Laboratory Preparation for Digital Medicine in Healthcare 4.0: An Investigation Into the Awareness and Applications of Big Data and Artificial Intelligence.

Background: Healthcare 4.0. refers to the integration of advanced technologies, such as artificial intelligence (AI) and big data analysis, into the healthcare sector. Recognizing the impact of Healthcare 4.0 technologies in laboratory medicine (LM), we seek to assess the overall awareness and implementation of Healthcare 4.0 among members of the Korean Society for Laboratory Medicine (KSLM). Methods: A web-based survey was conducted using an anonymous questionnaire. The survey comprised 36 questions covering demographic information (seven questions), big data (10 questions), and AI (19 questions). Results: In total, 182 (17.9%) of 1,017 KSLM members participated in the survey. Thirty-two percent of respondents considered AI to be the most important technology in LM in the era of Healthcare 4.0, closely followed by 31% who favored big data. Approximately 80% of respondents were familiar with big data but had not conducted research using it, and 71% were willing to participate in future big data research conducted by the KSLM. Respondents viewed AI as the most valuable tool in molecular genetics within various divisions. More than half of the respondents were open to the notion of using AI as assistance rather than a complete replacement for their roles. Conclusions: This survey highlighted KSLM members' awareness of the potential applications and implications of big data and AI. We emphasize the complexity of AI integration in healthcare, citing technical and ethical challenges leading to diverse opinions on its impact on employment and training. This highlights the need for a holistic approach to adopting new technologies.

What We Should Consider in Point of Care Blood Glucose Test; Current Quality Management Status of a Single Institution.

Background and Objectives: Point of care test (POCT) is generally performed by non-laboratory staff who often lack an understanding on the quality control and quality assurance programs. The purpose of this study was to understand the current status of quality management of point of care (POC) blood glucose testing in a single institution where non-laboratory staff perform the tests. Materials and Methods: From July to August 2020, management status of glucometer, test strips, quality control (QC) materials, quality assurance program, and operators' response to processing of displayed results was monitored in all Soonchunhyang University Bucheon hospital departments that performed POC blood glucose test. Results of the POC blood glucose test conducted from January 2019 to May 2020 were analyzed retrospectively. Results: A total 124 glucometers were monitored in 47 departments. Insufficient management of approximately 50% of blood sugar, test strips, and QC materials was observed. Although daily QC was conducted by 95.7% of the departments, the QC records were inaccurate. The method of recording test results varied with departments and operators. Various judgments and troubleshooting were performed on the unexpected or out of measurable range results, including some inappropriate processes. In POC blood glucose test results review, 4568 atypical results were identified from a total of 572,207 results. Conclusions: Sufficient training of the non-laboratory staff and ongoing assessment of competency through recertification is needed to maintain acceptable levels of POCT quality. In this study, various problems were identified in glucometer and reagent management, QC and post-analytic phase. We believe that these results provide meaningful basal information for planning effective operators' training and competency evaluation, and the development of an efficient POCT quality management system.

Blood urea nitrogen/creatinine change ratio as a delta check method for dialysis specimens.

The delta check is used in clinical laboratories to detect specimen mislabeling or misidentification. However, test results can differ markedly pre-versus post-dialysis, and the delta check in fact typically has little value, as well as being labor intensive. We propose the "blood urea nitrogen/creatinine change ratio" (BCCR) as a new delta check method for dialysis cases. A total of 1,116 specimens with same-day pre- and post-dialysis test results were analyzed. Also, the performance of the BCCR was evaluated by simulating specimen mix-up. Among the 1,116 specimens, the median BCCR was 0.80 and the 2.5th, 25th, 75th, and 97.5th percentiles were 0.62, 0.74. 0.84, and 0.93, respectively. In the simulated misidentification dataset, the median BCCR was 0.79 and the 2.5th, 25th, 75th, and 97.5th percentiles were 0.34, 0.61, 1.02, and 1.77, respectively. When the 2.5th and 97.5th percentile values of the BCCR were set as the upper and lower limits, the delta check detected 61.0% of the simulated misidentified specimens. In summary, the BCCR enables detection of changes in important measures and could reduce the rate of false-positives.

Clinical Usefulness of Human Epididymis Protein 4 in Lung Cancer.

Human epididymis protein 4 (HE4) has been suggested as a useful new biomarker of lung cancer; however, few relevant large-scale studies have been published. In this study, we evaluated the utility of serum HE4 for lung cancer detection. HE4 levels were measured in serum samples from 100 lung cancer patients, 57 patients with benign lung diseases, and 274 healthy controls by using a chemiluminescent immunoassay, and variations in HE4 levels were analyzed by clinical status such as lung cancer, benign lung disease, and healthy condition, Tumor, Lymph Nodes, Metastasis (TNM) stage, tumor score, and histological cancer type. Lung cancer patients had significantly higher serum HE4 levels than patients with benign lung diseases and healthy controls (P<0.0001). The area under the ROC curve for HE4 was 0.84 (95% confidence interval, 0.78-0.89; P<0.0001) between lung cancer patients and healthy controls. Serum HE4 levels were significantly higher in patients with advanced disease (according to TNM stage) than in healthy controls (P<0.0001). HE4 levels were significantly elevated in patients with tumors of all types, those of different histological subgroups, and those with the smallest tumors (P=0.002). This report supports the potential of serum HE4 as an ancillary diagnostic marker for lung cancer detection.

Pulmonary infection caused by Mycobacterium neoaurum: the first case in Korea.

Mycobacterium neoaurum is rapidly growing mycobacteria that can cause human infections. It commonly causes bloodstream infections in immunocompromised hosts, and unlike other mycobacteria species, it rarely causes pulmonary infections. We confirmed the first pulmonary infection case in Korea caused by M. neoaurum using full-length 16S rRNA gene sequencing.

Detection of fetal hemoglobin (HbF) using the G8 glycohemoglobin analyzer.

BACKGROUND: Abnormal HbF concentration has been proposed as a marker of solid tumor and myelodysplastic syndrome. As HbA1c is tested widely for glycemic control monitoring, some commercial glycated hemoglobin assays can provide additional information about these hemoglobin concentrations. However, few studies have investigated the clinical significance of increased HbF in current practice. METHODS: Between January 2012 and December 2012, HbAlc results, tested in the Department of Laboratory Medicine at Soonchunhyang University Bucheon Hospital, were analyzed. HbAlc was measured using a G8 Glycohemoglobin Analyzer (Tosho Bioscience, Tokyo, Japan) in the 1.6 minutes HbAlc mode. A total of 13,866 specimens from 9,545 patients were tested. RESULTS: The median HbF concentration was 0.7%, the 99.5th percentile was 3.2%, and 73 samples from 56 patients were > 3.2%. Among these patients, 37.5% (21/56) had malignancies: 16 had solid cancer and 5 had hematologic malignancies. The maximum HbF observed was 8.2% and elevated HbF showed no evidence of interference with the HbAlc test. However, the minimum HbF and LA1C+ fraction increased with increasing HbAlc, suggesting interference by elevated HbAlc. CONCLUSIONS: Care must be taken when interpreting HbF concentrations in samples with high HbAlc values determined using the HbA1c mode of the G8 Glycohemoglobin Analyzer.

Is prostate-specific antigen effective for population screening of prostate cancer? A systematic review.

BACKGROUND: The effectiveness of prostate-specific antigen (PSA) for population screening has presented controversial results in large trials and prior reviews. We investigated the effectiveness of PSA population screening in a systematic review. METHODS: The study was conducted using existing systematic reviews. We searched Ovid MEDLINE, Embase, Cochrane library, and the major Korean databases. The quality of the systematic reviews was assessed by two reviewers independently using AMSTAR. Randomized controlled trials were assessed using the risk of bias tool in the Cochrane group. Meta-analyses were conducted using Review Manager. The level of evidence of each outcome was assessed using GRADE. RESULTS: Prostate-cancer-specific mortality was not reduced based on similar prior reviews (relative risk [RR] 0.93; 95% confidence interval [CI], 0.81-1.07, P=0.31). The detection rate of stage 1 prostate cancer was not greater, with a RR of 1.67 (95% CI, 0.95-2.94) and high heterogeneity. The detection rate of all cancer stages in the screening group was high, with a RR of 1.45 (95% CI, 1.13-1.85). No difference in all-cause mortality was observed between the screening and control groups (RR, 0.99; 95% CI, 0.98-1.01, P=0.50). Prostate-cancer-specific mortality, all-cause mortality, and diagnosis of prostate cancer at stages 3-4 showed moderate levels of evidence. CONCLUSIONS: Differently from prior studies, our review included updated Norrköping data and assessed the sole effect of PSA testing for prostate cancer screening. PSA screening alone did not increase early stage prostate cancer detection and did not lower mortality.

Optical coherence tomographic findings of crystal deposits in the lens and cornea in Bietti crystalline corneoretinopathy associated with mutation in the CYP4V2 gene.

BACKGROUND: We report the optical coherence tomography (OCT) findings of crystalline deposits in the cornea and lens of a patient with Bietti crystalline dystrophy (BCD), thus providing evidence for a better understanding of the pathophysiology of BCD. PATIENT: A 49-year-old man showing typical chorioretinal degeneration with a CYP4V2 mutation was diagnosed with BCD. OBSERVATIONS: The anterior segment OCT images clearly showed flat hyperreflective plaques just beneath the corneal epithelium and in the lens epithelium. The crystals were not located on the outer surface of the lens capsule as previously described but on the inner surface of the anterior capsule. CONCLUSIONS: This finding suggests that the crystals in the lens of patients with BCD may be produced in the same way as corneal or retinal crystalline deposits and therefore result from a systemic abnormality of lipid metabolism rather than by previously considered possibilities, such as release from the retina adhering to the lens capsule.

Simultaneous translocation of both TCR Loci (14q11) with rare partner loci (Xq22 and 12p13) in a case of T-lymphoblastic leukemia.

The most common recurrent cytogenetic abnormalities in T-lymphoblastic leukemia (T-acute lymphoblastic leukemia [T-ALL]) involve T-cell receptor (TCR) loci and a variety of partner genes, including HOX11, HOX11L2, MYC, and TAL1. In this report, we present a rare case involving simultaneous translocation of the TCR α/δ loci with different partner loci (Xq22 and 12p13); this resulted in a poor prognosis. Chromosomal analysis showed 46,Y,t(X;14)(q22;q11.2),t(12;14)(p13;q11.2) and FISH analysis by using a T-cell receptor alpha delta DNA probe, Split Signal (DakoCytomation, Denmark), showed translocations at the same TCR α/δ locus on both chromosomes. FISH with 2 bacterial artificial chromosome clones showed break apart signal, which suggests involvement of the IRS4 gene. To our knowledge, this is the first report of T-ALL in which both TCR α/δ loci were translocated with different partner loci, and 1 of the partner loci, Xq22, was a rare translocation partner locus that included IRS4 gene.

Improving the blood collection process using the active-phlebotomist phlebotomy system.

BACKGROUND: Because the number of patients requiring phlebotomy varies significantly at different times throughout the day, it is difficult to control wait times during peak times. We tried to solve this problem by changing from the conventional fixed-phlebotomist phlebotomy system (CFPPS), in which the phlebotomist waits for patients at a fixed location to the active-phlebotomist phlebotomy system (APPS), in which a phlebotomist goes to patients actively. We compared the productivity of these two systems. METHODS: After changing the system at our hospital, we measured the waiting time before seeing phlebotomy staff and compared it to a comparable hospital that uses CFPPS. We reviewed the phlebotomy count recorded in the laboratory information system before and after the system change. RESULTS: After the system change, the average waiting time for phlebotomy was 2.34 min (median 1 min) and the waiting time was less than 5 min in all time slots, except 7:00 to 7:30 a.m. The new system significantly decreased the waiting time. In addition, the maximum number of patients seen by a phlebotomist during the peak time was higher in the APPS. CONCLUSION: The APPS enhanced the productivity of the phlebotomist and reduced waiting time with limited human resources in a Korean hospital.

Identification of a novel splicing mutation in the ARSA gene in a patient with late-infantile form of metachromatic leukodystrophy.

Metachromatic leukodystrophy (MLD; MIM 250100), a severe neurodegenerative disorder inherited as an autosomal recessive trait, is caused by mutations in the arylsulfatase A (ARSA) gene. Although several germ line ARSA mutations have been identified in patients with MLD of various ethnic backgrounds elsewhere in the world, no genetically confirmed cases of MLD have been reported in Korea. Recently, we identified a mutation in the ARSA gene of a Korean male with MLD. A male infant with late-infantile form of MLD had been admitted to our hospital for further examination. His neuromuscular symptoms, which included inability to walk at the age of 12 months, gradually worsened, even after allograft bone marrow transplantation; he died at the age of 9 yr. His elder brother had also been diagnosed with MLD. To confirm the presence of a genetic abnormality, all the coding exons of the ARSA gene and the flanking introns were amplified by PCR. A molecular analysis of the ARSA gene revealed both a novel heterozygous splicing mutation (c.1101+1G>T) in intron 6 and a heterozygous missense mutation in exon 2 (c.296G>A; Gly99Asp). The patient's elder brother who had MLD is believed to have had the same mutation, which may be correlated with a rapidly deteriorating clinical course. This study identified a novel mutation in the ARSA gene, related to a late-infantile form of MLD with a lethal clinical course and suggested that molecular diagnosis of patients may be useful in early diagnosis and for deciding intervention measures for their family members.

A novel KRIT1 gene mutation in a patient with cerebral and multiple spinal cavernous malformations.

Cavernous malformations (CMs) occur most often in the brain, but they have also been observed in extracranial regions. The synchronous finding of CMs in both the brain and spinal cord is rare. Furthermore, multiple spinal cord CMs are exceedingly rare, with only one reported case in Korea. Here, we present a 65-yr-old Korean male with cerebral CMs (CCMs) and multiple spinal CMs. The patient complained of a gait disturbance and left foot paresthesia. The lesions involved the entire neuraxis, including the temporal lobe, right thalamus, and the cervical, thoracic, and lumbar spinal cord. Molecular analysis of the KRIT1 (CCM1) gene identified a novel heterozygous frameshift mutation (c.816delG; p. Arg273GlufsX3) in the KRIT1 gene. Although genetic analyses were not performed in the patient's family members, the family history of cerebral hemorrhage in his mother, sons, sister, and the sister's sons suggests an autosomal dominant inheritance of the mutation. This study reveals a novel mutation of the KRIT1 gene related to CCM and multiple spinal CMs. Based on these findings, molecular diagnosis might be beneficial for early diagnosis and treatment of the family members.

[Clinical characteristics and ALB gene mutation analysis of Korean patients with bisalbuminemia].

BACKGROUND: Bisalbuminemia is a hereditary or an acquired condition characterized by the presence of 2 albumin variants with different mobilities on serum protein electrophoresis (SPE). The clinical significance of bisalbuminemia has not been clearly established. However, some regions of the albumin variant may affect the biochemical analysis of biomolecules such as steroid or thyroid hormones by altering their albumin-binding affinities. In this study, we analyzed the clinical manifestations, genetic variations, and the albumin-binding characteristics in Korean patients with bisalbuminemia. METHODS: We performed SPE for samples from 580 Korean subjects and identified bisalbuminemia on the basis of the results of SPE. The clinical and biochemical characteristics, ALB gene mutations, and the structures of the albumin variants of patients with bisalbuminemia were analyzed. RESULTS: SPE showed bisalbuminemia in 2 patients. One patient showed a genetic variation known as Nagasaki-1 (Asp293Gly) and the other showed a hitherto unreported missense mutation (c.593A>T; Lys198Ile). In both cases, the serum concentrations of the substances with binding affinity for albumin were not affected, and the mutation sites of the albumin were not located with the protein-binding loci. CONCLUSIONS: The 2 Korean patients with bisalbuminemia showed genetic variations, including a novel missense mutation. The ALB gene analysis with 3D modeling is useful for determining the nature of bisalbuminemia and for predicting the effects on the albumin-binding affinity of other biochemical compounds.

Rapid diagnosis of vivax malaria by the SD Bioline Malaria Antigen test when thrombocytopenia is present.

An easy and reliable diagnostic method for malaria is highly desirable. We examined the recently introduced SD Bioline Malaria Antigen test, which detects Plasmodium lactate dehydrogenase, with the additional aid of the presence or absence of thrombocytopenia to diagnose vivax malaria. We enrolled 732 patients with clinically suspected malaria in an area where vivax malaria is endemic. We performed microscopic examination of thin film, applied the SD Bioline Malaria Antigen test, and checked platelet counts. One hundred ninety-five patients were smear positive for vivax malaria. The sensitivity of the SD Bioline Malaria Antigen test was 96.4%, and its specificity was 98.9%. We found that 95.4% of malaria patients had thrombocytopenia, and the proportion with malaria increased as platelet counts decreased. A positive SD Bioline Malaria Antigen test when thrombocytopenia was present showed a 100% positive predictive value for vivax malaria. In conclusion, the SD Bioline Malaria Antigen test is a rapid and accurate diagnostic method for vivax malaria, and a platelet count can facilitate a rapid diagnosis of malaria.