Objectives: This study was conducted to develop a generalizable annotation tool for bilingual complex clinical text annotation, which led to the design and development of a clinical text annotation tool, ANNO. Methods: We designed ANNO to enable human annotators to support the annotation of information in clinical documents efficiently and accurately. First, annotations for different classes (word or phrase types) can be tagged according to the type of word using the dictionary function. In addition, it is possible to evaluate and reconcile differences by comparing annotation results between human annotators. Moreover, if the regular expression set for each class is updated during annotation, it is automatically reflected in the new document. The regular expression set created by human annotators is designed such that a word tagged once is automatically labeled in new documents. Results: Because ANNO is a Docker-based web application, users can use it freely without being subjected to dependency issues. Human annotators can share their annotation markups as regular expression sets with a dictionary structure, and they can cross-check their annotated corpora with each other. The dictionary-based regular expression sharing function, cross-check function for each annotator, and standardized input (Microsoft Excel) and output (extensible markup language [XML]) formats are the main features of ANNO. Conclusions With the growing need for massively annotated clinical data to support the development of machine learning models, we expect ANNO to be helpful to many researchers.

Objective: To elucidate whether clinical features and the weighted genetic risk score (wGRS) were associated with the presence of lupus nephritis (LN). Methods: We retrospectively divided patients with systemic lupus erythematosus (SLE, n=1,078) into biopsy-proven LN (n=507) and non-LN groups (non-LN, n=571). Baseline clinical features, serologic markers, and the wGRS were collected. The wGRS was calculated from 112 non-human leukocyte antigen (non-HLA) loci and HLA-DRβ1 amino acid haplotypes for SLE. Associations among clinical features, wGRS, and the presence of LN were identified. Results: In the multivariate analysis, patients with LN were younger at diagnosis (odds ratio [OR]=0.97, p＜0.001), had more pleuritis (OR=2.44, p＜0.001) and pericarditis (OR=1.62, p=0.029), had a higher detection rate of anti-double stranded deoxyribonucleic acid (anti-dsDNA antibodies, OR=2.22, p＜0.001), anti-Smith antibodies (anti-Sm antibodies, OR=1.70, p=0.002), low level of complement (OR=1.37, p=0.043) and absence of antiphospholipid antibodies (aPL antibodies, OR=1.60, p=0.002), and had higher wGRS (OR=1.16, p=0.012). Mediation analysis suggested that anti-Sm antibodies and low complement could be mediators in the relationship between high wGRS and the presence of LN. Conclusion Onset age, pleuritis, pericarditis, several serologic markers, and wGRS were associated with the presence of LN. Anti-Sm antibodies and low complement appeared to mediate the indirect relationship between wGRS and the presence of LN.

Objective: To elucidate whether clinical features and the weighted genetic risk score (wGRS) were associated with the presence of lupus nephritis (LN). Methods: We retrospectively divided patients with systemic lupus erythematosus (SLE, n=1,078) into biopsy-proven LN (n=507) and non-LN groups (non-LN, n=571). Baseline clinical features, serologic markers, and the wGRS were collected. The wGRS was calculated from 112 non-human leukocyte antigen (non-HLA) loci and HLA-DRβ1 amino acid haplotypes for SLE. Associations among clinical features, wGRS, and the presence of LN were identified. Results: In the multivariate analysis, patients with LN were younger at diagnosis (odds ratio [OR]=0.97, p＜0.001), had more pleuritis (OR=2.44, p＜0.001) and pericarditis (OR=1.62, p=0.029), had a higher detection rate of anti-double stranded deoxyribonucleic acid (anti-dsDNA antibodies, OR=2.22, p＜0.001), anti-Smith antibodies (anti-Sm antibodies, OR=1.70, p=0.002), low level of complement (OR=1.37, p=0.043) and absence of antiphospholipid antibodies (aPL antibodies, OR=1.60, p=0.002), and had higher wGRS (OR=1.16, p=0.012). Mediation analysis suggested that anti-Sm antibodies and low complement could be mediators in the relationship between high wGRS and the presence of LN. Conclusion Onset age, pleuritis, pericarditis, several serologic markers, and wGRS were associated with the presence of LN. Anti-Sm antibodies and low complement appeared to mediate the indirect relationship between wGRS and the presence of LN.

Objective: The aim of the study was to compare the mortality rates of patients with early-identified (EI) sepsis and late-identified (LI) sepsis. Methods: We performed a retrospective chart review of patients admitted to the emergency department and diagnosed with sepsis. EI sepsis was defined as patients with a Sequential Organ Failure Assessment (SOFA) score ≥2, based on 3 parameters of the SOFA score (Glasgow coma scale, mean arterial pressure, and partial pressure of oxygen/fraction of inspired oxygen ratio), measured within an hour of emergency department admission. The remaining patients were defined as LI sepsis. The primary outcome was in-hospital mortality. Results: Of the total 204 patients with sepsis, 113 (55.4%) had EI sepsis. Overall mortality rate was 15.7%, and EI sepsis group had significantly higher mortality than LI sepsis (23.0% vs. 6.6%, P=0.003). The patients with EI sepsis, compared to those with LI sepsis, had higher SOFA score (median: 4 vs. 2, P<0.001); Acute Physiology and Chronic Health Evaluation (APACHE) II score (median: 14 vs. 10, P<0.001); were more likely to progress to septic shock within 6 hours after admission (17.7% vs. 1.1%, P<0.001); were more likely to be admitted to the intensive care unit (2.2% vs. 1.1%, P=0.001). Conclusion Mortality was significantly higher in the EI sepsis group than in the LI sepsis group.

OBJECTIVE: The purpose of the present study was to compare the diagnostic performance of initial procalcitonin, lactate, and high-sensitive C-reactive protein (hsCRP) for predicting bacteremia in female patients with acute pyelonephritis (APN). METHODS: We conducted a retrospective study of female APN patients who visited the emergency department (ED) at the studied hospital between January 2015 and December 2016. The main outcome was bacteremia, which was reported via the first blood culture at ED. The patient demographics, co-morbidities, physiologies, and laboratory variables including initial procalcitonin, lactate, and hsCRP levels, were collected and analyzed to identify associations with the presence of bacteremia. The area under the receiver operating curve (AUROC) and sensitivity (SE)/specificity (SP) were calculated for each variable. RESULTS: During the study period, 282 patients were enrolled. A total of 105 (37.2%) patients had bacteremia. Escherichia coli was the most frequent pathogen. The AUROC was 0.70 (0.63–0.76), 0.70 (0.63–0.76), and 0.56 (0.49–0.63) for the procalcitonin, lactate, and hsCRP, respectively. At a cut-off value of 0.163 ng/mL, the procalcitonin level predicted bacteremia, with a SE/SP of 95.2%/22.6%, respectively. At a cut-off value of 0.7 mmol/L, the lactate level predicted bacteremia with a SE/SP of 96.2%/20.9%, respectively. The combination of a procalcitonin level >0.447 ng/mL or a lactate level >0.7 mmo/L was chosen, as they showed 100% SE and a 100% negative predictive value. CONCLUSION: The initial serum procalcitonin and lactate levels showed similar and fair discriminative performance for predicting bacteremia in female APN patients, while the hsCRP level showed poor performance. The combination of procalcitonin and lactate (procalcitonin level≤0.447 ng/mL and lactate≤0.7 mmol/L) can be used to identify patients at low risk of bacteremia.
Bacteremia ; C-Reactive Protein ; Demography ; Emergency Service, Hospital ; Escherichia coli ; Female ; Humans ; Lactic Acid ; Pyelonephritis ; Retrospective Studies

OBJECTIVE: The head-tilt/chin-lift (HT/CL) is a simple, routinely used maneuver to open the upper airway. Changes in the peak expiratory flow rate (PEFR) before and after the HT/CL maneuver have not been evaluated among conscious volunteers who are regarded as a control cohort.METHODS: Sixty healthy 20-year-old volunteers (30 males and 30 females) were enrolled. The supine position was defined as the position at which the ear-eye line was at a 10° angle to the horizontal. The HT/CL position was defined as the position at which the ear-eye line was at a 25° angle to the horizontal. PEFR was measured using a hand-held device with the subject in the supine position (pre-PEFR) and HT/CL position (post-PEFR), respectively. One set was defined as these two measurements. Five sets of measurements were performed on each subject (300 sets). The set with the maximal and minimal difference between pre-PEFR and post-PEFR were excluded from the analysis. We used a paired t-test to compare the mean pre-PEFR and post-PEFR values for the entire group and subgroups divided by sex, height, body weight, body mass index and response status.RESULTS: Overall, 360 measurements (180 sets) were analyzed. The mean pre-PEFR and post-PEFR were 316.1±87.6 and 346.5±94.7 L/min, respectively. Further, significant differences were observed for sex, height, body weight, and body mass index. In 10 subjects, post-PEFR was lower than pre-PEFR.CONCLUSION: PEFR increased by 9.6% after the HT/CL maneuver in young conscious subjects, but some subjects showed decreased PEFR after the HT/CL maneuver.
Airway Management ; Body Height ; Body Mass Index ; Body Weight ; Cohort Studies ; Humans ; Male ; Peak Expiratory Flow Rate ; Supine Position ; Volunteers ; Young Adult

OBJECTIVE: We compared the predictive value of the National Early Warning Score+Lactate (NEWS+L) score with those of other parameters such as the pre-endoscopic Rockall score (PERS), Glasgow-Blatchford score (GBS), and albumin, international normalized ratio, altered mental status, systolic blood pressure, age older than 65 years score (AIMS65) among patients with upper gastrointestinal bleeding (UGIB). METHODS: We conducted a retrospective study of patients with UGIB during 2 consecutive years. The primary outcome was the composite of in-hospital death, intensive care unit admission, and the need for ≥5 packs of red blood cell transfusion within 24 hours. RESULTS: Among 530 included patients, the composite outcome occurred in 59 patients (19 in-hospital deaths, 13 intensive care unit admissions, and 40 transfusions of ≥5 packs of red blood cells within 24 hours). The area under the receiver operating characteristic curve of the NEWS+L score for the composite outcome was 0.76 (95% confidence interval, 0.70 to 0.82), which demonstrated a significant difference compared to PERS (0.66, 0.59–0.73, P=0.004), but not to GBS (0.70, 0.64–0.77, P=0.141) and AIMS65 (0.76, 0.70–0.83, P=0.999). The sensitivities of NEWS+L scores of 3 (n=34, 6.4%), 4 (n=92, 17.4%), and 5 (n=171, 32.3%) were 100%, 98.3%, and 96.6%, respectively, while the sensitivity of an AIMS65 score of 0 (n=159, 30.0%) was 91.5%. CONCLUSION: The NEWS+L score showed better discriminative performance than the PERS and comparable discriminative performance to the GBS and AIMS65. The NEWS+L score may be used to identify low-risk patients among patients with UGIB.
Blood Pressure ; Erythrocyte Transfusion ; Erythrocytes ; Hemorrhage* ; Humans ; Intensive Care Units ; International Normalized Ratio ; Lactic Acid ; Mortality ; Retrospective Studies ; ROC Curve

BACKGROUND AND OBJECTIVES: Information about the role of the stromal cell-derived factor-1α (SDF-1α)/chemokine receptor type 4 (CXCR4) axis in ischemic postconditioning (IPOC) is currently limited. We hypothesized that the SDF-1α/CXCR4 signaling pathway is directly involved in the cardioprotective effect of IPOC. METHODS: Isolated rat hearts were divided into four groups. The control group was subjected to 30-min of regional ischemia and 2-hour of reperfusion (n=12). The IPOC group was induced with 6 cycles of 10-second reperfusion and 10-second global ischemia (n=8) in each cycle. The CXCR4 antagonist, AMD3100, was applied before reperfusion in the IPOC group (AMD+IPOC group, n=11) and control group (AMD group, n=9). Hemodynamic changes with electrocardiography were monitored and infarct size was measured. The SDF-1α, lactate dehydrogenase (LDH) and creatine kinase (CK) concentrations in perfusate were measured. We also analyzed extracellular signal-regulated kinase 1/2 (ERK1/2) and Akt phosphorylation state expression. RESULTS: IPOC significantly reduced infarct size, but AMD3100 attenuated the infarct reducing effect of IPOC. IPOC significantly decreased LDH and CK, but these effects were reversed by AMD3100. ERK1/2 and Akt phosphorylation increased with IPOC and these effects were blocked by AMD3100. CONCLUSION: Based on the results of this study, SDF-1α/CXCR4 signaling may be involved in IPOC cardioprotection and this signaling pathway couples to the ERK1/2 and Akt pathways.
Animals ; Creatine Kinase ; Electrocardiography ; Family Characteristics ; Heart* ; Hemodynamics ; Ischemia ; Ischemic Postconditioning* ; L-Lactate Dehydrogenase ; Phosphorylation ; Phosphotransferases ; Rats* ; Receptors, CXCR4 ; Reperfusion ; Reperfusion Injury

BACKGROUND: The activation of guanine nucleotide binding protein-coupled receptors, such as adenosine receptor (ADR) and opioid receptor (OPR), protects the heart against ischemia and reperfusion injury. We hypothesized that ADR or OPR might be involved in polyphenol (-)-epigallocatechin gallate (EGCG)-induced cardioprotection. METHODS: Langendorff perfused rat hearts were subjected to 30 min of regional ischemia and 2 h of reperfusion. Hearts were treated with 10 microM of EGCG, with or without the ADR or OPR antagonist at early reperfusion. Infarct size measured with 2,3,5-triphenyltetrazolium chloride staining was chosen as end-point. RESULTS: EGCG significantly reduced infarct volume as a percentage of ischemic volume (33.5 +/- 4.1%) compared to control hearts (14.4 +/- 1.1%, P < 0.001). A nonspecific ADR antagonist 8-(p-sulfophenyl) theophylline hydrate (27.1 +/- 1.9%, P < 0.05 vs. EGCG) but not a nonspecific OPR antagonist naloxone (14.3 +/- 1.3%, P > 0.05 vs. EGCG) blocked the anti-infarct effect by EGCG. The infarct reducing effect of EGCG was significantly reversed by 200 nM of the A1 ADR antagonist DPCPX (25.9 +/- 1.1%, P < 0.05) and 15 nM of the A2B ADR antagonist MRS1706 (29.3 +/- 1.7%, P < 0.01) but not by 10 microM of the A2A ADR antagonist ZM241385 (23.9 +/- 1.9%. P > 0.05 vs. EGCG) and 100 nM of the A3 ADR antagonist MRS1334 (24.1 +/- 1.8%, P > 0.05). CONCLUSIONS: The infarct reducing effect of EGCG appears to involve activation of ADR, especially A1 and A2B ADR, but not OPR.
Adenosine ; Animals ; Catechin ; Guanine ; Heart ; Ischemia ; Myocardial Infarction ; Naloxone ; Purines ; Rats ; Receptors, Opioid ; Receptors, Purinergic P1 ; Reperfusion ; Reperfusion Injury ; Tetrazolium Salts ; Theophylline ; Triazines ; Triazoles ; Xanthines

Polyphenol (-)-epigallocatechin gallate (EGCG), the most abundant catechin of green tea, appears to attenuate myocardial ischemia/reperfusion injury. We investigated the involvement of ATP-sensitive potassium (K(ATP)) channels in EGCG-induced cardioprotection. Isolated rat hearts were subjected to 30 min of regional ischemia and 2 hr of reperfusion. EGCG was perfused for 40 min, from 10 min before to the end of index ischemia. A nonselective K(ATP) channel blocker glibenclamide (GLI) and a selective mitochondrial K(ATP) (mK(ATP)) channel blocker 5-hydroxydecanoate (HD) were perfused in EGCG-treated hearts. There were no differences in coronary flow and cardiodynamics including heart rate, left ventricular developed pressure, rate-pressure product, +dP/dt(max), and -dP/dt(min) throughout the experiments among groups. EGCG-treatment significantly reduced myocardial infarction (14.5+/-2.5% in EGCG 1 micrometer and 4.0+/-1.7% in EGCG 10 micrometer, P<0.001 vs. control 27.2+/-1.4%). This anti-infarct effect was totally abrogated by 10 micrometer GLI (24.6+/-1.5%, P<0.001 vs. EGCG). Similarly, 100 micrometer HD also aborted the anti-infarct effect of EGCG (24.1+/-1.2%, P<0.001 vs. EGCG ). These data support a role for the K(ATP) channels in EGCG-induced cardioprotection. The mK(ATP) channels play a crucial role in the cardioprotection by EGCG.
Animals ; Anti-Arrhythmia Agents/pharmacology ; Antioxidants/*pharmacology ; Catechin/*analogs & derivatives/pharmacology ; Decanoic Acids/pharmacology ; Glyburide/pharmacology ; Heart/*drug effects/physiology/physiopathology ; Hemodynamics ; Humans ; Hydroxy Acids/pharmacology ; KATP Channels/*metabolism ; Male ; Mitochondria, Heart/*drug effects/metabolism ; Myocardial Infarction/*pathology ; Myocardial Ischemia/*pathology ; Potassium Channel Blockers/pharmacology ; Rats ; Rats, Wistar