Clinical outcomes of endoscopic detachable snare ligation for colonic diverticular hemorrhage: Multicenter cohort study.

OBJECTIVES: The hemostatic mechanism of endoscopic detachable snare ligation (EDSL) for colonic diverticular hemorrhage (CDH) is similar to that of endoscopic band ligation, which is effective and safe. However, because reports on EDSL are scarce, we conducted a two-center cohort study to evaluate its effectiveness. METHODS: This study analyzed 283 patients with CDH treated with EDSL at two Japanese hospitals between July 2015 and November 2021. Patient characteristics and clinical outcomes were retrospectively evaluated. A Kaplan-Meier analysis was performed to evaluate the cumulative probability of rebleeding after EDSL. A Cox proportional hazards regression analysis was performed to compare the effects of complete and incomplete ligation on rebleeding. RESULTS: The initial hemostasis success and early rebleeding rates were 97.9% and 11.0%, respectively. The time to hemostasis after identification of the bleeding site and total procedure time were 9 min and 44 min, respectively. Red blood cell transfusion was required for 32.9% of patients. The median hospital length of stay after EDSL was 5 days. The complete ligation rate of the early rebleeding group was significantly lower than that of the group without early rebleeding (P < 0.01). The 1-year cumulative rebleeding rate with EDSL was 28.2%. Complete ligation was associated with decreased cumulative rebleeding after EDSL (P < 0.01). One patient experienced colonic diverticulitis; however, colonic perforation was not observed. CONCLUSION: Complete ligation is associated with reduced short-term and long-term rebleeding. EDSL could be valuable for CDH because of its low rebleeding rate and the absence of serious adverse events.

Skipping Breakfast and Progression of Chronic Kidney Disease in the General Japanese Population: The Iki City Epidemiological Study of Atherosclerosis and Chronic Kidney Disease (ISSA-CKD).

INTRODUCTION: Breakfast-skipping habits are associated with adverse health outcomes including coronary heart disease, metabolic syndrome, and diabetes mellitus. However, it remains uncertain whether skipping breakfast affects chronic kidney disease (CKD) risk. This study aimed to examine the association between skipping breakfast and progression of CKD. METHODS: We retrospectively conducted a population-based cohort study using the data from the Iki City Epidemiological Study of Atherosclerosis and Chronic Kidney Disease (ISSA-CKD). Between 2008 and 2019, we included 922 participants aged 30 years or older who had CKD (estimated glomerular filtration rate <60 mL/min/1.73 m2 and/or proteinuria) at baseline. Breakfast skippers were defined as participants who skipped breakfast more than 3 times per week. The outcome was CKD progression defined as a decline of at least 30% in the estimated glomerular filtration rate (eGFR) from the baseline status. Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for CKD progression, adjusted for other CKD risk factors. RESULTS: During a follow-up period with a mean of 5.5 years, CKD progression occurred in 60 (6.5%) participants. The incidence rate (per 1,000 person-years) of CKD progression was 21.5 in the breakfast-skipping group and 10.7 in the breakfast-eating group (p = 0.029), respectively. The multivariable-adjusted HR (95% CI) for CKD progression was 2.60 (95% CI: 1.29-5.26) for the breakfast-skipping group (p = 0.028) compared with the group eating breakfast. There were no clear differences in the association of skipping breakfast with CKD progression in subgroup analyses by sex, age, obesity, hypertension, diabetes mellitus, baseline eGFR, and baseline proteinuria. CONCLUSION: Skipping breakfast was significantly associated with higher risk of CKD progression in the general Japanese population.

Fluoride-Based Deep Eutectic Solvents with Amide Dual-Hydrogen-Bond Donors.

Developing F--containing electrolytes is crucial for electrochemical and chemical fluorination. However, balancing the F- concentration and electrochemical stability of the electrolytes remains a challenge. In this study, fluoride-based deep eutectic solvents (F-DESs) were obtained by using amide hydrogen-bond donors (HBDs) containing dual N-H bonds. The obtained F-DES, [TMA]F·3.5[1,3-DMU], was prepared by facilely mixing solid compounds of tetramethylammonium fluoride ([TMA]F) and 1,3-dimethylurea (1,3-DMU), resulting in a high F- concentration (2.6 mol dm-3) and a wide electrochemical window (3.1 V) at room temperature. The electrochemical window was much wider than that of [TMA]F·3.5[EG] (EG, ethylene glycol) as another F-DES with an alcohol HBD (1.9 V). Moreover, [TMA]F·3.5[1,3-DMU] exhibited an ionic conductivity that was 2 orders of magnitude higher than that of [TMA]F·3.5[1,3-DMTU] (1,3-DMTU, 1,3-dimethylthiourea) around room temperature because of the bifurcated hydrogen bonds between the dual N-H bonds of 1,3-DMU and one F-. Thus, [TMA]F·3.5[1,3-DMU] was demonstrated to be applicable to electrochemical fluorination.

Lipoprotein glomerulopathy with markedly increased arterial stiffness successfully treated with a combination of fenofibrate and losartan: a case report.

BACKGROUND: Lipoprotein glomerulopathy (LPG) is a apolipoprotein E (ApoE)-related glomerular disease and has been associated with type III hyperlipidemia. Without appropriate treatment, chronic kidney disease (CKD) caused by LPG progresses, and approximately half of the patients develop end-stage kidney disease within 1-27 years of disease onset. However, few studies have highlighted the clinical course of cardiovascular diseases (CVDs) in patients with LPG. Herein, we report the first case of LPG in which the CVD risk was assessed using arterial stiffness. CASE PRESENTATION: A 32-year-old Japanese man was referred to our hospital due to persistent proteinuria. Kidney biopsy showed markedly dilated capillary lumens containing pale-stained thrombi, which stained positively with Oil Red O. Electron microscopy revealed the presence of thrombi in the capillary lumen with low electron density and vacuoles of various sizes in part of the thrombi. Toluidine blue and Sudan IV stains were used to stain the thin sections of Epon-embedded tissue samples for electron microscopy. Sudan IV-positive droplets were observed in the capillary lumens, vascular walls, and cytoplasm of tubular cells. Increased serum ApoE concentration was observed. Liquid chromatography-tandem mass spectrometry of laser-microdissected glomeruli from paraffin sections revealed an increase in ApoE. Direct deoxyribonucleic acid sequencing of ApoE revealed a heterozygous ApoE Sendai mutation (Arg145Pro). The patient was finally diagnosed with LPG with heterozygosity for ApoE-Sendai mutation (Arg145Pro). Notably, at the time of diagnosis, he had markedly increased arterial stiffness for his age. Arterial stiffness was measured using brachial-ankle pulse wave velocity (baPWV), which was equivalent to that of a 56-year-old man. After three months of treatment with fenofibrate and losartan, a significant reduction in proteinuria was achieved along with an improvement in baPWV. Furthermore, these effects were maintained despite the lack of decrease in serum ApoE levels. CONCLUSION: Herein, we report the case of a patient with LPG with markedly increased arterial stiffness at the time of diagnosis, in whom combination therapy with fenofibrate and losartan successfully improved proteinuria and arterial stiffness. To the best of our knowledge, this is the first case report of LPG in which CVD risk was assessed using arterial stiffness.

Cellular reprogramming in vivo initiated by SOX4 pioneer factor activity.

Tissue damage elicits cell fate switching through a process called metaplasia, but how the starting cell fate is silenced and the new cell fate is activated has not been investigated in animals. In cell culture, pioneer transcription factors mediate "reprogramming" by opening new chromatin sites for expression that can attract transcription factors from the starting cell's enhancers. Here we report that SOX4 is sufficient to initiate hepatobiliary metaplasia in the adult mouse liver, closely mimicking metaplasia initiated by toxic damage to the liver. In lineage-traced cells, we assessed the timing of SOX4-mediated opening of enhancer chromatin versus enhancer decommissioning. Initially, SOX4 directly binds to and closes hepatocyte regulatory sequences via an overlapping motif with HNF4A, a hepatocyte master regulatory transcription factor. Subsequently, SOX4 exerts pioneer factor activity to open biliary regulatory sequences. The results delineate a hierarchy by which gene networks become reprogrammed under physiological conditions, providing deeper insight into the basis for cell fate transitions in animals.

Relationship between abdominal circumference and the incidence of hyperuricemia in the general Japanese population.

In this study, we aimed to separately evaluate the relationship between waist circumference and the incidence of hyperuricemia in men and women in the general Japanese population. We performed a population-based longitudinal study using data from the annual health examination of residents of Iki City, Japan. A total of 5567 participants without hyperuricemia at baseline were included in the analysis. The men and women were placed into groups according to the tertile of waist circumference. The outcome was incident hyperuricemia (uric acid > 416 µmol/L [7.0 mg/dL]). The relationship between waist circumference and the incidence of hyperuricemia was investigated using Cox proportional hazards models. During the follow-up period, hyperuricemia developed in 697 people (551 men and 146 women). The incidence (per 1000 person-years) of hyperuricemia increased with increasing waist circumference in the men (34.9 for tertile 1, 49.9 for tertile 2 and 63.3 for tertile 3; Ptrend < 0.001) and women (5.5 for tertile 1, 6.3 for tertile 2 and 11.9 for tertile 3; Ptrend < 0.001). Significant associations were identified after adjustment for potential confounders (men: Ptrend < 0.001; women: Ptrend = 0.014). In conclusion, both men and women with larger waist circumferences were at higher risks of subsequent hyperuricemia.

Third nationwide surveillance of bacterial pathogens in patients with acute uncomplicated cystitis conducted by the Japanese surveillance committee during 2020 and 2021: Antimicrobial susceptibility of Escherichia coli, Klebsiella pneumoniae, and Staphylococcus saprophyticus.

The Japanese surveillance committee conducted a third nationwide surveillance of antimicrobial susceptibility of acute uncomplicated cystitis at 55 facilities throughout Japan between April 2020 and September 2021. In this surveillance, we investigated the susceptibility of Escherichia coli (E. coli), Klebsiella pneumoniae (K. pneumoniae), and Staphylococcus saprophyticus (S. saprophyticus) for various antimicrobial agents by isolating and culturing bacteria from urine samples. In total, 823 strains were isolated from 848 patients and 569 strains of target bacteria, including E. coli (n = 529, 92.9 %), K. pneumoniae (n = 28, 4.9 %), and S. saprophyticus (n = 12, 2.2 %) were isolated. The minimum inhibitory concentrations of 18 antibacterial agents were determined according to the Clinical and Laboratory Standards Institute manual. In premenopausal patients, there were 31 (10.5 %) and 20 (6.8 %) fluoroquinolone (FQ)-resistant E. coli and extended-spectrum ß-lactamase (ESBL)-producing E. coli, respectively. On the other hand, in postmenopausal patients, there were 75 (32.1 %) and 36 (15.4 %) FQ-resistant E. coli and ESBL-producing E. coli, respectively. The rate of FQ-resistant E. coli and ESBL-producing E. coli in post-menopausal women was higher than that for our previous nationwide surveillance (20.7 % and 32.1 %: p = 0.0004, 10.0 % and 15.4 %; p = 0.0259). For pre-menopausal women, there was no significant difference in the rate of FQ-resistant E. coli and ESBL-producing E. coli between this and previous reports, but the frequency of FQ-resistant E. coli and ESBL-producing E. coli exhibited a gradual increase. For appropriate antimicrobial agent selection and usage, it is essential for clinicians to be aware of the high rate of these antimicrobial-resistant bacteria in acute uncomplicated cystitis in Japan.

Feasibility and Outcome of Transjugular Intracardiac Echocardiography-Guided Transcatheter Aortic Valve Replacement.

Background: There are limited data on the impact of intracardiac echocardiography (ICE)-guided transcatheter aortic valve replacement (TAVR) on the new permanent pacemaker implantation (PPMI) rate. Objectives: This study investigated the feasibility and outcome of transjugular ICE (TJ-ICE) -guided TAVR, by visualizing the relationship between the membranous septum (MS) and the transcatheter aortic valve (TAV). Methods: Among patients with severe aortic stenosis who underwent TAVR between February 2017 and June 2020, this study enrolled a total of 163 patients with TJ-ICE-guided TAVR. MS length was measured by ICE. The primary endpoint of this study was the incidence of new PPMI at 30 days. Results: The mean age of the patients in this study was 84.9 ± 4.6 years, and 71.2% of the patients were female. Device success was 96.3% with TJ-ICE guidance. A TJ-ICE-related complication occurred in 1 case (0.6%). The median length of the MS was 5.8 mm (IQR: 5.0-6.9 mm). Excellent intraobserver (intraclass correlation coefficient [ICC]: 0.94; 95% CI:0.79-0.98; P < 0.001) and interobserver (ICC: 0.93; 95% CI: -0.05 to 0.98; P < 0.001) agreements were shown. The new PPMI rate was 6.7% at 30 days without a significant difference between balloon-expandable valves and self-expandable valves (3.4% vs 8.7%; P = 0.226). Patients with a TAV implantation depth less than MS length had a significantly lower incidence of new PPMI compared with patients with a TAV implantation depth greater than MS length (2.1% vs 13.4%; P = 0.005), regardless of baseline right bundle branch block presence (6.7% vs 66.7%; P = 0.004) or absence (1.2% vs 8.2%; P = 0.041). Conclusions: TJ-ICE-guided TAVR demonstrated remarkable feasibility and safety. The TJ-ICE-guided final TAV position had a significant impact on the new PPMI rate. (Tokai Valve Registry; UMIN000036671).