Combined effect of histological findings and diabetes mellitus on liver-related events in patients with metabolic dysfunction-associated steatotic liver disease.

AIM: Advanced fibrosis has a strong influence on the occurrence of liver-related events in patients with metabolic dysfunction-associated steatotic liver disease (MASLD), while diabetes mellitus (DM), which is often complicated by MASLD, is associated with the progression of MASLD. We stratified patients with MASLD according to the severity of liver pathological findings and the presence of DM, aiming to examine whether these indices could be used to accurately assess the risk of developing liver-related events. METHODS: A total of 282 patients with liver biopsy-proven MASLD were included. Liver-related events were defined as the occurrence of hepatocellular carcinoma (HCC) and complications of liver cirrhosis, such as ascites, hepatic encephalopathy, Child-Pugh class B and C, as well as treatment-eligible esophageal and gastric varices. RESULTS: Multivariate analysis adjusted for age, sex, body mass index, alanine aminotransferase, creatinine, hemoglobin A1c, smoking habits, dyslipidemia, hypertension, nonalcoholic fatty liver disease activity score (NAS), or fibrosis stage showed that advanced fibrosis with or without DM was a risk factor for liver-related events. The combined effect of DM and advanced fibrosis increased the risk of HCC onset. However, DM alone or in combination with NAS did not affect the development of liver-related events, including the occurrence of HCC and complications of liver cirrhosis. CONCLUSIONS: While the assessment of fibrosis in patients with MASLD is important for evaluating the risk of developing liver-related events, combining the assessment of DM may be possible to stratify groups at higher risk of developing HCC.

Changes in characteristics of gastroenterology center inpatients in Japan because of rapidly aging society.

BACKGROUND AND AIM: Rapidly aging societies have become a major issue worldwide including Japan. This study aimed to elucidate relative changes in the characteristics of inpatients in Japan related to this issue. METHODS: A total of 23 835 Japanese inpatients treated from 2010 to 2021 were enrolled (2010-2013, period I; 2014-2017, period II; 2018-2021, period III). Changes in clinical features were retrospectively analyzed based on ICD-10 diagnosis data. RESULTS: The percentage of patients aged over 75 years increased over time (period I, 38.0%; II, 39.5%, III, 41.4%). Emergency admissions comprised 27.5% of all in period I, which increased to 43.2% in period II and again to 44.5% in period III (P < 0.001). In period I, gastrointestinal disease, liver disease, pancreatic-biliary disease, and other disease types were noted in 47.4%, 29.5%, 19.2%, and 3.9%, respectively, while those values were 44.0%, 18.0%, 33.9%, and 4.1%, respectively, in period III (P < 0.001). The frequency of liver disease decreased by approximately 0.6-fold from periods I to III, while that of biliary-pancreatic disease increased by approximately 1.8-fold during that time. Both percentage and actual numbers of patients with biliary-pancreatic disease increased during the examined periods. Analysis of changes in the proportion of organs affected by malignancy during periods I, II, and III showed a marked increase in cases of biliary-pancreatic malignancy (11.6%, 19.5%, 26.6%, respectively) (P < 0.001). CONCLUSION: In association with the rapidly aging Japanese society, there has been an increasing frequency of biliary-pancreatic disease cases requiring hospitalization for treatment in the west Japan region of Shikoku.

Clinical features of patients with hepatocellular carcinoma treated with radiofrequency ablation therapy: developing a simple score to determine the need for immune-adjuvant therapy.

BACKGROUND/AIM: Unresectable recurrence after curative treatments for hepatocellular carcinoma (HCC) is a life-limited event. Although the IMbrave050 trial (IM050) showed a favorable reduction in recurrence with adjuvant immune-combination chemotherapy, inclusion criteria of the radiofrequency ablation (RFA) group were lower risk than that of the resection group. This study aimed to elucidate the clinical features of patients treated with RFA, which really need adjuvant-chemotherapy. METHODS: From 2000 to 2022, 528 patients with Child-Pugh A and HCC within the Milan criteria (MC), who met the IM050 criteria for RFA and undergone resection or RFA, were enrolled (71 years, HCV:HBV:HBV/HCV:alcohol:others = 337:44:5:53:89, multi-tumor = 138, RFA:resection = 309:219). Unresectable recurrence was defined as beyond the MC. Risk factors for recurrence beyond the MC were retrospectively evaluated. RESULTS: Multivariate Cox-hazard analysis showed HCV-positive (HR 1.49), AFP-L3 > 10% (HR 1.75), and DCP > 100 mAU/mL (HR1.80) as significant prognostic factors for recurrence beyond the MC (each P < 0.05). Summing of positive factors (1 point for each) was used for scoring (AD-ON score), which showed increased positive rates for micro-hepatic vein invasion (score 0:1:2:3 = 0%:1.1%:6.6%:15.8%), micro-portal vein invasion (0:1:2:3 = 2.0%:12.1%:14.1%:31.6%), and poor differentiation (0:1:2:3 = 6.0%:6.7%:15.3%:15.8%) in the resection group associated with a greater score (each P < 0.01). In patients treated with RFA, those with greater AD-ON scores showed shorter time to recurrence beyond the MC, recurrence-free time, and overall survival (score 0:1:2:3 = no-estimation:97:66:23 months, 35:27:20:12 months, and 91:82:67:52 months, respectively, each P < 0.05). CONCLUSION: HCC patients treated by RFA and with a high AD-ON score (≧2) should be considered for aggressive adjuvant-chemotherapy to prolong the period of recurrence beyond the MC.

Glycemic Control Is Associated with Histological Findings of Nonalcoholic Fatty Liver Disease.

Background: Poor lifestyle habits may worsen nonalcoholic fatty liver disease (NAFLD), with progression to nonalcoholic steatohepatitis (NASH) and cirrhosis. This study investigated the association between glycemic control status and hepatic histological findings to elucidate the effect of glycemic control on NAFLD. Methods: This observational study included 331 patients diagnosed with NAFLD by liver biopsy. Effects of the glycemic control status on histological findings of NAFLD were evaluated by comparing the following four glycemic status groups defined by the glycosylated hemoglobin (HbA1c) level at the time of NAFLD diagnosis: ≤5.4%, 5.5%-6.4%, 6.5%-7.4%, and ≥7.5%. Results: Compared with the lowest HbA1c group (≤5.4%), the higher HbA1c groups (5.5%-6.4%, 6.5%-7.4%, and ≥7.5%) were associated with advanced liver fibrosis and high NAFLD activity score (NAS). On multivariate analysis, an HbA1c level of 6.5%- 7.4% group was significantly associated with advanced fibrosis compared with the lowest HbA1c group after adjusting for age, sex, hemoglobin, alanine aminotransferase, and creatinine levels. When further controlling for body mass index and uric acid, total cholesterol, and triglyceride levels, the higher HbA1c groups were significantly associated with advanced fibrosis compared with the lowest HbA1c group. On the other hand, compared with the lowest HbA1c group, the higher HbA1c groups were also associated with a high NAS in both multivariate analyses. Conclusion: Glycemic control is associated with NAFLD exacerbation, with even a mild deterioration in glycemic control, especially a HbA1c level of 6.5%-7.4%, contributing to NAFLD progression.

Smoking and secondhand smoke exposure and carotid intima-media thickness: Baseline data from the Aidai Cohort Study in Japan.

INTRODUCTION: Epidemiological evidence regarding the relationship between smoking and secondhand smoke (SHS) exposure and carotid intima-media thickness (CIMT) has been limited in Asian populations. Employing baseline data from the Aidai Cohort Study, Japan, we evaluated the evidence in this cross-sectional study. METHODS: Study subjects were 727 men aged 35-88 years and 1297 women aged 34-85 years. Information on smoking, SHS exposure, and confounders was obtained through a self-administered questionnaire. An automated carotid ultrasonography device was used to measure the right and left CIMT. The greatest CIMT measurement in the left or right common carotid artery was considered the maximum CIMT, and a maximum CIMT >1.0 mm was indicative of carotid wall thickening. Age, alcohol consumption, leisure time physical activity, hypertension, dyslipidemia, diabetes mellitus, body mass index, waist circumference, employment, and education level were adjusted at one time. RESULTS: The prevalence of carotid wall thickening was 13.0%. The prevalence of never smoking was 30.5% in men and 90.1% in women. Among those who had never smoked, the prevalence of never SHS exposure at home and work was 74.3% and 48.2% in men and 38.3% and 56.3% in women, respectively. Active smoking and pack-years of smoking were independently positively related to carotid wall thickening regardless of sex, although the association with current smoking in women was not significant. Independent positive relationships were shown between former smoking and pack-years of smoking and maximum CIMT in men but not in women. No significant relationships were found between SHS exposure at home and work and carotid wall thickening or maximum CIMT in either men or women. CONCLUSIONS: Active smoking, especially pack-years of smoking, was positively associated with carotid wall thickening in both sexes. Such positive associations with maximum CIMT were found only in men; however, interactions between smoking and sex were not significant.

Functional AGXT2 SNP rs180749 variant and depressive symptoms: Baseline data from the Aidai Cohort Study in Japan.

No study has shown the relationship between alanine-glyoxylate aminotransferase 2 (AGXT2) single nucleotide polymorphisms (SNPs) and depressive symptoms. The present case-control study examined this relationship in Japanese adults. Cases and control participants were selected from those who participated in the baseline survey of the Aidai Cohort Study, which is an ongoing cohort study. Cases comprised 280 participants with depressive symptoms based on a Center for Epidemiologic Studies Depression Scale (CES-D) score ≥ 16. Control participants comprised 2034 participants without depressive symptoms based on the CES-D who had not been diagnosed by a physician as having depression or who had not been currently taking medication for depression. Adjustment was made for age, sex, smoking status, alcohol consumption, leisure time physical activity, education, body mass index, hypertension, dyslipidemia, and diabetes mellitus. Compared with the GG genotype of rs180749, both the GA and AA genotypes were significantly positively associated with the risk of depressive symptoms assessed by the CES-D: the adjusted odds ratios for the GA and AA genotypes were 2.83 (95% confidence interval [CI] 1.23-8.24) and 3.10 (95% CI 1.37-8.92), respectively. The TGC haplotype of rs37370, rs180749, and rs16899974 was significantly inversely related to depressive symptoms (crude OR 0.67; 95% CI 0.49-0.90), whereas the TAC haplotype was significantly positively associated with depressive symptoms (crude OR 1.24; 95% CI 1.01-1.52). This is the first study to show significant associations between AGXT2 SNP rs180749, the TGC haplotype, and the TAC haplotype and depressive symptoms.

Simple scoring system for esophagogastric varices prediction in hepatocellular carcinoma patients without liver stiffness evaluation.

BACKGROUND/AIM: For predicting esophagogastric varices (EGV), the Virtual Baveno VII Consensus Workshop has proposed a combination of liver stiffness determination and platelet count measurement using a FibroScan®. However, that is not available at all institutions. The present study aimed to develop a simple method to predict development of EGV using only general blood examination results. MATERIALS/METHODS: A total of 1090 hepatocellular carcinoma (HCC) patients were enrolled, after excluding 956 with major portal vein tumor thrombus (Vp3/Vp4) or without upper gastrointestinal endoscopy examination results available. Those with EGV (≥grade F2) or a history of treatment for the condition were defined as positive for significant EGV, then clinical factors were retrospectively evaluated to determine indicators of occurrence. RESULTS: Logistic multivariate analysis showed platelet count (≤12 x104/µL) [odds ratio (OR) 3.79, P<0.001], mALBI grade 2a (OR 1.52, P=0.036), and mALBI 2b or 3 (OR 3.46, P<0.001) as significant predictive factors. Based on the OR values, platelet count (≤12 x104/µL) and mALBI grade 2b/3 were each assigned 2 points and mALBI 2a was given 1 point, with the result termed Recommendation for EGV Screening (REGS) score. EGV occurrence was noted in 2.9% (9/311) of the patients with a REGS score 0, 11.0% (13/118) with a score 1, 19.3% (53/274) with a score 2, 29.5% (39/132) with a score 3, and 38.0% (97/255) with a score 4 (P<0.001). CONCLUSION: The findings indicate that REGS score can provide useful predictive information for development of significant EGV without the need for special equipment such as a FibroScan®.

Usefulness of aMAP Risk Score for Predicting Recurrence after Curative Treatment for Hepatocellular Carcinoma within Milan Criteria.

INTRODUCTION: The aMAP score is a prediction model for hepatocellular carcinoma (HCC) risk in chronic hepatitis patients. This study was conducted to elucidate the utility of this model for predicting initial recurrence of HCC in patients within the Milan criteria after undergoing curative treatment. METHODS: Patients with naïve HCC within the Milan criteria (n = 1,020) and treated from January 2000 to August 2022 were enrolled. The cohort was divided into two groups according to the aMAP score (high ≥60, low <60) and then compared for recurrence-free survival (RFS) and overall survival (OS). RESULTS: Comparisons between the high and low groups showed that etiology (HBV:HCV:HBV+HCV:NBNC = 41:79:2:37 vs. 65:589:11:196, p < 0.001), AST (36 vs. 46 IU/L, p < 0.001), and multiple HCC occurrence (15% vs. 22%, p = 0.026) were significantly different. Additionally, median RFS (59.8 vs. 30.9 months; p < 0.001) and median OS (154.1 vs. 83.4 months, p < 0.01) were greater in the low group. As for patients with HCC due to chronic viral hepatitis, there was a significant difference in median RFS between the groups (59.8 vs. 30.6 months, p < 0.001), especially for HCV-positive patients (53.1 vs. 27.2 months, p = 0.002). In patients with HCC due to a nonviral cause, the difference in median RFS between the low (70.9 months) and high (32.0 months) groups was not significant. DISCUSSION: Findings of this retrospective study indicate a significant association of elevated aMAP with worse RFS in patients with HCC caused by chronic viral hepatitis, especially those with HCV. The aMAP score is considered useful to predict not only HCC-carcinogenesis risk but also risk of recurrence following curative treatment.

Association of abnormal glucose tolerance with liver-related disease and cardiovascular diseases in patients with chronic hepatitis C.

AIM: Hepatitis C complicated by diabetes mellitus (DM) is considered a risk factor for the progression of fibrosis and development of hepatocellular carcinoma (HCC) and cardiovascular diseases. However, several studies may have lacked appropriate diagnosis of glucose intolerance. We aimed to examine the risk associated with abnormal glucose intolerance in the development of liver-related diseases, including HCC and complications of liver cirrhosis, such as ascites, esophageal and gastric varices, and hepatic encephalopathy, and cardiovascular diseases in patients with hepatitis C accurately diagnosed with impaired glucose tolerance. METHODS: This longitudinal retrospective study included 365 patients with chronic hepatitis C admitted to Ehime University Hospital for anti-hepatitis C therapy between September 1991 and January 2015. Patients were classified into normal glucose tolerance (NGT), prediabetes, and DM groups based on 75-g oral glucose tolerance test results. RESULTS: Both univariate and multivariate (adjusted for potential confounders) analyses revealed a significantly higher risk of developing HCC and cardiovascular events in the DM group than in the NGT group. However, in multivariate analysis, liver-related events, particularly liver cirrhosis complications, revealed no significant association. In addition, the prediabetes group had no significant risk of any outcome. CONCLUSIONS: Patients with hepatitis C complicated by DM, compared with patients with hepatitis C with NGT or complicated with prediabetes, have a higher risk of HCC and cardiovascular disease events, but not liver-related events, particularly in not developing liver cirrhosis complications. Therefore, appropriate follow-up is required for patients with hepatitis C based on their glucose tolerance status.

Role of B Cell-Activating Factor in Fibrosis Progression in a Murine Model of Non-Alcoholic Steatohepatitis.

Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease all over the world. Therapeutic strategies targeting its multidirectional pathways are required. Particularly, fibrosis is closely associated with its prognosis. We previously found that B cell-activating factor (BAFF) is associated with severity of NAFLD. Here, we determined the direct in vivo role of BAFF in the development of liver fibrosis. Histological and biochemical analyses were performed using wild-type and BAFF-deficient mice. We established a murine model of non-alcoholic steatohepatitis (NASH) using carbon tetrachloride injection accompanied by high-fat/high-cholesterol diet feeding. Additionally, in vitro analysis using mouse macrophage-like cell line RAW264.7 and primary hepatic stellate cells was performed. Hepatic steatosis and inflammation, and most importantly, the progression of liver fibrosis, were ameliorated in BAFF-deficient mice compared to those wild-type mice in our model. Additionally, BAFF deficiency reduced the number of CD11c+ M1-type macrophages in the liver. Moreover, BAFF stimulated RAW264.7 cells to secrete nitric oxide and tumor necrosis factor α, which drove the activation of hepatic stellate cells. This indicates that BAFF plays a crucial role in NASH development and may be a promising therapeutic target for NASH.

Fish and Polyunsaturated Fatty Acid Intake and Carotid Intima-Media Thickness in Japan: the Aidai Cohort Study in Yawatahama, Uchiko, Seiyo, and Ainan.

AIM: Epidemiological evidence regarding the relationship between fish and fatty acid intake and carotid intima-media thickness (CIMT) has been limited and inconsistent. The current cross-sectional study investigated this issue using baseline data from the Aidai Cohort Study. METHODS: Study subjects were 2024 Japanese men and women aged 34-88 years. Right and left CIMT were measured at the common carotid artery using an automated carotid ultrasonography device. Maximum CIMT was defined as the largest CIMT value in either the left or right common carotid artery. Carotid wall thickening was defined as a maximum CIMT value ＞1.0 mm. RESULTS: The prevalence of carotid wall thickening was 13.0%. In men, intake of n-3 polyunsaturated fatty acids (PUFA) was independently positively related to the prevalence of carotid wall thickening, while no associations were found between intake of fish and the other fatty acids and carotid wall thickening or maximum CIMT. In women, intake levels of fish, n-3 PUFA, eicosapentaenoic acid, docosahexaenoic acid, and arachidonic acid were independently inversely associated with carotid wall thickening and intake levels of fish, n-3 PUFA, α-linolenic acid, n-6 PUFA, and linoleic acid were independently inversely associated with the maximum CIMT. No significant relationships were found between intake of total fat, saturated fatty acids, or monounsaturated fatty acids and carotid wall thickening or maximum CIMT regardless of sex. CONCLUSIONS: In women, higher intake of fish and n-3 and n-6 PUFA may be associated with a lower prevalence of carotid wall thickening and a decrease in maximum CIMT.

Comparison of Surgical Resection and Percutaneous Ultrasonographic Guided Radiofrequency Ablation for Initial Recurrence of Hepatocellular Carcinoma in Early Stage following Curative Treatment.

Background/Aim: The SURF trial showed that surgical resection (SR) and percutaneous ultrasonographic guided radiofrequency ablation (RFA) had equal therapeutic effects for small hepatocellular carcinoma (HCC). However, consensus regarding which treatment is appropriate for initial recurrent early-stage HCC remains lacking. This study aimed to elucidate therapeutic efficacy differences between SR and RFA for initial recurrent early-stage HCC. Materials/Methods: From 2000 to 2021, 371 patients with recurrent early-stage HCC (≤3 cm, ≤3 nodules) after undergoing initial curative treatment with SR or RFA were enrolled (median age 72 years; males 269; Child−Pugh A:B, n = 328:43; SR:RFA, n = 36:335). Recurrence-free survival (RFS) and overall survival (OS) were retrospectively evaluated. Results: Although the median albumin−bilirubin (ALBI) score was better in the SR than the RFA group (−2.90 vs. −2.50, p < 0.01), there were no significant differences between them in regard to RFS (median 28.1 months, 95% CI 23.4−50.0 vs. 22.1 months, 95% CI 19.3−26.2; p = 0.34), OS (78.9 months, 95% CI 49.3­not applicable vs. 71.2 months 95% CI, 61.8−84.7; p = 0.337), or complications (8.3% vs. 9.3%; p = 1.0). In sub-analysis for RFS and OS according to ALBI grade revealed no significant differences between the SR and RFA groups (ALBI 1/2 = 28.2/17.5 vs. 24.0/23.4 months; p = 0.881/0684 and ALBI 1/2 = 78.9/58.9 vs. 115.3/52.6 months, p = 0.651/0.578, respectively). Conclusion: This retrospective study found no significant differences in regard to RFS or OS between patients in the SR and the RFA groups for initial recurrence of early-stage HCC after undergoing curative treatment. These results showing equal therapeutic efficacy of SR and RFA confirm the findings of the SURF trial.

Oral administration of human carbonic anhydrase I suppresses colitis in a murine inflammatory bowel disease model.

The incidence of inflammatory bowel disease (IBD) is increasing; hence, effective treatments are warranted. The therapeutic effect of human carbonic anhydrase I (hCA I) in IBD remains unknown. Therefore, we investigated whether oral tolerization to hCA I would induce antigen-specific protection from intestinal inflammation in vivo. Severe combined immunodeficient mice received hCA I, keyhole limpet hemocyanin (KLH), or phosphate-buffered saline (PBS) orally for 7 days. Colons and mesenteric lymph nodes (MLNs) were collected 4 weeks after cell transfer. Additionally, the mechanisms underlying the therapeutic effects were investigated. The comparison between the effects of well-established drugs and hCA I oral administration was investigated. Oral administration of hCA I ameliorated colitis remarkably. hCA I reached the cecum and ameliorated colitis more effectively than mesalazine and similarly to prednisolone. Compared with PBS treatment, hCA I treatment reduced interleukin (IL)-17a, IL-6, and retinoic acid-related orphan receptor gamma t (RORγt) expression in the colon or MLNs; moreover, hCA I markedly reduced IL-6, IL-17, and interferon-gamma (IFN-γ) levels in the MLN. Oral administration of hCA I induced immune tolerance and suppressed colitis in vivo. Thus, hCA I administration could be proposed as a new treatment option for IBD.

Plasma Fatty Acid Composition Is Associated with Histological Findings of Nonalcoholic Steatohepatitis.

The relationship between advanced nonalcoholic steatohepatitis (NASH) and plasma fatty acid composition remains unknown. We aimed to examine the plasma fatty acid composition in biopsy-confirmed nonalcoholic fatty liver disease (NAFLD) and evaluate the relationship between histological findings and fatty acid composition. Overall, 235 patients (134 women) with NAFLD were enrolled. Comprehensive blood chemistry tests and histological examinations of liver samples were conducted. Multivariate analyses adjusted for age, sex, body mass index, alanine aminotransferase, hemoglobin A1c, creatinine, total cholesterol, triglyceride, and NAFLD Activity Score values showed that lower levels of arachidic, behenic, α-linolenic, eicosatetraenoic, docosapentaenoic, and docosahexaenoic acids and higher levels of mead acid were associated with fibrosis stage 3-4. Furthermore, higher lauric acid, myristic acid, and palmitic acid levels and monounsaturated fatty acids such as palmitoleic acid and oleic acid were significantly associated with high NAS in analyses adjusted for the same factors and fibrosis stage. The plasma fatty acid composition was associated with the histological evidence of NASH. Increased synthesis of fatty acids is associated with NASH; insufficient intake of n-3 essential fatty acids and reduced elongation of fatty acids are associated with fibrosis in NASH. These features may help clinicians to understand and treat advanced NASH cases.

Functional AGXT2 SNP rs37369 Variant Is a Risk Factor for Diabetes Mellitus: Baseline Data From the Aidai Cohort Study in Japan.

OBJECTIVES: The relationship between alanine-glyoxylate aminotransferase 2 (AGXT2) single-nucleotide polymorphisms (SNPs) and diabetes mellitus (DM) has not been investigated. Therefore, we performed a case-control study to examine this relationship. METHODS: The study subjects included 2,390 Japanese men and women aged 34 to 88 years. In total, 190 cases were defined as having a fasting plasma glucose level ≥126 mg/dL, having a glycated hemoglobin ≥6.5% or currently using diabetic medication. The 2,200 remaining participants served as control subjects. RESULTS: Compared with study subjects with the CC genotype of AGXT2 SNP rs37369, those with the TT, but not CT, genotype had a significantly increased risk of DM: the adjusted odds ratio (OR) for the TT genotype was 1.83 (95% confidence interval [CI], 1.04 to 3.47). AGXT2 SNPs rs37370 and rs180749 were not significantly associated with the risk of DM. The CTA haplotype of rs37370, rs37369 and rs180749 was significantly positively associated with the risk of DM (crude OR, 1.25; 95% CI, 1.01 to 1.56), whereas the CCA haplotype was significantly inversely related to DM (crude OR, 0.53; 95% CI, 0.27 to 0.95). The multiplicative interaction between AGXT2 SNP rs37369 and smoking status with regard to the risk of DM was not significant (p=0.32 for interaction). CONCLUSIONS: This is the first study to show significant associations between AGXT2 SNP rs37369, the CTA haplotype, and the CCA haplotype and DM. No interaction with regard to the risk of DM was observed between rs37369 and smoking.

Relationship between hearing loss and prevalence of depressive symptoms in Japan: Baseline data from the Aidai Cohort study in Yawatahama and Uchiko.

OBJECTIVE: Epidemiological evidence on the relationship between hearing loss (HL) and depressive symptoms, especially in the middle aged, is limited. The present cross-sectional study investigated this issue in middle-aged and older Japanese individuals separately. METHODS: Study subjects were 1018 Japanese adults aged 36-84 years. We used the audiometric definition of HL, which identifies the speech-frequency pure tone average (PTA) hearing thresholds at 0.5, 1, 2, and 4 kHz as an average of four frequencies. HL was defined as present when PTA was > 25 dB HL in the better-hearing ear. Presence of depressive symptoms was defined as a Center for Epidemiological Studies Depression Scale score ≥ 16. Adjustment was made for age, sex, smoking status, alcohol consumption, leisure time physical activity, hypertension, dyslipidemia, diabetes mellitus, body mass index, waist circumference, employment, education, and household income. RESULTS: The prevalence values of HL and depressive symptoms were 11.5% and 15.0%, respectively, among the 575 subjects aged < 65 years and 42.2% and 10.4%, respectively, among the 443 subjects aged ≥ 65 years. Among the 1018 participants, HL was independently related to a higher prevalence of depressive symptoms: the multivariate-adjusted OR was 1.92 (95% CI: 1.19-3.08). This positive association was stronger among middle-aged participants, with a multivariate-adjusted OR of 2.70 (95% CI: 1.34-5.27), but was not significant in the elderly, with a multivariate-adjusted OR of 1.71 (95% CI: 0.83-3.54). CONCLUSION: HL may be positively associated with depressive symptoms in middle-aged, but not older, individuals.

Simultaneous combined endoscopic endonasal and transcranial surgery for giant pituitary adenomas: Tips and traps in operative indication and procedure.

OBJECTIVES: This retrospective analysis of patients treated with endoscopic endonasal transsphenoidal surgery (ETSS) alone or simultaneous combined surgery investigated imaging features suitable for surgical methods and pitfalls in simultaneous combined surgery for giant pituitary adenoma. PATIENTS AND METHODS: Ten patients with giant pituitary adenoma treated by ETSS alone or simultaneous combined endoscopic endonasal and transcranial surgery were enrolled. By analyzing tumor imaging features on magnetic resonance imaging (MRI), operative findings and clinical outcomes, we examined types of imaging features suitable for each surgical method. RESULTS: Four patients received ETSS alone and six patients underwent simultaneous combined endonasal and transcranial surgery. Four patients treated by ETSS alone and three patients treated by combined surgery had high resection rates and good outcomes. The remaining three patients with combined surgery achieved partial resection and visual deterioration in one patient. MRI features suitable for ETSS included an enlarged sella, upward tumor extension, and round surface, whereas those for combined surgery included normal/enlarged sella, anterior and/or unilateral tumor extension, and a multilobulated surface. Tumors extending extensively bilaterally or upward and encasing neurovascular structures could not be effectively resected even under combined surgery. CONCLUSION: Both ETSS alone and simultaneous combined endonasal and transcranial surgery showed good results for giant pituitary adenoma when the surgical methods matched suitable imaging features. Tumors with unilateral or anterior extension and a multilobulated surface were maximally resected without neurological deficit by combined surgery, but tumors showing extensive multi-directional extension and full encasement of neurovascular structures were not effectively resected even with combined surgery.

Observational Study on Unhealthy Eating Behavior and the Effect of Sodium-Glucose Cotransporter 2 Inhibitors: The Luseogliflozin Ehime Diabetes Study.

INTRODUCTION: Luseogliflozin is a sodium-glucose cotransporter 2 (SGLT2) inhibitor. Unhealthy eating behavior is associated with diabetes, hypertension, and obesity. However, evidence regarding the effect of medications, including SGLT2 inhibitors, on unhealthy eating behavior is limited. This study investigated the association between unhealthy eating behavior and the laboratory and physical findings of Japanese patients with type 2 diabetes given luseogliflozin once daily for 24 weeks. METHODS: Twenty-nine patients with type 2 diabetes mellitus were enrolled in a 24-week prospective, open-label, single-arm pilot study. The information regarding unhealthy eating behaviors (eating fast, late dinner, nighttime snack, skipping breakfast, and eating until full) was obtained using self-reported questionnaires. RESULTS: The baseline rate of eating fast, late dinner, nighttime snack, skipping breakfast, and eating until full was 51.7%, 24.1%, 24.1%, 10.3% and 55.2%, respectively. After administration of luseogliflozin, fasting plasma glucose, HbA1c, aspartate aminotransferase (ALT), weight, body mass index, and waist measurement all decreased significantly. High-density lipoprotein cholesterol and hematocrit increased significantly. In the healthy eating behavior group, the improvements of fasting plasma glucose and ALT, but not other variables, were attenuated. HbA1c level was significantly improved in patients with eating fast, while other unhealthy eating behaviors attenuated the effect of luseogliflozin for HbA1c. The effect of leseogliflozin on the relationship between eating behavior and weight reduction was inconsistent after administration luseogliflozin. CONCLUSION: Luseogliflozin might be more effective for controlling plasma glucose in patients with type 2 diabetes who have a tendency to eat fast, but it might have less effect on those with other unhealthy eating habits.

Combined evaluation of Fibrosis-4 index and fatty liver for stratifying the risk for diabetes mellitus.

AIMS/INTRODUCTION: To investigate whether the Fibrosis-4 index can help stratify the risk of diabetes mellitus in patients with fatty liver disease. MATERIALS AND METHODS: Based on fatty liver disease and Fibrosis-4 index (cut-off value 1.3), we retrospectively divided 9,449 individuals, who underwent at least two annual health checkups, into four groups stratified by sex: normal; high Fibrosis-4 index without fatty liver disease; low Fibrosis-4 index with fatty liver disease; and high Fibrosis-4 index with fatty liver disease. RESULTS: Onset rates for diabetes mellitus in the normal, high Fibrosis-4 index without fatty liver disease, low Fibrosis-4 index with fatty liver disease and high Fibrosis-4 index with fatty liver disease groups were 1.6%, 4.3%, 6.8% and 10.2%, respectively, in men, and 0.6%, 0.9%, 5.3% and 7.0%, respectively, in women. Compared with the normal group, the high Fibrosis-4 index without fatty liver disease, low Fibrosis-4 index with fatty liver disease and high Fibrosis-4 index with fatty liver disease groups were at a significant risk for diabetes mellitus onset in both male and female participants. Furthermore, in both sexes, high Fibrosis-4 index with fatty liver disease remained a significant risk factor on multivariate analysis (high fibrosis-4 index with fatty liver disease group: adjusted hazard ratio 4.03, 95% confidence interval 2.19-7.42 [men] and adjusted hazard ratio 6.40, 95% confidence interval 1.77-23.14 [women]). CONCLUSIONS: Individuals with fatty liver disease and high Fibrosis-4 index had a higher risk of diabetes mellitus onset. Therefore, Fibrosis-4 index can help stratify the risk of diabetes mellitus in patients with fatty liver disease and identify patients requiring intervention.