Identification of a compound heterozygous inactivating ABCC8 gene mutation responsible for young‐onset diabetes with exome sequencing

Activating mutations in the ABCC8 gene cause diabetes and inactivating mutations usually cause hyperinsulinemic hypoglycemia in infancy. Patients with hypoglycemia in infancy due to a heterozygous inactivating mutation have been reported to occasionally progress to diabetes later in life. We explored the gene responsible for diabetes in two brothers, who were suspected to have diabetes at 15 and 18 years‐of‐age, respectively, with whole exome sequencing, and identified a compound heterozygous ABCC8 gene mutation (p.Arg168Cys and p.Arg1421Cys). Although their father and mother were heterozygous carriers of the p.Arg168Cys and the p.Arg1421Cys mutation, respectively, neither parent had diabetes. These mutations have been reported to be responsible for hypoglycemia in infancy and function as an inactivating mutation. Our results suggest that the inactivating ABCC8 gene mutation is also important in the etiology of diabetes.     

Percentage of residual B cells after 2 weeks of rituximab treatment predicts the improvement of systemic sclerosis-associated interstitial lung disease

The benefit of rituximab (RTX) for systemic sclerosis-associated interstitial lung disease (SSc-ILD) has been shown in previous clinical trials. However, predictors of RTX efficacy have not been clarified. We investigated whether B-cell responsiveness to RTX is related to therapeutic effect. Ten SSc-ILD patients treated with RTX in an independent clinical trial (Japan Registry of Clinical Trials, jRCTs031180373) were included in this analysis. Peripheral B-cell counts were examined retrospectively before RTX administration (baseline) and at 2, 4, 12, and 24 weeks after the first RTX administration, along with percent-predicted forced vital capacity (%FVC) before and 24 weeks after RTX treatment. Relative to baseline, the percentage of residual peripheral blood B cells at 2 weeks after RTX was negatively correlated with the %FVC improvement at the 24-week assessment (r = ?0.41, p = 0.04). In the subgroup with less than 5% B-cell persistence at week 2, %FVC at the 24-week assessment was significantly improved compared to baseline (p = 0.02). In another subgroup with more than 5% residual B cells, %FVC was not significantly different after 24 weeks compared to baseline (p = 0.41). In conclusion, the removal rate of B cells after 2 weeks of RTX treatment may be a useful surrogate marker of subsequent SSc-ILD improvement.     

Successful Treatment of Necrotizing Retinitis with Epstein–Barr Virus-Positive Ocular Fluid by Intravitreal Methotrexate Injection

ABSTRACT

Purpose

To present a case of necrotizing retinitis with Epstein–Barr virus (EBV)-positive ocular fluid in a patient with sudden unilateral vision loss, which was successfully treated with intravitreal methotrexate (MTX) injections.     

Comprehensive Tool to Assess Oral Feeding Support for Functional Recovery in Post-acute Rehabilitation

Objective

To determine the influence of the Kuchi-kara Taberu (KT) index on rehabilitation outcomes during hospitalized convalescent rehabilitation.

Prognostic Significance of Complications after Curative Surgery for Gastric Cancer

Background

Postoperative complications such as anastomotic leakage were reported to be a major independent prognostic factor for long-term survival in gastrointestinal malignancies. This study sought to clarify the prognostic significance of postoperative inflammatory complications specifically for patients with gastric cancer.

Methods

This study included 1,395 patients who underwent curative resection for gastric cancer from 2005 to 2008. Complications were evaluated according to the Clavien-Dindo classification. Overall survival (OS) and disease-specific mortality (DSM) were compared between complication and no-complication groups. Presence of complications was modeled by the Cox proportional hazard model for OS and the Fine and Gray competing risk regression model for DSM to assess the correlation between complication and prognosis.

Results

The median follow-up time was 3.1 years. Two hundred seven patients (14.8 %) had complications of grade 2 or higher. Of 131 patients who died within this period, 87 died of gastric cancer. The 3-year OS in the complication group was 84.1 % compared to 93.1 % in the no-complication group (P < 0.0001). The cumulative incidence of DSM was also significantly worse in patients with complications (P < 0.0001). Multivariate analysis identified the same significant increasing risk of complication for both OS (hazard ratio 1.88; 95 % confidence interval 1.26–2.80) and DSM (hazard ratio 1.90; 95 % confidence interval 1.19–3.02).

Conclusions

Postoperative complications that can cause prolonged inflammation have an obvious impact not only on the OS but also on the DSM of patients with gastric cancer even if the tumor is resected curatively.     

TRPV2 Promotes Cell Migration and Invasion in Gastric Cancer via the Transforming Growth Factor-β Signaling Pathway

Annals of Surgical Oncology - Transient receptor potential vanilloid 2 (TRPV2) is a highly Ca2+-permeable ion channel that is involved in a number of cellular processes. It is expressed in various...     

Clinically mild encephalitis/encephalopathy with a reversible splenial lesion associated with febrile urinary tract infection

Common pathogens of clinically mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) are viruses, such as influenza virus. However, bacteria are rare pathogens for MERS. We report the first patient with MERS associated with febrile urinary tract infection. A 16-year-old lupus patient was admitted to our hospital. She had fever, headache, vomiting, and right back pain. Urinary analysis showed leukocyturia, and urinary culture identified Klebsiella pneumoniae. Cerebrospinal fluid examination and brain single-photon emission computed tomography showed no abnormalities. Therefore, she was diagnosed with febrile urinary tract infection. For further examinations, 99mTc-dimercaptosuccinic acid renal scintigraphy showed right cortical defects, and a voiding cystourethrogram demonstrated right vesicoureteral reflux (grade II). Therefore, she was diagnosed with right pyelonephritis. Although treatment with antibiotics administered intravenously improved the fever, laboratory findings, and right back pain, she had prolonged headaches, nausea, and vomiting. T2-weighted, diffusion-weighted, and fluid attenuated inversion recovery images in brain magnetic resonance imaging showed high intensity lesions in the splenium of the corpus callosum, which completely disappeared 1 week later. These results were compatible with MERS. To the best of our knowledge, our patient is the first patient who showed clinical features of MERS associated with febrile urinary tract infection. Conclusion: In patients with pyelonephritis and an atypical clinical course, such as prolonged headache, nausea, vomiting, and neurological disorders, the possibility of MERS should be considered.     

Diabetes is a predictor of coronary artery stenosis in patients hospitalized with heart failure

In patients with heart failure, coronary artery disease is the most common underlying heart disease, and is associated with increased mortality. However, estimating the presence or absence of coronary artery disease in patients with heart failure is sometimes difficult without coronary imaging. We reviewed 155 consecutive patients hospitalized with heart failure who underwent coronary angiography. The patients were divided into two groups: patients with (N = 59) and without (N = 96) coronary artery stenosis. The clinical characteristics and blood sampling data were compared between the two groups. The patients with coronary artery stenosis were older than those without. The prevalence of diabetes mellitus (DM), dyslipidemia and a history of revascularization was higher in the patients with coronary artery stenosis. Patients with coronary artery stenosis tended to have wall motion asynergy more frequently than those without. On the other hand, the prevalence of atrial fibrillation (AF) was lower in patients with coronary artery stenosis. The serum hemoglobin level and estimated glomerular filtration rate were lower in patients with coronary artery stenosis than in those without. In the multivariate analysis, DM (odds ratio 3.517, 95 % CI 1.601–7.727) was found to be the only the predictor of the presence of coronary artery stenosis in patients with heart failure. In conclusion, coronary imaging is strongly recommended for heart failure patients with DM to confirm the presence of coronary artery stenosis.