Federated machine learning for predicting acute kidney injury in critically ill patients: a multicenter study in Taiwan.

Purpose: To address the contentious data sharing across hospitals, this study adopted a novel approach, federated learning (FL), to establish an aggregate model for acute kidney injury (AKI) prediction in critically ill patients in Taiwan. Methods: This study used data from the Critical Care Database of Taichung Veterans General Hospital (TCVGH) from 2015 to 2020 and electrical medical records of the intensive care units (ICUs) between 2018 and 2020 of four referral centers in different areas across Taiwan. AKI prediction models were trained and validated thereupon. An FL-based prediction model across hospitals was then established. Results: The study included 16,732 ICU admissions from the TCVGH and 38,424 ICU admissions from the other four hospitals. The complete model with 60 features and the parsimonious model with 21 features demonstrated comparable accuracies using extreme gradient boosting, neural network (NN), and random forest, with an area under the receiver-operating characteristic (AUROC) curve of approximately 0.90. The Shapley Additive Explanations plot demonstrated that the selected features were the key clinical components of AKI for critically ill patients. The AUROC curve of the established parsimonious model for external validation at the four hospitals ranged from 0.760 to 0.865. NN-based FL slightly improved the model performance at the four centers. Conclusion: A reliable prediction model for AKI in ICU patients was developed with a lead time of 24 h, and it performed better when the novel FL platform across hospitals was implemented. Supplementary Information: The online version contains supplementary material available at 10.1007/s13755-023-00248-5.

The clinical efficacy of cefoperazone-sulbactam versus piperacillin-tazobactam in the treatment of severe community-acquired pneumonia.

The objective was to compare the clinical efficacy of cefoperazone-sulbactam with piperacillin-tazobactam in the treatment of severe community-acquired pneumonia (SCAP). The retrospective study was conducted from March 1, 2018 to May 30, 2019. Clinical outcomes were compared for patients who received either cefoperazone-sulbactam or piperacillin-tazobactam in the treatment of SCAP. A total of 815 SCAP patients were enrolled. Among them, 343 received cefoperazone-sulbactam, and 472 received piperacillin-tazobactam. Patients who received cefoperazone-sulbactam presented with higher Charlson Comorbidity Index scores. (6.20 ± 2.77 vs 5.72 ± 2.61; P = .009). The clinical cure rates and effectiveness for patients receiving cefoperazone-sulbactam and piperacillin-tazobactam were 84.2% versus 80.3% (P = .367) and 85.4% versus 83.3% (P = .258), respectively. In addition, the overall mortality rate of the cefoperazone-sulbactam group was 16% (n = 55), which was also comparable to the piperacillin-tazobactam group (17.8%, n = 84, P = .572). The primary clinical outcomes for patients receiving cefoperazone-sulbactam were superior compared to those receiving piperacillin-tazobactam after adjusting disease severity status. The clinical efficacy of cefoperazone-sulbactam in the treatment of adult patients with SCAP is comparable to that of piperacillin-tazobactam. After adjusting for disease severity, cefoperazone-sulbactam tended to be superior to piperacillin-tazobactam.

Caffeic acid phenethyl ester suppresses EGFR/FAK/Akt signaling, migration, and tumor growth of prostate cancer cells.

BACKGROUND: Epidermal growth factor receptor (EGFR) is upregulated in prostate cancer (PCa). However, suppression of EGFR did not improve the patient outcome, possibly due to the activation of PI3K/Akt signaling in PCa. Compounds able to suppress both PI3K/Akt and EGFR signaling may be effective for treating advanced PCa. PURPOSE: We examined if caffeic acid phenethyl ester (CAPE) simultaneously suppresses the EGFR and Akt signaling, migration and tumor growth in PCa cells. METHODS: Wound healing assay, transwell migration assay and xenograft mice model were used to determine the effects of CAPE on migration and proliferation of PCa cells. Western blot, immunoprecipitation, and immunohistochemistry staining were performed to determine the effects of CAPE on EGFR and Akt signaling. RESULTS: CAPE treatment decreased the gene expression of HRAS, RAF1, AKT2, GSK3A, and EGF and the protein expression of phospho-EGFR (Y845, Y1069, Y1148, Y1173), phospho-FAK, Akt, and ERK1/2 in PCa cells. CAPE treatment inhibited the EGF-induced migration of PCa cells. Combined treatment of CAPE with EGFR inhibitor gefitinib showed additive inhibition on migration and proliferation of PCa cells. Injection of CAPE (15 mg/kg/3 days) for 14 days suppressed the tumor growth of prostate xenografts in nude mice as well as suppressed the levels of Ki67, phospho-EGFR Y845, MMP-9, phospho-Akt S473, phospho-Akt T308, Ras, and Raf-1 in prostate xenografts. CONCLUSIONS: Our study suggested that CAPE can simultaneously suppress the EGFR and Akt signaling in PCa cells and is a potential therapeutic agent for advanced PCa.

Comparison of outcomes between cardiogenic and non-cardiogenic cardiac arrest patients receiving targeted temperature management: The nationwide TIMECARD multicenter registry.

BACKGROUND AND PURPOSE: Targeted temperature management (TTM) has been recommended for post-resuscitation care of cardiac arrest (CA) patients who remain comatose. However, the differences between cardiogenic and non-cardiogenic causes need further investigation. Thus, this study aimed to investigate the difference in outcomes between cardiogenic and non-cardiogenic CA patients receiving TTM. METHODS: The TIMECARD registry established the study cohort and database for patients receiving TTM between January 2013 and September 2019. A total of 543 patients were enrolled, with 305 and 238 patients in the cardiogenic and non-cardiogenic groups, respectively. RESULTS: Compared with the non-cardiogenic group, the cardiogenic group had higher proportion of initial shockable rhythm, better survival (cardiogenic: 45.9%; non-cardiogenic: 30.7%, P = 0.0017), and better neurologic performance at discharge. In the cardiogenic group, witnessed collapse (OR = 0.31, 95% CI: 0.13-0.72), and coronary intervention (OR = 0.45, 95% CI: 0.24-0.84) were positive predictors for overall outcome. Mean arterial pressure <65 mmHg led to poor outcome regardless in the cardiogenic (OR = 3.31, 95% CI: 1.46-7.52) or non-cardiogenic group (OR = 2.39, 95% CI: 1.06-5.39). CONCLUSION: Patients with cardiogenic CA post TTM had better survival and neurologic performance at discharge than those without cardiogenic CA. Cardiogenic etiology was a potential predictor of better cardiac arrest survival, but it was not an independent risk factor for overall outcome after adjusting for potential covariates. In the cardiogenic group, better outcomes were reported in patients with witnessed collapse, bystander cardiopulmonary resuscitation, as well as those receiving coronary intervention.

Score-based prediction model for severe vitamin D deficiency in patients with critical illness: development and validation.

BACKGROUND: Severe vitamin D deficiency (SVDD) dramatically increases the risks of mortality, infections, and many other diseases. Studies have reported higher prevalence of vitamin D deficiency in patients with critical illness than general population. This multicenter retrospective cohort study develops and validates a score-based model for predicting SVDD in patients with critical illness. METHODS: A total of 662 patients with critical illness were enrolled between October 2017 and July 2020. SVDD was defined as a serum 25(OH)D level of < 12 ng/mL (or 30 nmol/L). The data were divided into a derivation cohort and a validation cohort on the basis of date of enrollment. Multivariable logistic regression (MLR) was performed on the derivation cohort to generate a predictive model for SVDD. Additionally, a score-based calculator (the SVDD score) was designed on the basis of the MLR model. The model's performance and calibration were tested using the validation cohort. RESULTS: The prevalence of SVDD was 16.3% and 21.7% in the derivation and validation cohorts, respectively. The MLR model consisted of eight predictors that were then included in the SVDD score. The SVDD score had an area under the receiver operating characteristic curve of 0.848 [95% confidence interval (CI) 0.781-0.914] and an area under the precision recall curve of 0.619 (95% CI 0.577-0.669) in the validation cohort. CONCLUSIONS: This study developed a simple score-based model for predicting SVDD in patients with critical illness. TRIAL REGISTRATION: ClinicalTrials.gov protocol registration ID: NCT03639584. Date of registration: May 12, 2022.

Post-resuscitation diastolic blood pressure is a prognostic factor for outcomes of cardiac arrest patients: a multicenter retrospective registry-based analysis.

BACKGROUND: Post-resuscitation hemodynamic level is associated with outcomes. This study was conducted to investigate if post-resuscitation diastolic blood pressure (DBP) is a favorable prognostic factor. METHODS: Using TaIwan Network of Targeted Temperature ManagEment for CARDiac Arrest (TIMECARD) registry, we recruited adult patients who received targeted temperature management in nine medical centers between January 2014 and September 2019. After excluding patients with extracorporeal circulation support, 448 patients were analyzed. The first measured, single-point blood pressure after resuscitation was used for analysis. Study endpoints were survival to discharge and discharge with favorable neurologic outcomes (CPC 1-2). Multivariate analysis, area under the receiver operating characteristic curve (AUC), and generalized additive model (GAM) were used for analysis. RESULTS: Among the 448 patients, 182 (40.7%) patients survived, and 89 (19.9%) patients had CPC 1-2. In the multivariate analysis, DBP > 70 mmHg was an independent factor for survival (adjusted odds ratio [aOR] 2.16, 95% confidence interval [CI, 1.41-3.31]) and > 80 mmHg was an independent factor for CPC 1-2 (aOR 2.04, 95% CI [1.14-3.66]). GAM confirmed that DBP > 80 mmHg was associated with a higher likelihood of CPC 1-2. In the exploratory analysis, patients with DBP > 80 mmHg had a significantly higher prevalence of cardiogenic cardiac arrest (p = 0.015) and initial shockable rhythm (p = 0.045). CONCLUSION: We found that DBP after resuscitation can predict outcomes, as a higher DBP level correlated with cardiogenic cardiac arrest.

Clinical effectiveness of branded versus generic piperacillin-tazobactam for treating severe community-acquired pneumonia.

PURPOSE: To compare the clinical effectiveness of branded versus generic piperacillin-tazobactam for treating severe community-acquired pneumonia (CAP). PATIENTS AND METHODS: We identified patients with severe CAP who received piperacillin-tazobactam based on a nine-center registry database. Furthermore, we classified the patients in three hospitals, which used only branded piperacillin-tazobactam as the study group, and the patients in six other hospitals, which used both branded and generic products as the control group. RESULTS: A total of 472 patients (n = 263 in the study group and n = 209 in the control group) with severe CAP were included. The study group using branded piperacillin-tazobactam had higher odds of clinical cure (adjusted odds ratio [OR] = 3.77, 95 % confidence interval [CI], 1.93-7.37) and lower odds of treatment failure (adjusted OR = 0.28, 95 % CI, 0.13-0.58) than the control group receiving either branded or generic piperacillin-tazobactam. In addition, the study group was associated with higher odds of clinical effectiveness (adjusted OR = 2.95, 95 % CI, 1.46-6.11), less odds of clinical ineffectiveness (adjusted OR = 0.39, 95 % CI, 0.18-0.81), and lower risk of in-hospital mortality (adjusted OR = 0.39, 95 % CI, 0.21-0.73). CONCLUSION: Based on the findings of the present study using indirect comparison, the clinical effectiveness of generic piperacillin-tazobactam for treating patients with severe CAP might not be as good as that of brand-name products.

A Study on the Outcome of Targeted Temperature Management Comparing Cardiac Arrest Patients Who Received Bystander Cardiopulmonary Resuscitation With Those Who Did Not, Using the Nationwide TIMECARD Multicenter Registry.

Background and Purpose: Targeted temperature management (TTM) is associated with decreased mortality and improved neurological function after cardiac arrest. Additionally, studies have shown that bystander cardiopulmonary resuscitation (BCPR) doubled the survival of patients with out-of-hospital cardiac arrest (OHCA) compared to patients who received no BPCR (no-BCPR). However, the outcome benefits of BCPR on patients who received TTM are not fully understood. Therefore, this study aimed to investigate the outcome differences between BCPR and no-BCPR in patients who received TTM after cardiac arrest. Methods: The Taiwan Network of Targeted Temperature Management for Cardiac Arrest (TIMECARD) multicenter registry established a study cohort and a database for patients receiving TTM between January 2013 and September 2019. A total of 580 patients were enrolled and divided into 376 and 204 patients in the BCPR and no-BCPR groups, respectively. Results: Compared to the no-BCPR group, the BCPR group had a better hospital discharge and survival rate (42.25 vs. 31.86%, P = 0.0305). The BCPR group also had a better neurological outcome at hospital discharge. It had a higher average GCS score (11.3 vs. 8.31, P < 0.0001) and a lower average Glasgow-Pittsburgh cerebral performance category (CPC) scale score (2.14 vs. 2.98, P < 0.0001). After undertaking a multiple logistic regression analysis, it was found that BCPR was a significant positive predictor for in-hospital survival (OR = 0.66, 95% CI: 0.45-0.97, P = 0.0363). Conclusions: This study demonstrated that BCPR had a positive survival and neurological impact on the return of spontaneous circulation (ROSC) in patients receiving TTM after cardiac arrest.

Association of Tocilizumab and Invasive Aspergillosis in Critically Ill Patients with Severe COVID-19 Pneumonia and Acute Respiratory Distress Syndrome.

Coronavirus disease-2019 (COVID-19) causes severe pneumonia and acute respiratory distress syndrome. According to the current consensus, immunosuppressants, such as dexamethasone and anti-interleukin-6 receptor monoclonal antibodies, are therapeutic medications in the early stages of infection. However, in critically ill patients, viral, fungal, and bacterial coinfection results in higher mortality. We conducted a single-center, retrospective analysis of 29 mechanically ventilated patients with artificial airways. Patients were adults with confirmed COVID-19 infection and severe pneumonia. Acute respiratory distress syndrome was diagnosed according to the Kigali modification of the Berlin definition. Six patients had invasive pulmonary aspergillosis coinfection based on elevated serum galactomannan levels and/or bronchoalveolar lavage fluid. We present two cases with brief histories and available clinical data. We also conducted a literature review to determine whether immunosuppressants, such as tocilizumab, increase infection risk or invasive aspergillosis in patients with COVID-19. There is no conclusive evidence to suggest that tocilizumab increases coinfection risk. However, further studies are needed to determine the optimal dose, between-dose interval, and timing of tocilizumab administration in patients with COVID-19.

The Feasibility of a Machine Learning Approach in Predicting Successful Ventilator Mode Shifting for Adult Patients in the Medical Intensive Care Unit.

Background and Objectives: Traditional assessment of the readiness for the weaning from the mechanical ventilator (MV) needs respiratory parameters in a spontaneous breath. Exempted from the MV disconnecting and manual measurements of weaning parameters, a prediction model based on parameters from MV and electronic medical records (EMRs) may help the assessment before spontaneous breath trials. The study aimed to develop prediction models using machine learning techniques with parameters from the ventilator and EMRs for predicting successful ventilator mode shifting in the medical intensive care unit. Materials and Methods: A retrospective analysis of 1483 adult patients with mechanical ventilators for acute respiratory failure in three medical intensive care units between April 2015 and October 2017 was conducted by machine learning techniques to establish the predicting models. The input candidate parameters included ventilator setting and measurements, patients' demographics, arterial blood gas, laboratory results, and vital signs. Several classification algorithms were evaluated to fit the models, including Lasso Regression, Ridge Regression, Elastic Net, Random Forest, Extreme Gradient Boosting (XGBoost), Support Vector Machine, and Artificial Neural Network according to the area under the Receiver Operating Characteristic curves (AUROC). Results: Two models were built to predict the success shifting from full to partial support ventilation (WPMV model) or from partial support to the T-piece trial (sSBT model). In total, 3 MV and 13 nonpulmonary features were selected for the WPMV model with the XGBoost algorithm. The sSBT model was built with 8 MV and 4 nonpulmonary features with the Random Forest algorithm. The AUROC of the WPMV model and sSBT model were 0.76 and 0.79, respectively. Conclusions: The weaning predictions using machine learning and parameters from MV and EMRs have acceptable performance. Without manual measurements, a decision-making system would be feasible for the continuous prediction of mode shifting when the novel models process real-time data from MV and EMRs.

Factors affecting outcomes in patients with cardiac arrest who receive target temperature management: The multi-center TIMECARD registry.

BACKGROUND: Target temperature management (TTM) is a recommended therapy for patients after cardiac arrest (PCA). The TaIwan Network of Targeted Temperature ManagEment for CARDiac Arrest (TIMECARD) registry was established for PCA who receive TTM therapy in Taiwan. We aim to determine the variables that may affect neurologic outcomes in PCA who undergo TTM. METHODS: We retrieved demographic variables, resuscitation variables, and cerebral performance category (CPC) scale score at hospital discharge from the TIMECARD registry. The primary outcome was a favorable neurologic outcome, defined as a CPC scale of 1 or 2 at discharge. A total of 540 PCA treated between January 2014 and September 2019 were identified from the registry. Univariate and multivariate analyses were performed to identify significant variables. RESULTS: The mortality rate was 58.1% (314/540). Favorable neurologic outcomes were noted in 117 patients (21.7%). The factors significantly influencing the neurologic outcome (p < 0.05) were the presence of an initial shockable rhythm or pulseless electric activity, a witnessed cardiac-arrest event, bystander cardiopulmonary resuscitation, a smaller total dose of epinephrine, the diastolic blood pressure value at return of spontaneous circulation, a pre-arrest CPC score of 1, coronary angiography, new-onset seizure, and new-onset serious infection. Older patients and those with premorbid diabetes mellitus, chronic kidney disease, malignancy, obstructive lung disease, or cerebrovascular accident were more likely to have an unfavorable neurologic outcome. CONCLUSION: In the TIMECARD registry, some PCA baseline characteristics, cardiac arrest events, cardiopulmonary resuscitation characteristics, and post-arrest management characteristics were significantly associated with neurologic outcomes.

Clinical effectiveness of cefoperazone-sulbactam vs. piperacillin-tazobactam for the treatment of pneumonia in elderly patients.

OBJECTIVES: Both cefoperazone-sulbactam (CFP-SUL) and piperacillin-tazobactam (PIP-TAZ) are ß-lactam/ß-lactamase inhibitor antibiotics and have a similar antimicrobial spectrum. However, comparative clinical efficacy and safety of CFP-SUL and PIP-TAZ for the treatment of pneumonia remain largely unknown, especially in elderly patients. METHODS: Based on a multi-centre registry database, patients aged ≥65 years, diagnosed with severe community-acquired pneumonia (SCAP), hospital-acquired pneumonia (HAP) or ventilator-associated pneumonia (VAP), and given empirical therapy with CFP-SUL or PIP-TAZ were included in the analysis. The primary outcome of interest was the proportion of patients achieving clinical cure. Multi-variate logistic regression was conducted to compare odds ratios (OR) for the outcome between patients who received CFP-SUL and patients who received PIP-TAZ. RESULTS: In total, 941 elderly patients (624 with SCAP, and 317 with either HAP or VAP) were included in this study. Overall in-hospital mortality for the entire cohort was 19%. Clinical cure was achieved in 81% and 83% of patients with SCAP and HAP/VAP, respectively. Multi-variate logistic regression analysis showed similar odds for clinical cure for patients receiving CFP-SUL or PIP-TAZ among those with SCAP [adjusted OR 1.10, 95% confidence interval (CI) 0.71-1.70] or HAP/VAP (adjusted OR 0.72, 95% CI 0.30-1.76). Regarding safety, both CFP-SUL and PIP-TAZ were generally well tolerated with few reported adverse events. CONCLUSIONS: Among elderly patients with SCAP or HAP/VAP, empirical therapy with CFP-SUL is a viable alternative to PIP-TAZ, while considering antibiotic heterogeneity in the antimicrobial stewardship context.

Prevalence of Vitamin D Deficiency and Associated Factors in Critically Ill Patients: A Multicenter Observational Study.

Background: Vitamin D deficiency is common in the general population worldwide, and the prevalence and severity of vitamin D deficiency increase in critically ill patients. The prevalence of vitamin D deficiency in a community-based cohort in Northern Taiwan was 22.4%. This multicenter cohort study investigated the prevalence of vitamin D deficiency and associated factors in critically ill patients in Northern Taiwan. Methods: Critically ill patients were enrolled and divided into five groups according to their length of stay at intensive care units (ICUs) during enrolment as follows: group 1, <2 days with expected short ICU stay; group 2, <2 days with expected long ICU stay; group 3, 3-7 days; group 4, 8-14 days; and group 5, 15-28 days. Vitamin D deficiency was defined as a serum 25-hydroxyvitamin D (25(OH)D) level < 20 ng/ml, and severe vitamin D deficiency was defined as a 25(OH)D level < 12 ng/ml. The primary analysis was the prevalence of vitamin D deficiency. The exploratory analyses were serial follow-up vitamin D levels in group 2, associated factors for vitamin D deficiency, and the effect of vitamin D deficiency on clinical outcomes in critically ill patients. Results: The prevalence of vitamin D deficiency was 59% [95% confidence interval (CI) 55-62%], and the prevalence of severe vitamin D deficiency was 18% (95% CI 15-21%). The median vitamin D level for all enrolled critically ill patients was 18.3 (13.7-23.9) ng/ml. In group 2, the median vitamin D levels were <20 ng/ml during the serial follow-up. According to the multivariable analysis, young age, female gender, low albumin level, high parathyroid hormone (PTH) level, and high sequential organ failure assessment (SOFA) score were significantly associated risk factors for vitamin D deficiency. Patients with vitamin D deficiency had longer ventilator use duration and length of ICU stay. However, the 28- and 90-day mortality rate were not associated with vitamin D deficiency. Conclusions: This study demonstrated that the prevalence of vitamin D deficiency is high in critically ill patients. Age, gender, albumin level, PTH level, and SOFA score were significantly associated with vitamin D deficiency in these patients.

Outcomes of Targeted Temperature Management for In-Hospital and Out-Of-Hospital Cardiac Arrest: A Matched Case-Control Study Using the National Database of Taiwan Network of Targeted Temperature Management for Cardiac Arrest (TIMECARD) Registry.

BACKGROUND This study aimed to compare outcomes of targeted temperature management (TTM) for patients with in-hospital and out-of-hospital cardiac arrest using the national database of TaIwan network of targeted temperature ManagEment for CARDiac arrest (TIMECARD) registry. MATERIAL AND METHODS A retrospective, matched, case-control study was conducted. Patients with in-hospital cardiac arrest (IHCA) treated with TTM after the return of spontaneous circulation (ROSC) were selected as the case group and controls were defined as the same number of patients with out-of-hospital cardiac arrest (OHCA), matched for sex, age, Charlson comorbidity index, and cerebral performance category. Neurological outcome and survival at hospital discharge were the primary outcome measures. RESULTS Data of 103 patients with IHCA and matched controls with OHCA were analyzed. Patients with IHCA were more likely to experience witnessed arrest and bystander cardiopulmonary resuscitation (CPR). The duration from collapse to the beginning of CPR, CPR time, and the duration from ROSC to initiation of TTM were shorter in the IHCA group but their initial arterial blood pressure after ROSC was lower. Overall, 88% of patients survived to completion of TTM and 43% survived to hospital discharge. Hospital survival (42.7% vs 42.7%, P=1.00) and favorable neurological outcome at discharge (19.4% vs 12.7%, P=0.25) did not differ between the 2 groups. CONCLUSIONS The findings from the national TIMECARD registry showed that clinical outcomes following TTM for patients with IHCA were not significantly different from OHCA when baseline factors were matched.

Clinical Efficacy of Cefoperazone-Sulbactam versus Piperacillin-Tazobactam in the Treatment of Hospital-Acquired Pneumonia and Ventilator-Associated Pneumonia.

OBJECTIVE: The aim of this study was to compare the usefulness of cefoperazone-sulbactam and that of piperacillin-tazobactam in the treatment of hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP). METHODS: This retrospective study included the adult patients receiving cefoperazone-sulbactam or piperacillin-tazobactam against HAP/VAP in nine hospitals in Taiwan from March 1, 2018 to May 30, 2019. Primary outcome was clinical cure rate. RESULTS: A total of 410 patients were enrolled. Among them, 209 patients received cefoperazone-sulbactam and 201 patients received piperacillin-tazobactam. Overall, cefoperazone-sulbactam group had similar distribution of age, sex, or SOFA scores as piperacillin-tazobactam group. However, cefoperazone-sulbactam had higher comorbidity score and disease severity than piperacillin-tazobactam group (Charlson score: 6.5 ± 2.9 vs 5.7 ± 2.7, p < 0.001; APACHE II score: 21.4 ± 6.2 vs 19.3 ± 6.0, p = 0.002). Regarding clinical outcomes, no significant difference in clinical cure and failure rates was observed between cefoperazone-sulbactam and piperacillin-tazobactam group (clinical cure rate: 80.9% vs 80.1% and clinical failure rate: 17.2% vs 18.4%, p = 0.943). Moreover, no significant difference in clinical effectiveness and ineffectiveness rates was observed between cefoperazone-sulbactam and piperacillin-tazobactam group (clinical effective rate: 80.9% vs 80.6% and clinical ineffective rate: 17.7% vs 18.9%, p = 0.711). The all-cause mortality rates of the cefoperazone-sulbactam and piperacillin-tazobactam groups were similar (23.9% vs 20.9%, p = 0.48). After adjustment of Charlson score and APACHE II score, the similarities in these clinical outcomes did not change in overall patients and patients with HAP or VAP. CONCLUSION: For treating adult patients with nosocomial pneumonia, cefoperazone-sulbactam was as effective as piperacillin-tazobactam.

Significance of the Modified NUTRIC Score for Predicting Clinical Outcomes in Patients with Severe Community-Acquired Pneumonia.

Nutritional status could affect clinical outcomes in critical patients. We aimed to determine the prognostic accuracy of the modified Nutrition Risk in Critically Ill (mNUTRIC) score for hospital mortality and treatment outcomes in patients with severe community-acquired pneumonia (SCAP) compared to other clinical prediction rules. We enrolled SCAP patients in a multi-center setting retrospectively. The mNUTRIC score and clinical prediction rules for pneumonia, as well as clinical factors, were calculated and recorded. Clinical outcomes, including mortality status and treatment outcome, were assessed after the patient was discharged. We used the receiver operating characteristic (ROC) curve method and multivariate logistic regression analysis to determine the prognostic accuracy of the mNUTRIC score for predicting clinical outcomes compared to clinical prediction rules, while 815 SCAP patients were enrolled. ROC curve analysis showed that the mNUTRIC score was the most effective at predicting each clinical outcome and had the highest area under the ROC curve value. The cut-off value for predicting clinical outcomes was 5.5. By multivariate logistic regression analysis, the mNUTRIC score was also an independent predictor of both clinical outcomes in SCAP patients. We concluded that the mNUTRIC score is a better prognostic factor for predicting clinical outcomes in SCAP patients compared to other clinical prediction rules.

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.

Synthesis, Characterization, and Application of Superparamagnetic Iron Oxide Nanoprobes for Extrapulmonary Tuberculosis Detection.

A molecular imaging probe comprising superparamagnetic iron oxide (SPIO) nanoparticles and Mycobacterium tuberculosis surface antibody (MtbsAb) was synthesized to enhance imaging sensitivity for extrapulmonary tuberculosis (ETB). An SPIO nanoprobe was synthesized and conjugated with MtbsAb. The purified SPIO-MtbsAb nanoprobe was characterized using TEM and NMR. To determine the targeting ability of the probe, SPIO-MtbsAb nanoprobes were incubated with Mtb for in vitro imaging assays and injected into Mtb-inoculated mice for in vivo investigation with magnetic resonance (MR). The contrast enhancement reduction on magnetic resonance imaging (MRI) of Mtb and THP1 cells showed proportional to the SPIO-MtbsAb nanoprobe concentration. After 30 min of intravenous SPIO-MtbsAb nanoprobe injection into Mtb-infected mice, the signal intensity of the granulomatous site was enhanced by 14-fold in the T2-weighted MR images compared with that in mice receiving PBS injection. The MtbsAb nanoprobes can be used as a novel modality for ETB detection.

Elevation of androgen receptor promotes prostate cancer metastasis by induction of epithelial-mesenchymal transition and reduction of KAT5.

Androgen receptor (AR), an androgen-activated transcription factor, belongs to the nuclear receptor superfamily. AR plays an important role in the development and progression of prostate cancer (PCa). However, the role of AR in PCa metastasis is not fully understood. To investigate the role of AR in PCa metastasis, we examined AR expression level in primary and metastatic PCa by analyzing gene array data of 378 primary prostate tumors and 120 metastatic prostate tumors from Oncomine, as well as carrying out immunohistochemical (IHC) staining of 56 prostate cancer samples. Expression of mRNA and protein of AR as well as its target gene prostate-specific antigen (PSA) was much higher in metastatic prostate tumors than in primary prostate tumors. Knockdown of AR with siRNA or treating with anti-androgen Casodex reduced migration and invasion ability of C4-2B PCa cells. Knockdown of AR increased protein expression of E-cadherin and AR coregulator KAT5 but reduced expression of epithelial-mesenchymal transition (EMT) marker proteins Slug, Snail, MMP-2, vimentin, and ß-catenin. Knockdown of KAT5 increased migration of C4-2B cells, whereas overexpression of KAT5 suppressed cell migration. KAT5 knockdown rescues the suppressive effect of AR knockdown on migration of C4-2B cells. Gene expression level of AR and KAT5 showed a negative correlation. PCa patients with higher AR expression or lower KAT5 expression correlated with shorter recurrence-free survival. Our study suggested that elevation of AR expression and AR signaling in prostate tumors promotes PCa metastasis by induction of EMT and reduction of KAT5.

Determination of the energy requirements in mechanically ventilated critically ill elderly patients in different BMI groups using the Harris-Benedict equation.

BACKGROUND: Due to studies on calorie requirement in mechanically ventilated critically ill elderly patients are few, and indirect calorimetry (IC) is not available in every intensive care unit (ICU). The aim of this study was to compare IC and Harris-Benedict (HB) predictive equation in different BMI groups. METHODS: A total of 177 mechanically ventilated critically ill elderly patients (≧65 years old) underwent IC for measured resting energy expenditure (MREE). Estimated calorie requirement was calculated by the HB equation, using actual body weight (ABW) and ideal body weight (IBW) separately. Patients were divided into four BMI groups. One-way ANOVA and Pearson's correlation coefficient were used for statistical analyses. RESULTS: The mean MREE was 1443.6 ± 318.2 kcal/day, HB(ABW) was 1110.9 ± 177.0 kcal/day and HB(IBW) was 1101.5 ± 113.1 kcal/day. The stress factor (SFA = MREE ÷ HB(ABW)) was 1.43 ± 0.26 for the underweight, 1.30 ± 0.27 for the normal weight, 1.20 ± 0.19 for the overweight, and 1.20 ± 0.31 for the obese. The SFI (SFI = MREE ÷ HB(IBW)) was 1.24 ± 0.24 for the underweight, 1.31 ± 0.26 for the normal weight, 1.36 ± 0.21 for the overweight, and 1.52 ± 0.39 for the obese. MREE had significant correlation both with REE(ABW) = HB(ABW) × SFA (r = 0.46; P < 0.0001) and REE(IBW) = HB(IBW) × SFI (r = 0.43; P < 0.0001). CONCLUSION: IC is the best accurate method for assessing calorie requirement of mechanically ventilated critically ill elderly patients. When IC is not available, using the predictive HB equation is an alternative choice. Calorie requirement can be predicted by HB(ABW) × 1.20-1.43 for critically ill elderly patients according to different BMI groups, or using HB(IBW) × 1.24-1.52 for patients with edema, ascites or no available body weight data.