Performance Evaluation of Two Kinds of Rapid Antigen Test Kits for Detection of COVID-19 Infection.

BACKGROUND: The diagnostic standard for COVID-19 infection is real-time reverse transcription-polymerase chain reaction (rRT-PCR) of nasopharyngeal swab and oropharyngeal swab specimens. Rapid antigen tests are cheaper and easier to use than the rRT-PCR method. Although the COVID-19 pandemic is settling down, seasonal epi¬demic is expected. In this study, the performance of two rapid antigen test kits was evaluated based on rRT-PCR test results. METHODS: A total of 346 residual samples was tested by the PowerChek SARS-CoV-2 Real-time PCR Kit or STAN-DARD M nCoV Real-Time-Detection kit, STANDARD Q COVID-19 Ag test kit (SQ RAT), and ND COVID-19 Ag test kit (ND RAT). RESULTS: Compared to rRT-PCR as the standard method, the SQ RAT test kit yielded 77.1% sensitivity (101/131) and 100% specificity (215/215), and the ND RAT yielded 89.3% sensitivity (117/131) and 100% specificity (215/ 215). Both RATs showed sensitivity greater than 85% in samples with RdRp gene Ct value less than 25. There was a false-negative case suspected of prozone phenomenon. CONCLUSIONS: Both RATs showed significant performance, but users should beware of the prozone phenomenon.

Frequency histograms of three high-sensitivity cardiac troponin assays in a reference population.

BACKGROUND: Cardiac troponin (cTn) values above the 99th percentile upper reference limit (URL) indicate myocardial injury. We established 99th percentile URLs for three high-sensitivity cTn (hs-cTn) assays (Beckman Coulter Access hs-cTnI, Abbott STAT hs-cTnI, and Roche Elecsys hs-cTnT) using a healthy population in Korea. METHODS: Each cTn value was measured by three assays and analyzed by dividing by gender and age. RESULTS: The frequency histograms of log-transformed cTn values for Beckman and Abbott assays exhibited a bell-shaped distribution. The 99th percentile URLs were 9.8, 17.4, and 17.3 ng/L in the total population; 10.9/9.0, 18.9/17.0, and 18.9/17.7 ng/L in the male/female population (p < 0.001 for all three assays); and 11.2/7.2, 19.9/14.5, and 22.7/9.3 ng/L in the older/younger population (p < 0.001 for all three assays) for Beckman, Abbott, and Roche assays, respectively. CONCLUSION: Among the three assays, bell-shaped distributions were observed in a frequency histogram of log-transformed cTn values for healthy population in Beckman and Abbott assays. Also, our findings show that the 99th percentile URLs for cTn levels vary not only by gender but age.

Application of Thromboelastographic Markers to Predict the Survival in Acute Trauma Patients.

BACKGROUND: The aim of the study is to investigate the coagulation status in trauma patients using thromboelastography and their association with survival and blood transfusion. METHODS: We included 452 trauma patients who visited the trauma center of Uijeongbu St. Mary's Hospital. The thromboelastography (TEG) clotting variables and routine coagulation tests were evaluated. Also, we investigated the transfusion requirement and mortality during hospitalization period. RESULTS: The mean age was 52.3 years and the mortality rate was 39/452 (8.6%). Lower GCS, longer TEG K-time, and lower TEG MA were independent factors associated with mortality. The lower MA group demonstrated the highest probability of survival (odds ratio 0.207), followed by prolonged R-time (odds ratio 0.220). The patient numbers in fibrinolysis shutdown (SD), physiologic fibrinolysis, and hyperfibrinolysis groups were 219 (52.3%), 131 (31.4%), and 68 (16.3%), respectively. The mortality rates of fibrinolysis SD group (11.9%) and hyperfibrinolysis (8.8%) were higher than the physiologic fibrinolysis groups (3.8%). The cutoff obtained from ROC analysis was found to be suitable for predicting survival. The transfusion requirements were significantly higher in the fibrinolysis SD group than in the other two groups. CONCLUSIONS: TEG based markers were shown to be more useful to make a diagnosis of coagulopathies including dysfibrinolysis and predict the survival than routine coagulation tests. Dysfunctional fibrinolysis showed higher mortality than physiologic group. If multiple integrations of each TEG markers are used, it would be helpful for prompt diagnosis and management of coagulopathies and to decrease preventable deaths in trauma.

Epidemiologic Linkage of COVID-19 Outbreaks at Two University-affiliated Hospitals in the Seoul Metropolitan Area in March 2020.

BACKGROUND: Coronavirus disease 2019 (COVID-19) outbreaks emerged at two university-affiliated hospitals in Seoul (hospital A) and Uijeongbu City (hospital S) in the metropolitan Seoul area in March 2020. The aim of this study was to investigate epidemiological links between the outbreaks using whole genome sequencing (WGS) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: Fifteen patients were enrolled in the study, including four non-outbreak (A1-A4) and three outbreak cases (A5-A7) in hospital A and eight cases (S1-S8) in hospital S. Patients' hospital stays, COVID-19 symptoms, and transfer history were reviewed. RNA samples were submitted for WGS and genome-wide single nucleotide variants and phylogenetic relationships were analyzed. RESULTS: The index patient (A5) in hospital A was transferred from hospital S on 26 March. Patients A6 and A7 were the family caregiver and sister, respectively, of the patient who shared a room with A5 for 4 days. Prior to transfer, A5 was at the next bed to S8 in the emergency room on 25 March. Patient S6, a professional caregiver, took care of the patient in the room next to S8's room for 5 days until 22 March and then S5 for another 3 days. WGS revealed that SARS-CoV-2 in A2, A3, and A4 belong to clades V/B.2, S/A, and G/B.1, respectively, whereas that of A5-A7 and S1-S5 are of the V/B.2.1 clade and closely clustered. In particular, SARS-CoV-2 in patients A5 and S5 showed perfect identity. CONCLUSION: WGS is a useful tool to understand epidemiology of SARS-CoV-2. It is the first study to elucidate the role of patient transfer and caregivers as links of nosocomial outbreaks of COVID-19 in multiple hospitals.

Multilaboratory Evaluation of the MALDI-TOF Mass Spectrometry System, MicroIDSys Elite, for the Identification of Medically Important Filamentous Fungi.

With the increasing number of fungal infections and immunocompromised patients, rapid and accurate fungal identification is required in clinical microbiology laboratories. We evaluated the applicability of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) system, MicroIDSys Elite (ASTA Corp., South Korea) for the identification of medically important filamentous fungi. A total of 505 strains comprising 37 genera and 90 species collected from 11 Korean hospitals were sent to the microbiology laboratory of International St. Mary's Hospital. All isolates were tested using MicroIDSys Elite, and data were analyzed using the MoldDB v.1.22 database (ASTA). Correct identification rates were compared with the multigene sequencing results. MicroIDSys Elite correctly identified 86.5% (437/505) and 88.9% (449/505) of all tested isolates at the species and genus level, respectively. About 98.2% of Aspergillus isolates were identified at the species level, including cryptic and rare species of A. calidoustus, A. tamarii, A. lentulus, A. versicolor and A. aculeatus. MicroIDSys Elite identified 75.0% of basidiomycetes, including Schizophyllum commune, and 84.3% of the dermatophytes. It also distinguished Sprothrix globosa at the species level. The mean scores of total isolates corresponding to correct species identification were significantly higher than those obtained for genus-level identification (253.5 ± 50.7 vs. 168.6 ± 30.3, P < 0.001). MicroIDSys Elite showed high accuracy for the identification of filamentous fungi, including cryptic and rare Aspergillus species. It is suitable for use in clinical laboratories as a rapid and efficient tool for clinical mold identification. Further evaluations are recommended for MicroIDSys Elite as a rapid and efficient tool for the identification of medically important filamentous fungi.

Isolation of Coxiella burnetii in patients with nonspecific febrile illness in South Korea.

BACKGROUND: The number of human Q fever cases in South Korea has been rapidly increasing since 2015. We report the first isolation of Coxiella burnetii in Korea in two patients who initially presented with non-specific febrile illness and were finally diagnosed with acute Q fever in South Korea. CASE PRESENTATION: Two adult patients with fever had serologic tests against C. burnetii initially negative, and polymerase chain reaction against 16S rRNA using whole blood was also negative. After bacterial amplification of C. burnetii in immune-depressed mice, we isolated C. burnetii from patients with acute Q fever. The isolates KZQ2 and KZQ3 were confirmed by polymerase chain reaction, nucleotide sequence analysis, and morphologic observation using a transmission electron microscope. CONCLUSIONS: These results can help us understand the clinical and epidemiologic features of Q fever in South Korea.

ID1-Mediated BMP Signaling Pathway Potentiates Glucagon-Like Peptide-1 Secretion in Response to Nutrient Replenishment.

Glucagon-like peptide-1 (GLP-1) is a well-known incretin hormone secreted from enteroendocrinal L cells in response to nutrients, such as glucose and dietary fat, and controls glycemic homeostasis. However, the detailed intracellular mechanisms of how L cells control GLP-1 secretion in response to nutrients still remain unclear. Here, we report that bone morphogenetic protein (BMP) signaling pathway plays a pivotal role to control GLP-1 secretion in response to nutrient replenishment in well-established mouse enteroendocrinal L cells (GLUTag cells). Nutrient starvation dramatically reduced cellular respiration and GLP-1 secretion in GLUTag cells. Transcriptome analysis revealed that nutrient starvation remarkably reduced gene expressions involved in BMP signaling pathway, whereas nutrient replenishment rescued BMP signaling to potentiate GLP-1 secretion. Transient knockdown of inhibitor of DNA binding (ID)1, a well-known target gene of BMP signaling, remarkably reduced GLP-1 secretion. Consistently, LDN193189, an inhibitor of BMP signaling, markedly reduced GLP-1 secretion in L cells. In contrast, BMP4 treatment activated BMP signaling pathway and potentiated GLP-1 secretion in response to nutrient replenishment. Altogether, we demonstrated that BMP signaling pathway is a novel molecular mechanism to control GLP-1 secretion in response to cellular nutrient status. Selective activation of BMP signaling would be a potent therapeutic strategy to stimulate GLP-1 secretion in order to restore glycemic homeostasis.

Performance of a Novel Fluorogenic Assay for Detection of Carbapenemase-Producing Enterobacteriaceae from Bacterial Colonies and Directly from Positive Blood Cultures.

Rapid and accurate detection of carbapenemase-producing Enterobacteriaceae (CPE) is critical for appropriate treatment and infection control. We compared a rapid fluorogenic assay using a carbapenem-based fluorogenic probe with other phenotypic assays: modified carbapenem inactivation method (mCIM), Carba NP test (CNP), and carbapenemase inhibition test (CIT). A total of 217 characterized isolates of Enterobacteriaceae were included as follows: 63 CPE; 48 non-carbapenemase-producing carbapenem-resistant Enterobacteriaceae (non-CP-CRE); 53 extended-spectrum ß-lactamase producers; and 53 third-generation-cephalosporin-susceptible isolates. The fluorogenic assay using bacterial colonies (Fluore-C) was conducted by lysing the isolates followed by centrifugation and mixing the supernatant with fluorogenic probe. In addition, for the fluorogenic assay using spiked blood culture bottles (Fluore-Direct), pellets were obtained via the saponin preparation method, which can directly identify the pathogens using matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS). The fluorescence signal was measured over 50 min using a fluorometer. The fluorescent signal of CPE was significantly higher than that of non-CPE in both Fluore-C (median relative fluorescence units [RFU] [range], 5,814 [240 to 32,009] versus 804 [36 to 2,480], respectively; P < 0.0001) and Fluore-Direct (median RFU [range], 10,355 [1,689 to 31,463] versus 1,068 [428 to 2,155], respectively; P < 0.0001) tests. Overall, positive and negative percent agreements of Fluore-C, mCIM, CNP, CIT, and Fluore-Direct were 100% and 98.7%, 98.3% and 97.5%, 88.1% and 100%, 96.4% and 98.7%, and 98.3% and 98.1%, respectively. The relatively lower positive percent agreement (PPA) of CNP was mainly observed in OXA-type CPE. The fluorogenic assay showed excellent performance with bacterial colonies and also directly from positive blood cultures. We included many non-CP-CRE isolates for strict evaluation. The fluorogenic assay will be a useful tool for clinical microbiology laboratories.

Performance of the Dimension TAC assay and comparison of multiple platforms for the measurement of tacrolimus.

BACKGROUND: Therapeutic monitoring of tacrolimus is essential for reducing organ rejection and adverse effects. The measurement of tacrolimus in whole blood is taken by many automated platforms. We evaluated the analytical performance of the Dimension TAC assay, which is an upgraded reagent from the previous Dimension TACR assay. METHODS: The evaluations involved determination of precision, linearity, detection capability, and reagent lot-to-lot variability between three lot numbers. Correlation studies were conducted using the Dimension TACR assay, Architect, Elecsys assay, and MassTrak LC-MS/MS. RESULTS: The total coefficient of variation was below 10%. Acceptable linearity was observed in their respective reportable ranges. The limit of blank, limit of detection, and limit of quantification were 0.29, 0.47, and 0.81 ng/mL, respectively. Correlation analysis indicated that the Dimension TAC assay results were comparable to that of the Dimension TACR assay, Architect, and Elecsys results in liver and heart transplant patients. In kidney transplant patients, the Dimension TAC assay showed the poor correlation with Architect and Elecsys. The results from these assays were slightly higher than that of MassTrak. We found little lot-to-lot reagent variation among the reagents evaluated. CONCLUSION: The overall analytical performance of the Dimension TAC assay is acceptable for therapeutic monitoring in clinical practice. Our study that compared different platforms may provide some useful information regarding which test method to use.

Wire-guided intraduodenal ultrasonography using a catheter probe in the differential diagnosis of enlarged ampullary lesions.

BACKGROUND AND AIM: It can be difficult to identify the cause of an enlarged ampulla of Vater (AOV). This study evaluated the accuracy of wire-guided intraduodenal ultrasonography (US) for the differential diagnosis of an enlarged AOV during endoscopic retrograde cholangiopancreatography (ERCP). PATIENTS AND METHODS: Thirty-four patients with enlarged AOVs of unknown cause identified on imaging studies or endoscopic observations underwent wire-guided intraduodenal US using a catheter probe. RESULTS: The final diagnoses were malignant or premalignant tumors in 10 patients (29.4%), stones in nine patients (26.5%), inflammation in 14 patients (41.2%), and cyst in one patient (2.9%). The overall diagnostic accuracy of intraduodenal US for enlarged AOVs was 91.2%. The diagnostic accuracies of stones, inflammation, and AOV tumors were 100.0%, 94.1%, and 91.1%, respectively. CONCLUSIONS: Wire-guided intraduodenal US using a catheter probe is readily applicable during ERCP and may be useful in the differential diagnosis of enlarged ampullary lesions.

Clinical and Genetic Features of Coxiella burnetii in a Patient with an Acute Febrile Illness in Korea.

Although Q fever is an important zoonotic infection with a worldwide distribution, no human isolates of Coxiella burnetii have been identified in Korea. For the first time, we identified the nucleotide sequence of C. burnetii from a 32-year-old man with an acute febrile illness in Korea. Diagnosis of acute Q fever was confirmed by seroconversion using indirect immunofluorescence antibody assays. Phylogenetic analysis demonstrated high sequence similarity (99.6%-100%) with C. burnetii 16S rRNA sequences identified from the reservoir. These results are the first genetic analysis of C. burnetii in a human case of Q fever in Korea.

Effectiveness of a newly designed antireflux valve metal stent to reduce duodenobiliary reflux in patients with unresectable distal malignant biliary obstruction: a randomized, controlled pilot study (with videos).

BACKGROUND AND AIMS: In patients with unresectable distal malignant biliary obstruction (MBO), endoscopic biliary drainage by using self-expandable metal stents (SEMSs) is an established palliative treatment. However, the placement of a SEMS across the major duodenal papilla prompts reflux of duodenal contents. In this study, we evaluated stent patency and duodenobiliary reflux caused by a newly developed SEMS with an antireflux valve (ARV) of the windsock type, compared with a conventional covered SEMS (cSEMS) in patients with MBO. METHODS: Between January 2013 and September 2014, 77 patients with unresectable distal MBO were assigned randomly to groups treated with an ARV metal stent (ARVMS) group (39 patients) or a conventional cSEMS group (38 patients). In all patients, a barium meal examination was performed to evaluate reflux of barium within the SEMS and intrahepatic bile ducts. The primary outcome was stent patency duration. Secondary outcomes were the rates of technical and clinical success, duodenobiliary reflux on barium meal examination, factors causing stent dysfunction, overall patient survival, and adverse events. RESULTS: Stent placement was technically successful in all patients. The clinical success rates were not statistically significantly different between the ARVMS and cSEMS groups (97.4% vs 97.4%, P = 1.000). Overall reflux of barium was significantly lower in the ARVMS group than the cSEMS group (7.7% vs 100%, P < .001). The cumulative duration of stent patency was significantly longer in the ARVMS group than in the cSEMS group (median ± SD, 407 ± 92 vs 220 ± 37 days; P = .013). On multivariate analysis, complete duodenobiliary reflux (odds ratio, 5.7, P = .004) and ampullary cancer (odds ratio, 8.98, P = .012) were identified as independent risk factors for stent dysfunction. There was no significant difference between the 2 groups in overall patient survival or in the incidence of adverse events. CONCLUSIONS: The newly developed ARVMS seemed to have a superior duration of stent patency and comparable safety compared with the cSEMS. In addition, the duodenobiliary reflux related to stent dysfunction can be prevented effectively by ARVMS. Further randomized, controlled trials using large numbers of subjects are required to confirm the benefit of SEMSs with antireflux function. (Clinical trial registration number: UMIN000012734.).

Correlation of cystoscopically confirmed periureterally located hunner lesion with vesicoureteral reflux: preliminary study in patients with interstitial cystitis.

OBJECTIVE: The purpose of this study is to evaluate the incidence of vesicoureteral reflux (VUR) in patients with interstitial cystitis (IC) and to explore the correlation between periureterally located Hunner lesions and ipsilateral VUR. MATERIALS AND METHODS: We evaluated 344 patients with IC who underwent cystoscopy (March 2012 to July 2013). Among these patients, 25 underwent voiding cystourethrography (VCUG) to check for the presence of VUR. We reviewed the cystoscopy findings (grade and location of Hunner lesions) and the results of VCUG (presence and grade of VUR). The relationship between VUR and periureterally located Hunner lesions and the association between cystoscopic grading of IC and VUR were evaluated. RESULTS: Of the 25 patients with IC, seven (28%) had VUR (two bilateral and five unilateral). Among nine separate ureters with VUR, seven (78%) had associated periureterally located Hunner lesions, as evaluated cystoscopically. The median bladder capacity was 200 mL for patients with VUR and 230 mL for patients without VUR, with no statistically significant difference between the two groups (p>0.05). There was a strong correlation between the presence of VUR and ipsilateral periureterally located Hunner lesions (p<0.05). However, there was no association between the severity of cystoscopy grading and the presence of VUR (p>0.05). CONCLUSION: According to our study, VUR is not an uncommon complication in patients with IC, and there is a statistically significant correlation between VUR and periureterally located Hunner lesions. We assume that, along with the decrease in bladder capacity, a periureterally located Hunner lesion may be an important factor in the development of VUR.

Evaluation of the INNOVANCE PFA P2Y assay and its association with CYP2C19 genotypes.

The purpose of this study was to evaluate associations between INNOVANCE PFA P2Y (PFA P2Y) test results and CYP2C19 genotypes and provide baseline data for PFA P2Y testing to establish a therapeutic monitoring strategy for clopidogrel. A total of 75 new patients with acute coronary syndrome with planned percutaneous coronary intervention were enrolled between June 2012 and September 2012. All patients received clopidogrel at an initial loading dose of 600 mg followed by a 75-mg daily maintenance dose. Blood samples were obtained on the third morning after clopidogrel loading. PFA P2Y, VerifyNow P2Y12 and VASP assays were used to determine platelet inhibition due to clopidogrel, and the Verigene CYP2C19 test was used for CYP2C19 genotyping. The genotype frequency of 75 patients was as follows: CYP2C19 *1/*1 (wild type), 28 (37.3%); *1/*2, 31 (41.3%); *1/*3, 4 (5.3%); *2/*2, 5 (6.7%); *2/*3, 5 (6.7%); *1/*17, 1 (1.3%); and *2/*17, 1 (1.3%). Classified according to CYP2C19 genotypes, there were 29 (38.7%) extensive metabolizers (EM) or ultra rapid metabolizers (UM), 35 (46.7%) intermediate metabolizers (IM), and 10 (13.3%) poor metabolizers (PM). Median (interquartile range) PFA P2Y closure times (seconds) were 119 (101-260), 300 (130-300) and 300 (300-300) in the PM, IM and EM or UM groups, respectively (p < 0.05). Median (interquartile range) VerifyNow PRUs were 294 (213-297), 215 (165-320) and 189 (118-279); and the VASP platelet reactivity index (%) was 52.7 (33.3-91.9), 59.9 (41.4-72.8) and 38.9 (26.8-62.2) in the PM, IM and EM or UM groups, respectively (p > 0.05). Compared with non-carriers, carriers of reduced function CYP2C19 alleles tended to have higher platelet reactivity after clopidogrel treatment. The cut-off for PM versus other groups (IM and EM or UM) was ≤ 141 seconds (AUC 0.704, sensitivity 70%, specificity 76.6%) on the ROC curve. A statistically significant correlation between PFA P2Y (seconds) and VerifyNow (PRU) was found (ρ = -0.47, p < 0.0001). In conclusion, the PFA P2Y test showed a statistically significant association with CYP2C19 metabolizer phenotypes based on CYP2C19 genotyping and effectively determined the risk groups resistant to clopidogrel therapy, including PM.

Influence of Preanalytical Variables on Prothrombin Time, Activated Partial Thromboplastin Time, and Fibrinogen.

BACKGROUND: In the present study, the influence of preanalytical variables on prothrombin time (PT), activated partial thromboplastin time (aPTT), and fibrinogen testing is investigated. METHODS: Samples collected from 104 patients were used for the study. PT, aPTT, and fibrinogen levels were tested with 50%-filled tubes to investigate the influence of sample volume. We measured the same parameters immediately after sampling, after 6 hours, and after 24 hours to investigate the influence of storage time. Samples were also tested after 6 hours at 4 degrees C to investigate the influence of storage temperature. RESULTS: Use of 50%-filled tubes did not alter the results of PT and fibrinogen testing, but caused a significant bias to the aPTT test. The results of aPTT at 24 hours were also significantly different from results immediately after sampling. However, uncentrifuged citrated samples stored for 24 hours at room temperature may still be suitable for PT and fibrinogen testing. Incubation at 4 degrees C for up to 6 hours did not bias the results of PT, aPTT, or fibrinogen testing. CONCLUSIONS: Whilst aPTT is malleable to preanalytical variables, PT and fibrinogen showed stable results across variations in sample volume, storage time, and temperature.

Usefulness of intraductal ultrasonography in icteric patients with highly suspected choledocholithiasis showing normal endoscopic retrograde cholangiopancreatography.

BACKGROUND: Choledocholithiasis is one of the causes of jaundice and may require urgent treatment. Endoscopic retrograde cholangiopancreatography (ERCP) has been the primary management strategy for choledocholithiasis. However, small stones can be overlooked during ERCP. AIM: The aim of this study was to evaluate the accuracy of intraductal ultrasonography (IDUS) for detecting choledocholithiasis in icteric patients with highly suspected common bile duct (CBD) stones without definite stone diagnosis on ERCP. METHODS: Ninety-five icteric (bilirubin ≥ 3 mg/dL) patients who underwent ERCP for highly suspected choledocholithiasis without definite filling defects on cholangiography were prospectively enrolled in the present study. We evaluated the bile duct using IDUS for the presence of stones or sludge. Reference standard for choledocholithiasis was endoscopic extraction of stone or sludge. RESULT: Bile duct stones were detected with IDUS in 31 of 95 patients (32.6%). IDUS findings were confirmed by endoscopic stone extraction in all patients. The mean diameter of CBD stones detected by IDUS was 2.9 mm (range 1-7 mm). IDUS revealed biliary sludge in 24 patients (25.2%) which was confirmed by sludge extraction in 21 patients (87.5%). In dilated CBD, detection rate of bile duct stone/sludge based on IDUS was significantly higher than in non-dilated CBD (p = 0.004). CONCLUSION: IDUS is useful for the detection of occult CBD stone on ERCP in icteric patients with highly suspected CBD stones.

Comparison of the delta neutrophil index with procalcitonin and C-reactive protein in sepsis.

BACKGROUND: The purpose of this study was to compare the diagnostic performance of the delta neutrophil index (DNI) with procalcitonin and C-reactive protein (CRP) for the prediction of sepsis and its outcome. METHODS: A total of 128 consecutive patients who were tested by blood culture were enrolled. The DNI, procalcitonin, and CRP were measured, the blood was cultured, and other clinical data were obtained by retrospective chart review. RESULTS: The DNI, procalcitonin and CRP increased with increasing disease severity (p < 0.05). The DNI (area under the curve (AUC) 0.932 for sepsis, 0.800 for survival) and procalcitonin (AUC 0.918 for sepsis, 0.831 for survival) had high diagnostic performance for the prediction of sepsis and survival. CRP also has good diagnostic power in predicting sepsis and survival (AUC 0.819 for sepsis, 0.723 for survival). The combination of the DNI and procalcitonin had higher AUC (0.964) than each of the biomakers for the prediction of sepsis. The cutoffs for the DNI, procalcitonin, CRP, and 'procalcitonin + DNI' for the diagnosis of sepsis were 12.3%, > 1.44 ng/mL, > 6.84 mg/L, and > 19.24, respectively. At least one of the DNI or procalcitonin values was high (> cutoff levels) in all sepsis or septic shock patients. CONCLUSIONS: The DNI can be obtained easily from automated hematological analysis and is cost effective. Furthermore, the DNI has a high diagnostic power for predicting sepsis and survival, similar to procalcitonin and better than CRP. The combination of DNI and procalcitonin may improve the ability to predict the severity of sepsis and survival.

Enhancing Diabetes Care through a Mobile Application: A Randomized Clinical Trial on Integrating Physical and Mental Health among Disadvantaged Individuals.

Background: This study examines integrating physical and mental healthcare for disadvantaged persons with type 2 diabetes mellitus and mild-to-moderate depression in the community, using a mobile application within a public-private-academic partnership. Methods: The Korean Diabetes Association has developed a mobile application combining behavioral activation for psychological well-being and diabetes self-management, with conventional medical therapy. Participants were randomly assigned to receive the application with usual care or only usual care. Primary outcomes measured changes in psychological status and diabetes selfmanagement through questionnaires at week 12 from the baseline. Secondary outcomes assessed glycemic and lipid control, with psychological assessments at week 16. Results: Thirty-nine of 73 participants completed the study (20 and 19 in the intervention and control groups, respectively) and were included in the analysis. At week 12, the intervention group showed significant reductions in depression severity and perceived stress compared to the control group. Additionally, they reported increased perceived social support and demonstrated improved diabetes self-care behavior. These positive effects persisted through week 16, with the added benefit of reduced anxiety. While fasting glucose levels in the intervention group tended to improve, no other significant differences were observed in laboratory assessments between the groups. Conclusion: This study provides compelling evidence for the potential efficacy of a mobile application that integrates physical and mental health components to address depressive symptoms and enhance diabetes self-management in disadvantaged individuals with type 2 diabetes mellitus and depression. Further research involving larger and more diverse populations is warranted to validate these findings and solidify their implications.

Co-inhibition of glutaminolysis and one-carbon metabolism promotes ROS accumulation leading to enhancement of chemotherapeutic efficacy in anaplastic thyroid cancer.

Anaplastic thyroid cancer (ATC) is one of the most aggressive tumors with an extremely poor prognosis. Based on the several biological features related to glutamine metabolism in ATC, we hypothesized glutaminolysis inhibition induces cell death in ATC cells. However, glutamine metabolism inhibition triggered cell growth arrest independent of cell death in ATC, suggesting that other signaling pathways avoid glutamine metabolism inhibition-induced stress exist. To investigate the functional mechanism against glutamine metabolism inhibition, we conducted mRNA and ATAC-Sequencing data analysis and found that glutamine deprivation increased ATF4-mediated one-carbon metabolism. When we inhibited PHGDH, the first rate-limiting enzyme for one-carbon metabolism, cell growth arrest was promoted upon glutamine metabolism inhibition by accumulating intracellular ROS. We next observed that the co-inhibition of glutamine and one-carbon metabolism could augment the anticancer effects of drugs used in patients with ATC. Finally, single-cell RNA sequencing analysis revealed that one-carbon metabolism was strengthened through the evolutionary process from PTC to ATC. Collectively, our data demonstrate that one-carbon metabolism has a potential role of modulation of cell fate in metabolic stress and can be a therapeutic target for enhancing antitumor effects in ATC.

In vitro and in vivo phototoxicity on gastric mucosa induced by methylene blue.

Background: Methylene blue (MB) is used endoscopically to demarcate tumors and as a photosensitizer in photodynamic therapy (PDT). However, there are few in vivo studies about its toxicity in healthy stomach tissue. We performed sequential in vitro and in vivo analyses of MB-induced phototoxicity. Methods: We performed in vitro experiments using the AGS human gastric cancer cell line treated with light-emitting diode (LED) irradiation (3.6 J/cm2) and MB. Cytotoxicity was evaluated using terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay. In vivo toxicity was evaluated in the stomach of beagles using the same dose of fiber-optic LED via gastroscopy, after spraying 0.1% and 0.5% MB solutions. Stomach tissue was also evaluated using the TUNEL assay. Results: In vitro, increased concentrations of MB led to higher TUNEL scores. However, cell viability was significantly lower after MB plus LED irradiation than after treatment with MB alone (P < 0.001). In vivo, the TUNEL score was highest immediately after treatment with 0.1% or 0.5% MB plus light irradiation, and the score was significantly higher in the LED illumination plus MB group than in the control group (P < 0.05). The elevated TUNEL score was maintained for 3 days in the MB plus light irradiation group but returned to normal levels on day 10. Conclusions: : Endoscopic light application with MB 0.5% concentration to the stomach may be regarded as a safe procedure despite some DNA injuries in the early period.