JAK2 as Predictor of Therapeutic Response in Patients with Chronic Myeloid Leukemia Treated with Imatinib.

Background: Chronic myeloid leukemia (CML) or chronic granulocytic leukemia is a myeloproliferative neoplasm indicated by the presence of the Philadelphia (Ph+) chromosome. First-line tyrosine kinase inhibitor, imatinib, is the gold standard for treatment. However, there has been known unresponsiveness to treatment, especially due to the involvement of other genes, such as the Janus kinase 2 (JAK2) gene. This study aimed to evaluate the relationships between JAK2 levels and complete hematological response (CHR), as well as early molecular response (EMR) after 3 months of imatinib treatment in patients with chronic phase CML. Methods: Patients with Ph+ CML in the chronic phase (n = 40; mean age, 40 ± 11 years) were recruited to complete assessments consisting of clinical examination and blood test, including evaluation of complete blood counts and the JAK2 levels, at baseline and following 3 months of therapy with imatinib (at an oral dose of 400 mg per day). Subjects were divided into two groups according to the presence of CHR and EMR. Results: JAK2 gene levels, phosphorylated, and total JAK2 proteins at baseline were significantly lower in the group with the presence of CHR and EMR. In addition, baseline JAK2 levels, including JAK2 gene expression, phosphorylated, and total JAK2 proteins, were negatively correlated with the presence of CHR and EMR. Conclusions: Based on these findings, JAK2 levels may be a potential indicator for evaluating treatment response on imatinib due to its role in the pathophysiology of CML.

Pharmacological Treatment Options for Coronavirus Disease-19 in Renal Patients.

Patients with chronic kidney disease (CKD), including dialysis and transplant patients, are at greater risk of contracting SARS-CoV-2 due to kidney dysfunction and preexisting comorbidities. To date, a specific guideline on managing these high-risk patients infected with COVID-19 has not been established. As the current management of COVID-19 comprises mainly experimental drugs, the authors aim to provide information on dosing adjustments at different stages of kidney dysfunction and notable renal side effects. We performed a nonsystematical review of currently available COVID-19 drugs exploring several different clinical trial databases and search browsers. Several antivirals and monoclonal antibodies used in COVID-19 treatment require dosage adjustments in kidney dysfunction. In a global pandemic setting, nephrologists need to consider the appropriate dosage according to the renal function and closely monitor the side effects of different drug combinations to obtain the optimum therapeutic effect while avoiding further renal damage. Further studies are required to determine the safety and efficacy of these drugs in renal patients.

The use of Janus Kinase inhibitors in hospitalized patients with COVID-19: Systematic review and meta-analysis.

BACKGROUND: The evidence of using JAK inhibitors among hospitalized patients with COVID-19 is conflicting. The systematic review and meta-analysis aimed to address the efficacy of Janus Kinase (JAK) Inhibitors in reducing risk of mortality among hospitalized patients with COVID-19. METHODS: Several electronic databases, including PubMed, EuropePMC, and the Cochrane Central Register of Controlled Trials, with relevant keywords "COVID-19″ AND ("JAK inhibitor" OR "Ruxolitinib" OR "Tofacitinib" OR "Fedratinib" OR "Baricitinib") AND ("Severe" OR "Mortality"), were used to perform a systematic literature search up to December 11, 2020. All studies pertinent to the predetermined eligibility criteria were included in the analysis. Our outcome of interest was all types of mortality, clinical improvement, and clinical deterioration. Dichotomous variables of our outcomes of interest were analyzed using Maentel-Haenszel formula to obtain odds ratios (ORs) and 95% confidence intervals (CI) with random-effects modeling regardless of heterogeneity. RESULTS: Five studies with a total of 1190 patients and were included in this systematic review and meta-analysis. The use of JAK inhibitors was associated with a reduced risk of mortality (OR 0.51, 95% CI 0.28-0.93, P = 0.02; I2: 7.8%, P = 0.354) and clinical improvement (OR 1.76, 95% CI 1.05-2.95, P = 0.032; I2: 26.4%, P = 0.253). The use of JAK inhibitors was not associated with a reduced risk of clinical deterioration (OR 0.58, 95% CI 0.28-1.19, P = 0.136; I2: 24.1%, P = 0.267). CONCLUSION: The use of JAK inhibitors was significantly associated with a reduced risk of mortality, and clinical improvement in hospitalized patients with COVID-19.

Asthma does not increase COVID-19 mortality and poor outcomes: A systematic review and meta-analysis.

BACKGROUND: The Center for Disease Control and Prevention (CDC) has mentioned Coronavirus Disease 2019 (COVID-19) patients with moderate or severe asthma as a high risk group for severe illness. While WHO mentioned only chronic respiratory diseases, not specifically asthma as a risk factor for severe illness. There has been asthma prevalence discrepancy in studies of COVID-19 across the world. OBJECTIVE: This meta-analysis aims to investigate the association between asthma and composite poor outcome in patients with coronavirus disease (COVID-19). METHODS: We conducted a systematic literature search from PubMed and Embase database. We included all original research articles with adult COVID-19 patients > 18 years old and had information related to asthma as a risk factor. Studies with outcomes consisting of mortality, severe COVID-19, use of mechanical ventilation, ICU admission, and hospital admission were included in this study. The outcomes of interest were divided into severe COVID-19, mortality and other poor outcomes. RESULTS: Eleven studies were included in meta-analysis with a total of 6,046 patients. Asthma was not associated with composite poor outcomes with OR = 0.92 (95%CI 0.71-1.19, p = 0.61, and I2 = 8.49%). Furthermore, subgroup analysis showed that asthma was not associated with severe COVID (p = 0.76), mortality (p = 0.45), and other poor outcomes (p = 0.28). CONCLUSIONS: Our study showed that asthma was not associated with severe COVID-19, mortality, and other poor outcomes in patients with COVID-19.

May Measurement Month 2018: an analysis of blood pressure screening results from Indonesia.

Elevated blood pressure (BP) is a significant burden worldwide, leading to high cardio-cerebro-reno-vascular morbidity and mortality. For the second year of the May Measurement Month (MMM) campaign in Indonesia in 2018, we recruited 174 sites in 31 out of 34 provinces in Indonesia and screened through convenience sampling in public areas and rural primary health centres. Hypertension was defined as systolic BP ≥140 mmHg or diastolic BP ≥90 mmHg, or both, or on the basis of receiving antihypertensive medication. Blood pressure was measured three times followed the standard global MMM protocol, multiple imputation was used to estimate the mean of the 2nd and 3rd BP readings if these were not recorded. A total of 91 222 individuals were screened, and after multiple imputations, 27 331 (30.0%) had hypertension. Of individuals not receiving antihypertensive medication, 14 367 (18.4%) were hypertensive. Among the 47.4% of hypertensive individuals on antihypertensive medication, 10 106 (78.0%) had uncontrolled BP. MMM17 and MMM18 were still the most extensive standardized screening campaigns for BP measurement in Indonesia. Compared to the previous study, the proportion with uncontrolled BP on medication was significantly higher and provided the substantial challenges in managing hypertension in the rural community.

A Simple Tenckhoff Catheter Placement Technique for Continuous Ambulatory Peritoneal Dialysis (CAPD) Using the Bandung Method.

Insertion of Tenckhoff catheters for continuous ambulatory peritoneal dialysis by nephrologists remains uncommon in most developing countries, including Indonesia. The aim of this study is to describe our experience on a simple technique of Tenckhoff catheter insertion by a nephrologist called the Bandung method. We conducted a retrospective observational study from May 2012 until December 2018 in 230 patients with end-stage renal disease using the Bandung method, a blind percutaneous insertion approach modified from the Seldinger technique. Early complications after insertion were assessed. The mean age of patients was 47.28 years (range 14-84 years). Within 1 month after insertion, complications occurred in 34 patients: 13 (5.7%) malposition, 8 (3.5%) omental trapping, 6 (2.6%) outlow failure, 3 (1.3%) peritonitis, 1 (0.4%) catheter infections, 1 (0.4%) bleeding, 1 (0.4%) kinking, and 1 (0.4%) hernia. None of these complications led to catheter removal. One patient experienced a late (>1 month) post-insertion complication of malposition that could not be repositioned and led to catheter removal. The Bandung method is a simple, cost effective, and minimally invasive technique for Tenckhoff catheter insertion that is associated with the same rate of complications compared to other techniques. This technique may useful for application in developing countries.

May Measurement Month 2017: an analysis of the blood pressure screening campaign results in Indonesia-South-East Asia and Australasia.

Elevated blood pressure (BP) is a growing burden worldwide, leading to over 10 million deaths each year. Our previous primary health surveys in 2013 and 2018 show that 25.8% to 34.1% of adults have raised BP, which is associated with cardiovascular, cerebrovascular, and renovascular morbidity and mortality. May Measurement Month (MMM) is a global initiative aimed at raising awareness of high BP and to act as a temporary solution to the lack of screening programmes worldwide. An opportunistic cross-sectional survey of volunteers aged ≥18 was carried out in May 2017. Blood pressure measurement, the definition of hypertension and statistical analysis followed the standard MMM protocol. We recruited 292 sites in all 34 provinces in Indonesia, and screened in public areas and offices as well as health centres. A total of 69 307 individuals were screened. After multiple imputation, 23 892 (34.5%) had hypertension. Of individuals not receiving antihypertensive medication, 20.0% were hypertensive. Among individuals receiving antihypertensive medication, 7885 (62.8%) had uncontrolled BP. MMM17 was the largest standardized screening campaign for BP measurement in our country. The proportion of individuals identified with hypertension and the percentage of those with uncontrolled BP on medication provide evidence of the substantial challenges in managing hypertension in the community. These results suggest that opportunistic screening can identify significant numbers of individuals with raised BP.

Effect of angiotensin II receptor blocker on TGF-ß1, MMP-1, and collagen type I and type III concentration in New Zealand rabbit urethral stricture model.

INTRODUCTION: Urethral stricture is a disease with a high recurrence rate. Angiotensin II via AT1 receptor increases collagen formation through its effects on TGF-ß1 and inhibition of collagenase activity. In this study, we evaluated the antifibrotic effect of angiotensin II receptor blocker on urethral stricture formation by creating a urethral stricture model in a male rabbit. MATERIAL AND METHODS: Thirty three male adult rabbits were separated into 3 groups (control, treatment, and sham). Group I consisted of 15 rabbits with urethral stricture that did not undergo any treatment, group II consisted of 15 rabbits with urethral stricture that were treated with a daily dose of 15 mg/kg losartan, given orally. Group III consisted of 3 rabbits with normal urethra and without any treatment. After 1, 2, and 4 weeks, the urethral tissues were collected, processed, and examined for TGF-ß1, MMP-1, collagen type I, and collagen type III using enzyme-linked immunosorbent assay. Data were analyzed using 2-way analysis of variance using SPSS version 20.0. RESULTS: Urethral TGF-ß1 concentration in the treatment group was significantly lower during the 2nd and 4th week of observation (p<0.0001), MMP-1 was significantly higher in the 1st, 2nd, and 4th week of observation (p<0.0001), collagen type I was significantly lower during the 2nd (p=0.001) and 4th week (p<0.0001), and collagen type III concentration was significantly lower in the 2nd and 4th week of observation (p<0.0001). CONCLUSION: Angiotensin II receptor blocker could limit the progression of urethral stricture. The mechanism may be related to the AT1 blockage that leads to a decrease in TGF-ß1 concentration, eventually resulting in lower collagen concentration due to increased MMP-1 activity.

Cardiometabolic risk factors and acute kidney injury based on urinary neutrophil gelatinase associated lipocalin (NGALu) in acute coronary syndrome patients.

AIM: to analyze the association between cardiometabolic risk factors and acute kidney injury (AKI) based on urinary neutrophil gelatinase associated lipocalin (NGALu) in patients with acute coronary syndrome (ACS). METHODS: a cross-sectional study was conducted on the ACS patients who were admitted to the Emergency Room in Hasan Sadikin Hospital. Urinary samples were obtained at the time of the arrival and considered AKI if the urinary NGAL level 150 ng/ml. The cardiometabolic risk factors were in accord with the IDF criteria for MetS. RESULTS: there were 60 subjects that consisted of 39 men (65%) and 21 women (35%) and the average of was 58.47 (SD 9.9) years. There were 30 subjects (50%) considered AKI based on NGAL level. There were two significant CMR risk factors associated with AKI; blood pressure (hypertension) and HDL (p 0.05). HDL being the most significant cardiometabolic factor (p=0.037; OR 5.137 (95% CI 1.102-23.95)). The number of factors was also associated with the incidence of AKI; the more factors existed in a person the greater the incidence of AKI (p=0.03). CONCLUSION: blood pressure and HDL were cardiometabolic risk factors associated with AKI in ACS patients. The more cardiometabolic factors existed in a person the greater the incidence of AKI.

Prevention, control and treatment of HIV-AIDS among injecting drug use in Bandung, Indonesia.

Indonesia is facing a growing HIV-epidemic that in many areas is driven by injecting drug use (IDU). IDUs underutilize health services, partly because of legal aspects which also cause that many are held in prison, where further HIV- transmission may take place. Most HIV-infected patients present with advanced HIV-AIDS and many deaths before starting antiretroviral treatment. The growing HIV-epidemic in Indonesia has socio-economical implications for individual patients as well as for the health system and for society. IMPACT, a multidisciplinary university-based program in Bandung, West-Java, integrates HIV-prevention and treatment, combining research and implementation. Biomedical, public health and sociobehavioral expertise is used for educational programs for adolescents; scaling-up HIV-testing, harm reduction strategies and care for HIV/AIDS in hospital, community and prison; and institutional as well as individual capacity building related to IDU and HIV/AIDS. It is expected that these activities can make a significant contribution to control of HIV-AIDS in the context of injecting drug use in West-Java and Indonesia as a whole.