Qualification of In Vitro Dissolution Absorption System 2 (IDAS2) with Caco-2 and MDCK Cell Monolayers: Dose Sensitivity Study Using BCS Class I and III Drugs.

This study aimed to validate the In vitro Dissolution Absorption System 2 (IDAS2) containing a biological barrier of Caco-2 or Madin-Darby canine kidney (MDCK) cell monolayer through dose sensitivity studies. Metoprolol and propranolol were selected as Biopharmaceutics Classification System (BCS) Class I model drugs, and atenolol as a Class III model drug. The IDAS2 is comprised of a dissolution vessel (500 mL) and two permeation chambers (2 × 8.0 mL) mounted with Caco-2 or MDCK cell monolayer. One or two immediate-release tablet(s) of the model drug were added to the dissolution vessel, and the time profiles of dissolution and permeation were observed. Greater than 85% of metoprolol and propranolol (tested at two dosing concentrations) were dissolved by 15 min, and all drugs were fully dissolved by 30 min. All three drugs were more permeable across Caco-2 cells than MDCK cells with a linear increase in permeation across both cells at both dose concentrations. Thus, the dose sensitivity of the IDAS2 was demonstrated using both cell barriers. These results indicate a successful qualification of IDAS2 for the development/optimization of oral formulations and that MDCK cells can be utilized as a surrogate for Caco-2 cells.

Nationwide Survey for Current Status of Laboratory Diagnosis of Clostridioides difficile Infection in Korea.

BACKGROUND: The interest in Clostridioides difficile infection (CDI) has increased, and the choice of assays became wider since the first national survey in Korea on CDI diagnosis in 2015. We conducted a survey of the domestic CDI assays with more varied questions to understand the current situation in Korea. METHODS: In April 2018, about 50 questions on the current status of CDI assays and details on implementation and perceptions were written, and a survey questionnaire was administered to laboratory medicine specialists in 200 institutions. RESULTS: One-hundred and fifty institutions responded to the questionnaire, of which 90 (60.0%) including one commercial laboratory, performed CDI assays. The toxin AB enzyme immunoassay (toxin AB EIA), nucleic acid amplification test (NAAT), and C. difficile culture, glutamate dehydrogenase assay, alone or in combination with other assays, were used in 75 (84.3%), 52 (58.4%), 35 (36.0%), and 23 (25.8%), respectively, and 65 (73.0%) institutions performed a combination of two or more assays. The sensitivity of toxin AB EIA was more negatively perceived, and that on specificity was more positively perceived. The perception of sensitivity and specificity of NAAT was mostly positive. Perception on the algorithm test projected it as useful but in need of countermeasures. Sixty-three (73.3%) institutions responded that they performed surveillance on CDI. CONCLUSION: This study provides useful evidence on the current status of CDI laboratory diagnosis in Korea as well as on items that require improvement and is thought to aid in standardizing and improving the CDI laboratory diagnosis in Korea.

Usefulness of KL-6 for Predicting Clinical Outcomes in Hospitalized COVID-19 Patients.

Background: Krebs von den Lungen 6 (KL-6) is a novel biomarker for interstitial lung disease, and it reflects acute lung injury. We explored the usefulness of KL-6 to predict clinical outcomes in hospitalized coronavirus disease 2019 (COVID-19) patients. Methods: In a total of 48 hospitalized COVID-19 patients, KL-6 levels were measured using the HISCL KL-6 assay (Sysmex, Kobe, Japan) with the HISCL 5000 automated analyzer (Sysmex). Clinical outcomes (intensive care unit [ICU] admission, ventilator use, extracorporeal membrane oxygenation [ECMO] use, and 30-day mortality) were analyzed according to KL-6 percentiles. Age, initial KL-6 level, Charlson comorbidity index (CCI), and critical disease were compared using the receiver operating characteristic (ROC) curve and Kaplan-Meier methods for clinical outcomes. Results: KL-6 quartiles were associated with ICU admission, ventilator use, and ECMO use (all p < 0.05), except 30-day mortality (p = 0.187). On ROC curve analysis, initial KL-6 level predicted ICU admission, ventilator use, and ECMO use significantly better than age, CCI, and critical disease (all p < 0.05); age, initial KL-6 level, CCI, and critical disease predicted 30-day mortality comparably. On Kaplan−Meier survival analysis, hazard ratios (95% confidence interval) were 4.8 (1.2−19.3) for age, 4.7 (1.1−21.6) for initial KL-6 level, 3.9 (0.9−16.2) for CCI, and 2.1 (0.5−10.3) for critical disease. Conclusions: This study demonstrated that KL-6 could be a useful biomarker to predict clinical outcomes in hospitalized COVID-19 patients. KL-6 may contribute to identifying COVID-19 patients requiring critical care, including ICU admission and ventilator and/or ECMO use.

Prevalence of SARS-CoV-2 Antibody in 2,935 Healthcare Workers at 6 Major Hospitals, Daegu, Korea.

BACKGROUND: In Korea, the first community outbreak of coronavirus disease 2019 (COVID-19) occurred in Daegu on February 18, 2020. This study was performed to investigate the prevalence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) antibodies in healthcare workers (HCWs) at 6 major hospitals in Daegu. METHODS: Blood specimens of 2,935 HCWs at 6 major hospitals in Daegu from January 2021 to February 2021 were collected. Every specimen was tested for antibody against SARS-CoV-2 using both Elecsys Anti-SARS-CoV-2 electrochemiluminescence immunoassay (Roche Diagnostics, Rotkreuz, Switzerland) and R-FIND COVID-19 IgG/M/A enzyme-linked immunosorbent assay kit (SG medical Inc., Seoul, Korea) as screening tests. If 1 or more of these screening test results was positive, 2 additional antibody tests were performed using Abbott Anti-SARS-CoV-2 IgG assay (Abbott, Abbott Park, IL, USA) and cPass SARS-CoV-2 Neutralization Antibody Detection Kit (GenScript USA Inc., Piscataway, NJ, USA). If 2 or more of the total 4 test results were positive, it was determined as positive for the antibody against SARS-CoV-2. RESULTS: According to the criteria of SARS-CoV-2 antibody positivity determination, 12 subjects were determined as positive. The overall positive rate of the SARS-CoV-2 antibody was 0.41% (12/2,935). Of the 12 subjects determined as positive, 7 were diagnosed with COVID-19, and the remaining 5 were nondiagnosed cases of COVID-19. CONCLUSION: In early 2021, the overall seroprevalence of SARS-CoV-2 antibody among HCW located in Daegu was 0.41%, and 0.17% excluding COVID-19 confirmed subjects. These results were not particularly high compared with the general public and were much lower than HCWs in other countries.

Multilaboratory Evaluation of the MALDI-TOF Mass Spectrometry System, MicroIDSys Elite, for the Identification of Medically Important Filamentous Fungi.

With the increasing number of fungal infections and immunocompromised patients, rapid and accurate fungal identification is required in clinical microbiology laboratories. We evaluated the applicability of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) system, MicroIDSys Elite (ASTA Corp., South Korea) for the identification of medically important filamentous fungi. A total of 505 strains comprising 37 genera and 90 species collected from 11 Korean hospitals were sent to the microbiology laboratory of International St. Mary's Hospital. All isolates were tested using MicroIDSys Elite, and data were analyzed using the MoldDB v.1.22 database (ASTA). Correct identification rates were compared with the multigene sequencing results. MicroIDSys Elite correctly identified 86.5% (437/505) and 88.9% (449/505) of all tested isolates at the species and genus level, respectively. About 98.2% of Aspergillus isolates were identified at the species level, including cryptic and rare species of A. calidoustus, A. tamarii, A. lentulus, A. versicolor and A. aculeatus. MicroIDSys Elite identified 75.0% of basidiomycetes, including Schizophyllum commune, and 84.3% of the dermatophytes. It also distinguished Sprothrix globosa at the species level. The mean scores of total isolates corresponding to correct species identification were significantly higher than those obtained for genus-level identification (253.5 ± 50.7 vs. 168.6 ± 30.3, P < 0.001). MicroIDSys Elite showed high accuracy for the identification of filamentous fungi, including cryptic and rare Aspergillus species. It is suitable for use in clinical laboratories as a rapid and efficient tool for clinical mold identification. Further evaluations are recommended for MicroIDSys Elite as a rapid and efficient tool for the identification of medically important filamentous fungi.

Toxicity of Bioactive Molecule Andrographolide against Spodoptera litura Fab and Its Binding Potential with Detoxifying Enzyme Cytochrome P450.

Spodoptera litura Fab. is a polyphagous pest causing damage to many agriculture crops leading to yield loss. Recurrent usage of synthetic pesticides to control this pest has resulted in resistance development. Plant-derived diterpenoid compound andrographolide was isolated from the leaves of Andrographis paniculata. It was analysed by gas chromatography-mass spectroscopy and quantified by HPLC. Nutritional indices and digestive enzymatic profile were evaluated. Third, fourth and fifth instar larvae were treated with different concentrations of andrographolide. At 3, 6 and 9 ppm-treated concentrations the larvae showed decreased RGR, RCR, ECI, ECD values with adverse increase in AD. The digestive enzymes were significantly inhibited when compared with control. Conspicuously, andrographolide showed pronounced mortality of S. litura by inhibition of enzyme secretion and intake of food. The binding ability of andrographolide with CYTP450 showed high affinity with low binding energy. Andrographolide has the potential to be exploited as a biocontrol agent against S. litura as an eco-friendly pesticide.

Clinical and Radiographic Characteristics of Atypical Slipped Capital Femoral Epiphysis.

BACKGROUND: Slipped capital femoral epiphysis (SCFEs) can be idiopathic or atypical (associated with renal failure, radiation therapy, and endocrine disorders). It is important to estimate the likelihood that atypical SCFE shows different clinical and radiographic characteristics and complications with typical SCFEs. METHODS: We retrospectively reviewed 53 patients (66 hips) with SCFEs managed between 1995 and 2016. Sex, age, weight, height, the duration of symptoms the laterality of the slip, and complications were recorded. Bilateral hip and lower extremity long bone radiographs were utilized to record slip angle, genu valgus deformity. Statistical analyses were performed. RESULTS: Among 53 children (32 boys and 21 girls) with 66 SCFEs, 22 children had 29 atypical SCFEs, and 31 children had 38 typical SCFEs. The average age at the time of presentation for the initial SCFEs was 10.9±0.3 years. The average duration of symptoms was 14.1±21.8 weeks. The average Southwick slip angle difference was 23.3±14.8 degrees. There are 43 mild, 13 moderate, and 10 severe SCFEs. 58 were classified as stable, and 8 were unstable. There were significant differences in terms of average age (10.4±2.6 y for atypical SCFEs, 11.2±1.4 for typical SCFEs; P=0.036), average weight (36.2±22.3 kg for patients with atypical slips, compared with 56.9±9.9 kg for those with typical slips; P<0.001), height (132.1±17.6 cm for those with atypical slips, compared with 148.9±12.1 for those with typical slips; P<0.001), and the body mass index (19.4±5.6 kg/cm for those with atypical slips, compared with 25.8±4.6 for those with typical slips; P<0.001). In the group of 22 children with atypical slipped capital epiphysis, there were 19 children with neoplasm (8 neuroblastomas, 3 medulloblastomas, 3 retinoblastomas, 2 ependymomas, 1 craniopharyngioma, 1 Wilms tumor, 1 immature teratoma), 4 children with primary endocrine disorder. We categorized atypical SCFEs in 3 groups by etiology; endocrine disorder-associated (ENDA) SCFEs, chemotherapy-associated (CTA) SCFEs, and radiation therapy-associated (RTA) SCFEs. Subjects of RTA were included if exposed to pelvic irradiation or total body irradiation. There were 4 ENDA, 9 RTA, and 16 CTA. Atypical SCFEs had significantly more valgus slips (P<0.001) and genu valgus deformity (P<0.001) compared with in the group of typical slipped capital epiphysis. Among the group of atypical SCFEs, children with CTA had significantly low body weight, height, and body mass index. CONCLUSIONS: The markedly greater incidence of valgus displacement of proximal femoral epiphysis and genu valgum in childhood cancer survivors with pelvic irradiation and chemotherapy may be associated with atypical SCFE. The authors conclude that in pediatric cancer survivors with hip pain, consideration should be given to atypical SCFE with valgus slip and long-term follow-up of lower extremity alignment. LEVEL OF EVIDENCE: Level III-retrospective comparative study. See instructions for authors for a complete description of levels of evidence.

Preischemic transfusion of old packed RBCs exacerbates early-phase warm hepatic ischemia reperfusion injury in rats.

BACKGROUND: Hepatic innate immune cells are considered to play a central role in the early phase of hepatic ischemia reperfusion (IR) injury. Transfusion of old red blood cells (RBCs) is known to prime immune cells, and transfusion before IR may exacerbate liver injury because of the expected hyperresponsiveness of immune cells. MATERIALS AND METHODS: Twenty-four Sprague-Dawley rats were divided into four groups: sham operation (Sham); hepatic IR only (IR Control); and two transfusion groups, preischemic (Pre-T) and postischemic (Post-T), in which allogeneic RBCs stored for 2 weeks were transfused before hepatic IR or after reperfusion, respectively. Partial hepatic ischemia was induced for 90 min, and reperfusion was allowed for 120 min. Serum alanine transaminase levels, area of necrosis, and apoptotic cells were then assessed. Inflammatory (tumor necrosis factor alpha, interleukin 1 beta [IL-1ß], IL-6, IL-10, and cyclooxygenase 2) and oxidative mediators (heme oxygenase 1, superoxide dismutase, and glutathione peroxidase 1) were assessed for elucidating the relevant mechanisms underlying the hepatic injury. RESULTS: Pre-T, but not Post-T, showed increased serum alanine transaminase levels than IR Control (P < 0.05). Area of necrosis was more severe in Pre-T than in IR Control or Post-T (P < 0.01), and apoptotic cells were also more abundant in Pre-T than in IR Control (P < 0.01). tumor necrosis factor alpha and IL-6 levels were higher in Pre-T than in IR Control or Post-T (P < 0.05), with no significant difference in cytoprotective protein levels. CONCLUSIONS: Preischemic transfusion of old RBCs aggravated hepatic injury. Inflammatory cytokines seemed to play a crucial role in liver injury exacerbation. Our results indicate that transfusion before hepatic ischemia may be detrimental.

Emergence of IMP-4-Producing Enterobacter aerogenes Clinical Isolate.

BACKGROUND: IMP-4 class B metallo-ß-lactamase-producing Enterobacteriaceae are resistant to carbapenems. The aim of this study was to characterize of IMP-4 metallo-ß-lactamase (MBL)-producing Enterobacter aerogenes clinical isolate. METHODS: IMP-4 MBL-producing E. aerogenes clinical isolate was collected from a Korean Hospital in 2017. Antimicrobial susceptibility was determined by disk diffusion methods. Further, minimum inhibitory concentrations of ß-lactams were determined by Etest. Detection of bla genes was performed by PCR. The genetic organization of class 1 integron carrying the MBL gene cassette was investigated by PCR mapping and sequencing. RESULTS: E. aerogenes strain YN170501 exhibited resistance to penicillins, cephalosporins, and carbapenems and was susceptible to monobactam, aminoglycosides, fluoroquinolone, tigecycline, and trimethoprim-sulfamethoxazole. The blaIMP-4 gene was located in class 1 integron. CONCLUSIONS: The blaIMP-4 gene has never been reported in Enterobacter aerogenes clinical isolate from Korea.

What Factors Are Associated With Early Mortality in Patients Undergoing Femur Surgery for Metastatic Lung Cancer?

BACKGROUND: Pathologic fractures of the femur resulting from metastasis severely increase mortality in patients with nonsmall cell lung cancer (NSCLC). However, factors associated with early mortality after surgery have not been elucidated. QUESTIONS/PURPOSES: The purpose of this study was to identify clinical and laboratory factors available to surgeons before surgery for a metastatic femur in patients with metastatic lung cancer that might be associated with mortality at 1 and 3 months. METHODS: Between 2010 and 2014 we treated 126 patients for pathologic fracture of the femur caused by NSCLC. Of those, complete data sets for the parameters of interest (including clinical factors, laboratory factors, and survivorship) were available in 105 (83%). The factors we considered included sex, age, fracture location, surgical procedure, postoperative complications, blood cell counts, serum biomarkers, genetic alterations of primary cancer, chemotherapeutic agents, preoperative radiation therapy, pleural effusion, bone and internal organ metastasis, performance scores, and medical center where the treatment was performed. Multivariate logistic regression was performed to identify factors associated with mortality at 1 and 3 months. RESULTS: Intertrochanteric location was associated with a higher risk of death (odds ratio [OR], 17.0; 95% confidence interval [CI], 2.65-109.5), lower serum albumin level was associated with an increased risk of death (OR, 0.13; 95% CI, 0.028-0.60), and availability of a suitable chemotherapeutic target agent was associated with a lower risk of death (OR, 0.28; 95% CI, 0.08-0.91) within 3 months of surgery. Undergoing reconstruction with an endoprosthesis was associated with a higher risk of death (OR, 48.3; 95% CI, 1.7-1329) and elevated serum leukocyte count (OR, 1.2; 95% CI, 1.0-1.4) and elevated alanine aminotransferase (ALT) were associated with a higher risk of death (OR, 1.1; 95% CI, 1.0-1.2) within 1 month of surgery. CONCLUSIONS: Although the risk factors for early mortality need to be validated by prospective studies, surgical options need to be reconsidered in patients with femoral metastases from NSCLS showing high ALT or leukocytosis on the preoperative blood test. LEVEL OF EVIDENCE: Level III, prognostic study.

Ultrasound-guided steroid injection for the treatment of de Quervain's disease: an anatomy-based approach.

OBJECTIVE: To suggest different ultrasound-guided steroid injection (USI) techniques based on anatomical variations of the first extensor compartment (FEC), and to evaluate the usefulness of it, in patients with de Quervain's disease. MATERIALS AND METHODS: Twenty-eight patients who underwent USI for de Quervain's disease were included. Anatomical variations were classified into complete sub-compartmentalization (n = 11), distal incomplete sub-compartmentalization (n = 5), and no sub-compartmentalization (n = 12) on ultrasound. Involved sub-compartments were recorded in patients with complete sub-compartmentalization. USIs were performed based on the anatomical variations: in both sub-compartments (n = 2) or only in the affected sub-compartment (n = 9) depending on the location of tenosynovitis involvement, in patients with complete sub-compartmentalization; in proximal FEC in patients with distal incomplete sub-compartmentalization (n = 5); in the common compartment in patients with no sub-compartmentalization (n = 12). Medical charts were retrospectively reviewed for evaluation of clinical outcome at follow-up visits. RESULTS: Twenty-three out of 28 patients were followed up with a mean period of 31.2 days after injection (6~87 days). Mean VAS was 7.96 before injection (range: 4 to 10), which was significantly reduced to 0.65 at rest and 1.57 during activity at follow-up visits (p < 0.05). Twenty-two out of 23 patients were satisfied with the results. The mean proportion of subjective pain reduction was 82.0% (median 95%). CONCLUSION: Ultrasound-guided steroid injections using different injection techniques based on the anatomical variations of the FEC have shown to be beneficial in the management of de Quervain's disease.

Diagnostic accuracy of 3T conventional shoulder MRI in the detection of the long head of the biceps tendon tears associated with rotator cuff tendon tears.

OBJECTIVE: To evaluate the diagnostic performance (DP) of 3T (3 Tesla field strength) conventional shoulder magnetic resonance imaging (MRI) in detecting the long head of the biceps tendon (LHBT) tears in association with rotator cuff tendon tears. MATERIALS AND METHODS: This study included 80 consecutive patients who underwent arthroscopic surgery for rotator cuff tendon tears. Two radiologists independently evaluated the preoperative 3T shoulder MRI for the presence of LHBT tears. The DP of MRI was evaluated using the results of arthroscopy as the reference standard. We also evaluated the DP of several MR signs of LHBT in detection of partial LHBT tears. RESULTS: Arthroscopic examination revealed 35 partial and 5 complete tears. According to the results of evaluation by reviewers 1 and 2, shoulder MRI exhibited sensitivities of 77.14 and 80 % and specificities of 71.11 and 73.33 % in detection of partial LHBT tears and sensitivities of 80 and 100 % and a specificity of 100% (both) in detection of complete LHBT tears. In detecting partial LHBT tears, increased T2 signal intensity of the LHBT exhibited high sensitivities (reviewers 1 and 2; 82.85 and 80 %, respectively) and the presence of intratendinous defects or C-signs exhibited the highest specificities (reviewers 1 and 2; 95.55 and 93.33 %, respectively), followed by abnormalities in shape and outer margins of the LHBT (reviewers 1 and 2; 91.11 and 82 %; 91.11 and 86.66 %, respectively). CONCLUSION: Non-contrast-enhanced 3T shoulder MRI is potentially highly accurate in detection of complete LHBT tears, but moderately accurate in detection of partial LHBT tears.

Target and non-target toxicity of botanical insecticide derived from Couroupita guianensis L. flower against generalist herbivore, Spodoptera litura Fab. and an earthworm, Eisenia foetida Savigny.

Botanical insecticides may provide alternatives to synthetic insecticides for controlling Spodoptera litura (F.) and they are target specific, biodegradable, and harmless to mammals. Eight natural chemical compounds with larvicidal activity were identified from fraction F6 of C. guianensis flower extract. Probit analysis of 95% confidence level exposed an LC50 of 223ppm against S. litura third instar larvae. The growth and development of S. litura was affected in sub-lethal concentrations of fraction F6 (50, 100, 150 and 200ppm) compared to controls. Similarly nutritional indices values decreased significantly compared to controls. Fraction F6 also damaged the gut epithelial layer and brush border membrane (BBM). This study also resolved the effects of toxicity to non-target earthworm treated with fraction F6 and chemical pesticides (monotrophos and cypermethrin) and the results showed that fraction F6 had no harmful effect on E. fetida. Further, fraction F6 was eluted and sub fractions F6c (50ppm) showed high mortality against S. litura third instar larvae. Octacosane from fraction F6c was established and confirmed using IR spectrum and HPLC. The time of retention of fraction F6c was confirmed with the octacosane standard. Fraction F6 of C. guianensis extract caused dose-dependent mortality towards S. litura. Octacosane in fraction F6c was establish to be the prominent chemical compound associated with causing mortality but other compounds present in the fraction F6 were shown to be associated with changes in development of S. litura at low dosages. S. litura at low dosage. Therefore, these findings suggest that octacosane may be one of the major insecticidal compounds affecting S. litura survival.

Prevalence and Management of Venous Rupture Following Percutaneous Transluminal Angioplasty in Dysfunctional Arteriovenous Access: A Comparative Study of Primary Patency Rates with Non-Ruptured Access Circuits.

Purpose: This study aims to evaluate the incidence and management of venous ruptures after percutaneous transluminal angioplasty (PTA) for dysfunctional arteriovenous (AV) access. Materials and Methods: From January 1998 to December 2015, 13506 PTA, mechanical thrombectomy, and thrombolysis procedures were performed in 6732 patients. The venous rupture rate following PTA was obtained, and access circuit primary patency (ACPP) was compared according to the etiology (PTA, thrombotic occlusion, and treatment type) of the venous rupture present. Results: Venous rupture developed in 604 of the 13506 procedures. Venous ruptures were more frequent in female, AV graft cases, and in cases accompanied by thrombosis. Balloon tamponade was performed in 604 rupture cases, and stents were deployed in 119 cases where contrast extravasation and flow stasis persisted. ACPP was significantly better in the non-ruptured AV access circuits than in the ruptured group. However, AV access type and thrombosis was not associated with primary patency. In ruptured cases, ACPP is 8.4 months for prolonged balloon tamponade and 11.2 months for bare-metal stent insertion, showing statistically significant difference. Conclusion: Balloon tamponade and bare-metal stent placement are effective treatment for PTA-induced venous ruptures. In particular, stent placement showed a similar ACPP to that of non-ruptured AV access circuits.

Soluble ST2 as a Useful Biomarker for Predicting Clinical Outcomes in Hospitalized COVID-19 Patients.

Soluble suppression of tumorigenesis-2 (sST2) is an emerging biomarker for sepsis as well as for heart failure. We investigated the prognostic utility of sST2 for predicting clinical outcomes in hospitalized coronavirus disease 2019 (COVID-19) patients. In a total of 52 hospitalized COVID-19 patients, sST2 levels were measured using the ichroma ST2 assay (Boditech Med Inc., Chuncheon-si, Gang-won-do, Republic of Korea). Clinical outcomes included intensive care unit (ICU) admission, ventilator use, extracorporeal membrane oxygenation (ECMO) use, and 30-day mortality. sST2 was analyzed according to clinical outcomes. sST2, sequential organ failure assessment (SOFA) score, critical disease, and 4C mortality score were compared using the receiver operating characteristic (ROC) curve and Kaplan−Meier methods for clinical outcomes. The sST2 level differed significantly according to ICU admission, ventilator use, ECMO use, and 30-day mortality (all p < 0.05). On ROC curve analysis, sST2 predicted ICU admission, ventilator use, ECMO use, and 30-day mortality comparable to SOFA score but significantly better than critical disease. sST2 predicted ICU admission, ventilator use, and ECMO use significantly better than the 4C mortality score. On Kaplan−Meier survival analysis, hazard ratios (95% confidence interval) were 8.4 (2.7−26.8) for sST2, 14.8 (3.0−71.7) for SOFA score, 1.8 (0.5−6.5) for critical disease, and 11.7 (3.4−40.1) for 4C mortality score. This study demonstrated that sST2 could be a useful biomarker to predict ICU admission, ventilator use, ECMO use, and 30-day mortality in hospitalized COVID-19 patients. sST2 may be implemented as a prognostic COVID-19 biomarker in clinical practice.

Comparison of Non-Invasive Clinical Algorithms for Liver Fibrosis in Patients With Chronic Hepatitis B to Reduce the Need for Liver Biopsy: Application of Enhanced Liver Fibrosis and Mac-2 Binding Protein Glycosylation Isomer.

BACKGROUND: Non-invasive clinical algorithms for the detection of liver fibrosis (LF) can reduce the need for liver biopsy (LB). We explored the implementation of two serum biomarkers, enhanced liver fibrosis (ELF) and Mac-2 binding protein glycosylation isomer (M2BPGi), in clinical algorithms for LF in chronic hepatitis B (CHB) patients. METHODS: Two clinical algorithms were applied to 152 CHB patients: (1) transient elastography (TE) followed by biomarkers (TE/ELF and TE/M2GPGi); (2) biomarker test followed by TE (ELF/TE and M2BPGi/TE). Using the cut-off value or index for the detection of advanced LF (TE≥F3; 9.8 in ELF and 3.0 in M2BPGi), LB was expected to be performed in cases with discordant TE and biomarker results. RESULTS: In both algorithms, the expected number of LBs was lower when using M2BPGi than when using ELF (TE/ELF or ELF/TE, 13.2% [N=20]; TE/M2BPGi or M2BPGi/TE, 9.9% [N=15]), although there was no statistical difference (P=0.398). In the TE low-risk group (TE≤F2), the discordance rate was significantly lower in the TE/M2BPGi approach than in the TE/ELF approach (1.5% [2/136] vs. 11.0% [15/136], P=0.002). In the biomarker low-risk group, there was no significant difference between the ELF/TE and M2BPGi/TE approaches (3.9% [5/126] vs. 8.8% [13/147], P=0.118). CONCLUSIONS: Both ELF and M2BPGi can be implemented in non-invasive clinical algorithms for assessing LF in CHB patients. Given the lowest possibility of losing advanced LF cases in the low-risk group when using the TE/M2BPGi approach, this combination seems useful in clinical practice.

Perioperative Efficiency of Sugammadex Following Laparoscopic Cholecystectomy in Clinical Practice.

Background: Studies have proposed that the routine use of the modified gamma-cyclodextrin, sugammadex, could provide perioperative time savings. However, these investigations have been limited to small group analyses. The purpose of this study was to test the effectiveness of sugammadex on perioperative times when compared to neostigmine under general clinical practice conditions following rocuronium-induced neuromuscular blockade for laparoscopic cholecystectomy. Methods: Following institutional review board approval, data from 1,611 consecutive surgical records for laparoscopic cholecystectomy were reviewed. Patient characteristics, type of primary neuromuscular blocking reversal agent, operating room (OR) discharge times, and postanesthesia care unit (PACU) recovery times were the measures of interest. Equivalence testing was used to determine the between-group differences of the reversal agents in the two perioperative time periods of interest. Results: OR discharge times averaged 10.9 (95% CI, 10-11.8) minutes for patients administered sugammadex and 8.9 (95% CI, 8.2-9.7) minutes for patients administered neostigmine. PACU recovery times averaged 77.6 (95% CI, 74.1-81.1) minutes for sugammadex and 68.6 (95% CI, 65.9-71.3) minutes for neostigmine. Equivalence testing demonstrated no improvement in the two perioperative times with sugammadex. Conclusion: These results suggest no perioperative time savings with sugammadex when compared to neostigmine following laparoscopic cholecystectomy under general clinical practice conditions.

Prognostic Utility of Procalcitonin, Presepsin, and the VACO Index for Predicting 30-day Mortality in Hospitalized COVID-19 Patients.

BACKGROUND: Biomarkers and clinical indices have been investigated for predicting mortality in patients with coronavirus disease (COVID-19). We explored the prognostic utility of procalcitonin (PCT), presepsin, and the Veterans Health Administration COVID-19 (VACO) index for predicting 30-day-mortality in COVID-19 patients. METHODS: In total, 54 hospitalized COVID-19 patients were enrolled. PCT and presepsin levels were measured using the Elecsys BRAHMS PCT assay (Roche Diagnostics GmbH, Mannheim, Germany) and HISCL Presepsin assay (Sysmex, Kobe, Japan), respectively. The VACO index was calculated based on age, sex, and comorbidities. PCT and presepsin levels and the VACO index were compared using ROC curve, Kaplan-Meier method, and reclassification analysis for the 30-day mortality. RESULTS: ROC curve analysis was used to measure PCT and presepsin levels and the VACO index to predict 30-day mortality; the optimal cut-off values were 0.138 ng/mL for PCT, 717 pg/mL for presepsin, and 12.1% for the VACO index. On Kaplan-Meier survival analysis, hazard ratios (95% confidence interval) were 15.9 (4.1-61.3) for PCT, 26.3 (6.4-108.0) for presepsin, and 6.0 (1.7-21.1) for the VACO index. On reclassification analysis, PCT and presepsin in addition to the VACO index significantly improved the prognostic value of the index. CONCLUSIONS: This study demonstrated the prognostic utility of measuring PCT and presepsin levels and the VACO index in COVID-19 patients. The biomarkers in addition to the clinical index were more useful than the index alone for predicting clinical outcomes in COVID-19 patients.

Comprehensive Laboratory Data Analysis to Predict the Clinical Severity of Coronavirus Disease 2019 in 1,952 Patients in Daegu, Korea.

BACKGROUND: Laboratory parameter abnormalities are commonly observed in COVID-19 patients; however, their clinical significance remains controversial. We assessed the prevalence, characteristics, and clinical impact of laboratory parameters in COVID-19 patients hospitalized in Daegu, Korea. METHODS: We investigated the clinical and laboratory parameters of 1,952 COVID-19 patients on admission in nine hospitals in Daegu, Korea. The average patient age was 58.1 years, and 700 (35.9%) patients were men. The patients were classified into mild (N=1,612), moderate (N=294), and severe (N=46) disease groups based on clinical severity scores. We used chi-square test, multiple comparison analysis, and multinomial logistic regression to evaluate the correlation between laboratory parameters and disease severity. RESULTS: Laboratory parameters on admission in the three disease groups were significantly different in terms of hematologic (Hb, Hct, white blood cell count, lymphocyte%, and platelet count), coagulation (prothrombin time and activated partial thromboplastin time), biochemical (albumin, aspartate aminotransferase, alanine aminotransferase, lactate, blood urea nitrogen, creatinine, and electrolytes), inflammatory (C-reactive protein and procalcitonin), cardiac (creatinine kinase MB isoenzyme and troponin I), and molecular virologic (Ct value of SARS-CoV-2 RdRP gene) parameters. Relative lymphopenia, prothrombin time prolongation, and hypoalbuminemia were significant indicators of COVID-19 severity. Patients with both hypoalbuminemia and lymphopenia had a higher risk of severe COVID-19. CONCLUSIONS: Laboratory parameter abnormalities on admission are common, are significantly associated with clinical severity, and can serve as independent predictors of COVID-19 severity. Monitoring the laboratory parameters, including albumin and lymphocyte count, is crucial for timely treatment of COVID-19.

Comparison of Six Antifungal Susceptibilities of 11 Candida Species Using the VITEK2 AST-YS08 Card and Broth Microdilution Method.

We used a Vitek 2 AST-YS08 (YS08) system and the broth microdilution method (BMD) adopted by the Clinical and Laboratory Standards Institute (CLSI) to compare the susceptibility of 184 isolates of 11 Candida species to fluconazole, voriconazole, micafungin, caspofungin, amphotericin B, and flucytosine. In Candida albicans, the categorical agreement (CA) was 79.2%, 91.7%, 95.8%, and 95.8% for fluconazole, voriconazole, micafungin, and caspofungin, respectively. About 12.5% and 4.2% of very major errors were detected for fluconazole and voriconazole, respectively. C. glabrata showed excellent essential agreements (EAs) (>90%) for azoles but different MIC distributions for fluconazole and caspofungin. The CA between BMD fluconazole MICs and YS08 voriconazole MICs by the method-specific clinical breakpoint (CBP) was 90% in C. glabrata. Over 80% of C. glabrata and C. krusei isolates identified as micafungin-susceptible were labeled intermediate or resistant to caspofungin in YS08. In C. parapsilosis, 5.3% of very major errors and 10.5% of minor errors were found, whereas 33.3% of minor errors were observed in C. tropicalis for fluconazole. For C. tropicalis, 13 (61.9%) non-wild type (WT) isolates of fluconazole and 7 (33.3%) non-WTs of voriconazole were classified in YS08 as WT. For C. auris, the EAs were 93.3%, 100%, 82.2%, 97.8%, and 97.8% for fluconazole, voriconazole, micafungin, caspofungin, and amphotericin B, respectively. YS08 showed comparable results to the BMD. However, considering the lower YS08 fluconazole MIC results compared with BMD in Candida species and YS08 caspofungin results in C. glabrata and C. krusei, improvements are needed. IMPORTANCE The new Vitek 2 AST-YS08 (YS08) card has been updated to reflect the recently revised Clinical and Laboratory Standards Institute (CLSI) guideline. In this study, antifungal drug susceptibility tests were performed using the YS08 card and compared with the CLSI broth microdilution (BMD) method. In conclusion, YS08 showed similar results to BMD, including with C. auris. However, about 12.5% and 4.2% of major errors were detected for fluconazole and voriconazole, respectively, in C. albicans. More than 80% of C. glabrata and C. krusei isolates identified as susceptible to micafungin were labeled moderate or resistant to caspofungin in YS08. The categorical agreement between BMD fluconazole MICs and YS08 voriconazole MICs was 90% by the method-specific CBP of voriconazole, 80% by the current epidemiological cutoff value (ECV) (0.25 µg/mL) of voriconazole, and 85% by the previous ECV (0.5 µg/mL) of voriconazole. Further improvements in YS08 for the detection of fluconazole and echinocandin resistance are thus needed.