Regulation of stem cell identity by miR-200a during spinal cord regeneration.

Axolotls are an important model organism for multiple types of regeneration, including functional spinal cord regeneration. Remarkably, axolotls can repair their spinal cord after a small lesion injury and can also regenerate their entire tail following amputation. Several classical signaling pathways that are used during development are reactivated during regeneration, but how this is regulated remains a mystery. We have previously identified miR-200a as a key factor that promotes successful spinal cord regeneration. Here, using RNA-seq analysis, we discovered that the inhibition of miR-200a results in an upregulation of the classical mesodermal marker brachyury in spinal cord cells after injury. However, these cells still express the neural stem cell marker sox2. In vivo cell tracking allowed us to determine that these cells can give rise to cells of both the neural and mesoderm lineage. Additionally, we found that miR-200a can directly regulate brachyury via a seed sequence in the 3'UTR of the gene. Our data indicate that miR-200a represses mesodermal cell fate after a small lesion injury in the spinal cord when only glial cells and neurons need to be replaced.

Ammonia Toxicity and Associated Protein Oxidation: A Single-Cell Surface Enhanced Raman Spectroscopy Study.

Ammonia (NH3) is a commonly used industrial chemical to which exposure at high concentrations can result in severe skin damage. Moreover, high levels of ammonia in the human body can lead to hyperammonemia conditions and enhanced cancer metabolism. In this work, the toxicity mechanism of NH3 has been studied against human dermal fibroblast (HDF) cells using surface-enhanced Raman spectroscopy (SERS). For this purpose, gold nanoparticles of size 50 nm have been prepared and used as probes for Raman signal enhancement, after being internalized inside HDF cells. Following the exposure to ammonia, HDF cells showed a significant variation in the protein ternary structure's signals, demonstrating their denaturation and oxidation process, together with early signs of apoptosis. Meaningful changes were observed especially in the Raman vibrations of sulfur-containing amino acids (cysteine and methionine) together with aromatic residues. Fluorescence microscopy revealed the formation of reactive oxygen and nitrogen species in cells, which confirmed their stressed condition and to whom the causes of protein degradation can be attributed. These findings can provide new insights into the mechanism of ammonia toxicity and protein oxidation at a single-cell level, demonstrating the high potential of the SERS technique in investigating the cellular response to toxic compounds.

A new criterion including the aspartate aminotransferase-to-platelet ratio index and liver and spleen stiffness to rule out varices needing treatment in children with biliary atresia: Modification of the Baveno VII criteria.

AIMS: Biliary atresia (BA) is a congestive biliary disease that develops in the neonatal period or early infancy. It may present with portal hypertension and varices needing treatment (VNT) even after successful Kasai portoenterostomy. This study aimed to stratify the risk of VNT in children and adolescents with BA. METHODS: In this prospective cross-sectional study, we measured liver stiffness (LS) and spleen stiffness (SS) by two-dimensional shear wave elastography and checked for VNT endoscopically in 53 patients with BA who attended for follow-up between July 2018 and September 2022. Varices needing treatment were defined as large esophageal varices, esophageal varices of any size with red color signs, and/or gastric varices along the cardia. RESULTS: Twenty-five patients (aged 0-18 years) had VNT. Eighteen patients met the Baveno VI criteria (LS <20 kPa; platelet count >150 000/L) and were deemed to be at low risk of VNT (spared endoscopies) while three had missed VNT (16.7%). Applying the Baveno VII criteria, which combines the SS cut-off value of 40 kPa with the Baveno VI criteria, resulted in five missed VNTs among 22 spared endoscopies (22.7%). A modification of the Baveno VII criteria using the aspartate aminotransferase-to-platelet ratio index (APRI) instead of the platelet count with cut-off values of 25 kPa, 30 kPa, and 1.04 for LS, SS, and APRI, respectively, missed only one VNT (5.0%) among 20 spared endoscopies. CONCLUSIONS: A novel diagnostic criterion that combines LS, SS, and APRI reduced the risk of missing VNT to 5% in children and adolescents with BA.

Outcomes of immune checkpoint inhibitor-induced liver toxicity managed by hepatologists in a multidisciplinary toxicity team.

AIM: To detect immune-related adverse events (irAEs) early and treat them appropriately, our institute established an irAE-focused multidisciplinary toxicity team in cooperation with various departments. This study aimed to evaluate a consultation system involving a team of hepatologists in terms of its utility for the management of severe immune checkpoint inhibitor (ICI)-induced liver toxicity. METHODS: To analyze the diagnosis and treatment of severe ICI-induced liver toxicity (Grade 2 requiring corticosteroid therapy and Grade 3 or higher), we examined patients' clinical courses before and after the hepatologist consultation system was established (pre-period, September 2014 to February 2019; post-period, March 2019 to March 2023). RESULTS: The median follow-up period was 392 days. Of the 1247 patients with advanced malignancies treated with ICIs, 66 developed severe ICI-induced liver toxicity (n = 22 and 44 in the pre- and post-periods, respectively). In the pre-period, hepatologist consultations were sought for 15/22 patients, whereas in the post-period, 42/44 patients were referred to and treated by hepatologists. The time from the onset of liver toxicity to the consultation was significantly shorter in the post-period than in the pre-period (mean 1.9 vs. 6.5 days, respectively; p = 0.012). The number of patients with a biopsy-confirmed diagnosis of ICI-induced liver toxicity was significantly higher in the post-period than in the pre-period (n = 22 vs. n = 3, respectively; p = 0.006). Finally, there were no cases of immune-related cholangitis in the pre-period, compared to five cases in the post-period. CONCLUSION: A hepatologist consultation system in an irAE-focused multidisciplinary toxicity team is useful for managing severe ICI-induced liver toxicity.

Effects of 1-kestose on microbiome changes caused by vonoprazan: a randomized, double-blind, placebo-controlled pilot study.

BACKGROUND AND AIM: Potassium-competitive acid blockers more strongly suppress the gastric acid barrier than proton pump inhibitors and cause dysbiosis. However, preventive measures in this regard have not been established. We aimed to evaluate whether 1-kestose, a known prebiotic, was effective at alleviating dysbiosis caused by potassium-competitive acid blockers. METHODS: Patients scheduled to undergo endoscopic resection for superficial gastroduodenal tumors were enrolled and randomized 1:1 to receive either 1-kestose or placebo. All patients were started on potassium-competitive acid blocker (vonoprazan 20 mg/day) and took 1-kestose 10 g/day or placebo (maltose) 5 g/day for 8 weeks. The primary outcome was the effect of 1-kestose on potassium-competitive acid blocker-induced alterations in the microbiome. The fecal microbiome was analyzed before and after potassium-competitive acid blocker treatment via MiSeq (16S rRNA gene V3-V4 region). RESULTS: Forty patients were enrolled, and 16 in each group were analyzed. In the placebo group, the Simpson index, an alpha diversity, was significantly decreased and relative abundance of Streptococcus was significantly increased by 1.9-fold. In the kestose group, the Simpson index did not change significantly and relative abundance of Streptococcus increased 1.3-fold, but this was not a significant change. In both groups, no adverse events occurred, ulcers were well healed, and pretreatment and posttreatment short-chain fatty acid levels did not differ. CONCLUSIONS: The potassium-competitive acid blocker caused dysbiosis in the placebo group; this effect was prevented by 1-kestose. Thus, 1-kestose may be useful in dysbiosis treatment.

Monoclonal Antibodies Against Mature Interleukin-18 Ameliorate Colitis and Repair Goblet Cell Function.

BACKGROUND: Numerous biological interventions and small molecules are used to treat Crohn's disease; however, the effectiveness of these treatments varies largely. Non-responsiveness to biological therapies is associated with interleukin (IL)-18 gene polymorphisms and high IL-18 expression has been implicated in the pathogenesis of Crohn's disease. AIMS: The aim of this study was to elucidate the expression of precursor and mature IL-18 in patients with Crohn's disease who exhibited varied responses to cytokine-targeted treatments and determine whether selective inhibition of mature IL-18 offers a novel therapeutic avenue. METHODS: We generated a monoclonal antibody that specifically recognizes the neoepitope of caspase-cleaved mature IL-18. Expression of precursor and mature IL-18 was analyzed in patients with Crohn's disease. Anti-mature IL-18 monoclonal antibodies were intraperitoneally administered in an acute colitis mouse model, and the disease activity index, body weight loss, tissue pathology, proinflammatory cytokine expression, goblet cell function, and microbiota composition were assessed. RESULTS: Precursor and mature IL-18 expression was upregulated and goblet cell function was impaired in patients with Crohn's disease who were unresponsive to biological therapies. Administration of anti-mature IL-18 antibodies ameliorated induced colitis by repairing goblet cell function and restoring the mucus layer. CONCLUSIONS: The newly developed monoclonal antibody holds promise as a therapeutic alternative for Crohn's disease.

Abdominal pain accompanied by elevated serum inflammatory markers and biliary enzymes for diagnosing immune checkpoint inhibitor-induced sclerosing cholangitis.

Immune-related sclerosing cholangitis (irSC) is relatively rare and its clinical characteristics are not well known. In this study, we aimed to summarize the clinical features of irSC. Clinical data were collected retrospectively from 1,393 patients with advanced malignancy treated with immune-checkpoint inhibitors (ICIs) between August 2014 and October 2021. We analyzed patients with immune-related adverse events of liver injury (liver-irAEs) and compared irSC and non-irSC groups. Sixty-seven patients (4.8%) had a liver-irAE (≥ grade 3) during the follow-up period (median, 262 days). Among these, irSC was observed in eight patients (11.9%). All patients in the irSC group were treated with anti-PD-1/PD-L1 antibodies. Compared with the non-irSC group, the irSC group showed mainly non-hepatocellular liver injury (87.5 % vs 50.8 %, P = 0.065), and had elevated serum inflammatory markers (e.g., CRP and NLR) and biliary enzymes (e.g., GGTP and ALP) at the onset of liver-irAEs. Furthermore, most patients with irSC had abdominal pain. In the non-irSC group, the liver injury of 23 patients improved only with the discontinuation of ICIs, and 22 patients improved with medication including prednisolone (PSL). Conversely, almost all patients (n=7) in the irSC group were treated with PSL, but only two patients experienced an improvement in liver injury. We found that irSC is characterized by a non-hepatocellular type of liver injury with abdominal pain and a high inflammatory response and is refractory to treatment. Further examination by imaging is recommended to detect intractable irSC in cases with these characteristics.

Differences in the Intestinal Microbiome Associated with Diarrhea during Lenvatinib Treatment for Hepatocellular Carcinoma.

INTRODUCTION: Lenvatinib has been widely used for the treatment of advanced hepatocellular carcinoma (HCC). Some adverse events, including diarrhea, have been reported for lenvatinib. Diarrhea may be associated with the changes in the intestinal microbiome; however, the underlying mechanism has not been elucidated. AIM: In this study, we aimed to investigate the relationship between the intestinal microbiome and diarrhea caused by lenvatinib via analysis of fecal samples collected before treatment. METHODS: A total of 21 patients with advanced HCC who were treated with lenvatinib were enrolled. Fecal samples were collected from patients. The patients were divided into diarrhea (n = 8) and nondiarrhea groups (n = 12). We compared the characteristics of patients, incidence of adverse events, composition of the intestinal microbiome, and enrichment of functional pathways between both groups using QIIME2 and PICRUSt2. RESULTS: The median age of the two groups was 73 years. The nondiarrhea group comprised a relatively higher number of male patients than the diarrhea group; however, there were no significant differences in patient characteristics between both groups. The proportion of the microbiome was similar, and alpha and beta diversities were not significantly different between both groups. The relative abundance of order Bacteroidales, including Parabacteroides and Prevotella, was higher in the diarrhea group than in the nondiarrhea group. PICRUSt2 analysis showed some metabolic pathways, including butanoate (butyrate) metabolism, were enriched in the nondiarrhea group when compared with those in the diarrhea group. CONCLUSION: Differences in the intestinal microbiomes and their functions may influence the incidence of diarrhea during lenvatinib treatment.

Clustering using unsupervised machine learning to stratify the risk of immune-related liver injury.

BACKGROUND AND AIM: Immune-related liver injury (liver-irAE) is a clinical problem with a potentially poor prognosis. METHODS: We retrospectively collected clinical data from patients treated with immune checkpoint inhibitors between September 2014 and December 2021 at the Nagoya University Hospital. Using an unsupervised machine learning method, the Gaussian mixture model, to divide the cohort into clusters based on inflammatory markers, we investigated the cumulative incidence of liver-irAEs in these clusters. RESULTS: This study included a total of 702 patients. Among them, 492 (70.1%) patients were male, and the mean age was 66.6 years. During the mean follow-up period of 423 days, severe liver-irAEs (Common Terminology Criteria for Adverse Events grade ≥ 3) occurred in 43 patients. Patients were divided into five clusters (a, b, c, d, and e). The cumulative incidence of liver-irAE was higher in cluster c than in cluster a (hazard ratio [HR]: 13.59, 95% confidence interval [CI]: 1.70-108.76, P = 0.014), and overall survival was worse in clusters c and d than in cluster a (HR: 2.83, 95% CI: 1.77-4.50, P < 0.001; HR: 2.87, 95% CI: 1.47-5.60, P = 0.002, respectively). Clusters c and d were characterized by high temperature, C-reactive protein, platelets, and low albumin. However, there were differences in the prevalence of neutrophil count, neutrophil-to-lymphocyte ratio, and liver metastases between both clusters. CONCLUSIONS: The combined assessment of multiple markers and body temperature may help stratify high-risk groups for developing liver-irAE.

Astaxanthin Attenuates Nonalcoholic Steatohepatitis with Downregulation of Osteoprotegerin in Ovariectomized Mice Fed Choline-Deficient High-Fat Diet.

BACKGROUND: Postmenopausal estrogen decline increases the risk of developing nonalcoholic steatohepatitis (NASH), and it might accelerate progression to cirrhosis and hepatocellular carcinoma. AIMS: This study aimed to investigate a novel therapy for postmenopausal women who are diagnosed with NASH. METHODS: Seven-week-old female C57BL/6 J mice were divided into three experimental groups as follows: (1) sham operation (SHAM group), (2) ovariectomy (OVX group), and (3) ovariectomy + 0.02% astaxanthin (OVX + ASTX group). These three groups of mice were fed a choline-deficient high-fat (CDHF) diet for 8 weeks. Blood serum and liver tissues were collected to examine liver injury, histological changes, and hepatic genes associated with NASH. An in vitro study was performed with the hepatic stellate cell line LX-2. RESULTS: The administration of ASTX significantly improved pathological NASH with suppressed steatosis, inflammation, and fibrosis, in comparison with those in the OVX-induced estrogen deficiency group. As a result, liver injury was also attenuated with reduced levels of alanine aminotransferase and aspartate transaminase. In addition, our study found that ASTX supplementation decreased hepatic osteoprotegerin (OPG) in vivo, a possible factor that contributes to NASH development. In vitro, this study further confirmed that ASTX has an inhibitory effect on the secretion of OPG in LX-2 human hepatic stellate cells. CONCLUSIONS: Our findings suggest that ASTX alleviates CDHF-OVX-induced pathohistological NASH with downregulated OPG, possibly via suppression of the transforming growth factor beta pathway. ASTX could has promise for use in postmenopausal women diagnosed with NASH.

Memory for actions and reality monitoring in adults with autism spectrum disorder.

Reality monitoring is the cognitive process of distinguishing between internally and externally generated information sources such as imagined and performed actions. The purpose of this study was to examine self-self-monitoring with action in people with autism, which has not been examined previously, using subject performed tasks along with free recall and recognition. Twenty adults with ASD and 20 adults with typical development (TD) participated in this study. Participants memorized action sentences such as "write in pencil" and "under imagined, pantomime, or enacted conditions." Free recall, yes/no recognition, and reality monitoring tests were conducted immediately after and one week later. There was no difference in reality monitoring between the ASD and TD groups. The free recall and recognition performance of the ASD group was lower than that of the TD group. The results of the present study support the previously reported finding of unimpaired retrospective mechanisms of sense of agency related to reality monitoring in people with ASD. Moreover, low levels of free recall and recognition were discussed regarding difficulties in memory reconstruction and consolidation.

The presence of high-risk varices after sclerotherapy in biliary atresia.

BACKGROUND: Esophagogastric varices (EGVs) may develop as a result of portal hypertension in children with biliary atresia (BA). Although endoscopic injection sclerotherapy (EIS) with ethanolamine oleate (EO) is reported useful for children, risk factors associated with the presence of high-risk EGVs after treatment remain unknown. METHODS: The subjects were BA patients under 15 years of age who underwent EO-EIS. We retrospectively reviewed a total of 28 treatment sessions of EGVs with red signs and those larger than F2, which were considered to be at high risk of bleeding. Survival analysis was performed for the presence of high-risk EGVs at the time of follow-up endoscopy as the occurrence of an event. RESULTS: Univariate analysis showed a significantly increased risk of the presence of high-risk EGVs post-EO-EIS in patients with increased liver stiffness (LS) and Mac-2 binding protein glycan isomer (M2BPGi), with hazard ratios of 1.48 and 1.15, respectively. The median presence-free period was significantly shorter in the LS ≥ 2.8 m/s patients than in those with LS <2.8 m/s (189 vs. 266 days). Similarly, the median presence-free period was significantly shorter in patients with M2BPGi ≥ 4.0 than in those with M2BPGi < 4.0 (182 vs. 203 days). The results of multivariate analysis revealed that the risk of the presence of high-risk EGVs was significantly higher only in the high-LS group, with a hazard ratio of 2.76. CONCLUSIONS: Increased LS is associated with risk of the presence of high-risk EGVs following EO-EIS in children with BA.

Anti-Inflammatory Effects of ß-Cryptoxanthin on 5-Fluorouracil-Induced Cytokine Expression in Human Oral Mucosal Keratinocytes.

Oral mucositis is a typical adverse effect of chemotherapy, causing oral pain that significantly reduces the patient's quality of life. ß-cryptoxanthin (ß-cry) is a carotenoid abundant in citrus fruits with antioxidant and anti-inflammatory effects. However, the ß-cry effect on oral mucositis remains unclear. We investigated the effects of 5-fluorouracil (5-FU) and ß-cry on human normal oral mucosal keratinocytes (hOMK). hOMK was seeded on a culture plate and cultured with 5-FU and ß-cry. The cell number, mRNA expression of inflammatory cytokines and matrix metalloproteinases (MMPs), and production of inflammatory cytokines in hOMK were evaluated. Additionally, the cell count and inflammatory cytokine production were analyzed when hOMK was co-stimulated with Porphyromonas gingivalis lipopolysaccharide (P. gingivalis LPS) in addition to 5-FU. The numbers of hOMK significantly reduced with 5-FU stimulation, whereas it increased with ß-cry treatment. mRNA expression of interleukin (IL)-6, IL-8, metalloproteinase (MMP)-2, and MMP-9 and protein production of IL-6 and IL-8 in hOMK were augmented on 5-FU stimulation. Simultaneously, ß-cry treatment significantly suppressed IL-8 and MMP-9 mRNA expression, and IL-8 production was induced on 5-FU stimulation. Co-stimulation with P. gingivalis LPS and 5-FU enhanced IL-6 and IL-8 production in hOMK. ß-cry could enhance cell proliferation and suppress 5-FU-induced expression of inflammatory cytokines and MMP in hOMK. Thus, ß-cry can alleviate the symptoms of chemotherapy-induced oral mucositis, and its combination with oral care is effective in managing oral mucositis.

Immune-related Liver Injury is a Poor Prognostic Factor in Patients with Nonsmall Cell Lung Cancer Treated with Immune Checkpoint Inhibitors.

It remains unclear whether severe liver immune-related adverse events (liver-irAEs) can affect the prognosis in nonsmall cell lung carcinoma (NSCLC) patients. Of the 365 NSCLC patients treated with immune checkpoint inhibitors (ICIs), 19 suffered from severe liver-irAEs (grade ≥3). The median time-to-onset of liver-irAEs was 53 days postinjection of the first ICI. The progression-free survival and overall survival of the liver-irAEs group (median 69 and 262 days, respectively) were significantly worse than the nonliver-irAEs group (128 and 722 days; P = 0.010 and P = 0.007; respectively). In conclusion, liver-irAEs were associated with poor prognosis in NSCLC patients.

Changes in Body Composition Predict the Time to Treatment Failure of Lenvatinib in Patients with Advanced Hepatocellular Carcinoma: A Pilot Retrospective Study.

AIM: Changes in body composition parameters are important prognostic factors in hepatocellular carcinoma (HCC) treatment. This study aimed to assess the clinical impact of early changes in body composition during lenvatinib (LEN) treatment on its time to treatment failure (TTF) for patients with advanced HCC. METHODS: In this retrospective study, we enrolled 65 patients who were administered LEN as the first-line treatment for unresectable HCC and evaluated the body composition change using computed tomography. We focused on the body composition change after 2 weeks of LEN treatment and assessed its impact on TTF and prognosis. RESULTS: Significant changes in body composition were observed during 14 weeks of LEN treatment. Among these changes, mean-skeletal muscle attenuation (SMA) decreased significantly within 2 weeks (P = 0.004) without symptoms or changes in the other parameters. In multivariate analysis, this early change in mean-SMA after LEN treatment was a significant predictor of time to treatment failure (HR: 2.67, 95%CI: 1.338-5.081, P = 0.005) in patients with HCC. CONCLUSIONS: This study revealed that LEN treatment induces a change in the skeletal muscle asymptomatically for a short period, and evaluation of this change may help to predict the TTF of LEN treatment in patients with HCC.Supplemental data for this article is available online at https://doi.org/10.1080/01635581.2022.2049322 .

Changes in the gut microbiome in relation to the degree of gastric mucosal atrophy before and after Helicobacter pylori eradication.

OBJECTIVES: Helicobacter pylori infection causes atrophic gastritis, which affects the gut microbiome; the gastric acid concentration depends on the degree of atrophic gastritis. Helicobacter pylori eradication also affects gastric acidity. Here, we determined the differences in the post-eradication changes in the gut microbiome in relation to the progression of gastric atrophy. MATERIALS AND METHODS: Ten patients were included in the closed group and five in the open group, consisting of patients with non-progressive and progressive atrophy, respectively, diagnosed by endoscopy. The faecal microbiome was analysed and compared among three time-points: before eradication, 8 weeks after eradication, and 6 months after eradication. The microbiome was analysed by targeting 16S rRNA using Illumina Miseq. RESULTS: The relative abundance of 14 genera significantly differed between the closed and open groups before eradication, but only 12 and 6 genera presented a significant difference in the relative abundance at 8 weeks and 6 months after eradication, respectively. Of the 12 genera that differed between the closed and open groups before eradication, 8 genera, namely, Actinomyces, Aggregatibacter, Campylobacter, Granulicatella, Pyramidobacter, Streptococcus, Cardiobacterium, and Haemophilus, were oral-origin bacteria. Longitudinal changes showed that Haemophilus and Catenibacterium were consistently significantly more abundant in the open group than in the closed group during the follow-up period. CONCLUSION: The gut microbiome substantially differed depending on the progression of gastric atrophy, but this difference was decreased by eradication, especially the differences in the number of oral bacteria in the gut. Eradication therapy may improve dysbiosis that result from gastric atrophy.

Fecal microbiota transplantation in the treatment of irritable bowel syndrome: a single-center prospective study in Japan.

BACKGROUND: Fecal microbiota transplantation (FMT) is a potential treatment for irritable bowel syndrome (IBS), but its efficacy in Japanese IBS patients is unknown. This study aimed to evaluate the efficacy, side effects, and microbiome changes following FMT in Japanese IBS patients. METHODS: Seventeen Japanese patients with refractory IBS received FMT (4 donors) under colonoscopy. Responders were defined by an improvement in the IBS severity index (IBS-SI) of 50 points or more after 12 weeks. We evaluated the IBS-SI and Bristol Stool Form Scale (BSFS) and compared the diversity and microbiome before and 12 weeks after FMT. For the microbiome, we analyzed the V3-V4 region of the 16S rRNA gene. RESULTS: IBS-SI decreased an average of 115.58 points after 12 weeks, and 10 patients (58.8%) were considered responders. Eight patients with diarrhea (66.7%) and three patients with constipation (60.0%) showed improvement in the BSFS. Two patients complained of mild abdominal pain, but there were no cases with severe side-effects. α-diversity was increased only in the responder group (p = 0.017). Patients who closely paralleled the donor microbiome had a higher rate of IBS-SI improvement. The relative abundance of Neisseria and Akkermansia increased and Desulfovibrio and Delftia were decreased in the responder group after FMT. CONCLUSIONS: Following FMT, about 60% of Japanese patients with IBS showed improvement in both the IBS-SI and BSFS, without severe side effects. Increased α-diversity and similarity to the donor microbiome after FMT may be associated with better treatment effects. TRIAL REGISTRATION: This study was registered in the University Hospital Medical Information Network Clinical Trial Registration (UMIN000026363). Registered 31 May 2017, https://rctportal.niph.go.jp/s/detail/um?trial_id=UMIN000026363 . The study was registered prospectively.

Absence of large portal collateral vessels is associated with spontaneous improvement of cirrhotic portal vein thrombosis.

AIM: Portal vein thrombosis (PVT) is a major complication in patients with liver cirrhosis (LC). In some cases, PVT decreases spontaneously, but the factors that predict this are still not fully understood. METHODS: This was a retrospective, multicenter study that included 77 consecutive patients with cirrhotic PVT. Forty-eight patients did not undergo anticoagulation and 29 patients did between the time of the first diagnosis of PVT and the follow-up radiological imaging undertaken 1-6 months later. A complete disappearance and 25% shrinkage of PVT was defined as complete remission (CR) and partial remission (PR), respectively. Portosystemic collateral vessels larger than 9 mm in diameter were defined as large collateral vessels. RESULTS: Complete remission + PR was found in 37.5% of the anticoagulation-naïve patients. On univariate analysis, the absence of large collateral vessels, absence of PVT in the main trunk of the portal vein, a high platelet count, and a low FIB-4 index were significant factors associated with CR + PR. On multivariate analysis, the absence of large collateral vessels was the unique factor associated with CR + PR of PVT (odds ratio 5.9; 95% confidence interval, 1.73-20.1). The CR + PR rate for anticoagulated patients was 44.8%. However, no predictors for a good treatment effect of anticoagulation for PVT were identified. CONCLUSIONS: Spontaneous improvement of PVT in patients with LC can be expected when large collateral vessels are absent. For these patients, the option of observing them without anticoagulation can be considered in expectation of spontaneous reduction of PVT.

An improved method to assess skeletal muscle mass in patients with liver cirrhosis based on computed tomography images.

AIM: Conventionally, the skeletal muscle area with computed tomography (CT) attenuation ranging from -29 to +150 Hounsfield unit (HU) divided by height squared (the conventional skeletal muscle index [SMI]) was used as an index of skeletal muscle mass. However, it includes fat-infiltrated skeletal muscle, which is known to have poor function. This study aims to determine whether the low-fat SMI, which uses skeletal muscle mass with CT attenuation ranging from +30 to +150 HU, or conventional SMI appropriately reflects the function of skeletal muscle. METHODS: We retrospectively analyzed 120 patients with cirrhosis whose handgrip strength was measured. Among them, 48 patients underwent a physical performance assessment such as liver frailty index (LFI) and short physical performance battery (SPPB), and 80 underwent quality of life (QOL) assessment. The relationships between each SMI and handgrip strength, LFI, SPPB, and QOL were evaluated. RESULTS: Low-fat SMI was significantly correlated with handgrip strength (males, R = 0.393, p = 0.002; females, R = 0.423, p < 0.001) and LFI (males, R = -0.535, p = 0.035; females, R = -0.368, p = 0.039), whereas conventional SMI was not. When using low-fat SMI, patients with low skeletal muscle mass had significantly low handgrip strength, LFI, SPPB, and physical and social-related QOL score than those without. By contrast, no significant differences were found for any items when using conventional SMI. CONCLUSIONS: Low-fat SMI is a good index of skeletal muscle mass that appropriately reflects skeletal muscle function.

Emotional valence of self-defining memories in older adults: A longitudinal study.

The present study aimed to evaluate the pleasantness bias and fading affect bias in self-defining memories (SDMs) and to examine the relationship between their emotional valence of SDMs and cognitive function and serotonin transporter polymorphisms (5-HTTLPR) with a prospective longitudinal method. Ninety-two older adults recalled SDMs twice at an interval of one year (T1 and T2). The results showed a pleasantness bias and a fading affect bias in SDMs. The higher the working memory was, the higher the vividness of SDMs and the higher the concordance rate of SDMs between T1 and T2. Meanwhile, cognitive performance had no effect on the emotional valence of SDMs. Additionally, the repeatedly recalled SDMs in the S/S allele carriers of the 5-HTTLPR polymorphism changed with a lower negative valence at T2 than at T1. The 5-HTTLPR polymorphism may be a plasticity factor that predicts positive outcomes in positive situations.