Orthogonal antibody testing for COVID-19 among healthcare workers in a non-epidemic place and time: Japan’s Iwate Prefecture,May 18-31, 2020

Of the 47 prefectures in Japan, Iwate had the fewest cases of coronavirus disease 2019 (COVID-19), with the first diagnosis officially confirmed on July 28, 2020. A baseline serological survey of COVID-19 antibodies is essential to accurately evaluate an epidemic outbreak. The primary purpose of this study was to determine pre-epidemic prevalence of COVID-19 antibodies among healthcare workers, using two laboratory-based quantitative tests. In addition, a point-of-care (POC) qualitative test, rapid, simple, and convenient for primary care clinics, was compared with the laboratory-based tests. All antibody tests were performed on serum from 1,000 healthcare workers (mean age, 40 ± 11 years) in Iwate Prefectural Central Hospital, May 29-31, 2020. A COVID-19 case was defined as showing positive results in both laboratory-based quantitative tests. None of 1,000 samples had positive results in both of the laboratory immunoassays. The POC test showed positive results in 33 of 1,000 samples (3.3%) (95% confidence interval: 2.19-4.41), but no samples were simultaneously positive in both laboratory-based tests. In conclusion, COVID-19 cases were not serologically confirmed by a baseline control study of healthcare workers at our hospital in late May, 2020. Moreover, the POC qualitative test may offer no advantage in areas with very low prevalence of COVID-19, due to higher false-positive reactions compared with laboratory-based quantitative immunoassays.     

Genotoxicity studies of glycidol fatty acid ester (glycidol linoleate) and glycidol

Glycidol fatty acid esters (GEs) are found in refined edible oils. Safety concerns have been alleged due to the possible release of glycidol (G), an animal carcinogen.     

Disease-associated CIAS1 mutations induce monocyte death, revealing low-level mosaicism in mutation-negative cryopyrin-associated periodic syndrome patients

Cryopyrin-associated periodic syndrome (CAPS) is a spectrum of systemic autoinflammatory disorders in which the majority of patients have mutations in the cold-induced autoinflammatory syndrome (CIAS)1 gene. Despite having indistinguishable clinical features, some patients lack CIAS1 mutations by conventional nucleotide sequencing. We recently reported a CAPS patient with mosaicism of mutant CIAS1, and raised the possibility that CIAS1 mutations were overlooked in "mutation-negative" patients, due to a low frequency of mosaicism. To determine whether there were latent mutant cells in "mutation-negative" patients, we sought to identify mutation-associated biologic phenotypes of patients' monocytes. We found that lipopolysaccharide selectively induced necrosis-like cell death in monocytes bearing CIAS1 mutations. Monocyte death correlated with CIAS1 up-regulation, was dependent on cathepsin B, and was independent of caspase-1. Cell death was intrinsic to CIAS1-mutated monocytes, was not mediated by the inflammatory milieu, and was independent of disease severity or anti-IL-1 therapy. By collecting dying monocytes after lipopolysaccharide treatment, we succeeded in enriching CIAS1-mutant monocytes and identifying low-level CIAS1-mosaicism in 3 of 4 "mutation-negative" CAPS patients. Our findings reveal a novel effect of CIAS1 mutations in promoting necrosis-like cell death, and demonstrate that CIAS1 mosaicism plays an important role in mutation-negative CAPS patients.     

Evaluation of Ki-67 and p53 expression in primary and repeated liver metastases of GISTs

There has been little research evaluating changes related to tumor cell proliferation between primary and metastatic tumors of gastrointestinal tumors in the same case. We herein report the case of a 50-year-old woman with a gastric gastrointestinal stromal tumor (GIST), who developed metastatic liver tumors three times in the 7 years after proximal gastrectomy for GIST. The primary and all the metastatic liver tumors, except the second, showed fascicular/storiform architecture and the short spindle cell type. The diffuse epithelioid cell proliferation was observed in the second metastatic liver tumor. Although the immunostaining pattern with respect to GIST differentiation markers had been preserved in the primary tumor as well as in all of the metastatic tumors, the latter showed weaker positivity of both Ki-67 and p53 than the primary GIST. The primary tumor showed diffuse positive p53, and the highest value of Ki-67 labeling index (LI) among them. The metastatic liver tumors showed focal, negative or sporadic positive appearances of p53, however, Ki-67 LI were scattering among them. Immunohistochemical assessment of Ki-67 LI and p53 might be useful for evaluating changes related to tumor cell proliferation between primary and metastatic tumors of GISTs.     

Correlation of anatomic and hemodynamic features with aortic valve leaflet deformity in doubly committed subarterial ventricular septal defect

Summary The records of 153 patients with doubly committed subarterial ventricular septal defect (DCVSD) who underwent intracardiac repair were analyzed to evaluate factors responsible for aortic valve leaflet deformity. The patients were divided into two groups according to their echocardiographic and angiographic features as well as anatomic findings at operation: DCVSD without (17/153, 11.1%) and with arterial valve offsetting (136/153, 88.9%). Aortic regurgitation (AR) was much more prevalent in the patients with (50.0%) than in those without leaflet deformity (2.2%,P < 0.01). Arterial valve offsetting is one of the major contributing factors to the development of leaflet deformity, accounting for 5.9% in the patients without offsetting and 46.3% in those with offsetting (P < 0.01). Among the patients with arterial valve offsetting, the pulmonary-to-systemic pressure ratio was significantly higher (P < 0.01) in the patients without (0.76 ± 0.14) than in those with leaflet deformity (0.36 ± 0.12), suggesting that pulmonary hypertension might prevent the aortic valve leaflet from prolapsing in DCVSD. In addition, increased severity of aortic valve leaflet deformity and subsequent AR were observed with increasing age. These results suggest that aging and the presence of arterial valve offsetting as well as the absence of pulmonary hypertension might be factors responsible for aortic valve leaflet deformity and subsequent AR in DCVSD. The anatomic and hemodynamic features in DCVSD have a great impact on the development of aortic valve leaflet deformity and subsequent AR.     

Predictive value of microvolt T-wave alternans for sudden cardiac death in patients with preserved cardiac function after acute myocardial infarction: results of a collaborative cohort study.

OBJECTIVES: We conducted a collaborative cohort study to evaluate the predictive power of microvolt T-wave alternans (TWA) in patients with preserved left ventricular ejection fraction (LVEF) after myocardial infarction (MI). BACKGROUND: There is little information available about the prognostic value of risk stratification markers in this population. Although these patients have a relatively good prognosis, identifying high-risk patients is important in clinical practice. METHODS: This study enrolled 1,041 post-MI patients with an LVEF > or =40% (average 55 +/- 10%). Microvolt TWA testing was performed 48 +/- 66 days after acute MI, and 10 other risk variables were also evaluated. The end points were prospectively defined as sudden cardiac death or life-threatening arrhythmic events. RESULTS: During a follow-up of 32 +/- 14 months, 38 patients (3.7%) died of nonarrhythmic causes and were not considered for analysis. Of the 1,003 evaluable patients, 18 (1.8%) reached an end point. Microvolt TWA was positive in 169 patients (17%), negative in 747 (74%), and indeterminate in 87 (9%). A positive microvolt TWA test, nonsustained ventricular tachycardia, and ventricular late potentials were predictors of events, and percutaneous coronary intervention decreased the risk rate. On multivariate analysis, a positive microvolt TWA test was the most significant predictor, with a hazard ratio of 19.7 (p < 0.0001). This marker had the highest sensitivity and negative predictive value for events. CONCLUSIONS: In patients with preserved cardiac function, the incidence of indeterminate results of microvolt TWA is low, and a positive test result is associated with arrhythmic events. Microvolt TWA could be used for risk stratification in this low-risk population.     

Diagnostic accuracy of tumor staging and treatment outcomes in patients with superficial esophageal cancer

Background We examined the current status and diagnostic accuracy of currently available techniques for tumor staging and assessed treatment outcomes in patients with superficial esophageal cancer who received esophaguspreserving therapy, such as endoscopic mucosal resection (EMR) alone or combined with chemoradiotherapy (CRT). Methods In 274 patients with superficial esophageal cancer, we examined the depth of tumor invasion and the degree of lymph node metastasis by means of endoscopy, magnifying endoscopy, endoscopic ultrasonography (EUS), computed tomography (CT), and cervical and abdominal ultrasonography (US). We compared treatment outcomes among treatment groups according to the depth of tumor invasion. Results The rates of correctly diagnosing the depth of tumor invasion were 89.6% on conventional endoscopy, 90.1% on magnifying endoscopy, and 85% on scanning with a high-frequency miniature ultrasonic probe (miniature US probe). Diagnostic accuracy for the m3 or sm1 cancers was poor. Magnifying endoscopy allowed invasion to be more precisely estimated, thereby improving diagnostic accuracy. However, lesions that maintained their surface structure despite deep invasion were misdiagnosed on magnifying endoscopy. A miniature US probe was useful for the assessment of such lesions. The diagnostic accuracy of EUS for lymph node metastasis was 83%, with a sensitivity of 76%. The sensitivity of CT was 29%, and that of cervical and abdominal US was 17%. Patients with m1 or m2 cancer had good outcomes after esophagus-preserving therapy. Although there were no significant differences in survival rates, many patients with sm2 or sm3 cancer who received CRT died of their disease. Nodal recurrence was diagnosed by EUS. In patients who received CRT, the time to the detection of recurrence was slightly prolonged. Conclusions Long-term follow-up at regular intervals is essential in patients with m3 or sm esophageal cancers who receive esophagus-preserving treatment. At present, EUS is the most reliable technique for the diagnosis of lymph node metastasis and is therefore essential for pretreatment evaluation as well as for follow-up. Earlier detection of recurrence at a level that would potentially salvage treatment remains a topic for future research. Review articles on this topic also appeared in the previous issue (Volume 4 Number 3). An editorial related to this article is available at .