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Aim: This study aimed to establish the shear wave measurement (SWM) cut-off value for each fibrosis stage using magnetic resonance (MR) elastography values as a reference standard., Methods: We prospectively analyzed 594 patients with chronic liver disease who underwent SWM and MR elastography. Correlation coefficients (were analyzed, and the diagnostic value was evaluated by the area under the receiver operating characteristic curve. Liver stiffness was categorized by MR elastography as F0 (<2.61 kPa), F1 (≥2.61 kPa, <2.97 kPa, any fibrosis), F2 (≥2.97 kPa, <3.62 kPa, significant fibrosis), F3 (≥3.62 kPa, <4.62 kPa, advanced fibrosis), or F4 (≥4.62 kPa, cirrhosis)., Results: The median SWM values increased significantly with increasing fibrosis stage (p < 0.001). The correlation coefficient between SWM and MR elastography values was 0.793 (95% confidence interval 0.761-0.821). The correlation coefficients between SWM and MR elastography values significantly decreased with increasing body mass index and skin-capsular distance; skin-capsular distance values were associated with significant differences in sensitivity, specificity, accuracy, or positive predictive value, whereas body mass index values were not. The best cut-off values for any fibrosis, significant fibrosis, advanced fibrosis, and cirrhosis were 6.18, 7.09, 8.05, and 10.89 kPa, respectively., Conclusions: This multicenter study in a large number of patients established SWM cut-off values for different degrees of fibrosis in chronic liver diseases using MR elastography as a reference standard. It is expected that these cut-off values will be applied to liver diseases in the future., (© 2024 The Authors. Hepatology Research published by John Wiley & Sons Australia, Ltd on behalf of Japan Society of Hepatology.)

We have developed radical C-glycosylation using photoexcitable unprotected glycosyl borate. The direct excitation of glycosyl borate under visible light irradiation enabled the generation of anomeric radical without any photoredox catalysts. The in situ generated anomeric radical was applicable to the radical addition such as Giese-type addition and Minisci-type reaction to introduce alkyl and heteroaryl groups at the anomeric position. In addition, the radical-radical coupling between the glycosyl borate and acyl imidazolide provided unprotected acyl C-glycosides., (© 2024 Wiley-VCH GmbH.)

We analyzed the intraoperative kinematics of total knee arthroplasty (TKA) using a navigation system to investigate the influence of different inserts on kinematics. This was a retrospective observational study. The Vanguard individualized design (33 patients, 33 knees) XP and anterior-stabilized (AS) inserts were used in TKA for osteoarthritis. Kinematic data were intraoperatively recorded. The range of motion, tibiofemoral rotational angle, anteroposterior translation of the femur, and varus-valgus laxity were compared between the two inserts (XP vs. AS). There was no significant difference in the range of motion (extension: XP, 3.7° ± 3.3° vs. AS, 3.8° ± 3.3°, p  = 0.84; flexion: XP, 138.1° ± 10.2° vs. AS, 139.0° ± 13.3°, p  = 0.73). With the AS insert, the tibia was gradually internally rotated as the knee was flexed. At maximum extension, the internal rotation was smallest with AS (XP 6.5° ± 4.0° vs. AS 5.1° ± 3.4°, p  = 0.022), which was also associated with smaller anterior femoral translation (maximum extension: XP, 14.1 ± 4.8 mm vs. AS, 11.3 ± 4.7 mm, p  = 0.00036; 30°: XP, 23.7 ± 5.6 mm vs. AS, 20.7 ± 5.1 mm, p  = 0.000033; 45°: XP, 24.4 ± 4.9 mm vs. AS, 23.2 ± 4.5 mm, p  = 0.0038). The AS was associated with a lower varus-valgus laxity (30° XP 4.1° ± 3.4 vs. AS 3.3° ± 2.7°, p  = 0.036; 60°: XP, 3.2° ± 3.0° vs. AS, 2.4° ± 3.3°, p  = 0.0089). The AS insert facilitated sequential tibiofemoral rotation with varus-valgus stability in mid-flexion without restricting the range of motion., Competing Interests: None declared., (Thieme. All rights reserved.)

Background & Aims: The predictors of progression from steatosis to more advanced stages of metabolic dysfunction-associated steatotic liver disease (MASLD) remain unclear. We evaluated the association between the quantity of hepatic steatosis and longitudinal changes in liver stiffness measurements (LSMs) using magnetic resonance elastography (MRE) in patients with MASLD., Methods: We retrospectively analysed patients with MASLD who underwent at least two serial MRE and magnetic resonance imaging-based proton density fat fraction (MRI-PDFF) examinations at least 1 year apart. Fine-Gray competitive proportional hazard regression was used to identify LSM progression and regression factors., Results: A total of 471 patients were enrolled. Factors linked to LSM progression were steatosis grade 3 (MRI-PDFF ≥17.1%, adjusted hazard ratio [aHR] 2.597; 95% confidence interval [CI] 1.483-4.547) and albumin-bilirubin grade 2 or 3 (aHR 2.790; 95% CI 1.284-6.091), while the only factor linked to LSM regression was % decrease rate of MRI-PDFF ≥5% (aHR 2.781; 95% CI 1.584-4.883). Steatosis grade 3 correlated with a higher incidence rate of LSM progression than steatosis grade 1 (MRI-PDFF <11.3%) in patients with LSM stage 0 (<2.5 kilopascal [kPa]), and a % annual decrease rate of MRI-PDFF ≥5% correlated with a higher incidence rate of LSM regression than that of MRI-PDFF >-5% and <5% in patients with LSM stage 1 or 2-4 (≥2.5 kPa)., Conclusions: Severe hepatic steatosis was linked to significant LSM progression in patients with MASLD and low LSM (<2.5 kPa)., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Xenobiotic metabolic reactions in the hepatocyte endoplasmic reticulum (ER) including UDP-glucuronosyltransferase and carboxylesterase play central roles in the detoxification of medical agents with small- and medium-sized molecules. Although the catalytic sites of these enzymes exist inside of ER, the molecular mechanism for membrane permeation in the ER remains enigmatic. Here, we investigated that organic anion transporter 2 (OAT2) regulates the detoxification reactions of xenobiotic agents including anti-cancer capecitabine and antiviral zidovudine, via the permeation process across the ER membrane in the liver. Pharmacokinetic studies in patients with colorectal cancer revealed that the half-lives of capecitabine in rs2270860 (1324C > T) variants was 1.4 times higher than that in the C/C variants. Moreover, the hydrolysis of capecitabine to 5'-deoxy-5-fluorocytidine in primary cultured human hepatocytes was reduced by OAT2 inhibitor ketoprofen, whereas capecitabine hydrolysis directly assessed in human liver microsomes were not affected. The immunostaining of OAT2 was merged with ER marker calnexin in human liver periportal zone. These results suggested that OAT2 is involved in distribution of capecitabine into ER. Furthermore, we clarified that OAT2 plays an essential role in drug-drug interactions between zidovudine and valproic acid, leading to the alteration in zidovudine exposure to the body. Our findings contribute to mechanistically understanding medical agent detoxification, shedding light on the ER membrane permeation process as xenobiotic metabolic machinery to improve chemical changes in hydrophilic compounds., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The relationship between blood group and rebleeding in acute lower gastrointestinal bleeding (ALGIB) remains unclear. This study aimed to investigate the association between blood group O and clinical outcomes in patients with ALGIB. The study included 2336 patients with ALGIB whose bleeding source was identified during initial endoscopy (from the CODE BLUE-J Study). The assessed outcomes encompassed rebleeding and other clinical parameters. The rebleeding rates within 30 days in patients with blood group O and those without blood group O were 17.9% and 14.9%, respectively. Similarly, the rates within 1 year were 21.9% for patients with blood group O and 18.2% for those without blood group O. In a multivariate analysis using age, sex, vital signs at presentation, blood test findings, comorbidities, antithrombotic medication, active bleeding, and type of endoscopic treatment as covariates, patients with blood group O exhibited significantly higher risks for rebleeding within 30 days (odds ratio [OR] 1.31; 95% confidence interval [CI] 1.04-1.65; P = 0.024) and 1 year (OR 1.29; 95% CI 1.04-1.61; P = 0.020) compared to those without blood group O. However, the thrombosis and mortality rates did not differ significantly between blood group O and non-O patients. In patients with ALGIB, blood group O has been identified as an independent risk factor for both short- and long-term rebleeding., (© 2024. The Author(s).)

Aims: A multi-stakeholder consensus has proposed MASLD (metabolic dysfunction-associated steatotic liver disease). We aimed to investigate the pathological findings related to the mid-term mortality of patients with biopsy-proven MASLD in Japan., Methods: We enrolled 1349 patients with biopsy-proven MASLD. The observational period was 8010 person years. We evaluated independent factors associated with mortality in patients with MASLD by Cox regression analysis. We also investigated pathological profiles related to mortality in patients with MASLD using data-mining analysis., Results: The prevalence of MASH and stage 3/4 fibrosis was observed in 65.6% and 17.4%, respectively. Forty-five patients with MASLD died. Of these, liver-related events were the most common cause at 40% (n = 18), followed by extrahepatic malignancies at 26.7% (n = 12). Grade 2/3 lobular inflammation and stage 3/4 fibrosis had a 1.9-fold and 1.8-fold risk of mortality, respectively. In the decision-tree analysis, the profiles with the worst prognosis were characterised by Grade 2/3 hepatic inflammation, along with advanced ballooning (grade 1/2) and fibrosis (stage 3/4). This profile showed a mortality at 8.3%. Furthermore, the random forest analysis identified that hepatic fibrosis and inflammation were the first and second responsible factors for the mid-term prognosis of patients with MASLD., Conclusions: In patients with biopsy-proven MASLD, the prevalence of MASH and advanced fibrosis was approximately 65% and 20%, respectively. The leading cause of mortality was liver-related events. Hepatic inflammation and fibrosis were significant factors influencing mid-term mortality. These findings highlight the importance of targeting inflammation and fibrosis in the management of patients with MASLD., (© 2024 John Wiley & Sons Ltd.)

Background: Several preliminary reports have suggested the utility of ultrasound attenuation coefficient measurements based on B-mode ultrasound, such as iATT, for diagnosing steatotic liver disease. Nonetheless, evidence supporting such utility is lacking. This prospective study aimed to investigate whether iATT is highly concordant with magnetic resonance imaging (MRI)-based proton density fat fraction (MRI-PDFF) and could well distinguish between steatosis grades., Methods: A cohort of 846 individuals underwent both iATT and MRI-PDFF assessments. Steatosis grade was defined as grade 0 with MRI-PDFF < 5.2%, grade 1 with 5.2% MRI-PDFF < 11.3%, grade 2 with 11.3% MRI-PDFF < 17.1%, and grade 3 with MRI-PDFF of 17.1%. The reproducibility of iATT and MRI-PDFF was evaluated using the Bland-Altman analysis and intraclass correlation coefficients, whereas the diagnostic performance of each steatosis grade was examined using receiver operating characteristic analysis., Results: The Bland-Altman analysis indicated excellent reproducibility with minimal fixed bias between iATT and MRI-PDFF. The area under the curve for distinguishing steatosis grades 1, 2, and 3 were 0.887, 0.882, and 0.867, respectively. A skin-to-capsula distance of ≥ 25 mm was identified as the only significant factor causing the discrepancy. No interaction between MRI-logPDFF and MRE-LSM on iATT values was observed., Conclusions: Compared to MRI-PDFF, iATT showed excellent diagnostic accuracy in grading steatosis. iATT could be used as a diagnostic tool instead of MRI in clinical practice and trials. Trial registration This study was registered in the UMIN Clinical Trials Registry (UMIN000047411)., (© 2024. The Author(s).)

Ovarian fibrosis contributes to age-related ovarian dysfunction. In our previous study, we observed ovarian fibrosis in both obese and aging mice with intracellular lipid droplets in the fibrotic ovaries. Although the importance of mitochondria in ovarian fibrosis has been recognized in pharmacological studies, their role in lipid metabolism remains unclear. Globin peptide (GP), derived from hemoglobin, enhances lipid metabolism in obese mice. This study aimed to elucidate the importance of lipid metabolism in ovarian fibrosis by using GP. Treatment of ovarian stromal cells with GP increased mitochondrial oxygen consumption during β-oxidation. Lipid accumulation was also observed in the ovaries of granulosa cell-specific Nrg1 knockout mice (gcNrg1KO), and the administration of GP to gcNrg1KO mice for two months reduced ovarian lipid accumulation and fibrosis in addition to restoring the estrous cycle. GP holds promise for mitigating lipid-related ovarian issues and provides a novel approach to safeguarding ovarian health by regulating fibrosis via lipid pathways.

Aim: No pharmacotherapeutic treatment has been established for metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH). This trial compared the effects of pemafibrate and omega-3-acid ethyl ester on hepatic function in patients with hypertriglyceridemia complicated by MASLD., Methods: Patients with hypertriglyceridemia complicated by MASLD were enrolled, randomly assigned to the pemafibrate or omega-3-acid ethyl ester group, and followed for 24 weeks. The primary endpoint was the change in alanine aminotransferase (ALT) from baseline to week 24. The secondary endpoints included other hepatic enzymes, lipid profiles, and hepatic fibrosis biomarkers., Results: A total of 80 patients were enrolled and randomized. The adjusted mean change in ALT from baseline to week 24 was significantly lower in the pemafibrate group (-19.7±5.9 U/L) than in the omega-3-acid ethyl ester group (6.8±5.5 U/L) (intergroup difference, -26.5 U/L; 95% confidence interval, -42.3 to -10.7 U/L; p=0.001). Pemafibrate significantly improved the levels of other hepatic enzymes (aspartate aminotransferase and gamma-glutamyl transpeptidase), lipid profiles (triglycerides, total cholesterol, high-density lipoprotein cholesterol, and non-high-density lipoprotein cholesterol), and hepatic fibrosis biomarkers (Mac-2 binding protein glycan isomer and Fibrosis-4 index). No cases of discontinuation due to adverse drug reactions were identified in either group, and there were no safety concerns., Conclusions: Pemafibrate is recommended over omega-3-acid ethyl ester for lipid management and MASLD treatment in patients with hypertriglyceridemia complicated by MASLD. The study results may contribute to the development of future treatment strategies for patients with MASLD/MASH.

Background and Aims: Identifying patients with steatotic liver disease who are at a high risk of developing HCC remains challenging. We present a deep learning (DL) model to predict HCC development using hematoxylin and eosin-stained whole-slide images of biopsy-proven steatotic liver disease., Approach and Results: We included 639 patients who did not develop HCC for ≥7 years after biopsy (non-HCC class) and 46 patients who developed HCC <7 years after biopsy (HCC class). Paired cases of the HCC and non-HCC classes matched by biopsy date and institution were used for training, and the remaining nonpaired cases were used for validation. The DL model was trained using deep convolutional neural networks with 28,000 image tiles cropped from whole-slide images of the paired cases, with an accuracy of 81.0% and an AUC of 0.80 for predicting HCC development. Validation using the nonpaired cases also demonstrated a good accuracy of 82.3% and an AUC of 0.84. These results were comparable to the predictive ability of logistic regression model using fibrosis stage. Notably, the DL model also detected the cases of HCC development in patients with mild fibrosis. The saliency maps generated by the DL model highlighted various pathological features associated with HCC development, including nuclear atypia, hepatocytes with a high nuclear-cytoplasmic ratio, immune cell infiltration, fibrosis, and a lack of large fat droplets., Conclusions: The ability of the DL model to capture subtle pathological features beyond fibrosis suggests its potential for identifying early signs of hepatocarcinogenesis in patients with steatotic liver disease., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Aim: Hypothermia is associated with poor prognosis in patients with sepsis. However, no studies have explored the correlation between the severity of hypothermia and prognosis., Methods: Using data from the Japanese accidental hypothermia network registry (J-Point registry), we examined adult patients aged ≥18 years with infectious diseases whose initial body temperature was ≤35°C from April 1, 2011 to March 31, 2016, in 12 centers. Patients were divided into three groups according to their body temperature: Tertile 1 (T1) (32.0-35.0°C), Tertile 2 (T2) (28.0-31.9°C), and Tertile 3 (T3) (<28.0°C). In-hospital mortality was employed as a metric to assess outcomes. We conducted a multivariate logistic regression analysis to investigate the relationship between the three categories and the occurrence of in-hospital mortality., Results: A total of 572 patients were registered, and 170 eligible patients were identified. Of these patients, 55 were in T1 (32.0-35.0°C), 76 in T2 (28.0-31.9°C), and 39 in T3 (<28.0°C) groups. The overall in-hospital mortality rate in accidental hypothermia (AH) patients with infectious diseases was 34.1%. The in-hospital mortality rates in the T1, T2, and T3 groups were 34.5%, 36.8%, and 28.2%, respectively. The multivariable analysis demonstrated no significant differences regarding in-hospital mortality among the three groups (T2 vs. T1, adjusted odds ratio [OR]: 1.29; 95% confidence interval [CI]: 0.58-2.89 and T3 vs. T1, adjusted OR: 0.83; 95% CI: 0.30-2.31)., Conclusion: In this multicenter retrospective observational study, hypothermia severity was not associated with in-hospital mortality in AH patients with infectious diseases., Competing Interests: YO has received a research grant from the ZOLL Foundation and overseas scholarships from the Japan Society for Promotion of Science, the FUKUDA Foundation for Medical Technology, and the International Medical Research Foundation. These organizations have no role in conducting this study., (© 2024 The Author(s). Acute Medicine & Surgery published by John Wiley & Sons Australia, Ltd on behalf of Japanese Association for Acute Medicine.)

Background and Aims: Because the accuracy of the Fibrosis-4 (FIB-4) index for predicting liver fibrosis changes with age, the need for different cut-offs in various age groups has frequently been discussed. We developed the age-independent score, the Fibrosis-3 (FIB-3) index, and have shown its usefulness in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). This study aimed to validate the diagnostic ability of the FIB-3 index to predict fibrosis progression using a large new patient cohort., Methods: The ability of the FIB-3 index to predict liver fibrosis was analyzed by comparing it with that of the FIB-4 index using data from 1398 patients with MASLD enrolled in the Asia-based clinical outcome NAFLD study., Results: The areas under the receiver operating characteristic curves for predicting fibrosis stage F3 or higher were not different between the FIB-3 and FIB-4 indices in the entire cohort. Using the single ideal cut-offs of the indices (3.41 for FIB-3 index and 2.01 for FIB-4 index), the predictive accuracy of the FIB-3 index was not significantly different from that of the FIB-4 index among patients aged <60 years; however, the accuracy of the FIB-3 index was significantly higher than that of the FIB-4 index in those aged ≥60 years (0.645 and 0.529, respectively; p < 0.0001)., Conclusion: The high ability of the FIB-3 index with a single cut-off to predict liver fibrosis in patients with MASLD was confirmed. The FIB-3 index could serve as a useful tool for assessing liver fibrosis regardless of age., (© 2024 The Japan Society of Hepatology.)

Background and Aims: The diagnostic performance of the Fibrosis-4 (FIB-4) index and nonalcoholic fatty liver disease (NAFLD) fibrosis score (NFS) is poor in patients with type 2 diabetes mellitus (T2DM). We determined the usefulness of the Enhanced Liver Fibrosis (ELF) test in patients with T2DM., Methods: A total of 1228 patients with biopsy-proven NAFLD were enrolled. The diagnostic performance of the ELF test for predicting advanced fibrosis in participants with or without T2DM was evaluated in comparison with the FIB-4 index and NFS., Results: Overall, the area under the curve of the ELF test for predicting advanced fibrosis was greater (0.828) than that of the FIB-4 index (0.727) and NFS (0.733). The diagnostic performance of the ELF test (area under the curve, 0.820) was also superior to that of the FIB-4 index (0.698) and NFS (0.700) in patients with T2DM. With the low cutoff values for each noninvasive test, the ELF test provided an acceptable false negative rate (cutoff value 9.8, 6.7%) in this population, unlike the FIB-4 index (1.30, 14.5%) and NFS (-1.455, 12.4%). After propensity score matching to avoid selection bias including age, sex, body mass index, and the prevalence of advanced fibrosis, the ELF test with a low cutoff value showed a high sensitivity (≥91.4%) and a high negative predictive value (≥96.8%), irrespective of the presence or absence of T2DM., Conclusions: The high diagnostic performance of the ELF test for predicting advanced fibrosis in individuals with or without T2DM could address an unmet medical need for accurate assessment of liver fibrosis in patients with diabetes and NAFLD., (Copyright © 2024 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background/aims: Metabolic dysfunction-associated steatotic liver disease (MASLD) was recently proposed as an alternative disease concept to nonalcoholic fatty liver disease (NAFLD). We aimed to investigate the prognosis of patients with biopsy-confirmed MASLD using data from a multicenter study., Methods: This was a sub-analysis of the Clinical Outcome Nonalcoholic Fatty Liver Disease (CLIONE) study that included 1,398 patients with NAFLD. Liver biopsy specimens were pathologically diagnosed and histologically scored using the NASH Clinical Research Network system, the FLIP algorithm, and the SAF score. Patients who met at least one cardiometabolic criterion were diagnosed with MASLD., Results: Approximately 99% of cases (n=1,381) were classified as MASLD. Patients with no cardiometabolic risk (n=17) had a significantly lower BMI than patients with MASLD (20.9 kg/m2 vs. 28.0 kg/m2, P<0.001), in addition to significantly lower levels of inflammation, ballooning, NAFLD activity score, and fibrosis stage based on liver histology. These 17 patients had a median follow-up of 5.9 years, equivalent to 115 person-years, with no deaths, liver-related events, cardiovascular events, or extrahepatic cancers. The results showed that the prognosis for pure MASLD was similar to that for the original CLIONE cohort, with 47 deaths and one patient who underwent orthotopic liver transplantation. The leading cause of death was extrahepatic cancer (n=10), while the leading causes of liver-related death were liver failure (n=9), hepatocellular carcinoma (n=8), and cholangiocarcinoma (n=4)., Conclusion: Approximately 99% of NAFLD cases were considered MASLD based on the 2023 liver disease nomenclature. The NAFLD-only group, which is not encompassed by MASLD, had a relatively mild histopathologic severity and a favorable prognosis. Consequently, the prognosis of MASLD is similar to that previously reported for NAFLD.

Aim of the Study: This study aimed to compare the survival outcomes of adult patients with out-of-hospital cardiac arrest (OHCA) by drowning who were treated with either endotracheal intubation (ETI) or a supraglottic airway (SGA) device., Methods: We compared the outcomes of patients with OHCA by drowning according to airway management using a Japanese nationwide population-based registry (All-Japan Utstein Registry). Adult patients with OHCA treated in 2014-2020 with advanced airway management (ETI or SGA) were included. Patients who received ETI during cardiopulmonary resuscitation were matched with those treated with SGA based on propensity scores in a 1:1 ratio with a 0.2 calliper width. The outcome measures were the return of spontaneous circulation (ROSC), survival at one month, and favourable neurological outcomes defined as a Cerebral Performance Category Scale score of 1 or 2., Results: Of the 11,703 eligible patients, 4,467 (38.2%) and 7,236 (61.8%) underwent ETI and SGA, respectively. A total of 3,566 patients in each cohort were matched. The ROSC rate was higher in those treated with ETI versus SGA (207/3,566 [5.8%] versus 167/3,566 [4.7%], respectively; adjusted odds ratio, 1.25; 95% confidence interval [CI], 1.02-1.55). There was no intergroup difference in one-month survival or favourable neurological outcome (32/3566 [0.90%] versus 34/3566 [0.95%]; odds ratio, 0.94; 95% CI, 0.58-1.53; and 9/3566 [0.25%] versus 8/3566 [0.22%]; odds ratio, 1.13; 95% CI, 0.43-2.92), respectively., Conclusions: In this propensity score-matched study of adult OHCA by drowning, ETI compared to SGA was associated with ROSC but not associated with survival and favourable neurological outcomes at one month., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Taku Iwami reports financial support was provided by Japan Society for the Promotion of Science., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The study aimed to identify prognostic factors for patients with acute lower gastrointestinal bleeding and to develop a high-accuracy prediction tool. The analysis included 8254 cases of acute hematochezia patients who were admitted urgently based on the judgment of emergency physicians or gastroenterology consultants (from the CODE BLUE J-study). Patients were randomly assigned to a derivation cohort and a validation cohort in a 2:1 ratio using a random number table. Assuming that factors present at the time of admission are involved in mortality within 30 days of admission, and adding management factors during hospitalization to the factors at the time of admission for mortality within 1 year, prognostic factors were established. Multivariate analysis was conducted, and scores were assigned to each factor using regression coefficients, summing these to measure the score. The newly created score (CACHEXIA score) became a tool capable of measuring both mortality within 30 days (ROC-AUC 0.93) and within 1 year (C-index, 0.88). The 1-year mortality rates for patients classified as low, medium, and high risk by the CACHEXIA score were 1.0%, 13.4%, and 54.3% respectively (all P < 0.001). After discharge, patients identified as high risk using our unique predictive score require ongoing observation., (© 2024. The Author(s).)

Background: Totally implantable central venous access ports, are required for various purposes, ranging from chemotherapy to nutrition. Port infection is a common complication. In many patients with port infection, the ports are removed because antibiotics are ineffective. We evaluated the risk factors associated with port removal due to port infection., Methods: By retrospective chart review, we collected data of 223 patients who underwent port removal for any reason. Port infection was defined as infection symptoms, such as fever; elevated white blood cell counts or C-reactive protein levels; or redness at the port site, in the absence of other infections, which improved with port removal. The characteristics of patients with or without port infection were compared using univariate (chi-squared test, t -test) and multivariate logistic regression analyses., Results: We compared 172 patients without port infection to 51 patients with port infection. Univariate analysis identified sex ( p  = 0.01), body mass index (BMI) ⩽20 kg/m 2 ( p  = 0.00004), diabetes mellitus ( p  = 0.04), and purpose of use ( p  = 0.0000003) as significant variables. However, male sex ( p  = 0.03, 95% confidence interval [CI]: 0.01-0.23), BMI ⩽20 kg m 2 ( p  = 0.002, 95% CI: 0.06-0.29), and purpose of use (total parenteral nutrition (TPN); p  = 0.000005, 95% CI: 0.31-0.76) remained significant using multivariate analysis. Moreover, the patients with short bowel syndrome and difficulty in oral intake tended to be infected easily. Additionally, Staphylococcus species were the most common microbes involved in port infection., Conclusions: Male sex, BMI ⩽20 kg/m 2 , and purpose of use as a TPN were risk factors for port infection. Ports should not be used for long duration of TPN or used only in exceptional cases., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The urea cycle has been found to be closely associated with certain types of cancers and other diseases such as cardiovascular disease and chronic kidney disease. An analytical method for the precise quantification of urea cycle amino acids (arginine, ornithine, citrulline, and argininosuccinate) by off-line two-dimensional liquid chromatography (2D-LC) combined with fluorescence-based detection was developed. Before analysis, the amino acids were derivatised with 4-fluoro-7-nitro-2,1,3-benzoxadiazole (NBD-F) to obtain NBD-amino acids. The first dimension involved the reversed-phase separation, in which NBD derivatives of urea cycle amino acids were completely separated from each other and mostly separated from the 18 NBD-proteinogenic amino acids. The samples were eluted with stepwise gradient using 0.02% trifluoroacetic acid in water-acetonitrile as the mobile phase. In the second dimension, an amino column was used for the separation of NBD-ornithine, -citrulline, and -argininosuccinate, while a sulfonic acid column was used to separate NBD-arginine. The developed 2D-LC system was used to analyse human plasma samples. The fractions of NBD-urea cycle amino acids obtained in the first dimension were collected manually and introduced into the second dimension. By choosing appropriate mobile phases for the second dimension, each NBD-urea cycle amino acid eluted in the first dimension was well separated from the other proteinogenic amino acids and interference from endogenous substance. This could not be achieved in the first dimension. The urea cycle amino acids in human plasma sample were quantified, and the method was well validated. The calibration curves for each NBD-urea cycle amino acid showed good linearity from 3 (ASA) or 15 (Orn, Cit, and Arg) to 600 nM, with correlation coefficients higher than 0.9969. The intraday and interday precisions were less than 7.9% and 15%, respectively. The 2D-LC system is expected to be useful for understanding the involvement of the urea cycle in disease progression.

Background: Endoscopic submucosal dissection (ESD) is the standard treatment for early gastric neoplasms (EGN). Controlling intraoperative bleeding is crucial for ensuring safe and reliable procedures. ESD using the spray coagulation mode (SCM-ESD) has been developed to control bleeding more effectively than ESD using the conventional forced coagulation mode (FCM-ESD). This study aims to compare the hemostatic efficacies of SCM-ESD and FCM-ESD., Methods: This multicenter, prospective, parallel, randomized, open-label superiority trial will be conducted in five Japanese institutions. Patients with a preoperative diagnosis of intramucosal EGC will be randomized to undergo either SCM-ESD or FCM-ESD. The primary outcome measure is the completion of ESD with an electrosurgical knife alone, without the use of hemostatic forceps. Secondary outcomes include the number and duration of hemostasis using hemostatic forceps, procedure time, curability, and safety. A total of 130 patients will be enrolled in this study., Discussion: This trial will provide evidence on the hemostatic efficacy of SCM-ESD compared with FCM-ESD in patients with intramucosal EGN, potentially improving the safety and reliability of ESD procedures., Trial Registration: The trial has been registered at the University Hospital Medical Information Network Clinical Trials Registration (UMIN-CTR) as UMIN000040518. The reception number is R000054009., (© 2024. The Author(s).)

Background: Current evidence on the surgical rate, indication, procedure, risk factors, mortality, and postoperative rebleeding for acute lower gastrointestinal bleeding (ALGIB) is limited., Methods: We constructed a retrospective cohort of 10,342 patients admitted for acute hematochezia at 49 hospitals (CODE BLUE J-Study) and evaluated clinical data on the surgeries performed., Results: Surgery was performed in 1.3% (136/10342) of the cohort with high rates of colonoscopy (87.7%) and endoscopic hemostasis (26.7%). Indications for surgery included colonic diverticular bleeding (24%), colorectal cancer (22%), and small bowel bleeding (16%). Sixty-four percent of surgeries were for hemostasis for severe refractory bleeding. Postoperative rebleeding rates were 22% in patients with presumptive or obscure preoperative identification of the bleeding source and 12% in those with definitive identification. Thirty-day mortality rates were 1.5% and 0.8% in patients with and without surgery, respectively. Multivariate analysis showed that surgery-related risk factors were transfusion need ≥ 6 units (P < 0.001), in-hospital rebleeding (P < 0.001), small bowel bleeding (P < 0.001), colorectal cancer (P < 0.001), and hemorrhoids (P < 0.001). Endoscopic hemostasis was negatively associated with surgery (P = 0.003). For small bowel bleeding, the surgery rate was significantly lower in patients with endoscopic hemostasis as 2% compared to 12% without endoscopic hemostasis., Conclusions: Our cohort study elucidated the outcomes and risks of the surgery. Extensive exploration including the small bowel to identify the source of bleeding and endoscopic hemostasis may reduce unnecessary surgery and improve the management of ALGIB., (© 2023. Japanese Society of Gastroenterology.)