TP53 variants in p53 signatures and the clonality of STICs in RRSO samples

ObjectivePrecursor lesions may be identified in fallopian tube tissue after risk-reducing salpingo-oophorectomy (RRSO) in patients with pathogenic variants of BRCA1/2. Serous tubal intraepithelial carcinoma (STIC) is considered a precursor of high-grade serous carcinoma, whereas the significance of the p53 signature remains unclear. In this study, we investigated the relationship between the p53 signature and the risk of ovarian cancer.MethodsWe analyzed the clinicopathological findings and conducted DNA sequencing for TP53 variants of p53 signatures and STIC lesions isolated using laser capture microdissection in 13 patients with pathogenic variants of BRCA1/2 who underwent RRSO and 17 control patients with the benign gynecologic disease.Results TP53 pathogenic variants were detected significantly higher in RRSO group than control (p<0.001). No difference in the frequency of p53 signatures were observed between groups (53.8% vs 29.4%; p=0.17). TP53 sequencing and next-generation sequencing analysis in a patient with STIC and occult cancer revealed 2 TP53 mutations causing different p53 staining for STICs and another TP53 mutation shared between STIC and occult cancer.ConclusionThe sequence analysis for TP53 revealed 2 types of p53 signatures, one with a risk of progression to STIC and ovarian cancer with pathological variants in TP53 and the other with a low risk of progression without pathological variants in TP53 as seen in control.     

Reduction in the magnitude of serum potassium elevation in combination therapy with esaxerenone (CS‐3150) and sodium–glucose cotransporter 2 inhibitor in patients with diabetic kidney disease: Subanalysis of two phase III studies

Aims/IntroductionWe evaluated the effect of co‐administration of esaxerenone and a sodium–glucose cotransporter 2 (SGLT2) inhibitor on the magnitude of serum potassium elevation in Japanese patients with diabetic kidney disease.Materials and MethodsWe carried out a prespecified subanalysis of data from two phase III studies: a multicenter, randomized, double‐blind, placebo‐controlled trial in patients with type 2 diabetes and microalbuminuria (J308); and a multicenter, single‐arm, open‐label trial in patients with type 2 diabetes and macroalbuminuria (J309). Changes in serum potassium levels during the studies and other measures were evaluated according to SGLT2 inhibitor use.ResultsIn both studies, time‐course changes in serum potassium levels, and incidence rates of serum potassium elevation were lower in patients with co‐administration of SGLT2 inhibitor in both the placebo and esaxerenone groups than those without the inhibitor. In contrast, time‐course changes and mean percentage changes from baseline in urinary albumin‐to‐creatinine ratio, the proportion of patients with albuminuria remission and time‐course changes in blood pressure did not change with or without SGLT2 inhibitor, whereas the albumin‐to‐creatinine ratio and blood pressure were reduced with esaxerenone. The blood glucose‐lowering effect of SGLT2 inhibitor was not affected by esaxerenone.ConclusionsIn Japanese patients with type 2 diabetes and albuminuria treated with esaxerenone, concomitant use of SGLT2 inhibitor reduced the magnitude of serum potassium elevation without any change of its antihypertensive and albuminuria‐suppressing effects. Co‐administration of esaxerenone and SGLT2 inhibitor might be a beneficial treatment option for patients with diabetic kidney disease.     

Repeated Necrotizing Lymphadenitis with MEFV Gene Mutations

We herein report a 36-year-old man with repeated necrotizing lymphadenitis due to MEFV gene mutations. The patient''s chief complaints were a fever and painful cervical lymphadenopathy. We diagnosed him with necrotizing lymphadenitis based on the pathological findings of the lymph nodes and the exclusion of other differential diseases. The same episode recurred four times. We speculated the involvement of autoinflammatory backgrounds and detected MEFV gene mutations of E148Q (homo), P369S, and R408Q. Considering the elevation of interleukin-18, these mutations probably played roles in the repeated necrotizing lymphadenitis.     

Detection of in-stent restenosis of coronary stents using 40-detector row computed tomography in vitro

OBJECTIVE: To evaluate the performance of 40-detector row computed tomography (CT) in the detection of in-stent stenosis of coronary stents. METHODS: Seven patent vascular models, 7 stenotic models, and 7 obstructed models were scanned with a 40-detector CT. We made the vascular models using 3 types of stent (Bx-Velocity, Express2, Driver) with an inner diameter of about 2.5, 3.0, or 3.5 mm. We measured the stent lumen diameter and evaluated the in-stent stenosis visually for the 21 vascular models. We evaluated attenuation values of the stent lumen of the 9 patent models of 2.5-mm diameter. RESULTS: The inner diameters of the vascular models were underestimated by CT with mean measurement errors of -1.19 to -1.49 mm. The absolute mean overall measurement error decreased as the inner diameter increased. The direct visualization of in-stent stenosis was possible for the 3.0- and 3.5-mm diameter models, but impossible for the 2.5-mm diameter models. For patent vascular models of 2.5-mm diameter, the CT attenuation inside the stent was significantly higher than that of the unstented portion (P < 0.0001). For obstructed vascular models of 2.5-mm diameter, the CT attenuation inside the stent was significantly lower than that of the unstented portion (P < 0.0001). Also for stenotic vascular models of 2.5-mm diameter, the CT attenuation inside the stent was lower than that of the unstented portion. CONCLUSIONS: Visualization of stent lumen on CT is affected by the stent diameter. Measurement of stent lumen is useful for detection of in-stent stenosis, when the direct visualization of in-stent stenosis is impossible.     

Occupational Factors and Problem Drinking among a Japanese Working Population

Problem drinking is a serious public health problem in the workplace. However, few Japanese epidemiological studies have investigated the occupational characteristics of problem drinking. The purpose of this study is to clarify the occupational risk factors for problem drinking among a Japanese working population. We used data from a random-sampling survey about mental health and suicide, conducted among Hamamatsu City residents aged 15 to 79 yr old during May and June in 2008. The relation between occupational factors and problem drinking was analyzed with multiple logistic regression models stratified by gender. CAGE questionnaire was used to assess problem drinking. With regard to employment types, problem drinkers were more prevalent among self-employed women. With regard to occupational types, clerical and service professions had more problem drinkers of either sex, while administrative/managerial and sales professions had more women with such problem. With regard to company size, male problem drinkers were more prevalent in smaller companies than in larger ones. These results indicate that the prevalence of problem drinkers in the workplace depends on where one works. It is necessary to consider these characteristics to provide effective measures to address problem drinking in the workplace.     

A Novel Approach to Detecting Postpartum Hemorrhage Using Contrast-Enhanced Ultrasound

The aim of this study was to estimate the efficacy of contrast-enhanced ultrasound (CEUS) in detecting postpartum hemorrhage (PPH) after cesarean section. This is the first study of CEUS in obstetric hemorrhage. A total of 37 patients, operated at Nagoya University Hospital, underwent CEUS. We evaluated the findings of CEUS, which were qualitatively defined as positive when pooling or leakage of contrast agent was observed in the uterine cavity, by measuring the amount of bleeding during the first 4 h after cesarean section. The time–intensity curve patterns of leaked contrast agents were also analyzed for quantitative prediction of the amount of blood loss. Significant differences between the excessive hemorrhage (N = 7) and non-excessive hemorrhage groups (N = 30) were noted in the occurrence of positive CEUS (p = 0.011). Additionally, mean postpartum blood loss markedly increased in patients with a positive CEUS (p = 0.002). From a quantitative perspective, the time until leakage of contrast agents was detected correlated with the amount of bleeding, but the other characteristics of the time–intensity curve pattern did not provide valuable information. In conclusion, CEUS, which enables bedside assessment and rapid diagnosis, is a promising strategy for the detection of PPH.