infection.

Increased vegetable intake improves glycaemic control in adults with type 2 diabetes mellitus: a clustered randomised clinical trial among Indonesian white-collar workers.

Dietary patterns high in fibre and green leafy vegetables have shown an inverse association with lower risks of type 2 diabetes mellitus and improved glycaemic control. The study aimed to investigate the effects of increased vegetable intake and conventional diabetes diet on glycaemic control among type 2 diabetic patients. White-collar workers from one telecommunication company with type 2 diabetes were assigned to two treatment groups by cluster randomisation. Individuals with known type 2 diabetes and poor glycaemic control (HbA1c ≥8 g%) were eligible and a total of 84 subjects were recruited. Subjects in the intervention group (n 41) were offered to attend seminars and intensive coaching weekly to encourage them to increase raw vegetable intake. The control group (n 40) followed the conventional diet according to the guidelines of the Indonesian Society of Endocrinology. Glycated haemoglobin (HbA1c), plasma lipids, blood pressure, vegetable intake and anthropometric measurements were assessed at baseline and end line of 12 weeks intervention. A regression analysis was conducted using differences in HbA1C between baseline and 12 weeks as the dependent variable. Student's t test was conducted for the changes of biochemical indicators from baseline to end line during the period of 12 weeks intervention. Glycaemic control improved in the intervention group and mean HbA1C, fasting blood glucose and post-prandial blood glucose in the intervention group decreased significantly along with body weight, waist circumference and total cholesterol. The finding suggested that the intervention which emphasised raw vegetable intake contributed to improved glycaemic control among Indonesian adults with type 2 diabetes mellitus.

The Role of CYP2B6*6 Gene Polymorphisms in 3,5,6-Trichloro-2-pyridinol Levels as a Biomarker of Chlorpyrifos Toxicity Among Indonesian Farmers.

OBJECTIVES: One of the most widely used pesticides today is chlorpyrifos (CPF). Cytochrome P450 (CYP)2B6, the most prominent catalyst in CPF bioactivation, is highly polymorphic. The objective of our study was to evaluate the role of CYP2B6*6, which contains both 516G>T and 785A>G polymorphisms, in CPF toxicity, as represented by the concentration of 3,5,6-trichloro-2-pyridinol (TCPy), among vegetable farmers in Central Java, Indonesia, where CPF has been commonly used. METHODS: A cross-sectional study was conducted among 132 vegetable farmers. Individual socio-demographic and occupational characteristics, as determinants of TCPy levels, were obtained using a structured interviewer-administered questionnaire and subsequently used to estimate the cumulative exposure level (CEL). TCPy levels were detected with liquid chromatography-mass spectrometry. CYP2B6*6 gene polymorphisms were analyzed using a TaqMan® SNP Genotyping Assay and Sanger sequencing. Linear regression analysis was performed to analyze the association between TCPy, as a biomarker of CPF exposure, and its determinants. RESULTS: The prevalence of CYP2B6*6 polymorphisms was 31% for *1/*1, 51% for *1/*6, and 18% for *6/*6. TCPy concentrations were higher among participants with CYP2B6*1/*1 than among those with *1/*6 or *6/*6 genotypes. CYP2B6*6 gene polymorphisms, smoking, CEL, body mass index, and spraying time were retained in the final linear regression model as determinants of TCPy. CONCLUSIONS: The results suggest that CYP2B6*6 gene polymorphisms may play an important role in influencing susceptibility to CPF exposure. CYP2B6*6 gene polymorphisms together with CEL, smoking habits, body mass index, and spraying time were the determinants of urinary TCPy concentrations, as a biomarker of CPF toxicity.

Effects of Sambiloto (Andrographis paniculata) on GLP-1 and DPP-4 Concentrations between Normal and Prediabetic Subjects: A Crossover Study.

BACKGROUND: The extract of Andrographis paniculata (Burm. F.) Wall. Ex. Nees. (sambiloto) ( chuan xin lián) has been reported to have an antidiabetic effect on mice models and has been used traditionally in the community. The exact mechanism of sambiloto extract in decreasing plasma glucose is unclear, so we investigated the role of sambiloto extract in the incretin pathway in healthy and prediabetic subjects. METHODS: This study was a randomized, placebo-controlled, crossover, double-blind trial. It included 38 people who were healthy and 35 people who had prediabetes. All subjects were randomly assigned to receive either the intervention sambiloto extract or a placebo. All subjects were randomly assigned to receive the first intervention for 14 days. There was a washout period between subsequent interventions. The primary outcome was glucagon-like peptide 1 (GLP-1) concentration, and secondary outcomes were fasting insulin, 2-hour postprandial insulin, homeostasis model assessment of insulin resistance (HOMA-IR), fasting blood glucose, 2-hour postprandial blood glucose, dipeptidyl peptidase-4 (DPP-4), and glycated albumin before and after the intervention. RESULT: After the intervention, GLP-1 concentration significantly increased in prediabetes by 19.6% compared to the placebo (p=0.043). There were no significant differences in the changes of fasting insulin, 2-hour postprandial insulin, HOMA-IR, fasting blood glucose, 2-hour postprandial blood glucose, DPP-4, and glycated albumin levels after the intervention. Sambiloto extract did not inhibit the DPP-4 enzyme in healthy and prediabetic subjects. CONCLUSION: Sambiloto extract increased GLP-1 concentration without inhibiting the DPP-4 enzyme in prediabetic subjects. This trial is registered with ClinicalTrials.gov (ID: NCT03455049), registered on 6 March 2018-retrospectively registered (https://clinicaltrials.gov/ct2/show/NCT03455049).

Determination of factors affecting post-partum depression in primary healthcare during the COVID-19 pandemic.

Postpartum depression is a phenomenon that occurs in the first postpartum days. Symptoms of postpartum depression peak on days 3 to 5 postpartum with a duration ranging from a few hours to several days. Of course, this will be different during the Covid-19 pandemic. The aim of this study was to analyze the determinants that influence the incidence of post-partum depression in primary health during the pandemic. The method in this research is descriptive analysis with cross sectional approach with a total sample of 100 respondents. The research instrument used a standard instrument, namely the EPDS (Edinburgh Postnatal Depression Scale) instrument. The results of the study were the determinant factors of parity in primigravida and attitudes. From the results of this study, it can be concluded that the dominant factors that greatly influence the risk of post-partum depression in women in primary health during the pandemic are parity (primigravida) and the attitude of women who take it for granted when they know that they are at risk of post-partum depression.

The Effect of Vitamin D Supplementation on Symptoms of Depression in Patients with Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: The effect of vitamin D supplementation on depressive  symptoms in people with type 2 diabetes is still up for debate. The aim of this paper was to investigate the effect of vitamin D supplementation on symptoms of depression in type 2 diabetic patients. METHODS: The protocol for this review has been registered in PROSPERO:CRD42021231713. Searching for literature was conducted using Pubmed, EBSCOhost, and EMBASE. Randomised controlled trials (RCTs) regarding vitamin D supplementation in type 2 diabetic patients with depression were retrieved through a systematic search. The outcome measured was a change in depressive symptoms evaluated with any validated rating scale. Independent data extraction was conducted, and the study quality was assessed. A meta-analysis was carried out to calculate the improvement in depressive symptoms in the group receiving vitamin D and the control group. The available evidence in RCTs was analysed using the PRISMA approach, and clinical significance was determined using the GRADE system. Risk of bias was assessed using the Cochrane Risk of Bias Tool. RESULTS: Four RCTs were reviewed and three RCTs were meta-analysed. In two studies, vitamin D was statistically effective in improving depressive symptoms in type 2 diabetic patients. Three randomised controlled trials  were included in the meta-analysis with 161 subjects using depression score as an outcome assessment. Vitamin D is significantly more effective than placebo (95% CI: -0.70 to - 0.08, p = 0.01). CONCLUSION: Vitamin D supplementation is effective in improving depressive symptoms in type 2 diabetic patients. Future research with different geographical areas and larger samples should be done to further assess the benefits.

The Importance of the Timing of Tocilizumab Administration in Moderate to Severely Ill COVID-19: Single Centered Experience Case series.

One of the main causes of death in COVID-19 is the dysregulation of the host's immune system which leads to cytokine storm, a potentially fatal systemic inflammatory syndrome. Interleukin 6 (IL-6) is a pro-inflammatory cytokine that is produced in response to infections and tissue injuries and is believed to play a pivotal role in the event of a cytokine storm, as signified by its increase in the process. Considering the role of IL-6 as a pro-inflammatory cytokine in the process of cytokine storm in COVID-19, perceiving IL-6 as a therapeutic target could prove to be promising. Tocilizumab is a monoclonal antibody that competitively inhibits the binding of IL-6 to its receptor (IL-6R). The use of IL-6R blocker is recommended for severe COVID-19 patients in the latest therapeutic guideline published by the World Health Organization (WHO), but the timing of the administration has not been specified. While previous studies about the use of tocilizumab in COVID-19 patients have shown various results, these studies do not emphasize on plasma IL-6 levels when deciding the time of tocilizumab administration. In this case series, we present three patients with moderate to severe COVID-19 infections that receive tocilizumab as an adjunct to the standard of care therapy. This case series introduces the novel idea that the timely use of tocilizumab as signified by plasma IL-6 levels in moderate to severe COVID-19 patients could potentially improve overall clinical condition and increase survival rate.

Cumulative exposure characteristics of vegetable farmers exposed to Chlorpyrifos in Central Java - Indonesia; a cross-sectional study.

BACKGROUND: Agriculture is a major economic sector in Indonesia. Chemical pesticides are widely being used in agriculture for controlling pest. There is a growing concern that pesticide exposure, particularly chlorpyrifos (CPF) exposure, combined with other occupational characteristics that determine the level of exposure, can lead to further health impacts for farmers. Our objective was to evaluate the cumulative exposure characteristics among farmers exposed to CPF by using a validated algorithm. METHODS: We conducted a cross-sectional study of 152 vegetable farmers aged 18-65 who actively used CPF for at least 1 year in Central Java, Indonesia. Subject characteristics were obtained using a structured interviewer-administered questionnaire, addressed for sociodemographic and work-related characteristics. The cumulative exposure level (CEL) was estimated as a function of the intensity level of pesticide exposure (IL), lifetime years of pesticide use and the number of days spraying per year. CEL was subsequently classified into two groups, high and low exposure groups. The difference in characteristics of the study population was measured using Chi-square, independent-t or Mann-Whitney test. Association between CEL and its characteristics variables were performed by multiple linear regression. RESULTS: Seventy-one subjects (46.7%) were classified as the high exposure group. The use of multiple pesticide mixtures was common among our study population, with 94% of them using 2 or more pesticides. 73% reported direct contact with concentrated pesticides product, and over 80% reported being splashed or spilt during preparation or spraying activity. However, we found that the proportion of proper personal protective equipment (PPE) use in our subjects was low. Higher volume of mixture applied (p <  0.001) and broader acres of land (p = 0.001) were associated with higher cumulative exposure level, while using long-sleeved clothes and long pants (p <  0.05) during pesticide spraying were associated with lower cumulative exposure after adjusted for age and gender. CONCLUSIONS: These findings indicate an inadequate knowledge of using pesticides properly. Thus, we recommend comprehensive training on pesticide usage and encourage proper PPE to reduce the exposure level.

Serum TSH level as predictor of Graves' disease recurrence following antithyroid drug withdrawal: A systematic review.

Graves' disease (GD) has a high recurrence rate despite various and adequate treatment. Numerous studies have been performed to identify the predictor of disease recurrence. This report aims to investigate the role of thyroid stimulating hormone (TSH) level as a thyrotropin in predicting the recurrence of Graves' disease within 1 to 2 years following antithyroid drug (ATD) withdrawal. Literature searching was conducted on PubMed, Scopus, Cochrane, Proquest, EBSCO in August 2019 and Google Scholar in October 2020. The study criteria include the study that evaluates TSH level 4 weeks following ATD withdrawal, with subjects ≥18 years old who are retrospectively or prospectively followed up after 1 to 2 years following ATD withdrawal. Four eligible studies were selected based on inclusion/exclusion criteria, all of which measured TSH level at 4 weeks following ATD withdrawal. All studies had 1 to 2 years follow up. One study was an RCT, two studies were done in prospective cohort and another in retrospective cohort. All studies had comparable validity and applicability. Three out of four studies suggested that low TSH level measured 4 weeks following treatment withdrawal was associated with higher risk of disease recurrence. In conclusion, low TSH level obtained 4 weeks after ATD withdrawal was associated with higher rate of recurrence rate in GD.

The Differential Effects of Propylthiouracil and Methimazole as Graves' Disease Treatment on Vascular Atherosclerosis Markers: A Randomized Clinical Trial.

Background: Hyperthyroidism is related to vascular atherosclerosis. Propylthiouracil (PTU) and methimazole, other than their antithyroid effects, may have different mechanisms in preventing atherogenesis in Graves' disease. Objective: This study aimed to investigate the effect of antithyroid drugs on markers of vascular atherosclerosis in Graves' hyperthyroidism. Methods: This study was a single-blind, randomized clinical trial conducted on 36 patients with Graves' disease in Cipto Mangunkusumo General Hospital, Jakarta, Indonesia, from June 2019 until July 2020. Graves' disease was diagnosed from clinical manifestation of hyperthyroidism with diffuse goiter and then confirmed by thyroid stimulation hormone (TSH), free T4 (fT4), and TSH-receptor antibody (TRAb) measurements. Participants were randomly assigned to either a PTU or a methimazole treatment group and followed up for 3 months. Markers of vascular atherosclerosis were represented by adhesion molecules [intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin], carotid artery stiffness [pulse wave velocity (PWV)], and thickness [carotid intima media thickness (cIMT)]. Results: By the end of the study, 24 participants reached euthyroid condition (13 from the PTU group and 11 from the methimazole group). After 3 months of follow-up, in the PTU group, we noticed an improvement of ICAM-1 [pretreatment: 204.1 (61.3) vs. posttreatment: 141.6 (58.4) ng/ml; p = 0.001], VCAM-1 [837 (707-977) vs. 510 (402-630) ng/ml; p < 0.001] and E-selectin [32.1 (24.1-42.7) vs. 28.2 (21.6-36.8) ng/ml; p = 0.045] in the PTU group. In the methimazole group, only VCAM-1 improvement [725 (565-904) vs. 472 (367-590); p = 0.001] was observed. Meanwhile, we found no significant changes in PWV or cIMT in either group. Conclusion: Antithyroid treatment in Graves' disease leads to improvement in adhesion molecules, with a lesser effect on methimazole, whereas there were no significant changes in PWV or cIMT. PTU may have a better mechanism compared with methimazole in terms of improving adhesion molecules.

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.

Diagnostic Approach for Thyroid Nodules.

Thyroid nodule is a health problem which commonly found in daily practice, therefore clinical guidance is needed. This guideline was compiled by a multidisciplinary team and expected to be a guideline in diagnosing thyroid nodules on daily clinical practice.

Practical Guidelines Management of Graves Ophthalmopathy.

Graves' ophthalmopathy is the most common extra-thyroid manifestation in patients with Graves' disease, based on inflammatory and autoimmune conditions in orbital tissue. This practical guideline was formed by a multidiciplinary team, and is intended to provide guidance for diagnosis and management of Graves' ophthalmopathy in daily clinical practice to improve quality of care and treatment outcome.