Development and Characterization of Synthetic Norovirus RNA for Use in Molecular Detection Methods

Background: Reference materials are essential for the quality assurance of molecular detection methods. We developed and characterized synthetic norovirus GI and GII RNA reference materials. Methods: Norovirus GI and GII RNA sequences including the ORF1-ORF2 junction region were designed based on 1,495 reported norovirus sequences and synthesized via plasmid preparation and in vitro transcription. The synthetic norovirus GI and GII RNAs were evaluated using six commercial norovirus detection kits used in Korea and subjected to homogeneity and stability analyses. A multicenter study involving five laboratories and using four commercial real-time PCR norovirus detection assays was conducted for synthetic norovirus RNA characterization and uncertainty measurements. Results: The synthetic norovirus GI and GII RNAs were positively detected using the six commercial norovirus detection kits and were homogeneous and stable for one year when stored at -20°C or -70°C. All data from the five laboratories were within a range of 1.0 log copies/μL difference for each RNA, and the overall mean concentrations for norovirus GI and GII RNAs were 7.90 log copies/μL and 6.96 log copies/μL, respectively. Conclusions: The synthetic norovirus GI and GII RNAs are adequate for quality control based on commercial molecular detection reagents for noroviruses with high sequence variability. The synthetic RNAs can be used as reference materials in norovirus molecular detection methods.ope

Digital cognitive behavioral therapy for insomnia on depression and anxiety: a systematic review and meta-analysis

Despite research into the development of digital cognitive behavioral therapy for insomnia (dCBT-I), research into the outcomes of dCBT-I on insomnia and the associated clinical conditions of depression and anxiety have been limited. The PubMed, PsycINFO (Ovid), Embase, and Cochrane databases were searched for randomized controlled trials (RCTs) on adult patients with insomnia also having reported measures of depressive or anxiety symptoms. In total, 2504 articles were identified after duplicate removal, and 22 RCTs were included in the final meta-analysis. At the post-treatment assessment, the dCBT-I group had a small to moderate effect in alleviating depressive (standardized mean difference (SMD) = -0.42; 95% CI: -0.56, -0.28; p < 0.001; k = 21) and anxiety symptoms (SMD = -0.29; 95% CI: -0.40, -0.19; p < 0.001; k = 18), but had a large effect on sleep outcome measures (SMD = -0.76; 95% CI: -0.95, -0.57; p < 0.001; k = 22). When considering treatment adherence, the treatment effects of those in the high adherent groups identified a more robust outcome, showing greater effect sizes than those in the low adherent groups for depression, anxiety, and sleep outcomes. Furthermore, additional subgroup analysis on studies that have used the fully automated dCBT-I treatment without the support of human therapists reported significant treatment effects for depression, anxiety, and sleep outcomes. The results demonstrated that digital intervention for insomnia yielded significant effects on alleviating depressive and anxiety symptoms as well as insomnia symptoms. Specifically, the study demonstrated significant effects on the above symptoms when considering treatment adherence and implementing fully automated dCBT-I.ope

The Expression of Programmed Death-Ligand 1 on Immune Cells Is Related to a Better Prognosis in Biliary Tract Cancer

Background/Aims: Programmed death-ligand 1 (PD-L1) expression in tumor cells is associated with a poor biliary tract cancer (BTC) prognosis; tumor-infiltrating immune cells in the tumor microenvironment are associated with a better prognosis. The effect of PD-L1 expression on immune cells on survival is unclear. We investigated the relationship between PD-L1 expression in immune cells and BTC prognosis. Methods: PD-L1 expression was evaluated using an anti-PD-L1 22C3 mouse monoclonal primary antibody, and its relationships with clinical characteristics and prognosis were analyzed using the Cox proportional hazard model to investigate the prognostic performance of PD-L1 in BTC. Results: Among 144 analyzed cases, patients with positive PD-L1 expression in tumor cells and negative PD-L1 expression in immune cells showed poorer overall survival rates than those exhibiting other expressions (tumor cells: hazard ratio [HR]=1.023, p<0.001; immune cells: HR=0.983, p=0.021). PD-L1 expression in tumor cells was an independent predictor of poor overall survival (HR=1.024, p<0.001). In contrast, PD-L1 expression in immune cells was a predictive marker of good prognosis (HR=0.983, p=0.018). Conclusions: PD-L1 expression in immune cells may be used as an independent factor to evaluate the prognosis of patients with BTC. (Gut Liver, Published online December 13, 2022)ope

Utility of combining PIVKA-II and AFP in the surveillance and monitoring of hepatocellular carcinoma in the Asia-Pacific region

Even though the combined use of ultrasound (US) and alpha-fetoprotein (AFP) is recommended for the surveillance of hepatocellular carcinoma (HCC), the utilization of AFP has its challenges, including accuracy dependent on its cut-off levels, degree of liver necroinflammation, and etiology of liver disease. Though various studies have demonstrated the utility of protein induced by vitamin K absence II (PIVKA-II) in surveillance, treatment monitoring, and predicting recurrence, it is still not recommended as a routine biomarker test. A panel of 17 experts from Asia-Pacific, gathered to discuss and reach a consensus on the clinical usefulness and value of PIVKA-II for the surveillance and treatment monitoring of HCC, based on six predetermined statements. The experts agreed that PIVKA-II was valuable in the detection of HCC in AFP-negative patients, and could potentially benefit detection of early HCC in combination with AFP. PIVKA-II is clinically useful for monitoring curative and intra-arterial locoregional treatments, outcomes, and recurrence, and could potentially predict microvascular invasion risk and facilitate patient selection for liver transplant. However, combining PIVKA-II with US and AFP for HCC surveillance, including small HCC, still requires more evidence, whilst its role in detecting AFP-negative HCC will potentially increase as more patients are treated for hepatitis-related HCC. PIVKA-II in combination with AFP and US has a clinical role in the Asia-Pacific region for surveillance. However, implementation of PIVKA-II in the region will have some challenges, such as requiring standardization of cut-off values, its cost-effectiveness and improving awareness among healthcare providers.ope

Transcriptome profiling of skeletal muscles from Korean patients with Bethlem myopathy

Bethlem myopathy is one of the collagens VI-related muscular dystrophies caused by mutations in the collagen VI genes. The study was designed to analyze the gene expression profiles in the skeletal muscle of patients with Bethlem myopathy. Six skeletal muscle samples from 3 patients with Bethlem myopathy and 3 control subjects were analyzed by RNA-sequencing. 187 transcripts were significantly differentially expressed, with 157 upregulated and 30 downregulated transcripts in the Bethlem group. Particularly, 1 (microRNA-133b) was considerably upregulated, and 4 long intergenic non-protein coding RNAs, LINC01854, MBNL1-AS1, LINC02609, and LOC728975, were significantly downregulated. We categorized differentially expressed gene using Gene Ontology and showed that Bethlem myopathy is strongly associated with the organization of extracellular matrix (ECM). Kyoto Encyclopedia of Genes and Genomes pathway enrichment reflected themes with significant enrichment of the ECM-receptor interaction (hsa04512), complement and coagulation cascades (hsa04610), and focal adhesion (hsa04510). We confirmed that Bethlem myopathy is strongly associated with the organization of ECM and the wound healing process. Our results demonstrate transcriptome profiling of Bethlem myopathy, and provide new insights into the path mechanism of Bethlem myopathy associated with non-protein coding RNAs. © 2023 Lippincott Williams and Wilkins. All rights reserved.ope

Validation of original, alternative, and updated alternative fistula risk scores after open and minimally invasive pancreatoduodenectomy in an Asian patient cohort

Background: This study aimed to validate and compare the performance of the original fistula risk scores (o-FRS), alternative (a-FRS), and updated alternative FRS (ua-FRS) after open pancreatoduodenectomy (OPD) and laparoscopic pancreatoduodenectomy (LPD) in an Asian patient cohort. Methods: Data of 597 consecutive patients who underwent PD (305 OPD, 274 LPD) were collected from two tertiary centers. Model performance was assessed using the area under the receiver operating curve (AUC). Results: The overall AUC values of o-FRS, a-FRS, and ua-FRS were 0.67, 0.69, and 0.68, respectively, which were lower than those of the Western validation. Three FRS systems had similar AUC values in the overall and OPD groups, whereas ua-FRS had a higher AUC than o-FRS in the LPD group. The accuracy of ua-FRS (47.2%) was higher than that of o-FRS (39.0%) and a-FRS (19.5%) overall, but low specificity and low positive predictive value were observed regardless of the operative type across the three FRS systems. In the multivariate analysis, pathology, estimated blood loss, and body mass index were not independent risk factors for CR-POPF in the OPD and LPD groups. Conclusions: Current FRS systems have some limitations, including a relatively lower performance in an Asian cohort, low positive predictive values, and inclusion of insignificant risk factors.restrictio

Practical role of preoperative echocardiography in low-risk non-cardiac surgery

Background: Due to increased needs to reduce non-fatal as well as fatal cardiac events, preoperative echocardiography remains part of routine clinical practice in many hospitals. Data on the role of preoperative echocardiography in low-risk non-cardiac surgery (NCS) other than ambulatory surgeries do not exist. We aimed to investigate the role of preoperative echocardiography in predicting postoperative adverse cardiovascular events (CVEs) in asymptomatic patients undergoing low-risk NCS. Methods: The study population was derived from a retrospective cohort of 1,264 patients who underwent elective low-risk surgery at three tertiary hospitals from June 1, 2021, to June 30, 2021. Breast, distal bone, thyroid, and transurethral surgeries were included. Preoperative examination data including electrocardiography, chest radiography, and echocardiography were collected. The primary outcome was a composite of postoperative adverse CVEs including all-cause death, myocardial infarction, cerebrovascular events, newly diagnosed or acutely decompensated heart failure (HF), lethal arrhythmia such as sustained ventricular tachycardia/fibrillation, and new-onset atrial fibrillation within 30 days after the index surgery. Results: Preoperative echocardiography was performed in 503 patients (39.8%), most frequently in patients with breast surgery (73.5%), followed by transurethral (37.7%), distal bone (21.6%), and thyroid surgeries (11.9%). Abnormal findings were observed in 5.0% of patients with preoperative echocardiography. Postoperative adverse CVEs occurred in 10 (0.79%) patients. Although a history of previous HF was an independent predictor of postoperative CVE occurrence (adjusted odds ratio, aOR: 17.98; 95% confidence interval, CI: 1.21–266.71, P = 0.036), preoperative echocardiography did not significantly predict CVE in multivariate analysis (P = 0.097). However, in patients who underwent preoperative echocardiography, the presence of abnormal echocardiographic findings was independently associated with development of CVE after NCS (aOR: 23.93; 95% CI: 1.2.28–250.76, P = 0.008). In particular, the presence of wall motion abnormality was a strong predictor of postoperative adverse CVE. Conclusion: In real-world clinical practice, preoperative echocardiography was performed in substantial number of patients with potential cardiac risk even in low-risk NCS, and abnormal findings were independently associated with postoperative CVE. Future studies should identify patients undergoing low-risk NCS for whom preoperative echocardiography would be helpful to predict adverse CVE.ope

Feasibility of the virtual reality-based assessments in patients with panic disorder

Introduction: Recurrences and diagnostic instability of panic disorder (PD) are common and have a negative effect on its long-term course. Developing a novel assessment tool for anxiety that can be used in a multimodal approach may improve these problems in panic disorder patients. This study assessed the feasibility of virtual reality-based assessment in panic disorder (VRA-PD). Methods: Twenty-five patients with PD (ANX group) and 28 healthy adults (CON group) participated in the study. VRA-PD consisted of four modules based on the key components of cognitive behavior therapy for an anxiety disorder: “Baseline evaluation module” (M0), “Daily environment exposure module” (M1), “Relaxation module” (M2), and “Interoceptive exposure module” (M3). Multiple evaluations, including self-rating anxiety scores (AS) and physiological responses [heart rate variability (HRV) index], were performed in three steps at M1, M2, and M3, and once at M0. Comparisons between patients with PD and healthy controls, factor analysis of variables in VRA-PD, changes in responses within modules, and correlation analysis between variables in VRA-PD and anxiety symptoms assessed by psychological scales were performed. Results : All participants completed the VRA-PD without discontinuation. The ANX group reported significantly higher AS for all steps and a smaller HRV index in M1 (steps 1 and 2) and M2 (step 1). Repeated-measures analysis of covariance (ANCOVA) revealed significant interaction effects for AS in M1 (F = 4.09, p = 0.02) and M2 (F = 4.20, p = 0.02), and HRV index in M2 (F = 16.22, p < 0.001) and M3 (F = 21.22, p = 0.02). The HRV index only indicated a good model fit for the three-factor model, reflecting the construct of the VRA-PD. Both AS and HRV indexes were significantly correlated with anxiety and depression symptoms. Discussion : The current study provides preliminary evidence that the VRA-PD could be a valid anxiety behavior assessment tool.ope

Effect of Preoperative Administration of Intravenous Ferric Carboxymaltose in Patients with Iron Deficiency Anemia after Off-Pump Coronary Artery Bypass Grafting: A Randomized Controlled Trial

Patients scheduled for cardiac surgery often have anemia and iron deficiency. We investigated the effect of the preoperative administration of intravenous ferric carboxymaltose (IVFC) in patients with iron deficiency anemia (IDA) who were due to undergo off-pump coronary artery bypass grafting (OPCAB). Patients who were due to undergo elective OPCAB between February 2019 and March 2022 who had IDA (n = 86) were included in this single center, randomized, parallel-group controlled study. The participants were randomly assigned (1:1) to receive either IVFC or placebo treatment. Postoperative hematologic parameters [hemoglobin (Hb), hematocrit, serum iron concentration, total iron-binding capacity, transferrin saturation, transferrin concentration, and ferritin concentration] and the changes in these parameters during the follow-up period were the primary and secondary outcomes, respectively. The tertiary endpoints were early clinical outcomes, such as the volume of mediastinal drainage and the need for blood transfusions. IVFC treatment significantly reduced the need for red blood cell (RBC) and platelet transfusions. Despite receiving fewer RBC transfusions, patients in the treatment group had higher levels of Hb, hematocrit, and serum iron and ferritin concentrations during weeks 1 and 12 after surgery. No serious adverse events occurred during the study period. Preoperative IVFC treatment in patients with IDA undergoing OPCAB improved the values of the hematologic parameters and iron bioavailability. Therefore, is a useful strategy for stabilizing patients prior to OPCAB.ope

Statin use is associated with better post-operative prognosis among patients with hepatitis B virus-related hepatocellular carcinoma

Background: The high postoperative recurrence rate of hepatocellular carcinoma (HCC) is a significant challenge. Patient metabolic factors are potential disease modifiers and should be examined as risk factors for postoperative prognosis. Here, we assessed the association between long-term statin use and HCC recurrence after surgical resection of hepatitis B virus (HBV)-related HCC.Methods: Patients who initially underwent curative resection for HBV-related HCC between 2005 and 2015 were recruited and followed up until December 2019. Patients were classified into statin user and non-statin user groups based on whether or not they had been prescribed statins for >= 2 years. The primary outcome was HCC recurrence, and the secondary outcome was liver-related mortality. The cumulative incidence by statin use was estimated using the Kaplan-Meier method and compared using the log-rank test. Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using multivariable Cox regression.Results: Among 5653 patients with a median 6.1 years of follow-up, HCC recurrence and liver-related mortality occurred in 1603 and 316 patients, respectively. The 5-year cumulative incidence of HCC recurrence in the statin user group (15.9%) was significantly lower than that in the non-user group (21.3%; p = .019). From multivariable Cox regression analysis, statin use was significantly associated with a reduced risk of HCC recurrence (aHR 0.77, 95% CI: 0.61-0.98; p = .035) and liver-related mortality (aHR 0.48, 95% CI: 0.25-0.90; p = .023).Conclusion: Long-term statin use was significantly associated with reduced risk of HCC recurrence and liver-related mortality after curative resection of HBV-related HCC.restrictio