Efficacy and safety of rifaximin in patients with chronic intestinal pseudo-obstruction: a randomized, double-blind, placebo-controlled, phase II-a exploratory trial.

Chronic intestinal pseudo-obstruction (CIPO) is a rare intractable disease with limited treatment options. Small intestinal bacterial overgrowth (SIBO) often co-occurs with several diseases, including CIPO. While rifaximin (RFX) is effective in treating SIBO, its efficacy for CIPO remains unclear. Here, we aimed to investigate the efficacy and safety of RFX in adult patients with CIPO. Twelve patients were randomly assigned to receive RFX (400 mg three times daily, n=8) or a placebo (PBO, n=4) for 4 weeks. The global symptom score for abdominal bloating (GSS-bloating) and an original whole gastrointestinal symptoms score (O-WGSS) were collected, and a glucose hydrogen breath test (GHBT) and abdominal computed tomography (CT) were performed. No significant differences were observed in the primary endpoint. GSS-bloating improved by 75% and 25% in the PBO and RFX groups, respectively, and O-WGSS improved by 25% in both groups. No significant differences were observed in secondary and other endpoints, including the SIBO eradication rate in the GHBT and small intestinal volume on CT. In a post hoc analysis of SIBO-positive patients with CIPO (4/4 and 4/8 in the PBO and RFX groups), SIBO was eradicated in 25% and 75% of the patients (PBO and RFX groups, respectively) at the end of treatment, indicating a high eradication rate in the RFX group. Furthermore, the small intestinal gas volume decreased in the RFX group, and no severe adverse events occurred. Although no significant improvements were observed in subjective indicators, RFX may be beneficial in alleviating SIBO and reducing the small intestinal gas volume in SIBO-positive patients with CIPO.

Naldemedine and Magnesium Oxide as First-Line Medications for Opioid-Induced Constipation: A Comparative Database Study in Japanese Patients With Cancer Pain.

Introduction Naldemedine and magnesium oxide are common first-line early laxative medications used in the real-world scenario in Japan, for patients with cancer pain who receive opioid prescriptions, as per a nationwide hospital claims database study. However, the real-world prescription patterns and associated outcomes are unknown. Methods In this retrospective, cohort study using the Medical Data Vision (MDV) database (January 2018 to December 2020), data were collected from eligible patients (who had a long-term prescription of strong opioids, for >30 days) in Japan with naldemedine or magnesium oxide as the first-line laxative prescription, for a long-term opioid prescription for cancer pain with ≥6 months post-opioid observation period. A laxative prescription within three days after the opioid prescription date was termed an "early" prescription. The composite incidence of dose increase or addition/change of laxatives at three months after the start of the opioid prescription was the primary endpoint after adjusting baseline characteristics between the treatment arms by propensity score matching. Results After propensity score matching, 1717 and 544 patients who were prescribed naldemedine and magnesium oxide each were included in the early prescription and non-early prescription groups, respectively. Even after matching, the incidence of death was not adjusted enough and was significantly higher in the naldemedine arm than in the magnesium oxide arm in the non-early group but comparable in the early group. The incidence of addition, change, or dose increase was significantly higher in the naldemedine arm than in the magnesium oxide arm of the early prescription group (hazard ratio (95% confidence interval), 1.08 (1.00, 1.17); p=0.0402); the incidence was comparable between the arms of the non-early group. Conclusion These findings may provide valuable insights into real-world clinical treatment patterns and preliminary evidence for the selection of first-line medications to mitigate opioid-induced constipation in Japanese patients with cancer pain.

Associations of nutrition impact symptoms with dietary intake and eating-related distress in patients with advanced cancer.

BACKGROUND & AIMS: There is no definition of nutrition impact symptoms (NISs) in cancer care. Moreover, there is a lack of evidence on the associations of NISs with dietary intake and eating-related distress (ERD) in advanced cancer. Therefore, this study aimed to determine the associations of NISs with dietary intake and ERD in patients with advanced cancer. METHODS: This study entailed a secondary analysis of a multicenter self-reported questionnaire designed to develop measurements that assess ERD experienced by patients. Participants evaluated their dietary intake and 19 symptoms regarded as NISs using a 10-point scale. To determine the association between dietary intake and the number of NISs with a score ≥4, estimated adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for the logistic regression model were calculated. Furthermore, to assess the association between ERD and the number of NISs with a score ≥4, multiple regression analysis was performed. RESULTS: A total of 302 patients were included in the analysis. The higher the number of NISs with a score ≥4, the lower the dietary intake tended to be. In the logistic regression model, significantly higher adjusted ORs than in the no NISs with a score ≥4 group were observed in the 4-6 NISs group, 7-9 NISs group, and 10 or more group (0.19 [95% CI, 0.07-0.52], p = 0.001; 0.11 [95% CI, 0.03-0.42], p = 0.001; 0.07 [95% CI, 0.01-0.36], p = 0.002, respectively). In the multiple regression analysis, the number of NISs with a score ≥4 was identified as one of the factors significantly associated with ERD. CONCLUSIONS: Having 4 or more NISs with a score ≥4 was shown to be predictive of the likelihood of reduced dietary intake. Furthermore, the higher the number of NISs with a score ≥4, the more likely the eating-related quality of life was impaired in advanced cancer.

Identification of differentially methylated regions associated with both liver fibrosis and hepatocellular carcinoma.

BACKGROUND: Liver fibrosis is a major risk factor for hepatocellular carcinoma (HCC). We have previously reported that differentially methylated regions (DMRs) are correlated with the fibrosis stages of metabolic dysfunction-associated steatotic liver disease (MASLD). In this study, the methylation levels of those DMRs in liver fibrosis and subsequent HCC were examined. METHODS: The methylation levels of DMRs were investigated using alcoholic cirrhosis and HCC (GSE60753). The data of hepatitis C virus-infected cirrhosis and HCC (GSE60753), and two datasets (GSE56588 and GSE89852) were used for replication analyses. The transcriptional analyses were performed using GSE114564, GSE94660, and GSE142530. RESULTS: Hypomethylated DMR and increased transcriptional level of zinc finger and BTB domain containing 38 (ZBTB38) were observed in HCC. Hypermethylated DMRs, and increased transcriptional levels of forkhead box K1 (FOXK1) and zinc finger CCCH-type containing 3 (ZC3H3) were observed in HCC. The methylation levels of DMR of kazrin, periplakin interacting protein (KAZN) and its expression levels were gradually decreased as cirrhosis progressed to HCC. CONCLUSIONS: Changes in the methylation and transcriptional levels of ZBTB38, ZC3H3, FOXK1, and KAZN are important for the development of fibrosis and HCC; and are therefore potential therapeutic targets and diagnostic tools for cirrhosis and HCC.

The Prevalence and Characteristics of Symptomatic Uncomplicated Diverticular Disease Among Asian Patients With Unexplained Abdominal Symptoms.

Background/Aims: The precise incidence of symptomatic uncomplicated diverticular disease (SUDD) and its effects on the quality of life (QOL) remain unclear, particularly in Asian patients with right-sided SUDD. We assess the prevalence of SUDD and its impact on QOL in a real-world population. Methods: Five institutional cohorts of patients who received outpatient treatment for unexplained abdominal symptoms from January 15, 2020 to March 31, 2022, were included. All patients underwent colonoscopy. SUDD was defined as the presence of recurrent abdominal symptoms, particularly pain in the lower right or left quadrant lasting > 24 hours in patients with diverticulosis at the site of pain. The 36-item short-form health survey was used to assess QOL. Results: Diverticula were identified in 108 of 361 patients. Among these 108 patients, 31% had SUDD, which was right-sided in 39% of cases. Of the 50 patients with right-sided diverticula, 36% had SUDD, as did 15 of 35 patients with left-sided diverticula (43%). Among the 33 patients with SUDD, diverticula were right-sided, left-sided, and bilateral in 39%, 45%, and 15% of patients, respectively. Diarrhea was more frequent in the SUDD group than in the non-SUDD group. Patients with SUDD had significantly lower physical, mental, and role/social component scores than those without SUDD. Conclusions: It is important to recognize that patients with SUDD account for as high as 31% of outpatients with unexplained abdominal symptoms; these patients have diarrhea and a low QOL. The presence of right-sided SUDD was characteristic of Asian patients.

Current Treatment Practices for Adult Patients with Constipation in Japan.

BACKGROUND: The prevalence of constipation in Japan is estimated to be 2-5%. Constipation is a disease found in older adults. In particular, Japan is an aging society, with 65% of men and 80.5% of women aged 65 years or older accounting for the majority of its population. Chronic constipation may be associated with survival, cardiovascular events, decreased quality of life, and death. This study summarizes the recent findings regarding constipation treatment practice in Japan. SUMMARY: Until recently, the diagnosis of constipation was mainly based on medical interviews; however, with the recent development of handheld ultrasound devices, both physicians and nurses can easily and objectively diagnose fecal retention. Magnesium oxide and stimulant laxatives have been the mainstay treatments; however, since 2012, more than five new drugs for treating constipation have become available in Japan. KEY MESSAGES: Magnesium oxide is less effective in patients who use acid-secretion inhibitors and patients who have undergone total gastrectomy and should be cared for hypermagnesemia. In addition, regular use of stimulant laxatives may lead to colonic inertia and decreased bowel movements; therefore, they should be used only occasionally. The following is an overview of the different uses of conventional and newer laxatives for treating constipation.

Combined, elobixibat, and colestyramine reduced cholesterol toxicity in a mouse model of metabolic dysfunction-associated steatotic liver disease.

BACKGROUND: Cholesterol levels and bile acid metabolism are important drivers of metabolic dysfunction-associated steatohepatitis (MASH) progression. Using a mouse model, we investigated the mechanism by which cholesterol exacerbates MASH and the effect of colestyramine (a bile acid adsorption resin) and elobixibat (an apical sodium-dependent bile acid transporter inhibitor) concomitant administration on bile acid adsorption and MASH status. METHODS: Mice were fed a high-fat high-fructose diet with varying concentrations of cholesterol to determine changes in fatty liver according to liver status, water intake, defecation status, insulin resistance, bile acid levels, intestinal permeability, atherosclerosis (in apolipoprotein E knockout mice), and carcinogenesis (in diethylnitrosamine mice). Using small interfering ribonucleic acid (siRNA), we evaluated the effect of sterol regulatory element binding protein 1c (SREBP1c) knockdown on triglyceride synthesis and fatty liver status following the administration of elobixibat (group E), colestyramine (group C), or both (group EC). RESULTS: We found greater reductions in serum alanine aminotransferase levels, serum lipid parameters, serum primary bile acid concentrations, hepatic lipid levels, and fibrosis area in EC group than in the monotherapy groups. Increased intestinal permeability and watery diarrhea caused by elobixibat were completely ameliorated in group EC. Group EC showed reduced plaque formation rates in the entire aorta and aortic valve of the atherosclerosis model, and reduced tumor counts and tumor burden in the carcinogenesis model. CONCLUSIONS: Excessive free cholesterol in the liver can promote fatty liver disease. Herein, combination therapy with EC effectively reduced free cholesterol levels in MASH model mice. Our study provides strong evidence for combination therapy as an effective treatment for MASH.

Prior appendectomy and cerebral infarction as potential risk factors for recurrent ischemic colitis: A retrospective observational study.

Background and Aim: Ischemic colitis (IC) is a benign disease associated with acute lower gastrointestinal bleeding and frequent recurrence. While several studies have investigated risk factors for IC onset, few have assessed the risk factors for recurrent IC. This study aimed to identify risk factors for recurrent IC. Methods: Potential risk factors for recurrence were assessed by examining medical records and laboratory findings in this single-center retrospective study. We extracted the following data from the patients' medical records: patient characteristics, clinical signs and symptoms, laboratory findings, method of treatment, length of hospital stay, disease course, and the frequency of IC morbidities. Patients with IC were selected from a total of 439 312 patients over an 11-year period. Patients were divided into recurrent and nonrecurrent IC groups. Results: In total, 225 patients met the diagnostic criteria for IC during the specified study period; of these, 204 patients (90.7%) and 21 patients (9.3%) were included in the nonrecurrent and recurrent IC groups, respectively. Univariate and multivariate analyses showed a significant association between IC recurrence and both cerebral infarction (P = 0.008, odds ratio [OR] = 6.3) and history of appendectomy (P = 0.0005, OR = 6.2). The median (interquartile range [IQR]) follow-up time for all patients was 1556 (353-2768) days; this was much longer than the median (IQR) time to recurrence of 291 (64-907) days in the recurrent IC group. Conclusion: The results of this study suggest that prior cerebral infarction and appendicectomy may be risk factors for IC recurrence.

Prevalence and associated metabolic factors of nonalcoholic fatty liver disease in the general population from 2014 to 2018 in Japan: A large-scale multicenter retrospective study.

AIM: The prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing worldwide. The aim of this study was to determine the recent prevalence and clinical characteristics of NAFLD in Japan. METHODS: This study initially included 410 061 retrospectively enrolled adults from the medical health checkup registry for metabolic syndrome, chronic kidney disease, and fatty liver in Japan (MIRACLE-J; UMIN-CTR no. UMIN000049419), who were evaluated between 2014 and 2018 at 13 health centers in Japan. Individuals consuming >20 g of alcohol/day or with chronic liver disease were excluded. Fatty liver was diagnosed by ultrasonography. The probability of NAFLD with advanced fibrosis was estimated based on the fibrosis-4 index and NAFLD fibrosis score. RESULTS: A total of 71 254 participants were included in the final analysis. The overall prevalence of NAFLD was 25.8%. There was a significant, twofold difference in NAFLD prevalence between men (37.4%) and women (18.1%). Nonalcoholic fatty liver disease prevalence increased linearly with body mass index, triglycerides, and low-density lipoprotein cholesterol regardless of threshold values, even in the absence of obesity. Among patients with NAFLD, 14% had diabetes mellitus, 31% had hypertension, and 48% had dyslipidemia. The estimated prevalence of NAFLD with advanced fibrosis was 1.7% and 1.0% according to the fibrosis-4 index and NAFLD fibrosis score, respectively. CONCLUSIONS: The prevalence of NAFLD was approximately one-quarter of the general population in Japan. There was a linear relationship between NAFLD prevalence and various metabolic parameters, even in nonobese participants. The prevalence of NAFLD with advanced fibrosis was estimated to be 1%-2%.

Natural History of Chronic Intestinal Pseudo-obstruction and Need for Palliative Care.

Background/Aims: Natural history of chronic intestinal pseudo-obstruction (CIPO), a rare disease characterized by episodes of non-mechanical obstruction, is unclear in adults. This study evaluates the clinical course of CIPO and palliative care needs of patients. Methods: From October 2010 to September 2021, 74 patients who underwent cine MRI and had a definitive diagnosis of CIPO were prospectively included. We investigated disease etiology and outcomes, age at onset, nutritional status at consultation (body mass index and serum albumin), hydrogen breath test results, and total parenteral nutrition (TPN) during the disease course. Results: Forty-seven patients (64%) were women, with a mean age of 44 years at onset and 49 years at diagnosis. Primary CIPO was observed in 48 patients (65%). Secondary CIPO was observed in 26 cases (35%), of whom 18 (69%) had scleroderma. The mean body mass index, serum albumin level, and hydrogen breath test positivity rate were 17 kg/m2, 3.8 mg/dL, and 60%, respectively. TPN and invasive decompression therapy were required by 23 (31%) and 18 (24%) patients, respectively. Intestinal sterilization was performed in 51 (69%) patients and was effective in 33 (65%); of these, 28 (85%) were taking metronidazole. Seven (9%) patients used opioids. There were 9 deaths (12%), including 5 (56%) from infection and 2 (22%) from suicide. Of the deaths, 6 (67%) and 4 (44%) underwent TPN management and decompression therapy, respectively. Fifty-one patients (69%) wanted palliative care. Conclusion: CIPO is a rare, severe, and under-recognized disease. Standardization of treatment strategies, including palliative care and psychiatric interventions, is desired.

Comparison of pancreatic enzyme abnormalities and protease-activated receptor-2-positive eosinophils in the duodenum of patients with functional dyspepsia-irritable bowel syndrome overlap with functional dyspepsia alone in Asian populations.

BACKGROUND AND AIM: Some patients with functional gastrointestinal disorders exhibit pancreatic dysfunctions and pancreatic enzyme abnormalities. Thus, we aimed to clarify whether significant differences in clinical characteristics, prevalence of pancreatic enzyme abnormalities, duodenal inflammation, and protease-activated receptor 2 (PAR2) expression levels related to hypersensitivity exist between functional dyspepsia (FD) alone and FD-irritable bowel syndrome (IBS) overlap group. METHODS: Ninety-three patients based on the Rome IV criteria, FD alone (n = 44) and FD overlapped with IBS (n = 49) group were enrolled. The patients scored their own clinical symptoms after consuming high-fat meals. Serum trypsin, PLA2, lipase, p-amylase, and elastase-1 levels were measured. PAR2, eotaxin-3, and TRPV4 mRNA levels in duodenum were determined using real-time polymerase chain reaction methods. PRG2- and PAR2 in the duodenum were evaluated using immunostaining. RESULTS: FD score and global GSRS in patients with FD-IBS overlap were significantly higher than FD alone. Although the prevalence of pancreatic enzyme abnormalities in patients with FD alone was significantly (P < 0.01) higher than that in FD-IBS overlap, the ratio of aggravation of clinical symptoms following high-fat intake in patients with FD-IBS overlap was significantly higher (P = 0.007) than that in patients with FD alone. PAR2- and PRG2-double positive cells were localized in the degranulated eosinophils in the duodenum of patients with FD-IBS overlap. The number of PAR2- and PRG2-double positive cells in FD-IBS overlap was significantly (P < 0.01) higher than FD alone. CONCLUSIONS: Pancreatic enzyme abnormalities and PAR2 expression on degranulated eosinophils infiltrations in the duodenum may be associated with the pathophysiology of patients with FD-IBS overlap in Asian populations.

Difficulty swallowing and food bolus obstruction in advanced cancer: association with the cachexia-related quality of life.

BACKGROUND: Swallowing disorders including difficulty swallowing and food bolus obstruction, result in reduced dietary intake-a common occurrence that leads to cachexia in patients with advanced cancer. This study examined the effects of swallowing difficulty and food bolus obstruction on cachexia-related quality of life (QOL). METHODS: This study secondarily analyzed data from a self-reported questionnaire survey of adult patients with advanced cancer at 11 palliative care services. Difficulty swallowing and food bolus obstruction were measured using the 11-point Numeric Rating Scale (NRS), whereas dietary intake and cachexia-related QOL were assessed using the Ingesta-Verbal/Visual Analog Scale and the Functional Assessment of Anorexia/Cachexia Therapy Anorexia/Cachexia Subscale. A multiple logistic regression model was employed to determine the factors associated with varying degrees of difficulty swallowing and food bolus obstruction. RESULTS: Of the invited 495 patients, 378 agreed to participate (response rate 76.4%). After excluding participants with missing data, the data of 332 participants were analyzed; 26.5% had difficulty swallowing (NRS ≥1) and 28.3% had food bolus obstruction (NRS ≥1). Multivariate analysis revealed a substantial association between difficulty swallowing and food bolus obstruction and a decrease in cachexia-related QOL, regardless of performance status and the existence of cachexia. The coefficients for difficulty swallowing and food bolus obstruction were -6.34 [95% confidence interval (CI): -9.55 to -3.14, P<0.001] and -5.88 (95% CI: -8.68 to -3.09, P<0.001), respectively. CONCLUSIONS: Cachexia-related QOL deteriorated as difficulty swallowing and food bolus obstruction worsened; thus, healthcare providers must diagnose and treat swallowing disorders in a timely manner to prevent progression of cachexia and improve cachexia-related QOL.

A Nationwide Hospital Claims Database Analysis of Real-World Patterns of Laxative Use for Opioid-Induced Constipation in Japanese Patients with Cancer.

INTRODUCTION: Opioid-induced constipation (OIC) is one of the most common side effects in patients with cancer treated with opioid analgesics. The actual use of laxatives for OIC in Japan remains unelucidated. This study aimed to investigate the real-world patterns of laxative use for patients with cancer who newly initiated opioid analgesic therapy. METHODS: We used a Japanese nationwide hospital claims database (January 2018-December 2019). Patients with cancer newly receiving opioid analgesic therapy were included and classified on the basis of opioid classes (weak or strong) and route of administration (oral or transdermal) at initiation. The patients were divided into two groups on the basis of whether they received early medication (starting laxatives within 3 days after initiating opioid analgesic therapy), and patterns of laxative use were analyzed. RESULTS: There were 26,939 eligible patients, with 50.7% of them initiated with strong opioids. The proportion of patients who received early medication was 25.0% for weak opioids and 57.3% for strong opioids. Osmotic laxatives were most frequently used as first-line therapy in the early medication group (oral weak opioids: 12.3%, oral strong opioids: 29.4%, transdermal strong opioids: 12.8%). Stimulant laxatives were frequently used as first-line therapy, to the same extent or more than osmotic laxatives in the non-early medication group (oral weak opioids: 13.7%, oral strong opioids: 7.7%, transdermal strong opioids: 15.1%). Peripherally acting µ-opioid receptor antagonists were the second most frequently used in the early medication group for those on oral strong opioids (9.4%). CONCLUSION: This study demonstrated for the first time that the patterns of laxative use for OIC in Japanese patients with cancer were different, depending on the opioid types at initiation and the timing of laxative medication.

M-PAST score is better than MAST score for the diagnosis of active fibrotic nonalcoholic steatohepatitis.

BACKGROUND: Clinical trials enroll patients with active fibrotic nonalcoholic steatohepatitis (NASH) (nonalcoholic fatty liver disease [NAFLD] activity score ≥ 4) and significant fibrosis (F ≥ 2); however, screening failure rates are high following biopsy. We developed new scores to identify active fibrotic NASH using FibroScan and magnetic resonance imaging (MRI). METHODS: We undertook prospective primary (n = 176), retrospective validation (n = 169), and University of California San Diego (UCSD; n = 234) studies of liver biopsy-proven NAFLD. Liver stiffness measurement (LSM) using FibroScan or magnetic resonance elastography (MRE), controlled attenuation parameter (CAP), or proton density fat fraction (PDFF), and aspartate aminotransferase (AST) were combined to develop a two-step strategy-FibroScan-based LSM followed by CAP with AST (F-CAST) and MRE-based LSM followed by PDFF with AST (M-PAST)-and compared with FibroScan-AST (FAST) and MRI-AST (MAST) for diagnosing active fibrotic NASH. Each model was categorized using rule-in and rule-out criteria. RESULTS: Areas under receiver operating characteristic curves (AUROCs) of F-CAST (0.826) and M-PAST (0.832) were significantly higher than those of FAST (0.744, p = 0.004) and MAST (0.710, p < 0.001). Following the rule-in criteria, positive predictive values of F-CAST (81.8%) and M-PAST (81.8%) were higher than those of FAST (73.5%) and MAST (70.0%). Following the rule-out criteria, negative predictive values of F-CAST (90.5%) and M-PAST (90.9%) were higher than those of FAST (84.0%) and MAST (73.9%). In the validation and UCSD cohorts, AUROCs did not differ significantly between F-CAST and FAST, but M-PAST had a higher diagnostic performance than MAST. CONCLUSIONS: The two-step strategy, especially M-PAST, showed reliability of rule-in/-out for active fibrotic NASH, with better predictive performance compared with MAST. This study is registered with ClinicalTrials.gov (number, UMIN000012757).

Impact of taste/smell disturbances on dietary intakes and cachexia-related quality of life in patients with advanced cancer.

PURPOSE: Taste and smell are used to enjoy meals; however, impairments of these sensory perceptions seriously impact health and eating habits. This study is aimed at investigating the impact of taste and smell disturbances on dietary intakes and cachexia-related quality of life (QOL) in patients with advanced cancer. METHODS: Using a self-report questionnaire, we surveyed patients with advanced cancer undergoing treatment at 11 palliative care centers. Multivariate analyses were conducted to explore the impact of taste and smell disturbances on dietary intakes and cachexia-related QOL. Dietary intakes were assessed using the Ingesta-Verbal/Visual Analog Scale, while taste and smell disturbances were assessed using an 11-point Numeric Rating Scale (NRS). Cachexia-related QOL was assessed using the Functional Assessment of Anorexia/Cachexia Therapy Anorexia Cachexia Subscale (FAACT ACS). RESULTS: Overall, 378 patients provided consent to participate. After excluding patients with missing data, data were analyzed for 343 patients. Among them, 35.6% (n = 122; 95% [confidence interval (CI)] 0.28-0.38) and 20.9% (n = 72; 95% CI 0.17-0.25) experienced disturbances in taste (NRS ≥ 1) and smell (NRS ≥ 1), respectively. Multivariate analyses revealed that, independent of performance status and cancer cachexia, taste and smell disturbances were significantly associated with worse dietary intakes and deteriorating FAACT ACS scores. CONCLUSION: More severe taste and smell disturbances were associated with poorer dietary intakes and cachexia-related QOL. Diagnosing and treating such disturbances may improve dietary intakes and cachexia-related QOL, regardless of performance status and cachexia.

Effectiveness and Prognostic Factors of Everolimus in Patients with Pancreatic Neuroendocrine Neoplasms.

Objective The effectiveness of everolimus for the management of pancreatic neuroendocrine neoplasms (PNENs), including the G3/NEC types, remains unclear. We therefore investigated the effectiveness of the drug for the management of PNENs. Methods We analyzed the progression-free survival (PFS) and overall survival (OS) associated with everolimus and factors influencing the PFS and OS. Results One hundred patients were evaluated. The PFS associated with the G1/G2 types tended to be significantly longer than that associated with the G3/NEC types [hazard ratio (HR), 0.45; p=0.005]. A multivariate analysis showed that the significant factors influencing the PFS were age (<65 years old; HR, 0.44; p=0.002), grade (G1/G2; HR, 0.42; p=0.006), everolimus treatment line (≤2nd; HR, 0.55; p=0.031), and presence of treatment with metformin (yes; HR, 0.29; p=0.044). The median OS was 63.8 months. In the multivariate analysis, the significant factors influencing the OS were grade (G1/G2; HR, 0.21; p<0.001), volume of liver metastasis (≤25%; HR, 0.27; p<0.001), everolimus treatment line (≤2nd; HR, 0.27; p<0.001), and presence of primary tumor resection (yes; HR, 0.33; p=0.005). Conclusion The effectiveness of everolimus in the management of G3/NEC types and prognoses tended to be poorer than those associated with the G1/G2 types. Everolimus combined with metformin and early-line treatment with everolimus may be effective for managing advanced PNENs.

Development and validation of questionnaires for eating-related distress among advanced cancer patients and families.

BACKGROUND: Eating-related distress (ERD) is one type of psychosocial distress among advanced cancer patients and family caregivers. Its alleviation is a key issue in palliative care; however, there is no validated tool for measuring ERD. METHODS: The purpose of this study was to validate tools for evaluating ERD among patients and family caregivers. The study consisted of a development and validation/retest phase. In the development phase, we made preliminary questionnaires for patients and family caregivers. After face validity and content validity, we performed an exploratory factor analysis and discussed the final adoption of items. In the validation/retest phase, we examined factor validity with an exploratory factor analysis. We calculated Pearson's correlation coefficients between the questionnaire for patients, the Functional Assessment of Anorexia/Cachexia Therapy Anorexia Cachexia Subscale (FAACT ACS) and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Cachexia 24 (EORTC QLQ-CAX24) and Pearson's correlation coefficients between the questionnaire for family caregivers and the Caregiver Quality of Life Index-Cancer (CQOLC) for concurrent validity. We calculated Cronbach's alpha coefficients (Cronbach's alpha) and intraclass correlation coefficients (ICCs) for internal consistency and test-retest reliability. We performed the Mann-Whitney U test between the questionnaires and cancer cachexia based on criteria from the international consensus for known-group validity. RESULTS: In the development phase, 162 pairs of patients and family caregivers were asked to participate, and 144 patients and 106 family caregivers responded. In the validation/retest phase, 333 pairs of patients and family caregivers were asked to participate, and 234 patients and 152 family caregivers responded. Overall, 183 patients and 112 family caregivers did the retest. Seven conceptual groups were extracted for the ERD among patients and family caregivers, respectively. Patient factors 1-7 correlated with FAACT ACS (r = -0.63, -0.43, -0.55, -0.40, -0.38, -0.54, -0.38, respectively) and EORTC QLQ-CAX24 (r = 0.58, 0.40, 0.60, 0.49, 0.38, 0.59, 0.42, respectively). Family factors 1-7 correlated with CQOLC (r = -0.34, -0.30, -0.37, -0.37, -0.46, -0.42, -0.40, respectively). The values of Cronbach's alpha and ICC of each factor and all factors of patients ranged from 0.84 to 0.96 and 0.67 to 0.83, respectively. Those of each factor and all factors of family caregivers ranged from 0.84 to 0.96 and 0.63 to 0.84, respectively. The cachexia group of patients had significantly higher scores than the non-cachexia group for each factor and all factors. CONCLUSIONS: Newly developed tools for measuring ERD experienced by advanced cancer patients and family caregivers have been validated.

Meta-analysis of the diagnostic accuracy of serum type IV collagen 7S concentration for the staging of liver fibrosis in nonalcoholic fatty liver disease.

AIM: We aimed to evaluate the diagnostic accuracy of the measurement of serum type IV collagen 7S (T4C7S) concentration for the staging of liver fibrosis in patients with nonalcoholic fatty liver disease (NAFLD). METHODS: A systematic search or published works was carried out using the PubMed, Cochrane Library, and Web of Science Core Collection databases for studies of the accuracy of serum T4C7S concentration for the staging of fibrosis using Fibrosis stage (F)0-4 in patients with NAFLD diagnosed by liver biopsy. RESULTS: Nine articles describing 1475 participants with NAFLD were included. For fibrosis ≥F1, with n = 849, summary estimates of sensitivity of 0.79, specificity of 0.69, and area under the curve (AUC) of 0.80 were obtained using a median T7C4S cut-off value of 4.6 ng/ml. For fibrosis ≥F2, with n = 1,090, summary estimates of sensitivity of 0.78, specificity of 0.78, and AUC of 0.84 were obtained using a median cut-off value of 4.9 ng/ml. For fibrosis ≥F3, with n = 1311 participants and a median cut-off value of 5.4 ng/ml, a pooled sensitivity of 0.82, specificity of 0.81, and AUC of 0.83 were obtained. For fibrosis ≥F4, with n = 753 and a median cut-off value of 6.6 ng/ml, a pooled sensitivity of 0.85, specificity of 0.81, and AUC of 0.85 were obtained. CONCLUSIONS: Serum T4C7S concentration was found to be an accurate method of staging liver fibrosis in patients with NAFLD.

Development of a novel COMPAssion focused online psyChoTherapy for bereaved informal caregivers: the COMPACT feasibility trial protocol.

INTRODUCTION: An easy-to-access and effective psychotherapy for bereaved informal caregivers has not been established. People with higher self-compassion status tend to have lower bereavement related grief, psychotherapy focused on self-compassion can be promising for this population. This study aimed to examine the feasibility of online self-compassion focused psychotherapy for bereaved informal caregivers. METHOD AND ANALYSIS: A total of 60 study participants will undergo an intervention programme comprising online sessions of 2 hours per week for five consecutive weeks and undertake postsession work. The intervention personnel will comprise psychologists who have received more than 10 hours of structured training. The primary endpoint will be assessed on the intervention completion rate, with secondary endpoints consisting of the Complicated Grief Questionnaire, Patient Health Questionnaire-9, Generalised Anxiety Disorder-7, Brief Resilience Scale and Self-Compassion Scale. Evaluations will be conducted preintervention, immediately after intervention, and 4 and 12 weeks after intervention. ETHICS AND DISSEMINATION: This study has been reviewed and approved by the Ethics Committee of the Kyoto University Graduate School and Faculty of Medicine, Kyoto University Hospital, Japan (Approved ID: C1565). The results of this study will be disseminated through publication in a peer-reviewed journal and conference presentations. TRIAL REGISTRATION NUMBER: UMIN000048554.

Diagnostic comparison of vibration-controlled transient elastography and MRI techniques in overweight and obese patients with NAFLD.

Non-invasive imaging techniques have greatly advanced the assessment of liver fibrosis and steatosis but are not fully evaluated in overweight patients. We evaluated the diagnostic performance of vibration-controlled transient elastography (VCTE) and magnetic resonance elastography (MRE) to assess fibrosis and controlled attenuation parameter (CAP) and MR imaging (MRI)-proton density fat fraction (MRI-PDFF) to assess steatosis in overweight and obese patients with non-alcoholic fatty liver disease (NAFLD). We included 163 biopsy-proven patients with NAFLD who underwent VCTE, MRE/MRI-PDFF, and liver biopsy (years 2014-2020) who were classified according to their body mass index (BMI) as normal (BMI < 25 kg/m2, n = 38), overweight (25 ≤ BMI < 30 kg/m2, n = 68), and obese (BMI ≥ 30 kg/m2, n = 57). VCTE and MRE detected fibrosis of stages ≥ 2, ≥ 3, and 4 with an area under the receiver operating curve (AUROC) of 0.83-0.94 (VCTE) and 0.85-0.95 (MRE) in all groups, without considerable differences. MRI-PDFF detected steatosis of grades ≥ 2 and 3 with high AUROC in all groups (0.81-1.00). CAP's diagnostic ability (0.63-0.95) was lower than that of MRI-PDFF and decreased with increasing BMI compared to MRI-PDFF. VCTE and MRE similarly accurately assess fibrosis, although MRI-PDFF is more accurate than CAP in detecting steatosis in overweight and obese patients with NAFLD.