Background & Aims
Despite increasing reports of hepatitis B virus (HBV) reactivation in multiple myeloma (MM), HBV reactivation in patients with resolved hepatitis B hepatitis B surface antigen ...(HBsAg)‐negative/anti‐hepatitis B core antigen antibody (anti‐HBc)‐positive is still poorly characterized. The aim of this study was to clarify its frequency and risk factors.
Methods
A total of 230 MM patients with resolved hepatitis B were retrospectively reviewed for HBV reactivation and biochemical flare.
Results
During a median 2.4 years of follow‐up, HBV reactivation was diagnosed in 12 patients (5.2%). The cumulative rates of HBV reactivation at 2 years and 5 years were 5% and 8% respectively. A baseline anti‐HBs‐negative status (P = 0.033) and high‐dose therapy/autologous stem‐cell transplantation HDT/ASCT (P = 0.025) were significant risk factors that were positively associated with HBV reactivation. In subgroup analysis of patients treated with HDT/ASCT (n = 127), a baseline anti‐HBs‐negative status was the only significant risk factor for HBV reactivation (hazard ratio, 4.64; 95% CI, 1.47–14.7; P = 0.009).
Discussion
These data show that evaluation of anti‐HBc is needed for MM patients, and suggest that monitoring of HBV DNA should be considered for patients with resolved hepatitis B undergoing HDT/ASCT, especially those who are anti‐HBs‐negative.
In a hypoxic state, a glycolytic system is operating as a salvage pathway of generating ATP, and hexokinase II, the first enzyme in this system, might be over-expressed in hepatocellular carcinomas ...(HCCs). This study was to evaluate if hexokinase II is participating in HCC cell survival in a hypoxic state, and to analyze the mechanism of cell death caused by hexokinase II-specific inhibition.
Human hepatoma cell lines were grown either in a normoxic or hypoxic condition. Hexokinase II and hypoxia-inducible factor-1α (HIF-1α) expression were evaluated using immunoblot techniques. Cell growth was assessed using the MTS assay. Apoptotic signaling cascades were explored by immunoblot analysis.
Hypoxia stimulated HCC cellular growth through HIF-1α-dependent induction of hexokinase II expression. The hexokinase II-specific inhibitor, 3-bromopyruvate, significantly suppressed cellular growth in a hypoxic state compared to cells in a normoxic condition. This suppression was due to the induction of apoptosis through activating mitochondrial apoptotic signaling cascades.
This study demonstrates that hypoxia stimulates HCC cellular growth through hexokinase II induction, and its inhibition induces apoptotic cell death. Therefore, hexokinase II induction may participate in HCC progression and the blockage of this enzyme may therapeutically be efficacious in human HCCs.
Abstract Introduction The requirements of nondepolarizing neuromuscular blocking agent during liver transplantation show conflicting results. We sought to evaluate the requirements according to the ...operative phase and find extrahepatic factors that influence neuromuscular blocking agent requirements. Methods We enrolled 35 patients undergoing living donor liver transplantation. Continuous infusion of vecuronium was adjusted every 15 minutes for consistent neuromuscular blockade aimed at T1/Tc of 0.10 monitored with a neuromuscular transmission module. We compared the mean infusion dose in each phase, and investigated whether it is correlated with preoperative Model for End-Stage Liver Disease (MELD) score, Child-Turcotte-Pugh (CTP) score, graft-recipient weight ratio (GRWR), or time to recovery of first twitch response to train-of-four (TOF) stimulation. Results There was a significant difference between vecuronium doses during each phase ( P < .001): 0.48 ± 0.16 μg/kg/min, preanhepatic; 0.38 ± 0.14 μg/kg/min, anhepatic and 0.26 ± 0.07 μg/kg/min, neohepatic phase. There was a significant positive correlation between vecuronium infusion dose in the preanhepatic phase and CTP scores ( P = .006, correlation coefficient = 0.465). There was also a significant negative correlation between the time to recovery of first twitch response of TOF stimulation and vecuronium infusion dose in the preanhepatic phase ( P = .001, correlation coefficient = −0.546). The infusion dose during the preanhepatic phase was not associated with the MELD score, and that of neohapatic phase not with GRWR. Conclusions The vecuronium infusion dose requirement during the anhepatic decreased compared with that in the preanhepatic phase. It further decreased during the neohepatic phase compared with the previous phases. Vecuronium infusion dose reduction is suggested especially during the neohepatic phase for early extubation. The dose during the preanhepatic phase is suggested to be determined considering the CTP score and the time to recovery of the TOF response.
We have demonstrated the first example of carbon- and oxygen-free Cu(In,Ga)(SSe)2 (CIGSSe) absorber layers prepared by electrospraying a CuInGa (CIG) precursor followed by annealing, sulfurization, ...and selenization at elevated temperature. X-ray diffraction and scanning electron microscopy showed that the amorphous as-deposited (CIG) precursor film was converted into polycrystalline CIGSSe with a flat-grained morphology after post-treatment. The optimal post-treatment temperature was 300 °C for annealing and 500 °C for both sulfurization and selenization, with a ramp rate of 5 °C/min. The carbon impurities in the precursor film were removed by air annealing, and oxide that was formed during annealing was removed by sulfurization. The fabricated CIGSSe solar cell showed a conversion efficiency of 4.63% for a 0.44 cm2 area, with V oc = 0.4 V, J sc = 21 mA/cm2, and FF = 0.53.
Purpose: Direct oral anticoagulants (DOACs) are widely used for stroke prevention in atrial fibrillation. However, they have a bleeding complication. Breast cancer resistance protein, encoded by ...ABCG2, is known to be an efflux transporter of apixaban and rivaroxaban among DOACs. This study aimed to investigate the association between gene variants and bleeding complications during treatment with ABCG2 substrates (apixaban and rivaroxaban). Patients and Methods: Patients treated with apixaban and rivaroxaban were enrolled from June 2018 to December 2021. Five single nucleotide polymorphisms (SNPs) of ABCG2 were selected. Previously studied genes (ABCB1, CYP3A4, and CYP3A5) were further analyzed as possible confounders. Finally, a total of 16 SNPs were examined in this case-control study. The outcome was defined as major bleeding and clinically relevant non-major bleeding. Two models were constructed using the multivariable analysis. Results: Among 293 patients, 64 were cases. The mean age of the patients was 68.8 years, and males comprised 62.5% of the study population. Model I revealed that a history of bleeding, concurrent use of proton pump inhibitor (PPI), ABCG2 rs3114018, and ABCB1 rsl045642 were significantly associated with bleeding complications; the AORs (95% CI) were 6.209 (2.210-17.442), 2.385 (1.064-5.349), 2.188 (1.156-4.142), and 3.243 (1.371-7.671), respectively. Model II showed that modified HAS-BLED score, concurrent use of PPI, ABCG2 rs3114018, and ABCB1 rsl045642 were significantly associated with bleeding complications. Conclusion: The modified HAS-BLED score, a history of bleeding, concurrent use of PPI, ABCG2 rs3114018, and ABCB1 rsl045642 were significantly associated with the risk of bleeding complications in patients on apixaban and rivaroxaban, after adjusting for other confounders. These findings can be used to develop individualized treatment strategies for patients taking apixaban and rivaroxaban. Keywords: ABCG2, apixaban, bleeding complications, polymorphism, rivaroxaban
Abstract Cardiomyocytes in the body are subjected to cyclic mechanical strain induced by the rhythmic heart beating. In this study, we tested the hypothesis that cyclic strain promotes ...cardiomyogenesis of embryonic stem cell-derived cardiomyocytes (ESCs). ESCs cultured on elastic polymer poly(lactide- co -caprolactone), PLCL scaffolds subjected to cyclic strain in vitro displayed elevated cardiac gene expression compared to unstrained controls. Six weeks after implantation into infarcted rat myocardium, the elastic cardiac patches (ESC-seeded PLCL scaffolds) showed reduced fibrotic tissue formation, likely due to a combination of lower apoptotic activity, higher vascular endothelial growth factor (VEGF) expression, and more extensive angiogenesis in the strained versus unstrained control ESC-seeded, non-elastic poly(lactide- co -glycolide) scaffolds patches. Importantly, cardiac gene expression was upregulated in the elastic patches compared to control, with evidence for cardiomyocyte-specific microstructures including myofibrillar bundles and Z-lines. This study shows that the use of an elastic polymer scaffold designed to permit mechanical strain transduction as a cell transplantation vehicle significantly increases cardiomyogenesis of the implanted ESCs.
Abstract Introduction Mixed venous saturation (SvO2 ) reflects the balance between oxygen delivery and consumption throughout the body. A multifunction pulmonary artery catheter (PAC) can monitor ...continuous SvO2 after in vitro calibration (CSvO2 ), obviating the need for in vivo calibration with pulmonary arterial blood. In critically ill patients CSvO2 has shown a good correlation with measured SvO2 of pulmonary arterial blood using co-oximetry (MSvO2 ). The aim of this study was to compare CSvO2 and MSvO2 in liver transplantation (OLT) recipients. Methods We enrolled 44 OLT recipients for comparison with 24 coronary artery bypass graft (CABG) controls free of end-stage liver disease. After anesthetic induction, the PAC was inserted after in vitro calibration and CSvO2 and MSvO2 simultaneously measured. In OLT recipients, additional measurements of CSvO2 and MSvO2 were performed at anhepatic and postreperfusion phases. Pearson's correlation analysis was used to evaluate the correlation between the 2 measurements. A Bland-Altman analysis was used to determine precision of and bias between the 2 measurements. With ±3% regarded to be interchangeable. Results Cardiac output and intrapulmonary shunt in CABG patients were lower than among OLT recipients. OLT recipients, showed a significant correlation between CSvO2 and MSvO2 , but the coefficients were different during the three phases of OLT ( r = 0.597, 0.753, and 0.756). In addition, bias values between the two measurements were 6.0%, 6.4%, and 2.9% for the preanhepatic, anhepatic, and postreperfusion phases, respectively, with 29.5%, 31.8%, and 50% of them being interchangeable. In contrast CABG patients showed bias in −0.17% with 75% of measurements interchangeable. Conclusion While in vitro calibration of the PAC can be used in CABG patients, MSvO2 is higher than CSvO2 in OLT recipients. Therefore, in vivo calibration with pulmonary arterial blood is necessary for accurate monitoring of SvO2 in OLT recipients.
Automotive manufacturers have been trying to improve fuel efficiency without compromising the structural integrity and one of the ways to resolve the issue is to expand usage of tailor welded blanks ...(TWBs) in car body structure. Friction stir welding (FSW) is a joining process, which can be well fitted to obtaining aluminum tailored blanks when compared to other conventional joining processes. This paper presents an experimental and numerical study on TWBs produced by FSW with dissimilar aluminum 5083-H32 and 6061-T6 alloy sheets. The quality of the friction stir welded dissimilar joints was evaluated in terms of metallographic observations, hardness studies and tensile tests. Moreover, the local property changes in the weld regions were observed through digital image correlation (DIC) method. Formability of friction stir welded blanks was evaluated in the biaxial stretch forming mode using the limiting dome height (LDH) test. The failure location and the LDH values of the formed blanks were correlated to the hardness and local properties across the welds. The FE simulation of the LDH tests was also conducted incorporating Yld2000-2d anisotropy constitutive properties of the parent metal and further considering the properties of the non-homogeneous welded zone. The Marciniak-Kuczynski model was applied to predict the failure successfully in the FE model, and the results were validated with experimental data.
Risk factors associated with opioid-induced adverse reactions (OIARs) in the elderly population have not been well defined. The objective of this study was to determine effects of various risk ...factors on incidence of OIARs in male elderly patients.
A retrospective cohort study in Korea Veterans Hospital was performed. Data were analyzed in male patients aged 65 years and older who received morphine, oxycodone, or codeine. Binomial variables describing patient-related and drug-related characteristics were constructed. Associations between these variables and frequency of OIARs were determined. Odds ratio (OR) and adjusted odds ratio (AOR) were calculated from univariate and multivariable analyses, respectively. Attributable risk was obtained by (1-1/OR)*100%.
Of 316 patients, 28% experienced at least one adverse event. The most common adverse events were gastrointestinal problems (n = 59) and central nerve system adverse effects (n = 20). The odds of OIARs in patients with opioid use ≥12 weeks was increased by 80% compared to those with opioid use < 12 weeks. Attributable risk of GABA analogues was 64~78% in constructed Models. Compared to codeine users, patients using morphine and oxycodone had 653 and 473% increased odds for OIARs, respectively. MME ≥ 60 mg/day had a 317% increased odds for OIARs (95% CI: 1.92-9.04) compared to MME < 60 mg/day. Opioid combination therapy had a 139% increased odds for OIARs compared to monotherapy.
These findings have significant implications for clinical use of opioid in elderly patients. Our study suggests that low dose short-term use will pose less risk of OIARs for the elderly, whereas concomitant use of GABA analogues, strong opioids and dual-opioid therapy may increase the risk of OIARs. Therefore, clinician should carefully monitor patients when starting opioid therapy in older population.
The effects of vehicles and penetration enhancers on the in vitro permeation of ketorolac tromethamine (KT) across excised hairless mouse skins were investigated. Among pure vehicles examined, ...propylene glycol monolaurate (PGML) showed the highest permeation flux, which was 94.3 ± 17.3 µg cm2 h. Even though propylene glycol monocaprylate (PGMC) alone did not show high permeation rate, the skin permeability of KT was markedly increased by the addition of diethylene glycol monoethyl ether (DGME); the enhancement factors were 19.0 and 17.1 at 20% and 40% of DGME, respectively. When DGME was added to PGML, the permeation fluxes were almost two times at 20-60% of DGME compared to PGML alone. In the cosolvent system consisting of propylene glycol (PG)-oleyl alcohol, the permeation rate increased as the ratio of PG increased. In the study to investigate the effect of drug concentration on the permeation rate of KT, the permeation rates increased as the drug concentration increased in all vehicles used, and the dramatic increase in permeation rate was obtained when the drug concentration was higher than its solubility. For the effects of fatty acids on the permeation of KT, five fatty acids were added to PG at concentrations of 1%-, 3%-, 5%- and 10%-caprylic acid, capric acid, lauric acid, oleic acid, and linoleic acid. The enhancing effects of fatty acids were different, depending on the concentration as well as the sort of fatty acids. The highest enhancing effect was attained with 10% caprylic acid in PG; the permeation flux was 113.6 ± 17.5 µg cm2 h. The lag time of KT was reduced as the concentration of fatty acids increased except for caprylic acid.
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