Combined landscape of single-nucleotide variants and copy number alterations in clonal hematopoiesis

クローン性造血の臨床予後への影響を解明 --遺伝子変異とコピー数異常の統合的な知見--. 京都大学プレスリリース. 2021-07-09.Clonal hematopoiesis (CH) in apparently healthy individuals is implicated in the development of hematological malignancies (HM) and cardiovascular diseases. Previous studies of CH analyzed either single-nucleotide variants and indels (SNVs/indels) or copy number alterations (CNAs), but not both. Here, using a combination of targeted sequencing of 23 CH-related genes and array-based CNA detection of blood-derived DNA, we have delineated the landscape of CH-related SNVs/indels and CNAs in 11, 234 individuals without HM from the BioBank Japan cohort, including 672 individuals with subsequent HM development, and studied the effects of these somatic alterations on mortality from HM and cardiovascular disease, as well as on hematological and cardiovascular phenotypes. The total number of both types of CH-related lesions and their clone size positively correlated with blood count abnormalities and mortality from HM. CH-related SNVs/indels and CNAs exhibited statistically significant co-occurrence in the same individuals. In particular, co-occurrence of SNVs/indels and CNAs affecting DNMT3A, TET2, JAK2 and TP53 resulted in biallelic alterations of these genes and was associated with higher HM mortality. Co-occurrence of SNVs/indels and CNAs also modulated risks for cardiovascular mortality. These findings highlight the importance of detecting both SNVs/indels and CNAs in the evaluation of CH

metachronous gastric cancer and H. pylori eradication

Background: Although the relationship between H.pylori infection and gastric cancer has been proved in epidemiological studies and animal experiments, prophylactic effect of H. pylori eradication is controversial in human studies. Methods: We conducted a large-scale, multi-center, randomized controlled open-labeled study to determine whether eradication of H. pylori had inhibitory effects on the development of metachronous gastric carcinomas after endoscopic resection. The study included 542 subjects including patients diagnosed with early gastric cancer, either newly diagnosed and planning to have endoscopic treatment; or in the post-resection follow-up phase after endoscopic treatment. They were randomly allocated to eradication and control arms and examined endoscopically at 6, 12, 24, and 36 months after allocation. Diagnosis of new carcinoma at another site of stomach was defined as primary endpoint. Metachronous cancers were confirmed through histological examination. Results Between eradication and control groups, there were no significant differences in baseline characteristics. Overall successful eradication rate was 79.6%. During follow-up of three years, metachronous gastric cancer developed in 33 cases, including 9 in the eradication group and 24 in the control group. The incidence of metachronous gastric cancer in eradication group was significantly lower than in control group both in the analysis ignoring observation period (Odds ratio: 0.353, 95% CI: 0.161-0.775, p=0.009) and in the analysis considering it (Hazard ratio: 0.34, 95% CI: 0.16-0.70, p=0.003). Kaplan–Meier analysis revealed that the cumulative incidence of gastric cancer was different between the two groups. Conclusions: This study showed that the eradication of H. pylori is indicated to prevent development of metachronous gastric cancers after endoscopic resection

Development of serological assays to identify Helicobacter suis and H. pylori infections

Summary: Helicobacter suis, hosted by hogs, is the most prevalent gastric non-Helicobacter pylori Helicobacter species found in humans. Recent studies have suggested that H. suis infection has caused many cases of gastric disease, but the transmission route from hogs remains unclear. Diagnostic methods based on H. suis urease activity often yield negative results, and there is no reliable method for diagnosing H. suis infection in clinical practice without gastric biopsy specimens. This study presents the world’s first use of whole-bacterial cell ELISA to simultaneously assess H. suis and H. pylori infections. The ELISAs showed high accuracy, with an area under the ROC curve of 0.96, 100% sensitivity, 92.6% specificity, 76.9% positive predictive value, and 100% negative predictive value for the H. suis test, and an area under the ROC curve of 0.92, 88.2% sensitivity, 87.5% specificity, 65.2% positive predictive value, and 96.6% negative predictive value for the H. pylori test

Serological and Progression Differences of Joint Destruction in the Wrist and the Feet in Rheumatoid Arthritis - A Cross-Sectional Cohort Study - Fig 2

<p>(A) Comparison of joint destruction of the wrist and the feet in the duration of the disease. Larsen grade of the feet was significantly higher than that of the wrist in the first subgroup (p<0.001). (B) Comparison of difference of the joint destruction between the wrist and the feet in Larsen grade. <i>P</i> < 0.001.</p

Serological and Progression Differences of Joint Destruction in the Wrist and the Feet in Rheumatoid Arthritis - A Cross-Sectional Cohort Study

<div><p>Objective</p><p>To investigate clinical and radiological differences between joint destruction in the wrist and the feet in patients with RA.</p><p>Methods</p><p>A cross-sectional clinical study was conducted in an RA cohort at a single institution. Clinical data included age, sex and duration of disease. Laboratory data included sero-positivity for anti-cyclic citrullinated peptide (CCP) antibody and RF. Radiological measurements included Larsen grades and the modified Sharp/van der Heijde method (SHS) for the hands/wrists and the feet. Statistical analyses were performed using the Kruskal—Wallis H-test, a dummy variable linear regression model and multivariate logistic regression analysis with 95% confidence interval and odds ratios.</p><p>Results</p><p>A total of 405 patients were enrolled, and 314 patients were analysed in this study. The duration of disease in the foot-dominant group was significantly less than that in the wrist-dominant group. When patients were subdivided by duration of disease, the Larsen grade of the feet was significantly higher than that of the wrist in the first quadrant subgroup, but this was reversed with increasing duration of disease. Anti-CCP status was a significant predictive factor for joint destruction in the wrist but not in the feet, while RF status was not predictive in either the wrist or the feet.</p><p>Conclusions</p><p>Joint destruction in the feet started earlier than in the wrist, but the latter progresses faster with increasing duration of disease. Anti-CCP status predicts joint destruction in the wrist better than in the feet.</p></div