A Machine Learning-Based Applied Prediction Model for Identification of Acute Coronary Syndrome (ACS) Outcomes and Mortality in Patients during the Hospital Stay.

Nowadays, machine learning (ML) is a revolutionary and cutting-edge technology widely used in the medical domain and health informatics in the diagnosis and prognosis of cardiovascular diseases especially. Therefore, we propose a ML-based soft-voting ensemble classifier (SVEC) for the predictive modeling of acute coronary syndrome (ACS) outcomes such as STEMI and NSTEMI, discharge reasons for the patients admitted in the hospitals, and death types for the affected patients during the hospital stay. We used the Korea Acute Myocardial Infarction Registry (KAMIR-NIH) dataset, which has 13,104 patients' data containing 551 features. After data extraction and preprocessing, we used the 125 useful features and applied the SMOTETomek hybrid sampling technique to oversample the data imbalance of minority classes. Our proposed SVEC applied three ML algorithms, such as random forest, extra tree, and the gradient-boosting machine for predictive modeling of our target variables, and compared with the performances of all base classifiers. The experiments showed that the SVEC outperformed other ML-based predictive models in accuracy (99.0733%), precision (99.0742%), recall (99.0734%), F1-score (99.9719%), and the area under the ROC curve (AUC) (99.9702%). Overall, the performance of the SVEC was better than other applied models, but the AUC was slightly lower than the extra tree classifier for the predictive modeling of ACS outcomes. The proposed predictive model outperformed other ML-based models; hence it can be used practically in hospitals for the diagnosis and prediction of heart problems so that timely detection of proper treatments can be chosen, and the occurrence of disease predicted more accurately.

Immediate and Long-Term Outcomes of Reperfusion Therapy in Patients With Cancer.

Background and Purpose: Patients with acute stroke are often accompanied by comorbidities, such as active cancer. However, adequate treatment guidelines are not available for these patients. The purpose of this study was to evaluate the association between cancer and the outcomes of reperfusion therapy in patients with stroke. Methods: We compared treatment outcomes in patients who underwent reperfusion therapy, using a nationwide reperfusion therapy registry. We divided the patients into 3 groups according to cancer activity: active cancer, nonactive cancer, and without a history of cancer. We investigated reperfusion processes, 24-hour neurological improvement, adverse events, 3-month functional outcome, and 6-month survival and related factors after reperfusion therapy. Results: Among 1338 patients who underwent reperfusion therapy, 62 patients (4.6%) had active cancer, 78 patients (5.8%) had nonactive cancer, and 1198 patients (89.5%) had no history of cancer. Of the enrolled patients, 969 patients received intravenous thrombolysis and 685 patients underwent endovascular treatment (316 patients received combined therapy). Patients with active cancer had more comorbidities and experienced more severe strokes; however, they showed similar 24-hour neurological improvement and adverse events, including cerebral hemorrhage, compared with the other groups. Although the functional outcome at 3 months was poorer than the other groups, 36.4% of patients with active cancer showed functional independence. Additionally, 52.9% of the patients with determined stroke etiology showed functional independence despite active cancer. During the 6-month follow-up, 46.6% of patients with active cancer died, and active cancer was independently associated with poor survival (hazard ratio, 3.973 [95% CI, 2.528­6.245]). Conclusions: In patients with active cancer, reperfusion therapy showed similar adverse events and short-term outcomes to that of other groups. While long-term prognosis was worse in the active cancer group than the nonactive cancer groups, not negligible number of patients had good functional outcomes, especially those with determined stroke mechanisms.

In vitro and in vivo evaluation of the genotoxicity of Eriobotrya japonica leaf extract.

Eriobotrya japonica leaf is included in the Chinese Pharmacopoeia, and is widely used as a medicinal material in traditional medicine. The present study investigated the potential genotoxic effects of E. japonica leaf extract (EJE) using three standard battery systems. Genotoxicity tests were conducted following the test guidelines of the Organisation for Economic Cooperation and Development (OECD) and Ministry of Food and Drug Safety (MFDS), with application of Good Laboratory Practice. The bacterial reverse mutation test was conducted using the pre-incubation method in the presence or absence of the metabolic activation system (S9 mixture). The in vitro chromosome aberration test was performed using cultured Chinese hamster lung cell line in the presence or absence of the S9 mixture. The in vivo micronucleus test was performed using ICR mice. The bacterial reverse mutation test with Salmonella typhimurium strains TA98, TA100, TA1535, and TA1537 and Escherichia coli strain WP2uvrA showed that EJE did not induce gene mutations at any dose level in all the strains tested. EJE also did not show any chromosomal aberrations in the in vitro chromosomal aberration test and in the in vivo micronucleus test. These results showed that EJE did not induce mutagenicity or clastogenicity in either in vitro or in vivo systems.

Arthroscopic-assisted plate fixation for displaced large-sized comminuted greater tuberosity fractures of proximal humerus: a novel surgical technique.

PURPOSE: The purpose of the present study was to describe the use of a novel hybrid surgical technique-arthroscopic-assisted plate fixation-and evaluate its clinical and anatomical outcomes in the management of large, displaced greater tuberosity (GT) fractures with comminution. METHODS: From 2009 to 2011, this novel technique was performed in 11 patients [2 men and 9 women; median age, 64 years (range 41-83 years)] with large, comminuted GT fractures, with fragment displacements of >5 mm. The preoperative mean posterior and superior migration of the fractured fragment, as measured on computed tomography (CT), was 19.5 and 5.5 mm, respectively. Two patients had shoulder fracture-dislocation, and three had associated undisplaced surgical neck fracture. The mean duration between injury and surgery was 4 days. The mean follow-up duration was 26 months. RESULTS: At the final follow-up, the mean postoperative ASES, UCLA and SST scores were 84, 29, and 8, respectively. The mean range of motion was as follows: forward flexion, 138°; abduction, 135°; external rotation at the side, 19°; and internal rotation, up to the L2 level. The mean posterior and superior displacements of fracture fragments on postoperative CT scan [0.7 ± 0.8 mm (range 0-2.1 mm) and 2.8 ± 0.5 mm (range 3.4-5.3 mm), respectively] were significantly improved (p < 0.05). On arthroscopy, a partial articular-side supraspinatus tendon avulsion lesion was identified in 10 of 11 patients (91 %), and 1 of these patients had a partial tear of the biceps and 1 had a partial subscapularis tear, respectively (9 %). Intraoperatively, 1 anchor pullout and 1 anchor protrusion through the humeral head were noted and corrected. Postoperatively, the loss of reduction in the fracture fragment was noted in 1 patient at 4 weeks, after corrective reduction and fixation surgery. CONCLUSIONS: The novel arthroscopic-assisted anatomical plate fixation technique was found to be effective in reducing large-sized, displaced, comminuted GT fractures and in allowing concurrent management of intra-articular pathologies and early functional rehabilitation. Compared with the conventional plate fixation or arthroscopic suture anchor fixation technique, arthroscopic-assisted plate fixation enabled accurate restoration of the medial footprint of the GT fracture and provided an effective buttress to the large-sized GT fracture fragments. LEVEL OF EVIDENCE: Retrospective clinical study, Level IV.

Cilostazol decreases cerebral arterial pulsatility in patients with mild white matter hyperintensities: subgroup analysis from the Effect of Cilostazol in Acute Lacunar Infarction Based on Pulsatility Index of Transcranial Doppler (ECLIPse) study.

BACKGROUND: The Effect of Cilostazol in Acute Lacunar Infarction Based on Pulsatility Index of the Transcranial Doppler (ECLIPse) study showed a significant decrease in the transcranial Doppler (TCD) pulsatility index (PI) with cilostazol treatment at 90 days after acute lacunar infarction. The aim of the present study was to perform a subgroup analysis of the ECLIPse study in order to explore the effect of cilostazol in acute lacunar infarction based on cerebral white matter hyperintensities (WMH) volume. METHODS: The ECLIPse study was a multicenter, randomized, double-blind, placebo-controlled trial that evaluated the difference between the efficacy of cilostazol and a placebo to reduce the PI in patients with acute lacunar infarction using serial TCD examinations. The primary outcome was changes in the PIs of the middle cerebral artery (MCA) and basilar artery at 14 and 90 days from the baseline TCD study. For this subgroup analysis, using semi-automated computerized software, the WMH volume was measured for those subjects for whom fluid-attenuated inversion recovery (FLAIR) images were available. RESULTS: Of the 203 patients in eight hospitals in the ECLIPse study, 130 participants from six hospitals were included in this subgroup analysis. Cilostazol was given to 63 patients (48.5%) and placebo to 67 patients (51.5%). All baseline characteristics were well balanced across the two groups, and there were no significant differences in these characteristics except in the changes of PI from the baseline to the 90-day point. There was a significant decrease of TCD PIs at 90-day study from baseline in the cilostazol group (p = 0.02). The mean WMH volume was 11.57 cm(3) (0.13-68.45, median 4.86) and the mean MCA PI was 0.95 (0.62-1.50). The changes in PIs from the baseline to 14 days and to 90 days were 0.09 (-0.21 to 0.33) and 0.10 (-0.22 to 0.36). While there were no significant correlations between WMH volume and the changes in PIs, a trend of inverse correlation was observed between the WMH volume and the changes in PIs from the baseline to the 90-day point. For the subgroup analysis, the WMH volume was dichotomized based on its median value (4.90 cm(3)). Cilostazol decreased the TCD PIs significantly at the 90-day point in patients with WMH volumes ≤ 4.9 cm(3) (p = 0.002). Significant treatment effects were observed in the cilostazol group. CONCLUSIONS: This study showed that cilostazol decreased cerebral arterial pulsatility in patients with WMH. Our findings indicate the unique effect of cilostazol in small vessel disease (SVD), especially in patients with mild WMH changes. Further clinical trials focusing on WMH volume and clinical outcomes are required to assess the unique efficacy of cilostazol in SVD.

Lack of genotoxic potential of ZnO nanoparticles in in vitro and in vivo tests.

The industrial application of nanotechnology, particularly using zinc oxide (ZnO), has grown rapidly, including products such as cosmetics, food, rubber, paints, and plastics. However, despite increasing population exposure to ZnO, its potential genotoxicity remains controversial. The biological effects of nanoparticles depend on their physicochemical properties. Preparations with well-defined physico-chemical properties and standardized test methods are required for assessing the genotoxicity of nanoparticles. In this study, we have evaluated the genotoxicity of four kinds of ZnO nanoparticles: 20nm and 70nm size, positively or negatively charged. Four different genotoxicity tests (bacterial mutagenicity assay, in vitro chromosomal aberration test, in vivo comet assay, and in vivo micronucleus test, were conducted, following Organization for Economic Cooperation and Development (OECD) test guidelines with good laboratory practice (GLP) procedures. No statistically significant differences from the solvent controls were observed. These results suggest that surface-modified ZnO nanoparticles do not induce genotoxicity in in vitro or in vivo test systems.

A cost-sensitive deep neural network-based prediction model for the mortality in acute myocardial infarction patients with hypertension on imbalanced data.

Background and objectives: Hypertension is one of the most serious risk factors and the leading cause of mortality in patients with cardiovascular diseases (CVDs). It is necessary to accurately predict the mortality of patients suffering from CVDs with hypertension. Therefore, this paper proposes a novel cost-sensitive deep neural network (CSDNN)-based mortality prediction model for out-of-hospital acute myocardial infarction (AMI) patients with hypertension on imbalanced data. Methods: The synopsis of our research is as follows. First, the experimental data is extracted from the Korea Acute Myocardial Infarction Registry-National Institutes of Health (KAMIR-NIH) and preprocessed with several approaches. Then the imbalanced experimental dataset is divided into training data (80%) and test data (20%). After that, we design the proposed CSDNN-based mortality prediction model, which can solve the skewed class distribution between the majority and minority classes in the training data. The threshold moving technique is also employed to enhance the performance of the proposed model. Finally, we evaluate the performance of the proposed model using the test data and compare it with other commonly used machine learning (ML) and data sampling-based ensemble models. Moreover, the hyperparameters of all models are optimized through random search strategies with a 5-fold cross-validation approach. Results and discussion: In the result, the proposed CSDNN model with the threshold moving technique yielded the best results on imbalanced data. Additionally, our proposed model outperformed the best ML model and the classic data sampling-based ensemble model with an AUC of 2.58% and 2.55% improvement, respectively. It aids in decision-making and offers a precise mortality prediction for AMI patients with hypertension.

Effect of cilostazol in acute lacunar infarction based on pulsatility index of transcranial Doppler (ECLIPse): a multicenter, randomized, double-blind, placebo-controlled trial.

BACKGROUND: This study is intended to evaluate the propensities of cilostazol to reduce the pulsatility index (PI) in patients with acute lacunar infarction using the serial transcranial Doppler (TCD) examinations. METHODS: In a multicenter, randomized, double-blind, placebo-controlled trial, patients were randomly assigned to receive either placebo or 100 mg cilostazol twice a day as well as aspirin 100 mg a day. The primary outcomes were the changes of middle cerebral artery (MCA) and basilar artery (BA) PIs at 14 and 90 days from the baseline TCD study. This study is registered with ClinicalTrials.gov (NCT00741286). RESULTS: Trial medication was given to 203 patients, with 100 receiving cilostazol and 103 receiving placebo, and 164 were included in the per-protocol analysis of the primary outcome. Results from the linear mixed model showed that significant effects were obtained for time-by-group interactions (p = 0.008 in right MCA, p = 0.015 in left MCA, p = 0.002 in BA), suggesting that changes of PIs from the baseline to the 90-day study were different across the groups. CONCLUSIONS: Cilostazol further decreased TCD PIs at 90 days from baseline compared to placebo in acute lacunar infarction. This result may be related to pleiotropic effects, such as vasodilation, beyond its antiplatelet activity.

Effects of Trichostatin A on In vitro Development of Porcine Embryos Derived from Somatic Cell Nuclear Transfer.

Many different approaches have been developed to improve the efficiency of animal cloning by somatic cell nuclear transfer (SCNT), one of which is to modify histone acetylation levels using histone deacetylase inhibitors (HDACi) such as trichostatin A (TSA). In the present study, we examined the effect of TSA on in vitro development of porcine embryos derived from SCNT. We found that TSA treatment (50 nM) for 24 h following oocyte activation improved blastocyst formation rates (to 22.0%) compared with 8.9% in the non-treatment group and total cell number of the blastocysts for determining embryo quality also increased significantly (88.9→114.4). Changes in histone acetylation levels as a result of TSA treatment were examined using indirect immunofluorescence and confocal microscopy scanning. Results showed that the histone acetylation level in TSA-treated embryos was higher than that in controls at both acetylated histone H3 lysine 9 (AcH3K9) and acetylated histone H4 lysine 12 (AcH4K12). Next, we compared the expression patterns of seven genes (OCT4, ID1; the pluripotent genes, H19, NNAT, PEG1; the imprinting genes, cytokeratin 8 and 18; the trophoblast marker genes). The SCNT blastocysts both with and without TSA treatment showed lower levels of OCT4, ID1, cytokeratin 8 and 18 than those of the in vivo blastocysts. In the case of the imprinting genes H19 and NNAT, except PEG1, the SCNT blastocysts both with and without TSA treatment showed higher levels than those of the in vivo blastocysts. Although the gene expression patterns between cloned blastocysts and their in vivo counterparts were different regardless of TSA treatment, it appears that several genes in NT blastocysts after TSA treatment showed a slight tendency toward expression patterns of in vivo blastocysts. Our results suggest that TSA treatment may improve preimplantation porcine embryo development following SCNT.

Effects of repetitive ionomycin treatment on in vitro development of bovine somatic cell nuclear transfer embryos.

To artificially activate embryos in somatic cell nuclear transfer (SCNT), chemical treatment with ionomycin has been used to induce transient levels of Ca(2+) and initiate reprogramming of embryos. Ca(2+) oscillation occurs naturally several times after fertilization (several times with 15- to 30-min intervals). This indicates how essential additional Ca(2+) influx is for successful reprogramming of embryos. Hence, in this report, the experimental design was aimed at improving the developmental efficiency of cloned embryos by repetitive Ca(2+) transients rather than the commonly used ionomycin treatment (4 min). To determine optimal Ca(2+) inflow conditions, we performed three different repetitive ionomycin (10 µM) treatments in reconstructed embryos: Group 1 (4-min ionomycin treatment, once), Group 2 (30-sec treatment, 4 times, 15-min intervals) and Group 3 (1-min treatment, 4 times, 15-min intervals). Pronuclear formation rates were checked to assess the effects of repetitive ionomycin treatment on reprogramming of cloned embryos. Cleavage rates were investigated on day 2, and the formation rates of blastocysts (BLs) were examined on day 7 to demonstrate the positive effect of repeated ionomycin treatment. In Group 3, a significant increase in BL formation was observed [47/200 (23.50%), 44/197 (22.33%) and 69/195 (35.38%) in Groups 1, 2 and 3, respectively]. Culturing embryos with different ionomycin treatments caused no significant difference among the groups in terms of the total cell number of BLs (164.3, 158.5 and 145.1, respectively). Additionally, expression of the anti-apoptotic Bcl-2 gene and MnSOD increased significantly in Group 3, whereas the expression of the pro-apoptotic Bax decreased statistically. In conclusion, the present study demonstrated that repeated ionomycin treatment is an improved activation method that can increase the developmental competence of SCNT embryos by decreasing the incidence of apoptosis.

Deep learning-based prediction of heart failure rehospitalization during 6, 12, 24-month follow-ups in patients with acute myocardial infarction.

Heart failure is a clinical syndrome that occurs when the heart is too weak or stiff and cannot pump enough blood that our body needs. It is one of the most expensive diseases due to frequent hospitalizations and emergency room visits. Reducing unnecessary rehospitalizations is also an important and challenging task that has the potential of saving healthcare costs, enabling discharge planning, and identifying patients at high risk. Therefore, this paper proposes a deep learning-based prediction model of heart failure rehospitalization during 6, 12, 24-month follow-ups after hospital discharge in patients with acute myocardial infarction (AMI). We used the Korea Acute Myocardial Infarction-National Institutes of Health (KAMIR-NIH) registry which included 13,104 patient records and 551 features. The proposed deep learning-based rehospitalization prediction model outperformed traditional machine learning algorithms such as logistic regression, support vector machine, AdaBoost, gradient boosting machine, and random forest. The performance of the proposed model was accuracy, the area under the curve, precision, recall, specificity, and F1 score of 99.37%, 99.90%, 96.86%, 98.61%, 99.49%, and 97.73%, respectively. This study showed the potential of a deep learning-based model for cardiology, which can be used for decision-making and medical diagnosis tool of heart failure rehospitalization in patients with AMI.

Evaluation of genotoxicity of SUNACTIVE Zn-P240 in vitro and in vivo.

We evaluated the potential genotoxic effects of the nutrient supplement SUNACTIVE Zn-P240 in vitro and in vivo. Genotoxicity tests were performed at the Korea Testing and Research Institute, a GLP certification institution. A bacterial reverse mutation test was performed using the pre-incubation method, while the in vitro chromosome aberration test was performed using a cultured Chinese hamster lung cell line in the presence or absence of metabolic activation. The in vivo micronucleus test was performed using ICR mice. The bacterial reverse mutation test revealed that SUNACTIVE Zn-P240 did not induce genetic mutations at the tested doses in Salmonella typhimurium (TA98, TA100, TA1535, and TA1537) and Escherichia coli (WP2uvrA) tester strains. Meanwhile, the results of the in vitro chromosomal aberration and in vivo micronucleus tests revealed that SUNACTIVE Zn-P240 did not induce chromosomal aberrations. These results suggest that SUNACTIVE Zn-P240 did not exhibit mutagenic or clastogenic properties in vitro and in vivo.

Association between CHADS2, CHA2DS2-VASc, ATRIA, and Essen Stroke Risk Scores and Unsuccessful Recanalization after Endovascular Thrombectomy in Acute Ischemic Stroke Patients.

BACKGROUND: The CHADS2, CHA2DS2-VASc, ATRIA, and Essen scores have been developed for predicting vascular outcomes in stroke patients. We investigated the association between these stroke risk scores and unsuccessful recanalization after endovascular thrombectomy (EVT). METHODS: From the nationwide multicenter registry (Selection Criteria in Endovascular Thrombectomy and Thrombolytic therapy (SECRET)) (Clinicaltrials.gov NCT02964052), we consecutively included 501 patients who underwent EVT. We identified pre-admission stroke risk scores in each included patient. RESULTS: Among 501 patients who underwent EVT, 410 (81.8%) patients achieved successful recanalization (mTICI ≥ 2b). Adjusting for body mass index and p < 0.1 in univariable analysis revealed the association between all stroke risk scores and unsuccessful recanalization (CHADS2 score: odds ratio (OR) 1.551, 95% confidence interval (CI) 1.198-2.009, p = 0.001; CHA2DS2VASc score: OR 1.269, 95% CI 1.080-1.492, p = 0.004; ATRIA score: OR 1.089, 95% CI 1.011-1.174, p = 0.024; and Essen score: OR 1.469, 95% CI 1.167-1.849, p = 0.001). The CHADS2 score had the highest AUC value and differed significantly only from the Essen score (AUC of CHADS2 score; 0.618, 95% CI 0.554-0.681). CONCLUSION: All stroke risk scores were associated with unsuccessful recanalization after EVT. Our study suggests that these stroke risk scores could be used to predict recanalization in stroke patients undergoing EVT.

Association between CHADS2, CHA2DS2-VASc, ATRIA, and Essen Stroke Risk Scores and Functional Outcomes in Acute Ischemic Stroke Patients Who Received Endovascular Thrombectomy.

Background: CHADS2, CHA2DS2-VASc, ATRIA, and Essen stroke risk scores are used to estimate thromboembolism risk. We aimed to investigate the association between unfavorable outcomes and stroke risk scores in patients who received endovascular thrombectomy (EVT). Methods: This study was performed using data from a nationwide, multicenter registry to explore the selection criteria for patients who would benefit from reperfusion therapies. We calculated pre-admission CHADS2, CHA2DS2-VASc, ATRIA, and Essen scores for each patient who received EVT and compared the relationship between these scores and 3-month modified Rankin Scale (mRS) records. Results: Among the 404 patients who received EVT, 213 (52.7%) patients had unfavorable outcomes (mRS 3−6). All scores were significantly higher in patients with unfavorable outcomes than in those with favorable outcomes. Multivariable logistic regression analysis indicated that CHADS2 and the ATRIA score were positively correlated with unfavorable outcomes after adjusting for body mass index and variables with p < 0.1 in the univariable analysis (CHADS2 score: odds ratio [OR], 1.484; 95% confidence interval [CI], 1.290−1.950; p = 0.005, ATRIA score, OR, 1.128; 95% CI, 1.041−1.223; p = 0.004). Conclusions: The CHADS2 and ATRIA scores were positively correlated with unfavorable outcomes and could be used to predict unfavorable outcomes in patients who receive EVT.

A soft voting ensemble classifier for early prediction and diagnosis of occurrences of major adverse cardiovascular events for STEMI and NSTEMI during 2-year follow-up in patients with acute coronary syndrome.

OBJECTIVE: Some researchers have studied about early prediction and diagnosis of major adverse cardiovascular events (MACE), but their accuracies were not high. Therefore, this paper proposes a soft voting ensemble classifier (SVE) using machine learning (ML) algorithms. METHODS: We used the Korea Acute Myocardial Infarction Registry dataset and selected 11,189 subjects among 13,104 with the 2-year follow-up. It was subdivided into two groups (ST-segment elevation myocardial infarction (STEMI), non ST-segment elevation myocardial infarction NSTEMI), and then subdivided into training (70%) and test dataset (30%). Third, we selected the ranges of hyper-parameters to find the best prediction model from random forest (RF), extra tree (ET), gradient boosting machine (GBM), and SVE. We generated each ML-based model with the best hyper-parameters, evaluated by 5-fold stratified cross-validation, and then verified by test dataset. Lastly, we compared the performance in the area under the ROC curve (AUC), accuracy, precision, recall, and F-score. RESULTS: The accuracies for RF, ET, GBM, and SVE were (88.85%, 88.94%, 87.84%, 90.93%) for complete dataset, (84.81%, 85.00%, 83.70%, 89.07%) STEMI, (88.81%, 88.05%, 91.23%, 91.38%) NSTEMI. The AUC values in RF were (98.96%, 98.15%, 98.81%), ET (99.54%, 99.02%, 99.00%), GBM (98.92%, 99.33%, 99.41%), and SVE (99.61%, 99.49%, 99.42%) for complete dataset, STEMI, and NSTEMI, respectively. Consequently, the accuracy and AUC in SVE outperformed other ML models. CONCLUSIONS: The performance of our SVE was significantly higher than other machine learning models (RF, ET, GBM) and its major prognostic factors were different. This paper will lead to the development of early risk prediction and diagnosis tool of MACE in ACS patients.

Comorbidity index for predicting mortality at 6 months after reperfusion therapy.

The eligibility of reperfusion therapy has been expanded to increase the number of patients. However, it remains unclear the reperfusion therapy will be beneficial in stroke patients with various comorbidities. We developed a reperfusion comorbidity index for predicting 6-month mortality in patients with acute stroke receiving reperfusion therapy. The 19 comorbidities included in the Charlson comorbidity index were adopted and modified. We developed a statistical model and it was validated using data from a prospective cohort. Among 1026 patients in the retrospective nationwide reperfusion therapy registry, 845 (82.3%) had at least one comorbidity. As the number of comorbidities increased, the likelihood of mortality within 6 months also increased (p < 0.001). Six out of the 19 comorbidities were included for developing the reperfusion comorbidity index on the basis of the odds ratios in the multivariate logistic regression analysis. This index showed good prediction of 6-month mortality in the retrospective cohort (area under the curve [AUC], 0.747; 95% CI, 0.704-0.790) and in 333 patients in the prospective cohort (AUC, 0.784; 95% CI, 0.709-0.859). Consideration of comorbidities might be helpful for the prediction of the 6-month mortality in patients with acute ischemic stroke who receive reperfusion therapy.

Effects of recombinant relaxin on in vitro maturation of porcine oocytes.

Relaxin, a member of the insulin superfamily, has diverse functions in both reproductive and nonreproductive tissues. The aim of the present study was to evaluate the effects of recombinant relaxin on the in vitro maturation of porcine oocytes and their subsequent embryonic development following in vitro fertilization. Three concentrations of relaxin (1, 10, and 100 ng/ml) were used in the in vitro maturation (IVM) medium [TCM supplemented with 10% (v/v) porcine follicular fluid, 10 ng/ml of epidermal growth factor, 4 IU/ml of pregnant mare serum gonadotropin, and (only for the first 22 hr) 4 IU/ml of human chorionic gonadotropin]. Relaxin was used during the entire IVM period. Nuclear maturation of oocytes was examined under ultraviolet light following staining with bisbenzimide (Hoechst 33342) for 5 min and mounted on a glass slide. The glutathione (GSH) content in oocytes, an important indicator of cytoplasmic maturity, was measured using a micro-glutathione assay. Cryopreserved boar semen was used for in vitro fertilization. Embryos were cultured in modified NCSU-23 medium supplemented with 0.5 mM pyruvate and 5 mM lactate. Although nuclear maturation of oocytes did not vary, the GSH content in oocytes was significantly higher when cultured with 1 ng/ml (7.9 pmol/oocyte) and 10 ng/ml (8.47 pmol/oocyte) compared to a control group. However, no additional beneficial effect was observed when 100 ng/ml of relaxin was added to the IVM medium. A significantly higher rate of blastocyst formation was observed with 10 ng of relaxin (32.4%) compared to the control (14.4%) or 100 ng of relaxin (21.4%). No difference between 1 ng and 10 ng was observed in terms of the blastocyst production rate. The inner cell mass cell numbers in relaxin-treated groups were significantly higher than control, and trophectoderm cell number was the highest in the 10 ng relaxin group. Relaxin (10 ng/ml) can be supplemented in IVM medium to support the maturation of porcine oocytes.

Patient characteristics according to rehabilitation and employment status in Korean hemodialysis patients.

BACKGROUND: While the final goal of renal replacement therapy is to achieve normal social adaptation and employment, many studies to date have focused on the analysis of complications and causes of death. In contrast, the analysis of dialysis patients with normal job employment and exhibiting a good medical status can be important for clinical treatment policy. This study assessed various clinical parameters according to rehabilitation and employment status to elucidate characteristics correlated with better rehabilitation status among hemodialysis patients. METHODS: A total of 29,865 hemodialysis patients who were registered with rehabilitation status information in the Korean Society of Nephrology end-stage renal disease registration program from January 2017 to April 2019 were included and divided into five groups according to their rehabilitation status. RESULTS: About half (47%) of enrolled patients belonged to the "independent but without a job" group and 21% of patients belonged to the "employed with a full-time job" group. Analysis revealed significantly younger mean age, longer mean hemodialysis duration, a higher proportion of male sex, and a lower proportion of diabetic nephropathy cases in the full-time job group than in the other hemodialysis patient groups. Also, hemoglobin, albumin, and phosphorus levels were higher but the urea reduction ratio was lower in the full-time job group. CONCLUSION: A better rehabilitation and employment state of hemodialysis patients was associated with younger age, male sex, and underlying chronic glomerulonephritis. Patients with full-time jobs generally have better laboratory data but lower dialysis efficacy.

A machine learning-based 1-year mortality prediction model after hospital discharge for clinical patients with acute coronary syndrome.

Cardiovascular disease is the leading cause of death worldwide so, early prediction and diagnosis of cardiovascular disease is essential for patients affected by this fatal disease. The goal of this article is to propose a machine learning-based 1-year mortality prediction model after discharge in clinical patients with acute coronary syndrome. We used the Korea Acute Myocardial Infarction Registry data set, a cardiovascular disease database registered in 52 hospitals in Korea for 1 November 2005-30 January 2008 and selected 10,813 subjects with 1-year follow-up traceability. The ranges of hyperparameters to find the best prediction model were selected from four different machine learning models. Then, we generated each machine learning-based mortality prediction model with hyperparameters completed the range fitness via grid search using training data and was evaluated by fourfold stratified cross-validation. The best prediction model with the highest performance was found, and its hyperparameters were extracted. Finally, we compared the performance of machine learning-based mortality prediction models with GRACE in area under the receiver operating characteristic curve, precision, recall, accuracy, and F-score. The area under the receiver operating characteristic curve in applied machine learning algorithms was averagely improved up to 0.08 than in GRACE, and their major prognostic factors were different. This implementation would be beneficial for prediction and early detection of major adverse cardiovascular events in acute coronary syndrome patients.

Clopidogrel preventive effect based on cytochrome P450 2C19 genotype in ischaemic stroke: protocol for multicentre observational study.

INTRODUCTION: Clopidogrel is an antiplatelet agent that is widely used for the secondary prevention of cardiovascular and cerebrovascular events. The genotype of cytochrome P450 2C19 (CYP2C19) differentially affects the liver's metabolism of clopidogrel, which may influence the drug's response and efficacy for cardiovascular event prevention. In contrast to prior studies of patients with coronary artery diseases, little is known about whether the CYP2C19 genotype influences the preventive efficacy of clopidogrel in patients who had a stroke. We hypothesise that, among patients who had an acute ischaemic stroke who are prescribed clopidogrel, the patients with a loss-of-function CYP2C19 genotype (poor and intermediate metabolisers) may be at a higher risk of composite cardiovascular events than those who are non-carriers (extensive metabolisers). METHODS AND ANALYSIS: This prospective observational multicentre study was designed to determine whether composite cardiovascular events would differ among patients who had an ischaemic stroke prescribed clopidogrel according to CYP2C19 genotype (poor or intermediate vs extensive metabolisers). Inclusion criteria were patients who had an acute ischaemic stroke who underwent CYP2C19 genotype evaluation and received clopidogrel within 72 hours of stroke onset. The primary outcome is composite cardiovascular events (stroke, myocardial infarction, or cardiovascular death) within 6 months after acute ischaemic stroke between patients categorised as poor or intermediate metabolisers and those categorised as extensive metabolisers according to their CYP2C19 genotype. ETHICS AND DISSEMINATION: The Institutional Review Board of Severance Hospital, Yonsei University College of Medicine approved this study (3-2019-0195). We received study approval from the institutional review board of each participating hospital. We plan to disseminate our findings at relevant conferences and meetings and through peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04072705.