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Background/Aims Combination immunotherapy, exemplified by atezolizumab plus bevacizumab, has become the standard of care for inoperable hepatocellular carcinoma (HCC). However, the lack of predictive biomarkers and limited understanding of response mechanisms remain a challenge. Methods Using data from the IMbrave150plus cohort, we applied an immune signature score (ISS) predictor to stratify HCC patients treated with atezolizumab plus bevacizumab or with sorafenib alone into potential high and low response groups. By applying multiple statistical approaches including a Bayesian covariate prediction algorithm, we refined the signature to 10 key genes (ISS10) for clinical use while maintaining similar predictive power to the full model. We further validated ISS10 in an independent HCC cohort treated with nivolumab plus ipilimumab. Results The study identified a significant association between the ISS and treatment response. Among patients classified as high responders, those treated with the atezolizumab plus bevacizumab combination exhibited improved overall and progression-free survival as well as better objective response rate compared to those treated with sorafenib. We also observed a significant correlation between ISS10 and response to nivolumab plus ipilimumab treatment. Analysis of immune cell subpopulations revealed distinct characteristics associated with ISS subtypes. In particular, the ISS10 high subtype displayed a more favorable immune environment with higher proportions of antitumor macrophages and activated T-cells, potentially explaining its better response. Conclusions Our study suggests that ISS and ISS10 are promising predictive biomarkers for enhanced therapeutic outcomes in HCC patients undergoing combination immunotherapy. These markers are crucial for refining patient stratification and personalized treatment approaches to advance the effectiveness of standard-of-care regimens.

Abstract Background Surgical site infection (SSI) is not rare after loop ileostomy reversal. This study assessed the effects of a subcutaneous closed suction drain on reducing SSIs after loop ileostomy reversal with purse-string skin closure. Methods This retrospective study included 229 patients who underwent loop ileostomy reversal with purse-string closure at the Pusan National University Yangsan Hospital between January 2017 and December 2021. We divided the patients into those with a subcutaneous drain (SD group) and those without it (ND group). We analyzed variables that affected SSI occurrence in both groups. Results The SD and ND groups included 109 and 120 patients, respectively. The number of incisional SSIs was significantly lower in the SD than in the ND group (0 vs. 7 events). An average of 35.7 mL of fluid was collected in the drainage bulb during hospitalization. The C-reactive protein level on postoperative day 4 was significantly lower in the SD group than in the ND group. The insertion of a subcutaneous drain was the only factor associated with a reduced incidence of SSIs (p = 0.015). Conclusions Subcutaneous closed suction drain with purse-string skin closure in loop ileostomy reversal can reduce incisional SSI occurrence.

Abstract Background The impact of delaying atrial fibrillation catheter ablation (AFCA) for antiarrhythmic drug (AAD) management on the disease course remains unclear. This study investigated AFCA rhythm outcomes based on the diagnosis‐to‐ablation time (DAT) and AAD responsiveness in participants with persistent AF (PeAF). Methods We included data from 1038 AAD‐resistant PeAF participants, all of whom had a clear time point for AF diagnosis, especially PeAF at diagnosis time, and had undergone an AFCA for the first time. Participants who experienced recurrences of paroxysmal type on AAD therapy were analyzed as a cohort of AAD‐partial responders; those maintaining PeAF on AAD were AAD‐non‐responders. We determined the DAT cutoff for best discriminating long‐term rhythm outcomes using a maximum log‐likelihood estimation method based on the Cox proportional hazard regression model. Results Of the participants (79.8% male; median age 61), 806 (77.6%) were AAD‐non‐responders. AAD‐non‐responders had a higher body mass index and a larger left atrial diameter than AAD‐partial‐responders. They also had a higher incidence of AF recurrence after AFCA (adjusted hazard ratio 1.75, 95% confidence interval 1.33–2.30; log‐rank p

Highlights Blue micro-light-emitting diodes (μLED)-integrated gas sensors were fabricated as monolithic structure by directly loading sensing materials onto the μLED. SnO2 nanoparticles are activated by blue μLED and exhibit outstanding sensitivity to NO2 at μ-Watt power levels. Noble metal (Au, Pd, Pt)-decorated SnO2 showed the tunable gas selectivity for 4 target gases under blue light illumination.

Purpose To provide more accurate and definitive conclusions regarding the clinical and technical complications associated with the transperineal (TP) and transrectal (TR) approaches, a comprehensive review of observational studies and randomized controlled trials was conducted. This systematic review covered all eligible studies to facilitate a thorough comparison of complications linked to the two fiducial marker insertion methods, TP and TR. Methods A comprehensive search of the literature was conducted, encompassing databases such as PubMed, Embase, and the Cochrane Library, up to July 7, 2023. The relative risk and 95% confidence interval were utilized to evaluate the diagnosis and complication rates. Results The final selection for the methodological quality analysis included 13 observational studies that utilized TP and TR gold fiducial insertion approaches. The meta-analysis revealed significantly lower risks of urinary tract infections (UTI) and rectal bleeding with the TP approach. Conclusion The use of both TP and TR techniques for placing gold seed fiducial markers has proven to be an effective, safe, and well-tolerated method for image-guided radiation therapy in prostate cancer patients. A significant benefit of the TP technique is its ability to avoid rectal puncture, thereby reducing the risk of UTIs. Although the incidence of UTIs and rectal bleeding associated with the TR method is relatively low, these complications can disrupt patient wellbeing and potentially cause delays in treatment.

Background : Kidney transplantation (KT) improves physical and psychological prognoses for patients with end-stage kidney disease (ESKD). However, few comparative studies have examined depression and suicide rates among patients with ESKD treated with dialysis versus KT. Methods : Data on 21,809 patients with ESKD were extracted from the Korean National Health Insurance Service database, extending from January 2002 to December 2018. These patients exhibited no history of depression or insomnia before starting renal replacement therapy. Outcomes were compared between dialysis and KT recipients using 1:2 propensity score matching (PSM). Results : Of the patients, 17,649 received dialysis (hemodialysis, 15,537; peritoneal dialysis, 2,112), while 4,160 underwent KT. Of those on dialysis, 45.04% (7,949) experienced insomnia, compared to 25.72% (1,070) of KT recipients (P

In July 2022, stem rot symptom was found in a peony plant grown in a pot under a greenhouse at Jinju, Gyeongnam Province, South Korea. Two fungal species were isolated from the infected peony stems and cultured on 1/2-strength potato dextrose agar for identification. The morphological characteristics of the fungal isolates were examined, and nucleotide sequences of the internal transcribed spacer region, β-tubulin and translation elongation factor 1-α were analysed. The pathogenicity of the two isolates was confirmed in detached peony leaves, according to Koch's postulates. To our knowledge, this is the report of Neopestalotiopsis clavispora and Sclerotinia sclerotiorum as the causal agents of peony stem rots. Antifungal activity of chemical fungicide propineb and rhizobacterium Bacillus siamensis H30-3 was shown against the two plant pathogenic fungi N. clavispora and S. sclerotiorum. Unidentified diffusible and volatile compounds from B. siamensis H30-3 could suppress in vitro mycelial growths of N. clavispora JJ 8-2-1 and S. sclerotiorum JJ 8-2-2.

Abstract Background Hypertrophic cardiomyopathy (HCM) is frequently associated with atrial fibrillation (AF). We compared clinical, echocardiographic, and electrophysiological parameters between HCM subtypes and those without HCM at AF catheter ablation (AFCA) and analyzed post‐AFCA reverse remodeling and AF recurrence based on HCM presence and subtype. Methods Among 5161 consecutive patients who underwent de novo AFCA, we included HCM patients and control patients who were age‐, gender‐, and AF type‐matched. Between AF‐HCM patients and controls, we compared baseline values for left atrium (LA) wall thickness (LAWT), reverse remodeling at 1‐year follow‐up, and procedural outcomes over the course of follow‐up between two groups. Results A total of 122 AF‐HCM patients and 318 control patients were included. AF‐HCM patients had more frequent heart failure and higher LA diameter, E/Em, and LA pressure (all, p

Abstract Background The lack of distinct biomarkers for pancreatic cancer is a major cause of early-stage detection difficulty. The pancreatic cancer patient group with high metabolic tumor volume (MTV), one of the values measured from positron emission tomography—a confirmatory method and standard care for pancreatic cancer, showed a poorer prognosis than those with low MTV. Therefore, MTV-associated differentially expressed genes (DEGs) may be candidates for distinctive markers for pancreatic cancer. This study aimed to evaluate the possibility of MTV-related DEGs as markers or therapeutic targets for pancreatic cancer. Methods Tumor tissues and their normal counterparts were obtained from patients undergoing preoperative 18F-FDG PET/CT. The tissues were classified into MTV-low and MTV-high groups (7 for each) based on the MTV2.5 value of 4.5 (MTV-low: MTV2.5

Purpose Surgeons can treat debilitating conditions of uncontrollable complex anorectal fistulas with sepsis, even after repeated fistula surgeries, for curative intention. Adipose-derived stem cells have shown good outcomes for refractory Crohn fistula. Unfortunately, cell therapy has some limitations, including high costs. We have therefore attempted immediate cell-assisted lipotransfer (CAL) in treating refractory complex anal fistulas and observed its outcomes. Methods In a retrospective study, CAL, using a mixture of freshly extracted autologous stromal vascular fraction and fat tissues, was used to treat 22 patients of refractory complex anal fistula from March 2018 to May 2021. Preoperative and postoperative assessments were performed with direct visual inspection, digital palpation, and endoanal ultrasonography. A fistula was considered completely healed if (1) the patient had no symptoms of discharge or inflammation; (2) there were no visible secondary openings of fistula tract inside and outside of the anorectal unit and even in the perineum; and (3) there was no primary opening in the anus. The endpoint of complete remission was wound healing without signs of inflammation 3 months after CAL treatment. Results In a total of 22 patients who received CAL treatment, 19 patients showed complete remission, 1 patient showed partial improvement, and 2 patients showed no improvement. One of the 2 patients without improvement at primary endpoint showed complete remission 9 months after CAL. There were no significant adverse effects of the procedure. Conclusion We found that the immediately-collected CAL procedure for refractory complex anal fistula showed good outcomes without adverse side effects. It can be strongly recommended as an alternative surgical option for the treatment of complex anal fistula that is uncontrollable even after repeated surgical procedures. However, considering the unpredictable characteristics of stromal vascular fraction, long-term follow-up is necessary.

Abstract Background To report a case of central retinal artery occlusion (CRAO) after intravitreal injection of brolucizumab for a treatment-naïve neovascular age-related macular degeneration (nAMD) patient without comorbid cardiovascular disease history. Case presentation A 79-year-old Asian male without a cardiovascular disease history such as diabetes or hypertension underwent three times of monthly consecutive intravitreal brolucizumab injections for treatment of progressed nAMD in his left eye. Two days after the third injection, the patient presented with acute painless visual loss. Typical retinal whitening with a cherry red spot was observed on the fundus photograph, and retinal swelling with hyper-reflectivity was also identified on the optical coherence tomography (OCT) scan. On the fundus fluorescein angiography, arm-to-retina time and arteriovenous transit time were remarkedly delayed, but clinical findings suggesting an intraocular inflammation (IOI) were not observed. Therefore, CRAO was diagnosed, and anterior chamber paracentesis was administrated immediately. However, there had been no improvement in visual acuity during the follow-up period of three months, despite prolonged oral steroid and anti-platelet agent medication. Conclusions In rare cases, patients without cardiovascular comorbidities can develop CRAO after intravitreal brolucizumab injection without gross evidence of IOI. Therefore, CRAO should always be in consideration and careful observation is required after intravitreal brolucizumab injection for nAMD patients with old age, even if the patient does not have any other cardiovascular disease history.

Abstract Background Pneumococcal vaccination is a preventive method to reduce pneumonia related mortality. However, real-world data on efficacy of the pneumococcal vaccine in reducing mortality is lacking, especially in elderly patients. This study was conducted to assess the effects of prior pneumococcal vaccination in elderly pneumonia patients. Methods The data was procured from the Health Insurance Review and Assessment and Quality Assessment database. Hospitalized patients who met the criteria of community-acquired pneumonia (CAP) were included and they were grouped according to vaccination state. Patients were aged ≥ 65 years and treated with beta-lactam, quinolone, or macrolide. Patients were excluded when treatment outcomes were unknown. Results A total of 4515 patients were evaluated, and 1609 (35.6%) of them were vaccinated prior to hospitalization. Mean age was 77.0 [71.0;82.0], 54.2% of them were male, and mean Charlson comorbidity index (CCI) was 3.0. The patients in the vaccinated group were younger than those in the unvaccinated group (76.0 vs. 78.0 years; P

The Al alloy containing 17 wt% Zn exhibits enhanced strength through Zn precipitation after casting without the need for further aging treatment. DFT (Density Functional Theory) calculations revealed that the addition of Cu and Mg elements to Al-Zn alloy has the potential to stabilize the Zn phase in the Al matrix and reduce the interface energy between the Zn precipitate and Al matrix. Based on these findings, 0.5 wt% Cu and 0.1 wt% Mg were added to the Al-17 wt% Zn alloy. The trace element level of 0.1 wt% Mg addition led to a significant increase in both yield and tensile strength, from 132 to 278 and from 248 to 310 MPa, respectively, compared to the Al-17 wt% Zn alloy with 0.5 wt% Cu. Furthermore, their ductility surpassed 11 %. The trace amount of Mg greatly increased yield and tensile strength, while Cu enhanced the ductility in the Al-Zn alloy after casting without any aging treatment.

The Zn element precipitates during aging in the Al–Zn binary alloy. Increased Zn content and prolonged aging leads to discontinuous Zn precipitation. The addition of 2 wt% Cu to the Al-43 wt%Zn alloy accelerates this discontinuous precipitation, resulting in decreased thickness of Zn layers and inter-distance between them. This acceleration is attributed to the influence of Cu solutes on the Zn phase, thereby reducing the interface energy between Zn precipitates and the Al matrix. The Al–Zn–Cu alloy demonstrates exceptional behavior during tensile tests, displaying a simultaneous increase in tensile strength and ductility alongside an 75 % reduction in area at room temperature drawing. Notably, despite the drawn beyond uniform deformation limit, there is an observed increase in total elongation. Our demonstration highlights this phenomenon, attributing it to the sustained coherent interface between the Zn layer and the Al matrix, as well as the uninterrupted continuity of Zn layers during drawing.

Inclusion effect of different amount of jack mackerel meal (JMM) in the diets substituting 50% fish meal (FM) with corn gluten meal (CGM) on growth, feed availability, biochemical composition, plasma, and serum chemistry of olive flounder (Paralichthys olivaceus) was elucidated. Seven experimental diets were formulated. The control (Con) diet contained 60% FM. Fifty percent of FM in the Con diet was substituted with CGM, and then 5, 10, 20, 30, 40, and 50% JMM were added at the expense of FM to formulate the CJ5, CJ10, CJ20, CJ30, CJ40, and CJ50 diets, respectively. All formulated feeds were assigned to triplicate groups of fish. A total of 420 juvenile fish averaging 18 ± 0.01 g (mean ± SEM) was uniformly divided into 21, 50-L tanks, with 20 fish per tank. Fish were carefully hand-fed to satiation for 8 weeks. The weight gain of olive flounder fed the Con diet was significantly (p 0.05) different from that of fish fed the CJ30, CJ40, and CJ50 diets. Olive flounder fed the Con diet achieved significantly (p 0.05) different from those of fish fed the CJ20, CJ30, CJ40, and CJ50 diets. However, there were no significant (p > 0.05) differences in feed utilization, proximate composition, amino acid profiles, and plasma and serum parameters of olive flounder. In conclusion, incorporation of 30, and 20% JMM are the most desirable treatments in the olive flounder diets replacing 50% FM with CGM based on weight gain, and SGR and feed consumption, respectively. This study will be very helpful to develop low-FM diets for sustainable olive flounder culture.

The low fish meal (FM) diet commonly causes deteriorated palatability, and eventually leads to lowered feed consumption and growth performance of fish. This study was, therefore, designed to determine inclusion impact of the graded levels of jack mackerel meal (JMM) in olive flounder (P. olivaceus) diets replacing 50% FM with tuna by-product meal (TBM) on growth, feed availability, biochemical composition, blood chemistry, and economic efficiency. Six isonitrogenous (55.5%) and isolipidic (10.0%) diets were formulated. Sixty percent FM was incorporated in the control (Con) diet. In the Con diet, fifty percent of FM was replaced by TBM, and then 10, 20, 30, 40, and 50% JMM were included at the cost of FM, referred as the TJ10, TJ20, TJ30, TJ40, and TJ50 diets, respectively. Three hundred and sixty juvenile fish (18.0 ± 0.01g; mean ± SD) were delivered into 18, 50-L flow-through tanks. All diets were randomly assigned to triplicate groups of fish. Fish were hand-fed to apparent satiation twice daily for 56 days. Weight gain, specific growth rate, and feed consumption of fish fed the TJ30, TJ40, and TJ50 diets were significantly (P < 0.001, P < 0.001, and P < 0.002, respectively) greater than those of fish fed the Con and TJ10 diets, but not significantly (P > 0.05) different from those of fish fed the TJ20 diet. Feed utilization, proximate composition, amino acid profiles, and blood chemistry of fish were not significantly (P > 0.05) altered by dietary treatments. However, the TJ30 diet was the most recommendable to farmers in terms of economic profit index (EPI). Conclusively, 30% inclusion of JMM is the most recommendable in the olive flounder diet substituting 50% FM with TBM based on growth performance, feed availability, and EPI.

Abstract Idiopathic pulmonary fibrosis (IPF) is characterized by aberrant lung remodeling and the excessive accumulation of extracellular matrix (ECM) proteins. In a previous study, we found that the levels of ornithine aminotransferase (OAT), a principal enzyme in the proline metabolism pathway, were increased in the lungs of patients with IPF. However, the precise role played by OAT in the pathogenesis of IPF is not yet clear. The mechanism by which OAT affects fibrogenesis was assessed in vitro using OAT-overexpressing and OAT-knockdown lung fibroblasts. The therapeutic effects of OAT inhibition were assessed in the lungs of bleomycin-treated mice. OAT expression was increased in fibrotic areas, principally in interstitial fibroblasts, of lungs affected by IPF. OAT levels in the bronchoalveolar lavage fluid of IPF patients were inversely correlated with lung function. The survival rate was significantly lower in the group with an OAT level >75.659 ng/mL than in the group with an OAT level ≤75.659 ng/mL (HR, 29.53; p = 0.0008). OAT overexpression and knockdown increased and decreased ECM component production by lung fibroblasts, respectively. OAT knockdown also inhibited transforming growth factor-β1 (TGF)-β1 activity and TGF-β1 pathway signaling. OAT overexpression increased the generation of mitochondrial reactive oxygen species (ROS) by activating proline dehydrogenase. The OAT inhibitor L-canaline significantly attenuated bleomycin-induced lung injury and fibrosis. In conclusion, increased OAT levels in lungs affected by IPF contribute to the progression of fibrosis by promoting excessive mitochondrial ROS production, which in turn activates TGF-β1 signaling. OAT may be a useful target for treating patients with fibrotic lung diseases, including IPF.

Intervertebral disc herniation is frequently encountered in radiological practice. Sequestered disc herniation occurs when the disc material undergoes degeneration and completely loses continuity with the parent nucleus pulposus. Sequestered discs can reside within and outside the spinal canal, exerting a mass effect on adjacent structures, compressing nerve pathways, and eliciting a range of clinical symptoms. In particular, sequestered discs within the dura cannot be identified without durotomy. Therefore, precise preoperative localization is crucial for surgical planning. On MRI, the signal intensity of the sequestered disc may vary due to independent degeneration processes. Additionally, most sequestered disc fragments show varying degrees of peripheral enhancement depending on the degree of angiogenesis and granulation around the isolated tissue. In this article, we review various imaging findings and the location of the sequestered disc to provide patients with an accurate diagnosis and appropriate treatment direction.

The Cu–Ge solid solution alloys have a limited color range and relatively low strength due to its limitation of Ge solubility for a solid solution α-Cu phase at room temperature. To extend chromatic color range and to improve mechanical properties of Cu–Ge solid solution alloys, the Cu–Ge alloys with relatively higher Ge content than solubility limit on equilibrium state were fabricated by induction casting. The as-cast Cu–Ge alloys with 7–10 at.%Ge exhibited dual-phase structure composed of α-Cu and ζ-Cu17Ge3 phases with dendritic structure. By annealing at 700 °C for various times and followed quenching processing, the alloys successfully transformed into the supersaturated α-Cu single-phase structure. To confirm the color difference between the supersaturated single α-phase alloys with a high Ge content and the as-cast single α-phase alloys with low Ge content, the reflectivity analysis, CIE L*a*b* color space system, and color difference indicator were used. As a result, it was confirmed that there was a distinct color difference between supersaturated single α-phase alloys and as-cast single α-phase alloys, and the reflectivity and color difference of the alloys significantly depended on Ge content. Moreover, the Vickers hardness of as-cast and solution treated single α-phase alloys highly improved with an increase of Ge content. The influence of Ge content on phase formation, chromaticity and mechanical properties of solid solution Cu–Ge alloys was systematically discussed.

Abstract This study aims to assess the effect of replacing anchovy meal with chicken by‐product meal (CBM) in juvenile abalone (Haliotis discus hannai) feed. Five diets were formulated to contain 0 (CBM0), 25 (CBM25), 50 (CBM 50), 75 (CBM75), and 100% (CBM100) CBM in replacement to 24% fish meal (FM). Dried Saccharina japonica, which is the natural food for this species of abalone was also prepared. Each diet was fed to triplicate groups of abalone. 1260 abalone assigned into eighteen cages were fed for 16 weeks. After the 16‐week feeding trial, 30 abalones from each cage were exposed to air for 24 h, and survival was monitored for 7 days. Results showed that weight gain and specific growth rate of abalone fed the CBM0 (185.4 ± 12.83% and 0.93 ± 0.040%/day, respectively) diet were significantly (p 0.1 for Log Rank and Wilcoxon tests) difference among all formulated diets according to the analysis of the Kaplan–Meier survival curve. In conclusion, CBM can replace FM up to 50% in an abalone diet without compromising growth performance and survival.

Background/Objectives: This study aimed to investigate trends in antidiabetic drug use and assess the risk of metformin-associated lactic acidosis (MALA) in patients with chronic kidney disease (CKD). Methods: A retrospective observational analysis based on the common data model was conducted using electronic medical records from 2010 to 2021. The patients included were aged ≥18, diagnosed with CKD and type 2 diabetes, and had received antidiabetic medications for ≥30 days. MALA was defined as pH ≤ 7.35 and arterial lactate ≥4 mmol/L. Results: A total of 8318 patients were included, with 6185 in CKD stages 1–2 and 2133 in stages 3a–5. Metformin monotherapy was the most prescribed regimen, except in stage 5 CKD. As CKD progressed, metformin use significantly declined; insulin and meglitinides were most frequently prescribed in end-stage renal disease. Over the study period, the use of SGLT2 inhibitors (13.3%) and DPP-4 inhibitors (24.5%) increased significantly, while sulfonylurea use decreased (p < 0.05). Metformin use remained stable in earlier CKD stages but significantly decreased in stage 3b or worse. The incidence rate (IR) of MALA was 1.22 per 1000 patient-years, with a significantly increased IR in stage 4 or worse CKD (p < 0.001). Conclusions: Metformin was the most prescribed antidiabetic drug in CKD patients in Korea with a low risk of MALA. Antidiabetic drug use patterns varied across CKD stages, with a notable decline in metformin use in advanced CKD and a rise in SGLT2 inhibitor prescriptions, underscoring the need for further optimized therapy.

Background/Objectives: This study aimed to develop a fully validated HPLC-MS/MS method for quantifying total and unbound lenalidomide concentrations in human plasma. Methods: Unbound concentrations were measured using plasma ultrafiltrate prepared with Amicon® Centrifugal Filters. Lenalidomide and lenalidomide-d5 (internal standard) were extracted from 50 μL of human plasma using liquid–liquid extraction. Chromatography was conducted with a Halo® C18 column using 0.1% formic acid and methanol (20:80, v/v) as the mobile phase. The mass spectrometer was operated in a positive ion mode with an electrospray ionization interface and multiple reaction monitoring modes. Results: Calibration curves were linear over the range of 5 to 1000 ng/mL (r2 > 0.996) for both the total and unbound lenalidomide. For total lenalidomide concentrations, between-run precision (coefficients of variation) and accuracy were 1.70–7.65% and 94.45–101.10%, respectively. For unbound concentrations, inter-day precision and accuracy were 1.98–10.55% and 93.95–98.48%, respectively. Conclusions: We developed a highly reproducible, sensitive, and efficient bioanalytical method using a smaller volume of plasma sample (50 μL) with a relatively short run time (2.5 min). The proposed analytical method was successfully applied to measure total and unbound lenalidomide concentrations at various time points in multiple myeloma patients with renal impairment.

Hepatopancreaticoduodenectomy (HPD) is a controversial surgical technique for the treatment of perihilar cholangiocarcinoma. This study aimed to clarify the mortality, morbidity, and survival outcomes in patients with perihilar cholangiocarcinoma who underwent HPD at a small-volume hepatobiliary-pancreatic center. This retrospective study included 78 patients with perihilar cholangiocarcinoma who underwent HPD (n = 18) or major liver resection with bile duct resection (n = 60) at our center between October 2013 and December 2022. The primary endpoints were the in-hospital morbidity and 90-day mortality rates. The secondary endpoints included the recurrence-free and overall survival rates in both groups. Major complications (Clavien–Dindo grade ≥3) were more common in the HPD group (Group 1, 61.1%) than in the major liver resection group (Group 2; 23.3%, p = 0.03). The 1-, 3- and 5-year overall survival rates for Groups 1 and 2 were 66.7%, 41.7%, and 27.8% and 79.9%, 44.5%, and 22.7%, respectively (p = 0.89). The 1-, 3-, and 5-year recurrence-free survival rates for Groups 1 and 2 were 64.2%, 53.5%, and 35.6% and 85.3%, 46.8%, and 25.0%, respectively (p = 0.41). Although morbidity and mortality after HPD are higher than those after other surgeries, our findings suggest that HPD is a feasible treatment option for perihilar cholangiocarcinoma, even in small-volume centers. However, meticulous pre- and perioperative evaluation of the patient's overall health status, quality of life, and prospective advantages are required.

Abstract MARCKS (myristoylated alanine-rich C-kinase substrate) is a membrane-associated protein expressed in many cell types, including macrophages. MARCKS is functionally implicated in cell adhesion, phagocytosis, and inflammation. LPS (lipopolysaccharide) triggers inflammation via TLR4 (toll-like receptor 4).The presence of MARCKS and the formation of phospho-MARCKS in various cell types have been described, but the role(s) of MARCKS in regulating macrophage functions remain unclear. We investigated the role of MARCKS in inflammation. Confocal microscopy revealed that MARCKS and phospho-MARCKS increased localization to endosomes and the Golgi apparatus upon LPS stimulation.CRISPR-CAS9 mediated knockout of MARCKS in macrophages downregulated the production of TNF and IL6, suggesting a role for MARCKS in inflammatory responses. Our comprehensive proteomics analysis together with real-time metabolic assays comparing LPS-stimulation of WT and MARCKS knock-out macrophages provided insights into the involvement of MARCKS in specific biological processes including innate immune response, inflammatory response, cytokine production, and molecular functions such as extracellularly ATP-gated cation channel activity, electron transfer activity and oxidoreductase activity, uncovering specific proteins involved in regulating MARCKS activity upon LPS stimulation. MARCKS appears to be a key regulator of inflammation whose inhibition might be beneficial for therapeutic intervention in inflammatory diseases.

Abstract Background Krüppel-like factor 10 (KLF10) is involved in a positive feedback loop that regulates transforming growth factor β (TGFβ) signaling, and TGFβ plays an important role in the pathogenesis of liver disease. Here, we investigated whether KLF10 deletion affects the development of liver fibrosis and hepatocellular carcinoma (HCC). Methods We induced KLF10 deletion in C57BL/6 mice. Liver fibrosis was induced by feeding a diet high in fat and sucrose (high-fat diet [HFD]), whereas HCC was produced by intraperitoneal administration of N-diethylnitrosamine (DEN). An in vitro experiment was performed to evaluate the role of KLF10 in the cancer microenvironment using Hep3B and LX2 cells. An immunohistochemical study of KLF10 expression was performed using human HCC samples from 60 patients who had undergone liver resection. Results KLF10 deletion resulted in an increased DEN-induced HCC burden with significant upregulation of SMAD2, although loss of KLF10 did not alter HFD-induced liver fibrosis. DEN-treated mice with KLF10 deletion exhibited increased levels of mesenchymal markers (N-cadherin and SNAI2) and tumor metastasis markers (matrix metalloproteinases 2 and 9). KLF10 depletion in Hep3B and LX2 cells using siRNA was associated with increased invasiveness. Compared with co-culture of KLF10-preserved Hep3B cells and KLF10-intact LX2 cells, co-culture of KLF10-preserved Hep3B cells and KLF10-depleted LX2 cells resulted in significantly enhanced invasion. Low KLF10 expression in resected human HCC specimens was associated with poor survival. Conclusion The results of this study suggest that loss of KLF10 facilitates liver cancer development with alteration in TGFβ signaling.

In adults, spinal ependymomas are usually found in intramedullary locations. However, intradural extramedullary spinal ependymomas are rare. Additionally, spinal ependymomas usually show iso to hypointensity on T1-weighted images without hemorrhage. Herein, we present a rare case of a 43-year-old female with a pathologically confirmed intradural extramedullary ependymoma that showed hyperintensity on T1-weighted imaging accompanied by hemorrhage.

Abstract Inclusion of various sources of additives in aquafeeds is practically helpful to elevate the growth performance and disease resistance of aquatic animals. An 8‐week feeding trial was conducted to determine the inclusion effects of phyto‐additives (yacon, ginger, and blueberry) into diets on olive flounder growth, feed utilization, chemical composition, and plasma chemistry, and to challenge test against Edwardsiella tarda in comparison to a commercial probiotic SUP (Super lacto®). Six hundred juvenile olive flounder were randomly allocated into 15, 50 L flow‐through tanks (40 fish per tank). Five experimental diets were formulated. No additive was included in the control (Con) diet. One percent of yacon, ginger, and blueberry powders, and 0.5% Super Lacto® were included at the expense of wheat flour and water in the Con diet, also referred to as the YCP (yacon powder), GGP (ginger powder), BBP (blueberry powder), and SUP diets, respectively. All experimental diets were hand‐fed to triplicate groups of fish twice a day until they were visually satiated for a period of 8 weeks. Following the 4‐ and 8‐week feeding trials, 10 and 20 fish were taken from each tank and artificially infected with E. tarda, and then survival was monitored for the next 6 and 8 days after infection, respectively. At the end of the 8‐week feeding trial, no significant difference was observed in weight gain, feed consumption, feed utilization, chemical composition, and plasma chemistry in olive flounder. However, the survival of olive flounder fed the GGP diet was significantly (p

Abstract Dietary inclusion effects of various levels of jack mackerel meal (JMM) on growth, feed utilization, biochemical composition, and innate immune response of rockfish were determined. The control (Con) diet included 550 g/kg fish meal (FM). Ten, 30, 50, 100, 200, 400, 600, and 1000 g/kg of JMM were included in the Con diet, referred to as the JMM10, JMM30, JMM50, JMM100, JMM200, JMM400, JMM600, and JMM1000 diets, respectively. Eight hundred and ten fish (initial mean weight of 2.3 g) were distributed into 27 flow‐through tanks. The experimental diets were assigned to triplicate groups of fish. Fish were hand‐fed for 8 weeks. Weight gain of fish fed the JMM400 diet was statistically better than that of fish fed the Con, JMM10, JMM30, JMM50, JMM100, and JMM200 diets. Feed consumption of fish fed the JMM400 diet was statistically higher than that of fish fed the Con, JMM10, JMM30, and JMM50 diets. Dietary inclusion of JMM did not influence feed utilization, biochemical composition, and innate immune responses of fish. In conclusion, inclusion of JMM up to 400 g/kg of FM in diet improved growth and feed consumption of rockfish, and dietary optimum inclusion levels of JMM were estimated to be 396.7 and 403.1 g/kg based on regression analysis of weight gain and feed consumption, respectively.

Abstract Thus far, attempts to develop drugs that target corticotropin-releasing hormone receptor 1 (CRF1R), a drug target in stress-related therapy, have been unsuccessful. Studies have focused on using high-resolution G protein-coupled receptor (GPCR) structures to develop drugs. X-ray free-electron lasers (XFELs), which prevent radiation damage and provide access to high-resolution compositions, have helped accelerate GPCR structural studies. We elucidated the crystal structure of CRF1R complexed with a BMK-I-152 antagonist at 2.75 Å using fixed-target serial femtosecond crystallography. The results revealed that two unique hydrogen bonds are present in the hydrogen bond network, the stalk region forms an alpha helix and the hydrophobic network contains an antagonist binding site. We then developed two antagonists—BMK-C203 and BMK-C205—and determined the CRF1R/BMK-C203 and CRF1R/BMK-C205 complex structures at 2.6 and 2.2 Å, respectively. BMK-C205 exerted significant antidepressant effects in mice and, thus, may be utilized to effectively identify structure-based drugs against CRF1R.

Abstract Gastric adenocarcinoma (GAC) is a lethal disease characterized by genomic and clinical heterogeneity. By integrating 8 previously established genomic signatures for GAC subtypes, we identified 6 clinically and molecularly distinct genomic consensus subtypes (CGSs). CGS1 have the poorest prognosis, very high stem cell characteristics, and high IGF1 expression, but low genomic alterations. CGS2 is enriched with canonical epithelial gene expression. CGS3 and CGS4 have high copy number alterations and low immune reactivity. However, CGS3 and CGS4 differ in that CGS3 has high HER2 activation, while CGS4 has high SALL4 and KRAS activation. CGS5 has the high mutation burden and moderately high immune reactivity that are characteristic of microsatellite instable tumors. Most CGS6 tumors are positive for Epstein Barr virus and show extremely high levels of methylation and high immune reactivity. In a systematic analysis of genomic and proteomic data, we estimated the potential response rate of each consensus subtype to standard and experimental treatments such as radiation therapy, targeted therapy, and immunotherapy. Interestingly, CGS3 was significantly associated with a benefit from chemoradiation therapy owing to its high basal level of ferroptosis. In addition, we also identified potential therapeutic targets for each consensus subtype. Thus, the consensus subtypes produced a robust classification and provide for additional characterizations for subtype-based customized interventions.

This experiment was performed to evaluate the inclusion impact of various levels of jack mackerel meal (JMM) in olive flounder (P. olivaceus) feeds substituting 50% FM by duck by-product meal (DBM) on growth, feed availability, and economic efficiency. Seven experimental diets were prepared. The control (Con) diet contained 60% FM. Fifty percent FM in the Con diet was substituted with DBM, and then the graded levels (0%, 10%, 20%, 30%, 40%, and 50%) of JMM were added instead of FM, named the DJ0, DJ10, DJ20, DJ30, DJ40, and DJ50 diets, respectively. All feeds were assigned to triplicate fish groups. At the end of 56 days’ feeding, fish fed the DJ40 and DJ50 diets exhibited comparable weight gain and specific growth rate to fish fed the Con diet. Higher feed consumption was observed in fish fed the Con, DJ40, and DJ50 diets compared to fish fed the DJ0 and DJ10 diets. Lower feed conversion ratio was observed in fish fed the Con diet compared to fish fed the DJ0, DJ10, DJ20, and DJ30 diets. Furthermore, the DJ50 diet led to the highest economic profit index (EPI). In conclusion, inclusion of 50% JMM in the olive flounder diet replacing 50% FM with DBM seems to be the most recommendable dietary treatment based on growth and feed consumption of olive flounder and EPI.

Background and Objectives: Lateral ankle injuries are commonly encountered injuries, and the open modified Broström operation (OMBO) is the primary treatment option. Recently, an arthroscopic modification of the Broström operation (AMBO) was developed; many studies have shown that there are no significant differences in clinical and radiological outcomes between the two surgical methods. However, no studies have been conducted comparing the two surgical methods in terms of return to play (RTP) time. This study assesses the time to RTP and the functional clinical outcomes. Materials and Methods: Sixty patients were enrolled from January 2012 to July 2014. They were segregated into two cohorts: the AMBO group comprised 30 patients, while the OMBO group comprised another 30 patients. Each participant underwent standardized treatment and rehabilitation regimens and RTP time was measured using seven questions that explored the times to return of painless walking, running, jumping, squatting, climbing stairs, and rising up on the heels and toes. We compared the time intervals from the onset of instability to the date of surgery. Clinical outcomes were evaluated before the surgery, 6 weeks after surgery, and 6 months after surgery. The assessments included the American Orthopedic Foot & Ankle Society (AOFAS) ankle–hindfoot score, the pain visual analog scale (VAS) score, subjective satisfaction with rehabilitation, and activity level. Results: In terms of RTP, AMBO was associated with a shorter interval to walking without pain (7.07 ± 2.96 weeks) relative to OMBO (11.03 ± 8.58 weeks). No disparities were observed in the time to return to play (RTP) between OMBO and AMBO. While there were no discrepancies in the 6-month postoperative AOFAS or VAS scores, the 6-week postoperative VAS score was notably lower in the AMBO group compared to the OMBO group. AMBO provided a faster RTP in terms of two of the seven questions in a group exhibiting high-level physical activity. The rate of subjective satisfaction with rehabilitation was higher for AMBO than for OMBO. Conclusions: Aside from walking, the duration to return to play and the clinical outcomes were similar between AMBO and OMBO treatments for lateral ankle instability. AMBO is a good treatment option and should be carefully considered for athletes with lateral ankle instability. AMBO demonstrated positive outcomes in a group with higher activity levels compared to others, particularly in terms of time to RTP, subjective satisfaction, and postoperative pain.

Abstract Background Carbohydrate antigen (CA) 19–9 is a known pancreatic cancer (PC) biomarker, but is not commonly used for general screening due to its low sensitivity and specificity. This study aimed to develop a serum metabolites‐based diagnostic calculator for detecting PC with high accuracy. Methods A targeted quantitative approach of direct flow injection‐tandem mass spectrometry combined with liquid chromatography–tandem mass spectrometry was employed for metabolomic analysis of serum samples using an Absolute IDQ™ p180 kit. Integrated metabolomic analysis was performed on 241 pooled or individual serum samples collected from healthy donors and patients from nine disease groups, including chronic pancreatitis, PC, other cancers, and benign diseases. Orthogonal partial least squares discriminant analysis (OPLS‐DA) based on characteristics of 116 serum metabolites distinguished patients with PC from those with other diseases. Sparse partial least squares discriminant analysis (SPLS‐DA) was also performed, incorporating simultaneous dimension reduction and variable selection. Predictive performance between discrimination models was compared using a 2‐by‐2 contingency table of predicted probabilities obtained from the models and actual diagnoses. Results Predictive values obtained through OPLS‐DA for accuracy, sensitivity, specificity, balanced accuracy, and area under the receiver operating characteristic curve (AUC) were 0.9825, 0.9916, 0.9870, 0.9866, and 0.9870, respectively. The number of metabolite candidates was narrowed to 76 for SPLS‐DA. The SPLS‐DA‐obtained predictive values for accuracy, sensitivity, specificity, balanced accuracy, and AUC were 0.9773, 0.9649, 0.9832, 0.9741, and 0.9741, respectively. Conclusions We successfully developed a 76 metabolome‐based diagnostic panel for detecting PC that demonstrated high diagnostic performance in differentiating PC from other diseases.

Abstract Substitutability of broccoli by‐products (BBP) for Saccharina japonica in feed on growth, carcass chemical composition, and air exposure resistance of abalone (Haliotis discus) was investigated. One thousand and two hundred sixty abalones were randomly assigned into 18 cages (3 cages/diet; 70 abalone/cage). Two hundred g/kg of S. japonica was included in the control diet (BBP0). The BBP250, BBP500, BBP750, and BBP1000 diets were prepared by substituting 250, 500, 750, and 1000 g/kg of S. japonica with an equal amount of BBP. Additionally, dry S. japonica was prepared. Abalone were fed daily for 7 days a week for 16 weeks. Following the completion of the feeding trial, 20 abalone from each cage were exposed to air for 20 h prior to being monitored for the following 5 days. The greatest weight gain and specific growth rate (SGR) were achieved in abalone fed the BBP250 diet. Superior survival was obtained in abalone fed the BBP250, BBP500, BBP750, and BBP1000 diets to abalone fed the S. japonica control diet. The BBP250 and BBP500 diets achieved the highest survival of abalone. BBP appears to be a novel replacer for S. japonica in abalone diets, and 250 g/kg replacement of BBP for S. japonica produced the best weight gain and SGR.

Background: Patients who require initial venoarterial extracorporeal membrane oxygenation (VA ECMO) support may need to undergo veno-arteriovenous ECMO (VAV ECMO) conversion. However, there are no definitive criteria for conversion to VAV ECMO. We report 9 cases of VAV ECMO at Gyeongsang National University Changwon Hospital, Gyeongsang National University College of Medicine. Methods: Of 158 patients who received ECMO support between January 2017 and June 2019, 82 were supported by initial VA ECMO. We retrospectively reviewed the medical records of 9 patients (7 men and 2 women; age, 53.1±19.4 years) who had differential hypoxia and required VAV ECMO support. Percutaneous transaortic catheter venting was used to detect the differential hypoxia. Results: Among the 82 patients who received VA ECMO support, 9 (10.9%) had differential hypoxia and required conversion to VAV ECMO support. The mean time from VA ECMO support to VAV ECMO support and the mean duration of the VAV support were 2.1±2.2 days and 1.9±1.5 days, respectively. The average peak inspiratory pressure before and after VAV ECMO application was 23.89±3.95 cmH2O and 20.67±5.72 cmH2O, respectively, decreasing by an average of 3.2±3.5 cmH2O (p=0.040). The PaO2/FiO2 ratio was kept below 100 mm Hg in survivors and non-survivors for 116±65.4 and 250±124.9 minutes, respectively (p=0.016). Six patients underwent extracorporeal cardiopulmonary resuscitation, of whom 4 survived (67%). The overall survival rate of patients who underwent conversion from VA ECMO to VAV ECMO was approximately 56%. Conclusion: Rapid detection of differential hypoxia is required when VA ECMO is applied, and efficient conversion to VAV ECMO may be critical for patient survival.

Abstract Background Gabapentin is commonly prescribed for the treatment of neuropathic pain, restless leg syndrome, and partial-onset seizures. Although the most frequent side effects of gabapentin are associated with the central nervous system, gabapentin can also affect the cardiovascular system. Case reports and observational studies have showed that gabapentin can be associated with increased risk of atrial fibrillation. However, all the evidence is concentrated in patients older than 65 years old with comorbidities that predispose them to the development of arrhythmias. Case presentation We describe a case of an African American male in his 20s that presented to our chronic pain clinic with lumbar radiculitis and developed atrial fibrillation 4 days after being started on gabapentin. Laboratory workup did not show significant abnormalities, including normal complete blood count, comprehensive metabolic panel, toxicology screen, and thyroid-stimulating hormone. Transthoracic and transesophageal echocardiography showed a patent foramen ovale with right-to-left shunt. The patient was initially treated with diltiazem for heart rate control and apixaban. Direct current cardioversion with successful conversion to sinus rhythm was performed 24 hours after admission. The patient was then discharged on apixaban and diltiazem. Apixaban was changed to low-dose aspirin 1 month after discharge. Conclusion With rapidly increasing usage of gabapentin for approved and off-label indications, it is important to identify unintended adverse effects of this drug as they are considered safe alternatives to opioids. New-onset atrial fibrillation could be induced by gabapentin in young individuals.

Abstract Background Butane is an aliphatic hydrocarbon used in various commercial products. While numerous reports of sudden cardiac-related deaths from butane inhalation have been described, butane-associated acute encephalopathy has rarely been reported. Case presentation A 38-year-old man presented with cognitive dysfunction after butane gas inhalation. Neuropsychological test results showed impairments in verbal and visual memory, and frontal executive function. Diffusion weighted MRI revealed symmetric high-signal changes in the bilateral hippocampus and globus pallidus. FDG-PET demonstrated decreased glucose metabolism in the bilateral precuneus and occipital areas and the left temporal region. At the 8-month follow-up, he showed still significant deficits in memory and frontal functions. Diffuse cortical atrophy with white matter hyperintensities and extensive glucose hypometabolism were detected on follow-up MRI and FDG-PET, respectively. Brain autopsy demonstrated necrosis and cavitary lesions in the globus pallidus. Conclusions Only a few cases of butane encephalopathy have been reported to date. Brain lesions associated with butane encephalopathy include lesions in the bilateral thalamus, insula, putamen, and cerebellum. To the best of our knowledge, this is the first report on bilateral hippocampal and globus pallidal involvement in acute butane encephalopathy. The pathophysiology of central nervous system complications induced by butane intoxication is not yet fully understood. However, the direct toxic effects of butane or anoxic injury secondary to cardiac arrest or respiratory depression have been suggested as possible mechanisms of edematous changes in the brain after butane intoxication.

Abstract Proper lipid metabolism is crucial to maintain alveolar epithelial cell (AEC) function, and excessive AEC death plays a role in the pathogenesis of idiopathic pulmonary fibrosis (IPF). The mRNA expression of fatty acid synthase (FASN), a key enzyme in the production of palmitate and other fatty acids, is downregulated in the lungs of IPF patients. However, the precise role of FASN in IPF and its mechanism of action remain unclear. In this study, we showed that FASN expression is significantly reduced in the lungs of IPF patients and bleomycin (BLM)-treated mice. Overexpression of FASN significantly inhibited BLM-induced AEC death, which was significantly potentiated by FASN knockdown. Moreover, FASN overexpression reduced BLM-induced loss of mitochondrial membrane potential and the production of mitochondrial reactive oxygen species (ROS). Oleic acid, a fatty acid component increased by FASN overexpression, inhibited BLM-induced cell death in primary murine AECs and rescue BLM induced mouse lung injury/fibrosis. FASN transgenic mice exposed to BLM exhibited attenuated lung inflammation and collagen deposition compared to controls. Our findings suggest that defects in FASN production may be associated with the pathogenesis of IPF, especially mitochondrial dysfunction, and augmentation of FASN in the lung may have therapeutic potential in preventing lung fibrosis.

Incorporating feed stimulants and attractants in low fish meal (FM) diets is a very effective way to improve palatability and increase feed intake and fish growth. This research aims to elucidate the substitution impact of different levels of FM with various plant proteins in diets with jack mackerel meal (JMM) inclusion as feed stimulants on the growth and feed utilization of rockfish (Sebastes schlegeli). A two-way (2 substitution levels [25% and 50%] × 3 substitution sources [corn gluten meal (CGM), soybean protein concentrate (SPC), and corn protein concentrate (CPC)]) ANOVA experimental design was adopted. In total, 525 fish averaging 8.3 g were assigned to 21 tanks (25 juvenile/tank). Seven isoprotetic and isolipidic feeds were formulated. The control (Con) diet contained 55% FM. CGM, SPC, and CPC were replaced for 25% and 50% FM in the Con diet, and then 22% JMM as feed stimulants was included at the cost of FM, named as the CGM25, CGM50, SPC25, SPC50, CPC25, and CPC50 diets, respectively. All diets were assigned to triplicate groups of rockfish. Rockfish were hand-fed to apparent satiation twice a day for 8 weeks. Rockfish fed the 25% FM substitution diets achieved superior (p < 0.0001 for both) weight gain and specific growth rate (SGR) compared to rockfish fed the 50% FM substitution diets, while rockfish fed the CGM-replaced diets achieved superior (p < 0.0001 for both) weight gain and SGR compared to rockfish fed the SPC- and CPC-replaced diets. The weight gain and SGR of rockfish fed the Con and CGM25 diets were superior to rockfish fed all other diets. Rockfish fed the 25% FM substitution diets achieved superior (p < 0.0001 for both) feed efficiency (FE) and protein efficiency ratio (PER) compared to rockfish fed the 50% FM substitution diets, while rockfish fed the CGM-replaced diets achieved superior FE and PER compared to rockfish fed the CPC-replaced diets. Rockfish fed the 25% FM substitution diets led to superior (p < 0.0001) protein retention (PR) compared to rockfish fed the 50% FM substitution diets. The biological indices, proximate composition, and amino acid profiles of the whole body, as well as the plasma and serum parameters of rockfish, were not changed by either substitution level or substitution source. In conclusion, the replacement of CGM for 25% FM in the rockfish diet with JMM inclusion can be made without deteriorating growth performance, feed consumption and utilization, biochemical composition, and plasma and serum parameters.

This study aims to elucidate manipulation impacts of jack mackerel meal (JMM) in the red sea bream (Pagrus major) feeds replacing various animal protein sources for different levels of fish meal (FM) on growth and feed availability. Two-way ANOVA experimental design was applied with three substitution sources: animal protein sources (tuna byproduct meal (TBM), chicken byproduct meal (CBM), and meat meal (MM)) and two FM substitution levels (25% and 50%). The control (Con) diet contained 60% FM. In the Con diet, 25% and 50% of FM were replaced with TBM, CBM, and MM, respectively, and then 24% jack mackerel meal (JMM) was included at the expense of FM, named as the TBM25, TBM50, CBM25, CBM50, MM25, and MM50 diets, respectively. Red sea bream juveniles averaging 11.8 g were distributed in 21 flow-through tanks (20 fish per tank) with triplicate. Fish were carefully hand-fed to apparent satiation for 8 weeks. At the end of the 8-week feeding experiment, the TBM-substituted diets produced significantly (P

The increased global market value of fish meal (FM) and the overfishing of wild fishery resources have boosted efforts to identify protein sources that can be cheaply and reliably supplied as an alternative to FM, which is commonly used as a main protein source in fish diets. Numerous studies over the years have demonstrated that animal by-product meals are the effective alternatives for FM in fish diets. This study aimed to elucidate the effect of substituting FM with various by-product meals of swine-origin in diet on growth, feed utilization, chemical composition, plasma biochemical parameters, and superoxide dismutase (SOD) and lysozyme activity of juvenile olive flounder (P. olivaceus). All experimental diets were formulated with five isonitrogenous (56.5%) and isolipidic (10.0%) diets. The control (Con) diet included 65% FM and 12% dehulled soybean meal as the protein sources and 4.2% fish oil as a lipid source. Thirty percent of FM was replaced with plasma powder, heme powder, globin powder, and pork greaves meal, named as the PP, HP, GP, and PM diets, respectively. Three hundred and seventy-five juvenile (9.2 ± 0.01 g; mean ± SD) fish were placed into 15 flow-through tanks with three replicates. Fish were carefully hand-fed to apparent satiation twice a day for 56 days. At the end of the feeding period, weight gain and specific growth rate of fish fed the GP and PM diets were comparable to fish fed the Con diet. Feed consumption of fish fed the PP, GP, and PM diets was comparable to fish fed the Con diet. Feed utilization and condition factor of fish fed the HP diet were the lowest. Plasma biochemical parameters, chemical composition, amino acid profiles, and SOD and lysozyme activity of fish were unaffected by dietary treatments. Thus, GP and PM are the appropriate replacers for FM in the olive flounder diets, wherein 30% FM is substituted by diverse by-product meals of swine-origin.

Abstract Background Some studies have analyzed the frequency of HCV RNA testing and actual treatment among anti-HCV positive patients in Korea, which has a low prevalence of HCV infection. This study aimed to analyze the diagnosis process, treatment results, and prognosis according to care cascade in patients who are anti-HCV positive. Methods Three thousand two hundred fifty-three anti-HCV positive patients presented to a tertiary hospital between January 2005 and December 2020. The number of patients who underwent HCV RNA testing, treatment, and proportion of sustained virologic response (SVR) according to the type of antivirals was investigated. We investigated the cumulative incidence of hepatocellular carcinoma (HCC) and liver cirrhosis. Results Of a total of 3,253 people, 1,177 (36.2%) underwent HCV RNA testing and 858 (72.9%) were positive for HCV RNA. 494 (57.6%) of HCV RNA positive patients received antiviral treatment, and 443 (89.7%) of initiated hepatitis C treatment experienced SVR. Of the 421 treated patients, 16 (14.2%) developed HCC. The cumulative incidence of HCC at 15 years was significantly different according to the presence of liver cirrhosis (10/83, 29.5% vs. 6/338, 10.8%, p

Objective Carbon monoxide (CO) poisoning causes brain injury by hypoxia and inflammatory mechanisms. Hypoxic conditions result in increased serum phosphate concentration due to loss of polarity of the cell membrane, changes in membrane fluidity, and consequent destruction of phospholipids in the cell membrane. This study aimed to evaluate whether serum phosphate measured in the emergency department (ED) can serve as an early predictor of neurocognitive sequelae 1 month after acute CO poisoning. Methods We included patients ≥16 years with acute CO poisoning from a cohort who were treated at a single tertiary academic hospital in Wonju, Korea, between January 2006 and May 2021. Neurocognitive outcome was assessed using the Global Deterioration Scale score; patients were classified into favorable (1–3 points) or poor (4–7 points) neurocognitive outcome groups based on this score. These two groups were compared before and after propensity score matching. Results Data from 888 patients were analyzed. Seven hundred seventy-one patients (86.8%) were assigned to the favorable outcome group and 117 patients (13.2%) to the poor outcome group. Patients with a poor outcome had a higher mean serum phosphate level than those with a favorable outcome (3.9 mg/dL vs. 3.5 mg/dL, P=0.001). Propensity score matching yielded 85 matched patient pairs. After matching, serum phosphate level in the ED was not significantly different between the favorable and poor outcome groups (3.9 vs. 3.7 mg/dL, P=0.349). Conclusion Serum phosphate level measured in the ED did not predict poor neurocognitive outcomes 1 month after CO poisoning.

Abstract Obesity has been linked to atrial fibrillation (AF) burden and severity, and epidemiological studies suggest that AF is more prevalent in whites than Asian. We aimed to investigate whether obesity mediates associations with AF in Europe and Asia using patient-level data comparisons of two cohort studies. Using Korean National Health Insurance Service’s Health Screening (NHIS-HealS) and U.K. Biobank data, we included 401,206 Korean and 477,926 British aged 40–70 years without previous AF who received check-ups. The incidence and risk of AF were evaluated regarding different body mass index (BMI) values. The obese proportion (BMI ≥ 30.0 kg/m2, 2.8% vs. 24.3%, P

Background/Aims Daratumumab has shown an encouraging antitumor effect in patients with multiple myeloma (MM), and was known to alter the immune properties by off-targeting immunosuppressive cells. Here, we aimed to evaluate the change in absolute lymphocyte count (ALC) as a surrogate marker for predicting survival outcomes of patients treated with daratumumab. Methods Between 2018 and 2021, the medical records of patients with relapsed/refractory MM (RRMM) treated with daratumumab monotherapy at 10 centers in South Korea were reviewed. We collected the ALC data at pre-infusion (D0), day 2 after the first infusion (D2), and prior to the third cycle of daratumumab therapy (D56). Results Fifty patients who were administered at least two cycles of daratumumab were included. Overall response rate was 54.0% after two cycles of daratumumab treatment. On D2, almost all patients experienced a marked reduction in ALC. However, an increase in ALC on D56 (ALCD56) was observed in patients with non-progressive disease, whereas failure of ALC recovery was noted in those with progressive disease. Patients with ALCD56 > 700/μL (n = 39, 78.0%) had prolonged progression-free survival (PFS) and overall survival (OS) than those with ALCD56 ≤ 700/μL (median PFS: 5.8 months vs. 2.6 months, p = 0.025; median OS: 24.1 months vs. 6.1 months, p = 0.004). In addition, ALCD56 >700/μL was a significant favorable prognostic factor for PFS (hazard ratio [HR], 0.22; p = 0.003) and OS (HR, 0.23; p = 0.012). Conclusions Increase in ALC during daratumumab treatment was significantly associated with prolonged survival outcomes in patients with RRMM. The ALC value can predict clinical outcomes in patients treated with daratumumab.

Background and objectives: Diabetic foot stands out as one of the most consequential and devastating complications of diabetes. Many factors, including VIPS (Vascular management, Infection management, Pressure relief, and Source of healing), influence the prognosis and treatment of diabetic foot patients. There are many studies on VIPS, but relatively few studies on “sources of healing”. Nutrients that affect wound healing are known, but objective data in diabetic foot patients are insufficient. We hypothesized that “sources of healing” would have many effects on wound healing. The purpose of this study is to know the affecting factors related to the source of healing for diabetic foot patients. Materials and Methods: A retrospective review identified 46 consecutive patients who were admitted for diabetic foot management from July 2019 to April 2021 at our department. Several laboratory tests were performed for influencing factor evaluation. We checked serum levels of total protein, albumin, vitamin B, iron, zinc, magnesium, copper, Hb, HbA1c, HDL cholesterol, and LDL cholesterol. These values of diabetic foot patients were compared with normal values. Patients were divided into two groups based on wound healing rate, age, length of hospital stay, and sex, and the test values between the groups were compared. Results: Levels of albumin (37%) and Hb (89%) were low in the diabetic foot patients. As for trace elements, levels of iron (97%) and zinc (95%) were low in the patients, but levels of magnesium and copper were usually normal or high. There were no differences in demographic characteristics based on wound healing rate. However, when compared to normal adult values, diabetic foot patients in our data exhibited significantly lower levels of hemoglobin, total protein, albumin, iron, zinc, copper, and HDL cholesterol. When compared based on age and length of hospital stay, hemoglobin levels were significantly lower in both the older age group and the group with longer hospital stays. Conclusions: Serum levels of albumin, Hb, iron, and zinc were very low in most diabetic foot patients. These low values may have a negative relationship with wound healing. Nutrient replacements are necessary for wound healing in diabetic foot patients.

This study aims to reveal the substitution impact of fish meal (FM) with the combined meat meal and chicken by-product meal (CMC) in the olive flounder (P. olivaceus) feeds on growth and feed availability. Seven experimental feeds were formulated. The control (CMC0) diet included 65% FM. In the CMC0 diet, the various (10%, 20%, 40%, 60%, 80%, and 100%) levels of FM were replaced with CMC, named as the CMC10, CMC20, CMC40, CMC60, CMC80, and CMC100 diets, respectively. The total number of 525 juvenile fish (9.2 ± 0.01 g; mean ± SD) was placed into 21 50-L flow-through tanks (25 juveniles/tank) with three replicates. Fish were hand-fed to apparent satiation for 8 weeks. After the 8-week feeding experiment, olive flounder fed the CMC10 (40.0 ± 0.60 g/fish, 2.99 ± 0.021%/day, and 39.57 ± 0.542 g/fish; mean ± SD), CMC20 (47.3 ± 2.58 g/fish, 3.24 ± 0.082%/day, and 45.16 ± 0.760 g/fish), and CMC40 (40.2 ± 1.17 g/fish, 3.00 ± 0.040%/day, and 39.43 ± 0.930 g/fish) diets attained superior (p < 0.0001 for all) weight gain, specific growth rate (SGR), and feed consumption compared to olive flounder fed the CMC0 (35.1 ± 0.96 g/fish, 2.81 ± 0.039%/day, and 33.75 ± 0.544 g/fish), CMC60 (31.7 ± 1.62 g/fish, 2.66 ± 0.068%/day, and 31.60 ± 1.080 g/fish), CMC80 (24.7 ± 0.63 g/fish, 2.33 ± 0.033%/day, and 25.27 ± 0.689 g/fish), and CMC100 (17.8 ± 0.32 g/fish, 1.92 ± 0.021%/day, and 18.99 ± 0.592 g/fish, respectively) diets. Weight gain, SGR, and feed consumption of olive flounder fed the CMC60 diet were comparable to olive flounder fed the CMC0 diet. Feed efficiency and protein efficiency ratio of olive flounder fed the CMC60 diet (1.02 ± 0.007 and 1.79 ± 0.034) were comparable to fish fed the CMC0 diet (1.04 ± 0.012 and 1.85 ± 0.021, respectively). None of the plasma and serum measurements, proximate composition, amino acid profiles, or survival of olive flounder after S. iniae infection were influenced by dietary treatments. In conclusion, CMC can substitute FM up to 60% (39% FM protein in the diet) without deteriorating growth performance, feed availability, or the survival of fish after S. iniae infection.

This study was conducted to elucidate the impact on the growth and feed availability of rockfish (Sebastes schlegeli) from including jack mackerel meal (JMM) in feeds which otherwise substitute 20% fish meal (FM) with chicken by-product meal (CBM). Six formulated feeds were designed to be isonitrogenous and isolipidic. Specifically, 55% FM was included in the control (Con) diet. In the Con diet, 20% FM was substituted by CBM, and then the graded levels (0, 20, 40, 60, and 80%) of JMM were included instead of FM, named as the C20J0, C20J20, C20J40, C20J60, and C20J80 diets, respectively. Five hundred and forty juvenile rockfish (initial weight of 11.2 g) were assigned to 18 tanks. All experimental feeds were fed to triplicate groups of rockfish twice daily for 8 weeks. Superior weight gain, specific growth rate (SGR), and feed intake of rockfish fed the C20J60 and C20J80 diets compared to rockfish fed the Con and C20J0 diets were observed. However, the feed utilization, biological indices, proximate composition, amino acid profiles, and blood chemistry of the rockfish were not affected by the dietary treatments. The slightly but not significantly higher economic profit index and growth performance were obtained in the C20J60 diet compared to the C20J80 diet. In conclusion, the C20J60 diet was the most recommendable treatment based on the improvement in growth performance (weight gain and SGR) and feed intake of rockfish, and the highest economic return to farmers.