Using the MALDI Biotyper (Bruker), we verified the strains identified as Mycobacterium intracellulare by the COBAS TaqMan MAI. We compared the critical threshold (CT) value to evaluate the misidentification by COBAS TaqMan MAI. Furthermore, we reviewed the medical records of patients to analyze the characteristics of the discrepant strains. The discrepant strains identified by the MALDI Biotyper were M. lentiflavum (4/70), M. colombiense (2/70), M. marseillense (1/70), and M. arosiense (1/70). There was a significant difference in the CT value between M. lentiflavum and the other species. As for the virulence, combined treatment with antibiotics was not administered to the patients in whom the strains of M. lentiflavum (2/3) were isolated from sputa. We consider that the virulence of M. lentiflavum is different from that of M. intracellulare commonly causing pulmonary disease; therefore, accurate identification is important. On the other hand, the strains of M. colombiense (2/2) were isolated from skin lesions. Because infection with M. colombiense is very rare, the accumulation of cases is expected. In conclusion, the identification accuracy of the MALDI Biotyper is comparable to that of the molecular diagnostic method, and the MALDI Biotyper is useful for routine diagnostic tests. Moreover, it is considered that the misidentification of M. lentiflavum can be detected by confirming the CT value when COBAS TaqMan MAI identifies M. intracellulare.

Objective: The objective of this study is to standardize cell sampling and specimen processing and to improve the quality of cytologic preparations for oral brushing cytodiagnosis. Cellular specimens collected from an oral lesion by brushing with the Orcellex Brush^RT were processed using the BD CytoRich^TM (CR^TM) system (Becton, Dickinson and Company) with CytoRich^TM RED, a liquid-based cytology system for nongynecological use, to validate the applicability of the combined use of these systems. Methods: Oral brushing cytologic diagnoses made from March 2014 to March 2016 were reviewed. A specimen from each lesion was collected with five rotations of the shaft of the Orcellex Brush^RT, and the tip of the device was placed in a dedicated BD SurePath^TM collection vial. The cell specimen collected from each patient was processed using the CR^TM system for nongynecological use to obtain duplicate preparations, followed by Papanicolaou staining and PAS staining. The prepared slides were examined and scored on a six-grade scale in accordance with the Guidelines for Cytopathological Diagnosis 5 of the Japanese Society of Clinical Cytology (Digestive Organs 2015 edition). Presence/absence of fungal involvement was assessed on the basis of the PAS reaction of the specimens. Results: The specimen adequacy rate in the analysis using the CR^TM system was 99.5% (192/193 specimens). Of the 192 specimens assessed as being adequate, the cytodiagnoses were NILM in 146 specimens (75.6%), OLSIL in 22 specimens (11.4%), OHSIL in 5 specimens (2.6%), SCC in 10 specimens (5.2%), and IFN in 9 specimens (4.7%). One specimen (1/193, 0.5%) was judged as being inadequate, which was considered to be attributable to an excessively low cell yield. As for the PAS reaction, fungal involvement was evident in 21.8% of the specimens (42/193). Conclusion: The combined use of the Orcellex Brush^RT and CR^TM systems increased the quantity of cells collected and the cell yield, which may be expected to contribute to the spread of oral brushing cytology and improved cytodiagnostic assessment.

Anti-phospholipid syndrome (APS) is an autoimmune thrombosis that appears in association with various anti-phospholipid antibodies (aPLs) in a patient’s blood. The presence of aPLs is associated with clinical events, such as arterial and/or venous thrombosis and recurrent fetal loss. Therefore, it is important to simultaneously measure many aPLs of every patient and identify the types of aPL to determine the condition of APS patients appropriately. In the diagnosis of APS, the presence of aPLs is proved by direct detection using enzyme-linked immunosorbent assay (ELISA). However, while ELISA can determine the quantity of aPLs, it is difficult to measure many samples simultaneously. We have established an analytical system that enables the simultaneous measurement of aPLs, namely, the enzyme immunoassay system (aPLs-EIA) using “ACL AcuStar^®”, and examined the clinical usefulness of measuring the aPL concentration with this system. In this study, we established a diagnostic method that can predict thrombotic complications by measuring aPLs in patients with high thrombosis risk. Multivariate logistic regression analysis revealed that the presence of aDomain1-IgG was most closely associated with arterial thromboembolic complications. In contrast, the presence of aβ₂GPI-IgG was most closely related to venous thromboembolic complications. Moreover, ROC analysis revealed that the accuracy of predicting thrombotic complications based on the results of the multiplex EIA system was higher than that based on the results of aCL/β₂GPI-ELISA. Therefore, in the differential diagnosis of APS, it is essential to detect various aPL subclasses simultaneously, which can be done using this new automated EIA system.

Diabetic patients perform self-monitoring of blood glucose (SMBG) for glucose control. SMBG can be carried out in various environments, such as at home or on the road. For that reason, we examined the effects of temperature on five SMBG devices. The temperatures of the SMBG devices and sensors were verified by seven combinations of low temperature, normal temperature and high temperature. As a result, we found that the temperatures of the SMBG devices and sensors are within ISO 15197 tolerance at the same temperature of the environment. But when a temperature difference occurred between the SMBG device and the sensor, the blood glucose level deviated from within ISO 15197 tolerance. When the temperature of the SMBG devices were low and the temperature of the sensors were room temperature, the blood glucose level became abnormally high. Conversely, when the SMBG devices were at a high temperature and the sensor were at room temperature, the blood glucose level was abnormally low. Observation of changes in blood glucose during the process of returning the SMBG device and sensor to room temperature showed that after 5 minutes it was within ISO 15197 tolerance. After 10 minutes, no effect of the temperature was observed. On the basis of the results of this study, we avoid the use of heaters and air conditioners where there is a risk of sudden temperature differences between the SMBG devices and sensors. It was confirmed that it is necessary to acclimate the devices and sensors to room temperature for at least 10 minutes.

We performed basic evaluation studies of the urinary oxalic acid measurement by capillary electrophoresis. This method showed CVs of within-run and between-day precisions of less than 6.0%, and the relative error of dilution linearity was good. The recovery test also showed good results. No effects of hydrochloric acid or ascorbic acid on the urinary oxalic acid measurement were detected. In addition, the correlation of urine samples with high-performance ion chromatography and capillary electrophoresis was good (y = 0.971x + 0.380, r = 0.997, n = 50). This study revealed that this method using capillary electrophoresis is applicable in routine testing.

The purpose of this study was to compare the diagnostic capability of different immunoassay reagents for detecting serum carbohydrate antigen 19-9 (CA19-9). The five reagents used were as follows: Lumipulse Presto CA19-9, CA19-9XR, Elecsys CA19-9 II, HISCLTM CA19-9 Assay Kit, and VITROS Immunodiagnostic Products CA 19-9 Reagent Pack. In terms of repeatability, coefficients of variation (CVs) of 0.5 to 4.3% were confirmed for the reagents, except for the ARCHITECT reagent, which showed a CV of 3.7–21.8%. In the evaluation of CA19-9 correlation with each reagent, the correlation coefficient for comparison between the Cobas reagent and the Vitros reagent was the best, but the measured value of the Vitros reagent tended to be about twice as large as that of the Cobas reagent. Furthermore, from the correlation evaluation near the cutoff value of CA19-9, it was confirmed that the correlation coefficient for the comparison of CA19-9 with the architect reagent was larger than those for the comparison with the other four reagents. It was also confirmed that the correlation coefficient for the comparison of CA19-9 with the HISCL reagent in the immunoassay using a non-NS19-9 antibody was dispersed compared with those for the other four reagents. On the other hand, interestingly, the CA19-9 pancreatic cancer diagnostic capability of all the reagents evaluated using the receiver operating characteristics (ROC) curve was relatively good with an area under the ROC curve of 0.739 or more. Consequently, there was a discrepancy in the correlation coefficient in the comparison between CA19-9 and other reagents depending on the type of reagent, but there was almost no effect of the pancreatic cancer diagnostic capability in terms of CA19-9 values.

Several studies have reported an increased risk of venous thromboembolism (VTE) after a disaster such as an earthquake. We should determine blood D-dimer levels and/or perform an ultrasound testing to screen for VTE. However, automated and high-throughput screening tests would be required when an earthquake would occur and lifelines are stopped. In this study, we evaluated the performance of the waterless autoanalyzer VITROS XT7600 in plasma D-dimer level determination. We used the Nanopia D-dimer as the reagent for VITROS XT7600 and the LiasAuto D-dimer for CS-5100 for comparison. Intra-assay precision showed CVs of 5.0% (low level) and 1.6% (high level). The correlation was excellent (y = 0.7188x + 0.8013, r = 0.9253). VITROS XT7600 required 1 hour and 15 minutes to finish measuring 50 samples. These results suggest that VTE screening using the D-dimer for VITROS XT7600 is useful with high throughput and reliability.

The reagent management system, which is distributed free of charge on the Internet, was developed on the basis of prototypic development and operational experience, aiming at versatility and ease of implementation for the efficient reagent management operations in clinical laboratories. By using the GS1-128 symbol of the barcode written on the reagent package, this system can automatically acquire and record the expiration date and lot information of the reagent necessary for quality control. In addition, according to the setting of the reagent master, the barcode operation can be enabled to record each open date and expiration date by issuing and attaching the control number bar code label to the unit of reagent boxes or the number of individual packages. As a result, the effective inventory management and recording of reagents and the reduction of human error were achieved. This system is distributed free of charge after completion, and the number of downloads and inquiries from the installation facilities strongly supports its necessity and practicability. These results indicate that the development and free distribution of this management system is useful for clinical laboratory operations.

The rapid identification of Streptococcus spp. using Streptococcus-positive blood culture medium is important in patients with sepsis and bloodstream infection (BSI) because these are serious conditions. In this study, we examined whether Streptococcus spp. could be rapidly differentiated by the Lancefield grouping test, pyrrolidonyl arylaminidase (PYR) test, and pneumococcal antigen test using 57 samples of blood culture medium in which Streptococcus was detected. The Lancefield grouping test was performed on 12 isolates from blood culture medium suspected of having β-hemolytic gram-positive Streptococcus. Among the 12 isolates, six were classified into group B, two into group F, and four into group G. These groups B, F, and G were identified as Streptococcus agalactiae, Streptococcus constellatus, and Streptococcus dysgalactiae, respectively, using MALDI Biotyper. Among 45 isolates from the culture medium suspected of having non-β-hemolytic gram-positive Streptococcus, 41 were confirmed to be streptococci by the PYR test and four by the pneumococcal antigen test. Among the 41 isolates that were subjected to the PYR test, 18 were identified as Enterococcus faecalis and 23 as Enterococcus faecium. Similarly, the four isolates that were subjected to the pneumococcal antigen test were identified as Streptococcus pneumoniae. In conclusion, a rapid differentiation of Streptococcus spp. using Streptococcus-positive blood culture medium may be useful for predicting β-hemolytic Streptococcus, S. pneumoniae, and Enterococcus spp. in sepsis and BSI.

The levels of the soluble interleukin-2 receptor in serum are elevated in non-Hodgkin’s lymphoma and adult T-cell leukemia/lymphoma and reflect disease activity, so they are used for the assessment of treatment response, auxiliary diagnosis, and follow-up. Since the reagent “Lumipulse Presto IL-2R” that can be used with Lumipulse L2400 was developed this time, a basic study was carried out to introduce the reagent. Good results were obtained for within-run precision, between-day precision, dilution linearity, detection limit, and quantification limit. No effects of coexisting substances or container types were found. The correlation coefficient with “STACIA CLEIA IL-2R” was as high as 0.995, the regression equation was y = 1.17x − 34.33, and no extremely deviated sample was found. In conclusion, because of its good performance, it was suggested that the reagent can be introduced.

The working group (WG) committee for improving the internationalization of young biomedical laboratory scientists (BLS) was established in 2018 to improve internationalization. As one of the WG’s projects, the first International Young BLS Forum was held. In the near future, the working style of BLS will change considerably owing to the introduction of artificial intelligence (AI) into the medical fields. The aim of this forum is to discuss the future images of BLS worldwide. In this paper, we will introduce the details of our activities in the field of genomic medicine. We first listed up five questions on tissue fixation methods, which are important for genomic medicine in the pathology field and AI applications. In this forum, a member from each country answered them as pre-preparation methods. In all the participating countries, the 10% formaldehyde neutral buffer solution and fixation time are strictly implemented in accordance with the guidelines. We focused on the use of AI in the discussions during this forum. We considered that it might be possible to provide high-accuracy and high-efficiency medicine through the coexistence of BLS and AI, would greatly benefit the patients as a result. However, there will also be problems, such as the methods of educating BLS handling AI, the storage methods and uses of big data, the standardization of the learning model, and the solution of ethical issues. In this forum, we were able to understand the current problematic issues encountered in each country and the future images of BLS from an international viewpoint.

Our laboratory sometimes receives various complaints from outpatients regarding blood collection in the blood sampling room. However, there was no way of verifying such complaints without relying on memory. Therefore, it was difficult to provide feedback to our staff members. We set up network cameras in each booth allotted for blood sampling and began recording the venipuncture techniques and the approaches used in communicating between patients and staff members. In this report, we introduce the system and describe its configuration and practical uses. We monitored blood sampling on a desktop computer. The video data were stored on a network-attached storage for about 120 days. We developed the system to check the communications between patients and staff members, staff member’s manners, the instruments used, the site punctured, and the procedures followed in blood collection. This system helped us provide feedback to the staff members and improve their manners and techniques followed in blood sampling procedures.

Surveillance culture tests in the neonatal intensive care unit (NICU) are widely implemented to monitor horizontal transmissions and choose appropriate antimicrobials when patients have late-onset infections. However, the efficiency of surveillance culture tests has not been accurately evaluated. We examined the detection rates and costs before and after the change in the protocol of surveillance culture tests in 2017 from 2012 to March 2019 and determined the most efficient monitoring culture. Until 2016, NICU performed biweekly nasal swabs and fecal and navel examinations of all hospitalized patients. However, this surveillance method did not seem to be optimally cost-efficient because retrospective analyses of methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-susceptible Staphylococcus aureus (MSSA) isolates revealed that MRSA and MSSA were detected more often in nasal swab samples and subsequently colonized in most infants carrying them. Therefore, to be cost-efficient, we considered in 2017 to limit surveillance culture sampling to nasal swabs. As a result, we found that despite these changes, we found that the MRSA and MSSA detection rates did not significantly decrease, with a 65% decrease in sample number and a 73% decrease in cost compared with those in the 2018 surveillance culture tests. In conclusion, we found that there is less need to perform nasal swab and fecal and navel examinations simultaneously in surveillance culture tests. We showed that a protocol of surveillance culture tests targeting MRSA and MSSA by nasal swabs alone is cost-efficient.

Rotavirus (RV), norovirus (NV) and adenovirus (AV) are the major and important pathogens of childhood gastroenteritis. These antigens are being tested using rapid diagnostic kits at our hospital. The purpose of this study was to characterize on the basis of clinical laboratory findings the groups found to be positive for these antigens using the diagnostic kits. The medical records of patients (aged < 19 years) that were tested with these kits between January 2015 and December 2018 were reviewed, including the results of their clinical laboratory tests. A total of 633 patients (median age, 2 years) were tested for at least one antigen. For RV, out of 563 patients tested, 64 (11.4%) were positive. For NV, 46 (8.8%) out of 524 patients were positive, and for AV, 18 (5.8%) out of 312 patients were positive. In terms of age distribution, antigen-positive patients were mostly less than 3 years old. Seasonal distribution was seen for each virus. RV was identified mostly in spring (peaking in April), and the high season for NV was winter (December and January). We attempted to characterize each antigen-positive group on the basis of their clinical laboratory findings, namely, white blood cell count and CRP, AST, ALT, urea nitrogen, creatinine, glucose and sodium levels. However, the percentages of patients with abnormal values were not significantly different between each antigen-positive group and the antigen-negative group (the group in which none of the three antigens were detected). Our results suggest that it is difficult to characterize each antigen-positive group on the basis of clinical laboratory findings.

Here, we show the changes in the number of participating facilities and their evaluation in the clinical chemistry field from 2016 to 2018 through the Aichi Clinical Laboratory Quality Control Survey conducted by the Aichi Association of Medical Technologists (AAMT survey). The survey items were 29 in the clinical chemistry field, which were analyzed using the Japanese Association of Medical Technologist’s quality control survey project and data standardization project system (JAMTQC). The total numbers of facilities that participated in the AAMT survey were 135 in 2016, 136 in 2017, and 141 in 2018. Among them, the numbers of facilities in the clinical chemistry field were 113 in 2016, 120 in 2017, and 124 in 2018. We also conducted support projects through secondary surveys and results-review meetings. The numbers of facilities that participated in the secondary surveys were 4 in 2016, 11 in 2017, and 10 in 2018. In addition, the numbers of facilities that participated in the results-review meetings were 3 in 2016, 8 in 2017, and 7 in 2017. It is necessary to reveal the contents of the results-review meeting and create an environment where one can feel free to participate. Through the AAMT survey, we would like to continuously think about the best support for the medical facilities in Aichi.

Papillary fibroelastoma (PFE) is the second most common benign tumor of cardiac origin after myxoma. Most PFEs are single lesions, and multiple lesions are rare. A woman in her 50s underwent primary percutaneous coronary intervention for anterior acute myocardial infarction. Transthoracic echocardiography showed multiple masses of the aortic valvular structure. Transesophageal echocardiography revealed three round mobile structures on the aortic valves (5.0 × 3.6 mm and 4.4 × 3.2 mm on the left coronary cusp, and 2.3 × 3.8 mm on the noncoronary cusp). These masses were found at the same site by transthoracic echocardiography and transesophageal echocardiography. The transesophageal echocardiography showed these masses more clearly. These masses were considered to be PFEs, because some of them had pedicles. Embolization of these tumors could lead to serious complications; hence, these tumors were successfully resected. The surgical findings revealed six tumors in the aortic valve. On the basis of a pathological examination, these tumors were diagnosed as PFEs. Eventually, multiple PFEs were found in the aortic valve during the follow-up for myocardial infarction.

Cholangiolocellular carcinoma (CoCC) is a unique subtype of liver cancer with combined features of hepatocellular and cholangiocarcinoma. A tumor of 33 mm diameter was found in segment 6 of the liver of a woman in her seventies with a history of intravascular large B-cell lymphoma. On her ultrasound (US) images, the tumor was an ill-defined, irregularly shaped hyperechoic nodule. On her contrast-enhanced ultrasound (CEUS) images, the tumor demonstrated heterogenous enhancement on the arterial phase, a wash-out pattern on the portal phase, and a defect pattern on the postvascular phase. The tumor was hypervascular and showed enhancement on computed tomography (CT) during hepatic arteriography (CTHA) and a defect on CT during arterial portography (CTAP). Macroscopy analysis of a resected specimen showed a lobulated whitish firm mass without a capsule. Histopathological analysis revealed that the tumor had irregularly branched, anastomosing glands, with focal dilated glands that were architecturally similar to ductal plate malformation (DPM): irregular distorted glandlike structures with bridge/island formation and cystic dilatation. The tumor showed no mucin production. Immunohistochemistry results were as follows: cytokeratin (CK) 7 (+), CK19 (+), glypocan 3 (focal, +), Hep-par 1 (−), CEA (−), and EMA (+, apical staining pattern). The tumor was diagnosed as CoCC with the DPM pattern. By comparative research analysis between the US imaging and histopathological findings, we estimated that the hyperechoic pattern on B-mode images may be the result of the DPM-like pattern.

Small cell neuroendocrine carcinoma (SCNEC) of the uterine cervix is a relatively rare, highly aggressive tumor. We report a case of SCNEC of the uterine cervix that could be diagnosed preoperatively by cytology. The patient was a woman in her 20s. Owing to persistent uterine bleeding, cervical smear cytology was performed. The cytological diagnosis was SCNEC based on cell cluster arrangement with no specific structure, nuclear molding, naked nuclei-like cells with scant cytoplasm, and finely granular nuclear chromatin. On the other hand, the presence of squamous cell carcinoma was also suspected from the cytologic findings of atypical cell clusters rich in cytoplasm and having large nuclei. The histological diagnosis was also SCNEC based on a concentrated proliferation of small single cells with a high N/C ratio. Subsequently, radical hysterectomy was performed, and immunohistochemical examination led to the final diagnosis of SCNEC with the squamous cell carcinoma component. The tumor in this case was 6 cm in diameter and was positive for para-aortic lymph node metastasis, but no recurrence or metastasis was observed for 36 months after surgery. The cytological diagnosis of SCNEC requires the presence of cell arrangement with no specific structure, nuclear molding, and finely granular nuclear chromatin.

We here report a case of left subclavian artery stenosis in which the subclavian artery steal phenomenon was not detected owing to the anomalous origin of the left vertebral artery. A man in his seventies complained of numbness on the left side of his body and visited our hospital. He was diagnosed as having cerebral infarction by head CT and MRI, and he underwent carotid ultrasonography to find its cause. There were no findings that indicated an occlusion or stenosis of the right and left carotid arteries, and the blood flow in the vertebral arteries did not regurgitate. The next day, we performed 3DCTA and found left subclavian artery stenosis. In addition, the left vertebral artery was branched directly from the aortic arch. We performed carotid ultrasonography again and observed the left subclavian artery. A mosaic signal was observed on the central side of the artery, and the maximum flow velocity exceeded 4 m/s. Usually, if there is a more-than-moderate stenosis on the central side of the subclavian artery, the subclavian artery steal phenomenon can be detected. However, in this case, the blood flow of the left vertebral arteries did not regurgitate because of an anomalous origin. In this case, we were able to prevent oversight by auscultation and comparing between the right and left upper limb blood pressures before the examinations.

We encountered a case with hemophagocytic macrophages in a peripheral blood smear for the first time in our laboratory. It is believed that such a case is quite rare; however, a report mentioned that the detectability of hemophagocytic macrophages could be increased by an extensive screening method. We subsequently carefully performed investigations considering the possibility of this condition, and we identified four additional cases within five months. Although only one case met the criteria for the diagnosis of hemophagocytic syndrome, all cases showed decreases in the numbers of some types of blood cells during the clinical course. Additionally, bilateral pleural fluid was noted in all five cases; however, its significance is unclear. These findings indicate that the presence of hemophagocytic macrophages in a peripheral blood smear is not very rare. For detection, it is important to carefully investigate the side and feathered edges of a blood smear, especially in cases showing decreases in the numbers of some types of blood cells and in those presenting clinical features of possible hemophagocytic syndrome.