Yusuke Saigusa

Palmitate-induced lipotoxicity is crucial for the pathogenesis of nonalcoholic fatty liver disease in cooperation with gut-derived endotoxin

Although previous studies have indicated important roles of palmitate, a saturated fatty acid, in the pathogenesis of nonalcoholic fatty liver disease (NAFLD), it remains unclear how palmitate contributes to inflammation and fibrosis in the liver. Administration of palmitate in high fat diet (HFD)-fed but not basal diet (BD)-fed mice resulted in an increase in serum alanine aminotransferase (ALT) levels. Surprisingly, combined administration of very low dose lipopolysaccharide in palmitate-treated mice led to a marked increase in serum ALT levels despite BD-fed conditions. Administration of palmitate alone in BD-fed mice caused inflammatory cell infiltration and liver fibrosis mediated by the toll-like receptor 4 pathway without ALT elevation. In addition, a significant correlation between serum free fatty acid levels and liver fibrosis stage was observed in patients with NAFLD. These results indicate that palmitate may play crucial roles in the pathogenesis of NAFLD in the presence of gut-derived endotoxin.

Short- and long-term efficacy of adalimumab salvage therapy after failure of calcineurin inhibitors in steroid-refractory ulcerative colitis

Abstract Objective: Calcineurin inhibitors are highly effective in patients with corticosteroid-refractory ulcerative colitis (UC). When therapy with calcineurin inhibitors fails, adalimumab can be considered to avoid colectomy. The efficacy and safety of this sequential alternative salvage therapy remain unknown. Therefore, the present study was performed to investigate the short- and long-term efficacy and safety of adalimumab after failure of calcineurin inhibitors in corticosteroid-refractory UC. Materials and methods: Patients with a corticosteroid-refractory flare of UC who did not respond to calcineurin inhibitors and received continuing salvage therapy with adalimumab were included in this retrospective, observational, single-centre study. The cumulative rates of colectomy were calculated using the Kaplan–Meier method. Clinical remission and response were evaluated based on the Rachmilewitz index. The cumulative rates of colectomy were calculated. Predictive factors for clinical remission and colectomy were identified. In the safety evaluation, any adverse event occurring after the administration of adalimumab was considered. Results: Forty-one patients were enrolled; 78% had extensive colitis and 87% had moderate to severe colitis. Seventeen patients (41%) underwent colectomy during the follow-up period. At week 8, 26, and 52 after adalimumab injection, 27%, 39%, and 32% of patients achieved clinical remission, respectively. The adverse event rate was 17%, including one case of tuberculosis. Conclusions: The efficacy of adalimumab for calcineurin inhibitor-refractory UC was examined for the first time. Treatment with adalimumab avoided the need for colectomy in two-thirds of patients with corticosteroid-refractory UC in whom calcineurin inhibitors had failed. However, attention is needed to avoid adverse events, especially infection.

Extended Marginal Homogeneity Model Based on Complementary Log-Log Transform for Square Tables

For square contingency tables with the same ordinal row and column classifications, McCullagh (1977) gave the marginal cumulative logistic model, which is an extension of the marginal homogeneity (MH) model using the logit transform. The present paper proposes a different extension of the MH model using the complementary log-log transform. In addition, the present paper gives the theorem that the MH model is equivalent to the proposed model and the equality of row and column marginal means holding simultaneously. In data analysis, if the MH model fits the data poorly, the theorem may be useful for seeing the reason for the poor fit. As example, the occupational status data for British father-son pairs are analyzed.

Association between dysfunction of autonomic nervous system activity and mortality in schizophrenia

BACKGROUND Patients with schizophrenia have a higher mortality risk than the general population. Additionally, the autonomic nervous system (ANS) activity of patients with schizophrenia is lower and more dysfunctional than that of the general population. Nonetheless, the association between ANS dysfunction and mortality in schizophrenia is unclear. The aim of this study was to investigate the association between ANS activity and mortality in schizophrenia and to evaluate the predictive values of heart rate variability for long-term survival. METHODS This study involves the 10-year follow-up of a sample population consisting of 59 Japanese inpatients with schizophrenia between 60 and 70 years of age from 2007 to 2016. The ANS activity of all patients was evaluated using heart rate variability in 2007. RESULTS Fifty-three participants could be followed up because they stayed in the hospital during the follow-up period. Of these patients, 11 died during follow-up. Their mean age at death was 70.55 ± 3.45 years. The parasympathetic activity of nonsurvivors was significantly lower than that of survivors, and multiple logistic regression analysis showed a significant association between death and parasympathetic activity. CONCLUSION We suggest that decreased parasympathetic activity could be associated with 10-year all-cause mortality in older schizophrenic patients.

Decompositions of Symmetry using Extended Palindromic Symmetry Models for Square Contingency Tables

For square contingency tables with ordered categories, this paper gives the theorem that the symmetry model holds if and only if the following three models hold: (1) extended palindromic symmetry, (2) equality of marginal moments, and (3) subsymmetry of cumulative probabilities from the upper right and lower left corners of the table.