Antiretroviral Genotypic Resistance Mutations in HIV-1 Infected Korean Patients with Virologic Failure

Resistance assays are useful in guiding decisions for patients experiencing virologic failure (VF) during highly-active antiretroviral therapy (HAART). We investigated antiretroviral resistance mutations in 41 Korean human immunodeficiency virus type 1 (HIV-1) infected patients with VF and observed immunologic/virologic response 6 months after HAART regimen change. Mean HAART duration prior to resistance assay was 45.3±27.5 months and commonly prescribed HAART regimens were zidovudine/lamivudine/nelfinavir (22.0%) and zidovudine/lamivudine/efavirenz (19.5%). Forty patients (97.6%) revealed intermediate to high-level resistance to equal or more than 2 antiretroviral drugs among prescribed HAART regimen. M184V/I mutation was observed in 36 patients (87.7%) followed by T215Y/F (41.5%) and M46I/L (34%). Six months after resistance assay and HAART regimen change, median CD4+ T cell count increased from 168 cells/µL (interquartile range [IQR], 62-253) to 276 cells/µL (IQR, 153-381) and log viral load decreased from 4.65 copies/mL (IQR, 4.18-5.00) to 1.91 copies/mL (IQR, 1.10-3.60) (P<0.001 for both values). The number of patients who accomplished viral load <400 copies/mL was 26 (63.4%) at 6 months follow-up. In conclusion, many Korean HIV-1 infected patients with VF are harboring strains with multiple resistance mutations and immunologic/virologic parameters are improved significantly after genotypic resistance assay and HAART regimen change

Isolated Left Ventricular Noncompaction Cardiomyopathy Accompanied by Severe Mitral Regurgitation

Isolated left ventricular noncompaction cardiomyopathy (IVNC) is a cardiomyopathy thought to be caused by arrest of normal embryogenesis of the endocardium and myocardium. This abnormality is often associated with other congenital cardiac defects. A 21-year-old man presented to the emergency department with worsening exertional dyspnea during the previous 2 months. Two-dimensional and Doppler echocardiography revealed an enlarged left atrium (LA) and a markedly dilated left ventricle (LV) with preserved LV systolic function, severe mitral valve regurgitation, and prolapse due to chordae rupture. The myocardium of the LV and right ventricle (RV) had excessively prominent trabeculations and deep intertrabecular recesses. He is the first patient in Korea who has undergone mitral valve replacement surgery because of severe mitral valve regurgitation and prolapse due to chordae rupture accompanied by IVNC

Temporary bilateral sensorineural hearing loss following cardiopulmonary bypass -A case report-

Sudden sensorineural hearing loss has been reported to occur following anesthesia and various non-otologic surgeries, mostly after procedures involving cardiopulmonary bypass. Unilateral sensorineural hearing loss resulting from microembolism is an infrequent complication of cardiopulmonary bypass surgery that has long been acknowledged. Moreover, there are few reports on the occurrence of bilateral sensorineural hearing loss without other neurologic deficits and its etiology has also not been determined. We describe here a rare case of bilateral hearing loss without other neurologic deficits in an otherwise healthy 27-year-old woman who underwent cardiopulmonary bypass surgery for repair of severe mitral valve stenosis. The patient suffered from profound sensorineural hearing loss in both ears that was recognized immediately upon extubation, and audiometry tests confirmed the diagnosis. Without any treatment, her hearing recovered almost completely by the time of her discharge one week after surgery

Complete Atrioventricular Block-Induced Torsade de Pointes, Manifested by Epilepsy

Complete atrioventricular (AV) block is frequently regarded as a cause of informed syncopal attacks, even though the escape rhythm is maintained. Torsade de pointes (TdP) may be a significant complication of AV block associated with QT prolongation. Here, we report the case of a 42-year-old female who was referred to our hospital due to recurrent seizure-like attacks while taking anti-convulsant drugs at a psychiatric hospital. TdP with a long QT interval (corrected QT = 0.591 seconds) was observed on an electrocardiogram (ECG) taken in the emergency department. The patient's drug history revealed olanzapine as the suspicious agent. Even after the medication was stopped, however, the QT interval remained within an abnormal range and multiple episodes of TdP and related seizure-like symptoms were found via ECG monitoring. A permanent pacemaker was thus implanted, and the ventricular rate was set at over 80 beats/min. There was no recurrence of tachyarrhythmia or other symptoms

The prophylactic use of recombinant factor VIIa in a patient with DeBakey type III aortic dissection -A case report-

Little is known about the prophylactic use of recombinant factor VIIa (rFVIIa) in patients undergoing surgery for a bleeding aorta employing cardiopulmonary bypass. We report the successful use of rFVIIa in a patient undergoing hypothermic circulatory arrest and prolonged cardiopulmonary bypass for repair of a DeBakey type III aortic dissection

Anesthetic considerations of percutaneous transcatheter aortic valve implantation: first attempt in Korea -A report of 2 cases-

Conventional aortic valve replacement for severe aortic stenosis is associated with a high operative mortality in the elderly patients with significant comorbidities, including severe respiratory dysfunction, renal insufficiency, and compromised cardiac function. Human transcatheter aortic valve implantation was first reported in 2002 and has become a valid alternative in selected high-risk patients in Europe and North America. This article describes the first attempt of transfemoral transcatheter aortic valve implantation in Korea. The procedure was applied in two consecutive patients with severe aortic stenosis. Despite several intra-operative complications during procedure, the post-operative outcomes were good for both patients. At post-operative 30 days there was satisfactory prosthetic valve function and hemodynamic stability

Developmental endothelial locus-1 as a potential biomarker for the incidence of acute exacerbation in patients with chronic obstructive pulmonary disease

Background Despite the high disease burden of chronic obstructive pulmonary disease (COPD) and risk of acute COPD exacerbation, few COPD biomarkers are available. As developmental endothelial locus-1 (DEL-1) has been proposed to possess beneficial effects, including anti-inflammatory effects, we hypothesized that DEL-1 could be a blood biomarker for COPD. Objective To elucidate the role of plasma DEL-1 as a biomarker of COPD in terms of pathogenesis and for predicting acute exacerbation. Methods Cigarette smoke extract (CSE) or saline was intratracheally administered to wild-type (WT) and DEL-1 knockout (KO) C57BL/6 mice. Subsequently, lung sections were obtained to quantify the degree of emphysema using the mean linear intercept (MLI). Additionally, plasma DEL-1 levels were compared between COPD and non-COPD participants recruited in ongoing prospective cohorts. Using negative binomial regression analysis, the association between the plasma DEL-1 level and subsequent acute exacerbation risk was evaluated in patients with COPD. Results In the in vivo study, DEL-1 KO induced emphysema (KO saline vs. WT saline; P = 0.003) and augmented CSE-induced emphysema (KO CSE vs. WT CSE; P < 0.001) in 29 mice. Among 537 participants, patients with COPD presented plasma log (DEL-1) levels lower than non-COPD participants (P = 0.04), especially non-COPD never smokers (P = 0.019). During 1.2 ± 0.3 years, patients with COPD in the lowest quartile of Log(DEL-1) demonstrated an increased risk of subsequent acute exacerbation, compared with those in the highest quartile of Log(DEL-1) (adjusted incidence rate ratio, 3.64; 95% confidence interval, 1.03–12.9). Conclusion Low DEL-1 levels are associated with COPD development and increased risk of subsequent COPD acute exacerbation. DEL-1 can be a useful biomarker in patients with COPD.This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (No. 2019R1C1C1007918). This research was also supported by funds (2016ER670100, 2016ER670101, 2016ER670102 and 2018ER670100, 2018ER670101, 2018ER670102) from Research of Korea Centers for Disease Control and Prevention

The 5p15.33 Locus Is Associated with Risk of Lung Adenocarcinoma in Never-Smoking Females in Asia

Genome-wide association studies of lung cancer reported in populations of European background have identified three regions on chromosomes 5p15.33, 6p21.33, and 15q25 that have achieved genome-wide significance with p-values of 10−7 or lower. These studies have been performed primarily in cigarette smokers, raising the possibility that the observed associations could be related to tobacco use, lung carcinogenesis, or both. Since most women in Asia do not smoke, we conducted a genome-wide association study of lung adenocarcinoma in never-smoking females (584 cases, 585 controls) among Han Chinese in Taiwan and found that the most significant association was for rs2736100 on chromosome 5p15.33 (p = 1.30×10−11). This finding was independently replicated in seven studies from East Asia totaling 1,164 lung adenocarcinomas and 1,736 controls (p = 5.38×10−11). A pooled analysis achieved genome-wide significance for rs2736100. This SNP marker localizes to the CLPTM1L-TERT locus on chromosome 5p15.33 (p = 2.60×10−20, allelic risk = 1.54, 95% Confidence Interval (CI) 1.41–1.68). Risks for heterozygote and homozygote carriers of the minor allele were 1.62 (95% CI; 1.40–1.87), and 2.35 (95% CI: 1.95–2.83), respectively. In summary, our results show that genetic variation in the CLPTM1L-TERT locus of chromosome 5p15.33 is directly associated with the risk of lung cancer, most notably adenocarcinoma

Multiplatform Analysis of 12 Cancer Types Reveals Molecular Classification within and across Tissues of Origin

Recent genomic analyses of pathologically-defined tumor types identify “within-a-tissue” disease subtypes. However, the extent to which genomic signatures are shared across tissues is still unclear. We performed an integrative analysis using five genome-wide platforms and one proteomic platform on 3,527 specimens from 12 cancer types, revealing a unified classification into 11 major subtypes. Five subtypes were nearly identical to their tissue-of-origin counterparts, but several distinct cancer types were found to converge into common subtypes. Lung squamous, head & neck, and a subset of bladder cancers coalesced into one subtype typified by TP53 alterations, TP63 amplifications, and high expression of immune and proliferation pathway genes. Of note, bladder cancers split into three pan-cancer subtypes. The multi-platform classification, while correlated with tissue-of-origin, provides independent information for predicting clinical outcomes. All datasets are available for data-mining from a unified resource to support further biological discoveries and insights into novel therapeutic strategies

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts