Background and Aim
Liver function can be improved in patients with chronic hepatitis C virus (HCV) infection who achieved sustained virologic response (SVR) with direct-acting antiviral (DAA) ...treatment. However, to our knowledge, the impact of liver function improvement after SVR on prognosis has not been investigated.
Methods
A total of 716 patients with chronic HCV infection and compensated advanced liver fibrosis who began receiving DAA treatment between September 2014 and August 2018 in 25 Japanese hospitals and achieved SVR were enrolled.
Results
The median age was 73 years, and 336 (47%) and 380 (53%) patients had albumin-bilirubin (ALBI) grade 1 and grade 2, respectively. Improvement to ALBI grade 1 at 1 year after the end of treatment (EOT) was observed in 76% of the patients with baseline ALBI grade 2. Among 380 patients with baseline ALBI grade 2, alanine aminotransferase (ALT) levels ≥ 40 U/L (
p
< 0.001) and modified ALBI (mALBI) grade 2a (
p
< 0.001) were significantly associated with improvement to ALBI grade 1 at 1 year after EOT in multivariate analysis. During the median observation period of 51.8 months, 4 and 10 patients with baseline ALBI grade 1 and 2, respectively, died. In patients with baseline ALBI grade 2, only the absence of improvement to ALBI grade 1 at 1 year after EOT was significantly associated with all-cause mortality in univariate analysis.
Conclusions
Baseline ALT levels and mALBI grade were significantly associated with improvement in liver function after SVR. Patients whose liver function improved after SVR could have better prognosis.
We assessed the impact of 24 months of treatment with ipragliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, on endothelial function in patients with type 2 diabetes as a sub-analysis of ...the PROTECT study.
In the PROTECT study, patients were randomized to receive either standard antihyperglycemic treatment (control group, n = 241 ) or add-on ipragliflozin treatment (ipragliflozin group, n = 241) in a 1:1 ratio. Among the 482 patients in the PROTECT study, flow-mediated vasodilation (FMD) was assessed in 32 patients in the control group and 26 patients in the ipragliflozin group before and after 24 months of treatment.
HbA1c levels significantly decreased after 24 months of treatment compared to the baseline value in the ipragliflozin group, but not in the control group. However, there was no significant difference between the changes in HbA1c levels in the two groups (7.4 ± 0.8% vs. 7.0 ± 0.9% in the ipragliflozin group and 7.4 ± 0.7% vs. 7.3 ± 0.7% in the control group; P = 0.08). There was no significant difference between FMD values at baseline and after 24 months in both groups (5.2 ± 2.6% vs. 5.2 ± 2.6%, P = 0.98 in the ipragliflozin group; 5.4 ± 2.9% vs. 5.0 ± 3.2%, P = 0.34 in the control group). There was no significant difference in the estimated percentage change in FMD between the two groups (P = 0.77).
Over a 24-month period, the addition of ipragliflozin to standard therapy in patients with type 2 diabetes did not change endothelial function assessed by FMD in the brachial artery.
Registration Number for Clinical Trial: jRCT1071220089 ( https://jrct.niph.go.jp/en-latest-detail/jRCT1071220089 ).
To clarify the effect of setting organic photovoltaic (OPV) panels on tomato fruit production, we examined the yield, fruit quality, plant growth, and photosynthetic characteristics of tomatoes in ...greenhouses with OPV (OPV greenhouse) and without OPV (control greenhouse) during fall-winter and spring-summer cultivations. We installed 86 and 106 OPV panels on the OPV greenhouse for fall-winter and spring-summer cultivations, respectively. During both cultivations, solar radiation inside the OPV greenhouse decreased compared with the control greenhouse. Although there was no significant difference in yield between the control and OPV greenhouses in both cultivations, fruit dry matter weight in the OPV greenhouse was 23% lower than in the control greenhouse in the fall-winter cultivation with lower solar radiation. We also investigated plant growth and photosynthesis-related traits in both greenhouses during fall-winter and spring-summer cultivations. The results showed that photosynthesis-related traits decreased in the OPV greenhouse for both cultivations, whereas plant growth decreased significantly during fall-winter cultivation compared with spring-summer cultivation as with the fruit dry matter weight. These results indicate that OPV panels reduced the fruit dry matter weight and plant growth in periods of low solar radiation, suggesting that solar sharing in tomato cultivation is effective when solar cells are removed during periods of low solar radiation and installed during periods of high solar radiation.
Cyclic AMP responsive element (CRE)‐binding protein (CREB) is known to activate transcription when its Ser133 is phosphorylated. Two independent investigations have suggested the presence of ...Ser133‐independent activation. One study identified a kinase, salt‐inducible kinase (SIK), which repressed CREB; the other isolated a novel CREB‐specific coactivator, transducer of regulated CREB activity (TORC), which upregulated CREB activity. These two opposing signals are connected by the fact that SIK phosphorylates TORC and induces its nuclear export. Because LKB1 has been reported to be an upstream kinase of SIK, we used LKB1‐defective HeLa cells to further elucidate TORC‐dependent CREB activation. In the absence of LKB1, SIK was unable to phosphorylate TORC, which led to constitutive activation of CRE activity. Overexpression of LKB1 in HeLa cells improved the CRE‐dependent transcription in a regulated manner. The inactivation of kinase cascades by 10 nm staurosporine in LKB1‐positive HEK293 cells also induced unregulated, constitutively activated, CRE activity. Treatment with staurosporine completely inhibited SIK kinase activity without any significant effect on the phosphorylation level at the LKB1‐phosphorylatable site in SIK or the activity of AMPK, another target of LKB1. Constitutive activation of CREB in LKB1‐defective cells or in staurosporine‐treated cells was not accompanied by CREB phosphorylation at Ser133. The results suggest that LKB1 and its downstream SIK play an important role in silencing CREB activity via the phosphorylation of TORC, and such silencing may be indispensable for the regulated activation of CREB.
Abstract Objectives To efficiently detect somatic UBA1 variants and establish a clinical scoring system predicting patients with pathogenic variants in VEXAS (vacuoles, E1 enzyme, X-linked, ...autoinflammatory, somatic) syndrome. Methods Eighty-nine Japanese patients with clinically suspected VEXAS syndrome were recruited 81 males and 8 females; median age of onset 69.3 years (interquartile range 62.1–77.6). Peptide nucleic acid–clamping PCR (PNA-PCR), regular PCR targeting exon 3 clustering UBA1 variants and subsequent Sanger sequencing were conducted for variant screening. Partitioning digital PCR or targeted amplicon deep sequencing was also performed to evaluate the variant allele frequency (VAF). We developed our clinical scoring system to predict UBA1 variant-positive and -negative patients and assessed the diagnostic value of our system using receiver operating characteristics (ROC) curve analysis. Results Forty patients (44.9%) with reported pathogenic UBA1 variants were identified, including a case having a variant with VAF of 1.7%, using a highly sensitive method. Our clinical scoring system considering age >50 years, cutaneous lesions, lung involvement, chondritis and macrocytic anaemia efficiently predicted patients with UBA1 variants (the area under the curve for the scoring total was 0.908). Conclusion Genetic screening with the combination of regular PCR and PNA-PCR detected somatic UBA1 variants with high sensitivity and specificity. Our scoring system could efficiently predict patients with UBA1 variants.
The Japanese Dermatological Association prepared guidelines focused on the treatment of skin ulcers associated with connective tissue disease/vasculitis practical in clinical settings of ...dermatological care. Skin ulcers associated with connective tissue diseases or vasculitis occur on the background of a wide variety of diseases including, typically, systemic sclerosis but also systemic lupus erythematosus (SLE), dermatomyositis, rheumatoid arthritis (RA), various vasculitides and antiphospholipid antibody syndrome (APS). Therefore, in preparing the present guidelines, we considered diagnostic/therapeutic approaches appropriate for each of these disorders to be necessary and developed algorithms and clinical questions for systemic sclerosis, SLE, dermatomyositis, RA, vasculitis and APS.
Here we report that the lifespan of mice cloned from somatic cells is significantly shorter than that of genotype- and sex-matched controls, most likely due to severe pneumonia and hepatic failure. ...This finding demonstrates the possibility of long-term deleterious effects of somatic-cell cloning, even after normal birth.
An association between Hymenoptera (bee and wasp) stings and nephrotic syndrome has been rarely reported. We report a case of nephrotic syndrome after multiple Hymenoptera stings, and membranous ...nephropathy was later diagnosed by a kidney biopsy. The patient was a 79-year-old woman who was stung by Hymenoptera at seven sites on her body. A weight gain of 3.7 kg was observed in the patient at 1 week after being stung, and she had considerable edema in both lower extremities. A urine protein concentration of 14.8 g/g creatinine and a serum albumin concentration of 1.7 g/dL led to the diagnosis of nephrotic syndrome. A percutaneous kidney biopsy 8 days after the Hymenoptera stings showed stage I membranous nephropathy. She was in complete remission 1 week after the administration of oral prednisolone 40 mg/day, which was started 14 days after Hymenoptera stings, and had no relapse of nephrotic syndrome. To the best of our knowledge, this is the first report of biopsy-proven membranous nephropathy caused by Hymenoptera stings.
Osteoporosis and compression fractures of the lumbar spine are some of the major adverse effects of glucocorticoid therapy in patients with systemic lupus erythematosus (SLE). This study examined the ...association between bone mineral density, bone turnover markers, presence of vertebral fractures, and Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index in SLE patients.
This was a cross-sectional study of 246 outpatients with SLE at the Kyoto University Hospital. Lumbar and femoral bone mineral density was measured with dual-energy X-ray absorptiometry, and the presence of vertebral fractures was determined using X-ray, computed tomography, or magnetic resonance imaging.
On multiple regression analysis, both high lumbar and femoral T-scores were associated with the concomitant use of hydroxychloroquine (P = .018 and P = .037, respectively), no use of bisphosphonate or denosumab (P = .004 and P = .038, respectively), high body mass index (P < .001), and low bone-specific alkaline phosphatase level (P = .014 and P = .002, respectively). Vertebral fractures showed a significant association with Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index score (P < .001) and femoral T-score (P < .001).
Vertebral fracture was associated with SLE-associated organ damage, and serum bone-specific alkaline phosphatase level is a potentially useful marker for osteoporosis monitoring in SLE patients.
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