QT interval and repolarization dispersion changes during the administration of hydroxychloroquine/chloroquine with/without azithromycin in early COVID 19 pandemic: A prospective observational study from two academic hospitals in Indonesia.

BACKGROUND: Hydroxychloroquine/chloroquine (HCQ/CQ) treatment for COVID-19 was associated with QT interval prolongation and arrhythmia risks. This study aimed to investigate QTc interval and ventricular repolarization dispersion changes, as markers of arrhythmia risks, after HCQ/CQ administration with/without azithromycin (AZT) during COVID-19 pandemic. METHODS: A prospective observational study was performed in two academic hospitals in Indonesia. Adult patients who received HCQ/CQ alone and HCQ/CQ + AZT concomitant treatments for COVID-19 infection were enrolled. Baseline and post HCQ/CQ treatment electrocardiograms were obtained. Baseline and post HCQ/CQ treatment QT interval by Bazett (B-QTc) and Fridericia (F-QTc) formulas and ventricular repolarization dispersion indices by Tpeak-Tend (Tp-e) interval and Tpeak-Tend/QT (Tp-e/QT) ratio were calculated and analyzed. RESULTS: The study enrolled 55 (HCQ/CQ alone) and 77 subjects (HCQ/CQ + AZT concomitant). F-QTc interval significantly lengthened in subjects with HCQ/CQ + AZT (mean difference 11.89 ms [P = .028]). The incidences of severe B-QTc and F-QTc lengthening were 13.1% and 12.3%, B-QTc and F-QTc prolongation were 25.4% and 12.3%, and severe B-QTc and F-QTc prolongation were 6.2% and 3.2%. Tp-e interval lengthened significantly from baseline to posttreatment in HCQ/CQ alone and HCQ/CQ + AZT (mean difference 10.83 ms [P = .006] and 18.73 ms [P < .001], respectively). Tp-e/QT ratio increased significantly from baseline to posttreatment in HCQ/CQ + AZT concomitant (mean difference 0.035 [P < .001]). No fatal arrhytmia occurred. CONCLUSIONS: During COVID-19 pandemic, HCQ/CQ + AZT concomitant treatment caused significant F-QTc lengthening, significantly increased Tp-e interval and increased Tp-e/QT ratio. HCQ/CQ alone only caused significant increase of Tp-e interval. Incidences of severe QTc lengthening and prolongation were low in both HCQ/CQ alone and HCQ/CQ + AZT concomitant.

Molecular epidemiology of SARS-CoV-2 isolated from COVID-19 family clusters.

BACKGROUND: Transmission within families and multiple spike protein mutations have been associated with the rapid transmission of SARS-CoV-2. We aimed to: (1) describe full genome characterization of SARS-CoV-2 and correlate the sequences with epidemiological data within family clusters, and (2) conduct phylogenetic analysis of all samples from Yogyakarta and Central Java, Indonesia and other countries. METHODS: The study involved 17 patients with COVID-19, including two family clusters. We determined the full-genome sequences of SARS-CoV-2 using the Illumina MiSeq next-generation sequencer. Phylogenetic analysis was performed using a dataset of 142 full-genomes of SARS-CoV-2 from different regions. RESULTS: Ninety-four SNPs were detected throughout the open reading frame (ORF) of SARS-CoV-2 samples with 58% (54/94) of the nucleic acid changes resulting in amino acid mutations. About 94% (16/17) of the virus samples showed D614G on spike protein and 56% of these (9/16) showed other various amino acid mutations on this protein, including L5F, V83L, V213A, W258R, Q677H, and N811I. The virus samples from family cluster-1 (n = 3) belong to the same clade GH, in which two were collected from deceased patients, and the other from the survived patient. All samples from this family cluster revealed a combination of spike protein mutations of D614G and V213A. Virus samples from family cluster-2 (n = 3) also belonged to the clade GH and showed other spike protein mutations of L5F alongside the D614G mutation. CONCLUSIONS: Our study is the first comprehensive report associating the full-genome sequences of SARS-CoV-2 with the epidemiological data within family clusters. Phylogenetic analysis revealed that the three viruses from family cluster-1 formed a monophyletic group, whereas viruses from family cluster-2 formed a polyphyletic group indicating there is the possibility of different sources of infection. This study highlights how the same spike protein mutations among members of the same family might show different disease outcomes.

The Prevalence of the EML4-ALK Fusion Gene in Cytology Specimens from Patients with Lung Adenocarcinoma.

BACKGROUND: Under the National Comprehensive Cancer Network (NCCN) guidelines for non-small-cell lung carcinoma (NSCLC), anaplastic lymphoma kinase (ALK) gene rearrangement is required to be assessed. However, data showing the prevalence of the ALK rearrangement is still deficient and is not yet available in Indonesia. This study used direct smear preparation from transthoracic needle specimens that are minimally invasive. The main objective of the study is to identify the prevalence of the ALK fusion rearrangement gene in cytological specimens. MATERIALS AND METHODS: A total of 35 direct smear preparations diagnosed as lung adenocarcinoma and EGFR mutation negative were involved in this study. The samples were taken between 2017 and 2019. These samples were examined for EML4-ALK fusion rearrangement gene using qRT-PCR. The EML4-ALK rearrangement status was determined by qRT-PCR with high-resolution melting (HRM) analysis. RESULTS: A total of 28 (80%) samples were from males, and 7 samples were from females. Seven (20% 95% CI: 8.4%-36.9%) samples were EML4-ALK rearrangement positive. The average age of the patients was 63.5 years old. The most common sites of metastasis in this study were pleural cavity, bone, liver, and CNS. CONCLUSIONS: qRT-PCR successfully identified EML4-ALK fusion rearrangement in direct smear preparations of lung adenocarcinoma. Direct smear samples can be used for EML4-ALK rearrangement detection using qRT-PCR. The EML4-ALK rearrangement gene has high prevalence in selected lung adenocarcinoma and EGFR mutation-negative populations. ALK inhibitors in lung cancer can be openly considered for use in Indonesian patients to improve the outcome of this subset of patients.

Traumatic Inhalation due to Merapi Volcanic Ash.

Pneumonoultramicroscopicsilicovolcanoconiosis is fibrotic lung diseases of the pulmonary parenchyma following chronic inhalation of inorganic dusts containing crystalline silicon dioxide. The acute manifestations observed after heavy ashfalls include attacks of asthma and bronchitis, with an increased reporting of cough, breathlessness, chest tightness, and wheezing due to irritation of the lining of the airways. The chronic health condition of most concern is silicosis, a diffuse nodular fibrosis of the lungs, develops slowly, usually appearing 10 to 30 years after first exposure. A 35 years old male was admitted to Sardjito Hospital, Yogyakarta with complaints of progressive dyspnoea, right side chest pain since last 3 month and periodic episodes of dry cough. He had history of exposure to volcanic ash at the location around volcano eruption for about 10 month. Examination revealed hyperresonant note, diminished vesicular breath sounds in lower right side of the chest. The chest X-ray presence leads to bleb. Based on the clinical and radiological suspicion of pneumoconiosis the patient was submitted to computed tomography of the chest and revealed bilateral multiple bullae mainly at the right lung field. The biopsy specimen verified the diagnosis of anthrocosilicosis. There is no proven specific therapy for any form of silicosis. Symptomatic therapy should include treatment of airflow limitation with bronchodilators, aggressive management of respiratory tract infection with antibiotics, and use of supplemental oxygen (if indicated) to prevent complications of chronic hypoxemia.

Pulmonary involvement predicts mortality in severe leptospirosis patients.

AIM: To evaluate the influence of pulmonary involvement at admission in predicting mortality among patients with severe leptospirosis. METHODS: Reprospective cohort study from medical record registry in Dr. Sardjito Hospital, Yogyakarta from 2003 to 2007. Pulmonary involvement was defined by the presence of pulmonary infiltrate, consolidation or pleural effusion in thorax radiography. Pulmonary edema was excluded. Admission data were collected. Follow-up records were noted until patients were discharged or died. The correlation between predictors (some patient characteristics on admission) and outcome (mortality) were evaluated using univariate analysis, and then proceeded to multivariable logistic regression analysis. P < 0.05 is considered statistically significant. RESULTS: Sixty patients with severe leptospirosis as a main diagnosis were evaluated. Fifty-five subjects were eligible for analysis, male patients 37 (67.3%) and mean age 42 +/- 15 years old. Pulmonary involvement was presence in 7 patients (12.7%). In univariate analysis only the presence of meningismus and pulmonary involvement were associated with mortality (p=0.001 and 0.006 respectively). In multivariable logistic regression, pulmonary involvement was independently a strong predictor of mortality (OR 9.9 95% CI (1.17 - 84.03), p=0.035). CONCLUSION: Pulmonary involvement at admission is a strong predictor of mortality among patients with severe leptospirosis.

Total lymphocyte count and hemoglobin combined to predict CD4 lymphocyte counts of less than 200 cells/mm(3) in HIV/AIDS.

AIM: to obtain the sensitivity and specificity of combining total lymphocyte count and hemoglobin to predict the CD4 lymphocyte count below 200 cells/m3. METHODS: this is a cross sectional study. Subject characteristics were patient with HIV/AIDS who have not been initiated ARV therapy, the age above 15 years, have a CD4 lymphocyte count data. A total of 72 patients were recruited from clinic of Edelweis or hospitalized patients at Dr. Sardjito Hospital Yogyakarta in March 2002 - March 2007. Independent t test and Mann-Whitney test was used to find out the differences of continue variable. P < or = 0.05 was considered significant. RESULTS: a total of 72 patients were studied. Of these,50 patients (69.4%) were male, 22 patients (30.6%) were female. 53 patients with CD4 below 200 cells/mm3 and 19 patients with CD4 above 200 cells/mm3. Mean of TLCin HIV/AIDS patients with CD4 below 200 cells/mm3 were: 1013.24+/- 96.06 and CD4 above 200 cells/mm3 were 2161.36 +/- 214.66. Mean of Hb in HIV/AIDS patients with CD4 below 200 cells/mm3 were: 11.61+/- 0.30 and CD4 above 200 cells/mm3 were 12.47 +/- 0.59.Sensitivity of combined TLC+Hb man (algorithms a,b) were 80.95%, 88.09% Vs TLC 66.66%; Sensitivity of combined TLC+Hb woman (algorithms a, b) were 54.54%,54.54% Vs TLC 54.54%; Specificity of combined TLC+Hbman (algorithms a, b) were 87.50%, 87.50% Vs TLC 87.50%; Specificity of combined TLC+Hb woman (algorithms a, b)were 63.63%, 54.54% Vs TLC 90.90%. CONCLUSION: adding hemoglobin to TLC (algorithms aand b in man) increased sensitivity, there by reducing the risk of false-negative results.