Abnormal Liver Function in Patients with Sjogren\u27s Syndrome

We measured the liver function tests of 145 patients with Sjogren\u27s syndrome (SjS) (75 patients with primary SjS, 70 patients with secondary SjS), and characterized the SjS patients with abnormal liver function tests from several points of view : 1, the incidence of them in the primary SjS comparing with that in secondary SjS. 2, the staining pattern of anti-nuclear antibodies, and 3, the existence of antihepatitis C virus (HCV) antibody, hepatitis B surface (HBs) antigen, and antibody against human T-lymphotropic virus type I (HTLV-I). Abnormal liver function tests were detected in 38 out of 145 patients (26.2%) with SjS. Fifteen of the 38 patients (20.0%) had primary SjS while the remaining patients (32.9%) had secondary SjS. Histopathological examination identified primary biliary cirrhosis (PBC) in 2 patients, autoimmune hepatitis in 4 patients, and autoimmune cholangitis in a single patient with SjS. No significant difference in the presence of antinuclear antibody (ANA) was found between SjS patients with and without abnormal liver function tests. However, the incidence of discrete speckled pattern was significantly higher in SjS patients with abnormal liver function than in the patients with normal liver function. Two sera showing cytoplasmic pattern of ANA were also positive for anti-mitochondrial M2 antibody, allowing the diagnosis of PBC. All 11 sera exhibiting discrete speckled pattern contained significant amounts of anti-centromere antibody. Abnormal liver function tests were detected in 8 of 11 sera with these antibodies, 2 patients with PBC, 2 patients with autoimmune hepatitis, one patient with autoimmune cholangitis, one patient with chronic hepatitis B and 2 other patients with unconfirmed diagnosis. The percentages of anti-HCV antibody-positive, HBs-Agpositive and anti-HTLV-I antibody-positive in sera of patients were higher than those of blood donors from the same geographical area. However, no significant difference was seen of these percentages in sera between the patients with and without abnormal liver function. Taken together, present study indicated that SjS patients with anti-centromere antibody may have some susceptibility for acquiring autoimmune liver disease

Effects of drug discontinuation after short-term daily alendronate administration on osteoblasts and osteocytes in mice

In order to determine whether osteoclastic bone resorption is restarted after withdrawn of bisphosphonates, we conducted histological examinations on murine osteoclasts, osteoblasts and osteocytes after discontinuation of a daily regimen of alendronate (ALN) with a dosage of 1 mg/kg/day for 10 days. After drug discontinuation, metaphyseal trabecular number and bone volume remained unaltered for the first 4 days. Osteoclast number did not increase, while the number of apoptotic osteoclasts was elevated. On the other hand, tissue non-specific alkaline phosphatase-immunoreactive area was markedly reduced after ALN discontinuation. In addition, osteocytes showed an atrophic profile with empty lacunar areas during and after ALN treatment. Interestingly, as early as 36 h after a single ALN injection, osteocytes show signs of atrophy despite the presence of active osteoblasts. Structured illumination microscopy system showed shortening of osteocytic cytoplasmic processes after drug cessation, suggesting a possible morphological and functional disconnection between osteocytes and osteoblasts. Taken together, it appears that osteoclastic bone resorption is not resumed after ALN discontinuation; also, osteoblasts and osteocytes hardly seem to recover once they are inactivated and atrophied by ALN. In summary, it seems that one must pay more attention to the responses of osteoblasts and osteocytes, rather focusing on the resuming of osteoclastic bone resorption after the ALN discontinuation

Background Factors Affecting Visual Acuity at Initial Visit in Eyes with Central Retinal Vein Occlusion : Multicenter Study in Japan

Purpose: To determine the baseline characteristics of patients with central retinal vein occlusion (CRVO) that were significantly associated with the best-corrected visual acuity (BCVA) at the initial examination. Methods: This was a retrospective multicenter study using the medical records registered in 17 ophthalmological institutions in Japan. Patients with untreated CRVO (≥20-years-of-age) who were initially examined between January 2013 and December 2017 were studied. The patients’ baseline factors that were significantly associated with the BCVA at the initial examination were determined by univariate and multivariate linear regression analyses. Results: Data from 517 eyes of 517 patients were analyzed. Univariate analyses showed that an older age (r = 0.194, p < 0.001) and the right eye (r = −0.103, p < 0.019) were significantly associated with poorer BCVA at the initial visit. Multivariate analyses also showed that an older age (β = 0.191, p < 0.001) and the right eye (β = −0.089, p = 0.041) were significantly associated with poorer BCVA at the initial visit. Conclusions: The results indicate that an older age, a known strong factor, and the right eye were significantly associated with poorer BCVA at the initial visit to the hospital. These results suggest that functional and/or anatomical differences between the right and left eyes may be involved in these results

Urinary protein and renal prognosis in idiopathic membranous nephropathy: a multicenter retrospective cohort study in Japan

Background: Several studies have revealed a relationship between proteinuria and renal prognosis in idiopathic membranous nephropathy (IMN). The benefit of achieving subnephrotic proteinuria (<3.5 g/day), however, has not been well described. Methods: This multicenter, retrospective cohort study included 171 patients with IMN from 10 nephrology centers in Japan. The relationship between urinary protein over time and a decrease of 30% in estimated glomerular filtration rate (eGFR) was assessed using time-dependent multivariate Cox regression models adjusted for clinically relevant factors. Results: During the observation period (median, 37 months; interquartile range, 16–71 months), 37 (21.6%) patients developed a 30% decline in eGFR, and 2 (1.2%) progressed to end-stage renal disease. Time-dependent multivariate Cox regression models revealed that lower proteinuria over time were significantly associated with a lower risk for a decrease of 30% in eGFR (primary outcome), adjusted for clinically relevant factors. Complete remission (adjusted hazard ratio [HR], 0.005 [95%CI, 0.0–0.09], p < .001), incomplete remission with <1.0 g/day of urine protein (ICR I) (adjusted HR, 0.01 [95%CI, 0.001–0.20], p = .002), and 1.0 to 3.5 g/day (ICR II) (adjusted HR, 0.12 [95%CI, 0.02–0.64], p = .013) were significantly associated with avoiding a 30% decrease in eGFR, compared to that at no remission. Conclusions: Attaining lower proteinuria predicts good renal survival in Japanese patients with IMN. This study quantifies the impact of proteinuria reduction in IMN and the clinical relevance of achieving subnephrotic proteinuria in IMN as a valuable prognostic indicator for both the clinician and patient

Circulating pancreatic cancer exosomal RNAs for detection of pancreatic cancer

Diagnostic biomarkers for the early diagnosis of pancreatic cancer are needed to improve prognosis for this disease. The aim of this study was to investigate differences in the expression of four messenger RNAs (mRNAs: CCDC88A, ARF6, Vav3, and WASF2) and five small nucleolar RNAs (snoRNAs: SNORA14B, SNORA18, SNORA25, SNORA74A, and SNORD22) in serum of patients with pancreatic cancer and control participants for use in the diagnosis of pancreatic cancer. Results were compared with the expression of sialylated Lewis (a) blood group antigen CA19‐9, the standard clinical tumor biomarker. Reverse transcription quantitative real‐time PCR showed that all of the mRNAs and snoRNAs, except CCDC88A, were encapsulated in exosomes and secreted from cultured pancreatic cancer cells, and present in cell culture medium. In a discovery‐stage clinical study involving 27 pancreatic cancer patients and 13 controls, the area under the receiver operating characteristic curve (AUC) of two mRNAs (WASF2 and ARF6) and two snoRNAs (SNORA74A and SNORA25) was > 0.9 for distinguishing pancreatic cancer patients from controls; the AUC of CA19‐9 was 0.897. Comparing serum levels of WASF2, ARF6, SNORA74A, SNORA25, and CA19‐9 revealed that levels of WASF2 were the most highly correlated with the risk of pancreatic cancer. The AUCs of WASF2, ARF6, SNORA74A, and SNORA25 in serum from patients in the early stages of pancreatic cancer (stages 0, I, and IIA) were > 0.9, compared with an AUC of 0.93 for the level of CA19‐9. The results of this study suggest that WASF2, ARF6, SNORA74A, and SNORA25 may be useful tools for the early detection of pancreatic cancer. Monitoring serum levels of WASF2 mRNA may be particularly useful, as it was the most highly correlated with pancreatic cancer risk