Background: Worldwide, sepsis is the leading cause of death in hospitals. If mortality rates in patients with sepsis can be predicted early, medical resources can be allocated efficiently. We constructed machine learning (ML) models to predict the mortality of patients with sepsis in a hospital emergency department. Methods: This study prospectively collected nationwide data from an ongoing multicenter cohort of patients with sepsis identified in the emergency department. Patients were enrolled from 19 hospitals between September 2019 and December 2020. For acquired data from 3,657 survivors and 1,455 deaths, six ML models (logistic regression, support vector machine, random forest, extreme gradient boosting [XGBoost], light gradient boosting machine, and categorical boosting [CatBoost]) were constructed using fivefold cross-validation to predict mortality. Through these models, 44 clinical variables measured on the day of admission were compared with six sequential organ failure assessment (SOFA) components (PaO 2 /FIO 2 [PF], platelets (PLT), bilirubin, cardiovascular, Glasgow Coma Scale score, and creatinine).The confidence interval (CI) was obtained by performing 10,000 repeated measurements via random sampling of the test dataset. All results were explained and interpreted using Shapley’s additive explanations (SHAP). Results: Of the 5,112 participants, CatBoost exhibited the highest area under the curve (AUC) of 0.800 (95% CI, 0.756–0.840) using clinical variables. Using the SOFA components for the same patient, XGBoost exhibited the highest AUC of 0.678 (95% CI, 0.626–0.730). As interpreted by SHAP, albumin, lactate, blood urea nitrogen, and international normalization ratio were determined to significantly affect the results. Additionally, PF and PLTs in the SOFA component significantly influenced the prediction results. Conclusion Newly established ML-based models achieved good prediction of mortality in patients with sepsis. Using several clinical variables acquired at the baseline can provide more accurate results for early predictions than using SOFA components. Additionally, the impact of each variable was identified.

Background: There are limited data on the accuracy of cloud-based speech recognition (SR) open application programming interfaces (APIs) for medical terminology. This study aimed to evaluate the medical term recognition accuracy of current available cloud-based SR open APIs in Korean. Methods: We analyzed the SR accuracy of currently available cloud-based SR open APIs using real doctor–patient conversation recordings collected from an outpatient clinic at a large tertiary medical center in Korea. For each original and SR transcription, we analyzed the accuracy rate of each cloud-based SR open API (i.e., the number of medical terms in the SR transcription per number of medical terms in the original transcription). Results: A total of 112 doctor–patient conversation recordings were converted with three cloud-based SR open APIs (Naver Clova SR from Naver Corporation; Google Speech-toText from Alphabet Inc.; and Amazon Transcribe from Amazon), and each transcription was compared. Naver Clova SR (75.1%) showed the highest accuracy with the recognition of medical terms compared to the other open APIs (Google Speech-to-Text, 50.9%, P < 0.001; Amazon Transcribe, 57.9%, P < 0.001), and Amazon Transcribe demonstrated higher recognition accuracy compared to Google Speech-to-Text (P< 0.001). In the sub-analysis, Naver Clova SR showed the highest accuracy in all areas according to word classes, but the accuracy of words longer than five characters showed no statistical differences (Naver Clova SR, 52.6%; Google Speech-to-Text, 56.3%; Amazon Transcribe, 36.6%). Conclusion Among three current cloud-based SR open APIs, Naver Clova SR which manufactured by Korean company showed highest accuracy of medical terms in Korean, compared to Google Speech-to-Text and Amazon Transcribe. Although limitations are existing in the recognition of medical terminology, there is a lot of rooms for improvement of this promising technology by combining strengths of each SR engines.

Background/Aims: Using a nationwide cohort, we investigated the cancer risk in Korean patients with gout. Methods: Data were obtained from the Korean National Health Insurance Service Database. Patients with gout were defined as those aged ≥ 20 years who were diagnosed with gout and received anti-gout medication (allopurinol, colchicine, and benzbromarone) between 2008 and 2010. Patients with nail disorders were randomly assigned to a control group (1:1 ratio) after frequency matching for age and sex. Cancer incidence was then investigated between 2012 and 2018. Cox proportional hazard regression analysis was used to investigate the association between gout and cancer after adjusting for concomitant diseases. Results: This study included 179,930 patients with gout and an equal number of matched controls. The incidence of overall cancer was higher in patients with gout than in controls (incidence rate ratio, 1.08). Cox proportional hazards regression analysis showed that gout was associated with a hazard ratio of 1.053 (95% confidence interval ,1.031 to 1.077) after adjusting for concomitant diseases. Conclusions Gout was associated with a significantly high risk of cancer, especially esophageal, stomach, colon, liver, pancreatic, lung, ovarian, renal, and bladder cancers.

Receptor-interacting serine/threonine-protein kinase (RIPK) 3 is a member of the TNF receptor-I signaling complex and mediates necroptosis, an inflammatory cell death. Ulcerative colitis (UC) is an excessive inflammatory disease caused by uncontrolled T cell activation. The current study is aimed to determine whether RIPK3 inhibitor attenuates UC development inhibiting inflammation and necroptosis using experimental colitis mice model. Dextran sulfate sodium-induced colitis mice were administered RIPK3 inhibitor (3 mg/ml) 3 times and their tissues were analyzed by immunohistochemistry. RIPK3, mixed lineage kinase domain-like (MLKL), phosphorylated MLKL, IL-17, and CD4 in colitis patient colon tissues were detected using confocal microscopy. Protein levels were measured using immunohistochemistry and ELISA. The differentiation of Th17 cells was evaluated using flow cytometry. The expression of proinflammatory cytokines and necroptosis in peripheral blood mononuclear cells from UC patients was decreased markedly by RIPK3 inhibitor treatment. We also observed that the injection of RIPK3 inhibitor improves colitis severity and protects intestinal destruction. RIPK3 inhibitor reduced necroptosis factors and proinflammatory cytokines in the colon and consequently protected colon devastation. The expression of inflammatory mediators in experimental colitis mice splenocytes was decreased significantly by RIPK3 inhibitor treatment. These results suggest that RIPK3 inhibitor ameliorates severity of experimental colitis and reduces inflammation through the inhibition of inflammatory response and necroptosis and support RIPK3-targeting substances for treatment of UC.

The protein encoded by the Gene Associated with Retinoid-Interferon-Induced Mortality-19 (GRIM-19) is located in the mitochondrial inner membrane and is homologous to the NADH dehydrogenase 1-alpha subcomplex subunit 13 of the electron transport chain.Multiple sclerosis (MS) is a demyelinating disease that damages the brain and spinal cord.Although both the cause and mechanism of MS progression remain unclear, it is accepted that an immune disorder is involved. We explored whether GRIM-19 ameliorated MS by increasing the levels of inflammatory cytokines and immune cells; we used a mouse model of experimental autoimmune encephalomyelitis (EAE) to this end. Six-to-eight-week-old male C57BL/6, IFNγ-knockout (KO), and GRIM-19 transgenic mice were used; EAE was induced in all strains. A GRIM-19 overexpression vector (GRIM19 OVN) was electrophoretically injected intravenously. The levels of Th1 and Th17 cells were measured via flow cytometry, immunofluorescence, and immunohistochemical analysis. IL-17A and IFNγ expression levels were assessed via ELISA and quantitative PCR. IL-17A expression decreased and IFNγ expression increased in EAE mice that received injections of the GRIM19 OVN. GRIM-19 transgenic mice expressed more IFNγ than did wild-type mice; this inhibited EAE development. However, the effect of GRIM-19 overexpression on the EAE of IFNγ-KO mice did not differ from that of the empty vector. GRIM-19 expression was therapeutic for EAE mice, elevating the IFNγ level. GRIM-19 regulated the Th17/Treg cell balance.

OBJECTIVE: We investigated the clinical characteristics of men with testosterone replacement therapy (TRT)-induced hypogonadism and its effect on assisted reproductive technology (ART) in infertile couples.METHODS: This study examined the records of 20 consecutive male patients diagnosed with azoospermia or severe oligozoospermia (<5×10⁶/mL) who visited a single infertility center from January 2008 to July 2018. All patients were treated at a primary clinic for erectile dysfunction or androgen deficiency symptoms combined with low serum testosterone. All men received a phosphodiesterase 5 inhibitor and TRT with testosterone undecanoate (Nebido®) or testosterone enanthate (Jenasteron®). Patients older than 50 years or with a chronic medical disease such as diabetes were excluded.RESULTS: The mean age of patients was 37 years and the mean duration of infertility was 16.3±11.6 months. At the initial presentation, eight patients had azoospermia, nine had cryptozoospermia, and three had severe oligozoospermia. Serum follicle-stimulating hormone levels were below 1.0 mIU/mL in most patients. Three ongoing ART programs with female factor infertility were cancelled due to male spermatogenic dysfunction; two of these men had normal semen parameters in the previous cycle. After withholding TRT, serum hormone levels and sperm concentrations returned to normal range after a median duration of 8 months.CONCLUSION: TRT with high-dose testosterone can cause spermatogenic dysfunction due to suppression of the hypothalamic-pituitary-testicular axis, with adverse effects on infertility treatment programs. TRT is therefore contraindicated for infertile couples attempting to conceive, and the patient's desire for fertility must be considered before initiation of TRT in a hypogonadal man.
Azoospermia ; Cyclic Nucleotide Phosphodiesterases, Type 5 ; Erectile Dysfunction ; Family Characteristics ; Female ; Fertility ; Follicle Stimulating Hormone ; Humans ; Hypogonadism ; Infertility ; Infertility, Male ; Male ; Oligospermia ; Reference Values ; Reproductive Techniques, Assisted ; Semen ; Spermatozoa ; Testosterone

BACKGROUND: Lung cancer is the most common cause of cancer-related mortality worldwide. We previously reported the identification of a new genetic marker, cellular retinoic acid binding protein 2 (CRABP2), in lung cancer tissues. The aim of this study was to assess plasma levels of CRABP2 from patients with non-small cell lung cancer (NSCLC). METHODS: Blood samples that were collected from 122 patients with NSCLC between September 2009 and September 2013 were selected for the analysis, along with samples from age- (± 5 years), sex-, and cigarette smoking history (± 10 pack-years [PY])-matched controls from the Korea Biobank Network. The control specimens were from patients who were without malignancies or pulmonary diseases. We measured plasma levels of CRABP2 using commercially available enzyme-linked immunosorbent assay kits. RESULTS: The mean age of the NSCLC patients was 71.8 ± 8.9 years, and the median cigarette smoking history was 32 PY (range, 0–150 PY). Plasma CRABP2 levels were significantly higher in patients with NSCLC than in the matched controls (37.63 ± 28.71 ng/mL vs. 24.09 ± 21.09 ng/mL, P < 0.001). Higher plasma CRABP2 levels were also correlated with lower survival rates in NSCLC patients (P = 0.014). CONCLUSION: Plasma CRABP2 levels might be a novel diagnostic and prognostic marker in NSCLC.
Biomarkers ; Carcinoma, Non-Small-Cell Lung* ; Carrier Proteins ; Enzyme-Linked Immunosorbent Assay ; Genetic Markers ; Humans ; Korea ; Lung Diseases ; Lung Neoplasms ; Mortality ; Plasma* ; Smoking ; Survival Rate ; Tretinoin

Thermodynamically immiscible poly(lactic acid) (PLA) and poly(ε-caprolactone) (PCL) were blended and solution-cast by adding the 3% compatibilizer (tributyl citrate, TBC) of the PCL weight. In the PLA/PCL composition range of 99/1–95/5 wt%, mechanical properties of the PLA/PCL films with TBC were always superior to those of the films without TBC. The tensile strength of 42.9 ± 3.5 MPa and the elongation at break of 10.3 ± 2.7% were observed for the 93/7 PLA/PCL films without TBC, indicating that PCL addition is effective for strength and ductility. However, the tensile strength of 54.1 ± 3.4 MPa and the elongation at break of 8.8 ± 1.8% were found for the 95/5 PLA/PCL with TBC, indicating that the effect of co-addition of PCL and TBC on mechanical properties of the films is more pronounced. No cytotoxicity was observed for the PLA/PCL films regardless of TBC addition.
Cell Proliferation ; Citric Acid ; Tensile Strength

PURPOSE: Parathyroid adenoma detection with dual-phase (99m)Tc-sestamibi (MIBI) scintigraphy depends on differential MIBI washout from thyroid. However, autoimmune thyroid disease (AITD) may cause MIBI to be retained in the thyroid gland and reduce parathyroid detection.We evaluated the impact of AITD on MIBI thyroid retention and additional benefit of SPECT/CT in these patients.METHODS: Dual phase planar MIBI and SPECT/CT was performed on 82 patients. SPECT/CTwas performed immediatelyafter delayed planar scan. Thyroid density (Hounsfield unit, CT-HU) and size were measured on CT component of SPECT/CT. MIBI uptake in early scans and retention in delayed scans were visually graded and correlated with clinical factors and CT findings. Finally, planar and SPECT/CT findings were compared for parathyroid lesion visualization according to thyroid MIBI retention.RESULTS: In early scan, multivariate analysis showed only thyroid size predicted early uptake. In delayed scan, multivariate analysis showed higher visual grade in early scan, lower CTHU or AITD were significant predictors for delayed thyroid parenchymal retention. Overall, ten more parathyroid lesions were visualized on SPECT/CT compared to planar scans (57 vs. 47, p = 0.002). SPECT/CT was especially more useful in patients with thyroidal MIBI retention, as eight out of the ten additional lesions detected were found in patients with thyroid MIBI retention.CONCLUSION: AITD is an important factor for MIBI thyroid parenchymal retention on delayed scans, and may impede parathyroid lesion detection. Patients with MIBI retention in the thyroid parenchyma on delayed scans are likely to benefit from an additional SPECT/CT.
Humans ; Multivariate Analysis ; Parathyroid Neoplasms ; Radionuclide Imaging ; Thyroid Diseases ; Thyroid Gland

BACKGROUND: Rotaviruses are the primary cause of severe acute gastroenteritis in infants and young children worldwide. We evaluated the performance of the new GENEDIA Rotavirus Ag Rapid test (Greencross Medical Science, Korea) immunochromatographic assay (ICA) for detecting human rotavirus in stool specimens, in comparison with ELISA and PCR assays. METHODS: One hundred rotavirus-positive stool samples and 150 rotavirus-negative stool samples, confirmed by ELISA and PCR tests, were analysed using the GENEDIA Rotavirus Ag rapid test. The positive agreement (sensitivity), negative agreement (specificity), and total agreement rates of the ICA compared to ELISA and PCR were determined. To assess the analytical performance of the ICA, we tested its detection limit, reproducibility, and cross-reactivity. RESULTS: The positive, negative, and total agreement rates of the ICA were 99%, 100%, and 99.6%, respectively, when compared with the results confirmed by ELISA and PCR. The total turnaround time of the ICA was less than 20 minutes. The lower limit of detection of the ICA for rotavirus was 1.33x10(3) TCID50/mL, which was similar to that of ELISA but higher than that of PCR. No cross-reactivity was detected for 11 viruses and 19 bacteria. CONCLUSIONS: The GENEDIA Rotavirus Ag rapid test was easy to perform and provided rapid results, which showed high agreement with those obtained using ELISA and PCR. This test appears to be a useful tool for the diagnosis of rotavirus infection.
Bacteria ; Child ; Diagnosis ; Enzyme-Linked Immunosorbent Assay ; Gastroenteritis ; Humans ; Immunochromatography* ; Infant ; Limit of Detection ; Polymerase Chain Reaction ; Rotavirus Infections ; Rotavirus*