Abstract Background: The aim of this study was to evaluate the clinical performance of a newly developed automated immunoassay HISCL SARS-CoV-2 Antigen assay kit designed to detect the nucleocapsid (N) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Methods: The HISCL SARS-CoV-2 Antigen assay kit is composed of automated chemiluminescence detection systems. Western blot analysis confirmed that anti-SARS-CoV antibodies detected SARS-CoV-2 N proteins. The best cut-off index (COI) was determined using human serum samples obtained from coronavirus disease-2019 (COVID-19) patients and patients without COVID-19. To test the clinical performance, 115 samples obtained from 46 patients with COVID-19 and 69 individuals who tested negative for COD-19 using reverse transcription quantitative polymerase chain reaction (RT-qPCR) were used. Results: The HISCL antigen assay kit showed a sensitivity of 95.4 % in the samples with copy numbers of >100, and a sensitivity of 16.6 % in the samples with copy numbers of <99. The kit did not cross-react with other human corona viruses causing seasonal common cold (HCoV 229E, OC43, NL63, and HKU1) and influenza (H1N1, H3N2, and B), and none of the 69 individuals with negative RT-qPCR results were diagnosed as positive. Importantly, 81.8 % of the samples with low virus load (<50 copy numbers) were diagnosed as negative. Thus, use of the HISCL antigen assay kit may reduce overdiagnosis compared with RT-qPCR tests. Conclusion: The rapid and high-throughput HISCL SARS-CoV-2 Antigen assay kit developed in this study can be used as a suitable screening test for infectious COVID-19, and may play a role in controlling the pandemic.
We experienced a patient on continuous ambulatory peritoneal dialysis (CAPD) who showed hypererythropoietinemia (Epo concentration: 86.7 mU/ml, normal range: 8-36 mU/ml), erythrocytosis, high renin concentration (26.5 pg/ml) and chronic hypotension. In this patient the erythrocytosis progressed along with exacerbation of the chronic severe hypotensive state. This patient had systemic circulatory insufficiency as suggested by the fact that he had a fibrous myocardium and an increased anion gap. We hypothesized that circulatory insufficiency due to chronic severe hypotension may lead to the stimulation of the Epo production, due to a decreased oxygen supply to peripheral tissues and/or to the stimulation of the renin angiotensin system even in patients with end-stage renal failure.
Aberrant immune responses to viral pathogens contribute to pathogenesis, but our understanding of pathological immune responses caused by viruses within the human virome, especially at a population scale, remains limited. We analyzed whole-genome sequencing datasets of 6,321 Japanese individuals, including patients with autoimmune diseases (psoriasis vulgaris, rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), pulmonary alveolar proteinosis (PAP) or multiple sclerosis) and coronavirus disease 2019 (COVID-19), or healthy controls. We systematically quantified two constituents of the blood DNA virome, endogenous HHV-6 (eHHV-6) and anellovirus. Participants with eHHV-6B had higher risks of SLE and PAP; the former was validated in All of Us. eHHV-6B-positivity and high SLE disease activity index scores had strong correlations. Genome-wide association study and long-read sequencing mapped the integration of the HHV-6B genome to a locus on chromosome 22q. Epitope mapping and single-cell RNA sequencing revealed distinctive immune induction by eHHV-6B in patients with SLE. In addition, high anellovirus load correlated strongly with SLE, RA and COVID-19 status. Our analyses unveil relationships between the human virome and autoimmune and infectious diseases. Analysis of the blood DNA virome in patients with COVID-19 and autoimmune disease associates endogenous HHV-6 (eHHV-6) and high anellovirus load with increased disease risk, most notably for systemic lupus erythematosus. eHHV-6 carriers show a distinct immune response.
This study reports a novel method for assessment of leukocyte rheological activation with a new designed microchannel array chip to mimic the human microvascular network for microchannel array flow analysis (MCFAN). Study subjects were 79 healthy volunteers and 42 patients with type 2 diabetes mellitus (DM) and 36 patients with acute coronary syndrome (ACS). Using the anticoagulants heparin and ethylene-diamine-tetraacetic acid (EDTA)-2Na which inhibits platelets and leukocytes by chelating Ca2+, we were able to quantify leukocyte rheological activation by the subtraction of passage time of blood treated with both heparin and EDTA-2Na from that of blood treated with heparin only. We confirmed that passage times of whole blood with heparin + EDTA-2Na were always shorter than those of whole blood with only heparin in healthy subjects and patients with DM or ACS under suction pressures of − 30 cmH2O. There was a significant correlation between delta whole blood passage time {(heparin tube) − (EDTA-2Na + heparin)} and serum levels of myeloperoxidase and adhesive leukocyte number, respectively, even in blood from patients with DM or ACS, who suffered from inflammation. In conclusion we have developed a clinically feasible method for assessing leukocyte rheological activation in whole blood in ex vivo.
Abstract Severe mitral annular calcification is frequently encountered in patients with chronic renal failure requiring dialysis. The procedures are described for the implantation of mitral prostheses in two dialysis patients with mitral stenosis who exhibited heavily calcified mitral annuli. In both cases the calcifications extended around the entire mitral annulus as well as the valve leaflets, papillary muscle, atrial wall and ventricular myocardium, making it impossible to secure prosthetic valves to the mitral annuli. Before implantation, the calcification was partially debrided ultrasonically, and an 'atrioventricular channel' created. A mechanical valve with a polyester fabric collar was fixed on the atrial side of the calcified annulus using double sutures and gelatin-resorcin-formol glue. Perivalvular leakage, obstruction of valve opening or tortuous movements of prosthetic valve ring were not observed, and neither patient developed heart failure after surgery. This technique represents a potentially useful approach in the surgical treatment of patients with severely calcified mitral annuli.
We report 4 cases of cystic renal cell carcinoma (RCC), one of simple cystic type (case 2) and three of multilocular cystic type (case 1, 3 and 4). All cases were diagnosed preoperatively as malignant neoplasms on the basis of radiological examinations, including CT scan and angiography. Pathological examination revealed that intrinsic cystic growth was the probable cause in the three cases of multilocular cystic RCC, while the simple cystic case was probably caused by secondary cyst formation as a result of tumor necrosis. Radical nephrectomy was performed in cases 1, 2 and 4 and partial nephrectomy in case 3. We recommend nephron-sparing surgery as an option in the management of select cystic RCC, given that many cystic RCCs are low grade and enveloped by distinct pseudocapsules with fibrous tissues.
Background Although lung ultrasound has been reported to be a portable, cost-effective, and accurate method to detect pneumonia, it has not been widely used because of the difficulty in its interpretation. Here, we aimed to investigate the effectiveness of a novel artificial intelligence-based automated pneumonia detection method using point-of-care lung ultrasound (AI-POCUS) for the coronavirus disease 2019 (COVID-19). Methods We enrolled consecutive patients admitted with COVID-19 who underwent computed tomography (CT) in August and September 2021. A 12-zone AI-POCUS was performed by a novice observer using a pocket-size device within 24 h of the CT scan. Fifteen control subjects were also scanned. Additionally, the accuracy of the simplified 8-zone scan excluding the dorsal chest, was assessed. More than three B-lines detected in one lung zone were considered zone-level positive, and the presence of positive AI-POCUS in any lung zone was considered patient-level positive. The sample size calculation was not performed given the retrospective all-comer nature of the study. Results A total of 577 lung zones from 56 subjects (59.4 ± 14.8 years, 23% female) were evaluated using AI-POCUS. The mean number of days from disease onset was 9, and 14% of patients were under mechanical ventilation. The CT-validated pneumonia was seen in 71.4% of patients at total 577 lung zones (53.3%). The 12-zone AI-POCUS for detecting CT-validated pneumonia in the patient-level showed the accuracy of 94.5% (85.1%– 98.1%), sensitivity of 92.3% (79.7%– 97.3%), specificity of 100% (80.6%– 100%), positive predictive value of 95.0% (89.6% - 97.7%), and Kappa of 0.33 (0.27–0.40). When simplified with 8-zone scan, the accuracy, sensitivity, and sensitivity were 83.9% (72.2%– 91.3%), 77.5% (62.5%– 87.7%), and 100% (80.6%– 100%), respectively. The zone-level accuracy, sensitivity, and specificity of AI-POCUS were 65.3% (61.4%– 69.1%), 37.2% (32.0%– 42.7%), and 97.8% (95.2%– 99.0%), respectively. Interpretation AI-POCUS using the novel pocket-size ultrasound system showed excellent agreement with CT-validated COVID-19 pneumonia, even when used by a novice observer.
