QuantiFERON monitor predicts early cytomegalovirus infection and viral burden in allogeneic hematopoietic stem cell transplantation.

INTRODUCTION: Cytomegalovirus (CMV) infection is a major cause of transplantation-related morbidity and mortality. This study assessed the utility of the QuantiFERON monitor (QFM; Qiagen) for the prediction of early CMV infection and viral burden. METHODS: QuantiFERON-CMV (QF-CMV; Qiagen) and QFM were measured at the post-allogeneic hematopoietic stem cell transplantation (HSCT) week 4. CMV DNA was measured at every visit until post-HSCT week 24. The QFM cutoff specific to CMV infection was established. RESULT: At the post-HSCT week 4, the QFM cutoff predicting CMV infection was 86.95 IU/mL. While QF-CMV results at the post-HSCT week 4 were associated with high-level CMV infection (CMV DNA ≥ 5,000 IU/mL) but not with CMV infection (CMV DNA ≥ 500 IU/mL), QFM was associated with both CMV infection and high-level CMV infection. Both indeterminate QF-CMV and nonreactive QFM were associated with increased peak CMV DNA. CONCLUSION: Low QFM is a risk factor for CMV infection and increased CMV viral loads. QFM at post-HSCT week 4 can be utilized as an assay to predict the risk and burden of early CMV infection in HSCT recipients, in conjunction with other risk factors.

Effect of Helicobacter pylori infection and its eradication on the expression of tight junction proteins in the gastric epithelium in relation to gastric carcinogenesis.

BACKGROUND: Tight junction proteins (TJPs) play a role in epithelial defense mechanisms. However, the effect of Helicobacter pylori (Hp) on TJPs remains unclear. This study aimed to evaluate the expression of TJPs in relation to Hp infection and eradication in gastric carcinogenesis. METHODS: In total, 510 subjects (284 controls and 226 gastric cancer [GC] patients) were prospectively enrolled in the study. The expression of claudin-1 and -2 (CLDN-1, -2), occludin (OCLN), and tight junction protein 1 (TJP1) was measured based on their Hp infection status in normal corpus mucosa and evaluated following Hp eradication using quantitative real-time polymerase chain reaction (qPCR) and immunohistochemistry (IHC). RESULTS: The expression of TJP1 in Hp+ controls was significantly lower than that in Hp- controls (p = 0.006), whereas it was higher in Hp+ than in Hp- GC patients (p = 0.001). Moreover, the increased expression of TJP1 in Hp+ GC patients was reduced to levels in Hp- within a year after Hp eradication and was maintained for more than 5 years. Furthermore, IHC results for TJP1 were similar to qPCR results. In particular, the higher IHC staining intensity of TJP1 in the cytosol of GC patients (p = 0.019) decreased after Hp eradication (p = 0.040). CONCLUSION: Hp infection affects TJP expression. The high expression of TJP1 in Hp+ GC patients was restored to control levels after Hp eradication, suggesting that TJP1 plays a role in gastric carcinogenesis.

Diffusible Signaling Factor, a Quorum-Sensing Molecule, Interferes with and Is Toxic Towards Bdellovibrio bacteriovorus 109J.

Bdellovibrio bacteriovorus 109J is a predatory bacterium which lives by predating on other Gram-negative bacteria to obtain the nutrients it needs for replication and survival. Here, we evaluated the effects two classes of bacterial signaling molecules (acyl homoserine lactones (AHLs) and diffusible signaling factor (DSF)) have on B. bacteriovorus 109J behavior and viability. While AHLs had a non-significant impact on predation rates, DSF considerably delayed predation and bdelloplast lysis. Subsequent experiments showed that 50 µM DSF also reduced the motility of attack-phase B. bacteriovorus 109J cells by 50% (38.2 ± 14.9 vs. 17 ± 8.9 µm/s). Transcriptomic analyses found that DSF caused genome-wide changes in B. bacteriovorus 109J gene expression patterns during both the attack and intraperiplasmic phases, including the significant downregulation of the flagellum assembly genes and numerous serine protease genes. While the former accounts for the reduced speeds observed, the latter was confirmed experimentally with 50 µM DSF completely blocking protease secretion from attack-phase cells. Additional experiments found that 30% of the total cellular ATP was released into the supernatant when B. bacteriovorus 109J was exposed to 200 µM DSF, implying that this QS molecule negatively impacts membrane integrity.

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.

On the Feasibility of Using an Ear-EEG to Develop an Endogenous Brain-Computer Interface.

Brain-computer interface (BCI) studies based on electroencephalography (EEG) measured around the ears (ear-EEGs) have mostly used exogenous paradigms involving brain activity evoked by external stimuli. The objective of this study is to investigate the feasibility of ear-EEGs for development of an endogenous BCI system that uses self-modulated brain activity. We performed preliminary and main experiments where EEGs were measured on the scalp and behind the ears to check the reliability of ear-EEGs as compared to scalp-EEGs. In the preliminary and main experiments, subjects performed eyes-open and eyes-closed tasks, and they performed mental arithmetic (MA) and light cognitive (LC) tasks, respectively. For data analysis, the brain area was divided into four regions of interest (ROIs) (i.e., frontal, central, occipital, and ear area). The preliminary experiment showed that the degree of alpha activity increase of the ear area with eyes closed is comparable to those of other ROIs (occipital > ear > central > frontal). In the main experiment, similar event-related (de)synchronization (ERD/ERS) patterns were observed between the four ROIs during MA and LC, and all ROIs showed the mean classification accuracies above 70% required for effective binary communication (MA vs. LC) (occipital = ear = central = frontal). From the results, we demonstrated that ear-EEG can be used to develop an endogenous BCI system based on cognitive tasks without external stimuli, which allows the usability of ear-EEGs to be extended.

TSWIFT, a novel method for iterative staining of embedded and mounted human brain sections.

Comprehensive characterization of protein networks in mounted brain tissue represents a major challenge in brain and neurodegenerative disease research. In this study, we develop a simple staining method, called TSWIFT, to iteratively stain pre-mounted formalin fixed, paraffin embedded (FFPE) brain sections, thus enabling high-dimensional sample phenotyping. We show that TSWIFT conserves tissue architecture and allows for relabeling a single mounted FFPE sample more than 10 times, even after prolonged storage at 4 °C. Our results establish TSWIFT as an efficient method to obtain integrated high-dimensional knowledge of cellular proteomes by analyzing mounted FFPE human brain tissue.

Common Data Model-based Analysis of Selective Leukoreduction Protocol Compliance at Three Hospitals.

Background: The selective leukoreduction protocol (SLP) is limited in that patients who require it can be overlooked. We estimated SLP compliance (SLPC) using the Observational Medical Outcomes Partnership common data model (CDM). Methods: Patients were classified into eight groups: pre- and post-hematology disease (A and B), pre- and post-solid organ transplantation (C and D), solid cancer (E), immunodeficiency (F), anticancer therapy (G), and cardiovascular surgery (H). We examined the red blood cell (RBC) transfusion history from three hospital datasets comprising approximately three million patients over 20 years using CDM-based analysis. SLPC was calculated as the percentage of patients who received only leukoreduced RBCs in total patients transfused RBCs. Results: In total, 166,641 patients from three hospitals were enrolled in this study. From 2001 to 2021, SLPC in all groups, except H, tended to increase, although there were differences among the hospitals. Based on the most recent values (2017-2021), the SLPC in groups A, B, D, and G was maintained at ≥75% until 1,095 days before or after diagnosis or treatment. Groups E, F, and H had < 50% SLPC one day after diagnosis and treatment. Conclusions: CDM analysis supports the review of large datasets for SLPC evaluation. Although SLPC tended to improve in most patient groups, additional education and monitoring are needed for groups that continue to show low SLPC.

The new HLA-DQA1*03:50Q allele discovered by next-generation sequencing in a Korean family.

DQA1*03:50Q differs from DQA1*03:02:01:01 by a three-nucleotide insertion at gDNA position 3968 in exon 2.

Identification of a novel HLA-B allele, HLA-B*54:47, in a Korean individual.

B*54:47 allele differs from B*54:01:01:01 in codon 74 in exon 2.

Evaluation of Real-Time Endogenous Brain-Computer Interface Developed Using Ear-Electroencephalography.

While previous studies have demonstrated the feasibility of using ear-electroencephalography (ear-EEG) for the development of brain-computer interfaces (BCIs), most of them have been performed using exogenous paradigms in offline environments. To verify the reliable feasibility of constructing ear-EEG-based BCIs, the feasibility of using ear-EEG should be further demonstrated using another BCI paradigm, namely the endogenous paradigm, in real-time online environments. Exogenous and endogenous BCIs are to use the EEG evoked by external stimuli and induced by self-modulation, respectively. In this study, we investigated whether an endogenous ear-EEG-based BCI with reasonable performance can be implemented in online environments that mimic real-world scenarios. To this end, we used three different mental tasks, i.e., mental arithmetic, word association, and mental singing, and performed BCI experiments with fourteen subjects on three different days to investigate not only the reliability of a real-time endogenous ear-EEG-based BCI, but also its test-retest reliability. The mean online classification accuracy was almost 70%, which was equivalent to a marginal accuracy for a practical two-class BCI (70%), demonstrating the feasibility of using ear-EEG for the development of real-time endogenous BCIs, but further studies should follow to improve its performance enough to be used for practical ear-EEG-based BCI applications.

Which Health Impacts of Medical Device Adverse Event Should Be Reported Immediately in Korea?

OBJECTIVE: Immediate medical device adverse event (MDAE) reporting indications of Korea include death, life-threatening, hospitalization (initial or prolonged), disability or permanent damage, and congenital malformation or abnormalities. With the advent of new codes from the International Medical Device Regulators Forum, a study was undertaken to explore the applicability of health impact codes as immediate MDAE reporting indications in the Republic of Korea. METHOD: This domestic cross-sectional survey study was conducted for members from Medical Device Safety Information Monitoring Center in November 2019. For the annex F (health impact) codes defining health impact of an MDAE, we checked whether each code matched with the current indication and asked experts whether they agreed with each code as an indication of immediate reporting. Consensus was reached when ≥70% of experts agreed. RESULTS: A total of 28 experts from 19 centers responded to the survey. Of a total of 64 codes, 29 matched with the current indication. However, in an expert survey, 17 of 29 codes were not agreed for immediate reporting and 5 codes were found to be unmatched codes. For these 5 codes, experts agreed that they would need reporting immediately. Finally, only 17 codes achieved consensus for immediate reporting. CONCLUSIONS: There is a discrepancy between the code matched to the current immediate MDAE reporting indication and experts' consensus. Sufficient discussion and agreement would be needed to apply health impact codes for immediate reporting.

ABO-Incompatible Transfusion Events Reported in Written Judgments and in the Korean Hemovigilance System.

Fatal ABO-incompatible (ABOi) transfusion is one of the most common causes of transfusion-related death, but its reporting has been limited in Korea. We comprehensively reviewed ABOi transfusion events in Korea by analyzing cases reported in literature, Korean hemovigilance system (KOHEVIS) annual reports, and written judgments. Written judgments were assessed using a written judgment management system or a comprehensive legal information system. We found nine cases of ABOi transfusion events in written judgments (from 1953 to 2019), 16 in the KOHEVIS (from 2008 to 2018), and nine in published reports (from 1978 to 2019). One case was found in all three sources. Overall, we found 32 cases of ABOi transfusion events. Four cases died and 23 survived, while the outcomes for five were unavailable. ABOi transfusion errors occurred at the administration (50%, 16/32), sample (13%, 4/32), and testing (9%, 3/32) stages. The causes of errors were unavailable for nine cases (28%, 9/32). We report the status of ABOi transfusions in Korea and expect our results to contribute to the prevention of adverse reactions due to ABOi transfusion.

The novel HLA-B*40:489 allele identified in a Korean hematopoietic stem cell donor.

Single nucleotide substitution in codon 140 of HLA-B*40:02:01:01 results in the novel HLA-B*40:489 allele.

Preliminary feasibility assessment of CDM-based active surveillance using current status of medical device data in medical records and OMOP-CDM.

In recent years, there has been an emerging interest in the use of claims and electronic health record (EHR) data for evaluation of medical device safety and effectiveness. In Korea, national insurance electronic data interchange (EDI) code has been used as a medical device data source for common data model (CDM). This study performed a preliminary feasibility assessment of CDM-based vigilance. A cross-sectional study of target medical device data in EHR and CDM was conducted. A total of 155 medical devices were finally enrolled, with 58.7% of them having EDI codes. Femoral head prosthesis was selected as a focus group. It was registered in our institute with 11 EDI codes. However, only three EDI codes were converted to systematized nomenclature of medicine clinical terms concept. EDI code was matched in one-to-many (up to 104) with unique device identifier (UDI), including devices classified as different global medical device nomenclature. The use of UDI rather than EDI code as a medical device data source is recommended. We hope that this study will share the current state of medical device data recorded in the EHR and contribute to the introduction of CDM-based medical device vigilance by selecting appropriate medical device data sources.

The establishment of the Korean medical device safety information monitoring center: Reviewing ten years of experience.

Medical devices may revolutionize healthcare delivery but can lead to serious adverse events for treated patients and users. While reporting of adverse events related to medical devices is an essential starting point for post-market surveillance, underreporting of medical device adverse events is a global problem. Korea introduced a voluntary medical device adverse event reporting system in 2010, called the Medical Device Safety Information Monitoring Center, which has led to an increase in adverse event reports. For 10 years, the Medical Device Safety Information Monitoring Center has analyzed medical device adverse events systematically and has provided active feedback to the manufacturers and education on safe use. Recently, the Medical Device Safety Information Monitoring Center contributed to harmonization of international medical device vigilance through the sharing of adverse events. This experience of Korea might contribute to improvements in medical device vigilance, which is a critical prerequisite for improving medical device policies and regulations.

C3d-Positive Preformed DSAs Tend to Persist and Result in a Higher Risk of AMR after Kidney Transplants.

C3d-binding assays have been introduced as methods for the prediction of the presence of complement-binding functional antibodies; however, the prognostic value of C3d-positive preformed donor-specific antibodies (pDSAs) has not been fully evaluated. In this study, we performed a retrospective investigation of the association of pDSAs and their C3d-binding capacity with one-year clinical outcomes. pDSAs were defined as donor-specific antibodies (DSAs) that were produced before kidney transplants (KTs) (pre-pDSAs) or within the first four weeks after KTs, owing to rebound immune response (post-pDSAs). Of 455 adult KT recipients, pre-pDSAs and post-pDSAs were found in 56 (12.3%) and 56 (12.3%) recipients, respectively, and C3d-positive post-pDSAs were found in 13 recipients (2.9%) in total. Approximately half of the C3d-negative pre-pDSAs (37/73, 50.7%) disappeared after transplantation; however, all C3d-positive pre-pDSAs (8/8, 100%) persisted after transplantation despite desensitization (p = 0.008). C3d-positive pDSAs were significantly associated with a higher incidence and risk of AMR (p < 0.001, OR 94.467-188.934). Identification of the C3d-binding activity of pDSAs before and early after KT is important for predicting the persistence of pDSAs and the risk of AMR induced by the presence of pDSAs.

Flow Cytometry for the Diagnosis of Primary Immunodeficiency Diseases: A Single Center Experience.

PURPOSE: While there is an urgent need for diagnosis and therapeutic intervention in patients with primary immunodeficiency diseases (PIDs), current genetic tests have drawbacks. We retrospectively reviewed the usefulness of flow cytometry (FCM) as a quick tool for immunophenotyping and functional assays in patients suspected to have PIDs at a single tertiary care institute. METHODS: Between January 2001 and June 2018, patients suspected of having PIDs were subjected to FCM tests, including lymphocyte subset analysis, detection of surface- or intracellular-target proteins, and functional analysis of immune cells, at Samsung Medical Center, Seoul, Korea. The genetic diagnosis was performed using Sanger or diagnostic exome sequencing. RESULTS: Of 60 patients diagnosed with definite or probable PID according to the European Society of Immune Deficiencies criteria, 24 patients were provided with useful information about immunological dysfunction after initial FCM testing. In 10 patients, the PID diagnosis was based on abnormal findings in FCM testing without genetic tests. The FCM findings provided strong evidence for the diagnosis of severe combined immunodeficiency (n = 6), X-linked chronic granulomatous diseases (CGD) (n = 6), leukocyte adhesion deficiency type 1 (n = 3), X-linked agammaglobulinemia (n = 11), autoimmune lymphoproliferative syndrome-FASLG (n = 1), and familial hemophagocytic lymphohistiocytosis type 2 (n = 1), and probable evidence for autosomal recessive-CGD (n = 2), autosomal dominant-hyper-immunoglobulin E (IgE)-syndrome (n = 1), and STAT1 gain-of-function mutation (n = 1). In PIDs derived from PIK3CD (n = 2), LRBA (n = 2), and CTLA4 mutations (n = 3), the FCM test provided useful evidence of immune abnormalities and a tool for treatment monitoring. CONCLUSIONS: The initial application of FCM, particularly with known protein targets on immune cells, would facilitate the timely diagnosis of PIDs and thus would support clinical decisions and improve the clinical outcome.

Inducing Transient Mixed Chimerism for Allograft Survival Without Maintenance Immunosuppression With Combined Kidney and Bone Marrow Transplantation: Protocol Optimization.

BACKGROUND: Tolerance induction is an important goal in the field of organ transplantation. We have sequentially modified our conditioning regimen for induction of donor-specific tolerance in recipients of major histocompatibility complex-mismatched combined kidney and bone marrow transplantation (CKBMT). METHODS: From December 2011 to May 2017, 8 major histocompatibility complex-mismatched patients received CKBMT. The initial conditioning regimen (protocol 1) consisted of cyclophosphamide (CP), rituximab, rabbit antithymocyte globulin, and thymic irradiation. Tacrolimus and steroids were used for the maintenance of immunosuppression (IS). RESULTS: This regimen was complicated by transient acute kidney injury, which has been the major clinical feature of engraftment syndrome and side effects of CP, although one of 2 subjects successfully discontinued his IS for 14 months. The conditioning regimen was modified by reducing the CP dose and adding fludarabine (protocol 2). The final modification was reducing the fludarabine and rabbit antithymocyte globulin doses (protocol 3). Mixed chimerism, detected by the short tandem repeat method, was achieved transiently in all subjects for 3-20 weeks. Among the 3 subjects treated with protocol 2, IS was successfully discontinued for >35 months in one subject, but the other 2 subjects suffered from severe BK virus-associated nephritis. All 3 subjects treated with protocol 3 tolerated the protocol well and have successfully discontinued IS for >4-41 months. Interestingly, de novo donor-specific antibody was not detected in any subject during all the follow-up periods. CONCLUSIONS: Our clinical trial has shown that long-term renal allograft survival without maintenance IS can be achieved by induction of mixed chimerism following CKBMT.

Effects of Different Re-referencing Methods on Spontaneously Generated Ear-EEG.

In recent years, electroencephalography (EEG) measured around the ears, called ear-EEG, has been introduced to develop unobtrusive and ambulatory EEG-based applications. When measuring ear-EEGs, the availability of a reference site is restricted due to the miniaturized device structure, and therefore a reference electrode is generally placed near the recording electrodes. As the electrical brain activity recorded at a reference electrode closely placed to recording electrodes may significantly cancel or influence the brain activity recorded by the recording electrodes, an appropriate re-referencing method is often required to mitigate the impact of the reference brain activity. In this study, therefore, we systematically investigated the impact of different re-referencing methods on ear-EEGs spontaneously generated from endogenous paradigms. To this end, we used two ear-EEG datasets recorded behind both ears while subjects performed an alpha modulation task [eyes-closed (EC) and eyes-open (EO)] and two mental tasks [mental arithmetic (MA) and mental singing (MS)]. The measured ear-EEGs were independently re-referenced using five different methods: (i) all-mean, (ii) contralateral-mean, (iii) ipsilateral-mean, (iv) contralateral-bipolar, and (v) ipsilateral-bipolar. We investigated the changes in alpha power during EO and EC tasks, as well as event-related (de) synchronization (ERD/ERS) during MA and MS. To evaluate the effects of re-referencing methods on ear-EEGs, we estimated the signal-to-noise ratios (SNRs) of the two ear-EEG datasets, and assessed the classification performance of the two mental tasks (MA vs. MS). Overall patterns of changes in alpha power and ERD/ERS were similar among the five re-referencing methods, but the contralateral-mean method showed statistically higher SNRs than did the other methods for both ear-EEG datasets, except in the contralateral-bipolar method for the two mental tasks. In concordance with the SNR results, classification performance was also statistically higher for the contralateral-mean method than it was for the other re-referencing methods. The results suggest that employing contralateral mean information can be an efficient way to re-reference spontaneously generated ear-EEGs, thereby maximizing the reliability of ear-EEG-based applications in endogenous paradigms.