Intracorporeal versus extracorporeal anastomosis in minimally invasive right hemicolectomy: systematic review and meta-analysis of randomized controlled trials.

Purpose: Compared with extracorporeal anastomosis (ECA), intracorporeal anastomosis (ICA) is expected to provide some benefits, including a shorter operation time and less intraoperative bleeding. Nevertheless, the benefits of ICA have mainly been evaluated in nonrandomized studies. Owing to the recent update of randomized controlled trials (RCTs) for minimally invasive surgery (MIS) of right hemicolectomy (RHC), the need to measure the actual effect by synthesizing the outcomes of these studies has emerged. Methods: We performed a comprehensive search of the PubMed, Embase, and Cochrane databases (from inception to January 30, 2023) for studies that applied ICA and ECA for RHC with MIS. We included 7 RCTs. The operation time, intraoperative blood loss, conversion rate, length of incision, and postoperative outcomes such as ileus, anastomosis leakage, length of hospitalization, and postoperative pain were compared between ICA and ECA. Results: A total of 740 patients were included in the study. Among them, 377 and 373 underwent ICA and ECA, respectively. There were significant differences in age (P = 0.003) and incision type (P < 0.001) between ICA and ECA. ICA was associated with a significantly longer operation time (P = 0.033). Although the postoperative pain associated with ICA was significantly lower than that associated with ECA on postoperative day 2 (POD 2) (P = 0.003), it was not different on POD 3 between the groups. Other perioperative outcomes were similar between the 2 groups. Conclusion: In this meta-analysis, ICA did not significantly improve short-term outcomes compared to ECA; other advantages to overcome ICA's longer operation time are not clear.

COVID-19 spike polypeptide vaccine reduces the pathogenesis and viral infection in a mouse model of SARS-CoV-2.

The SARS-CoV-2 coronavirus, which causes a respiratory disease called COVID-19, has been declared a pandemic by the World Health Organization (WHO) and is still ongoing. Vaccination is the most important strategy to end the pandemic. Several vaccines have been approved, as evidenced by the ongoing global pandemic, but the pandemic is far from over and no fully effective vaccine is yet available. One of the most critical steps in vaccine development is the selection of appropriate antigens and their proper introduction into the immune system. Therefore, in this study, we developed and evaluated two proposed vaccines composed of single and multiple SARS-CoV-2 polypeptides derived from the spike protein, namely, vaccine A and vaccine B, respectively. The polypeptides were validated by the sera of COVID-19-vaccinated individuals and/or naturally infected COVID-19 patients to shortlist the starting pool of antigens followed by in vivo vaccination to hACE2 transgenic mice. The spike multiple polypeptide vaccine (vaccine B) was more potent to reduce the pathogenesis of organs, resulting in higher protection against the SARS-CoV-2 infection.

Establishment of multicenter COVID-19 therapeutics preclinical test system in Republic of Korea.

Throughout the recent COVID-19 pandemic, South Korea led national efforts to develop vaccines and therapeutics for SARS-CoV-2. The project proceeded as follows: 1) evaluation system setup (including Animal Biosafety Level 3 (ABSL3) facility alliance, standardized nonclinical evaluation protocol, and laboratory information management system), 2) application (including committee review and selection), and 3) evaluation (including expert judgment and reporting). After receiving 101 applications, the selection committee reviewed pharmacokinetics, toxicity, and efficacy data and selected 32 final candidates. In the nonclinical efficacy test, we used golden Syrian hamsters and human angiotensin-converting enzyme 2 transgenic mice under a cytokeratin 18 promoter to evaluate mortality, clinical signs, body weight, viral titer, neutralizing antibody presence, and histopathology. These data indicated eight new drugs and one repositioned drug having significant efficacy for COVID-19. Three vaccine and four antiviral drugs exerted significant protective activities against SARS-CoV-2 pathogenesis. Additionally, two anti-inflammatory drugs showed therapeutic effects on lung lesions and weight loss through their mechanism of action but did not affect viral replication. Along with systematic verification of COVID-19 animal models through large-scale studies, our findings suggest that ABSL3 multicenter alliance and nonclinical evaluation protocol standardization can promote reliable efficacy testing against COVID-19, thus expediting medical product development.

Short-term carcinogenicity study of N-methyl-N-nitrosourea in FVB-Trp53 heterozygous mice.

Carcinogenicity tests predict the tumorigenic potential of various substances in the human body by studying tumor induction in experimental animals. There is a need for studies that explore the use of FVB/N-Trp53em2Hwl/Korl (FVB-Trp53+/-) mice, created by TALEN-mediated gene targeting in Korea, in carcinogenicity tests. This study was performed to determine whether FVB-Trp53+/- mice are a suitable model for short-term carcinogenicity studies. To compare the carcinogenicity at different concentrations, 25, 50, and 75 mg/kg of N-methyl-N-nitrosourea (MNU), a known carcinogen, were administered intraperitoneally to FVB-Trp53+/- and wild-type male mice. After 26 weeks, the survival rate was significantly reduced in FVB-Trp53+/- mice compared to the wild-type mice in the 50 and 75 mg/kg groups. The incidence of thymic malignant lymphoma (TML) in the 50 and 75 mg/kg groups was 54.2 and 59.1% in FVB-Trp53+/- male mice, respectively. TML metastasized to the lungs, spleen, lymph nodes, liver, kidney, and heart in FVB-Trp53+/- male mice. Furthermore, the incidence of primary lung tumors, such as adenomas and adenocarcinomas, was 65.4, 62.5, and 45.4% in the FVB-Trp53+/- mice of the 25, 50, and 75 mg/kg groups, respectively. The main tumor types in FVB-Trp53+/- mice were TML and primary lung tumors, regardless of the dose of MNU administered. These results suggest that systemic tumors may result from malfunctions in the p53 gene and pathway, which is an important factor in the pathogenesis of human cancers. Therefore, FVB-Trp53 heterozygous mice are suitable for short-term carcinogenicity tests using positive carcinogens, and that the best result using MNU, a positive carcinogen, might have a single dose of 50 mg/kg.

Development of transgenic models susceptible and resistant to SARS-CoV-2 infection in FVB background mice.

Coronavirus disease (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), is currently spreading globally. To overcome the COVID-19 pandemic, preclinical evaluations of vaccines and therapeutics using K18-hACE2 and CAG-hACE2 transgenic mice are ongoing. However, a comparative study on SARS-CoV-2 infection between K18-hACE2 and CAG-hACE2 mice has not been published. In this study, we compared the susceptibility and resistance to SARS-CoV-2 infection between two strains of transgenic mice, which were generated in FVB background mice. K18-hACE2 mice exhibited severe weight loss with definitive lethality, but CAG-hACE2 mice survived; and differences were observed in the lung, spleen, cerebrum, cerebellum, and small intestine. A higher viral titer was detected in the lungs, cerebrums, and cerebellums of K18-hACE2 mice than in the lungs of CAG-hACE2 mice. Severe pneumonia was observed in histopathological findings in K18-hACE2, and mild pneumonia was observed in CAG-hACE2. Atrophy of the splenic white pulp and reduction of spleen weight was observed, and hyperplasia of goblet cells with villi atrophy of the small intestine was observed in K18-hACE2 mice compared to CAG-hACE2 mice. These results indicate that K18-hACE2 mice are relatively susceptible to SARS-CoV-2 and that CAG-hACE2 mice are resistant to SARS-CoV-2. Based on these lineage-specific sensitivities, we suggest that K18-hACE2 mouse is suitable for highly susceptible model of SARS-CoV-2, and CAG-hACE2 mouse is suitable for mild susceptible model of SARS-CoV-2 infection.

Laboratory information management system for COVID-19 non-clinical efficacy trial data.

BACKGROUND: As the number of large-scale studies involving multiple organizations producing data has steadily increased, an integrated system for a common interoperable format is needed. In response to the coronavirus disease 2019 (COVID-19) pandemic, a number of global efforts are underway to develop vaccines and therapeutics. We are therefore observing an explosion in the proliferation of COVID-19 data, and interoperability is highly requested in multiple institutions participating simultaneously in COVID-19 pandemic research. RESULTS: In this study, a laboratory information management system (LIMS) approach has been adopted to systemically manage various COVID-19 non-clinical trial data, including mortality, clinical signs, body weight, body temperature, organ weights, viral titer (viral replication and viral RNA), and multiorgan histopathology, from multiple institutions based on a web interface. The main aim of the implemented system is to integrate, standardize, and organize data collected from laboratories in multiple institutes for COVID-19 non-clinical efficacy testings. Six animal biosafety level 3 institutions proved the feasibility of our system. Substantial benefits were shown by maximizing collaborative high-quality non-clinical research. CONCLUSIONS: This LIMS platform can be used for future outbreaks, leading to accelerated medical product development through the systematic management of extensive data from non-clinical animal studies.

Comparison of long-term outcomes of endoscopic submucosal dissection and surgery for undifferentiated-type early gastric cancer meeting the expanded criteria: a systematic review and meta-analysis.

BACKGROUND: There have been concerns over the long-term outcomes of endoscopic submucosal dissection (ESD) for undifferentiated-type early gastric cancer (UD EGC). We aimed to compare the long-term outcomes of ESD and surgery for patients with UD EGC. METHODS: We searched PubMed, Embase, and Cochrane Library databases through March 2021 to identify studies that compared the long-term outcomes of ESD and surgery for UD EGC meeting expanded criteria for curative resection. The risk of bias was assessed with the Cochrane tool for non-randomized studies. The risk ratio (RR) was estimated using a fixed-effect model. RESULTS: Overall, 1863 patients from five retrospective cohort studies, including 908 patients with propensity score matching (PSM), were eligible for meta-analysis. ESD was associated with inferior overall survival (OS) compared to surgery in the overall cohort (RR 2.11; 95% CI 1.26-3.55) but not in the PSM cohort (RR 1.18; 95% CI 0.60-2.32). In the PSM cohort, ESD had a lower disease-free survival (DFS) (RR 2.49; 95% CI 1.42-4.35) and higher recurrence (RR 12.61; 95% CI 3.43-46.37), gastric recurrence (RR 11.25; 95% CI 3.06-41.40), and extragastric recurrence (RR 4.23; 95% CI 0.47-37.93). Recurrence outcomes were similar between the overall and PSM cohorts. Disease-specific survival was not significantly different between the two groups in both the overall and PSM cohorts. CONCLUSION: Although OS after curative ESD for UD EGC was not different from that after surgery in the PSM cohort, DFS and recurrence were inferior after ESD. Limitations included a lack of randomized trials. Further prospective studies comparing the long-term outcomes of ESD and surgery for UD EGC are needed (PROSPERO CRD 42021237097).

Detecting serum galactomannan to diagnose acute invasive Aspergillus sinusitis: a meta-analysis.

PURPOSE: The serum galactomannan test has been used for diagnosing acute invasive fungal sinusitis (AIFS), especially invasive Aspergillus. We aimed to assess the accuracy of the test to diagnose acute invasive Aspergillus sinusitis (AIAS). METHODS: We searched all relevant articles published in PubMed, Embase, the Cochrane Library, and Web of Science databases up until September 14, 2020. The available data for serum galactomannan test to diagnose AIAS from selected studies were assessed. The diagnostic odds ratio (DOR), summary receiver operating characteristics (SROC), sensitivity, specificity, positive likelihood ratio (PLR), and negative likelihood ratio (NLR) were estimated. Additionally, we analysed four studies with a cut-off value of 0.5. RESULTS: Five eligible articles were selected in this study. The total number of enrolled patients was 118, and 62 patients had confirmed AIAS. Among these 62 patients, the summary estimates of the serum galactomannan assay were as follows: DOR, 3.37 (95% confidence interval [CI]: 1.47-6.66); sensitivity, 0.63 (95% CI 0.50-0.74); specificity, 0.65 (95% CI 0.51-0.76); PLR, 1.83 (95% CI 1.21-2.74); NLR, 0.58 (95% CI 0.39-0.83). The SROC was 0.68. CONCLUSION: In this current meta-analysis, the serum galactomannan test was classified as less accurate for purposes of diagnosing confirmed AIAS. These results suggest that the initial diagnosis of AIAS should not solely be dependent upon serum galactomannan test results. More studies of the test are needed in patients with AIAS to more accurately assess its diagnostic value.

Patient safety educational interventions: A systematic review with recommendations for nurse educators.

AIM: This study identified and evaluated tested patient safety educational interventions. This study also described the content, curricular structures and teaching strategies of the educational interventions and determined the methods used for evaluating patient safety learning outcomes. DESIGN: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines directed this review. METHODS: Searches for articles describing and evaluating patient safety educational interventions were conducted using four scholarly databases. Study quality was assessed using the McMaster Critical Review Form. RESULTS: Seven studies met the inclusion criteria. Educational interventions were either presented as stand-alone courses or as lessons embedded in an existing course. All studies employed a mixture of various teaching modalities and several evaluation methods and outcomes. Mixed results were observed in terms of the effects of educational interventions. Future researchers should continue to develop patient safety curricula and examine their effect on student competencies with stronger methodological rigour.

Sonochemical activation in aqueous medium for solid-state synthesis of BaTiO3 powders.

BaTiO3-based oxide compounds are important ceramic materials for multilayer ceramic capacitors. In this paper, we report a sonochemical activation process of BaCO3 and TiO2 in an aqueous medium for the synthesis of BaTiO3 powders through a solid-state process. Owing to the physical and chemical effects of the ultrasonication in aqueous medium on the raw materials, BaTiO3 powders could be successfully synthesized at relatively low temperatures through a solid-state reaction, which was significantly enhanced as compared to the case in ethanol medium. Detailed investigations on the resulting BaTiO3 powders and ceramics were performed, and a model to understand the role of aqueous medium on the enhancement of the solid-state reaction was proposed in terms of Ba2+ ion leaching and zeta potential of TiO2, which are strongly affected by the pH of the aqueous medium. Our results are not only helpful for cost-effective synthesis of BaTiO3 through the highly reliable solid-state reaction process, but they also provide an understanding of the role of aqueous medium for the sonochemical process using raw materials with partial solubility in water.

Sarcopenia's Prognostic Impact on Patients Treated with Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis.

BACKGROUND: Although sarcopenia has been reported to predict survival in cancer patients, its impact on patients who received immune checkpoint inhibitors (ICIs) has not been thoroughly investigated. This systematic review aimed to assess the long-term oncologic impact of sarcopenia on patients who received ICIs. METHODS: A systematic review of studies indexed in the PubMed, Embase, and Cochrane databases, up to April 1, 2021, was conducted. Studies that reported hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS) based on sarcopenia in patients treated with ICIs were included. The inverse variance method was used with a random-effects model for data analysis. RESULTS: A total of 1284 patients from 14 studies were included. Among the patients who received ICIs, patients with sarcopenia had a significant increase in overall mortality compared to patients without sarcopenia in univariate analyses (HR = 1.66, 95% CI = 1.20-2.29, p = 0.002) and in adjusted HRs (HR = 1.55, 95% CI = 1.15-2.10, p = 0.004). The same results were obtained for PFS by both univariate analysis (HR = 1.75, 95% CI = 1.37-2.23, p < 0.001) and adjusted HRs (HR = 1.63, 95% CI 1.28-2.09, p < 0.001). CONCLUSIONS: Sarcopenia appears to be an effective biomarker for predicting long-term oncologic outcomes in patients receiving ICI therapy and hence plays an important role when making treatment decisions. However, the fundamental role of this association with survival should be further investigated in large cohorts and clinical trials.

Endoscopic Vacuum Therapy in Patients with Transmural Defects of the Upper Gastrointestinal Tract: A Systematic Review with Meta-Analysis.

A transmural defect of the upper gastrointestinal (UGI) tract is a life-threatening condition associated with high morbidity and mortality. Recently, endoscopic vacuum therapy (EVT) was used for managing UGI defects and showed promising results. We conducted a systematic review and meta-analysis to synthesize evidence on the efficacy of EVT in patients with transmural defects of the UGI tract. We searched the PubMed, Cochrane Library, and Embase databases for publications on the effect of EVT on successful closure, mortality, complications, and post-EVT strictures. Methodological quality was assessed using the Newcastle-Ottawa quality assessment scale. This meta-analysis included 29 studies involving 498 participants. The pooled estimate rate of successful closure with EVT was 0.85 (95% confidence interval [CI]: 0.81-0.88). The pooled estimate rates for mortality, complications, and post-EVT strictures were 0.11, 0.10, and 0.14, respectively. According to the etiology of the transmural defect (perforation vs. leak and fistula), no significant difference was observed in successful closure (odds ratio [OR]: 1.45, 95% CI: 0.45-4.67, p = 0.53), mortality (OR: 0.77, 95% CI: 0.24-2.46, p = 0.66), complications (OR: 0.94, 95% CI: 0.17-5.15, p = 0.94), or post-EVT stricture rates (OR: 0.70, 95% CI: 0.12-4.24, p = 0.70). The successful closure rate was significantly higher with EVT than with self-expanding metal stent (SEMS) placement (OR: 3.14, 95% CI: 1.23-7.98, p = 0.02). EVT is an effective and safe treatment for leaks and fistulae, as well as for perforations in the UGI. Moreover, EVT seems to be a better treatment option than SEMS placement for UGI defects.

Repeated Pancreatectomy for Isolated Local Recurrence in the Remnant Pancreas Following Radical Pancreatectomy for Pancreatic Ductal Adenocarcinoma: A Pooled Analysis.

The mainstream treatment for recurrent pancreatic cancer is potent chemotherapy or chemoradiotherapy. However, recent clinical investigations have suggested a potential oncologic role of local resection of recurrent pancreatic cancer. This systemic review with a pooled analysis aimed to assess the potential role of local repeated pancreatectomy with respect to the survival outcomes for patients with recurrent pancreatic ductal adenocarcinoma (PDAC) in the remnant pancreas. The PubMed database was searched, and 15 articles reporting on repeated pancreatectomy for local recurrence of PDAC in the remnant pancreas were identified. The pooled individual data were examined for the clinical outcomes of repeated pancreatectomy for recurrent PDAC. The survival analysis was performed using the Kaplan-Meier method. In the pooled analysis, the mean time interval from initial pancreatectomy to repeated pancreatectomy was 41.3 months (standard deviation (SD), 29.09 months). Completion total pancreatectomy was most commonly performed as repeated pancreatectomy (46 patients, 92.0%), and partial pancreatic resection was performed for only 4 (10.3%) patients. Twenty (40.9%) patients received postoperative chemotherapy following repeated pancreatectomy. The median overall survival was 60 months (95% confidential interval (CI): 45.99-74.01) after repeated pancreatectomy for isolated local recurrence in the remnant pancreas. Overall survival was markedly longer considering the timing of the initial pancreatectomy for pancreatic cancer (median, 107 months (95% CI: 80.37-133.62). The time interval between the initial and subsequent repeated pancreatectomy for pancreatic cancer was not associated with long-term oncologic outcomes (p = 0.254). Repeated pancreatectomy cannot completely replace adjuvant chemotherapy but should be considered for patients with isolated local recurrent PDAC in the remnant pancreas.