TIMECARD score: An easily operated prediction model of unfavorable neurological outcomes in out-of-hospital cardiac arrest patients with targeted temperature management.

BACKGROUND: Targeted temperature management (TTM) is recommended for comatose out-of-hospital cardiac arrest (OHCA) survivors. Several prediction models have been proposed; however, most of these tools require data conversion and complex calculations. Early and easy predictive model of neurological prognosis in OHCA survivors with TTM warrant investigation. MATERIALS AND METHODS: This multicenter retrospective cohort study enrolled 408 non-traumatic adult OHCA survivors with TTM from the TaIwan network of targeted temperature ManagEment for CARDiac arrest (TIMECARD) registry during January 2014 to June 2019. The primary outcome was unfavorable neurological outcome at discharge. The clinical variables associated with unfavorable neurological outcomes were identified and a risk prediction score-TIMECARD score was developed. The model was validated with data from National Taiwan University Hospital. RESULTS: There were 319 (78.2%) patients presented unfavorable neurological outcomes at hospital discharge. Eight independent variables, including malignancy, no bystander cardiopulmonary resuscitation (CPR), non-shockable rhythm, call-to-start CPR duration >5 min, CPR duration >20 min, sodium bicarbonate use during resuscitation, Glasgow Coma Scale motor score of 1 at return of spontaneous circulation, and no emergent coronary angiography, revealed a significant correlation with unfavorable neurological prognosis in TTM-treated OHCA survivors. The TIMECARD score was established and demonstrated good discriminatory performance in the development cohort (area under the receiver operating characteristic curve [AUC] = 0.855) and validation cohorts (AUC = 0.918 and 0.877, respectively). CONCLUSION: In emergency settings, the TIMECARD score is a practical and simple-to-calculate tool for predicting neurological prognosis in OHCA survivors, and may help determine whether to initiate TTM in indicated patients.

The CSP (Cardiogenic Shock Prognosis) Score: A Tool for Risk Stratification of Cardiogenic Shock.

Background: Cardiogenic shock (CS) is a critical condition and the leading cause of mortality after acute myocardial infarction (AMI). Scores that predict mortality have been established, but a patient's clinical course is often nonlinear. Thus, factors present during acute care management may be explored. This study intended to develop a risk-predictive model for patients with CS. Methods: In this observational study, adult patients who received inotropic support at the Emergency Room (ER) from January 2017 to August 2020 and were admitted to the cardiac care unit (CCU) with a diagnosis of CS were enrolled in this study. Patients with out-of-hospital cardiac arrest, inotropic support for bradycardia, and survival <24 h after ER arrival were excluded. A total of 311 patients were enrolled and categorized into derivation (n = 243) and validation (n = 68) cohorts. Results: A history of coronary artery disease, multiple inotrope use, ejection fraction <40%, lower hemoglobin concentration, longer cardiopulmonary resuscitation duration, albumin infusion, and renal replacement therapy were identified as independent prognostic factors for in-hospital mortality. The cardiogenic shock prognosis (CSP) score was established as a nomogram and three risk groups were identified: low-risk (score 115, 0% of mortality), medium-risk (score 116-209, 8.75% of mortality), and high-risk (score 210, 66.67% of mortality). The area-under-the-curve (AUC) of the CSP score was 0.941, and the discrimination value in the validation cohort was consistent (AUC = 0.813). Conclusions: The CSP score represents a risk-predictive model for in-hospital mortality in patients with CS in acute care settings. Patients identified as the high-risk category may have a poor prognosis.

The Differences of CPR duration between Shockable and Nonshockable Rhythms in Predicting the Benefit of Target Temperature Management.

BACKGROUND: Among cardiac arrest (CA) survivors, whether the combination of duration of cardiopulmonary resuscitation (CPR) and shockable/nonshockable rhythms during resuscitation can help predict the benefit of targeted temperature management (TTM) remains un-investigated. MATERIALS AND METHODS: This multicenter retrospective cohort study enrolled 479 nontraumatic adult CA survivors with TTM and CPR duration < 60 min during January 2014 to June 2019 from the Taiwan network of targeted temperature ManagEment for CARDiac arrest (TIMECARD) registry. The differences of CPR duration between shockable and nonshockable rhythms in predicting outcomes in the studied population was evaluated. RESULTS: We observed that 205 patients (42.8%) survived to hospital discharge and 100 patients (20.9%) presented favorable neurological outcomes at discharge. The enrolled patients were further re-classified into four groups according to shockable/nonshockable rhythms and CPR duration. Patients with shockable rhythms and shorter CPR duration had better survival-to-discharge (adjusted odds ratio [OR] = 2.729, 95% confidence interval [CI] = 1.384-5.383, P = 0.004) and neurological recovery (adjusted OR = 9.029, 95%CI = 3.263-24.983, P  < 0.001) than did those with nonshockable rhythms and longer CPR duration. CONCLUSION: The CPR duration for predicting outcomes differs between CA patients with shockable and nonshockable rhythms. The combination of shockable/nonshockable rhythms and CPR duration may help predict the prognosis in CA survivors undergoing TTM.

Predicting the survivals and favorable neurologic outcomes after targeted temperature management by artificial neural networks.

BACKGROUND: To identify the outcome-associated predictors and develop predictive models for patients receiving targeted temperature management (TTM) by artificial neural network (ANN). METHODS: The derived cohort consisted of 580 patients with cardiac arrest and ROSC treated with TTM between January 2014 and August 2019. We evaluated the predictive value of parameters associated with survival and favorable neurologic outcome. ANN were applied for developing outcome prediction models. The generalizability of the models was assessed through 5-fold cross-validation. The performance of the models was assessed according to the accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve (AUC). RESULTS: The parameters associated with survival were age, duration of cardiopulmonary resuscitation, history of diabetes mellitus (DM), heart failure, end-stage renal disease (ESRD), systolic blood pressure (BP), diastolic BP, body temperature, motor response after ROSC, emergent coronary angiography or percutaneous coronary intervention (PCI), and the cooling methods. The parameters associated with the favorable neurologic outcomes were age, sex, DM, chronic obstructive pulmonary disease, ESRD, stroke, pre-arrest cerebral-performance category, BP, body temperature, motor response after ROSC, emergent coronary angiography or PCI, and cooling methods. After adequate training, ANN Model 1 to predict survival achieved an AUC of 0.80. Accuracy, sensitivity, and specificity were 75.9%, 71.6%, and 79.3%, respectively. ANN Model 4 to predict the favorable neurologic outcome achieved an AUC of 0.87, with accuracy, sensitivity, and specificity of 86.7%, 77.7%, and 88.0%, respectively. CONCLUSION: The ANN-based models achieved good performance to predict the survival and favorable neurologic outcomes after TTM. The models proposed have clinical value to assist in decision-making.

Post-Cardiac Arrest Hydrocortisone Use Ameliorates Cardiac Mitochondrial Injury in a Male Rat Model of Ventricular Fibrillation Cardiac Arrest.

Background Steroid use after cardiac arrest has been reported to improve survival and neurological outcome in cardiac arrest survivors. The study aimed to evaluate the effect of post-arrest hydrocortisone use on myocardial damage and cardiac mitochondrial injury in a rat model of ventricular fibrillation cardiac arrest. Methods and Results Ventricular fibrillation cardiac arrest was induced and left untreated for 5 minutes in adult male Wistar rats. Cardiopulmonary resuscitation and electric shocks were then applied to achieve return of spontaneous circulation (ROSC). Successfully resuscitated animals were randomized into 3 groups: control, low-dose hydrocortisone (2 mg/kg), and high-dose hydrocortisone (8 mg/kg). The low-dose hydrocortisone and high-dose hydrocortisone (treatment) groups received intravenous hydrocortisone immediately after ROSC and the control group received saline as placebo. Each group consisted of 15 animals. Within 4 hours of ROSC, both treatment groups showed a higher cardiac output than the control group. At the fourth hour following ROSC, histological examination and transmission electron microscopy demonstrated less myocardial damage and mitochondrial injury in the animals treated with hydrocortisone. In the treatment groups, hydrocortisone mitigated the acceleration of Ca2+-induced mitochondrial swelling and suppression of complex activity observed in the control group. At the 72nd hour after ROSC, a significantly higher proportion of animals treated with hydrocortisone survived and had good neurological recovery compared with those given a placebo. Conclusions Hydrocortisone use after cardiac arrest may mitigate myocardial injury and cardiac mitochondrial damage and thus improve survival, neurological and histological outcomes in a rat model of ventricular fibrillation cardiac arrest.

Ventilator Parameters in the Diagnosis and Prognosis of Acute Respiratory Distress Syndrome in Postoperative Patients: A Preliminary Study.

This study investigated the usefulness of ventilator parameters in the prediction of development and outcome of acute respiratory distress syndrome (ARDS) in postoperative patients with esophageal or lung cancer on admission to the surgical intensive care unit (SICU). A total of 32 post-operative patients with lung or esophageal cancer from SICU in a tertiary medical center were retrospectively analyzed. The study patients were divided into an ARDS group (n = 21) and a non-ARDS group (n = 11). The ARDS group contained the postoperative patients who developed ARDS after lung or esophageal cancer surgery. The ventilator variables were analyzed in this study. Principal component analysis (PCA) was performed to reduce the correlated ventilator variables to a small set of variables. The top three ventilator variables with large coefficients, as determined by PCA, were considered as sensitive variables and included in the analysis model based on the rule of 10 events per variable. Firth logistic regression with selective stepwise elimination procedure was performed to identify the most important predictors of morbidity and mortality in patients with ARDS. Ventilator parameters, including rapid shallow breath index during mechanical ventilation (RSBIv), rate pressure product of ventilation (RPPv), rate pressure volume index (RPVI), mechanical work (MW), and inspiration to expiration time ratio (IER), were analyzed in this study. It was found that the ARDS patients had significantly greater respiratory rate (RR), airway resistance (Raw), RSBIv, RPPv, RPVI, positive end-expiratory pressure (PEEP), and IER and significantly lower respiratory interval (RI), expiration time (Te), flow rate (V˙), tidal volume (VT), dynamic compliance (Cdyn), mechanical work of ventilation (MW), and MW/IER ratio than the non-ARDS patients. The non-survivors of ARDS had significantly greater peak inspiratory pressure above PEEP (PIP), RSBIv, RPPv, and RPVI than the survivors of ARDS. By using PCA, the MW/IER was found to be the most important predictor of the development of ARDS, and both RPPv and RPVI were significant predictors of mortality in patients with ARDS. In conclusion, some ventilator parameters, such as RPPv, RPVI, and MW/IER defined in this study, can be derived from ventilator readings and used to predict the development and outcome of ARDS in mechanically ventilated patients on admission to the SICU.

Long-Term Effect of Device-Guided Slow Breathing on Blood Pressure Regulation and Chronic Inflammation in Patients with Essential Hypertension Using a Wearable ECG Device.

BACKGROUND: Hypertension is related to autonomic nervous system (ANS) dysfunction, atherosclerosis and chronic inflammation. The stimulation of baroreflex regulation by slow-breathing exercise may improve the interplay among these systems. The objective of this study was to investigate the effect of device-guided slow breathing on ANS, cardiovascular system and chronic inflammation in hypertensive patients. METHODS: We prospectively collected 36 essential hypertension patients who were requested to practice slow-breathing exercise 5 times per day for 3 months. The breathing exercise was guided by a cellphone app with a wearable electrocardiography device and a rhythm of 6 cycles per minute. Cardiovascular indicators including heart rate variability (HRV), blood pressure, pulse wave velocity and baroreflex indexes were sampled 3 times: at the first visit, and 1 month and 3 months after the intervention. The levels of blood inflammatory biomarkers, including tumor necrosis factor-alpha (TNF-α), interleukin-6, interleukin-1 receptor antagonist and C-reactive protein were also collected at all 3 visits. The longitudinal differences in these variables and their correlations were tested. RESULTS: There was a significant decrease in blood pressure after 1 month of exercise. A significantly continuous decrease in TNF-α was also observed. The baroreflex indexes were significantly increased in the acute intervention of slow-breathing but not in the longitudinal effect. The HRV variables did not show differences with time. There were positive correlations between sympathetic index and TNF-α and galectin-3. CONCLUSIONS: The effect of slow-breathing exercise on blood pressure and chronic inflammation was significant. HRV indexes may also be used to assess chronic inflammation.

Post-cardiac arrest care and targeted temperature management: A consensus of scientific statement from the Taiwan Society of Emergency & Critical Care Medicine, Taiwan Society of Critical Care Medicine and Taiwan Society of Emergency Medicine.

BACKGROUND: Post-cardiac arrest care is critically important in bringing cardiac arrest patients to functional recovery after the detrimental event. More high quality studies are published and evidence is accumulated for the post-cardiac arrest care in the recent years. It is still a challenge for the clinicians to integrate these scientific data into the real clinical practice for such a complicated intensive care involving many different disciplines. METHODS: With the cooperation of the experienced experts from all disciplines relevant to post-cardiac arrest care, the consensus of the scientific statement was generated and supported by three major scientific groups for emergency and critical care in post-cardiac arrest care. RESULTS: High quality post-cardiac arrest care, including targeted temperature management, early evaluation of possible acute coronary event and intensive care for hemodynamic and respiratory care are inevitably needed to get full recovery for cardiac arrest. Management of these critical issues were reviewed and proposed in the consensus CONCLUSION: The goal of the statement is to provide help for the clinical physician to achieve better quality and evidence-based care in post-cardiac arrest period.

Probing age-related changes in cardio-respiratory dynamics by multimodal coupling assessment.

Quantifying respiratory sinus arrhythmia (RSA) can provide an index of parasympathetic function. Fourier spectral analysis, the most widely used approach, estimates the power of the heart rate variability in the frequency band of breathing. However, it neglects the time-varying characteristics of the transitions as well as the nonlinear properties of the cardio-respiratory coupling. Here, we propose a novel approach based on Hilbert-Huang transform, called the multimodal coupling analysis (MMCA) method, to assess cardio-respiratory dynamics by examining the instantaneous nonlinear phase interactions between two interconnected signals (i.e., heart rate and respiration) and compare with the counterparts derived from the wavelet-based method. We used an online database. The corresponding RSA components of the 90-min ECG and respiratory signals of 20 young and 20 elderly healthy subjects were extracted and quantified. A cycle-based analysis and a synchro-squeezed wavelet transform were also introduced to assess the amplitude or phase changes of each respiratory cycle. Our results demonstrated that the diminished mean and standard deviation of the derived dynamical RSA activities can better discriminate between elderly and young subjects. Moreover, the degree of nonlinearity of the cycle-by-cycle RSA waveform derived from the differences between the instantaneous frequency and the mean frequency of each respiratory cycle was significantly decreased in the elderly subjects by the MMCA method. The MMCA method in combination with the cycle-based analysis can potentially be a useful tool to depict the aging changes of the parasympathetic function as well as the waveform nonlinearity of RSA compared to the Fourier-based high-frequency power and the wavelet-based method.

The Combination of Astragalus membranaceus and Angelica sinensis Inhibits Lung Cancer and Cachexia through Its Immunomodulatory Function.

Lung cancer and its related cachexia are the leading cause of cancer death in the world. In this study, we report the inhibitory effect of the combined therapy of Astragalus membranaceus and Angelica sinensis, on tumor growth and cachexia in tumor-bearing mice. Lewis lung carcinoma cells were inoculated into male C57BL/6 and CAnN.Cg-Foxn1nu nude mice. After tumor inoculation, mice were fed orally by the combination of AM and AS in different doses. In C57BL/6 mice, the combination of AM and AS significantly inhibited the growth of cancer tumor and prevented the loss of body weight and skeletal muscle. It also diminished the formation of free radicals and cytokines, stimulated the differentiation of NK and Tc cells, and rebalanced the ratios of Th/Tc cells, Th1/Th2 cytokines, and M1/M2 tumor-associated macrophages. The herbal combination also downregulated the expression of NFκΒ, STAT3, HIF-1α, and VEGF in tumors. In contrast, the findings were not observed in the nude mice. Therefore, the combination of AM and AS is confirmed to inhibit the progression of lung cancer, cancer cachexia, and cancer inflammation through the immunomodulatory function.

Robust Fetal Heart Beat Detection via R-Peak Intervals Distribution.

Monitoring fetal heart rate during pregnancy is essential to assist clinicians in making more timely decisions. Non-invasive monitoring of fetal heart activities using abdominal ECGs is useful for diagnosis of heart defects. However, the extracted fetal ECGs are usually too weak to be robustly detected. Thus, it is a necessity to enhance fetal R-peak since their peaks may be hidden within the signal due to the immaturity of the fetal cardiovascular system. Therefore, to improve the detection of the fetal heartbeat, a novel fetal R-peak enhancement technique was proposed to statistically generate the weighting mask according to the distribution of the neighboring temporal intervals between each pair of peaks. Two sets of simulations were designed to validate the reliability of the method: challenges with different levels of (1) noise contamination and (2) R-peak interval changing rate. The simulation results showed that the weighting mask improved the accuracy of the R-peak detection rate by 25% and decreased the false alarm rate by 20% with white noise contamination, and ensured high R-peak detection rate (>80%), especially with mild noise contamination (noise amplitude ratio <1.5 and noise rate per minute <25%). For the simulations with continuous R-peak intervals changing, the masking process can still effectively eliminate noise contamination especially when the amplitude of the sinusoidal fetal R-R intervals is lower than 50 ms. For the real fetus ECGs, the detection rate was increased by 3.498%, whereas the false alarm rate was decreased by 3.933%. Next, we implemented the fetal R-peak enhancement technique to investigate fractal regulation and multiscale entropy of the real fetal heartbeat intervals. Both scaling exponent (∼0.6 to ∼1 in scale 4-15) and entropy measure (scale 6-10) increased with gestational ages (22-40 weeks). The results confirmed fractal slope and complexity of fetal heartbeat intervals can reflect the maturation of fetus organism.

Pediatric otitis media in Fiji: Survey findings 2015.

OBJECTIVE: Otitis media (OM), as a common infectious disease, is a major cause of hearing impairment among the general population. OM remains a major public health threat in the Pacific islands, but the risks of OM have not been thoroughly explored in this region. The objective of this study is to investigate the prevalence, clinical features, and quality-of-life impacts of OM in Fiji. METHODS: In the medical service trip entitled "Healing and Hope - Taiwan Cathay Heart and Hearing Medical Mission to Fiji" (TCHHMMF), we conducted a cross-sectional OM survey study in Suva and Sigatoka areas (Korolevu, Cuvu, and Lomawai) in the summer of 2015. The otitis media - 6 (OM-6) was used to survey the OM-related quality of life. RESULTS: In the 467 pediatric patients (aged 0-18 years old) screened, 13 (2.78%) have acute otitis media (AOM), 37 (7.92%) have otitis media with effusion (OME), and 19 (4.1%) have chronic otitis media (COM). Age (OR 0.53, 95% CI: 0.36-0.77) is a significant predictor of AOM, whereas male gender (OR 2.46, 95% CI: 1.13-5.37), smoke exposure (OR 2.81, 95% CI: 1.01-7.82), and concomitant chronic sinusitis (OR 6.05, 95% CI: 2.31-15.88) are significant predictors of OME. The mean OM-6 item scores are highest in caregiver concerns (3.8), physical suffering (3.7), and hearing loss (3.4) domains. CONCLUSION: OM is an important primary care disease in Fiji that remains under-served. It is critical to educate professionals, parents, and patients to detect and to improve care for OM.

Epidemiology of medical adverse events: perspectives from a single institute in Taiwan.

BACKGROUND/PURPOSE: Epidemiology data of medical adverse events (MAEs) are crucial for patient safety policymaking. However, no epidemiological data on MAE exist in Taiwan. In this study, we aimed to investigate the incidence of MAEs at a major medical center in northern Taiwan. METHODS: The Harvard Medical Practice Study methodology was modified using a criterion-based screening algorithm and critical medical record review process to investigate the risks and incidences of MAEs. A Criterion-Based Screening for Medical Adverse Events (CBSMAE) checklist was developed, and a three-tier strategy was applied to screen and review 2007 inpatient hospitalizations from a single institution. RESULTS: A total of 2934 charts was sampled (Tier 1) and 950 possible MAEs were identified (Tier 2). One hundred and sixty-one probable MAE cases were subsequently critically reviewed (Tier 3). Nineteen (0.7%) MAE cases were confirmed. The MAEs involved 10 women and nine men (mean age, 70 years). Most MAEs were from the surgery department [11 (57.9%) patients]. The major admission diagnoses were cardiac diseases [7 (36.8%) patients] with a cardiac problem [13 (31.7%) patients] as the major comorbidity. Major MAE attributes were a staff technique problem [12 (46.2%) patients] and patients' underlying conditions (likelihood rating, 2.2). Eight (42.1%) patients required additional medical management, four (21.1%) patients had a disability, and five (26.3%) patients had in-hospital mortality. Night MAEs (47.4%) were considered preventable. CONCLUSION: Surgical patients with cardiac conditions were at risk of MAE, particularly patients who received invasive procedures. The epidemiology information from this study can serve as baseline data to monitor a patient safety improvement campaign.

Reversible Changes of Brain Perfusion SPECT for Carbon Monoxide Poisoning-Induced Severe Akinetic Mutism.

PURPOSE: This study aimed to characterize changes in regional cerebral blood flow (rCBF) in patients who experienced carbon monoxide (CO) poisoning and subsequently developed severe delayed neuropsychiatric sequelae (DNS) with akinetic mutism. We determined whether these changes were reversible in parallel with improvements in neuropsychological function in response to treatment, including hyperbaric oxygen therapy. METHODS: Patients who developed severe DNS with akinetic mutism after acute CO intoxication between 2007 and 2011 were enrolled. Tc-ECD brain SPECT findings were compared between the patients with severe akinetic mutism and age-matched control subjects to characterize the pattern of rCBF. Perfusion SPECT was correlated with clinical outcomes after treatment with statistical parametric mapping (SPM8); the height threshold was P < 0.01 at peak level, and the corrected false discovery rate was P < 0.05 at the cluster level. RESULTS: Seven patients with akinetic mutism were analyzed. All patients had neurological symptoms caused by acute CO exposure, and all recovered to nearly normal daily function after initial treatments. In all cases, after a "lucid interval," DNS progressed to akinetic mutism. The SPECT images acquired at the onset of akinetic mutism demonstrated variable hypoperfusion in frontal-temporal-parietal regions, with the greatest severity in the left temporal-parietal regions. In parallel, we performed functional neuropsychiatric tests. After treatment, the brain SPECT showed significantly fewer hypoperfusion regions, and neuropsychiatric tests showed dramatically improved function. CONCLUSIONS: Our findings demonstrated both cerebral cortical and subcortical injuries in patients with CO-induced akinetic mutism. Improvement in rCBF correlated well with functional recovery after treatment.

Carbamazepine attenuates inducible nitric oxide synthase expression through Akt inhibition in activated microglial cells.

UNLABELLED: Abstract Background: Carbamazepine, which was developed primarily for the treatment of epilepsy, is now also useful for the treatment of non-epileptic disorders and inflammatory hyperalgesia. However, the mechanism of its anti-neuroinflammatory action remains poorly understood. OBJECTIVE: This study elucidates the anti-neuroinflammatory capacity of carbamazepine on microglial activation and the relative mechanisms involved. MATERIALS AND METHODS: The microglial BV-2 cells were pretreated with carbamazepine for 15 min before activation by lipopolysaccharide (LPS). After LPS stimulation, the expression of inducible nitric oxide synthase (iNOS) was analyzed by Western blotting (WB) and reverse transcription-polymerase chain reaction. Signaling proteins and cyclooxygenase (COX)-2 were also evaluated by WB. The levels of nitrate and tumor necrosis factor (TNF)-α were analyzed by the Griess method and enzyme-linked immunosorbant assay, respectively. The formation of intracellular reactive oxygen species (ROS) was examined by fluorescent analysis. RESULTS: Carbamazepine strongly attenuated LPS-induced production of NO and iNOS protein at concentrations of 5, 10, and 20 µM. Consistently, it could markedly suppress iNOS mRNA expression stimulated by LPS. Among the signaling pathways, LPS-mediated IκBα degradation or JNK MAPK phosphorylation was not affected by carbamazepine. Interestingly, it was found that carbamazepine could concentration-dependently inhibit LPS-activated phospho-Akt expression. Nevertheless, LPS-induced ROS production was not affected by carbamazepine. Carbamazepine (20 µM) affected either COX-2 expression or TNF-α production induced by LPS with approximately 70% and 51% inhibition, respectively. DISCUSSION AND CONCLUSION: Our findings showed that carbamazepine exerted selective inhibition on LPS-induced microglial iNOS expression through the down-regulation of Akt activation, and thus may play a pivotal role of anti-neuroinflammation in its therapeutic efficacy.

Prediction of survival of ICU patients using computational intelligence.

This paper presents a computational-intelligence-based model to predict the survival rate of critically ill patients who were admitted to an intensive care unit (ICU). The prediction input variables were based on the first 24 h admission physiological data of ICU patients to forecast whether the final outcome was survival or not. The prediction model was based on a particle swarm optimization (PSO)-based Fuzzy Hyper-Rectangular Composite Neural Network (PFHRCNN) that integrates three computational intelligence tools including hyper-rectangular composite neural networks, fuzzy systems and PSO. It could help doctors to make appropriate treatment decisions without excessive laboratory tests. The performance of the proposed prediction model was evaluated on the data set collected from 300 ICU patients in the Cathy General Hospital in 2012. There were 10 input variables in total for the prediction model. Nine of these variables (e.g. systolic arterial blood pressures, systolic non-invasive blood pressures, respiratory rate, heart rate, and body temperature) were routinely available for 24 h in ICU and the last variable is patient's age. The proposed model could achieve a 96% and 86% accuracy rate for the training data and testing data, respectively.

Aristolochic acid downregulates monocytic matrix metalloproteinase-9 by inhibiting nuclear factor-κB activation.

Aristolochic acid (AA)-associated nephropathy was described as being characterized by a rapid progressive enhancement of interstitial renal fibrosis. Renal tissue fibrosis occurs because of an imbalance of extracellular matrix (ECM) accumulation and matrix metalloproteinase (MMP) activation. Much evidence indicates that inflammatory renal disease including monocyte and mesangial interactions is linked to the development and progression of renal remodeling. In this study, we found that AA showed concentration-dependent inhibition of tumor necrosis factor (TNF)-α-induced MMP-9 activation with an IC(50) value of 6.4±0.5µM in human monocytic THP-1 cells. A similar effect was also noted with different ratios of AAs (types I and II). However, AA had no inhibitory effect on the intact enzymatic activity of MMP-9 at a concentration of 20µM. On the other hand, the level of tissue inhibitor of metalloproteinase (TIMP)-1 was not induced by AA, but it suppressed TNF-α-induced MMP-9 protein and messenger RNA expressions. AA also significantly inhibited TNF-α-induced IκBα degradation. Furthermore, an electrophoretic mobility shift assay and a reported gene study, respectively, revealed that AA inhibited TNF-α-induced NF-κB translocation and activation. In addition, compared to other NF-κB inhibitors, AA exerted significant inhibition of MMP-9 activation and monocyte chemotactic protein-1-directed invasion. From these results, we concluded that AA, a natural compound, inhibits TNF-α-induced MMP-9 in human monocytic cells possibly through the NF-κB signal pathway. These results also imply that AA may be involved in alteration of matrix homeostasis during renal fibrosis in vivo.

Decreasing dosage of irinotecan, 5-flurouracil (5-FU) and leucovorin (LV) in the treatment of advanced and/or metastatic colorectal cancer: a phase II study.

BACKGROUND: In this study, we attempted to determine the efficacy and toxicity of decreasing dosage of irinotecan plus 5-fluorouracil (5-FU) and leucovorin (LV) in the treatment of advanced colorectal cancer. METHODS: A total of 250 mg/m2 Irinotecan (CPT-11) intravenous infusion for 90 minutes was administered every 3 weeks. A 24-hour intravenous infusion with 2000 mg/m2 5-FU and 200 mg/m2 LV was administered through a port-A catheter system weekly for 2 consecutive weeks. Each treatment cycle was repeated every 3 weeks. Progression-free survival and survival curves were drawn according to Kaplan-Meier method. Tumor responses were determined according to the RECIST guidelines. Toxicities were evaluated using the WHO criteria. RESULTS: Thirty-eight patients were enrolled from September 2001 through October 2004. The median number of treatment courses was 8.1 (range, 1-14). Based on the intent-to-treat principle, the response rate was 39.5% (95% CI: 25.4-54.4%) which included 5.3% complete response (CR) and 34.2% partial response (PR). The time to tumor progression was 8.4 months (range, 2-12 months). The median time of survival was 18.4 months (range, 4-26 months). The major toxicities were grade 1 neutropenia and grade 2 diarrhea. Toxic death was not found in this study. The efficacy of this regimen was compatible with the reports of the clinical trials in the United States and European countries but fewer incidence of toxicity was found in our results. CONCLUSION: The results revealed that our combination regimen of 5-FU/LV + CPT-11 is a highly effective and acceptable protocol. This treatment is easily performed in an outpatient clinic. The biggest advantage is that all patients were intensively cared by the physicians to maintain a quality of life, and only 26.3% of patients showed progressive disease. Therefore, this regimen may be considered to be used in the treatment of patients with terminal cancer. A further randomized study comparing this regimen with oral fluoropyrimidines plus irinotecan is warranted.

A randomized trial comparing intravesical instillations of mitoxantrone and doxorubicin in patients with superficial bladder cancer.

BACKGROUND: This randomized trial was conducted to compare the efficacy and side effects of intravesical mitoxantrone instillation with those of doxorubicin in superficial bladder cancer following transurethral resection. METHODS: Sixty-three patients were randomized into mitoxantrone and doxorubicin groups. Most of the patients enrolled were elderly people (mean age, 71 years). The instilled doses of doxorubicin and mitoxantrone were 30 and 14 mg, respectively. Disease recurrence and side effects were compared using Fisher's exact test. The interval to recurrence was shown by Kaplan-Meier survivorship curves, and the log-rank test was used to compare the time to recurrence. RESULTS: The median follow-up period was 36 months. Thirty-three patients received mitoxantrone, whereas 30 patients used doxorubicin. The recurrence rate in the doxorubicin group was 30% (95% CI: 19.8%-38.8%), while it was 27.3% (95% CI: 17.5%-36.8%) in the mitoxantrone group. The median recurrence-free survival in the mitoxantrone group and in the doxorubicin group was 22 and 20 months, respectively (p=0.580). Higher recurrence rates were found for Grade III and multiple primary tumors. There was no significant difference in response rates (p=0.784). The incidence of side effects was 20% in the doxorubicin group and 21.2% in the mitoxantrone group. However, the difference was not significant (p>0.99). CONCLUSIONS: The results revealed that the efficacy and side effects of mitoxantrone were similar to those of doxorubicin. Especially for patients with pulmonary tuberculosis or aged patients with primary bladder tumors, mitoxantrone and doxorubicin may be the tolerable and effective intravesical agents.