A Novel Single-Stranded RNA-Based Adjuvant Improves the Immunogenicity of the SARS-CoV-2 Recombinant Protein Vaccine

The research and development (R&D) of novel adjuvants is an effective measure for improving the immunogenicity of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) recombinant protein vaccine. Toward this end, we designed a novel single-stranded RNA-based adjuvant, L2, from the SARS-CoV-2 prototype genome. L2 could initiate retinoic acid-inducible gene-I signaling pathways to effectively activate the innate immunity. ZF2001, an aluminum hydroxide (Al) adjuvanted SARS-CoV-2 recombinant receptor binding domain (RBD) subunit vaccine with emergency use authorization in China, was used for comparison. L2, with adjuvant compatibility with RBD, elevated the antibody response to a level more than that achieved with Al, CpG 7909, or poly(I:C) as adjuvants in mice. L2 plus Al with composite adjuvant compatibility with RBD markedly improved the immunogenicity of ZF2001; in particular, neutralizing antibody titers increased by about 44-fold for Omicron, and the combination also induced higher levels of antibodies than CpG 7909/poly(I:C) plus Al in mice. Moreover, L2 and L2 plus Al effectively improved the Th1 immune response, rather than the Th2 immune response. Taken together, L2, used as an adjuvant, enhanced the immune response of the SARS-CoV-2 recombinant RBD protein vaccine in mice. These findings should provide a basis for the R&D of novel RNA-based adjuvants.     

Performance of Remsima® Monitor Drug Level versus RIDASCREEN IFX Monitoring in therapeutic drug monitoring of infliximab in patients with inflammatory bowel disease: A study of diagnostic accuracy

Therapeutic drug monitoring (TDM) is effective in optimizing the efficacy of infliximab in patients with inflammatory bowel disease (IBD). An affordable way of monitoring is in high demand. This study evaluated the analytical and clinical performances of the newly available Remsima monitor kits and compared them with the established enzyme-linked immunosorbent assay kits. The trough level of infliximab in patients with IBD treated with an infliximab originator (Remicade) or biosimilar compounds (Remsima and Remaloce) was measured using a Remsima® Monitor Drug Level (Remsima) kit at the Samsung Medical Center, Seoul, Korea. Twenty-six plasma samples were collected immediately before the infusion of infliximab from 18 patients with IBD (Remicade, n = 8; Remsima, n = 6; and Remaloce, n = 4). The intra-assay intraclass correlation coefficient (ICC) of the RIDA and Remsima kits was 0.951 (95% CI = 0.908–0.976) and 0.990 (95% CI = 0.981–0.995). The inter-assay ICC of infliximab trough level between the RIDA and Remsima kits was very high (R = 0.971; 95% CI = 0.935–0.987), and the mean difference between the kits was 1.458 (95% limits of agreement = −3.302 to 6.219). The intra- and inter-assay reliabilities of all types of infliximab did not show significant differences. Qualitative stratification revealed substantial similarities between the kits (weighted kappa = 0.798). This study indicated that the Remsima kit was reproducible and highly correlated with the RIDA kit.     

Endoscopist-Driven Sedation Practices in South Korea: Re-evaluation Considering the Nationwide Survey in 2019

Background/AimsThis study aimed to determine changes in endoscopist-driven sedation practices 5 years after the first nationwide survey in 2014 by the Korean Society of Gastrointestinal Endoscopy (KSGE).MethodsA 59-item survey covering current practices was electronically mailed to all members of the KSGE in 2019.ResultsIn total, 955 (12.8%) out of 7,486 questionnaires were returned. A total of 738 (77.7%) out of 955 respondents attended dedicated sedation education programs. The American Society of Anesthesiologists class was recorded by 464 (51.2%) out of 907 respondents. The recording rate was higher in respondents who completed sedation education (p=0.014) and worked in general or tertiary hospitals (p<0.001). Compared to that reported in the previous survey, the reported use of propofol was higher in 2019. The respondents had higher satisfaction scores for propofol-based sedation compared with midazolam monotherapy (p<0.001). The rates of oxygen supplementation (p<0.001) and oxygen saturation level monitoring (p<0.001) during sedative endoscopy were higher in 2019 than in the previous survey. A total of 876 (98.4%) out of 890 respondents reported a separate recovery bay, and 615 (70.5%) out of 872 respondents reported that personnel were assigned solely to the recovery bay.ConclusionsEndoscopist-driven sedation and monitoring practices in 2019 were significantly different than those in 2014. The respondents favored propofol-based sedation and utilized oxygen supplementation and monitoring of O₂ saturation more frequently in 2019 than in 2014. (Gut Liver, Published online August 1, 2022)     

Mean platelet volume is the most valuable hematologic parameter in differentiating testicular torsion from epididymitis within the golden time

BackgroundWe aimed to assess the diagnostic value of hematologic parameters in the differential diagnosis of testicular torsion and epididymitis within and after the golden time.MethodsWe retrospectively reviewed the records of 250 patients aged <25 years who were diagnosed with epididymitis (n=119) or testicular torsion (n=131). The characteristics and hematologic parameters of patients in the two groups were analyzed. Receiver operating characteristic (ROC) curves were used to assess the validity of hematologic parameters as differential diagnostic tools with respect to the golden time (defined as 6 h of symptom duration). Further, we evaluated the predictive factors associated with orchiectomy in patients with testicular torsion.ResultsThe mean patient age was 14.4 years. Among patients with testicular torsion, 91.40% (53 of 58) underwent detorsion and orchiopexy within the golden time, whereas only 27.40% (20 of 73) of the affected testes were preserved after the golden time. Within the golden time, mean platelet volume (MPV) seemed to be the most valuable hematologic parameter [area under the curve (AUC) 0.855, 95% confidence interval (CI): 0.778–0.932]. In a multivariate analysis, symptom duration (symptoms beyond the golden time) was associated with orchiectomy in patients with testicular torsion.ConclusionsMPV showed the greatest hematologic value in the early stage of testicular torsion and epididymitis, suggesting its potential use for the differential diagnosis of these two conditions within the golden time.     

Relationship between predisposing and facilitating factors: Does it influence the risk of developing peri‐operative pressure injuries?

This study examined the relationship between the personal predisposing factors of patients and the severity of pressure injuries (PIs) developed during surgery. This retrospective cohort study collected 439 cases of peri‐operative PIs. Using binary logistic regression to identify the variables associated with PI severity, the effects of interactions between associated variables were then tested. The results of this study revealed that among the personal predisposing factors, only higher patient age (P = .001) and higher body mass index (P < .001) posed a greater risk of stage 2 PIs or higher. Among the surgery‐related facilitating factors, only patients who were placed in the prone position during surgery and patients who lost ≥1000 mL of blood during surgery were at greater risk of stage 2 PIs or higher, compared, respectively, to those placed in the supine position and those who lost ≤100 mL of blood. Furthermore, the amount of blood lost during surgery moderated the influence of age on PI severity. For elderly patients who are expected to lose a large blood volume during surgery or lose an immeasurable amount of blood due to the use of cardiopulmonary bypass, taking more precautionary measures to prevent PIs is recommended.     

Silybin suppresses ovarian cancer cell proliferation by inhibiting isocitrate dehydrogenase 1 activity

Metabolic reprogramming is a sign of malignant tumors, and targeting the metabolism of tumor cells has become a promising therapeutic approach. Here, we report that Silybin (a nontoxic flavonoid commonly used for liver protection) exhibits prominent anti‐tumor effects on human ovarian cancer cells. Treatment of an ovarian cancer cell line with Silybin interfered with glutamine metabolism and the tricarboxylic acid cycle. We applied the drug affinity responsive target stability approach to show that Silybin binds to isocitrate dehydrogenase 1 (IDH1). This combination leads to reduced phosphorylation of IDH1 and inhibits enzyme activity. IDH1 dysfunction significantly increases the ratio of NADP/NADPH in the cell, causing an increase in reactive oxygen species generation. Immunohistochemistry demonstrated that IDH1 was increased in ovarian cancer samples compared with normal para‐tumoral tissues. Xenograft murine experiments indicated that Silybin administered orally suppressed the growth of the tumor formed by ovarian cancer cells. In combination, our data strongly suggest that Silybin targets IDH1 in ovarian cancer cells and may be a novel treatment candidate.     

Development and validation of a survival prediction model for 113,239 patients with colon cancer: a retrospective cohort study

BackgroundColon cancer (CC) is the third most commonly diagnosed malignant tumor and remains the second leading cause of cancer-related deaths worldwide. However, the risk assessment of poor prognosis of CC is limited in previous studies. This study aimed to develop a predictive nomogram for the survival of CC patients.MethodsIn this retrospective cohort study, 113,239 CC patients from the Surveillance, Epidemiology, and End Results (SEER) database were randomly divided into training (n=56,619) and testing (n=56,620) sets with a ratio of 1:1. Demographic, clinical data and survival status of patients were extracted. The outcomes were 3- and 5-year survival of CC. Univariate and multivariate Cox regression analyses were used to screen the predictors to develop the predictive nomogram. Internal validation and stratified analyses were further assessed the nomogram. The C-index and area under the curve (AUC) were calculated to estimate the model’s predictive capacity, and calibration curves were adopted to estimate the model fit.ResultsTotally 38,522 (34.02%) patients died during the 5-year follow-up. The nomogram incorporated variables associated with the prognosis of CC patients, including age, gender, marital status, insurance status, tumor grade, stage (T/N/M), surgery, and number of nodes examined, with a C-index of 0.775 in the training set and 0.774 in the testing set. The AUCs of the nomogram for the 3- and 5-year survival prediction in the training set were 0.817 and 0.808, with the sensitivity of 0.688 and 0.716, and the specificity of 0.785 and 0.740, respectively. Similar results were found in the testing set. The C-index of the predictive nomogram for male, female, White, Black, and other races was 0.769, 0.779, 0.773, 0.770, and 0.770, respectively. The calibration curves for the nomogram in the above five cohorts showed a good agreement between actual and predicted values.ConclusionsThe nomogram may exhibit a certain predictive performance based on the SEER database, which may provide individual survival predictions for CC patients.