Search

Hoon Choi,1 Jae Yen Song,2 Eun Jee Oh,3 Min Suk Chae,1 Sanghyuck Yu,1 Young Eun Moon1 1Department of Anesthesiology and Pain Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea; 2Department of Obstetrics and Gynecology, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea; 3Department of Laboratory Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of KoreaCorrespondence: Young Eun Moon, Department of Anesthesiology and Pain Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, 222, Banpo-daero, Seocho-gu, Seoul, 06591, Republic of Korea, Tel +82-2-22586163, Fax +82-2-5371951, Email momo0910@catholic.ac.krPurpose: Opioid-free anesthesia (OFA) is an emerging technique that eliminates intraoperative use of opioids and is associated with lower postoperative opioid consumption and reduced adverse postoperative events. The present study investigated the effect of OFA on the quality of recovery in patients undergoing gynecological laparoscopy.Patients and Methods: Seventy-five adult patients undergoing elective gynecological laparoscopy were randomly assigned to the OFA group with dexmedetomidine and lidocaine or the remifentanil-based anesthesia (RA) group with remifentanil. Patients, surgeons, and medical staff members providing postoperative care and assessing outcomes were blinded to group allocation. The anesthesiologist performing general anesthesia could not be blinded due to the different drug administration protocols by groups. The primary outcome was the quality of recovery measured using the Quality of Recovery-40 (QoR-40) questionnaire. Secondary outcomes were postoperative pain score, intraoperative and postoperative adverse events, and stress hormones levels.Results: The patients in both groups had comparable baseline characteristics. The QoR-40 score on postoperative day 1 was significantly higher in the OFA group than in the RA group (155.9 ± 21.2 in the RA group vs 166.9 ± 17.8 in the OFA group; mean difference: − 11.0, 95% confidence interval: − 20.0, − 2.0; p = 0.018). The visual analog scale score at 30 min after surgery was significantly lower in the OFA group than in the RA group (6.3 ± 2.3 in the RA group vs 4.1 ± 2.1 in the OFA group; p < 0.001). The incidences of nausea and shivering in the post-anesthetic care unit were also significantly lower in the OFA group (p = 0.014 and 0.025; respectively). Epinephrine levels were significantly lower in the OFA group (p = 0.002).Conclusion: OFA significantly improved the quality of recovery in patients undergoing gynecological laparoscopy.Keywords: opioid-free anesthesia, quality of recovery, laparoscopy, gynecology, opioids

The use of basiliximab induction therapy has increased in standard immunological risk patients. The objective of this study was to identify whether pretransplant donor-reactive interferon-γ enzyme-linked immunosorbent spot (ELISPOT) assay results were associated with post-transplant clinical outcomes in patients receiving basiliximab induction therapy and whether this could be helpful for choosing an efficacious immunosuppressive regimen. In 154 living donor renal transplant recipients who received basiliximab induction therapy without desensitization, we determined pretransplant ELISPOT frequencies and correlated the results with clinical outcomes based on the use of calcineurin inhibitors (tacrolimus [TAC] or cyclosporine [CSA]). The ELISPOT (+) patients had higher rate of post-transplant biopsy-proven acute rejection (AR) than ELISPOT (-) patients (P = 0.001) regardless of immunosuppressive regimen. In the logistic and multivariate regression analysis, ELISPOT was the only significant correlate of AR (P = 0.002), and the patients with increased ELISPOT results and CSA therapy were associated with AR. Our results suggest that the pretransplant ELISPOT (+) may assess the risk of poor post-transplant outcomes in patients with basiliximab induction. [ABSTRACT FROM AUTHOR]

Background: The incidence and findings of tuberculous invasion of the peripheral bronchus have not been fully investigated with MDCT. Purpose To evaluate the prevalence and findings of MDCT abnormalities of small- and medium-sized bronchus (SMB) in active pulmonary tuberculosis (TB). Material and Methods: Using multiplanar reformation, 35 consecutive MDCT scans (follow-up exams available in 14 patients with a mean interval of 8.1 months) were assessed for following abnormalities of SMB: bronchial impaction (BI), wall thickening, dilatation, peribronchial cuff of soft tissue, and bronchocavitary fistula. It was also assessed whether tree-in-buds (TIB) have a tendency to distribute in the territories of diseased SMB, and whether SMB abnormalities are present in patients with relatively mild disease. Results: SMB abnormalities were observed in 23 (65.7%) patients with active TB. The most frequent finding was wall thickening (n = 18, 51.4%), followed by BI (n = 13, 37.1%; zigzag-shaped in four), dilatation (n = 11, 31.4%), amputated appearance of air column (n = 11, 31.4%), peribronchial cuff of soft tissue (n = 10, 28.6%), and bronchocavitary fistula (n =8, 22.9%). TIB (n = 29; absent in two patients with SMB) was mainly within (n = 14) or close to (n = 4) the territory of diseased SMB. Follow-up CT frequently showed improvement of wall thickening (11/12) and persistence of bronchial dilatation (11/13). SMB abnormality was present in all of six patients with mild disease. Conclusion: MDCT shows that tuberculous invasion of the peripheral bronchus may be more frequent than previously thought, of which findings include wall thickening, BI, dilatation, amputated appearance of air column, peribronchial cuff of soft tissue and bronchocavitary fistula. [ABSTRACT FROM AUTHOR]

Background: Proper anesthesia management is required to maintain immobilization and stable breathing of the patient to improve catheter contact and stability during catheter ablation for PVI. However, it remains unclear whether the depth of neuromuscular blockade affects the results of RFCA under general anesthesia., Methods: The patients were randomly assigned to either the moderate neuromuscular blockade group (Group M, train-of-four 1 to 2) or the deep neuromuscular blockade group (Group D, posttetanic count 1-2). The primary outcome was the 12-month AF recurrence rate using confirmed electrocardiographic diagnosis after the ablation procedure at two different neuromuscular blockade depths., Results: Total 94 patients (47 in each group) were included in the analysis. Recurrence of AF during the A 12-month follow-up was 12 (25%) in group D and 22 (46%) in group M. The AF recurrence rate was significantly higher in group M (p =  0.03). The relative risk (RR) for the risk of 12-month AF recurrence was 0.545 in group D. AF symptom recurrence was observed during the A 12-month follow-up in 12 (25%) and 26 (54%) patients in groups D and M, respectively., Conclusions: Compared to moderate neuromuscular blockade, deep neuromuscular blockade while performing RFCA under general anesthesia reduced 12-month AF recurrence rate. Deep neuromuscular blockade under general anesthesia is thought to increase the success rate by providing a stable surgical environment during the RFCA procedure., Trial Registration: Clinical trials of Korea KCT 0003371., Competing Interests: No authors have competing interests., (Copyright: © 2025 Oh et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Remimazolam is a novel ultra-short-acting benzodiazepine known for its hemodynamic stability over propofol. However, its hemodynamic effects compared to those of etomidate are not well established. This study aimed to determine whether the use of remimazolam is non-inferior to etomidate with regard to the occurrence of post-induction hypotension in patients undergoing coronary arterial bypass grafting., Methods: Patients were randomly assigned to either the remimazolam group (6 m/kg/h) or the etomidate group (0.3 mg/kg) for induction of anesthesia. Anesthetic depth was adjusted based on the bispectral index (BIS). Primary outcome was the incidence of post-induction hypotension, defined as a mean arterial pressure (MAP) less than 65 mmHg within 15 min after endotracheal intubation, with a non-inferiority margin of 12%., Results: A total of 144 patients were finally analyzed. Incidence of post-induction hypotension was 36 / 71 (50.7%) in the remimazolam group and 25 / 73 (34.2%) in the etomidate group, with a rate difference of 16.5% (95% CI, 3.0-32.6) between the two groups that was beyond the prespecified non-inferiority margin of 12.0%. The number of patients who needed vasopressors was similar in the two groups., Conclusions: In this non-inferiority trial, remimazolam failed to show non-inferiority to etomidate in terms of post-induction hypotension when used as an induction drug for general anesthesia in patients undergoing coronary arterial bypass grafting. However, different doses or infusion techniques of remimazolam must be compared with etomidate in various patient groups to fully assess its hemodynamic non-inferiority during induction of anesthesia.

Objective: To identify associations between inpatient hospital design features and empirical patient clinical outcomes as well as changes over time. Background: A growing body of literature has emerged evaluating the association of hospital design features with measurable clinical outcomes during inpatient hospital admissions. However, there has been limited effort to evaluate the scope and quality of studies examining individual, inpatient hospital design features on empirical patient clinical outcomes. Methods: Primary research articles published in English between 1980 and 2021 evaluating inpatient clinical outcomes were included. Key terms for hospital designs and clinical outcomes were used. Ovid Medline, Embase, CINAHL, Web of Science, Scopus, Cochrane Library, Elsevier Embase, and Google Scholar were searched on May 28, 2021. Data were independently extracted by two authors, with arbitration from the third author. Results: Forty-six research articles were included for analysis. Predominantly studied inpatient hospital design features included: single versus multibedded rooms/wards, windows, furnishings, installed lighting, ward size and spatial arrangement, noise level, air ventilation, and patient visibility. Although nearly half (43%) of the articles lack appropriate methods to account for residual confounding, a trend of improvement in the use of appropriate methods was identified with 68% of studies in the last decade having appropriate methods. Studies demonstrating positive associations were more likely to be cited than those with negative associations (average citation per article, 508 vs. 27). Conclusion: Our study demonstrates the use of empirical patient clinical outcomes as a feasible approach to evaluate hospital design features, and identified an incremental improvement in the methods being applied., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: Housing instability is a significant contributor to poor health but remains understudied among surgical patients. We evaluated the association between housing instability and rates of unplanned surgical procedures, as well as resultant health and financial outcomes, for patients with access-sensitive conditions., Methods: Using the Healthcare Cost and Utilization Project National Inpatient Sample, we identified patients who underwent one of four selected procedures for access-sensitive surgical conditions (abdominal aortic aneurysm repair, colectomy, incisional hernia repair, and lower extremity bypass). Housing status was determined using International Classification of Disease, 10th Revision, Clinical Modification codes Z59.0 (homelessness) and Z59.1 (lack of adequate housing). Risk-adjusted multivariable logistic regression compared outcomes between patients with and without housing instability., Results: Of 1,761,965 individuals admitted for access-sensitive surgical conditions, 2280 were experiencing housing instability. Housing-unstable individuals had more than four times the odds of undergoing unplanned surgery than housing-stable individuals (odds ratio 4.41, P < 0.001). Across all procedures, individuals with housing instability experienced longer lengths of stay (planned: 5 d versus 4 d, P < 0.001; unplanned: 8 d versus 7 d, P < 0.001) and higher costs per admission following planned surgery ($20,379 versus $18,152, P < 0.001) than housing-stable individuals. Housing-unstable individuals had lower odds of complications and in-hospital mortality following planned surgeries. No differences in morbidity or mortality were identified following unplanned surgeries., Conclusions: Patients experiencing housing instability had higher odds of undergoing unplanned surgical procedures, had longer hospital stays and higher costs, and had similar or better outcomes following surgery. Efforts to expand affordable housing opportunities may improve access to timely surgical care., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: To investigate the accuracy of machine learning (ML) algorithms in stratifying risk of prolonged radiation treatment duration (RTD), defined as greater than 50 days, for patients with oropharyngeal squamous cell carcinoma (OPSCC)., Study Design: Retrospective cohort study., Setting: National Cancer Database (NCDB)., Methods: The NCDB was queried between 2004 to 2016 for patients with OPSCC treated with radiation therapy (RT) or chemoradiation as primary treatment. To predict risk of prolonged RTD, 8 different ML algorithms were compared against traditional logistic regression using various performance metrics. Data was split into a distribution of 70% for training and 30% for testing., Results: A total of 3152 patients were included (1928 prolonged RT, 1224 not prolonged RT). As a whole, based on performance metrics, random forest (RF) was found to most accurately predict prolonged RTD compared to both other ML methods and traditional logistic regression., Conclusion: Our assessment of various ML techniques showed that RF was superior to traditional logistic regression at classifying OPSCC patients at risk of prolonged RTD. Application of such algorithms may have potential to identify high risk patients and enable early interventions to improve survival., (© 2024 American Academy of Otolaryngology–Head and Neck Surgery Foundation.)

Background : Cellular and humoral immunity are key to the immune response against SARS-CoV-2, but the comparability and correlation across different assays remain underexplored. This study compares three T-cell and three antibody assays in two vaccine groups. Methods : This prospective longitudinal cohort study involved 46 naïve healthcare workers: a total of 11 in the homologous mRNA-1273 group (three doses) and 35 in the heterologous ChAd group (two ChAd doses followed by a BNT booster). Blood samples were collected at five time points. Cellular immunity was assessed using ELISPOT and two commercial interferon-gamma release assays: (IGRA)-QuantiFERON SARS-CoV-2 (QF) and Covi-FERON ELISA (CoVF). Humoral immunity was evaluated using total and IgG antibody assays and a surrogate virus neutralization test. Results : The mRNA-1273 group exhibited stronger and more consistent responses than the ChAd group. The correlations between ELISPOT and IGRA varied from weak to moderate (ρ = 0.300-0.410), while QF-IGRA and CoVF-IGRA showed stronger correlations (ρ = 0.700-0.737). The ELISPOT assay showed substantial agreement with QF [Ag2]-IGRA (k = 0.697-0.774) and CoVF [O-sp]-IGRA (k = 0.641-0.718), and an 80.4% agreement rate (k = 0.608) was found between the QF [Ag2]- and CoVF [O-sp]-IGRA tests. Three antibody assays demonstrated very strong correlations with each other and substantial to near-perfect agreement with ELISPOT (k = 0.866-0.949), QF [Ag2]-IGRA (k = 0.807-0.831), and CoVF [O-sp]-IGRA (k = 0.753-0.777). Conclusions : SARS-CoV-2-specific cellular and antibody responses vary by platform and vaccine type, highlighting the importance of measuring both T-cell and B-cell responses using multiple assays to comprehensively assess immune status.

Destabilization of heme proteins is recognized to play a role in acute kidney injury (AKI). Hemopexin (Hpx), known for its role in binding heme, mitigates free heme toxicity. Despite this, the potential adverse effects of Hpx deposition in kidney tissues and its impact on kidney function are not fully understood. Deferoxamine (DFO) chelates iron released from heme and mitigates associated kidney damage. Therefore, this study aimed to evaluate whether Hpx contributes to kidney injury in an ischemia-reperfusion injury (IRI) induced AKI model and to investigate if DFO could alleviate this damage. Mice were categorized into five groups: Sham-Vehicle, Sham-Hpx, IRI-Vehicle, IRI-Hpx, and IRI-Hpx-DFO. Decline in kidney function was observed exclusively in the IRI group, independent of Hpx injection. Serum Hpx levels remained comparable across all groups, and administration of Hpx did not alter serum Hpx levels or kidney function after 24 hours. Although increased Hpx deposition in kidneys was noted in both the IRI and Hpx groups, this accumulation did not correlate with impaired kidney function. Additionally, DFO did not exhibit a protective effect against kidney injury. In summary, Hpx does not directly induce kidney injury and cannot be considered a biomarker for kidney damage caused by IRI.

Arteriovenous malformations (AVMs) are characterized by direct connections between arteries and veins without intervening capillaries, with the concomitant formation of abnormal vascular networks associated with angiogenesis. However, the current understanding of the diagnosis and treatment of AVMs is limited, and no in vitro disease models exist at present for studying this condition. In this study, we produced endothelial cells (ECs) in two-dimensional cultures and three-dimensional (3D) blood vessel organoids (BVOs), comparing gene expression profiles between normal and AVM organoids. The normal and AVM organoids were examined via immunofluorescence staining using CD31 and phalloidin. The AVM organoids showed significantly higher expression levels of CD31 and phalloidin than the normal organoids. Genes such as FSTL1, associated with angiogenesis, showed significantly higher expression in the AVM organoids than in the normal organoids. In contrast, the MARCKS gene exhibited no significant difference in expression between the two types of organoids. The capillaries and related CSPG4 genes exhibited the lowest expression in the 3D AVM organoids. Furthermore, hsa-mir-135b-5p, a small RNA related to AVMs, showed elevated expression in AVM tissues and significantly higher levels in 3D AVM organoids. In our study, we were able to successfully establish AVM organoids (hBVOs) containing ECs and mural cells through advancements in stem cell and tissue engineering. These organoids serve as valuable models for investigating disease mechanisms, drug development, and screening potential therapeutic interventions in drug discovery. These findings contribute essential insights for the development of treatment strategies targeting AVMs.

Background: Diabetic nephropathy (DN) is a progressive complication among patients with diabetes and the most common cause of end-stage kidney disease. Neutrophil extracellular traps (NETs) are known to play a role in kidney disease, thus this study aimed to determine their role in the development of diabetic kidney disease using diabetic murine models., Results: Protein and histological analyses revealed that db/db mice and streptozotocin DN models expressed no significant NET-related proteins, myeloperoxidase, citrullinated histone H3 (citH3), neutrophil elastase, and lymphocyte antigen 6 complex locus G6D (Ly6G). However, the inflamed individuals in the DN model showed that citH3 and Ly6G were highly deposited in the renal system based on immunohistochemistry images. In vitro, NET treatment did not induce apoptosis in glomerular endothelial and renal tubular epithelial cells. NET inhibition by DNase administration demonstrated no significant changes in cell apoptosis., Conclusions: NET-related proteins were only expressed in the DN model with tubulointerstitial inflammation. Our study revealed that NETs are only induced in mice with hyperglycemia-induced inflammation., (© 2024. The Author(s).)

Cardiac biomarkers, especially high-sensitivity cardiac troponin C or I (hs-cTnC or hs-cTnI, respectively), are vital for diagnosing acute myocardial infarction (AMI). Despite the specificity of hs-cTn as a biomarker, the creatine kinase-myocardial band (CK-MB) is commonly used alongside hs-cTn in emergency departments (EDs). We analyzed 23,771 simultaneous hs-cTn (hs-cTnT or hs-cTnI) and CK-MB requests for 17,185 patients in tertiary hospital ED in 2022. The objective of this study was to assess their practical value in diagnosing AMI in real-world settings. Among all 17,185 patients tested, 98.0% underwent hs-cTnT and CK-MB tests, and substantially fewer underwent hs-cTnI testing. We observed concordance between the initial hs-cTn and CK-MB results in 71.3% of patients. Of 131 AMI cases, 57 were positive for both biomarkers, 63 for hs-cTn only, and none for CK-MB alone. CK-MB positivity was often found in the absence of AMI. Discrepancies between the hs-cTnT and hs-cTnI results occurred in 30.0% of patients. Indiscriminate CK-MB testing for diagnosing AMI in EDs should be reconsidered. Efficient use of CK-MB is important for reducing costs and ensuring optimal patient care.

This study aimed to explore how pulsed electric field (PEF) treatment affects the structural, physicochemical, and emulsification properties of porcine-derived myofibrillar proteins (MPs). Increasing PEF treatment induced partial polarization and protein unfolding, resulting in notable denaturation that affected both the secondary and tertiary structures. PEF treatment also improved the solubility and emulsification ability of MPs by reducing their pH and surface hydrophobicity. Confocal laser scanning microscopy confirmed the effective adsorption of MPs and PEF-treated MPs at the oil/water interface, resulting in well-fabricated Pickering emulsions. A weak particle network increased the apparent viscosity in short-term PEF-treated Pickering emulsions. Conversely, in emulsions with long-term PEF-treated MP, rheological variables decreased, and dispersion stability increased. These results endorse the potential application of PEF-treated porcine-derived MPs as efficient Pickering stabilizers, offering valuable insights into the creative use of PEF for enhancing high-quality meat products, meeting the increasing demand for clean-label choices., Competing Interests: Declaration of competing interest All authors declare that there is no conflict of interest., (Copyright © 2024. Published by Elsevier Ltd.)

As firms increasingly depend on artificial intelligence to evaluate people across various contexts (e.g., job interviews, performance reviews), research has explored the specific impact of algorithmic evaluations in the workplace. In particular, the extant body of work focuses on the possibility that employees may perceive biases from algorithmic evaluations. We show that although perceptions of biases are indeed a notable outcome of AI-driven assessments (vs. those performed by humans), a crucial risk inherent in algorithmic evaluations is that individuals perceive them as lacking respect and dignity. Specifically, we find that the effect of algorithmic (vs. human) evaluations on perceptions of disrespectful treatment (a) remains significant while controlling for perceived biases (but not vice versa), (b) is significant even when the effect on perceived biases is not, and (c) is larger in size than the effect on perceived biases. The effect of algorithmic evaluations on disrespectful treatment is explained by perceptions that individuals' detailed characteristics are not properly considered during the evaluation process conducted by AI., (© 2024. The Author(s).)

Chikungunya virus (CHIKV), responsible for a mosquito-borne viral illness, has rapidly spread worldwide, posing a significant global health threat. In this study, we explored the immunogenic variability of CHIKV envelope 2 (E2), a pivotal component in the anti-CHIKV immune response, using an in silico approach. After extracting the representative sequence types of the CHIKV E2 antigen, we predicted the structure-based B-cell epitopes and MHC I and II binding T-cell epitopes. Variations in key T-cell epitopes were further analyzed using molecular docking simulations. We extracted 258 E2 gene sequences from a pool of 1660 blast hits, displaying homology levels ranging from 93.6% to 100%. This revealed 44 sequence types, each representing a unique genetic variant. Phylogenetic analysis revealed distinct geographically distributed clonal lineages (clades I-IV). The B-cell linear and discontinuous epitopes demonstrated a similar distribution across the E2 protein of different strains, spanning domains A, B, and C, with some slight variations. Moreover, T-cell epitope prediction revealed eight conserved MHC class I hot spots and three MHC II hot spots, displaying variations among lineages. Among clade II strains, there were significant variations (N5H, S118G, G194S, L248F/S, and I255V/T) observed in epitopes, distinct from strains belonging to other lineages. Additionally, molecular docking showed that variations in MHC I epitopes across clonal lineages induced changes in the structure of the peptide-MHC complexes, potentially resulting in immunogenic disparities. We expect that this in silico approach will serve as a complementary tool to experimental platforms for exploring immunogenic variation or developing biomarkers for vaccine design and other related studies.

Background: Postoperative cognitive dysfunction (POCD) is one of the major complications after surgery, with devastating clinical outcomes. Although POCD is a condition with a multifactorial pathophysiology, blood-brain barrier (BBB) dysfunction and neuronal injury have been shown to play a critical role, especially in the elderly. Previous studies have demonstrated that the choice of anesthetics affect BBB permeability and neuroinflammation. However, most studies are carried out on animals, with limited research undertaken on humans. Therefore, we will compare the effect of intravenous anesthetics and inhaled anesthetics on BBB dysfunction and the change of inflammatory markers after surgery., Methods: One hundred and fifty-four patients who are 60 years of age or older undergoing major surgery for more than 2 h will be randomly allocated to two anesthetics groups (intravenous, inhaled) in a 1:1 ratio. In the intravenous anesthetics group (group P), propofol will be infused with a target-controlled infusion (TCI) system throughout the entire surgery. In the inhaled anesthetics group (group G), bolus injection of propofol will be administered for loss of consciousness, and simultaneously sevoflurane will be initiated for the maintenance of anesthesia. The primary outcome is the change in serum S100 calcium binding protein β (S100β) at four time points: before induction of anesthesia, at the end of surgery, 4 h after surgery, postoperative day 1. Secondary outcomes include changes in the inflammatory markers, serum interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)-α, and C-reactive protein; the incidence of delirium; and the change in the cognitive function between groups. In patients pre-scheduled for postoperative intensive care unit admission, the cerebrospinal fluid/serum albumin quotient (Qalb) between the two groups will be compared before and after surgery, and change in inflammatory markers in serum and CSF will be analyzed in relation to the Qalb., Discussion: The current study will compare the effect of intravenous versus inhaled anesthetics on blood-brain barrier permeability and, as a result, the difference in neuroinflammation in elderly patients. Also, the study results will provide additional information to develop intraoperative anesthetic strategies to reduce POCD., Trial Registration: The trial was prospectively registered at Clinical Trials protocol registration with identifier 2310-117-126 on April 9, 2024., (© 2024. The Author(s).)

Serum erythropoietin (sEPO) is an initial screening tool for distinguishing polycythemia vera (PV) from secondary erythrocytosis (SE), but defining 'subnormal' sEPO levels for PV diagnosis remains contentious, complicating its clinical utility. This study compares the diagnostic performance of sEPO across established subnormal limits, including reference interval (RI), clinical decision limit (CDL), and functional reference limit. sEPO levels were analyzed in 393 healthy donors (HDs) and 90 patients (41 PV and 49 SE), who underwent bone marrow biopsy and genetic tests due to erythrocytosis. The RI (2.5-97.5 percentile from HDs) of sEPO was 5.3-26.3 IU/L. A CDL of 3.1 IU/L, determined by ROC analysis in erythrocytosis patients, had a sensitivity of 80.5% and specificity of 87.8% for diagnosing PV. A functional reference limit of 7.0 IU/L, estimated based on the relationship between sEPO and hemoglobin, hematocrit, and WBC, increased sensitivity to 97.6% but decreased specificity to 46.7%. Using 5.3 IU/L as a 'subnormal' limit identified all three JAK2-negative PV cases, increasing the sensitivity and negative predictive value to 97.6% and 97.0%, respectively. Combining the RI, CDL, and functional reference limit may improve PV diagnostic accuracy.

The use of integrative Korean medicine treatment (IKMT) for patients with knee osteoarthritis (OA) has been reported previously; however, to date, no studies have investigated the long-term prognosis of these patients following IKMT for primary knee OA. We aimed to examine the long-term effects of IKMT in patients diagnosed with primary knee OA and receiving IKMT during hospitalization. This retrospective observational study, complemented by a follow-up survey, included patients with primary knee OA who received IKMT during hospitalization across 7 Korean medicine hospitals. The primary outcome was the Numerical Rating Scale knee-pain score, whereas the secondary outcomes were the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), EuroQol-5 dimension-5 level questionnaire (EQ-5D-5L), and Patient Global Impression of Change scores. Patients were evaluated at admission, discharge, and during follow-up. Of the 180 included patients, 81 responded to the survey. Compared with the corresponding values at admission, the Numerical Rating Scale score decreased by 2.44 (2.08-2.81) points at discharge and 1.89 (1.5-2.26) points at follow-up. Additionally, compared with their scores at admission, the WOMAC score decreased by 17.20 (13.68-20.71) points at discharge and 25.74 (22.22-29.26) points at follow-up, whereas the EuroQol-5 dimension-5 level questionnaire score improved by -0.15 (-0.18 to -0.12) points at discharge and -0.12 (-0.15 to -0.09) points at follow-up. The patients expressed high satisfaction with pharmacopuncture (65.4%), acupuncture (54.03%), physical therapy (35.8%), and herbal medicine (34.6%). Regarding Patient Global Impression of Change, 96.30% of the patients reported improvement. IKMT was effective in improving pain, functional disability, and quality of life in patients with primary knee OA. Its effects were maintained throughout the long-term follow-up period, and physical functions continuously improved., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Clavibacter michiganensis is a Gram-positive bacterium that causes diverse disease symptoms in tomatoes and Nicotiana benthamiana, a surrogate host plant, including canker, blister lesions, and wilting. Previously, we reported that C. michiganensis also causes necrosis in N. benthamiana leaves. Here, to identify novel virulence genes of C. michiganensis required for necrosis development in N. benthamiana leaves, we screened 1,862 transposon-inserted mutants and identified a mutant strain that exhibited weak and delayed necrosis, whereas there was no discernible difference in blister lesions, canker, or wilting symptoms. Notably, this mutant caused canker similar to that of the wild-type strain, but caused mild wilting in tomato. This mutant carried a transposon in a chromosomal gene, called Clavibactervirulence gene A1 (cviA1). CviA1 encodes a 180-amino acid protein with a signal peptide (SP) at the N-terminus and two putative transmembrane domains (TMs) at the C-terminus. Interestingly, deletion of the SP or the C-terminus, including the two putative TMs, in CviA1 failed to restore full necrosis in the mutant, highlighting the importance of protein secretion and the putative TMs for necrosis. A paralog of cviA1, cviA2 is located on the large plasmid pCM2 of C. michiganensis. Despite its high similarity to cviA1, the introduction of cviA2 into the cviA1 mutant strain did not restore virulence. Similarly, the introduction of cviA1 into the Clavibacter capsici type strain PF008, which initially lacks cviA1, did not enhance necrosis symptoms. These results reveals that the chromosomal cviA1 gene in C. michiganensis plays an important role in necrosis development in N. benthamiana leaves., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Introduction: The aim of this study is to investigate the clinical validity of donor-derived cell-free DNA (dd-cfDNA) in comparison with that of donor specific anti-HLA antibody (DSA) for predicting biopsy-proven rejection (BPR)and severe microvascular inflammation (severe MVI) in kidney transplant recipients (KTRs)., Methods: In this prospective observational investigation, 64 KTRs who underwent the indicated biopsies were included. Blood samples collected prior to biopsy were tested for dd-cfDNA and DSA. Biopsy specimens were classified by a renal pathologist according to the Banff classification. The predictive performance of dd-cfDNA and DSA for histological allograft diagnosis was assessed., Results: KTRs were categorized into the high and low dd-cfDNA groups based on a level of 0.4%. Eighteen patients (28.1%) had positive DSA at biopsy, exhibiting higher dd-cfDNA levels than the DSA-negative patients. BPR and severe MVI incidences were elevated in the high dd-cfDNA group (BPR: 42.9% vs. 3.4%, P <0.001; severe MVI: 37.1% vs. 3.4%, P = 0.001). Also, elevated glomerulitis and MVI scores were observed in the high dd-cfDNA group. DSA showed the highest predictive value for BPR (AUC = 0.880), whereas dd-cfDNA alone excelled in predicting severe MVI (AUC = 0.855). Combination of DSA and dd-cfDNA (>0.4%) yielded sensitivities of 80.0% and 50.0% with specificities of 90.7% and 88.0% for antibody-mediated rejection and severe MVI detection, respectively., Conclusion: The dd-cfDNA test is a predictive tool for BPR and severe MVI, and it can improve the performance, especially when combined with DSA for BPR., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Kim, Bae, Kang, Lee, Eum, Yang, Choi, Chung and Oh.)

Chronic graft-versus-host disease (cGVHD) is a long-term complication of allogeneic hematopoietic stem cell transplantation associated with poor quality of life and increased morbidity and mortality. Currently, there are several approved treatments for patients who do not respond to steroids, such as ruxolitinib. Nevertheless, a significant proportion of patients fail second-line treatment, indicating the need for novel approaches. Mesenchymal stem cells (MSCs) have been considered a potential treatment approach for steroid-refractory cGVHD. To evaluate the safety and efficacy of repeated infusions of MSCs, we administered intravenous MSCs every two weeks to ten patients with severe steroid-refractory cGVHD in a prospective phase I clinical trial. Each patient received a total of four doses, with each dose containing 1 × 10 6 cells/kg body weight from the same donor and same passage. Patients were assessed for their response to treatment using the 2014 National Institutes of Health (NIH) response criteria during each visit. Ten patients with diverse organ involvement were enrolled, collectively undergoing 40 infusions as planned. Remarkably, the MSC infusions were well tolerated without severe adverse events. Eight weeks after the initial MSC infusion, all ten patients showed partial responses characterized by the amelioration of clinical symptoms and enhancement of their quality of life. The overall response rate was 60%, with a complete response rate of 20% and a partial response (PR) rate of 40% at the last follow-up. Overall survival was 80%, with a median follow-up of 381 days. Two patients died due to relapse of their primary disease. Immunological analyses revealed a reduction in inflammatory markers, including Suppression of Tumorigenicity 2 (ST2), C-X-C motif chemokine ligand (CXCL)10, and Secreted phosphoprotein 1(SPP1), following the MSC treatment. Repeated MSC infusions proved to be both feasible and safe, and they may be an effective salvage therapy in patients with steroid-refractory cGVHD. Further large-scale clinical studies with long-term follow-up are needed in the future to determine the role of MSCs in cGVHD.

Background: The aim of this study is to investigate the specific pathway involved in human leukocyte antigen (HLA) sensitization using single-cell RNA-sequencing analysis and an allo-sensitized mouse model developed with an HLA.A2 transgenic mouse., Methods: For sensitization, wild-type C57BL/6 mouse received two skin grafts from C57BL/6-Tg(HLA-A2.1)1Enge/J mouse (allogeneic mouse, ALLO). For syngeneic control (SYN), skin grafts were transferred from C57BL/6 to C57BL/6. We performed single-cell RNA-sequencing analysis on splenocytes isolated from ALLO and SYN and compared the gene expression between them., Results: We generated 9,190 and 8,890 single-cell transcriptomes from ALLO and SYN, respectively. Five major cell types (B cells, T cells, natural killer cells, macrophages, and neutrophils) and their transcriptome data were annotated according to the representative differentially expressed genes of each cell cluster. The percentage of B cells was higher in ALLO than it was in SYN. Kyoto Encyclopedia of Genes and Genomes enrichment analyses indicated that the highly expressed genes in the B cells from ALLO were mainly associated with antigen processing and presentation pathways, allograft rejection, and the Th17 cell differentiation pathway. Upregulated genes in the T cells of ALLO were involved in the interleukin (IL)-17 signaling pathway. The ratio of Th17 cluster and Treg cluster was increased in the ALLO. On flow cytometry, the percentage of Th17 (IL-17+/CD4+ T) cells was higher and regulatory T cells (FOXP3+/CD4+ T) was lower in the ALLO compared to those in the SYN., Conclusion: Our results indicate that not only the B cell lineage but also the Th17 cells and their cytokine (IL-17) are involved in the sensitization to HLA.

Objectives: This study aimed to identify the cause of false-positive serum Aspergillus antigen galactomannan (GM) results in our centre., Methods: We performed a case-control study aiming to elucidate the factors associated with false-positive GM results. Independent risk factors for false-positive GM were evaluated through a multivariable regression analysis. An interrupted time series analysis was used to evaluate the effectiveness of an intervention removing the identified factors., Results: Among 568 patients tested, GM was positive in 130 patients of whom 97 had false-positive GM (cases). These were compared with 427 patients with true-negative GM (controls). Administration of dextrose-containing fluids within 6 days before GM testing was an independent predictor for false-positive GM results (adjusted odds ratio [aOR], 18.60; 95% CI, 8.95-38.66. An analysis of GM presence in different dextrose-containing fluids revealed positivity in 34.8% (8 of 23) (manufacturer A) and 33.3% (5 of 15) (manufacturer B) of the samples. Investigation of the manufacturing process revealed that the saccharification process employed enzymes derived from Aspergillus niger. After identifying the root cause of false positivity, GM-containing dextrose fluid use was restricted. Interrupted time series analysis showed an immediate reduction of GM false-positivity (-6.5% per week, p = 0.045) and a declining trend (-0.33% per week, p = 0.005) postintervention., Conclusions: Administering dextrose-containing fluids was the primary factor causing false-positive serum Aspergillus antigen GM assay results. Our investigation led to a modification of the manufacturing process of the dextrose-containing fluids., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Flow cytometric immunophenotyping of hematolymphoid neoplasms (FCI-HLN) is essential for diagnosis, classification, and minimal residual disease (MRD) monitoring. FCI-HLN is typically performed using in-house protocols, raising the need for standardization. Therefore, we surveyed the current status of FCI-HLN in Korea to obtain fundamental data for quality improvement and standardization., Methods: Eight university hospitals actively conducting FCI-HLN participated in our survey. We analyzed responses to a questionnaire that included inquiries regarding test items, reagent antibodies (RAs), fluorophores, sample amounts (SAs), reagent antibody amounts (RAAs), acquisition cell number (ACN), isotype control (IC) usage, positive/negative criteria, and reporting., Results: Most hospitals used acute HLN, chronic HLN, plasma cell neoplasm (PCN), and MRD panels. The numbers of RAs were heterogeneous, with a maximum of 32, 26, 12, 14, and 10 antibodies used for acute HLN, chronic HLN, PCN, ALL-MRD, and multiple myeloma-MRD, respectively. The number of fluorophores ranged from 4 to 10. RAs, SAs, RAAs, and ACN were diverse. Most hospitals used a positive criterion of 20%, whereas one used 10% for acute and chronic HLN panels. Five hospitals used ICs for the negative criterion. Positive/negative assignments, percentages, and general opinions were commonly reported. In MRD reporting, the limit of detection and lower limit of quantification were included., Conclusions: This is the first comprehensive study on the current status of FCI-HLN in Korea, confirming the high heterogeneity and complexity of FCI-HLN practices. Standardization of FCI-HLN is urgently needed. The findings provide a reference for establishing standard FCI-HLN guidelines.

Arteriovenous malformations (AVMs) are congenital vascular anomalies with a poor prognosis. AVMs are considered intractable diseases, as there is no established approach for early diagnosis and treatment. Therefore, this study aimed to provide new evidence by analyzing microRNAs (miRNAs) associated with AVM. We present fundamental evidence for the early diagnosis and treatment of AVM by analyzing miRNAs in the endothelial cells of AVMs. This study performed sequencing and validation of miRNAs in endothelial cells from normal and AVM tissues. Five upregulated and two downregulated miRNAs were subsequently analyzed under hypoxia and vascular endothelial growth factor (VEGF) treatment by one-way analysis of variance (ANOVA). Under hypoxic conditions, miR-135b-5p was significantly upregulated in the AVM compared to that under normal conditions, corresponding to increased endothelial activity ( p -value = 0.0238). VEGF treatment showed no significant increase in miR-135b-5p under normal conditions, however, a surge in AVM was observed. Under both hypoxia and VEGF treatment, comparison indicated a downregulation of miR-135b-5p in AVM. Therefore, miR-135b-5p was assumed to affect the pathophysiological process of AVM and might play a vital role as a potential biomarker of AVMs for application related to diagnosis and treatment.

Clavibacter bacteria use secreted apoplastic effectors, such as putative serine proteases, for virulence in host plants and for hypersensitive response (HR) induction in nonhost plants. Previously, we have shown that Clavibacter capsici ChpG Cc is important for the necrosis development in pepper ( Capsicum annuum ) leaves. Here, we determine the function of ChpG Cc , along with three paralogous proteins, for HR induction in the apoplastic space of a nonhost plant, Nicotiana tabacum . The full-length and signal peptide-deleted (ΔSP) mature forms of all proteins fused with the tobacco PR1b signal sequence were generated. The full-length and ΔSP forms of ChpG Cc and only the ΔSP forms of ChpE Cc and Pat-1 Cc , but none of the ChpC Cc , triggered HR. Based on the predicted protein structures, ChpG Cc carries amino acids for a catalytic triad and a disulfide bridge in positions like Pat-1 Cm . Substituting these amino acids of ChpG Cc with alanine abolished or reduced HR-inducing activity. To determine whether these residues are important for necrosis development in pepper, alanine-substituted chpG Cc genes were transformed into the C . capsici PF008ΔpCM1 strain, which lacks the intact chpG Cc gene. The strain with any variants failed to restore the necrosis-causing ability. These results suggest that ChpG Cc has a dual function as a virulence factor in host plants and an HR elicitor in nonhost plants. Based on our findings and previous results, we propose Clavibacter apoplastic effectors, such as ChpG Cc , Pat-1 Cm , Chp-7 Cs , and ChpG Cm , as hypersensitive response and virulence (Hrv) proteins that display phenotypic similarities to the hypersensitive response and pathogenicity (Hrp) proteins found in gram-negative bacteria. [Formula: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license., Competing Interests: The author(s) declare no conflict of interest.

The immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) becomes increasingly complex as individuals receive different combinations of vaccine doses and encounter breakthrough infections. Our study focused on the immunogenicity observed over a two-year period in healthy individuals who completed a two-dose series and then experienced booster and/or Omicron infection. In June 2023, we recruited 78 healthcare workers who had previously participated in clinical research initiated in March 2021 at a single medical center in South Korea. At 1, 5, 11, and 25 months after a second dose, we assessed SARS-CoV-2-specific humoral and cellular immune responses. Longitudinal monitoring revealed a significant decline in humoral immunity levels after the second vaccine dose, followed by a substantial increase post-third vaccination or breakthrough infection. In contrast, stable cellular immune responses were consistently observed, with peak humoral and cellular immune measures reached at 25 months after the second dose. Among infection-naïve participants, three-dose vaccinated individuals had decreased neutralizing activity against wild-type (WT) and negative activities against Omicron subvariants BA.2 and BA.4/5, whereas those who received a fourth dose of bivalent BNT had significantly increased neutralizing activity ( p < 0.05). All immune metrics tended to increase as the number of vaccine doses increased. Among participants with 4-exposure, homologous vaccination (mRNA × 4) led to higher humoral immunity, whereas heterologous vaccination (ChAd × 2/mRNA × 2) induced stronger cellular responses against multiple SARS-CoV-2 variants by enzyme-linked immunospot assays ( p < 0.05). Immune responses from bivalent vaccines or Omicron infection did not show statistically significant differences among exposure number-matched participants ( p > 0.05). Omicron exposure significantly increased cross-neutralizing activity, but magnitude of cellular immunity was not significantly altered by Omicron exposure. Our longitudinal study highlights the evolving complexity of SARS-CoV-2 immune responses, showing enhanced immunity with multiple vaccine doses and robust cellular responses from heterologous vaccination. These findings emphasize the need for ongoing surveillance to optimize vaccination strategies against emerging variants.

The emergence of microdebrider technology has revolutionized endoscopic sinus surgery (ESS). Although widely used, it has been associated with complications such as cerebrospinal fluid leakage, ocular and brain injuries, and synechia formation. However, reports on cases of skin abrasion associated with the use of microdebriders in ESS are scarce. We herein present a unique observation of bilateral nostril abrasion after ESS using the microdebrider in a 53-year-old man. The patient underwent ESS and septoplasty for nasal obstruction and polyps. Bilateral nostril erythema and skin abrasion were observed after surgery, which resolved without scarring. Nostril abrasion is attributed to the lever-like use of the microdebrider against the medial aspect of the nostril during the procedure, particularly among inexperienced surgeons. This prompts the need for a cautious approach when using microdebriders in ESS to minimize complications. Increased awareness and precautionary measures can enhance the safety of microdebriders in ESS., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 by Mutaz B. Habal, MD.)

This article report discusses a pediatric patient who suffered a corneal chemical burn injury after tonsillectomy and adenoidectomy surgery due to skin preparation with chlorhexidine. In this case, inadequate sealing of the eye shield during skin preparation allowed the chlorhexidine-alcohol solution to accumulate at its edge and gradually penetrate, resulting in the corneal injury. Prompt ophthalmological intervention and appropriate eye care treatment led to a gradual improvement in the patient's symptoms. The authors aim to present the case, share the revisions made to our skin preparation policy, and emphasize the importance of cautious antiseptic use to minimize the risk of adverse events. Adverse effects of chlorhexidine, such as hypersensitivity reactions and burns, including corneal damage, are highlighted. Health care providers should exercise caution when selecting and applying antiseptics, considering patient-specific factors, and comprehensive training should be provided to promote adherence to safe antiseptic practices during surgical procedures., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 by Mutaz B. Habal, MD.)

Mucic acid holds promise as a platform chemical for bio-based nylon synthesis; however, its biological production encounters challenges including low yield and productivity. In this study, an efficient and high-yield method for mucic acid production was developed by employing genetically engineered Saccharomyces cerevisiae expressing the NAD + -dependent uronate dehydrogenase (udh) gene. To overcome the NAD + dependency for the conversion of pectin to mucic acid, xylose was utilized as a co-substrate. Through optimization of the udh expression system, the engineered strain achieved a notable output, producing 20 g/L mucic acid with a highest reported productivity of 0.83 g/L-h and a theoretical yield of 0.18 g/g when processing pectin-containing citrus peel waste. These results suggest promising industrial applications for the biological production of mucic acid. Additionally, there is potential to establish a viable bioprocess by harnessing pectin-rich fruit waste alongside xylose-rich cellulosic biomass as raw materials., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Soo Rin Kim reports financial support was provided by National Research Foundation of Korea., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Sensitization to HLA can result in allograft loss for kidney transplantation (KT) patients. Therefore, it is required to develop an appropriate desensitization (DSZ) technique to remove HLA-donor-specific anti-HLA antibody (DSA) before KT. The aim of this research was to investigate whether combined use of the IL-6 receptor-blocking antibody, tocilizumab (TCZ), and bone-marrow-derived mesenchymal stem cells (BM-MSCs) could attenuate humoral immune responses in an allo-sensitized mouse model developed using HLA.A2 transgenic mice. Wild-type C57BL/6 mice were sensitized with skin allografts from C57BL/6-Tg (HLA-A2.1)1Enge/J mice and treated with TCZ, BM-MSC, or both TCZ and BM-MSC. We compared HLA.A2-specific IgG levels and subsets of T cells and B cells using flow cytometry among groups. HLA.A2-specific IgG level was decreased in all treated groups in comparison with that in the allo-sensitized control (Allo-CONT) group. Its decrease was the most significant in the TCZ + BM-MSC group. Regarding the B cell subset, combined use of TCZ and BM-MSC increased proportions of pre-pro B cells but decreased proportions of mature B cells in BM ( p < 0.05 vs. control). In the spleen, an increase in transitional memory was observed with a significant decrease in marginal, follicular, and long-lived plasma B cells ( p < 0.05 vs. control) in the TCZ + BM-MSC group. In T cell subsets, Th2 and Th17 cells were significantly decreased, but Treg cells were significantly increased in the TCZ+BM-MSC group compared to those in the Allo-CONT group in the spleen. Regarding RNA levels, IL-10 and Foxp3 showed increased expression, whereas IL-23 and IFN-γ showed decreased expression in the TCZ + BM-MSC group. In conclusion, combined use of TCZ and BM-MSC can inhibit B cell maturation and up-regulate Treg cells, finally resulting in the reduction of HLA.A2-specific IgG in a highly sensitized mouse model. This study suggests that the combined use of TCZ and BM-MSC can be proposed as a novel strategy in a desensitization protocol for highly sensitized patients.

Purpose: Even after uncomplicated surgery, postoperative fatigue prevalence has been reported to be 30-80% for various surgeries. We evaluated postoperative fatigue according to anesthetic technique in patients who underwent colorectal surgery., Methods: One hundred thirty patients who underwent colorectal surgery were randomly assigned to either propofol-remifentanil total intravenous anesthesia (propofol-remifentanil group, n = 65) or sevoflurane-fentanyl anesthesia (sevoflurane-fentanyl group, n = 65). The primary outcome was the prevalence of postoperative fatigue, as defined by the Chalder Fatigue Questionnaire (total score ≥ 16), at 24 h postoperatively. Secondary outcomes were early postoperative complications during hospitalization and laboratory examination., Results: The final analyses included 127 patients. The prevalence of postoperative fatigue on the 1st postoperative day was lower in the propofol-remifentanil group than the sevoflurane-fentanyl group: 56.3% (36/64) in the propofol-remifentanil group and 73.0% (46/63) in the sevoflurane-fentanyl group (relative risk [RR] = 0.77, 95% confidence interval [CI] 0.59-1.00; P = 0.048). However, there was no difference between the two groups in postoperative fatigue at postoperative day 3. Other postoperative outcomes including the severity of pain and the incidence of nausea/vomiting were not different between the two groups, but postoperative atelectasis on chest X-ray was higher in the sevoflurane-fentanyl group (2/64 [3.1%] vs. 9/63 [14.3%], P = 0.025). C-reactive protein change from preoperative to postoperative day 1 and 5 was significantly lower in the propofol-remifentanil group (P = 0.044)., Conclusion: Propofol-remifentanil total intravenous anesthesia was associated with reduced postoperative fatigue at the 1st postoperative day compared with sevoflurane-fentanyl anesthesia. Clinical trial The Korean Clinical Research Registry (study identifier: KCT0006917, principal investigator's name: MiHye Park, date of registration: January 12, 2022)., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Despite the growing awareness of the negative financial impact of traumatic injury on patients' lives, the association between financial toxicity and long-term health-related quality of life (hrQoL) among trauma survivors remains poorly understood., Methods: Patients from nine trauma centers participating in a statewide trauma quality collaborative had responses from longitudinal survey data linked to inpatient trauma registry data. Financial toxicity was defined based on patient-reported survey responses regarding medical debt, work or income loss, nonmedical financial strain, and forgone care due to costs. A financial toxicity score ranging from 0 to 4 was calculated. Health-related quality of life was assessed using the EuroQol 5 Domain tool. Multivariable regression models evaluated the association between financial toxicity and hrQoL outcomes while adjusting for patient demographics, injury severity and inpatient treatment intensity, and health systems variables., Results: Among the 403 patients providing 510 completed surveys, rates of individual financial toxicity elements ranged from 21% to 46%, with 65% of patients experiencing at least one element of financial toxicity. Patients with any financial toxicity had worse summary measures of hrQoL and higher rates of problems in all five EuroQol 5 Domain domains ( p < 0.05 for all). Younger age, lower household income, lack of insurance, more comorbidities, discharge to a facility, and air ambulance transportation were independently associated with higher odds of financial toxicity ( p < 0.05 for all). Injury traits and inpatient treatment intensity were not independently associated with financial toxicity., Conclusion: A majority of trauma survivors in this study experienced some level of financial toxicity, which was independently associated with worse risk-adjusted health outcomes across all hrQoL measures. Risk factors for financial toxicity are not related to injury severity or treatment intensity but rather to sociodemographic variables and measures of prehospital and posthospital health care resource utilization. Targeted interventions and policies are needed to address financial toxicity and ensure optimal recovery for trauma survivors., Level of Evidence: Prognostic and Epidemiological; Level III., (Copyright © 2023 American Association for the Surgery of Trauma.)

With the ongoing evolution of severe acute respiratory virus-2 (SARS-CoV-2), the number of confirmed COVID-19 cases continues to rise. This study aims to investigate the impact of vaccination status, SARS-CoV-2 variants, and disease severity on the humoral immune response, including cross-neutralizing activity, in hospitalized COVID-19 patients. This retrospective cohort study involved 122 symptomatic COVID-19 patients hospitalized in a single center. Patients were categorized based on the causative specific SARS-CoV-2 variants (33 wild-type (WT), 54 Delta and 35 Omicron) and their vaccination history. Sequential samples were collected to assess binding antibody responses (anti-S/RBD and anti-N) and surrogate virus neutralization tests (sVNTs) against WT, Omicron BA.1, and BA.4/5. The vaccinated breakthrough infection group (V) exhibited higher levels of anti-S/RBD compared to the variant-matched unvaccinated groups (UVs). The Delta infection resulted in a more rapid production of anti-S/RBD levels compared to infections with WT or Omicron variants. Unvaccinated severe WT or Delta infections had higher anti-S/RBD levels compared to mild cases, but this was not the case with Omicron infection. In vaccinated patients, there was no difference in antibody levels between mild and severe infections. Both Delta (V) and Omicron (V) groups showed strong cross-neutralizing activity against WT and Omicron (BA.1 and BA.4/5), ranging from 79.3% to 97.0%. WT (UV) and Delta (UV) infections had reduced neutralizing activity against BA.1 (0.8% to 12.0%) and BA.4/5 (32.8% to 41.0%). Interestingly, patients who received vaccines based on the ancestral spike exhibited positive neutralizing activity against BA.4/5, even though none of the study participants had been exposed to BA.4/5 and it is antigenically more advanced. Our findings suggest that a previous vaccination enhanced the humoral immune response and broadened cross-neutralizing activity to SARS-CoV-2 variants in hospitalized COVID-19 patients.

Study Objective: The emergence profiles in patients undergoing total intravenous anesthesia with either propofol or remimazolam with flumazenil reversal were compared., Design: A prospective, double-blind, randomized trial., Setting: An operating room and a post-anesthesia care unit (PACU)., Patients: Adult patients (n = 100) having American Society of Anesthesiologists (ASA) physical status of I-III undergoing general anesthesia were enrolled and randomly assigned to the propofol or the remimazolam group., Interventions: The propofol group received target-controlled infusion of propofol, and the remimazolam group received continuous infusion of remimazolam. Continuous infusion of remifentanil was used in both groups. For emergence, flumazenil was used in increments of 0.2 mg in the remimazolam group., Measurements: The primary outcome was the time required for the patient to obey verbal commands. The secondary outcomes included the time to bispectral index (BIS) over 80, the time to laryngeal mask airway (LMA) removal, the Richmond Agitation-Sedation Scale (RASS) scores in the PACU, and adverse events throughout the study period., Main Results: The time taken to obey verbal commands was significantly longer in the propofol group than the remimazolam group (14 [9, 19]) vs. 5 [3, 7]) minutes, P < 0.001; median difference -9, 95% confidence interval -11 to -6). The times to BIS over 80 and to LMA removal were also significantly longer in the propofol group. In addition, the RASS score upon arrival to the PACU differed significantly between the two groups (P = 0.006). Re-sedation in the PACU was observed in 11 (22%) of the patients in the remimazolam group., Conclusions: Remimazolam-based total intravenous anesthesia with flumazenil reversal may be effective in reducing emergence time, but a significant incidence of re-sedation was observed in the PACU. Further studies are needed to determine adequate dose and timing of routine flumazenil use and minimize the risk of re-sedation., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: To examine the association between intellectual disability and both severity of disease and clinical outcomes among patients presenting with common emergency general surgery (EGS) conditions., Background: Accurate and timely diagnosis of EGS conditions is crucial for optimal management and patient outcomes. Individuals with intellectual disabilities may be at increased risk of delayed presentation and worse outcomes for EGS; however, little is known about surgical outcomes in this population., Methods: Using the 2012-2017 Nationwide Inpatient Sample, we conducted a retrospective cohort analysis of adult patients admitted for 9 common EGS conditions. We performed multivariable logistic and linear regression to examine the association between intellectual disability and the following outcomes: EGS disease severity at presentation, any surgery, complications, mortality, length of stay, discharge disposition, and inpatient costs. Analyses were adjusted for patient demographics and facility traits., Results: Of 1,317,572 adult EGS admissions, 5,062 (0.38%) patients had a concurrent ICD-9/-10 code consistent with intellectual disability. EGS patients with intellectual disabilities had 31% higher odds of more severe disease at presentation compared with neurotypical patients (aOR 1.31; 95% CI 1.17-1.48). Intellectual disability was also associated with a higher rate of complications and mortality, longer lengths of stay, lower rate of discharge to home, and higher inpatient costs., Conclusion: EGS patients with intellectual disabilities are at increased risk of more severe presentation and worse outcomes. The underlying causes of delayed presentation and worse outcomes must be better characterized to address the disparities in surgical care for this often under-recognized but highly vulnerable population., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

We evaluated the effect of specific HLA alleles and haplotypes on cytomegalovirus (CMV)-specific cell mediated immunity (CMI) in kidney transplant (KT) candidates. CMV-specific ELISPOT against pp65 and IE-1 antigens (hereafter referred to as pp65 and IE-1, respectively) was performed in 229 seropositive KT candidates. We analyzed the results related to 44 selected HLA alleles (9 HLA-A, 15 HLA-B, 9 HLA-C, and 11 HLA-DR) and 13 HLA haplotypes commonly found in study participants. The pp65 and IE-1 results in 229 seropositive candidates were 227.5 (114.5-471.5) and 41.0 (8.8-185.8) (median [interquartile range]) spots/2 × 10 5 PBMCs, respectively. The pp65 and IE-1 results showed significant differences between candidates with different HLA alleles (A*02 vs. A*26 [p = 0.016], A*24 vs. A*30 [p = 0.031], B*07 vs. B*46 [p = 0.005], B*54 vs. B*35 [p = 0.041], B*54 vs. B*44 [p = 0.018], B*54 vs. B*51 [p = 0.025], and C*06 vs. C*14 [p = 0.034]). HLA-A*02 and B*54 were associated with increased pp65 and IE-1 results, respectively (p = 0.005 and p < 0.001, respectively). In contrast, the HLA-A*26 and B*46 alleles were associated with a decreased pp65 response, whereas the A*30 allele was associated with a decreased IE-1 response (p < 0.05). The pp65 results correlated with the HLA-A allele frequencies (R = 0.7546, p = 0.019) and the IE-1 results correlated with the HLA-C allele frequencies of the study participants (R = 0.7882, p = 0.012). Among 13 haplotypes, HLA-A*30 ~ B*13 ~ C*06 ~ DRB1*07 showed decreased CMV-CMIs compared to the other HLA haplotypes, probably due to a combination of HLA alleles associated with lower CMV-CMIs. Our results demonstrated that CMV-specific CMIs may be influenced by the HLA allele as well as the HLA haplotype. To better predict CMV reactivation, it is important to estimate risk in the context of HLA allele and haplotype information., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Assessing immune responses post-SARS-CoV-2 vaccination is crucial for optimizing vaccine strategies. This prospective study aims to evaluate immune responses and breakthrough infection in 235 infection-naïve healthcare workers up to 13-15 months after initial vaccination in two vaccine groups (108 BNT/BNT/BNT and 127 ChAd/ChAd/BNT). Immune responses were assessed using the interferon-gamma enzyme-linked immunospot (ELISPOT) assay, total immunoglobulin, and neutralizing activity through surrogate virus neutralization test at nine different time points. Both groups exhibited peak responses one to two months after the second or third dose, followed by gradual declines over six months. Notably, the ChAd group exhibited a gradual increase in ELISPOT results, but their antibody levels declined more rapidly after reaching peak response compared to the BNT group. Six months after the third dose, both groups had substantial cellular responses, with superior humoral responses in the BNT group ( p < 0.05). As many as 55 breakthrough infection participants displayed higher neutralization activities against Omicron variants, but similar cellular responses compared to 127 infection-naïve individuals, suggesting cross-immunity. Distinct neutralization classifications (<30%, >80% inhibition) correlated with different ELISPOT results. Our study reveals diverse immune response patterns based on vaccine strategies and breakthrough infections, emphasizing the importance of understanding these dynamics for optimized vaccination decisions.

Background and Objectives: The guidelines for cochlear implantation (CIs) are expanding, and the number of CI procedures performed on the elderly is increasing. The purpose of this study was to analyze the results and safety of cochlear implantation in the elderly, as well as to evaluate the predictive factors on CI outcomes., Subjects and Methods: The study included 56 patients aged ≥40 years, who received CIs between 2009 and 2020. They were divided into two groups: 27 younger adults (40-64 years) and 29 elderly (>64 years). The study compared their pre- and postoperative speech perception and category of auditory performance (CAP) scores, surgical complications, and hospitalization periods. It also evaluated associated factors in the elderly group by examining categorical and continuous variables and postoperative CAP score., Results: There was a significant improvement in speech recognition tests (both word and sentence) and CAP scores in both groups compared to the pre-implantation scores (p<0.001). Postoperative results were slightly lower in the elderly group than in younger adults for sentence recognition and CAP scores, except for word recognition. No significant associated factors were found on postoperative CAP scores, except for etiology. Postoperative CAP significantly improved in the sudden hearing loss group compared to the groups with other etiologies (p=0.045). The elderly group had more comorbidities than that in the younger adult group (p=0.026), but there were no significant differences in postoperative complications and hospitalization periods., Conclusions: While speech recognition and CAP scores were relatively lower in the elderly group compared to the younger adults, the elderly group showed significant improvements in audiological results after CI. Moreover, CI was safe and well tolerated in elderly patients.

Introduction: Polyomavirus (BKV) infection can lead to major complications and damage to the graft in kidney transplant recipients (KTRs). We investigated whether pretransplant BK serostatus and BK-specific cell-mediated immunity (CMI) predicts post-transplant BK infection., Methods: A total of 93 donor-recipient pairs who underwent kidney transplantation (KT) and 44 healthy controls were examined. Assessment of donor and recipient BKV serostatus and BKV-CMI in recipients was performed prior to transplantation using BKV-IgG ELISA and BKV-specific IFN-g ELISPOT assays against five BK viral antigens (LT, St, VP1, VP2, and VP3). BK viremia was diagnosed when blood BKV-DNA of 104 copies/mL or more was detected during follow-up periods., Results: Anti-BKV IgG antibody was detected in 74 (79.6%) of 93 KTRs and in 68 (73.1%) of 93 KT donors. A greater percentage of KTRs who received allograft from donors with high levels of anti-BKV IgG had posttransplant BK viremia (+) than KTRs from donors with low anti-BKV IgG (25.5% [12/47] vs. 4.3% [2/46], respectively; P = 0.007). Pretransplant total BKV-ELISPOT results were lower in BK viremia (+) patients than in patients without viremia (-) 20.5 [range 9.9-63.6] vs. 72.0 [43.2 - 110.8]; P = 0. 027). The sensitivity and specificity of the total BKV-ELISPOT assay (cut-off ≤ 53 spots/3×105 cells) for prediction of posttransplant BK viremia were 71.4 (95% CI: 41.9-91.6) and 54.4 (42.8-65.7), respectively. The combination of high donor BKV-IgG, low recipient BKV-IgG, and low total BKV-ELISPOT results improved specificity to 91.1%., Discussion: Our study highlights the importance of pretransplant BKV-IgG serostatus and BKV-specific CMI in predicting posttransplant BKV infection in KTRs. The combination of high donor BKV-IgG, low recipient BKV-IgG, and low total BKV-ELISPOT results predicted BK viremia after KT. Pretransplant identification of patients at highrisk for BK viremia could enable timely interventions and improve clinical outcomes of KTRs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Bae, Jung, Chung, Yang and Oh.)

Induction immunosuppressive therapy for kidney transplant recipients (KTRs) primarily includes interleukin-2 receptor antagonists, such as basiliximab (BXM) or lymphocyte-depleting agents, and anti-thymocyte globulin (ATG). This study aimed to investigate their effects on T cell dynamics during the early post-transplantation period. This prospective observational study included 157 KTRs. Peripheral blood samples were collected from each patient within 5 days before and 4 and 12 weeks after transplantation. Flow cytometric analysis was performed to assess various T cell subsets whose changes were then analyzed. In the ATG group, CD4 + T cell expression decreased significantly compared with that in the BXM group. However, CD4 + CD161 + and CD4 + CD25 + CD127low T cell expression levels increased significantly. In the CD8 + T cell subset, a decrease in CD8 + CD28nullCD57 + and CD8 + CCR7 + T cell expression was observed in the ATG group. However, among patients diagnosed with biopsy-proven acute rejection, T cell subset expression did not significantly differ relative to non-rejection cases. In conclusion, ATG induction therapy resulted in more pronounced changes in T lymphocyte subsets than BXM induction, with increased CD4 + CD161 + and CD4 + CD25 + CD127low T cells and an early decrease in CD8 + CD28nullCD57 + and CD8 + CCR7 + T cells, some of which are associated with acute rejection.

Mesenchymal stem cell (MSC)-based therapy has emerged as a promising regenerative therapeutic approach for wound healing. To determine the effects of cultured MSCs as a 2D monolayer (2D-MSCs) and 3D spheroids (3D-MSCs) on their secretomes, and to examine the effect of 3D-MSC secretomes on endothelial cells (ECs) and MSCs in a burn injury mouse model. MSCs were cultured as 2D monolayers (2D-MSCs) and 3D spheroids (3D-MSCs) and their cellular characteristics were evaluated by western blotting. 2D-MSC and 3D-MSC secretomes (condition medium: CM) were analyzed using an angiogenic array. The activation of ECs by 2D-MSC and 3D-MSC CMs was examined in cellular proliferation, migration, and tube formation assays. The wound healing effects of 2D-MSCs and 3D-MSCs were determined in vivo using a burn injury mouse model. 3D culture conditions altered the markers of components that regulate cell survival, cytoskeletal, adhesion, and proliferation. Interleukin-6 (IL-6), vascular endothelial growth factor A (VEGFA), IL-8, and chemokine (CXC motif) ligand 1 (CXCL1) were present at high levels in the CM of 3D-MSCs compared with 2D-MCs. 3D-MSC-CMs promoted the proliferation, migration, and tube formation of ECs. Furthermore, 3D-MSC treatment enhanced wound healing in a burn injury mouse model. 3D culture improves proangiogenic factors in the MSC secretome and 3D-MSCs represent a new cell-based treatment strategy for wound healing., Competing Interests: Declaration of competing interest All the authors report no relevant conflicts of interest for this article., (Copyright © 2023 Elsevier Inc. All rights reserved.)