Few studies have shown the relationship between electrocardiogram (ECG) findings and long-term outcomes after malignant tumor resection. In this study, we aimed to evaluate the relationship between preoperative ECG findings and relapse-free survival (RFS) in patients who underwent curative resection for colorectal cancer (CRC). The study included 431 patients who underwent R0-resection for Stages II and III CRC, and data for the following parameters were collected: age, sex, tumor location (left or right side of the colon or rectum), tumor depth (T), lymph node metastasis (N), stage, postoperative adjuvant chemotherapy, preoperative ECG findings (heart rate, PR interval, QRS interval, QTc interval, and left ventricular hypertrophy (LVH)), and RFS. Univariate analysis revealed that age, tumor location, T, N, stage, postoperative adjuvant chemotherapy, and LVH were significantly associated with RFS. Multivariate analysis revealed that age, stage, QRS interval, and LVH were independent significant prognostic factors. Patients with a QRS interval ≥ 120 ms and/or LVH showed significantly shorter RFS than those without either of these factors (p = 0.0475) in Stage III CRC. Thus, a QRS interval ≥ 120 ms and LVH on preoperative ECG may be long-term prognostic factors for patients undergoing curative resection for CRC.
The spread of antibiotic-resistant bacteria has long been a serious global problem. At present, carbapenem antibiotics are used as drugs of last resort against antibiotic-resistant bacterial infections caused by extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae. However, the emergence of carbapenem-resistant Enterobacteriaceae (CRE) renders this treatment ineffective. In Japan, a health-care-associated infection with CRE at a medical facility in Osaka City was recorded in 2014 and has been reported extensively as one of the earliest known incidents of CRE infection. In this study, 25 strains of carbapenem-resistant Escherichia coli detected in a medical facility in northern Osaka Prefecture during a 4-year period, beginning in 2012, were compared to the strains involved in the incident that occurred in Osaka City. Upon analyzing the genetic factors responsible for drug resistance, it was found that all strains contained the CTX-M-2 group of ESBL genes. In addition, 24 strains contained the IMP-6-type metallo-β-lactamase gene. This corresponds to the characteristics of the drug-resistant Enterobacteriaceae reported in the Osaka City incident, suggesting that by 2012, similar strains of Enterobacteriaceae had already been detected in northern Osaka. In addition, when PCR-based ORF typing was performed and the longitudinal dynamics analyzed, it was found that there was an annual increase in the number and diversity of detected strains. Besides, in 2016, a strain of carbapenem-resistant E. coli, which was very rarely reported in Japan, was also found to be resistant to amikacin. Consequently, it is necessary to closely monitor this strain from this point onward.
Disseminated intravascular coagulation (DIC) is an acquired syndrome characterized by the systemic activation of blood coagulation occurring in the presence of various serious diseases, resulting in microvascular thrombosis in various organs. The main objective of this study was to clarify the role of oxidative stress and tissue factor (TF) in the pathogenesis of DIC in patients with acute leukemia. We measured both oxidation and anti-oxidation activities simultaneously in sera from 40 patients with acute myelogenous leukemia (AML), 20 patients with chronic myelogenous leukemia (CML), and 665 healthy volunteers. To obtain a parameter representing an overall shift toward oxidative stress, the oxidative stress index (OSI) was calculated using the following formula: OSI = (d-ROMs/BAP) × 8.85. We found that the OSIs were clearly higher in sera of AML patients than in those of CML patients and healthy volunteers, and the OSIs were significantly higher in AML patients with DIC than in those without DIC. In addition, the present study confirmed that the prevalence of DIC was significantly higher in AML patients with high TF concentrations (8/11 patients, 72.7%) than in those with normal TF concentrations (3/29 patients, 10.3%). These results suggest that the evaluations of OSI and TF are useful for predicting the development and progression of DIC in AML patients.
The removal of colon polyps can reduce the risk of colon cancer. Recently, cold snare polypectomy (CSP), which does not use electricity, has become a widely accepted treatment for colon polyps. However, the horizontal margin of specimens resected by CSP is often unclear. CSP specimens are small and difficult to paste with a pin. Therefore, they are formalin-fixed without pasting. We devised a method to extend and fix the specimens on filter paper. In this study, we investigated the effect of horizontal margin on evaluation by pasting CSP lesion specimens on filter paper. We compared 1,040 colorectal adenoma specimens obtained by CSP (470 lesion specimens in the pasting group, 570 lesion specimens in the conventional group) from January to June 2018. In the pasting group, the specimens were extended with a toothpick and affixed to filter paper and then fixed in formalin. In the conventional group, they were formalin-fixed without pasting. Results showed that the median ages in the pasting and conventional groups were 70 and 72 years, respectively, and the median lesion size was 4 mm in both groups. The area of the unclear horizontal margin was significantly smaller in 167 specimens (35.5%) in the pasting group than in 326 specimens (57.2%) in the conventional group (p < 0.01). In conclusion, pasting CSP lesion specimens on paper significantly reduced the number of the specimens with an unclear horizontal margin.
Mycoplasma pneumoniae antigen tests are widely used in many medical laboratories since their approval by the Japan national health insurance in 2013. Because M. pneumoniae primarily infects the lower respiratory tract, the sampling technique considerably affects the kit performance as throat swabs are usually used as specimens. Therefore, we used bacterial cultures to study the performances of five commercially available kits. M. pneumoniae strains ATCC15531 and ATCC29342 were cultured for 4 and 14 days. The 4-day cultures contain live bacterial cells and the 14-day cultures contain dead bacterial cells. Some kits showed better sensitivity in the 4-day cultures, whereas others showed better sensitivity in the 14-day cultures. This difference is due to the antigen species recognized by the antibodies in the different kits. Cytoplasmic proteins such as the L7/L12 ribosomal protein and DnaK are recognized by the kits with better performances in the 4-day cultures, whereas the plasma membrane attachment proteins such as P1 and P30 are recognized by the kits with better performances in the 14-day cultures. In conclusion, this study showed that different M. pneumoniae kits detect different bacterial proteins, which in turn reflect the bacterial state, i.e., alive or dead.
Mycophenolate mofetil (MMF), a mycophenolic acid (MPA) prodrug, has been commonly used in immunosuppressive therapy after organ transplantation. Since the pharmacokinetics of MPA has a large interindividual variability, therapeutic drug monitoring (TDM) is needed. MPA concentration has been measured by liquid chromatography tandem mass spectrometry (LC-MS/MS) or the enzyme-multiplied immunoassay technique (EMIT). However, the LC-MS/MS method is complicated and needs many hours; on the other hand, EMIT detects both MPA and its metabolites. In this study, we examined the performance of the particle-enhanced turbidimetric inhibition immunoassay (PETINIA) for the measurement of MPA in terms of its within-run and day-to-day run reproducibilities, linearity, and detection limits, and the effects of interfering substances, serum-separating agents, storage condition, as well as wide-range relationship with LC-MS/MS. PETINIA showed a satisfactory performance in terms of sensitivity, reproducibility, and specificity. In addition, serum-separating agents did not affect the concentration measurements, and the storage stability was equivalent to the data described in the attached document of the reagent. The correlation with the LC-MS/MS method was satisfactory (y = 1.18x − 0.09, r = 0.980, p < 0.01), but plasma samples more than 15 μg/mL MPA showed higher MPA concentrations in PETINIA. In conclusion, the clinical usefulness of PETINIA for the measurement of plasma MPA concentrations was suggested in the lower range; on the other hand, the higher plasma MPA concentrations measured by PETINIA should be carefully interpreted.
At our hospital, the laboratory ordering system does not issue test tubes with labels attached, but only the labels. Therefore, the nurses must find the appropriate tubes and attach the labels manually. The nurses sometimes make mistakes in selecting the test tubes; to avoid such mistakes, the nurses call the laboratory to inquire about the tube selections. These calls are time-consuming for both nurses and laboratory technicians. Thus, we developed a new search-and-display system for laboratory examination inquiries utilizing the existing FileMaker Pro server and client system. With this system, users can scan or manually enter patient IDs and examination dates to find what types of examination were ordered by the doctor and the appropriate test tubes and labels. This system can also display cautionary messages while obtaining blood samples and provide information on important issues related to blood transfusion. This system collects logs describing which tubes are frequently searched, enabling the laboratory technicians to obtain feedback about which examinations/tubes that nurses have questions. With this system, the number of mistakes resulting in redrawing blood and the number of inquiry calls from nurses to the laboratory section have been reduced.
Nagoya University Hospital is designated as a regional disaster base hospital in Aichi Prefecture. According to the Business Continuity Plan (BCP) formulated by our hospital, it is assumed that the external infrastructure around the hospital during a disaster will be shut down for two weeks for water supply and three days for electricity. However, medical treatment and preoperative examination during disasters are indispensable. The fully automated VITROS XT 7600 integrated system does not require a water supply/drainage device, and is expected to contribute to medical care during a disaster. Here, VITROS XT 7600 was used to compare the performance of the examinations for infection-related diseases that may be required during disasters with the analyzer used in the hospital, and its usefulness was verified. The hepatitis B surface (HBs) antigen, hepatitis C virus (HCV) antibody, Treponema pallidum (TP) antibody and human immunodeficiency virus (HIV) antigen/antibody were verified as the markers for infection-related diseases. The concordance rates of the results of examinations for infection-related diseases were 98.0% for the HBs antigen (98/100), 92.3% for the HCV antibody (60/65), 100% for the TP antibody (53/53), and 100% for the HIV antigen/antibody (67/67). Moreover, the early detection capability of a seroconversion panel was evaluated for the HBs antigen, HCV antibody, and HIV antigen/antibody. Results showed that the early detection capability was almost the same for all items. Taken together, it was considered that VITROS XT 7600 is useful for examinations of infection-related diseases during disasters.
The Tokyo Metropolitan Matsuzawa Hospital has 898 beds (808 beds for psychiatric patients), and conducts high-sensitivity troponin I (hs-TnI) examination at the time of emergency consultation. In the past, the hs-TnI positive rate after introduction is at least three times higher in odds ratio than the prevalence rate of acute myocardial infarction (AMI) calculated in our hospital. Therefore, to confirm the reliability of the hs-TnI value, measurements with other analyzers and nonspecific reactions using heterophilic antibody inhibitors were first examined, but no particular problems were observed. Next, the AMI diagnostic specificity of myocardial markers was evaluated. As myocardial markers, hs-TnI, CK-MB mass, CK-MB activity, and human-heart-type fatty acid binding protein were used. Then, 27 items of blood and biochemical data were added, and an AMI diagnosis guide using a decision tree was made on a trial basis. Only hs-TnI showed a significant difference for the presence or absence of AMI diagnosis and was a myocardial marker independent of other factors. In the decision tree, chloride, hs-TnI concentration, and CK-MB mass value at the time when a positive hs-TnI result was obtained were derived as branch nodes. The combination of these extraction factors showed improvement in AMI diagnostic accuracy. However, the positive predictive value of less than 50% is insufficient, suggesting the need for diagnostic guidelines to which qualitative data such as the blood collection results and electrocardiograms can be added over time.
Candida spp. are dimorphic fungal residents of the normal mucosa such as the oral cavity and intestinal tract. Candida albicans is the most common causative agent of candidiasis; however, an increase in the incidence of candidiasis caused by non-albicans Candida (NAC) spp. has been observed. Candida spp. have many pathogenic factors that contribute to the establishment of host infection, such as the production of extracellular secretory enzymes (ESEs). These enzymes are considered to be involved in host destruction and the growth of Candida. In this study, we aimed to measure the activities of ESEs [namely, secreted aspartyl protease (SAP), phospholipase (PL), esterase, hemolysin, and phytase] and compare them in both C. albicans and NAC species. The activities were calculated by the method reported by Price (1982) with modification. C. albicans was positive for all the ESEs. C. glabrata showed activities of mainly PL, hemolysin, and esterase, but no SAP activity or esterase. C. tropicalis was positive for almost all the ESEs, but some strains did not show activities of the ESEs. Candida spp. produce ESEs and may invade the host tissue. The amounts of ESEs produced by the different species and the differences among the species were also determined.
Liver biopsy is considered the “gold standard” for the evaluation of hepatic fibrosis. On the other hand, we widely use serum fibrosis markers in routine practice because measuring them is less invasive. In recent years, the efficiency of hepatitis C therapy has considerably improved owing to the development of DAA therapy, but the effect of DAA therapy on the levels of fibrosis markers is unclear. In this study, we compared the levels of fibrosis markers before and after therapy in 54 patients with chronic hepatitis C, who were treated with DAAs in our hospital. Furthermore, we compared these levels by classifying patients into those with advanced and those with nonadvanced liver fibrosis on the basis of the results of liver biopsy to examine the difference in the changes depending on the stage of liver fibrosis. Results showed that there were significant changes in platelet counts and the levels of the Mac-2 binding protein glycosylation isomer and type IV collagen 7S in serum after DAA therapy, regardless of the severity of liver fibrosis. On the other hand, although there was no significant difference in the level of type IV collagen in the preclassification comparison, the postclassification comparison showed a significant increase in the type IV collagen level in the patients with nonadvanced liver fibrosis but not in those with advanced liver fibrosis. It was considered that this is due to changes in the expression levels of type IV collagenolytic enzymes depending on the severity of liver fibrosis and inflammation improvement. It is necessary to be careful in the interpretation of the levels of fibrosis markers after DAA therapy because each marker shows different changes. Liver fibrosis assessment based on the levels of fibrosis markers should be carried out comprehensively considering the dynamics among these parameters.
The basic requirements demanded from a red blood cell washing system in tests of blood transfusion are the efficiency of washing cells and a sufficient number of red blood cells remaining in a test tube. We tried to examine the usefulness of the automatic blood cell washing system called “cell washer UltraCW II” (Helmer) in a test of blood transfusion wherein the conditions were set for each parameter in the washing process. We calculated the amount of liquid that remained in the test tube from the difference in the weight of the test tube before and after washing cells. We calculated the washing dilution factor by measuring the absorbance at 478 nm using OrangeG. We calculated the number of red blood cells that remained in the hemolysis liquid with distilled water by measuring the absorbance at 541 nm. The factor that affected most the washing efficiency of red blood cells was the number of revolutions of DECANT. It made the red blood cells decrease in number when the number of washings (FILL) was too high. Extending the time of SPIN led to the extension of the washing time. Using a parameter provided by the manufacturer, we determined the intra-assay precisions of 24 test tubes. The washing dilution factor showed a mean of 109 and a CV of 3.7% for a 10 mm test tube, and a mean of 165 and a CV of 6.1% for a 12 mm test tube. The red blood cell residual rate showed a mean of 72.2% and a CV of 12.2% for a 10 mm test tube, and a mean of 78.6% and a CV of 5.2% for a 12 mm test tube. The results indicated a good performance of the system. In the anti-D titration with PEG-IAT in high-protein and high-globulin specimens, antiglobulins were not neutralized owing to washing insufficiency, and agglutination detection was possible. From these results, we found that UltraCWII was useful for the washing of red blood cells in the test of blood transfusion.
We investigated the usefulness of hepatitis B virus surface antigen (HBsAg) highly sensitive quantitative reagent “Lumipulse presto HBsAg-HQ (HBsAg-HQ assay)’’ by analyzing daily patient data. Among negative cases (92.05%, 7,857/8,536), the mismatch after retest was 0.04% (3/7,843), and the rate of negative HBsAg suppression test was 0.14% (11/7,843). Among the positive cases, the highly sensitive area was 2.95% (20/679), the rate of negative HBsAg suppression test was 56% (14/25), and 13 cases tested were positive for HBcAb. From these results, we confirmed that the HBsAg-HQ assay has high specificity and can capture HBsAg with high sensitivity. In addition, the results of HBsAg assay and HBV-DNA continuous analysis in two cases of HBV reactivation prevention suggest that the HBsAg-HQ assay is useful for monitoring HBV reactivation.
A working group committee (young WG) for improving the internationalization of young biomedical laboratory scientists (BLSs) was established in 2018. Its purpose is to train young BLSs to think about what is necessary for improving their internationalization. We will introduce the details of the international young BLSs forum, which is the first event organized by the young WG at the 68th Japanese Association of Medical Technologists (JAMT) congress in Shimonoseki. There are three themes: “Will artificial intelligence be a useful tool for quality control in the future?”, “The evolving genomic medicine—The future image of genomic medicine”, and “The BLSs’ future vision of telemedicine”. Our team discussed the first theme across the nations. We looked into the problems and circumstances surrounding quality control (QC) before the forum, and then we discussed the possibility of AI as a tool to fight those problems during the forum. As one of our achievements, we made a presentation about what we should do after introducing AI technology, with some examples. We concluded that the action for the internationalization through this forum is an efficient way to improve the internationalization of young BLSs, and we are hopeful for the future actions arising from this forum.
The International Young Biomedical Laboratory Scientists Forum was held during the 68th JAMT congress in May 2019. This forum is the first project organized by the Young Professionals Internationalization Improvement Working Group, which was established by the Japan Association of Medical Technologists in 2018. We held discussions on telemedicine and artificial intelligence (AI) with the biomedical laboratory scientists (BLS) of Korea and Taiwan. Each country described the current situation and issues related to telemedicine and AI in advance. At the forum, we also discussed the future vision of telemedicine and BLS. As there are many common social elements in our three countries, such as declining birthrate, aging populations, and uneven distribution of medical workers, we considered the use of AI in the telemedicine field as an indispensable resource for solving these problems. However, many issues remain to be solved, such as the development of security and legal systems, and the definition of responsibility for medical errors caused by AI. Therefore, we agreed that it is desirable to acquire the knowledge necessary for information security and AI in the educational curriculum of BLS. Although there are few BLS active in the field of telemedicine, coexistence with AI and teaming up with experts outside the medical field will produce benefits for patients and medical staff, and further expand the possibility of BLS.
A man, aged 68, was admitted to our hospital because of seizure during sleep. Video polysomnography (PSG) using 10–20 full montage electroencephalography (EEG) and sleep apnea sensors was performed to confirm the diagnosis. PSG revealed an interictal sharp wave in the right frontotemporal lobe and frequent apnea–hypopnea events, which led to the diagnosis of temporal lobe epilepsy and obstructive sleep apnea syndrome (OSAS). Administration of an anti-epileptic drug (AED) and continuous positive airway pressure (CPAP) was started for the treatment. However, after a while, the patient stopped these treatments on his own free will, which resulted in the recurrence of seizures; thus, CPAP was resumed. Then, PSG with CPAP titration was carried out, which demonstrated the reduction in the frequency of obstructive apnea–hypopnea events by CPAP therapy. Nevertheless, central apnea events following EEG epileptiform discharges were observed five times over the night. Because no convulsion was observed on the video at those times, we regarded the events as nonconvulsive epileptic seizures. Epilepsy and OSAS comorbidity is not rare. It is shown by this case that there are two types of sleep disordered breathing in cases with this comorbidity: one type is characterized by events caused by upper airway obstruction and the other type by events following epileptic seizures. The therapies appropriate for these two types are different: CPAP for the former and AED for the latter. To differentiate these two types, the skill to interpret EEG recordings correctly is required.
A female patient in her 80s was transported to our hospital with fever and hypoxia. Gram-negative bacillus cells were isolated from one aerobic blood culture vial. However, the bacterium was not identified by conventional phenotypic assays and matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry. A 16S ribosomal RNA (rRNA) gene sequencing technique revealed the bacterium to be Paenibacillus vini. P. vini has hardly been reported to be isolated from blood culture. In this study, we identified P. vini isolated from blood culture by the 16S rRNA gene sequencing technique. For the identification of Paenibacillus species, sequencing of the 16S rRNA gene was effective. In Spain, of the 136 Paenibacillus strains isolated between 1999 and 2015, only one strain was identified as P. vini.
Background: A plasma cell neoplasm with aberrant expression of T-cell-related antigens is exceedingly rare. In this study, we report a case of dual CD3- and CD4-positive plasma cell neoplasm (PCN). Case: The patient was an 80-year-old woman who was referred to our hospital owing to her general fatigue. There was no palpable mass in the contrast-enhanced CT images; however, laboratory tests revealed high levels of LDH and soluble IL-2R. MRI examination detected an abnormal signal in the cervical spine. Bone marrow biopsy was performed and blastic plasmacytoid dendritic cell neoplasm (BPDCN) was suspected. Four months later, bilateral pleural effusion occurred, and right pleural effusion was obtained for cytological examination. Cytological smears showed mononuclear and multinuclear tumor cells with a perinuclear halo resembling plasma cells. Immunocytochemistry of cell block preparations revealed that the tumor cells were positive for CD3, CD4, CD56, CD138, and kappa light chains. The final diagnosis was PCN. Conclusion: In this patient, although the tumor cells had morphological features of PCN, they were positive for CD3 and CD4. It is important to recognize a plasma cell neoplasm with aberrant expression of T-cell antigens.
Here we report a case of chronic lymphoproliferative disorders (CLPDs) of natural killer (NK) cells (CLPD-NK), which are a very rare group of diseases. A man in his 80s presented with shortness of breath, cough, and pleural effusions, and was admitted to our hospital for further examination and treatment. His complete blood count with differential showed leukocytosis, neutropenia, and lymphocytosis. The peripheral blood smear revealed that 91.0% of the lymphocytes were large granular lymphocytes (LGLs). The blood chemistry tests showed a slightly high total protein level and a slightly low albumin/globulin ratio. Flow cytometry (FCM) of the peripheral blood revealed a CD3(−) CD56(+) immunophenotype, which represents an NK cell immunophenotype. The LGL counts were 7,024/μL on admission and 3,365/μL after six months. These laboratory results of the patient fulfilled the diagnostic criteria of CLPD-NK. Compared with patients with T-cell large granular lymphocytic leukemia (T-LGLL), this patient with CLPD-NK showed significantly larger diameter granular lymphocytes (p < 0.01). However, the difference in the diameter of LGLs between patients with CLPD-NK and T-LGLL was only 1 μm. Therefore, it is difficult to distinguish the origin of LGLs on the basis of morphology. To prevent a misdiagnosis of CLPD-NK, it is important to confirm the presence of LGLs, which can be identified by their specific morphology from the blood smear in the case of lymphocytosis, and to analyze the expression of LGL surface markers by FCM.
The task of sharing clinical works as much as possible in non-physician occupations, along with streamlining of clinical laboratory work, promotion of high-level expertise, promotion of information sharing, and promotion of team medical care, is required. The environment surrounding biomedical laboratory scientists (BLS) is diversifying daily. Furthermore, with the advancement of science and technology, transportation and communication methods have markedly developed, people, goods and information have frequently traveled across countries, and globalization is increasing. Also, medical tourism is increasing. It is important to advance the internationalization of BLS to deepen their experience and understanding of the world. In other words, concerning the acquisition of specialized knowledge as a BLS, it is necessary to develop human resources who have the knowledge, language ability, response capability, and research ability that are of international standard. Therefore, we think that it is extremely important to enhance international exchange activities conducted by organizations centered on the Japanese Association of Medical Technologists (JAMT). On the basis of this background, JAMT established the Working Group for improving the internationals skills of young BLS in 2018. We think that this opportunity to discuss the future roles of BLS and to collaborate with the BLS of the three countries while remaining respectful to each other and without being restricted by borders was a great asset to them. We are convinced that this forum has been a good opportunity for young BLS to engage in internationalization activities in preparation for the future.