Modified cardiovascular SOFA score in sepsis: development and internal and external validation

Background : The Sepsis-3 criteria introduced the system that uses the Sequential Organ-Failure Assessment (SOFA) score to define sepsis. The cardiovascular SOFA (CV SOFA) scoring system needs modification due to the change in guideline-recommended vasopressors. In this study, we aimed to develop and to validate the modified CV SOFA score. Methods : We developed, internally validated, and externally validated the modified CV SOFA score using the suspected infection cohort, sepsis cohort, and septic shock cohort. The primary outcome was 28-day mortality. The modified CV SOFA score system was constructed with consideration of the recently recommended use of the vasopressor norepinephrine with or without lactate level. The predictive validity of the modified SOFA score was evaluated by the discrimination for the primary outcome. Discrimination was assessed using the area under the receiver operating characteristics curve (AUC). Calibration was assessed using the calibration curve. We compared the prognostic performance of the original CV/total SOFA score and the modified CV/total SOFA score to detect mortality in patients with suspected infection, sepsis, or septic shock. Results : We identified 7,393 patients in the suspected cohort, 4038 patients in the sepsis cohort, and 3,107 patients in the septic shock cohort in seven Korean emergency departments (EDs). The 28-day mortality rates were 7.9%, 21.4%, and 20.5%, respectively, in the suspected infection, sepsis, and septic shock cohorts. The model performance is higher when vasopressor and lactate were used in combination than the vasopressor only used model. The modified CV/total SOFA score was well-developed and internally and externally validated in terms of discrimination and calibration. Predictive validity of the modified CV SOFA was significantly higher than that of the original CV SOFA in the development set (0.682 vs 0.624, p < 0.001), test set (0.716 vs 0.638), and all other cohorts (0.648 vs 0.557, 0.674 vs 0.589). Calibration was modest. In the suspected infection cohort, the modified model classified more patients to sepsis (66.0 vs 62.5%) and identified more patients at risk of septic mortality than the SOFA score (92.6 vs 89.5%). Conclusions : Among ED patients with suspected infection, sepsis, and septic shock, the newly-developed modified CV/total SOFA score had higher predictive validity and identified more patients at risk of septic mortality.National Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science and ICT (NRF2020R1A2C3004508) to Kyuseok Kim. National Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science and ICT (NRF2020R1F1A1052908) to Tae Gun Shin

Neogenin expression may be inversely correlated to the tumorigenicity of human breast cancer

BACKGROUND: Neogenin is expressed in cap cells that have been suggested to be mammary stem or precursor cells. Neogenin is known to play an important role in mammary morphogenesis; however its relationship to tumorigenesis remains to be elucidated. METHODS: To compare the expression levels of neogenin in cells with different tumorigenicity, the expression levels in M13SV1, M13SV1R2 and M13SV1R2N1 cells, which are immortalized derivatives of type I human breast epithelial cells, were evaluated. Then we measured the expression level of neogenin in paired normal and cancer tissues from eight breast cancer patients. Tissue array analysis was performed for 54 human breast tissue samples with different histology, and the results were divided into four categories (none, weak, moderate, strong) by a single well-trained blinded pathologist and statistically analyzed. RESULTS: The nontumorigenic M13SV1 cells and normal tissues showed stronger expression of neogenin than the M13SV1R2N1 cells and the paired cancer tissues. In the tissue array, all (8/8) of the normal breast tissues showed strong neogenin expression, while 93.5% (43/46) of breast cancer tissues had either no expression or only moderate levels of neogenin expression. There was a significant difference, in the expression level of neogenin, in comparisons between normal and infiltrating ductal carcinoma (p < 0.001). CONCLUSION: Neogenin may play a role in mammary carcinogenesis as well as morphogenesis, and the expression may be inversely correlated with mammary carcinogenicity. The value of neogenin as a potential prognostic factor needs further evaluation

Combination therapy of vitamin C and thiamine for septic shock in a multicentre, double-blind, randomized, controlled study (ATESS): study protocol for a randomized controlled trial

Background Septic shock is a life-threatening condition with underlying circulatory and cellular/metabolic abnormalities. Vitamin C and thiamine are potential candidates for adjunctive therapy; they are expected to improve outcomes based on recent experimental and clinical research. The aim of the Ascorbic Acid and Thiamine Effect in Septic Shock (ATESS) trial is to evaluate the effects of early combination therapy with intravenous vitamin C and thiamine on recovery from organ failure in patients with septic shock. Methods This study is a randomized, double-blind, placebo-controlled, multicentre trial in adult patients with septic shock recruited from six emergency departments in South Korea. Patients will be randomly allocated into the treatment or control group (1:1 ratio), and we will recruit 116 septic shock patients (58 per group). For the treatment group, vitamin C (50 mg/kg) and thiamine (200 mg) will be mixed in 50 ml of 0.9% saline and administered intravenously every 12 h for a total of 48 h. For the placebo group, an identical volume of 0.9% saline will be administered in the same manner. The primary outcome is the delta Sequential Organ Failure Assessment (SOFA) score (ΔSOFA = initial SOFA at enrolment – follow-up SOFA after 72 h). Discussion This trial will provide valuable evidence about the effectiveness of vitamin C and thiamine therapy for septic shock. If effective, this therapy might improve survival and become one of the main therapeutic adjuncts for patients with septic shock. Trial registration ClinicalTrials.gov, NCT03756220. Registered on 5 December 2018.This work was supported by a National Research Foundation of Korea grant funded by the Korean government (No. 2018R1C1B6006821). The government did not have any role in the study design; collection, management, analysis, and interpretation of data; writing of the report; and the decision to submit the report for publication

Anisotropic and nonlinear magnetodielectric effects in orthoferrite ErFeO3 single crystals

Abstract In rare-earth orthoferrites, strongly correlated order parameters have been thoroughly investigated, which aims to find multiple functionalities such as multiferroic or magnetoelectric properties. We have discovered highly anisotropic and nonlinear magnetodielectric effects from detailed measurements of magnetoelectric properties in single-crystalline orthoferrite, ErFeO3. Isothermal dielectric constant varies in shapes and signs depending on the relative orientations between the external electric and magnetic fields, which may be ascribed to the spin-phonon couplings. In addition, a dielectric constant with both electric and magnetic fields along the c axis exhibits two symmetric sharp anomalies, which are closely relevant to the spin-flop transition, below the ordering temperature of Er3+ spins, T Er = 3.4 K. We speculate that the magnetostriction from the exchange couplings between Er3+ and Fe3+ magnetic moments would be responsible for this relationship between electric and magnetic properties. Our results present significant characteristics of the orthoferrite compounds and offer a crucial guide for exploring suitable materials for magnetoelectric functional applications

Giant and highly anisotropic magnetocaloric effects in single crystals of disordered-perovskite RCr0.5Fe0.5O3 (R = Gd, Er)

Abstract Magnetic anisotropy is crucial in examining suitable materials for magnetic functionalities because it affects their magnetic characteristics. In this study, disordered-perovskite RCr0.5Fe0.5O3 (R = Gd, Er) single crystals were synthesized and the influence of magnetic anisotropy and additional ordering of rare-earth moments on cryogenic magnetocaloric properties was investigated. Both GdCr0.5Fe0.5O3 (GCFO) and ErCr0.5Fe0.5O3 (ECFO) crystallize in an orthorhombic Pbnm structure with randomly distributed Cr3+ and Fe3+ ions. In GCFO, the long-range order of Gd3+ moments emerges at a temperature of T Gd (the ordering temperature of Gd3+ moments) = 12 K. The relatively isotropic nature of large Gd3+ moment originating from zero orbital angular momentum exhibits giant and virtually isotropic magnetocaloric effect (MCE), with a maximum magnetic entropy change of $$\Delta {S}_{M}$$ Δ S M ≈ 50.0 J/kg·K. In ECFO, the highly anisotropic magnetizations result in a large rotating MCE characterized by a rotating magnetic entropy change $$\Delta {S}_{\theta }$$ Δ S θ = 20.8 J/kg·K. These results indicate that a detailed understanding of magnetically anisotropic characteristics is the key for exploring improved functional properties in disordered perovskite oxides

Effects of Annealing Temperature on Microstructure and Tensile Properties in Ferritic Lightweight Steels

An investigation was conducted into the effects of annealing temperature on microstructure and tensile properties of ferritic lightweight steels. Two steels were fabricated by varying the C content, and were annealed at 573 K to 1173 K (300 A degrees C to 900 A degrees C) for 1 hour. According to the microstructural analysis results, kappa-carbides were formed at about 973 K (700 A degrees C), which was confirmed by equilibrium phase diagrams calculated from a THERMO-CALC program. In the steel containing low carbon content, needle-shaped kappa-carbides were homogeneously dispersed in the ferrite matrix, whereas bulky band-shaped martensites were distributed in the steel containing high carbon content. In the 973 K (700 A degrees C)-annealed specimen of the steel containing high carbon content, deformation bands were formed throughout the specimen, while fine carbides were sufficiently deformed inside the deformation bands, thereby resulting in the greatest level of strength and ductility. These results indicated that the appropriate annealing treatment of steel containing high carbon content was useful for the improvement of both strength and ductility over steel containing low carbon content.X112327sciescopu

Tunable magnetization steps in mixed valent ferromagnet Eu2CoMnO6

Magnetic properties can be manipulated to enhance certain functionalities by tuning different material processing parameters. Here, we present the controllable magnetization steps of hysteresis loops in double-perovskite single crystals of Eu2CoMnO6. Ferromagnetic order emerges below T-C approximate to 122 K along the crystallographic c axis. The difficulty in altering Co2+ and Mn4+ ions naturally induces additional antiferromagnetic clusters in this system. Annealing the crystals in different gas environments modifies the mixed magnetic state, and results in the retardation (after O-2-annealing) and bifurcation (after Ar-annealing) of the magnetization steps of isothermal magnetization. This remarkable variation offers an efficient approach for improving the magnetic properties of double-perovskite oxides.11Nsciescopu