Overcoming the age-dependent SARS-CoV-2 vaccine response through hybrid immunity: analysis of humoral and cellular immunity with mass cytometry profiling.

BACKGROUND: Age-dependent immune responses to coronavirus disease 2019 (COVID-19) vaccinations and breakthrough infections (BIs) in young and middle-aged individuals are unclear. METHODS: This nationwide multicenter prospective cohort study analyzed immune responses in participants of the ChAdOx1 (ChAd)-ChAd-mRNA vaccine group using cytometry by time-of-flight, anti-spike protein antibody (Sab) and anti-nucleocapsid antibody (Nab) titers, plaque reduction neutralization tests (PRNTs), and interferon-gamma (IFN-γ) release assays at various time points. RESULTS: We evaluated 347 participants with an average age of 38.9 ± 9.4 years (range: 21-63). There was a significant inverse correlation between age and Sab levels after the second dose (slope - 14.96, P = 0.032), and this was more pronounced after the third dose (slope - 208.9, P < 0.001). After BIs, older participants showed significantly higher Sab titers (slope 398.8, P = 0.001), reversing the age-related decline observed post-vaccination. This reversal was also observed in PRNTs against wild-type SARS-CoV-2 and the BA.1 and BA.5 variants. IFN-γ responses increased markedly after the third dose and Bis, but showed a weak positive correlation with age, without statistical significance. Immune cell profiling revealed an age-dependent decrease in the proportions of B-cell lineage cells. The proportions of naive CD4+ and CD8+ T cells were inversely correlated with age, whereas the proportions of mature T cell subsets with memory function, including memory CD4+ T, CD8+ TEM, CD8+ TEMRA, and TFH cells, increased with age. CONCLUSIONS: Age-dependent waning of the serologic response to COVID-19 vaccines occurred even in middle-aged individuals, but was reversed after BIs. IFN-γ responses were preserved, compensating for the decrease in naive T cell populations, with an increase in memory T cell populations.

Characteristics and standards of severe sagittal imbalance in adult patients with spinal deformities: a retrospective analysis.

OBJECTIVE: To analyze the characteristics of "severe" dynamic sagittal imbalance (DSI) in patients with adult spinal deformity (ASD) and establish criteria for them. METHODS: We retrospectively analyzed 102 patients with ASD presenting four cardinal signs of lumbar degenerative kyphosis. All patients underwent deformity corrective surgery and were divided into three groups according to the diagnostic criteria based on the Oswestry disability index and dynamic features (△Timewalk: time until C7 sagittal vertical axis [C7SVA] reaches ≥ 20 cm after the start of walking) of sagittal imbalance. The paravertebral back muscles were analyzed and compared using T2-weighted axial imaging. We performed a statistically time-dependent spinopelvic sagittal parameter analysis of full standing lateral lumbar radiographs. Lumbar flexibility was analyzed using dynamic lateral lumbar radiography. RESULTS: The patients were classified into the mild (△Timewalk ≥ 180 s, 35 patients), moderate (180 s > △Timewalk ≥ 30 s, 38 patients), and severe (△Timewalk < 30 s, 29 patients) groups. The back muscles in the severe group exhibited a significantly higher signal intensity (533.4 ± 237.5, p < 0.05) and larger area of fat infiltration (35.2 ± 5.4, p < 0.05) than those in the mild (223.8 ± 67.6/22.9 ± 11.9) and moderate groups (294.4 ± 214.7/21.6 ± 10.6). The analysis of lumbar flexibility revealed significantly lower values in the severe group (5.8° ± 2.5°, p < 0.05) than in the mild and moderate groups (14.2° ± 12.4° and 11.4° ± 8.7°, respectively). The severe group had significantly lower lumbar lordosis (LL, 25.1° ± 22.7°, p < 0.05) and Pelvic incidence-LL mismatch (PI-LL, 81.5° ± 26.6°, p < 0.001) than those of the mild (8.2° ± 16.3°/58.7° ± 18.8°) and moderate (14.3° ± 28.6°/66.8° ± 13.4°) groups. On receiver operating characteristic curve analysis, PI-LL was statistically significant, with an area under the curve of 0.810 (95% confidence interval) when the baseline was set at 75.3°. The severe group had more postoperative complications than the other groups. CONCLUSIONS: Our results suggest the following criteria for severe DSI: C7SVA > 20 cm within 30 s of walking or standing, a rigid lumbar curve < 10° on dynamic lateral radiographs, and a PI-LL mismatch > 75.3°.

Coronal vertical fracture of vertebral body following minimally invasive lateral lumbar interbody fusion: risk factor analysis in consecutive case series.

BACKGROUND: To investigate the incidence and risk factors of coronal vertical vertebral body fracture (CV-VBF) during lateral lumbar interbody fusion (LLIF) for degenerative lumbar disease. METHODS: Clinical data, including age, sex, body mass index, and bone mineral density, were reviewed. Radiological assessments, such as facet joint arthrosis, intervertebral disc motion, index disc height, and cage profiles, were conducted. Posterior instrumentation was performed using either a single or staged procedure after LLIF. Demographic and surgical data were compared between patients with and without VBF. RESULTS: Out of 273 patients (552 levels), 7 (2.6%) experienced CV-VBF. Among the 552 levels, VBF occured in 7 levels (1.3%). All VBF cases developed intraoperatively during LLIF, with no instances caused by cage subsidence during the follow-up period. Sagittal motion in segments adjacent to VBF was smaller than in others (4.6° ± 2.6° versus 6.5° ± 3.9°, P = 0.031). The average grade of facet arthrosis was 2.5 ± 0.7, indicating severe facet arthrosis. All fractures developed due to oblique placement of a trial or cage into the index disc space, leading to a nutcracker effect. These factors were not related to bone quality. CONCLUSIONS: CV-VBF after LLIF occurred in 2.6% of patients, accounting for 1.3% of all LLIF levels. A potential risk factor for VBF involves the nutcracker-impinging effect due to the oblique placement of a cage. Thorough preoperative evaluations and surgical procedures are needed to avoid VBF when considering LLIF in patients with less mobile spine.

Difference in Baseline Antimicrobial Prescription Patterns of Hospitals According to Participation in the National Antimicrobial Monitoring and Feedback System in Korea.

This study aimed to evaluate the differences in the baseline characteristics and patterns of antibiotic usage among hospitals based on their participation in the Korea National Antimicrobial Use Analysis System (KONAS). We obtained claims data from the National Health Insurance for inpatients admitted to all secondary- and tertiary-care hospitals between January 2020 and December 2021 in Korea. 15.9% (58/395) of hospitals were KONAS participants, among which the proportion of hospitals with > 900 beds (31.0% vs. 2.6%, P < 0.001) and tertiary care (50.0% vs. 5.2%, P < 0.001) was higher than that among non-participants. The consumption of antibiotics targeting antimicrobial-resistant gram positive bacteria (33.7 vs. 27.1 days of therapy [DOT]/1,000 patient-days, P = 0.019) and antibiotics predominantly used for resistant gram-negative bacteria (4.8 vs. 3.7 DOT/1,000 patient-days, P = 0.034) was higher in KONAS-participating versus -non-participating hospitals. The current KONAS data do not fully represent all secondary- and tertiary-care hospitals in Korea; thus, the KONAS results should be interpreted with caution.

Clinical utility of quantitative immunoassays and surrogate virus neutralization tests for predicting neutralizing activity against the SARS-CoV-2 Omicron BA.1 and BA.5 variants.

Developing new antibody assays for emerging SARS-CoV-2 variants is challenging. SARS-CoV-2 surrogate virus neutralization tests (sVNT) targeting Omicron BA.1 and BA.5 have been devised, but their performance needs to be validated in comparison with quantitative immunoassays. First, using 1749 PRNT-positive sera, we noticed that log-transformed optical density (OD) ratio of wild-type (WT) sVNT exhibited better titer-correlation with plaque reduction neutralization test (PRNT) than % inhibition value. Second, we tried 798 dilutional titration tests with 103 sera, but nonlinear correlation between OD ratio and antibody concentration limited titration of sVNT. Third, the titer-correlations of two sVNT kits for BA.1 and two quantitative immunoassays for WT were evaluated with BA.1 and BA.5 PRNT. All tested kits exhibited a linear correlation with PRNT titers, but the sVNT kits exhibited high false-negative rates (cPass-BA.1 kit, 45.4% for BA.1 and 44.2% for BA.5; STANDARD F-BA.1 kit, 1.9% for BA.1 and 2.2% for BA.5), while quantitative immunoassays showed 100% sensitivity. Linear mixed-effects model suggested superior titer-correlation with PRNT for quantitative immunoassays compared to sVNT kits. Taken together, the use of quantitative immunoassays for WT, rather than rapid development of new kits, would be practical for predicting neutralizing activities against emerging new variants.

Assessment of the therapeutic potential of Hsp70 activator against prion diseases using in vitro and in vivo models.

Introduction: Prion diseases are deadly neurodegenerative disorders in both animals and humans, causing the destruction of neural tissue and inducing behavioral manifestations. Heat shock proteins (Hsps), act as molecular chaperones by supporting the appropriate folding of proteins and eliminating the misfolded proteins as well as playing a vital role in cell signaling transduction, cell cycle, and apoptosis control. SW02 is a potent activator of Hsp 70 kDa (Hsp70). Methods: In the current study, the protective effects of SW02 against prion protein 106-126 (PrP106-126)-induced neurotoxicity in human neuroblastoma cells (SH-SY5Y) were investigated. In addition, the therapeutic effects of SW02 in ME7 scrapie-infected mice were evaluated. Results: The results showed that SW02 treatment significantly increased Hsp70 mRNA expression levels and Hsp70 ATPase activity (p < 0.01). SW02 also significantly inhibited cytotoxicity and apoptosis induced by PrP106-126 (p < 0.01) and promoted neurite extension. In vivo, intraperitoneal administration of SW02 did not show a statistically significant difference in survival time (p = 0.16); however, the SW02-treated group exhibited a longer survival time of 223.6 ± 6.0 days compared with the untreated control group survival time of 217.6 ± 5.4 days. In addition, SW02 reduced the PrPSc accumulation in ME7 scrapie-infected mice at 5 months post-injection (p < 0.05). A significant difference was not observed in GFAP expression, an astrocyte marker, between the treated and untreated groups. Conclusion: In conclusion, the potential therapeutic role of the Hsp70 activator SW02 was determined in the present study and may be a novel and effective drug to mitigate the pathologies of prion diseases and other neurodegenerative diseases. Further studies using a combination of two pharmacological activators of Hsp70 are required to maximize the effectiveness of each intervention.

The first report of single nucleotide polymorphisms in the open reading frame of the prion-like protein gene in rabbits.

Background: Natural cases of prion disease have not been reported in rabbits, and prior attempts to identify a prion conversion agent have been unsuccessful. However, recent applications of prion seed amplifying experimental techniques have sparked renewed interest in the potential susceptibility of rabbits to prion disease infections. Among several factors related to prion disease, polymorphisms within the prion-like protein gene (PRND), a member of the prion protein family, have been reported as significantly associated with disease susceptibility in various species. Therefore, our study aimed to investigate polymorphisms in the PRND gene of rabbits and analyze their genetic characteristics. Methods: Genomic DNA was extracted from 207 rabbit samples to investigate leporine PRND polymorphisms. Subsequently, amplicon sequencing targeting the coding region of the leporine PRND gene was conducted. Additionally, linkage disequilibrium (LD) analysis was employed to assess the connection within and between loci. The impact of non-synonymous single nucleotide polymorphisms (SNPs) on the Doppel protein was evaluated using PolyPhen-2. Results: We found nine novel SNPs in the leporine PRND gene: c.18A > G, c.76G > C, c.128C > T, c.146C > T, c.315A > G, c.488G > A, c.525G > C, c.544G > A, and c.579A > G. Notably, seven of these PRND SNPs, excluding c.525G > C and c.579A > G, exhibited strong LD values exceeding 0.3. In addition, LD analysis confirmed a robust link between PRNP SNP c.234C > T and PRND SNPs at c.525G > C and c.579A > G. Furthermore, according to PolyPhen-2 and SIFT analyses, the four non-synonymous SNPs were predicted to have deleterious effects on the function or structure of the Doppel protein. However, PANTHER and Missense3D did not indicate such effects. Conclusion: In this paper, we have identified novel SNPs in the rabbit PRND gene and predicted their potential detrimental effects on protein function or structure through four non-synonymous SNPs. Additionally, we observed a genetic linkage between SNPs in the PRND and PRNP genes. These findings may provide insights into understanding the characteristics of rabbits as partially resistant species. To the best of our knowledge, this study is the first to genetically characterize PRND SNPs in rabbits.

Novel polymorphisms and genetic studies of the shadow of prion protein gene (SPRN) in pheasants.

Background: Prion diseases in mammals are caused by the structural conversion of the natural prion protein (PrPC) to a pathogenic isoform, the "scrapie form of prion protein (PrPSc)." Several studies reported that the shadow of prion protein (Sho), encoded by the shadow of prion protein gene (SPRN), is involved in prion disease development by accelerating the conformational conversion of PrPC to PrPSc. Until now, genetic polymorphisms of the SPRN gene and the protein structure of Sho related to fragility to prion disease have not been investigated in pheasants, which are a species of poultry. Methods: Here, we identified the SPRN gene sequence by polymerase chain reaction (PCR) and compared the SPRN gene and Sho protein sequences among various prion disease-susceptible and -resistant species to identify the distinctive genetic features of pheasant Sho using Clustal Omega. In addition, we investigated genetic polymorphisms of the SPRN gene in pheasants and analyzed genotype, allele, and haplotype frequencies, as well as linkage disequilibrium among the genetic polymorphisms. Furthermore, we used in silico programs, namely Mutpred2, MUpro and AMYCO, to investigate the effect of non-synonymous single nucleotide polymorphisms (SNPs). Finally, the predicted secondary and tertiary structures of Sho proteins from various species were analyzed by Alphafold2. Results: In the present study, we reported pheasant SPRN gene sequences for the first time and identified a total of 14 novel SNPs, including 7 non-synonymous and 4 synonymous SNPs. In addition, the pheasant Sho protein sequence showed 100% identity with the chicken Sho protein sequence. Furthermore, amino acid substitutions were predicted to affect the hydrogen bond distribution in the 3D structure of the pheasant Sho protein. Conclusion: To the best of our knowledge, this is the first report of the genetic and structural features of the pheasant SPRN gene.

The First Genetic Characterization of the SPRN Gene in Pekin Ducks (Anas platyrhynchos domesticus).

Prion diseases are fatal neurodegenerative disorders characterized by an accumulation of misfolded prion protein (PrPSc) in brain tissues. The shadow of prion protein (Sho) encoded by the shadow of prion protein gene (SPRN) is involved in prion disease progress. The interaction between Sho and PrP accelerates the PrPSc conversion rate while the SPRN gene polymorphisms have been associated with prion disease susceptibility in several species. Until now, the SPRN gene has not been investigated in ducks. We identified the duck SPRN gene sequence and investigated the genetic polymorphisms of 184 Pekin ducks. We compared the duck SPRN nucleotide sequence and the duck Sho protein amino acid sequence with those of several other species. Finally, we predicted the duck Sho protein structure and the effects of non-synonymous single nucleotide polymorphisms (SNPs) using computational programs. We were the first to report the Pekin duck SPRN gene sequence. The duck Sho protein sequence showed 100% identity compared with the chicken Sho protein sequence. We found 27 novel SNPs in the duck SPRN gene. Four amino acid substitutions were predicted to affect the hydrogen bond distribution in the duck Sho protein structure. Although MutPred2 and SNPs&GO predicted that all non-synonymous polymorphisms were neutral or benign, SIFT predicted that four variants, A22T, G49D, A68T, and M105I, were deleterious. To the best of our knowledge, this is the first report about the genetic and structural characteristics of the duck SPRN gene.

Determining the vertebra for pedicle subtraction osteotomy in surgical correction for ankylosing spondylitis with thoracolumbar kyphosis.

OBJECTIVE: This study aimed to provide a method for determining the apical vertebra for pedicle subtraction osteotomy (PSO) in corrective surgery for patients with ankylosing spondylitis (AS) with thoracolumbar kyphosis (TLK). METHODS: The medical records of AS patients with TLK who underwent PSO between May 2009 and August 2022 were retrospectively reviewed, and 235 patients were included in the study. Using the proposed method, choosing the vertebra based on Kim's apex (KA), which is defined as the farthest vertebra from a line drawn from the center of the T10 vertebral body to the midpoint of the S1 upper endplate, the authors analyzed 229 patients with apices at T12, L1, or L2 (excluding L3 because of the small sample size, n = 6). They divided all patients into two groups. Group A (n = 144) underwent PSO at the KA vertebra, while group B (n = 85) underwent PSO at a different level. Demographic and radiological data, including sagittal spinopelvic parameters of the entire spine, were collected. An additional analysis was performed on patients with the same KA vertebra. RESULTS: The vertebra distributions of patients based on KA were T12 (28 [12.2%]), L1 (119 [52.0%]), and L2 (82 [35.8%]). The corrections of sagittal vertical axis (SVA; 101.0 ± 48.5 mm vs 82.0 ± 53.8 mm, p = 0.010), global kyphosis (GK; 31.6° ± 10.0° vs 26.4° ± 10.5°, p = 0.005), and TLK (29.4° ± 10.2° vs 24.2° ± 12.9°, p = 0.012) in group A were significantly greater than those in group B, and there was no difference in the corrections of thoracic kyphosis (TK), lumbar lordosis, and pelvic incidence between the two groups. On further analysis, group A showed greater correction in TK (26.2° ± 13.7° vs 0.1° ± 8.1°, p = 0.013) for patients with T12 as the KA; greater improvements in SVA (101.5 ± 44.2 mm vs 73.4 ± 48.7 mm, p = 0.020), GK (30.6° ± 11.0° vs 25.0° ± 10.4°, p = 0.046), and TLK (32.6° ± 7.8° vs 26.7° ± 9.9°, p = 0.012) for those with L1 as the KA; and significant correction in TLK (30.0° ± 6.3° vs 4.3° ± 19.5°, p = 0.008) for patients with L2 as the KA, compared with group B. CONCLUSIONS: PSO at the apical vertebra provides a greater degree of correction of sagittal imbalance. The proposed method, selecting the vertebra based on KA, is easily reproducible for determining the apex level in AS patients with TLK.

Ten-year trends of antibiotics used for patients with pneumonia at long-term care hospitals in the Republic of Korea: An analysis based on national health insurance claims data.

Aim: To determine the trends in the usage of antimicrobial drugs by patients with pneumonia with prescriptions from long-term care (LTC) hospitals in the Republic of Korea. Method: This retrospective study was conducted from 2011 to 2022 using the National Health Insurance Review and Assessment Service claim data in Korea. We calculated antibiotic usage expressed as a daily defined dose (DDD) per 1000 patients per day (DID). Results: The number of patients with pneumonia in LTC hospitals increased by 2.7 times, from 30,000 in 2011 to 79,000 in 2022. Furthermore, antibiotic consumption per episode by patients with pneumonia in LTC hospitals increased from 17.14 DDD in 2011 to 18.11 DDD in 2022. Among the Access, Watch, and Reserve classification groups, the Watch group showed the highest usage; further, the Access group showed a decreasing trend, whereas the Watch and Reserve groups showed an increasing trend (p < 0.01). In the Watch group, the most commonly used antibiotic was J01CR05 (piperacillin and beta-lactamase inhibitor), followed in order by J01DD04 (ceftriaxone), J01MA12 (levofloxacin), and J01DH02 (meropenem). In the Reserve group, J01XB01 (colistin) and J01AA12 (tigecycline) were commonly used. Conclusion: The antibiotics prescribed for pneumonia in LTC hospitals have continuously increased the use of broad-spectrum antibiotics. Accordingly, appropriate use of antibiotics in LTC hospital settings and assessment of antibiotics used are warranted.

First Report of Single Nucleotide Polymorphisms (SNPs) of the Leporine Shadow of Prion Protein Gene (SPRN) and Absence of Nonsynonymous SNPs in the Open Reading Frame (ORF) in Rabbits.

Prion disorders are fatal infectious diseases that are caused by a buildup of pathogenic prion protein (PrPSc) in susceptible mammals. According to new findings, the shadow of prion protein (Sho) encoded by the shadow of prion protein gene (SPRN) is associated with prion protein (PrP), promoting the progression of prion diseases. Although genetic polymorphisms in SPRN are associated with susceptibility to several prion diseases, genetic polymorphisms in the rabbit SPRN gene have not been investigated in depth. We discovered two novel single nucleotide polymorphisms (SNPs) in the leporine SPRN gene on chromosome 18 and found strong linkage disequilibrium (LD) between them. Additionally, strong LD was not found between the polymorphisms of PRNP and SPRN genes in rabbits. Furthermore, nonsynonymous SNPs that alter the amino acid sequences within the open reading frame (ORF) of SPRN have been observed in prion disease-susceptible animals, but this is the first report in rabbits. As far as we are aware, this study represents the first examination of the genetic features of the rabbit SPRN gene.

Effectiveness of self-management program for gastric cancer patients: A randomized controlled trial comparing gain vs. loss message framing.

OBJECTIVE: This study aims to evaluate the effectiveness of a self-management program using gain/loss-framed messages in patients with gastric cancer. METHODS: In this randomized controlled trial, 69 patients with gastric cancer who underwent gastrectomy at a university hospital were assigned to the gain- or loss-framed message group. The self-management program consisted of: 1) face-to-face education, 2) gain/loss-framed text messages, and 3) self-monitoring of health behaviors. Health outcomes (i.e., nutritional status, physical activity, exercise intensity, and distress), and health behaviors (i.e., dietary habits, physical activity performance, and distress management) were measured, and a generalized estimating equation was used for the analysis. RESULTS: Nutritional status and dietary habits in the loss framed message group were statistically higher after the intervention compared to the counterpart (ß = -1.72, p = .049; ß = 0.36, p = .033, respectively). There was no time-group interaction effect on physical activity, exercise intensity, physical activity performance, distress or distress management. CONCLUSIONS: A self-management program employing loss-framed messages was effective in promoting nutrition-related self-management among patients with gastric cancer. PRACTICE IMPLICATIONS: Message-framing is an effective communication technique that can be easily used in clinical settings, and a loss-message-framing strategy may enhance nutrition-related self-management in patients with gastric cancer.

Anterior Column Realignment Through Open Pre-posterior Release-Anterior-Posterior Fusion Versus Hybrid Minimally Invasive-Anterior-Posterior Fusion for Dynamic Sagittal Imbalance of the Spine.

STUDY DESIGN: Retrospective comparative study. OBJECTIVES: To investigate the clinical and radiological outcomes after anterior column realignment (ACR) through pre-posterior release-anterior-posterior surgery (PAP) and minimally invasive surgery -lateral lumbar interbody fusion (MIS-LLIF) using hybrid anterior-posterior surgery (AP). METHODS: A total of 91 patients who underwent ACR with long fusions from T10 vertebra to the sacropelvis with a follow-up period of at least 2 years after corrective surgery for adult spinal deformity were included and divided into two groups by surgical method: AP and PAP. AP was performed in 26 and PAP in 65 patients. Clinical outcomes and radiological parameters were investigated and compared. A further comparison was conducted after propensity score matching between the groups. RESULTS: The more increase of LL and decrease of PI-LL mismatch were observed in the PAP group than in the AP group postoperatively. After propensity score matching, total operation time and intraoperative bleeding were greater, and intensive care unit care and rod fracture were more frequent in the PAP group than in the AP group with statistical significance. Reoperation rate was higher in PAP (29.2%) than in AP (16.7%) without statistical significance. CONCLUSIONS: PAP provides a more powerful correction for severe sagittal malalignment than AP procedures. AP results in less intraoperative bleeding, operation time, and postoperative complications. Therefore, this study does not suggest that one treatment is superior to the other. LEVEL OF EVIDENCE: III.

One-year mortality and morbidities of severe fever with thrombocytopenia syndrome compared with other diseases: A nationwide cohort study in South Korea.

BACKGROUND: The long-term mortality and morbidity of patients with severe fever with thrombocytopenia syndrome (SFTS) remain unclear. METHODS: This retrospective cohort study was conducted using the National Health Insurance Service dataset on hospitalized patients with SFTS aged ≥20 years between 2016 and 2021 (n = 1,217). Each SFTS case was matched with three controls hospitalized for non-SFTS-related diseases using propensity score matching. The all-cause mortality of patients with SFTS was evaluated during the one-year follow-up and compared with that of controls. Post-discharge events were investigated to determine the effects of SFTS on post-acute sequelae. RESULTS: Finally, 1,105 patients with SFTS and 3,315 controls were included. Patients with SFTS had a higher risk of death during the one-year follow-up than that of controls (hazard ratio [HR], 2·26; 95% confidence interval [CI], 1·82-2·81). Thirty-day mortality was significantly higher in the SFTS group (HR, 3·99; 95% CI, 3·07-5·19) than in the control group. An increased risk of death after 31-365 days was observed among controls, though this difference was significant only among patients in their 80s (HR, 0·18; 95% CI, 0·06-0·57). For post-discharge events, patients in the SFTS group exhibited a higher risk of readmission (HR, 1·17; 95% CI, 1·04-1·32) and emergency room visit (HR, 2·32; 95% CI, 1·96-2·76) than those in the control group. CONCLUSION: SFTS induces a higher risk of short-term mortality and post-acute sequelae in hospitalized patients during a one-year follow-up than non-SFTS-related diseases. Our results provide guidance for the management of SFTS.

Nationwide Analysis of Antimicrobial Prescription in Korean Hospitals between 2018 and 2021: The 2023 KONAS Report.

BACKGROUND: Data on antimicrobial use at the national level are crucial for establishing domestic antimicrobial stewardship policies and enabling medical institutions to benchmark each other. This study aimed to analyze antimicrobial use in Korean hospitals. MATERIALS AND METHODS: We investigated antimicrobials prescribed in Korean hospitals between 2018 and 2021 using data from the Health Insurance Review and Assessment. Primary care hospitals (PCHs), secondary care hospitals (SCHs), and tertiary care hospitals (TCHs) were included in this analysis. Antimicrobials were categorized according to the Korea National Antimicrobial Use Analysis System (KONAS) classification, which is suitable for measuring antimicrobial use in Korean hospitals. RESULTS: Among over 1,900 hospitals, PCHs constituted the highest proportion, whereas TCHs had the lowest representation. The most frequently prescribed antimicrobials in 2021 were piperacillin/ß-lactamase inhibitor (9.3%) in TCHs, ceftriaxone (11.0%) in SCHs, and cefazedone (18.9%) in PCHs. Between 2018 and 2021, the most used antimicrobial classes according to the KONAS classification were 'broad-spectrum antibacterial agents predominantly used for community-acquired infections' in SCHs and TCHs and 'narrow spectrum beta-lactam agents' in PCHs. Total consumption of antimicrobials decreased from 951.7 to 929.9 days of therapy (DOT)/1,000 patient-days in TCHs and 817.8 to 752.2 DOT/1,000 patient-days in SCHs during study period; however, no reduction was noted in PCHs (from 504.3 to 527.2 DOT/1,000 patient-days). Moreover, in 2021, the use of reserve antimicrobials decreased from 13.6 to 10.7 DOT/1,000 patient-days in TCHs and from 4.6 to 3.3 DOT/1,000 patient-days in SCHs. However, in PCHs, the use increased from 0.7 to 0.8 DOT/1,000 patient-days. CONCLUSION: This study confirmed that antimicrobial use differed according to hospital type in Korea. Recent increases in the use of total and reserve antimicrobials in PCHs reflect the challenges that must be addressed.

Microstructural Evolution, Hardness and Wear Resistance of WC-Co-Ni Composite Coatings Fabricated by Laser Cladding.

This study investigated how process parameters of laser cladding affect the microstructure and mechanical properties of WC-12Co composite coating for use as a protective layer of continuous caster rolls. WC-Co powders, WC-Ni powders, and Ni-Cr alloy powder with various wear resistance characteristics were evaluated in order to determine their applicability for use as cladding materials for continuous caster roll coating. The cladding process was conducted with various parameters, including laser powers, cladding speeds, and powder feeding rates, then the phases, microstructure, and micro-hardness of the cladding layer were analyzed in each specimen. Results indicate that, to increase the hardness of the cladding layer in WC-Co composite coating, the dilution of the cladding layer by dissolution of Fe from the substrate should be minimized, and the formation of the Fe-Co alloy phase should be prevented. The mechanical properties and wear resistance of each powder with the same process parameters were compared and analyzed. The microstructure and mechanical properties of the laser cladding layer depend not only on the process parameters, but also on the powder characteristics, such as WC particle size and the type of binder material. Additionally, depending on the degree of thermal decomposition of WC particles and evolution of W distribution within the cladding layer, the hardness of each powder can differ significantly, and the wear mechanism can change.

Persistent differences in the immunogenicity of the two COVID-19 primary vaccines series, modulated by booster mRNA vaccination and breakthrough infection.

INTRODUCTION: The long-term impact of initial immunogenicity induced by different primary COVID-19 vaccine series remains unclear. METHODS: A prospective cohort study was conducted at 10 tertiary hospitals in Korea from March 2021 to September 2022. Immunogenicity assessments included anti-spike protein antibody (Sab), SARS-CoV-2-specific interferon-gamma releasing assay (IGRA), and multiplex cytokine assays for spike protein-stimulated plasma. Spike proteins derived from wild-type SARS-CoV-2 and alpha variant (Spike1) and beta and gamma variant (Spike2) were utilized. RESULTS: A total of 235 healthcare workers who had received a two-dose primary vaccine series of either ChAdOx1 or BNT162b2, followed by a third booster dose of BNT162b2 (166 in the ChAdOx1/ChAdOx1/BNT162b2 (CCB) group and 69 in the BNT162b2/BNT162b2/BNT162b2 (BBB) group, based on the vaccine series) were included. Following the primary vaccine series, the BBB group exhibited significantly higher increases in Sab levels, IGRA responses, and multiple cytokines (CCL2/MCP-1, CCL3/MIP-1α, CCL4/MIP-1ß, interleukin (IL)-1ra, IFN-γ, IL-2, IL-4, and IL-10) compared to the CCB group (all P < 0.05). One month after the third BNT162b2 booster, the CCB group showed Sab levels comparable to those of the BBB group, and both groups exhibited lower levels after six months without breakthrough infections (BIs). However, among those who experienced BA.1/2 BIs after the third booster, Sab levels increased significantly more in the BBB group than in the CCB group (P < 0.001). IGRA responses to both Spike1 and Spike2 proteins were significantly stronger in the BBB group than the CCB group after the third booster, while only the Spike2 response were higher after BIs (P = 0.007). The BBB group exhibited stronger enhancement of T-cell cytokines (IL-2, IL-4, and IL-17A) after BIs than in the CCB group (P < 0.05). CONCLUSION: Differences in immunogenicity induced by the two primary vaccine series persisted, modulated by subsequent booster vaccinations and BIs.