Characterization of the Outer Membrane Vesicles of Pseudomonas aeruginosa Exhibiting Growth Inhibition against Acinetobacter baumannii.

We investigated the Pseudomonas aeruginosa (PA) outer membrane vesicles (OMVs) and their effect on Acinetobacter baumannii (AB) growth in vitro. The inhibitory effects of PA on AB were assessed using a cross-streak assay. The OMVs were extracted through high-speed centrifugation, tangential flow filtration, and ultracentrifugation and characterized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), transmission electron microscopy (TEM), and nanoparticle tracking assays (NTAs). Proteomic analysis was conducted to compare the OMVs of different PA strains. PA022 exhibited more pronounced inhibition of AB growth compared with PA ATCC 27853. TEM confirmed the presence of OMVs in both PA022 and PA ATCC 27853, revealing phospholipid bilayer structures. The NTA revealed similar sizes and concentrations. Proteomic analysis identified 623 and 538 proteins in PA022 and PA ATCC 27853 OMVs, respectively, with significant proportions of the outer membrane and extracellular proteins, respectively. Importantly, PA022 OMVs contained six known virulence factors and motility-associated proteins. This study revealed the unique characteristics of PA OMVs and their inhibitory effects on AB growth, shedding light on their role in bacterial interactions. Proteomic analysis provides valuable insights into potential pathogenic functions and therapeutic applications against bacterial infections.

Chemoembolization as first-line treatment for hepatocellular carcinoma invading segmental portal vein with tumour burden limited to a monosegmental level.

OBJECTIVES: To evaluate the safety and effectiveness of chemoembolization for hepatocellular carcinoma (HCC) with portal vein tumour thrombosis (PVTT) confined to a monosegment of the liver. METHODS: A total of 192 treatment-naive patients who received chemoembolization between March 2008 and January 2023 as a first-line treatment for locally advanced HCC with PVTT limited to a monosegment were retrospectively analysed. Overall survival (OS) and the identification of pretreatment risk factors related to OS were investigated using Cox regression analysis. Complications, radiologic tumour response, and progression-free survival (PFS) following chemoembolization were investigated. RESULTS: After chemoembolization, the 1-, 3-, and 5-year OS rates were 86%, 48%, and 39%, respectively, and the median OS was 33 months. Multivariable analyses revealed four significant pretreatment risk factors: infiltrative HCC (P = .02; HR, 1.60), beyond the up-to-11 criteria (P = .002; HR, 2.26), Child-Pugh class B (P = .01; HR, 2.35), and serum AFP ≥400 ng/mL (P = .01; HR, 1.69). The major complication rate was 5%. Of the 192 patients, 1 month after chemoembolization, 35% achieved a complete response, 47% achieved a partial response, 11% had stable disease, and 7% showed progressive disease. The median PFS after chemoembolization was 12 months. CONCLUSIONS: Chemoembolization shows high safety and efficiency, and contributes to improved survival in patients with HCC with PVTT confined to a monosegment. Four risk factors were found to be significantly associated with improved survival rates after chemoembolization in patients with HCC with PVTT confined to a monosegment. ADVANCES IN KNOWLEDGE: (1) Although systemic therapy with a combination of atezolizumab and bevacizumab (Atezo-Bev) is recommended as the first-line treatment when HCC invades the portal vein, chemoembolization is not infrequently performed in HCC cases in which tumour burden is limited. (2) Our study cohort (n=192) had a median OS of 33 months and a 5% major complication rate following chemoembolization, findings in the range of candidates typically accepted as ideal for chemoembolization. Thus, patients with HCC with PVTT confined to a monosegment may be good candidates for first-line chemoembolization.

Br doping-induced evolution of the electronic band structure in dimorphic and hexagonal SnSe2 thermoelectric materials.

SnSe2 with its layered structure is a promising thermoelectric material with intrinsically low lattice thermal conductivity. However, its poor electronic transport properties have motivated extensive doping studies. Br doping effectively improves the power factor and converts the dimorphic SnSe2 to a fully hexagonal structure. To understand the mechanisms underlying the power factor improvement of Br-doped SnSe2, the electronic band parameters of Br-doped dimorphic and hexagonal SnSe2 should be evaluated separately. Using the single parabolic band model, we estimate the intrinsic mobility and effective mass of the Br-doped dimorphic and hexagonal SnSe2. While Br doping significantly improves the mobility of dimorphic SnSe2 (with the dominant hexagonal phase), it results in a combination of band convergence and band flattening in fully hexagonal SnSe2. Br-doped dimorphic SnSe2 is predicted to exhibit higher thermoelectric performance (zT ∼0.23 at 300 K) than Br-doped fully hexagonal SnSe2 (zT ∼0.19 at 300 K). Characterisation of the other, currently unidentified, structural phases of dimorphic SnSe2 will enable us to tailor the thermoelectric properties of Br-doped SnSe2.

Evaluation of basal rate infusion in intravenous patient-controlled analgesia for post-cesarean section pain management: A randomized pilot study.

OBJECTIVE: Administering opioids via intravenous patient-controlled analgesia is a prevalent approach for managing postoperative pain. Nevertheless, due to concerns about opioid-related side effects and the potential for opioid tolerance, there is a growing emphasis on adopting opioid-sparing techniques for postoperative pain management. We aimed to investigate the effect of adding a basal rate infusion in fentanyl-based IVA following a cesarean section (CS). METHOD: Forty-eight patients, who received pain management through IVA after CS, were assigned randomly into 3 groups based on the background rate setting: Group 0 (0 mcg/hour, n = 16), Group 1 (15 mcg/hour, n = 16), and Group 2 (30 mcg/hour, n = 16). We assessed the impact of the basal infusion rate on opioid consumption and the visual analog scale (VAS) scores during the first 48 hours post-CS and also investigated opioid-induced side effects and the requirement for rescue analgesics in the ward during the first 48 hours after CS. RESULTS: In the initial 24 hours following CS, fentanyl consumption significantly increased in Group 2 compared with Group 0 and Group 1 (P = .037). At 24 hours, VAS scores both at rest and during movement, tended to decrease, as the basal rate increased; however, no significant differences were observed between the groups (P = .218 and 0.827, respectively). Between the first 24- and 48-hours post-CS, fentanyl consumption showed a marked increase in both Group 1 and Group 2 compared to Group 0 (P < .001). At 48 hours, the VAS scores at rest displayed a trend toward reduction; however, no significant differences between groups were evident (P = .165). Although the incidence of opioid-induced complications was noted, no statistically significant differences were recorded between groups during the initial 24 hours and subsequent 24 to 48 hours period (P = .556 and P = .345, respectively). CONCLUSION: The inclusion of a basal fentanyl infusion in the IVA protocol did not provide any advantages over an IVA devoid of a basal rate infusion in managing acute pain following CS.

Clinical and molecular predictors of mortality in patients with carbapenem-resistant Acinetobacter baumannii bacteremia: A retrospective cohort study.

BACKGROUND/PURPOSE: To investigate the virulence profiles and identify clinical and microbiological predictors of mortality in patients with carbapenem-resistant Acinetobacter baumannii (A. baumannii) bacteremia. METHODS: This retrospective cohort study enrolled adult patients with carbapenem-resistant A. baumannii (CRAB). Multivariate logistic regression was used to identify the predictors of 30-day mortality. All isolates were subjected to real-time polymerase chain reaction for virulence factors and genotyped using multilocus sequence typing. RESULTS: Among the 153 patients with CRAB bacteremia, 66 % received appropriate definitive antibiotic therapy. The in-hospital and 30-day mortality rates were 58.3 and 23.5 %, respectively. Ultimately, we enrolled 125 patients with CRAB bacteremia in the analysis, excluding early mortality cases. All CRAB isolates carried blaOXA-23 and blaOXA-51. The clinical strains belonged to 10 sequence types (STs), and the major genotypes were ST191, ST195, ST451, and ST784. The distribution of virulence factors included surface adhesion (Ata, 84.8 %; ChoP, 7.2 %), biofilm formation (OmpA, 76.8 %), killing of host cells (AbeD, 99.2 %), toxins (LipA, 99.2 %), and conjugation (BfmR, 90.4 %). In multivariate logistic regression analysis, hemodialysis due to acute kidney injury and moderate to severe thrombocytopenia were significant risk factors associated with 30-day mortality. However, microbiological factors were not significant predictors. CONCLUSIONS: Clinical factors such as hemodialysis due to acute renal injury and moderate to severe thrombocytopenia have a greater influence on mortality in CRAB bacteremia compared with microbiological factors.

Genomic hypomethylation in cell-free DNA predicts responses to checkpoint blockade in lung and breast cancer.

Genomic hypomethylation has recently been identified as a determinant of therapeutic responses to immune checkpoint blockade (ICB). However, it remains unclear whether this approach can be applied to cell-free DNA (cfDNA) and whether it can address the issue of low tumor purity encountered in tissue-based methylation profiling. In this study, we developed an assay named iMethyl, designed to estimate the genomic hypomethylation status from cfDNA. This was achieved through deep targeted sequencing of young LINE-1 elements with > 400,000 reads per sample. iMethyl was applied to a total of 653 ICB samples encompassing lung cancer (cfDNA n = 167; tissue n = 137; cfDNA early during treatment n = 40), breast cancer (cfDNA n = 91; tissue n = 50; PBMC n = 50; cfDNA at progression n = 44), and ovarian cancer (tissue n = 74). iMethyl-liquid predicted ICB responses accurately regardless of the tumor purity of tissue samples. iMethyl-liquid was also able to monitor therapeutic responses early during treatment (3 or 6 weeks after initiation of ICB) and detect progressive hypomethylation accompanying tumor progression. iMethyl-tissue had better predictive power than tumor mutation burden and PD-L1 expression. In conclusion, our iMethyl-liquid method allows for reliable noninvasive prediction, early evaluation, and monitoring of clinical responses to ICB therapy.

Molecular and virulence characteristics of carbapenem-resistant Acinetobacter baumannii isolates: a prospective cohort study.

This study aimed to characterize the molecular features and virulence profiles of carbapenem-resistant Acinetobacter baumannii (CRAB) isolates. Clinical CRAB isolates were obtained from blood cultures of adult patients with CRAB bacteremia, collected between July 2015 and July 2021 at a Korean hospital. Real-time polymerase chain reaction was used to detect 13 virulence genes, genotyping was conducted via multilocus sequence typing (MLST), and a Tenebrio molitor infection model was selected for survival analysis. Herein, 170 patients, from whom CRAB isolates were collected, showed the in-hospital mortality rate of 57.6%. All 170 clinical CRAB isolates harbored blaOXA-23 and blaOXA-51. MLST genotyping identified 11 CRAB sequence types (STs), of which ST191 was predominant (25.7%). Virulence genes were distributed as follows: basD, 58.9%; espA, 15.9%; bap, 92.4%; and ompA, 77.1%. In the T. molitor model, ST195 showed a significantly higher mortality rate (73.3% vs. 66.7%, p = 0.015) than the other groups. Our findings provide insights into the microbiological features of CRAB blood isolates associated with high mortality. We suggest a potential framework for using a T. molitor infection model to characterize CRAB virulence. Further research is warranted to elucidate the mechanisms by which virulence improves clinical outcomes.

Vibrio-infecting bacteriophages and their potential to control biofilm.

The emergence and spread of antibiotic-resistant pathogenic bacteria have necessitated finding new control alternatives. Under these circumstances, lytic bacteriophages offer a viable and promising option. This review focuses on Vibrio-infecting bacteriophages and the characteristics that make them suitable for application in the food and aquaculture industries. Bacteria, particularly Vibrio spp., can produce biofilms under stress conditions. Therefore, this review summarizes several anti-biofilm mechanisms that phages have, such as stimulating the host bacteria to produce biofilm-degrading enzymes, utilizing tail depolymerases, and penetrating matured biofilms through water channels. Additionally, the advantages of bacteriophages over antibiotics, such as a lower probability of developing resistance and the ability to infect dormant cells, are discussed. Finally, this review presents future research prospects related to further utilization of phages in diverse fields.

Clinical impact of COVID-19 in patients with carbapenem-resistant Acinetobacter baumannii bacteraemia.

The aim of this study was to evaluate the impact of coronavirus disease 2019 (COVID-19) on treatment outcomes in critically ill patients with carbapenem-resistant Acinetobacter baumannii (CRAB) bloodstream infection (BSI). This single-centre, retrospective cohort study was conducted in a 1,048-bed university-affiliated tertiary hospital in the Republic of Korea from January 2021 to March 2022. The study participants included consecutive hospitalised adult patients (aged ≥18 years) in the intensive care unit with CRAB monomicrobial BSI. During the study period, a total of 70 patients were included in our study, and 24 (34.3%) were diagnosed with COVID-19. The 28-day mortality rate was 64.3%. In the multivariate Cox proportional hazard regression analysis, diagnosis of COVID-19 (hazard ratio (HR), 2.91; 95% confidence interval (CI): 1.45-5.87), neutropenia (HR, 2.76; 95% CI: 1.04-7.29), Pitt bacteraemia score (per point; HR, 1.30; 95% CI: 1.19-1.41), and appropriate definite antibiotic therapy (HR, 0.31; 95% CI: 0.15-0.62) were independent predictors of 28-day mortality in patients with CRAB BSI. In conclusion, our findings suggested that COVID-19 has a negative prognostic impact on patients with CRAB BSI. Further study is needed to investigate the specific mechanisms of how COVID-19 worsens the prognosis of CRAB infection.

Widespread somatic L1 retrotransposition in normal colorectal epithelium.

Throughout an individual's lifetime, genomic alterations accumulate in somatic cells1-11. However, the mutational landscape induced by retrotransposition of long interspersed nuclear element-1 (L1), a widespread mobile element in the human genome12-14, is poorly understood in normal cells. Here we explored the whole-genome sequences of 899 single-cell clones established from three different cell types collected from 28 individuals. We identified 1,708 somatic L1 retrotransposition events that were enriched in colorectal epithelium and showed a positive relationship with age. Fingerprinting of source elements showed 34 retrotransposition-competent L1s. Multidimensional analysis demonstrated that (1) somatic L1 retrotranspositions occur from early embryogenesis at a substantial rate, (2) epigenetic on/off of a source element is preferentially determined in the early organogenesis stage, (3) retrotransposition-competent L1s with a lower population allele frequency have higher retrotransposition activity and (4) only a small fraction of L1 transcripts in the cytoplasm are finally retrotransposed in somatic cells. Analysis of matched cancers further suggested that somatic L1 retrotransposition rate is substantially increased during colorectal tumourigenesis. In summary, this study illustrates L1 retrotransposition-induced somatic mosaicism in normal cells and provides insights into the genomic and epigenomic regulation of transposable elements over the human lifetime.

Risk of venous thromboembolism in Korean patients with rheumatoid arthritis treated with Janus kinase inhibitors: A nationwide population-based study.

OBJECTIVE: There was a safety concern about an increased risk of thromboembolic events in patients with rheumatoid arthritis (RA) treated with Janus kinase inhibitors (JAKis). This study aimed to determine the risk of venous thromboembolism (VTE) in Korean patients with RA treated with JAKis compared with tumour necrosis factor (TNF) inhibitors. METHODS: Using the National Health Insurance Service database between 2015 and 2019, patients with prevalent RA who started JAKi or TNF inhibitor were selected as the study population. All participants were naïve to targeted therapy. Patients that had experienced any VTE event or used anticoagulant agents within 30 days were excluded. Demographic and clinical characteristics were all balanced by stabilised inverse probability of treatment weighting (sIPTW) using propensity score. The Cox proportional hazard model considering death as a competing risk was used to evaluate the risk of VTE in JAKi users compared with TNF inhibitor users. RESULTS: A total of 4,178 patients were included: 871 JAKi users and 3,307 TNF inhibitor users were followed up for 1,029.2 person-years (PYs) and 5,940.3 PYs, respectively. With a balanced sample after sIPTW, the incidence rates (IR) of VTE were 0.06 per 100 PYs (95% confidence interval [CI] 0.00-1.23) in JAKi users and 0.38 per 100 PYs (95% CI 0.25-0.58) in TNF inhibitor users. The hazard ratio was 0.18 (95% CI 0.01-3.47) after adjusting for unbalanced variables after performing sIPTW. CONCLUSION: There is no increased risk of VTE in RA patients treated with JAKis compared with TNF inhibitors in Korea.

Clinical significance of antinuclear antibody positivity in patients with severe coronavirus disease 2019.

BACKGROUND/AIMS: This study aimed to investigate the clinical characteristics and outcomes of fluorescent antinuclear antibody (FANA)-positive patients admitted for coronavirus disease 2019 (COVID-19) and identify FANA as a prognostic factor of mortality. METHODS: This retrospective study was conducted at a university-affiliated hospital with 1,048 beds from September 2020 to March 2022. The participants were consecutive patients who required oxygenation through a high-flow nasal cannula, non-invasive or mechanical ventilation, or extracorporeal membrane oxygenation, and conducted the FANA test within 48 hours of admission. RESULTS: A total of 132 patients with severe COVID-19 were included in this study, of which 77 (58.3%) had FANA-positive findings (≥ 1:80). FANA-positive patients were older and had higher inflammatory markers and 28-day mortality than FANA- negative patients. In the multivariate Cox proportional hazard regression analysis, FANA-positive findings (hazard ratio [HR], 2.65; 95% confidence interval [CI], 1.04-6.74), age (per 1-year; HR, 1.05; 95% CI, 1.01-1.10), underlying pulmonary disease (HR, 3.16; 95% CI, 0.97-10.26), underlying hypertension (HR, 2.97; 95% CI, 1.28-6.87), and blood urea nitrogen > 20 mg/dL (HR, 3.72; 95% CI, 1.09-12.64) were independent predictors of 28-day mortality. Remdesivir (HR, 0.34; 95% CI, 0.15-0.74) was found to be an independent predictor that reduced mortality. CONCLUSION: Our findings revealed an autoimmune phenomenon in patients with severe COVID-19, which provides an ancillary rationale for strategies to optimize immunosuppressive therapy. In particular, this study suggests the potential of FANA to predict the outcomes of COVID-19.

DeepNeo: a webserver for predicting immunogenic neoantigens.

Non-self epitopes, whether originated from foreign substances or somatic mutations, trigger immune responses when presented by major histocompatibility complex (MHC) molecules and recognized by T cells. Identification of immunogenically active neoepitopes has significant implications in cancer and virus medicine. However, current methods are mostly limited to predicting physical binding of mutant peptides and MHCs. We previously developed a deep-learning based model, DeepNeo, to identify immunogenic neoepitopes by capturing the structural properties of peptide-MHC pairs with T cell reactivity. Here, we upgraded our DeepNeo model with up-to-date training data. The upgraded model (DeepNeo-v2) was improved in evaluation metrics and showed prediction score distribution that better fits known neoantigen behavior. The immunogenic neoantigen prediction can be conducted at https://deepneo.net.

Intravenous patient-controlled analgesia regimen in postoperative pain management following elective cesarean section: A single-center retrospective evaluation.

Intravenous patient-controlled analgesia (IV PCA; IVA) is the most widely used method for postoperative pain management. An appropriate IVA regimen is required, depending on the expected intensity of pain after surgery. This study expected that a decrease in the second prescription rate of IVA after elective cesarean section (CS) would help establish an appropriate regimen for the initial IVA. We retrospectively reviewed the records of 632 patients who were prescribed IVA after CS. We classified patients into phase 1 (basal rate 15.00 mcg/hours, bolus dose 15.00 mcg, total volume 100 mL) and phase 2 (basal rate 31.25 mcg/hours, bolus dose 31.25 mcg, nefopam 60 mg, paracetamol 3 g, total volume 160 mL) according to the IVA regimen, and patients in phase 2 were classified into the basal 15 group and basal 30 group according to the basal rate of IVA. We compared the rates of second prescription, drug removal, and side effects of IVA between the 2 phases and the 1 group. We analyzed the data of 631 eligible patients. The second prescription rate of IVA in phase 2 was 3.77%, a significant decrease compared to that in phase 1 (27.48%); however, the incidence of complications in phase 2 was 6.92%, a significant increase compared to that in phase 1 (0.96%). Within phase 2, in the basal 30 group, the basal rate was almost double that in the basal 15 group. However, there were no significant differences in the rate of second prescription, removed drug IVA, or adverse events between the basal 15, and 30 groups. In the case of CS, which has a high degree of postoperative pain, it is beneficial to control acute pain by properly setting the regimen of the initial IVA with a basal rate infusion to nullify a second prescription.

Clinical prediction rule for identifying older patients with toxigenic clostridioides difficile at the time of hospital admission.

BACKGROUND: This study aimed to develop and validate a clinical prediction rule to screen older patients at risk of being toxigenic Clostridioides difficile carriers at the time of hospital admission. METHODS: This retrospective case-control study was performed at a university-affiliated hospital. Active surveillance using a real-time polymerase chain reaction (PCR) assay for the toxin genes of C. difficile was conducted among older patients (≥ 65 years) upon admission to the Division of Infectious Diseases of our institution. This rule was drawn from a derivative cohort between October 2019 and April 2021 using a multivariable logistic regression model. Clinical predictability was evaluated in the validation cohort between May 2021 and October 2021. RESULTS: Of 628 PCR screenings for toxigenic C. difficile carriage, 101 (16.1%) yielded positive findings. To establish clinical prediction rules in the derivation cohort, the formula was derived using significant predictors for toxigenic C. difficile carriage at admission, such as septic shock, connective tissue diseases, anemia, recent use of antibiotics, and recent use of proton-pump inhibitors. In the validation cohort, the sensitivity, specificity, and positive and negative predictive values of the prediction rule, based on a cut-off value of ≥ 0.45, were 78.3%, 70.8%, 29.5%, and 95.4%, respectively. CONCLUSION: This clinical prediction rule for identifying toxigenic C. difficile carriage at admission may facilitate the selective screening of high-risk groups. To implement it in a clinical setting, more patients from other medical institutions need to be prospectively examined.

Gram-Negative Bacteria's Outer Membrane Vesicles.

Outer membrane vesicles (OMVs) are spherical bilayered nanoparticles derived from the outer layer of Gram-negative bacteria. Bacteria communicate with nearby bacteria, their environment, and the cells of their host by secreting OMVs, which are essential for their survival. OMVs also play a critical role in bacterial pathogenesis since they are loaded with virulence factors, toxins, and enzymes. OMVs may modulate the immune response of the host by initiating inflammation through cytokine production and activating the innate immune response. OMVs also contribute to the resistance of bacteria to antibiotics by carrying antibiotic-degrading enzymes and acting as natural protection barriers. Concerns have also been raised regarding OMVs mediating the transfer of antibiotic resistance. Due to their advantageous properties, OMVs are attractive platforms for vaccine discovery and drug delivery research. In this review, we discuss the fundamental structure and biogenesis mechanisms of OMVs as well as their multifaceted roles in bacterial infection pathogenesis and host immune responses. We also discuss application examples of OMVs.

Self-expandable metallic stents as a bridge to surgery in obstructive right- and left-sided colorectal cancer: a multicenter cohort study.

The insertion of a self-expandable metal stent (SEMS) has been proposed as an alternative to emergent surgery (ES) for obstructive colorectal cancer (CRC). We aimed to evaluate the perioperative and oncologic outcomes of SEMS as a bridge to surgery in obstructive CRC, as compared with ES. We retrospectively reviewed the medical records of patients who underwent curative resection of obstructive CRC at four Hallym University-affiliated hospitals between January 2010 and December 2019. All patients were analyzed overall colon, then according to the side of obstruction (overall, right or left). Of 167 patients, 52 patients underwent ES and 115 underwent SEMS insertion and surgery (SEMS group). The postoperative hospital stay and time to soft diet were shorter in the SEMS group than in the ES group for overall and both sided cancer. The SEMS group had lower rates of stoma formation and severe complications for overall and for left-sided cancer. The 5-year overall survival (P = 0.682) and disease-free survival (P = 0.233) rates were similar in both groups. SEMS insertion as a bridge to surgery was associated with faster recovery, a lower rate of stoma formation with similar oncologic outcomes to those of ES.

MHC II immunogenicity shapes the neoepitope landscape in human tumors.

Despite advances in predicting physical peptide-major histocompatibility complex I (pMHC I) binding, it remains challenging to identify functionally immunogenic neoepitopes, especially for MHC II. By using the results of >36,000 immunogenicity assay, we developed a method to identify pMHC whose structural alignment facilitates T cell reaction. Our method predicted neoepitopes for MHC II and MHC I that were responsive to checkpoint blockade when applied to >1,200 samples of various tumor types. To investigate selection by spontaneous immunity at the single epitope level, we analyzed the frequency spectrum of >25 million mutations in >9,000 treatment-naive tumors with >100 immune phenotypes. MHC II immunogenicity specifically lowered variant frequencies in tumors under high immune pressure, particularly with high TCR clonality and MHC II expression. A similar trend was shown for MHC I neoepitopes, but only in particular tissue types. In summary, we report immune selection imposed by MHC II-restricted natural or therapeutic T cell reactivity.

Safety Profiles of mRNA COVID-19 Vaccines Using World Health Organization Global Scale Database (VigiBase): A Latent Class Analysis.

INTRODUCTION: Although messenger RNA (mRNA) vaccines have been developed and widely utilized to mitigate the coronavirus disease (COVID-19) pandemic, it is essential to describe the adverse events (AEs) following immunization. This study aimed to identify the patterns associated with serious AE reports after mRNA COVID-19 vaccination in the World Health Organization (WHO)'s global scale database (VigiBase). METHODS: This study performed a latent class analysis (LCA) of reports of serious AEs following mRNA COVID-19 vaccination from VigiBase between December 28, 2020 , and February 28, 2022 (N = 312878). The Medical Dictionary for Regulatory Activities (MedDRA) System Organ Class (SOC) terms were selected for LCA. The reporting characteristics in accordance with the cluster were described. We used a multinomial logistic regression model to estimate the association between potential factors and each cluster. RESULTS: Five clusters of AE reports were distinguished through LCA: infection AEs (cluster 1), cardiac AEs (cluster 2), respiratory/thrombotic AEs (cluster 3), systemic AEs (cluster 4), and nervous system AEs (cluster 5). Compared to cluster 4, cluster 2 had a higher proportion of males (OR 2.98; 95% confidence interval (CI) 2.87-3.09), and cluster 1 had a longer time to onset than other AEs (≥ 14 days) (OR 16.2; 95% CI 15.5-16.9). CONCLUSION: Using LCA, we found five clusters of serious AEs following mRNA COVID-19 vaccination. Each cluster was distinguished by potential factors such as age, gender, region, and time to onset. We suggest that monitoring should carefully consider the patterns of young males with cardiac AEs and elderly individuals with thrombosis after respiratory AEs. Our findings could contribute to enhancing understanding of safety profiles and establishing management strategies for serious AEs of special interest following mRNA COVID-19 vaccination.