Dichloroacetate reduces cisplatin-induced apoptosis by inhibiting the JNK/14-3-3/Bax/caspase-9 pathway and suppressing caspase-8 activation via cFLIP in murine tubular cells.

Cisplatin-induced injury to renal proximal tubular cells stems from mitochondrial damage-induced apoptosis and inflammation. Dichloroacetate (DCA), a pyruvate dehydrogenase kinase (PDK) inhibitor, a potential generator of ROS and ATP, protects against cisplatin-induced nephrotoxicity by promoting the TCA cycle. However, its effects on apoptotic pathways and ROS production in renal tubular cells remain unclear. Here, we investigated the detailed molecular mechanisms of the DCA's effects by immunoblot, RT-PCR, RNA-sequencing, and RNA-silencing in a murine renal proximal tubular (mProx) cell line and mouse kidneys. In mProx cells, DCA suppressed cisplatin-induced apoptosis by attenuating the JNK/14-3-3/Bax/caspase-9 and death receptor/ligand/caspase-8 pathways without impeding inflammatory signaling. RNA-sequencing demonstrated that DCA increased the cisplatin-reduced expression of cFLIP, a caspase-8 inactivator, and decreased the expression of almost all oxidative phosphorylation (OXPHOS) genes. DCA also increased NF-kB activation and ROS production, probably enhancing the cFLIP induction and OXPHOS gene reduction, respectively. Furthermore, cFLIP silencing weakened the DCA's anti-apoptotic effects. Finally, in mouse kidneys, DCA attenuated cisplatin-caused injuries such as functional and histological damages, caspase activation, JNK/14-3-3 activation, and cFLIP reduction. Conclusively, DCA mitigates cisplatin-induced nephrotoxicity by attenuating the JNK/14-3-3/Bax/caspase-9 pathway and inhibiting the caspase-8 pathways via cFLIP induction, probably outweighing the cisplatin plus DCA-derived cytotoxic effects including ROS.

Comparison of early versus late addition of granulocyte and monocyte adsorption for incomplete remission induction in ulcerative colitis.

Background and aim: Ulcerative colitis (UC) is characterized by repeated relapse and remission. Because no fundamental therapeutic strategy has been established, the treatment goal is generally to maintain the remission phase for a long period after rapid remission induction. Granulocyte and monocyte adsorption (GMA) for UC is reportedly quite safe because it does not affect immunosuppression. Moreover, it is useful in combination with other remission induction therapy. The aim of this study was to evaluate the difference in efficacy by the timing of the addition of GMA with corticosteroids, calcineurin inhibitors, and anti-cytokine therapy for active UC. Methods: The study included 59 patients. Patients who started GMA of 5-11 days were in the early GMA combination group. Patients who started GMA 12 days or more were in the late GMA combination group. The primary endpoint was difference in the effect of additional GMA according to the timing of the intervention. The secondary endpoint was difference in the time to remission induction between the two groups. Results: Of the 32 early GMA group patients, 24 achieved remission induction. Of the 27 late group patients, 18 achieved remission induction. No significant difference in induction rates was found (P = 0.481). The early group had shorter mean time to remission induction (P < 0.001). Conclusions: In conclusion, results suggest that early addition of GMA might lead to earlier remission in patients who have had an inadequate response to remission induction therapy with corticosteroids, calcineurin inhibitors, and anti-cytokine therapy.

Estimated Proximal Tubule Fluid Phosphate Concentration and Renal Tubular Damage Biomarkers in Early Stages of Chronic Kidney Disease.

OBJECTIVE: An increase in proximal tubule fluid phosphate concentration is caused by increased serum fibroblast growth factor-23 (FGF23) levels, which resulted in renal tubular damage in a mouse model of chronic kidney disease (CKD). However, few human studies have supported this concept. This study aimed to explore the association among estimated proximal tubule fluid phosphate concentration (ePTFp), serum FGF23 levels, and renal tubular damage biomarkers in middle-aged and older populations with mild decline in renal function. METHODS: This cross-sectional study included 218 participants aged ≥45 with CKD stages G2-G4. Anthropometric measurements, blood tests, spot urine biomarkers, renal ultrasonography, cardiovascular assessment, smoking status, and medication usage were obtained in the morning in fasted states. The ePTFp was calculated using serum creatinine, urine phosphate, and creatinine concentrations. Urinary ß2-microglobulin (ß2-MG) and liver-type fatty acid-binding protein (L-FABP) levels were evaluated to assess renal tubular damage. RESULTS: PTFp, serum FGF23, urinary ß2-MG, and urinary L-FABP levels increased with CKD stage progression (stages G2, G3, and G4). However, serum and urine phosphate concentrations were comparable across the CKD stages. Univariate analysis revealed a stronger correlation of ePTFp with serum FGF23, urinary ß2-MG, and urinary L-FABP levels than with the corresponding serum and urine phosphate concentrations. Multivariate analyses demonstrated that increased ePTFp was independently associated with elevated serum FGF23 and urinary ß2-MG levels, even after adjusting for potential covariates, including the estimated glomerular filtration rate and urinary albumin-to-creatinine ratio. CONCLUSIONS: Our results are consistent with the concept in mouse model and suggest that increased ePTFp are associated with increased serum FGF23 levels and renal tubular damage during the early stages of CKD.

Symptomatic duodenal intramural hematoma caused by weight training: a report of two cases.

Symptoms of traumatic duodenal intramural hematoma, a rare disease caused by trauma, blood disease, or antithrombotic therapy, can include abdominal pain. Case 1 is that of a 35-year-old man at a gym who dropped a 100 kg barbell on his abdomen. It was diagnosed as a duodenal obstruction caused by a traumatic intestinal wall hematoma. In Case 2, a 16-year-old male adolescent performing deadlift training at a gym had subsequent abdominal pain. It was diagnosed as intestinal wall hematoma. Both patients improved with conservative treatment. Malignancy is sometimes suspected from imaging findings. Detailed patient history and imaging studies can avoid unnecessary surgery.

Risk Factors for Developing Metachronous Superficial Gastric Epithelial Neoplasms after Endoscopic Submucosal Dissection.

Background: Although endoscopic submucosal dissection (ESD) provides a high rate of curative resection, the remaining gastric mucosa after ESD is at risk for metachronous superficial gastric epithelial neoplasms (MSGENs). It leaves room for risk factors for developing MSGENs after ESD. This study aimed to identify clinicopathological risk factors for the occurrence of MSGENs, and to evaluate the association of Helicobacter pylori (H. pylori) with the MSGENs. Methods: We conducted a retrospective cohort study including 369 patients with 382 lesions that underwent ESD for adenoma/early gastric cancer. Results: Twenty-seven MSGENs occurred. The subjects were divided into MSGEN and not-MSGEN groups. There was a significantly higher frequency of histological intestinal metaplasia (HIM) and initial neoplasm location in the upper or middle parts (INUM) in the MSGEN group. The HIM and INUM groups had a significantly higher cumulative incidence of MSGENs. We compared 27 patients from the MSGEN group and 27 patients from the not-MSGEN group that were matched to the MSGEN group for variables including HIM and INUM. There was a significantly higher frequency of the spontaneous disappearance of H. pylori in the MSGEN group. Conclusions: HIM, INUM, and the spontaneous disappearance of H. pylori may be clinicopathological risk factors for developing MSGENs after ESD.

Urine oxygenation predicts COVID-19 risk.

Since February, 2023, the omicron variant has accounted for essentially all new coronavirus infections in Japan. If future infections involve mutant strains with the same level of infectivity and virulence as omicron, the government's basic policy will be to prevent the spread of infection, without compromising socioeconomic activities. Objectives include protecting pregnant women and elderly persons, and focusing on citizens requiring hospitalization and those at risk of serious illness, without imposing new social restrictions. Although the government tries to raise public awareness through education, most people affected by COVID-19 stay at home, and by the time patients become aware of the seriousness of their disease, it has often reached moderate or higher severity. In this review, we discuss why this situation persists even though the disease seems to have become milder with the shift from the delta variant to omicron. We also propose a pathophysiological method to determine the risk of severe illness. This assessment can be made at home in the early stages of COVID-19 infection, using urine analysis. Applicability of this method to drug discovery and development is also discussed.

D-alanine Inhibits Murine Intestinal Inflammation by Suppressing IL-12 and IL-23 Production in Macrophages.

BACKGROUND AND AIMS: Free D-amino acids, which have different functions from L-amino acids, have recently been discovered in various tissues. However, studies on the potential interactions between intestinal inflammation and D-amino acids are limited. We examined the inhibitory effects of D-alanine on the pathogenesis of intestinal inflammation. METHODS: We investigated serum D-amino acid levels in 40 patients with ulcerative colitis and 34 healthy volunteers. For 7 days [d], acute colitis was induced using dextran sulphate sodium in C57BL/6J mice. Plasma D-amino acid levels were quantified in mice with dextran sulphate sodium-induced colitis, and these animals were administered D-alanine via intraperitoneal injection. IFN-γ, IL-12p35, IL-17A, and IL-23p19 mRNA expression in the colonic mucosa was measured using real-time polymerase chain reaction [PCR]. In vitro proliferation assays were performed to assess naïve CD4+ T cell activation under Th-skewing conditions. Bone marrow cells were stimulated with mouse macrophage-colony stimulating factor to generate mouse bone marrow-derived macrophages. RESULTS: Serum D-alanine levels were significantly lower in patients with ulcerative colitis than in healthy volunteers. Dextran sulphate sodium-treated mice had significantly lower plasma D-alanine levels than control mice. D-alanine-treated mice had significantly lower disease activity index than control mice. IFN-γ, IL-12p35, IL-17A, and IL-23p19 mRNA expression levels were significantly lower in D-alanine-administered mice than in control mice. D-alanine suppressed naïve T cell differentiation into Th1 cells in vitro, and inhibited the production of IL-12p35 and IL-23p19 in bone marrow-derived macrophages. CONCLUSIONS: Our results suggest that D-alanine prevents dextran sulphate sodium-induced colitis in mice and suppresses IL-12p35 and IL-23p19 production in macrophages.

Elevation of Urinary Liver-Type Fatty Acid-Binding Protein Is a Harbinger of Poor Patient Prognosis after Allogeneic Stem Cell Transplantation.

Several recent studies have demonstrated that urinary levels of liver-type fatty acid-binding protein (L-FABP) can be used to stratify the prognosis of cardiac disease, cardiac intensive care unit admission, cirrhosis, and coronavirus disease 2019. Our initial prospective study revealed that urinary L-FABP (uL-FABP) was associated with a high probability of acute kidney injury after stem cell transplantation (SCT); however, the relevance of elevated uL-FABP to the prognosis of patients undergoing SCT remains to be determined. We aimed to investigate whether uL-FABP levels can be used to stratify patient prognosis after SCT. To achieve this aim, we conducted a new long-term follow-up study using data from patients enrolled in our preceding prospective cohort study. Patients were classified into high and low uL-FABP groups based on levels measured at baseline (ie, before initiating the conditioning regimen), using an uL-FABP cutoff of 8.4 µg/gCr, which was determined based on data from healthy adults. uL-FABP levels were also measured on days 0, 7, and 14 after SCT. Cox proportional hazard regression was used to examine the effects of each factor on survival outcomes, and Fine-Gray regression was used in the presence of competing risks. Multivariate analysis incorporating confounders was then performed for factors with P < .1 in univariate analysis. In total, 20 of 84 patients (23.8%), 57 of 84 patients (67.9%), 34 of 49 patients (69.4%), and 34 of 46 patients (73.9%) were classified into the high uL-FABP group at baseline and on days 0, 7, and 14, respectively. The 5-year overall survival (OS) rate was 23.9% in the high uL-FABP group and 68.9% in the low uL-FABP group. The multivariate analysis identified a high uL-FABP level at baseline as a significant prognostic factor for poor OS (hazard ratio [HR], 3.54; P = .002). The 5-year cumulative incidence rate for nonrelapse mortality (NRM) was 50.0% in the high uL-FABP group and 19.9% in the low uL-FABP group. In the multivariate analysis, high uL-FABP at baseline was a significant prognostic factor for NRM (HR, 3.37; P = .01). uL-FABP levels did not significantly stratify the cumulative incidence of relapse (HR, 2.13; P = .11). uL-FABP levels on days 0, 7, and 14 were not significant predictors of survival. High uL-FABP level before initiation of conditioning significantly influences OS and NRM following SCT, whereas a high uL-FABP level at any point after the conditioning regimen does not. Our results show that measuring uL-FABP level at baseline may be a simple way to predict survival in patients undergoing SCT.

Urinary liver-type fatty acid binding protein is a biomarker reflecting renal damage and the ameliorative effect of drugs at an early stage of histone-induced acute kidney injury.

AIM: Circulated histones play a crucial role in the pathogenesis of infectious diseases and severe trauma, and it is one of the potential molecular targets for therapeutics. Recently, we reported that histone is one of the causative agents for urinary L-FABP increase. However, the mechanism is still unclear, especially in severe cases. We further investigated the mechanism of urinary L-FABP increase using a more severe mouse model with histone-induced kidney injury. This study also aims to evaluate the therapeutic responsiveness of urinary L-FABP as a preliminary study. METHODS: Human L-FABP chromosomal transgenic mice were administrated 30 mg/kg histone from a tail vein with a single dose. We also performed a comparative study in LPS administration model. For the evaluation of the therapeutic responsiveness of urinary L-FABP, we used heparin and rolipram. RESULTS: The histological change with cast formation as a characteristic of the models was observed in proximal tubules. Urinary L-FABP levels were significantly elevated and these levels tended to be higher in those with more cast formation. Heparin and rolipram had the ameliorative effect of the cast formation induced by histone and urinary L-FABP levels significantly decreased. CONCLUSION: Histone is one of the causative agents for the increase of urinary L-FABP at an early stage of AKI. In addition, it suggested that urinary L-FABP may be useful as a subclinical AKI marker reflecting kidney damage induced by histone. Furthermore, urinary L-FABP reflected the degree of the damage after the administration of therapeutic agents such as heparin and PDE4 inhibitor.

Association of Lower Extremity Muscle Strength and Function with Renal Resistive Index in Individuals with and without Chronic Kidney Disease.

Age-related loss of lower extremity muscle strength is pronounced in individuals with chronic kidney disease (CKD). In contrast, an increase in intrarenal flow pulsatility results in initial age-related changes in renal hemodynamics, leading to the development of CKD. To date, it remains unclear whether lower extremity muscle strength determines elevated renal flow pulsatility. This study aimed to determine the association of lower extremity muscle strength and function with intrarenal hemodynamics in individuals with and without CKD. One hundred seventy-six individuals without CKD (aged 63 ± 9 years) and 101 individuals with CKD (aged 66 ± 8 years) were included in this study. Using Doppler ultrasound, the renal resistive index (RI) was measured as a parameter of renal hemodynamics. Knee extensor muscle strength (KES), gait speed (GS), and the 30 s chair stand test (30s-CST) were used to measure lower extremity muscle strength and function. Multivariate analyses showed that GS and 30s-CST scores were independent determinants of renal RI, whereas the KES score was not associated with renal RI in individuals with and without CKD. In the two-way analysis of covariance, renal RI was the highest in individuals with CKD who had lower KES, GS, and 30s-CST scores. Reduced lower extremity muscle strength and function are independent determinants of elevated renal flow pulsatility in individuals with and without CKD.

Clinical Background Factors as Predictors of the Efficacy of 5-Aminosalicylic Acid Suppositories in Patients with Ulcerative Colitis.

Introduction: Although the efficacy of 5-aminosalicylic acid (ASA) suppositories for ulcerative colitis (UC) has been reported in many studies, many studies have also described poor adherence to 5-ASA suppository regimens. We aimed to identify the clinical background factors that influence adherence to 5-ASA suppositories to improve adherence and efficacy of the treatment. Methods: We conducted a retrospective cohort study of 61 patients with active UC who were using 5-ASA suppositories. All patients underwent endoscopy and rectal biopsy for histological diagnosis prior to 5-ASA suppository treatment. The efficacy of 5-ASA suppository treatment was compared in relation to clinical background factors (sex, age, disease duration, disease type, clinical activity, Ulcerative Colitis Endoscopic Index of Severity, histological activity, serum C-reactive protein level, concomitant use of immunomodulators, history of steroid use, and dose of oral 5-ASA). Results: The efficacy of 5-ASA suppositories was significantly related to low Lichtiger Colitis Activity Index (LCAI) scores and proctitis type prior to its use. In terms of sex, females tended to show higher efficacy. Multivariate logistic regression analysis using these three factors showed high predictive value for the efficacy of 5-ASA suppositories (AUC, 0.788; sensitivity, 87.2%; and specificity, 63.7%). Conclusion: This study is the first to extract clinical background factors for predicting the efficacy of 5-ASA suppositories. The use of 5-ASA suppositories in patients who are expected to show efficacy will be effective in improving patient co-operation.

Investigating COVID-19 Pandemic Effects on Acute Pancreatitis Development-From the Perspective of Alcohol Sales (Consumption) in a Japanese Regional Hospital.

[Aim and Background] People's lifestyles changed considerably due to the coronavirus disease 2019 (COVID-19) pandemic. The number of patients with acute pancreatitis (AP) can be expected to decrease as alcohol consumption decreases. This study was conducted to assess COVID-19 pandemic effects on AP patients in a Japanese regional hospital. [Methods] Based on the first and second states of emergency declarations in Tochigi Prefecture, the survey periods were set as follows: period A, 16 April-14 May; period B, 15 May-13 January; period C, 14 January-7 February; and period D, 8 February-15 April. Using data acquired in 2017, 2018, 2019, and 2020, we retrospectively reviewed the number of patients admitted to our hospital with a diagnosis of AP, and their clinical characteristics. [Results] According to a National Tax Agency survey, the average alcohol sales per adult in Tochigi Prefecture were 71.3 L in 2017 before the pandemic, and 64.0 L in 2021 under the pandemic. The number of AP patients in 2020 was 38% lower than in 2017. Comparing 2017 with 2020, the number of alcoholic AP patients was lower in 2020 (p = 0.007). [Conclusions] The findings suggest that COVID-19-pandemic-related lifestyle changes contributed to the decrease in AP patients.

Proposal and Validation of New Diagnostic Criteria for Diagnostic Weights of Endoultrasonographic Findings for Early Chronic Pancreatitis.

[Background and study aim] A commonly applied method for diagnosing chronic pancreatitis (CP) uses endoscopic ultrasonography (EUS), assigning weights to each EUS diagnostic finding. It is the Rosemont classification (RC). In 2019, to improve EUS diagnostic specificity, Japanese diagnostic criteria for early chronic pancreatitis (ECP) were revised. Nevertheless, the criteria use no weighting of EUS diagnostic findings, as the RC does. This study was undertaken to propose diagnostic criteria that would weight each EUS finding of ECP and that would be more specific than the RC. [Methods] By EUS of the pancreas, 773 patients underwent detailed observation from January 2018 to March 2019 at our institution. An expert finalized all cases when patients were diagnosed. Using data from the medical records, 97 consecutive patients with EUS diagnostic findings of ECP based on the Japanese diagnostic criteria of ECP2009 (JDCECP2009) were selected. The definition under the RC of "Indeterminate for CP" was equivalent to ECP. Each case was diagnosed using (1) JDCECP2009 and (2) the Japanese diagnostic criteria of ECP2019 (JDCECP2019). Moreover, the four diagnostic EUS findings in JDCECP2019 were applied to the RC, weighted (modified-JDCECP2019), and subsequently compared with the earlier diagnostic criteria. As Modified-JDCECP2019, we suggested (3) RC-A-the current four items scored related to the RC, and (4) RC-B-the five items scored by dividing lobularity with and without honeycombing. [Results] Diagnoses produced based on each criterion were normal: ECP = (1) 20:77, (2) 46:51, (3) 52:42, and (4) 60:35. [Conclusions] Modified-JDCECP2019 may provide EUS diagnoses for ECP with higher specificity.

Elevated urinary angiotensinogen excretion links central and renal hemodynamic alterations.

Inappropriate activation of intrarenal renin-angiotensin system (RAS) may contribute to the pathogenesis of cardio-renal syndrome (CRS). We aimed to examine the cross-sectional associations of urinary angiotensinogen (AGT) excretion, a biomarker of intrarenal RAS activity, with central (aortic) and renal hemodynamic parameters in middle-aged and older adults, including patients with chronic kidney disease. Aortic and renal hemodynamic parameters were measured using applanation tonometry and duplex ultrasonography in 282 participants. Urinary AGT, liver-type fatty acid-binding protein (L-FABP), and plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels were measured for each participant. Multiple linear regression analyses demonstrated that urinary AGT levels were associated with aortic blood pressures, pulsatile measures of renal blood flow, plasma NT-proBNP and urinary L-FABP levels after adjusting for potential covariates, including age, sex, body mass index, estimated glomerular filtration rate (GFR), and medication use. Additionally, when classified based on GFR stages and urinary AGT levels, plasma NT-proBNP and urinary L-FABP levels increased in participants with lower GFR and higher AGT groups. Our findings suggest that urinary AGT excretion is a shared determinant of central (aortic) and renal hemodynamics in middle-aged and older adults, providing clinical evidence for the potential role of intrarenal RAS activity in the development of CRS.

Urinary liver-type fatty acid binding protein is increased in the early stages of the disease with a risk of acute kidney injury induced by histone.

AIM: Urinary liver-type fatty acid binding protein (L-FABP) has potential utility as an early prognostic biomarker ahead of traditional severity scores in coronavirus disease 2019 and sepsis, however, the mechanism of elevated urinary L-FABP in the disease has not been clearly elucidated. We investigated the background mechanisms of urinary L-FABP excretion through non-clinical animal model focusing on histone, which is one of the aggravating factors in these infectious diseases. METHODS: Male Sprague-Dawley rats were placed in central intravenous catheters, and these rats were given a continuous intravenous infusion of 0.25 or 0.5 mg/kg/min calf thymus histones for 240 min from caudal vena cava. RESULTS: After the administration of histone, urinary L-FABP and gene expression of an oxidative stress marker in the kidney increased in a histone dose-dependent manner before increased serum creatinine. Upon further investigation, fibrin deposition in the glomerulus was observed and it tended to be remarkable in the high dose administrated groups. The levels of coagulation factor were significantly changed after the administration of histone, and these were significantly correlated with the levels of urinary L-FABP. CONCLUSIONS: Firstly, it was suggested that histone is one of the causative agents for the urinary L-FABP increase at an early stage of the disease with a risk of acute kidney injury. Secondly, urinary L-FABP could be a marker reflecting the changes of coagulation system and microthrombus caused by histone in the early stage of acute kidney injury before becoming severely ill and maybe a guide to early treatment initiation.

Mechanism for exercise-mediated prevention against muscle wasting on extensor digitorum longus muscle in Spontaneously Diabetic Torii fatty rats.

We previously reported the significant increase in limb muscle strength and cross-sectional area of the type IIb muscle fibers in the extensor digitorum longus (EDL) muscle in a type 2 diabetic animal model, with Spontaneously Diabetic Torii (SDT) fatty rats (n = 6) undergoing regular treadmill exercise from 8 to 16 weeks of age compared with sedentary SDT fatty rats (n = 6). This study investigated the mechanism by which exercise training prevented skeletal muscle wasting in the EDL muscle of the SDT fatty rats. The endurance exercise for 8 weeks downregulated the expression of muscle RING-finger protein-1 (an E3 ubiquitin ligase) and upregulated the expression of CD31, insulin receptor substrate-2, and phosphorylated endothelial nitric oxide synthase in the EDL muscle of 16-week-old SDT fatty rats.Endurance exercise training might reduce muscle wasting by preventing muscle degradation and increasing the angiogenic response in the EDL muscle in type 2 diabetes.

Urinary L-Type Fatty Acid-Binding Protein Predicts Oxygen Demand of COVID-19 in Initially Mild Cases.

Early detection of illness trajectory in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infected patients is crucial for patients and healthcare workers. An effective, noninvasive approach, with simple measurement for decision-making, is necessary in a pandemic to discriminate between high- and low-risk patients, even though both groups may exhibit mild symptoms in the beginning. OBJECTIVES: To predict COVID-19 disease severity within 10 days, distinguishing cases that will progress to moderate or severe versus mild, patient urinary L-type fatty acid-binding protein (L-FABP) was assayed within 4 days of receiving a diagnosis. The study also examined whether L-FABP point of care (POC) test is helpful in risk screening. DESIGN: Symptomatic subjects who tested positive for SARS-CoV-2 and were hospitalized were prospectively enrolled at the National Center for Global Health and Medicine (NCGM), Yamanashi Prefectural Central Hospital (YPCH), and Sinai Hospital in Maryland. The outcome of each case was evaluated 7 days after admission and the diagnostic performance of L-FABP was assessed. SETTING AND PARTICIPANTS: Subjects were treated for COVID-19 at public healthcare centers in Japan from January 31, 2020, to January 31, 2021, to NCGM, YPCH, and at Sinai Hospital in Baltimore, MD, during the same period. MAIN OUTCOMES AND MEASURES: The primary outcome was to determine whether urinary L-FABP within 48 hours of admission can predict the patient's severity of COVID-19 1 week later. We obtained demographic data, information on clinical symptoms, radiographic images, and laboratory data. RESULTS: Diagnostic performance was assessed using receiver operating characteristic analysis. Of the 224 participants in the study, 173 initially had a mild form of COVID-19. The area under the curve (AUC) for a severe outcome was 93.5%. L-FABP POC risk prediction of a severe outcome had an AUC of 88.9%. CONCLUSIONS AND RELEVANCE: Urinary L-FABP can predict patient risk of COVID-19 illness severity. L-FABP POC is implementable for patient management. (ClinicalTrials.gov number, NCT04681040).

Serum titer of neutralizing antibodies after COVID-19 vaccination in Japanese patients with inflammatory bowel disease.

Vaccination is an important strategy to reduce the infection rate and adverse events of coronavirus disease 2019 (COVID-19). However, the effect of COVID-19 vaccination for Japanese patients with inflammatory bowel disease (IBD) has not been fully elucidated. In the present study, we investigated the serum titer of neutralizing antibodies after COVID-19 vaccination in patients with IBD, treated with and without immunosuppressive therapy. The study consisted of 108 patients with IBD [76 with ulcerative colitis (UC) and 32 with Crohn's disease (CD)] from the gastroenterology outpatient clinic at the Hospital of the Kyoto Prefectural University of Medicine who underwent anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. The control group included 64 healthy subjects who received the anti-SARS-CoV-2 vaccine. When 10 AU/ml of neutralizing antibodies was used as cut-off value, the positive rates of neutralizing antibodies of patients with UC, patients with DC, and the control group were 97.3%, 84.3%, and 100%, respectively. The neutralizing antibody titer showed no difference between patients treated with and without immunosuppressive therapy. These results indicate that COVID-19 vaccination may be useful in patients with IBD, treated with or without immunosuppressive therapy.

Partially hydrolyzed guar gum increased colonic mucus layer in mice via succinate-mediated MUC2 production.

Colonic mucus layers protect intestinal tissues against intestinal bacteria. We investigated the effects of dietary fiber and its metabolites on mucus production in the colonic mucosa. Mice were fed a partially hydrolyzed guar gum (PHGG)-containing diet and a fiber-free diet (FFD). The colon mucus layer, fecal short-chain fatty acid (SCFA) levels, and gut microbiota were evaluated. Mucin 2 (MUC2) expression was assessed in SCFA-treated LS174T cells. The role of AKT in MUC2 production was investigated. The mucus layer in the colonic epithelium was significantly increased in the PHGG group compared with that in the FFD group. In the PHGG group, an increase in Bacteroidetes in the stool was observed, and fecal acetate, butyrate, propionate, and succinate levels were significantly increased. However, MUC2 production was significantly increased only in succinate-stimulated LS174T cells. The succinate-induced MUC2 production was associated with AKT phosphorylation. Succinate mediated the PHGG-induced increase in the colon mucus layer.