Performance Assessment of Xpert MTB/RIF Assay for Detecting Pulmonary Tuberculosis and Rifampin Resistance in a Tertiary Care Hospital in Korea.

In this study, we aimed to assess the performance of the Xpert MTB/RIF assay for the detection of pulmonary tuberculosis compared to the acid-fast bacilli (AFB) smear and culture analysis, and the incidence of rifampin resistance using the drug susceptibility test. The specimens referred for AFB smear and culture analysis and Xpert MTB/RIF assay from April 2015 to March 2018 were retrospectively reviewed. The sensitivity, specificity, and mean cycle threshold (Ct) values obtained in Xpert MTB/RIF assay and for rifampin resistance were analyzed. The results of Xpert MTB/RIF assay for pulmonary tuberculosis were evaluated based on the AFB smear grade. Among 3,840 specimens, 491 were positive in Xpert MTB/RIF assay and 626 in culture analysis. The sensitivity and specificity of Xpert MTB/RIF assay were 75.6% and 99.4%, respectively. The sensitivity of Xpert MTB/RIF assay for smear-positive/culture-positive specimens was 98.6% and that of smear-negative and -trace/culture-positive specimens was 63.1%. The positivity of Xpert MTB/RIF assay for culture-positive specimens was 89.9%, 98.6%, 95.7%, 100.0%, and 100.0% for the smear grades trace, 1+, 2+, 3+, 4+, respectively. The Ct values of 491 specimens significantly decreased as the AFB smear grade increased (P < 0.0001). The Ct values of smear-positive, -trace, and -negative specimens were 21.7 ± 4.2, 26.5 ± 3.9, and 27.4 ± 3.6, respectively. Rifampin resistance evaluated using Xpert MTB/RIF assay and culture analysis exhibited a correlation of 98.3%. The region covered by probe E was the most frequently mutated region (50.0%). Xpert MTB/RIF assay demonstrated reliable performance in detecting pulmonary tuberculosis from smear-positive and culture-positive specimens; however, further improvements are still required to detect smear-negative and culture-positive specimens.

Nationwide External Quality Assessment of SARS-CoV-2 Molecular Testing, South Korea.

External quality assessment (EQA) is essential for ensuring reliable test results, especially when laboratories are using assays authorized for emergency use for newly emerging pathogens. We developed an EQA panel to assess the quality of real-time reverse transcription PCR assays being used in South Korea to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). With the participation of 23 public health organization laboratories and 95 nongovernmental laboratories involved in SARS-CoV-2 testing, we conducted qualitative and semiquantitative performance assessments by using pooled respiratory samples containing different viral loads of SARS-CoV-2 or human coronavirus OC43. A total of 110 (93.2%) laboratories reported correct results for all qualitative tests; 29 (24.6%) laboratories had >1 outliers according to cycle threshold values. Our EQA panel identified the potential weaknesses of currently available commercial reagent kits. The methodology we used can provide practical experience for those planning to conduct evaluations for testing of SARS-CoV-2 and other emerging pathogens in the future.

Fibrosis-4, aspartate transaminase-to-platelet ratio index, and gamma-glutamyl transpeptidase-to-platelet ratio for risk assessment of hepatocellular carcinoma in chronic hepatitis B patients: comparison with liver biopsy.

BACKGROUND AND AIMS: It is well known that hepatocellular carcinoma (HCC) develops as a consequence of hepatic fibrosis progression. Thus, early identification of advanced liver fibrosis is very important. This study evaluated the prognostic value of FIB-4, the aspartate transaminase to-platelet ratio index (APRI), and the gamma-glutamyl transpeptidase-toplatelet ratio (GPR) for predicting HCC development using histological fibrosis stage as a reference in Asian chronic hepatitis B (CHB) patients. METHODS: A total of 444 CHB patients who underwent liver biopsy and serological tests for determining noninvasive serum fibrosis markers were enrolled. All patients were followed to monitor HCC development. RESULTS: The histological fibrosis stage showed best performance in predicting HCC development at 5 (area under the receiver operating characteristic curve [AUROC] = 0.783) and 7 years (AUROC = 0.766), followed by FIB-4 (AUROC = 0.753 at 5 years, 0.698 at 7 years), APRI (AUROC = 0.658 at 5 years, 0.572 at 7 years), and GPR (AUROC = 0.638 at 5 years, 0.603 at 7 years). When we classified risk groups according to the histological fibrosis stage (F4 vs. F0-3) and FIB-4 (FIB-4 ≥ 3.25 vs. FIB-4 < 3.25), patients in the high-risk group were found to have a significantly higher probability of developing HCC than those in the low-risk group (P=0.005 and 0.022, respectively, log-rank test). CONCLUSION: Our study demonstrated that FIB-4 is useful for the noninvasive prediction of HCC development, while APRI and GPR were less useful.

Assessment of the Left Ventricular Diastolic Function and Its Association with the Left Atrial Pressure in Patients with Atrial Fibrillation.

Background and Objectives: The evaluation of left ventricular (LV) diastolic function in patients with atrial fibrillation (AF) is challenging. This study aimed to investigate the efficacy of the diagnostic algorithm for LV diastolic dysfunction (LVDD) in the current guidelines and to evaluate the association between increased left atrial pressure (LAP) and LV diastolic parameters. Methods: One hundred and twenty-four patients with non-valvular AF and a preserved LV ejection fraction who had the same rhythm status on echocardiography and LAP measurements during catheter ablation were included. LV diastolic function was classified as normal, indeterminate, or LVDD according to the recent guidelines. Increased LAP was defined as mean LAP (mLAP) ≥15 mmHg. Results: The mLAP was not different among the normal, indeterminate, and LVDD groups. However, the prevalence of increased LAP was higher in the LVDD group. Among the LV diastolic parameters, only medial E/e' was independently associated with mLAP in the whole study population. In patients with persistent AF (PeAF), E/e' and e' were significantly associated with mLAP, whereas in paroxysmal AF (PAF), mLAP was not associated with the LV diastolic parameters but with left atrial conduit function. Conclusions: In general, increased LAP is known to be closely related with LVDD. However, the algorithm for LVDD from recent guidelines does not reflect well the increased LAP in AF patients. The diastolic parameters may aid in estimating the increased LAP in PeAF but may only have limited value for assessing increased LAP in PAF.

Longitudinal assessment of alpha-fetoprotein for early detection of hepatocellular carcinoma in patients with cirrhosis.

Background/aims: Cirrhosis is an important risk factor for hepatocellular carcinoma (HCC), and the surveillance of patients with cirrhosis is, therefore, highly recommended. However, the role of alpha-fetoprotein (AFP) in HCC surveillance is controversial. The aim of this study was to determine the role of AFP in HCC surveillance among patients with cirrhosis.Methods: The study population consisted of 392 patients with cirrhosis. Ultrasound (US) and laboratory tests including AFP were regularly performed to detect HCC development. The cutoff level of AFP for suspicion of HCC was 7 ng/mL.Results: During the median follow-up period of 4.7 (interquartile range, 3.4-5.6) years, HCC developed in 64 (16.3%) patients. Their mean age was 53.6 years, and they were predominantly male (63.5%). For the detection of HCCs, the sensitivity and specificity of US were 56.3% and 100%, respectively. The sensitivity and specificity of AFP were 62.5% and 94.5%, respectively. Using US and AFP in combination increased the sensitivity of surveillance to 89.1% with a specificity of 94.5%. Mean AFP levels were significantly higher in patients with than without HCC at the time of HCC diagnosis, at 6 months and 12 months before the diagnosis. The area under the receiver operating characteristic curve of AFP was highest at the time of HCC diagnosis (0.867), and also was acceptable at 6 months (0.823) and 12 months (0.792) before the diagnosis.Conclusions: These results suggest the complementary use of AFP and US to improve the effectiveness of HCC surveillance in patients with cirrhosis.

Epicardial adipose tissue is related to cardiac function in elderly women, but not in men.

BACKGROUND AND AIM: Epicardial adipose tissue (EAT) is easily quantifiable visceral adipose tissue that is closely associated with cardiometabolic disease including heart failure with preserved left ventricular (LV) ejection fraction. As body fat distribution and metabolism are different between men and women, we evaluated the sex difference in EAT thickness and its relationship to cardiac function. METHODS AND RESULTS: A total of 152 consecutive patients (76 men) with mean age of 62 ± 9 years were enrolled. Conventional echocardiography was performed and EAT thickness was measured perpendicularly on the right ventricular free wall at end systole. Mean EAT thickness in all patients was 6.5 ± 2.0 mm. EAT thickness was associated with patient age, body mass index, and the presence of hypertension. EAT thickness was not different by sex in patients younger than 60 years (men, 6.4 ± 2.0 mm; women, 6.2 ± 1.8 mm, p = 0.716); however, among patients aged 60 years or older, EAT thickness was significantly greater in women than men (men, 6.0 ± 1.7 mm; women 7.7 ± 2.1 mm, p < 0.001). LV function represented by E/e' and s' was significantly related to EAT thickness only in women (E/e', ß = 0.330, p = 0.002; lateral s', ß = -0.225, p = 0.042). CONCLUSION: EAT thickness was greater in women than men after 60 years old and its relationship with LV function was significant only in women. Greater increase in EAT thickness in elderly women after menopause might partially account for this difference.

Risk Assessment of Hepatocellular Carcinoma Using Transient Elastography Vs. Liver Biopsy in Chronic Hepatitis B Patients Receiving Antiviral Therapy.

Liver stiffness (LS) assessed using transient elastography (TE) can assess the risk of developing hepatocellular carcinoma (HCC). We evaluated whether TE, when compared with histological data as a reference standard, can predict the risk of HCC development in chronic hepatitis B (CHB) patients starting antiviral therapy.Observational cohort database of 381 patients with CHB who underwent liver biopsy (LB) and TE were reviewed. All patients underwent surveillance for HCC development using ultrasonography and alpha-fetoprotein.During the median follow-up period of 48.1 (interquartile range 30.3-69.3) months, HCC developed in 34 (8.9%) patients. In patients with HCC development, age, proportion of diabetes mellitus, histological fibrosis stage, and LS value were significantly higher than those in patients without (all P <0.05). The cumulative incidence rates of HCC increased significantly in association with elevated LS value in 3 stratified groups (LS value <8, 8-13, and >13 kPa; log-rank test, P <0.001), and with higher histological fibrosis stage in 3 stratified groups (F0-2, F3, and F4; log-rank test, P <0.001). On multivariate analysis, along with age, LS value was an independent predictor of HCC development (hazard ratio 1.041, P <0.001), whereas histological staging was not (P >0.05).TE predicted HCC development independently in patients with CHB starting antiviral therapy. However, further investigation is needed to determine whether the current surveillance strategy can be optimized based on the LS value at the time of starting antiviral therapy.

External Quality Assessment of MERS-CoV Molecular Diagnostics During the 2015 Korean Outbreak.

BACKGROUND: The largest outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) infection outside Middle East Asia in 2015 has necessitated the rapid expansion of laboratories that conduct MERS-CoV molecular testing in Korea, together with external quality assessment (EQA) to evaluate the assays used. METHODS: The EQA program consisted of two phases; self-validation and blind assessment. For the first EQA phase, in vitro transcribed upstream region of the envelope gene (upE) and the open reading frame (ORF)1a RNAs were used at a concentration of 1,000 copies/µL. The test panel for the second EQA phase consisted of RNA extracts from three samples, which were obtained from two MERS-CoV positive patients and one MERS-CoV negative patient. RESULTS: The first EQA phase results for 46 participants showed a linear relationship between the threshold cycle (C(T)) values of RNA materials and the logarithmic concentrations for both upE and ORF1a gene targets (R²=0.73 and 0.75, respectively). The mean C(T) value for each concentration was different depending on which commercial kit was used for the assay. Among the three commonly used kits, PowerChek MERS Real-Time PCR kit (KogeneBiotech, Korea) showed the lowest C(T) values at all concentrations of upE and most concentrations of ORF1a. The second EQA phase results for 47 participants were 100% correct for all tested samples. CONCLUSIONS: This EQA survey demonstrates that the MERS-CoV molecular testing performed in Korea during the 2015 outbreak is of robust capability. However, careful establishment and validation of a cut-off value are recommended to ensure good analytical sensitivity.

Assessment of Left Ventricular Function by Layer-Specific Strain and Its Relationship to Structural Remodelling in Patients With Hypertension.

BACKGROUND: Systemic arterial hypertension causes functional and structural remodelling of the left ventricle, which is related to subclinical left ventricular (LV) dysfunction and heart failure. This study assessed LV functional change using layer-specific strain and its relationship to structural remodelling in patients with hypertension. METHODS: A total of 145 patients (61 ± 12 years) with primary hypertension and preserved LV ejection fraction and 31 normotensive controls (63 ± 9 years) were prospectively included. Longitudinal strains of the endocardium, myocardium, and epicardium (LSendo, LSmyo, and LSepi) were obtained by averaging peak systolic strain of the left ventricle, with 18 segments in each layer. RESULTS: Layer-specific strains showed a decreasing gradient from the endocardium to the epicardium in both controls and patients with hypertension (P < 0.001 in both) and were significantly different between controls and patients with hypertension in all 3 layers (LSendo, -20.4% ± 2.4% vs -19.2% ± 2.2%; P = 0.007; LSmyo, -15.8% ± 2.0% vs -14.8% ± 1.9%; P = 0.005; LSepi, -11.8% ± 2.0% vs -11.0% ± 1.8%,; P = 0.04). Both LSendo and LSmyo were lower even in patients with hypertension and no LV hypertrophy than in controls (both P < 0.05), although global LS was not different. New patients with hypertension showed more decreased LSendo and LSmyo than controls even with their younger age. LSs of all 3 layers were related to LV mass index and mitral annular velocity parameters. CONCLUSIONS: Layer-specific evaluation of the left ventricle provides an understanding of the layer-specific properties of the LV wall and the process of LV impairment, and it may be helpful in managing patients with hypertension, thus preventing further damage.

Evolution from WHO to EASL and mRECIST for hepatocellular carcinoma: considerations for tumor response assessment.

Radiological response assessment criteria in hepatocellular carcinoma (HCC) have evolved to accurately evaluate tumor responses. The WHO criteria and the subsequent Response Evaluation Criteria in Solid Tumors (RECIST) evaluate change in tumor size; however, these criteria generally ignore tumor necrosis and therefore may underestimate treatment responses. Thus, a panel of experts of the European Association for the Study of Liver (EASL) amended the response criteria to take into account tumor necrosis. In 2010, the modified RECIST (mRECIST) was developed, which consider both the concept of tumor viability based on arterial enhancement and single linear summation, ultimately simplifying EASL criteria. Currently, the mRECIST represents the gold standard for radiologically evaluating tumor response during HCC treatment. Here, the authors review application and performance of mRECIST as well as other HCC response assessment criteria and discuss unmet and open issues regarding response evaluation for HCC treatments.

Assessment of the appropriateness of hand surface coverage for health care workers according to World Health Organization hand hygiene guidelines.

We monitored hand surface coverage technique in health care workers in a tertiary care hospital using a 5-item hand hygiene assessment tool based on World Health Organization guidelines. Overall hand hygiene compliance was 86.7% (4,300/4,960). Appropriate hand surface coverage was observed in only 7.9% (182/2,297) of hand hygiene procedures.

Risk assessment of liver-related events using transient elastography in patients with chronic hepatitis B receiving entecavir.

GOALS: We investigated whether liver stiffness (LS) values can predict liver-related events (LREs) development in patients with chronic hepatitis B (CHB). BACKGROUND: LS values using transient elastography provides accurate assessment of liver fibrosis in patients with chronic liver disease. METHODS: Between June 2007 and May 2010, a total of 162 patients with CHB who completed 2-year entecavir (ETV) treatment were evaluated. The primary endpoint was LRE development (hepatic decompensation, hepatocellular carcinoma, or liver-related death) during the 2-year ETV treatment. RESULTS: The median age of the patients (99 men, 63 women) was 51 years, and the median LS value was 14.8 kPa. During the 2-year ETV treatment, 15 (9.3%) patients experienced LREs. On univariate analysis, age, the proportion of patients with liver cirrhosis, platelet counts, and baseline LS values were significantly associated with LRE development (all P<0.05). Together with age, multivariate analysis identified baseline LS values as an independent predictor of LRE development (P=0.046; hazard ratio, 1.040; 95% confidence interval, 1.101-1.084). The cutoff LS value maximizing the sum of sensitivity and specificity was 12.0 kPa (area under the receiver operating characteristics curve, 0.736; P=0.003; sensitivity, 93.3%; specificity, 42.2%). In addition, the changes in LS values between baseline and 1-year ETV treatment showed significant correlations with LRE development (P=0.030). CONCLUSIONS: Our data suggest that LS values are predictive of LRE development during 2-year ETV treatment in patients with CHB. The potential role of LS value as a monitoring tool for predicting dynamic changes in the risk of LRE development during long-term ETV treatment should be investigated further.

Genetic diversity among Korean Candida albicans bloodstream isolates: assessment by multilocus sequence typing and restriction endonuclease analysis of genomic DNA by use of BssHII.

Multilocus sequence typing (MLST) has been successfully applied to the epidemiology of Candida albicans isolates not only within the hospital setting but also in multiple locations nationwide. We performed MLST to investigate the genetic relatedness among bloodstream infection (BSI) isolates of C. albicans recovered from 10 Korean hospitals over a 12-month period. The 156 isolates yielded 112 unique diploid sequence types (DSTs). While 95 DSTs were each derived from a single isolate, 17 DSTs were shared by 61 isolates (39.1%). Interestingly, 111 (71.1%) isolates clustered within previously known clades, and 29 (18.6%) clustered within a new clade that includes strains of Asian origin previously typed as singletons. This MLST study was complemented by restriction endonuclease analysis of genomic DNA using BssHII (REAG-B) in order to evaluate whether strains with identical DSTs and originating from the same hospital corresponded to nosocomial clusters. Importantly, only those isolates with a strong epidemiological relationship showed ≥95% identical REAG-B types. Our results indicate that REAG-B typing can be complementary to MLST but should be limited to the investigation of isolates of identical DSTs and when interhuman transmission is suspected.