Safety and efficacy of intracoronary artery administration of human bone marrow-derived mesenchymal stem cells in STEMI of Lee-Sung pigs—A preclinical study for supporting the feasibility of the OmniMSC-AMI phase I clinical trial

BackgroundThis study tested whether early left intracoronary arterial (LAD) administration of human bone marrow-derived mesenchymal stem cells (hBMMSCs, called OmniMSCs) in acute ST-segment elevation myocardial infarction (STEMI) of Lee-Sung pigs induced by 90 min balloon-occluded LAD was safe and effective.Methods and resultsYoung male Lee-Sung pigs were categorized into SC (sham-operated control, n = 3), AMI-B (STEMI + buffer/21 cc/administered at 90 min after STEMI, n = 6), and AMI-M [acute myocardial infarction (AMI) + hBMMSCs/1.5 × 107/administered at 90 min after STEMI, n = 6] groups. By 2 and 5 months after STEMI, the cardiac magnetic resonance imaging demonstrated that the muscle scar score (MSS) and abnormal cardiac muscle exercise score in the infarct region were significantly increased in the AMI-B than in the SC group that were significantly reversed in the AMI-M group, whereas the left ventricular ejection function by each month (from 1 to 5) displayed an opposite pattern of MSS among the groups (all p < 0.001). By 5 months, histopathological findings of infarct and fibrosis areas and isolectin-B4 exhibited an identical pattern, whereas the cellular expressions of troponin-I/troponin-T/von Willebrand factor exhibited an opposite pattern of MSS among the groups (all p < 0.001). The ST-segment resolution (>80%) was significantly earlier (estimated after 6-h AMI) in the AMI-M group than in the AMI-B group (p < 0.001). The protein expressions of inflammation (IL-1β/TNF-α/NF-κB)/oxidative stress (NOX-1/NOX-2/oxidized protein)/apoptosis (cleaved caspase-3/cleaved PARP)/DNA damage (γ-H2AX) displayed an identical pattern to MSS among the groups, whereas the protein expressions of angiogenesis factors (SDF-1α/VEGF) were significantly and progressively increased from SC, AMI-B, to AMI-M groups (all p < 0.001).ConclusionEarly intra-LAD transfusion of OmniMSC treatment effectively reduced the infarct size and preserved LV function in porcine STEMI

Automated Long-Term Monitoring of Parallel Microfluidic Operations Applying a Machine Vision-Assisted Positioning Method

As microfluidics has been applied extensively in many cell and biochemical applications, monitoring the related processes is an important requirement. In this work, we design and fabricate a high-throughput microfluidic device which contains 32 microchambers to perform automated parallel microfluidic operations and monitoring on an automated stage of a microscope. Images are captured at multiple spots on the device during the operations for monitoring samples in microchambers in parallel; yet the device positions may vary at different time points throughout operations as the device moves back and forth on a motorized microscopic stage. Here, we report an image-based positioning strategy to realign the chamber position before every recording of microscopic image. We fabricate alignment marks at defined locations next to the chambers in the microfluidic device as reference positions. We also develop image processing algorithms to recognize the chamber positions in real-time, followed by realigning the chambers to their preset positions in the captured images. We perform experiments to validate and characterize the device functionality and the automated realignment operation. Together, this microfluidic realignment strategy can be a platform technology to achieve precise positioning of multiple chambers for general microfluidic applications requiring long-term parallel monitoring of cell and biochemical activities

One-year cardiovascular outcomes of drug-eluting stent versus bare-metal stent implanted in diabetic patients with acute coronary syndrome

AbstractBackgroundThe outcomes of drug-eluting stent (DES) versus bare-metal stent (BMS) use in patients with diabetic mellitus (DM) and acute coronary syndrome (ACS) are rarely reported in Taiwan. This study aimed to investigate the 1-year cardiovascular outcomes of DESs versus BMSs implanted in Taiwanese patients with DM and ACS.MethodsFor this study, we collected and analyzed patient information from the database of the Taiwan ACS Full Spectrum registry regarding characteristics and cardiovascular events in participants with DM and ACS who received implantation of either BMS (BMS group) or DES (DES group) from October 2008 to January 2010.ResultsWe found that several characteristics significantly varied between the groups. Compared with the BMS group (n = 575), the DES group (n = 199) had significantly lower rates of in-hospital cardiogenic shock (1.5% vs. 4.9%, p = 0.037) and acute renal failure (0.5% vs. 4.5%, p = 0.008), all-cause mortality (5.0% vs. 8.9%, p = 0.048), and major adverse cardiac events (MACEs) at 1 year (11.1% vs. 18.6%, p = 0.006) with an identical target vessel revascularization (TVR) rate (6.0% vs. 7.3%, p = 0.395). The BMS group had significantly higher risk-adjusted all-cause mortality [hazard ratio (HR) = 2.4, 95% confidence interval (CI) 1.0–5.7; p = 0.048] and MACE (HR = 2.2, 95% CI 1.2–3.9; p = 0.011) at 1 year with identical risks of TVR (HR = 1.3, 95% CI 0.6–2.9; p = 0.505) and nonfatal myocardial infarction (HR = 1.5, 95% CI 0.5–4.4; p = 0.478).ConclusionThe results of this study support the use of DES over BMS in Taiwanese patients with DM and ACS, providing the clinical benefits of lower rates of total mortality and MACE, and without increased TVR at 1 year in a real-world setting

Performance of screening tests for oesophageal squamous cell carcinoma: a systematic review and meta-analysis

Background and Aims: This systematic review and meta-analysis aims to compare the pooled diagnostic accuracy of the currently available esophageal squamous cell carcinoma (ESCC) screening tests. Methods: A comprehensive literature search of Embase and Medline (up to October 31, 2020) was performed to identify eligible studies. We pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) for ESCC screening tools using a bivariate random-effects model. The summary receiver operating characteristic (sROC) curves with area under the curve (AUC) were plotted for each screening test. Results: We included 161 studies conducted in 81 research articles involving 32,209 subjects. The pooled sensitivity, specificity, and AUC (95% CIs) of the major screening tools were: (1). Endoscopy (per-oral endoscopy): 0.94 (0.87-0.97), 0.92 (0.87-0.95), and 0.97 (0.96-0.99); (2) Endoscopy (transnasal endoscopy): 0.85 (0.70-0.93), 0.96 (0.91-0.98), and 0.97 (0.95, -0.98); (3). MicroRNA: 0.77 (0.75-0.80), 0.78 (0.75-0.80), and 0.85 (0.81-0.87); (4). Autoantibody: 0.45 (0.36-0.53), 0.91 (0.89-0.93), and 0.84 (0.81-0.87); and (5). Cytology: 0.82 (0.60-0.93), 0.97 (0.88-0.99), and 0.97 (0.95-0.98). There was high heterogeneity. Conclusions: The diagnostic accuracy seems comparable between Cytology and endoscopy, whilst autoantibody and microRNAs bear potential as future non-invasive screening tools for ESCC. To reduce ESCC-related death in the high-risk populations, it is important to develop a more accurate and less invasive screening test

Effect of real-time computer-aided polyp detection system (ENDO-AID) on adenoma detection in endoscopists-in-training: a randomized trial

Background The effect of computer-aided polyp detection (CADe) on adenoma detection rate (ADR) among endoscopists-in-training remains unknown. Methods We performed a single-blind, parallel-group, randomized controlled trial in Hong Kong between April 2021 and July 2022 (NCT04838951). Eligible subjects undergoing screening/surveillance/diagnostic colonoscopies were randomized 1:1 to receive colonoscopies with CADe (ENDO-AID(OIP-1), Olympus Co., Japan) or not (control) during withdrawal. Procedures were performed by endoscopists-in-training with <500 procedures and <3 years’ experience. Randomization was stratified by patient age, sex, and endoscopist experience (beginner vs intermediate-level, <200 vs 200-500 procedures). Image enhancement and distal attachment devices were disallowed. Subjects with incomplete colonoscopies or inadequate bowel preparation were excluded. Treatment allocation was blinded to outcome assessors. The primary outcome was ADR. Secondary outcomes were ADR for different adenoma sizes and locations, mean number of adenomas, and non-neoplastic resection rate. Results 386 and 380 subjects were randomized to CADe and control groups, respectively. The overall ADR was significantly higher in CADe than control group (57.5% vs 44.5%, adjusted relative risk 1.41, 95%CI 1.17-1.72, p<0.001). The ADRs for <5mm (40.4% vs 25.0%) and 5-10mm adenomas (36.8% vs 29.2%) were higher in CADe group. The ADRs were higher in CADe group in both right (42.0% vs 30.8%) and left colon (34.5% vs 27.6%), but there was no significant difference in advanced ADR. The ADRs were higher in CADe group among beginners (60.0% vs 41.9%) and intermediate-level endoscopists (56.5% vs 45.5%). Mean number of adenomas (1.48 vs 0.86) and non-neoplastic resection rate were higher in CADe group (52.1% vs 35.0%). Conclusions Among endoscopists-in-training, the use of CADe during colonoscopies was associated with increased overall ADR. (ClinicalTrials.gov: NCT04838951

Erratum to: Erythropoietin improves long-term neurological outcome in acute ischemic stroke patients: a randomized, prospective, placebo-controlled clinical trial.

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Evolutionary and Transmission Dynamics of Reassortant H5N1 Influenza Virus in Indonesia

H5N1 highly pathogenic avian influenza (HPAI) viruses have seriously affected the Asian poultry industry since their recurrence in 2003. The viruses pose a threat of emergence of a global pandemic influenza through point mutation or reassortment leading to a strain that can effectively transmit among humans. In this study, we present phylogenetic evidences for the interlineage reassortment among H5N1 HPAI viruses isolated from humans, cats, and birds in Indonesia, and identify the potential genetic parents of the reassorted genome segments. Parsimony analyses of viral phylogeography suggest that the reassortant viruses may have originated from greater Jakarta and surroundings, and subsequently spread to other regions in the West Java province. In addition, Bayesian methods were used to elucidate the genetic diversity dynamics of the reassortant strain and one of its genetic parents, which revealed a more rapid initial growth of genetic diversity in the reassortant viruses relative to their genetic parent. These results demonstrate that interlineage exchange of genetic information may play a pivotal role in determining viral genetic diversity in a focal population. Moreover, our study also revealed significantly stronger diversifying selection on the M1 and PB2 genes in the lineages preceding and subsequent to the emergence of the reassortant viruses, respectively. We discuss how the corresponding mutations might drive the adaptation and onward transmission of the newly formed reassortant viruses