Background: Enzyme immunoassays (EIAs), which detect glutamate dehydrogenase (GDH) and toxin A/B, are widely used to screen for Clostridioides difficile infection (CDI); however, their sensitivity is lower than that of molecular assays. This study aimed to evaluate the performance of two EIAs, C. Diff Quik Chek Complete (QCC) and RIDASCREEN (RIDA), and investigate the cycle threshold (Ct) values from two real-time polymerase chain reaction (PCR) assays (Allplex GI–Bacteria(I) and Xpert C. difficile) in EIA-discordant samples. Methods: A total of 180 clinical stool samples were tested using QCC, RIDA, and Allplex GI-Bacteria(I) PCR assays. The Xpert C. difficile assay was used to analyze discordant results. Results: QCC and RIDA showed high sensitivities for GDH detection, 100.0% and 94.4%, respectively. QCC was significantly more sensitive than RIDA for toxin detection (51.4% vs. 28.6%, p = 0.007). In 25 EIA-discordant, Xpert positive samples, the Ct values of the toxin B gene ranged from 31.5 to 44.8 (mean, 38.1) for Allplex PCR and from 23.7 to 36.3 (mean, 30.4) for Xpert PCR. The Ct values of the two PCR assays were not significantly correlated (r = 0.201, p = 0.324). Conclusion: QCC is a suitable initial immunological test for diagnosing CDI. The lack of correlation in the Ct values between the two real-time PCR assays suggests that assay-specific validation is necessary for cutoff level interpretation.

Malignant pericardial effusion (PE) and subsequent effusive-constrictive pericarditis (ECP) are significant clinical challenges in patients with advanced cancer. We report three patients with metastatic breast or lung cancer who experienced recurrent, life-threatening cardiac tamponade despite multiple pericardiocenteses (PCC) and systemic anti-inflammatory treatment (AIT). In all cases, pericardial disease recurred despite conventional management, while chronic systemic corticosteroid use led to debilitating adverse effects. Following complete drainage of the PE, a single high-dose bolus of 200 mg triamcinolone was administered via an intrapericardial catheter with a 12-h clamping protocol. This intervention was associated with sustained pericardial stabilization for 8 to 47 months across all three patients. Pericardial stabilization was maintained despite subsequent progression of the underlying malignancy. In this case series, high-dose (200 mg) intrapericardial corticosteroid therapy may represent a feasible therapeutic option for selected patients with recurrent malignant PE after prior PCC when systemic AIT is ineffective or poorly tolerated.

11C-acetate positron emission tomography (PET) enables simultaneous quantification of myocardial blood flow (MBF) and oxidative metabolism; however, sex-specific normative data under vasodilator stress remain insufficiently defined. We aimed to characterize these parameters in healthy individuals. Eighteen healthy individuals (9 males and 9 females, age/sex-matched; median age 43 years [range 34–65]) with normal echocardiography and no underlying cardiovascular disease underwent one-day rest-stress dynamic 11C-acetate PET with adenosine. Median stress MBF was 2.73 (2.24–3.11) mL/min/g and rest MBF 0.99 (0.82–1.14) mL/min/g. Stress kmono was 0.074 (0.063–0.082)/min, and rest kmono was 0.061 (0.050–0.068)/min. External cardiac work, total myocardial oxygen consumption (MVO₂), and MEE were 4.24 (3.75–5.54) × 10⁵ mL·mmHg/min, 16.5 (14.9–20.9) mL/min, and 17.7

Myelodysplastic syndromes (MDSs) are a group of hematologic neoplasms accompanied by dysplasia of bone marrow (BM) hematopoietic cells with cytopenia. Recently, digitalized pathology and pathomics using computerized feature analysis have been actively researched for classifying and predicting prognosis in various tumors of hematopoietic tissues. This study analyzed the pathomic features of hematopoietic cells in BM aspiration smears of patients with MDS according to each hematopoietic cell lineage and dysplasia. We included 24 patients with an MDS and 21 with normal BM. The 12,360 hematopoietic cells utilized were to be classified into seven types: normal erythrocytes, normal granulocytes, normal megakaryocytes, dysplastic erythrocytes, dysplastic granulocytes, dysplastic megakaryocytes, and others. Four hundred seventy-six pathomic features quantifying cell intensity, shape, and texture were extracted from each segmented cell. After comparing the combination of feature selection and machine learning classifier methods using 5-fold cross-validation area under the receiver operating characteristic curve (AUROC), the quadratic discriminant analysis (QDA) with gradient boosting decision tree (AUROC = 0.63) and QDA with eXtreme gradient boosting (XGB) (AUROC = 0.64) showed a high AUROC combination. Through a feature selection process, 30 characteristics were further analyzed. Dysplastic erythrocytes and granulocytes showed lower median values on heatmap analysis compared to that of normal erythrocytes and granulocytes. The data suggest that pathomic features could be applied to cell differentiation in hematologic malignancies. It could be used as a new biomarker with an auxiliary role for more accurate diagnosis. Further studies including prediction survival and prognosis with larger cohort of patients are needed.

BackgroundCoronavirus disease 2019 (COVID-19) has been widespread for over four years and has progressed to an endemic stage. Accordingly, the evaluation of host immunity in infected patients and the development of markers for prognostic prediction in the early stages have been emphasized. Soluble immune checkpoints (sICs), which regulate T cell activity, have been reported as promising biomarkers of viral infections.MethodsIn this study, quantitative values of 17 sICs and 16 cytokines (CKs) were measured using the Luminex multiplex assay. A total of 148 serum samples from 100 patients with COVID-19 were collected and the levels were compared between survivors vs. non-survivors and pneumonic vs. non-pneumonic conditions groups. The impact of these markers on overall survival were analyzed using a machine learning algorithm.ResultssICs, including sCD27, sCD40, herpes virus entry mediator (sHVEM), T-cell immunoglobulin and mucin-domain containing-3 (sTIM-3), and Toll-like receptor 2 (sTLR-2) and CKs, including chemokine CC motif ligand 2 (CCL2), interleukin-6 (IL-6), IL-8, IL-10, IL-13, granulocyte-macrophage colony-stimulating factor (GM-CSF), and tumor necrosis factor-α (TNF- α), were statistically significantly increased in the non-survivors compared to those of in the survivors. IL-6 showed the highest area under the receiver-operating curve (0.844, 95% CI = 0.751–0.913) to discriminate non-survival, with a sensitivity of 78.9% and specificity of 82.4%. In Kaplan-Meier analysis, patients with procalcitonin over 0.25 ng/mL, C-reactive protein (CRP) over 41.0 mg/dL, neutrophil-to-lymphocyte ratio over 18.97, sCD27 over 3828.8 pg/mL, sCD40 over 1283.6 pg/mL, and IL-6 over 21.6 pg/mL showed poor survival (log-rank test). In the decision tree analysis, IL-6, sTIM-3, and sCD40 levels had a strong impact on survival. Moreover, IL-6, CD40, and CRP levels were important to predict the probability of 90-d mortality using the SHapley Additive exPlanations method.ConclusionsICs and CKs, especially IL-6, sCD27, sCD40, and sTIM-3 are expected to be useful in predicting patient outcomes when used in combination with existing markers.

BACKGROUND The long-term prognosis after the discontinuation of cardioprotective therapy (CPT) in patients with cancer therapeutics-related cardiac dysfunction (CTRCD) that has shown improvement remains unclear. OBJECTIVES This study aims to assess the prognosis after CPT withdrawal in patients exhibiting improved CTRCD. METHODS In this retrospective analysis of a single-center prospective cohort study, patients with improved CTRCD, defined as an increase in left ventricular ejection fraction (LVEF) >= 10 percentage points from the time of CTRCD diagnosis, were included. We analyzed their clinical outcomes, which included hospitalization for heart failure or a decrease in LVEF >= 10 percentage points within 2 years after CTRCD improvement, alongside echocardiographic changes. RESULTS The cohort comprised 134 patients with improved CTRCD. The median follow-up duration after CTRCD diagnosis was 368.3 days (Q1-Q3: 160-536 days). After improvement, 90 patients continued CPT (continued group [CG]) and 44 withdrew CPT (withdrawn group [WG]). Among patients whose baseline LVEF at CTRCD diagnosis ranged from 45% to 55%, the final mean LVEF was comparable between both groups (CG: 64.9% f 4.4% vs WG: 62.9% f 4.2%; P = 0.059). However, for patients with a baseline LVEF <45%, the final mean LVEF was significantly lower in the WG (CG: 53.3% f 6.4% vs WG: 48.2% f 6.9%; P < 0.001). The occurrence of composite major clinical events was notably higher in the WG (HR: 3.06; 95% CI: 1.51-7.73; P = 0.002). CONCLUSIONS Patients who withdrew CPT after demonstrating improvement in CTRCD experienced worse clinical outcomes. Notably, a significant decrease in LVEF was observed after CPT withdrawal in patients with a baseline LVEF <45%.

Objective To investigate the incidence, characteristics, and outcomes of COVID-19 vaccine–related pericarditis (VRP) without myocarditis, we analyzed nationwide Korean data. Patients and Methods This is a retrospective nationwide report including all vaccinated Koreans with COVID-19 vaccine of any platform (BNT162b2, mRNA-1273, ChAdOx1, or Ad26.COV2.S) from February 26 to December 31, 2021. We analyzed the confirmed cases of COVID-19 VRP by the Expert Adjudication Committee. The incidence, clinical characteristics, and outcomes of COVID-19 VRP were analyzed. Results Among 44,322,068 Koreans with least one dose of COVID-19 vaccination, COVID-19 VRP was confirmed in 179 cases, with 1.73 per million shots (95% CI, 1.48 to 2.00 per million shots). The incidence of VRP was significantly higher in males than females (2.01 per 1 million doses vs 1.45 per 1 million doses, respectively; P=.029), in mRNA vaccines than in other vaccines (2.09 per 1 million doses vs 0.36 per 1 million doses, respectively; P<.001), and in those younger than 40 years of age than those older than 40 years of age (3.52 per 1 million doses vs 0.89 per 1 million doses, respectively; P<.001). The incidence of VRP was highest in males between the ages of 12 and 17 years (7.38 per 1 million doses; 95% CI, 2.01 to 16.07). Although there was no case of mortality, hemodynamically significant pericardial effusion requiring pericardial drainage was noted in 10 cases (5.6%). Conclusion COVID-19 VRP was very rare and developed mainly in association with mRNA vaccines, especially in males younger than 40 years of age. The clinical course of VRP was excellent, and there were no cases of mortality. However, the development of hemodynamically significant pericardial effusion should be carefully monitored.

BACKGROUND/AIM:The expression level of the voltage-dependent potassium channel Kv 11.1 was shown to be associated with the clinicopathological features, aggressiveness, and prognosis of human breast cancer. Canine mammary gland tumor (cMGT) is the most common tumor type in intact female dogs; however, the significance of Kv 11.1 in cMGT is unknown. The aim of this study was to identify Kv 11.1 expression in 57 benign and malignant cMGT tissues from dogs and to investigate the correlation of Kv 11.1 expression with the clinicopathological parameters and prognosis of cMGT.MATERIALS AND METHODS:A total of 57 samples were collected from cMGTs surgically resected at the Veterinary Medical Teaching Hospital, Seoul National University and subjected to immunohistochemistry assay using rabbit anti-Kv 11.1 polyclonal antibody. Immunohistochemical staining results were evaluated as the sum of intensity and percentage scores. The correlation between immunohistochemistry scores and clinicopathological parameters was investigated.RESULTS:Immunohistochemical analysis revealed that Kv 11.1 immunoreactivity was higher in benign cMGTs than in malignant cMGTs. Kv 11.1 expression was significantly associated with tumor malignancy (p<0.001), tumor size (p<0.001), histological grade (p<0.05), and age at the time of mastectomy (p<0.05).CONCLUSION:This study presents the first evidence of Kv 11.1 expression in cMGTs and indicates an inverse correlation between Kv 11.1 expression and tumor malignancy. Kv 11.1 expression can be used as a prognostic biomarker and a tool for the management of cMGTs.

Objective: To investigate the incidence, characteristics, and outcomes of COVID-19 vaccine-related pericarditis (VRP) without myocarditis, we analyzed nationwide Korean data. Patients and Methods: This is a retrospective nationwide report including all vaccinated Koreans with COVID-19 vaccine of any platform (BNT162b2, mRNA-1273, ChAdOx1, or Ad26.COV2.S) from February 26 to December 31, 2021. We analyzed the confirmed cases of COVID-19 VRP by the Expert Adjudication Committee. The incidence, clinical characteristics, and outcomes of COVID-19 VRP were analyzed. Results: Among 44,322,068 Koreans with least one dose of COVID-19 vaccination, COVID-19 VRP was confirmed in 179 cases, with 1.73 per million shots (95% CI, 1.48 to 2.00 per million shots). The incidence of VRP was significantly higher in males than females (2.01 per 1 million doses vs 1.45 per 1 million doses, respectively; P 1 / 4 .029), in mRNA vaccines than in other vaccines (2.09 per 1 million doses vs 0.36 per 1 million doses, respectively; P< .001), and in those younger than 40 years of age than those older than 40 years of age (3.52 per 1 million doses vs 0.89 per 1 million doses, respectively; P< .001). The incidence of VRP was highest in males between the ages of 12 and 17 years (7.38 per 1 million doses; 95% CI, 2.01 to 16.07). Although there was no case of mortality, hemodynamically significant pericardial effusion requiring pericardial drainage was noted in 10 cases (5.6%). Conclusion: COVID-19 VRP was very rare and developed mainly in association with mRNA vaccines, especially in males younger than 40 years of age. The clinical course of VRP was excellent, and there were no cases of mortality. However, the development of hemodynamically significant pericardial effusion should be carefully monitored. (c) 2024 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved. Mayo Clin Proc. 2024;99(10):1577-1588

Respiratory tract infections caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza viruses are persistent and critical. The Cobas Liat SARS-CoV-2 & influenza A/B assay (Multiplex Liat), the FDA-authorized point-of-care reverse transcriptase polymerase chain reaction (RT-PCR) assay, has a turnaround time of 20 min and high accuracy. This study evaluates the pooled performance of this assay to provide practical information. This meta-analysis was registered in PROSPERO (registration number: CRD42023467579). A systematic literature search was conducted within PubMed, Ovid-EMBASE, and the Cochrane Library for articles evaluating the accuracy of the Multiplex Liat assay through September 2023. A random-effects model was used to calculate the pooled diagnostic values with real-time RT-PCR (rRT-PCR) as a reference test. A total of 4,705 samples from eight studies were included in the primary meta-analysis. The overall pooled sensitivity and specificity of Multiplex Liat were 100.0 % (95 % confidence interval [CI] = 96.7 %-100.0 %) and 99.7 % (95 % CI = 98.7 %-99.9 %), respectively. The presence of variants of concern or in-house rRT-PCR assays as reference standards did not significantly affect the pooled diagnostic performance of the Multiplex Liat. When 5,333 samples from nine studies were assessed for sensitivity, the pooled sensitivity was 100.0 % (95 % CI = 85.8 %- 100.0 %) without a significant difference. This meta-analysis demonstrates the usefulness of Multiplex Liat for the detection of SARS-CoV-2 based on pooled diagnostic values. These practical findings may facilitate appropriate settings for the diagnosis and management of patients with respiratory tract infections.

Background/Aims The SAMe-TT2R2 score is used for assessing anticoagulation control (AC) quality with warfarin. However, it is hard to apply SAMe-TT2R2 score in Asian patients with atrial fibrillation (AF), because it has not been proven in those populations. This study aimed to validate the SAMe-TT2R2 score in Asian patients with AF and suggest a modified SAMe-TT2R2 score for this population. Methods We analyzed 710 Korean patients with AF who were using warfarin. The AC quality was assessed as the mean time in therapeutic range (TTR). Each component of SAMe-TT2R2 score was evaluated for the relationship with AC. Further clinical factors that predict AC were analyzed. Identified factors were re-assorted and constructed as SA2Me-TTR scoring system. Results Of the components of the SAMe-TT2R2 score, female, age, and rhythm control were associated with AC. Heart failure and renal insufficiency were newly identified factors associated with AC. The modified SA2Me-TTR score was reconstructed with the relevant risk factors (S, female gender, 1 point; A, age < 60 yr, 2 points; Me, medical history of heart failure, 1 point; T, treatment for rhythm control, 1 point; T, history of stroke or transient ischemic attack, 1 point; R, renal insufficiency, 1 point). The modified SA2Me-TTR score demonstrated an excellent relationship with the grading of AC. The modified SA2Me-TTR score ≤ 1 identified patients with good AC (hazard ratio 2.46, 95% CI 1.75–3.47). Conclusions The modified SA2Me-TTR score was useful for guiding oral anticoagulants selection in Asian patients with AF.

Pasteurella spp. can cause fatal zoonotic infections in humans. We performed a multicenter study to investigate the prevalence and clinical features of Pasteurella infections in South Korea during 2018-2022. We also conducted a collaborative systematic review and meta- analysis of the global burden of Pasteurella bacteremia. The study included 283 cases and found an increasing trend in Pasteurella infections. Blood cultures were positive in 8/35 (22.9%) cases sampled, for an overall bacteremia-associated rate of 2.8% (8/283). Aging was a significant risk factor for bacteremia (odds ratio 1.05 [95% CI1.01-1.10]), according to multivariate analyses. For the meta-analysis, we included a total of 2,012 cases from 10 studies. The pooled prevalence of bacteremia was 12.4% (95% CI 7.3%-18.6%) and of mortality 8.4% (95% CI 2.7%-16.5%). Our findings reflect the need for greater understanding of the increase in Pasteurella infections and the global burden of Pasteurella bacteremia to determine appropriate case management.

INTRODUCTION:Although osimertinib, a third-generation EGFR tyrosine kinase inhibitor, as the first-line therapy for metastatic NSCLC was found to have substantial survival benefits, concerns have arisen regarding its potential cardiotoxicity, particularly in real-world clinical settings. We aimed to investigate the incidence, risk factors, and reversibility of osimertinib-related cardiotoxicity. METHODS:We analyzed 1126 patients with NSCLC treated with osimertinib from May 2016 to April 2023 in two cancer centers. Osimertinib-related cardiotoxicity was defined as a composite of osimertinib-related cardiac dysfunction (ORCD), newly developed arrhythmia, and cardiac death. Total follow-up duration was 20.6 (10.8-35.2) months. RESULTS:The osimertinib was administered for a median of 12.4 months. The incidence of osimertinib-related cardiotoxicity was 4.7%. Advanced age (adjusted hazard ratio with 95% confidence interval: 1.07 [1.04-1.09], p < 0.001), a history of heart failure (3.35 [1.67-9.64], p = 0.025), atrial fibrillation (3.42 [1.27-9.22], p = 0.015), and baseline low left ventricle strain (0.87 [0.79-0.96], p = 0.005) were independently associated with development of cardiotoxicity. The recovery rate of ORCD was 82.4%, which did not differ between patients who discontinued medication and those who did not. CONCLUSIONS:In real-world practice, the incidence of osimertinib-related cardiotoxicity was 4.7%, including 3.4% for ORCD requiring cardiologic intervention, which is higher than previously reported. Given the long-term medication of osimertinib and increased mortality associated with cardiotoxicity, vigilant monitoring is crucial, especially in patients with advanced age, history of heart failure, atrial fibrillation, or decreased baseline left ventricular strain.

Background Carbapenem-resistant Pseudomonas aeruginosa (CrPA) is a leading cause of healthcare-associated urinary tract infections (UTIs). Carbapenemase production is an important mechanism that significantly alters the efficacy of frequently used anti-pseudomonal agents. Reporting the current genotypic distribution of carbapenemase-producing P. aeruginosa (CPPA) isolates in relation to antimicrobial susceptibility, UTI risk factors, and mortality is necessary to increase the awareness and control of these strains. Methods In total, 1,652 non-duplicated P. aeruginosa strains were isolated from hospitalized patients between 2015 and 2020. Antimicrobial susceptibility, carbapenemase genotypes, risk factors for UTI, and associated mortality were analyzed. Results The prevalence of carbapenem-non-susceptible P. aeruginosa isolates showed a decreasing trend from 2015 to 2018 and then increased in the background of the emergence of New Delhi metallo-β-lactamase (NDM)-type isolates since 2019. The CPPA strains showed 100.0% non-susceptibility to all tested antibiotics, except aztreonam (94.5%) and colistin (5.9%). Carbapenems were identified as a risk and common predisposing factor for UTI (odds ratio [OR]=1.943) and mortality (OR=2.766). Intensive care unit (ICU) stay (OR=2.677) and white blood cell (WBC) count (OR=1.070) were independently associated with mortality. Conclusions The changing trend and genetic distribution of CPPA isolates emphasize the need for relentless monitoring to control further dissemination. The use of carbapenems, ICU stay, and WBC count should be considered risk factors, and aggressive antibiotic stewardship programs and monitoring may serve to prevent worse outcomes.

Despite significant advancements in systemic anticancer therapies, cardiac tamponade remains a serious and potentially life-threatening complication in metastatic breast cancer (MBC). However, there is a paucity of comprehensive research investigating alternative management approaches, such as pericardiocentesis and anti-inflammatory therapy (AIT), to effectively address cardiac tamponade and mitigate the risk of heart failure arising from constrictive physiology (CP) in patients with MBC when traditional systemic anticancer drugs fail to yield favorable outcomes. Herein, we describe two cases of MBC with cardiac tamponade that occurred despite the administration of effective systemic anticancer drugs. In each case, pericardial effusion was detected in a patient who was undergoing palliative anticancer therapy for human epidermal growth factor receptor 2 (HER2)-positive MBC. The patients in these cases were successfully treated with pericardiocentesis and AIT (prednisolone and colchicine) for subsequent CP without substitution with their systemic anticancer drugs. Cardiac tamponade and CP are regarded as signs of advanced cancer and are associated with a worse clinical outcome in general; however, they can still be treated with an effective anticancer drug, pericardiocentesis, and management of CP by cardiooncology specialists.