Reconstructing Signaling Networks Using Biosensor Barcoding.

Understanding how signaling networks are regulated offers valuable insights into how cells and organisms react to internal and external stimuli and is crucial for developing novel strategies to treat diseases. To achieve this, it is necessary to delineate the intricate interactions between the nodes in the network, which can be accomplished by measuring the activities of individual nodes under perturbation conditions. To facilitate this, we have recently developed a biosensor barcoding technique that enables massively multiplexed tracking of numerous signaling activities in live cells using genetically encoded fluorescent biosensors. In this chapter, we detail how we employed this method to reconstruct the EGFR signaling network by systematically monitoring the activities of individual nodes under perturbations.

Prehospital ultrasound scanning for abdominal free fluid detection in trauma patients: a systematic review and meta-analysis.

INTRODUCTION: Focused assessment with sonography for trauma helps detect abdominal free fluid. Prehospital ultrasound scanning is also important because the early diagnosis of hemoperitoneum may reduce the time to definitive treatment in the hospital. This study investigated whether prehospital ultrasound scanning can help detect abdominal free fluid. MATERIALS AND METHODS: In this systematic review, relevant databases were searched for studies investigating prehospital ultrasound examinations for abdominal free fluid in trauma patients. The prehospital ultrasound results were compared with computed tomography, surgery, or hospital ultrasound examination data. The pooled sensitivity and specificity values were analyzed using forest plots. The overall predictive power was calculated by the summary receiver operating characteristic curve. The quality of the included studies was assessed using the quality assessment of diagnostic accuracy studies tool. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) was performed to assess the certainty of evidence. RESULT: This meta-analysis comprised six studies that included 1356 patients. The pooled sensitivity and specificity values were 0.596 (95% confidence interval [CI] = 0.345-0.822) and 0.970 (95% CI = 0.953-0.983), respectively. The pooled area under the summary receiver operating characteristic curve was 0.998. The quality assessment tool showed favorable results. In the GRADE analysis, the quality of evidence was very low for sensitivity and high for specificity when prehospital ultrasound was used for hemoperitoneum diagnosis. CONCLUSION: The specificity of abdominal free fluid detection using prehospital ultrasound examinations in trauma patients was very high.

Diagnostic Accuracy for Acute Rib Fractures: A Cross-sectional Study Utilizing Automatic Rib Unfolding and 3D Volume-Rendered Reformation.

RATIONALE AND OBJECTIVES: The aim of this study was to compare the use of computed tomography (CT) with automatic rib unfolding and three-dimensional (3D) volume-rendered imaging in the detection and characterization of rib fractures and flail chest. MATERIALS AND METHODS: A total of 130 patients with blunt chest trauma underwent whole-body CT, and five independent readers assessed the presence and characterization of rib fractures using traditional CT images, automatic rib unfolding, and 3D volume-rendered images in separate readout sessions at least 2 weeks apart. A gold standard was established by consensus among the readers based on the combined analysis of conventional and reformatted images. RESULTS: Automatic rib unfolding significantly reduced mean reading time by 47.5%-74.9% (P < 0.0001) while maintaining a comparable diagnostic performance for rib fractures (positive predictive value [PPV] of 82.1%-93.5%, negative predictive value [NPV] of 96.8%-98.2%, and 69.4%-94.2% and 96.9%-99.1% for conventional axial images and 70.4%-85.1% and 95.2%-96.6% for 3D images) and better interobserver agreement (kappa of 0.74-0.87). For flail chest, automatic rib unfolding showed a PPV of 85.7%-100%, NPV of 90.4%-99.0%, and 80.0%-100% and 89.7%-100% for conventional axial images and 76.9%-100% and 89.0%-92.1% for 3D images. CONCLUSION: Automatic rib unfolding demonstrated equivalent diagnostic performance to conventional images in detecting acute rib fractures and flail chest, with good interobserver agreement and time-saving benefits.

The Coronary Reperfusion Effect and Safety of Prehospital P2Y12 Inhibitor in Primary-PCI STEMI Patients: A Systematic Review and Meta-Analysis.

BACKGROUND: The concept of early administration of P2Y12 inhibitor in ST-elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI) is widely accepted, but whether prehospital administration results in greater coronary reperfusion remains unclear. Our study aims to analyze the benefit and safety of prehospital P2Y12 inhibitor compared to in-hospital P2Y12 inhibitor administration. METHOD: Three databases (PubMed, EMBASE, and Cochrane Library) were searched from database inception to June 2023. We included all types of studies except for conference publications, abstract presentations, reviews, and case reports. The primary outcomes were pre-PCI TIMI flow grade 2-3 (TIMI = Thrombolysis in Myocardial Infarction) and major bleeding. The secondary outcomes included post-PCI TIMI flow grade 2-3, major adverse cardiac events (MACE), recurrent myocardial infarction (MI), and short-term (30-day) mortality. RESULT: Eight individual studies with a total of 10823 patients were included in our meta-analysis. Compared with in-hospital P2Y12 inhibitor, prehospital P2Y12 inhibitor were associated with significantly higher rates of pre-PCI TIMI flow grade 2-3 (OR 1.32, 95% CI: 1.09-1.61, p = 0.005) and post-PCI TIMI flow grade 2-3 (OR 1.43, 95% CI: 1.04-1.97, p = 0.03), and a significantly lower risk of recurrent MI (OR 0.69, 95% CI: 0.49-0.96, p = 0.03). There were no significant difference in the risk of major bleeding (OR 1.00, 95% CI: 0.75-1.32, p = 0.98), MACE (OR 0.94, 95% CI: 0.70-1.25, p = 0.65), or short-term mortality (OR 0.87, 95% CI: 0.50-1.51, p = 0.61). CONCLUSION: Prehospital P2Y12 inhibitor compared to in-hospital P2Y12 inhibitor is associated with a significantly higher rate of pre-PCI and post-PCI TIMI flow grade 2-3, a reduced risk of recurrent MI, and no increase in major bleeding in STEMI patients undergoing primary PCI.

The adjusted impact of different severities of acute exacerbations and medications on the risk of developing dementia in COPD patients.

BACKGROUND: Although a relationship between chronic obstructive pulmonary disease (COPD) and dementia has been reported, the initial severity upon emergency department (ED) visits and the medications used have not been well evaluated as risk factors for increased dementia occurrence. We aimed to analyze the risks of dementia development over 5 years among patients with COPD compared to matched controls (primary) and the impact of different severities of acute exacerbations (AEs) of COPD and medications on the risk of dementia development among COPD patients (secondary). METHOD: This study used the Taiwanese government deidentified health care database. We enrolled patients during the 10-year study period (January 1, 2000, to December 31, 2010), and each patient was followed up for 5 years. Once these patients received a diagnosis of dementia or died, they were no longer followed up. The study group included 51,318 patients who were diagnosed with COPD and 51,318 matched (in terms of age, sex, and the number of hospital visits) non-COPD patients from the remaining patients as the control group. Each patient was followed up for 5 years to analyze the risk of dementia with Cox regression analysis. Data on medications (antibiotics, bronchodilators, corticosteroids) and severity at the initial ED visit (ED treatment only, hospital admission, or ICU admission) were collected for both groups, as well as demographics and baseline comorbidities, which were considered confounding factors. RESULTS: In the study and control groups, 1,025 (2.0%) and 423 (0.8%) patients suffered from dementia, respectively. The unadjusted HR for dementia was 2.51 (95% CI: 2.24-2.81) in the study group. Bronchodilator treatment was associated with the HRs, especially among those who received long-term (> 1 month) treatment (HR = 2.10, 95% CI: 1.91-2.45). Furthermore, among 3,451 AE of COPD patients who initially visited the ED, patients who required ICU admission (n = 164, 4.7%) had a higher risk of dementia occurrence (HR = 11.05, 95% CI: 7.77-15.71). CONCLUSION: Bronchodilator administration might be associated with a decreased risk of dementia development. More importantly, patients who suffered AEs of COPD and initially visited the ED and required ICU admission had a higher risk of developing dementia.

Comparison between botulinum toxin and steroid septal injection in the treatment of allergic rhinitis.

OBJECTIVE: To compare the effects of botulinum toxin and steroid septal injections in treating allergic rhinitis (AR) by evaluating improvements in the rhinitis control assessment test (RCAT), visual analog scale (VAS), nasal obstruction symptom evaluation (NOSE) scores, and active anterior rhinomanometry (RMM) measurements. METHODS: This prospective, single-blinded cohort study was conducted at the Department of Otolaryngology, Taipei City Hospital between January 2017 and December 2018. Ninety-five patients were randomized to receive botulinum toxin, dexamethasone, or normal saline (group A, group B, and placebo, respectively). The main outcome measures were pretreatment subjective nasal symptoms (RCAT, VAS, and NOSE) and active anterior RMM measurements. All measurements were repeated during posttreatment 1, 2, and 3 months. RESULTS: No significant difference was observed in pretreatment questionnaire scores and RMM values between the study and placebo groups. The mean posttreatment RCAT, VAS, and NOSE scores after 1 and 2 months significantly improved in the treatment groups compared to placebo. The VAS and NOSE at posttreatment 2 months and RCAT, VAS, and NOSE at posttreatment 3 months were significantly different comparing group A to group B. All RMM parameters showed better values in group A than in group B at 1, 2, and 3 months posttreatment, with significant differences in four parameters in posttreatment 3 months. CONCLUSIONS: Botulinum toxin septal injection is a safe treatment option for AR and improves subjective nasal symptoms for 3 months. Botulinum toxin A injection tended to be more effective than steroid septal injection in terms of duration and degree.Level of Evidence: 2b, individual cohort study.

The effect of the head-up position on cardiopulmonary resuscitation: a systematic review and meta-analysis.

OBJECTIVE: Experimental studies of head-up positioning (HUP) during cardiopulmonary resuscitation (CPR) have had some degree of conflicting published results. The current study aim was to analyze and reconcile those discrepancies in order to better clarify the effects of HUP CPR compared to conventional supine (SUP) CPR. METHODS: Three databases (PubMed, EMBASE and Cochrane Library) were searched comprehensively (from each respective database's inception to May 2021) for articles addressing HUP CPR. The primary outcome to be observed was cerebral perfusion pressure (CerPP), and secondary outcomes were mean intracranial pressure (ICP), mean arterial pressure (MAP), coronary perfusion pressure (CoPP) and frequencies of return of spontaneous circulation (ROSC). RESULTS: Seven key studies involving 131 animals were included for analysis. Compared to SUP CPR, CerPP (MD 10.37; 95% CI 7.11-13.64; p < 0.01; I2 = 58%) and CoPP (MD 7.56; 95% CI 1.84-13.27, p = 0.01; I2 = 75%) increased significantly with HUP CPR, while ICP (MD - 13.66; 95% CI - 18.6 to -8.71; p < 0.01; I2 = 96%) decreased significantly. Combining all study methodologies, there were no significant differences detected in MAP (MD - 1.63; 95% CI - 10.77-7.52; p = 0.73; I2 = 93%) or frequency of ROSC (RR 0.9; 95% CI 0.31-2.60; p = 0.84; I2 = 65%). However, in contrast to worse outcomes in studies using immediate elevation of the head in a reverse Trendelenburg position, study outcomes were significantly improved when HUP (head and chest only) was introduced in a steady, graduated manner following a brief period of basic CPR augmented by active compression-decompression (ACD) and impedance threshold (ITD) devices. CONCLUSION: In experimental models, gradually elevating the head and chest following a brief interval of circulatory priming with ACD and ITD devices can enhance CoPP, lower ICP and improve CerPP significantly while maintaining MAP. This effect is immediate, remains sustained and is associated with improved outcomes.

Clinical treatment and medication in decreasing the development of major depression caused by spinal fracture.

BACKGROUND: Chronic pain and limited activities of daily living after spinal fracture may induce the occurrence of major depression (MD); however, risk factors regarding medications, surgical intervention, and severity of fracture are unclear. We aimed to analyze risk factors of MD development after spinal fracture. METHODS: This was a retrospective database study, using the health care database of the Taiwan government. We included 11,225 patients with new spinal fracture (study group), and 33,675 matched patients without fracture (comparison group). We respectively reviewed data of each participant for 3 years to assess the development of MD. The Cox proportional hazards model was used to determine the prevalence of MD, after adjusting for patient demographics, medications, surgical interventions, spinal cord involvement, and postfracture comorbidities. RESULTS: In total, 187 fracture patients (1.7%) and 281 nonfracture patients (0.8%) developed new-onset MD (hazard ratio [HR]:1.96, (95% confidence interval [CI]: 1.63-2.36)). Spinal cord involvement (HR: 2.96, 95% CI: 2.54-3.42) and postfracture comorbidities (HR: 3.51, 95% CI: 2.86-3.97) obviously increased the risk of MD. CONCLUSIONS: Patients with spinal fracture (spinal cord involvement and postfracture comorbidities) were more likely to develop MD. Early surgical interventions (vertebroplasty) and medications (narcotics) may decrease the risk of MD.

Relationship between pancreatic cancer-associated diabetes and cachexia.

BACKGROUND: Pancreatic cancer-associated diabetes mellitus (PCDM) is a paraneoplastic phenomenon characterized by worsening hyperglycaemia and weight loss. Galectin-3 and S100A9, mediators of PCDM, have pro-inflammatory functions and might thereby induce systemic inflammation and cachexia. We aimed to examine whether PCDM directly mediates cachexia. METHODS: Consecutive pancreatic cancer (PC) patients with and without PCDM (n = 88 each) with complete information were included. Cachexia was defined as weight loss >5% within 6 months or weight loss >2% and body mass index <20 kg/m2 or sarcopenia. Skeletal muscle mass was measured with lumbar skeletal muscle index (SMI) using computed tomography images. Cachexia-related parameters (prevalence of cachexia, weight loss, and SMI) were compared between patients with and without PCDM. Relations between cachexia-related parameters and fasting blood glucose or serum levels of galectin-3 and S100A9 were analysed by Spearman correlation and logistic regression analyses. RESULTS: One hundred two (58.0%) patients had cachexia at diagnosis. No significant differences existed between patients with and without PCDM in prevalence of cachexia (64.8% vs. 51.1%, P = 0.093), percentage of weight loss (median 6.8 vs. 4.0, P = 0.085), and SMI (median 45.8 vs. 45.3 cm2 /m2 in men, P = 0.119; 34.9 vs. 36.3 cm2 /m2 in women, P = 0.418). In patients with cachexia, the percentage of weight loss and SMI were also similar between patients with and without PCDM. In patients with PCDM, fasting blood glucose was comparable between patients with and without cachexia (P = 0.458) and did not correlate with the percentage of weight loss (P = 0.085) or SMI (P = 0.797 in men and 0.679 in women). Serum S100A9 level correlated with fasting blood glucose (correlation coefficient 0.213, P = 0.047) but not with the percentage of weight loss (P = 0.977) or SMI (P = 0.247 in men and 0.458 in women). Serum galectin-3 level also did not correlate with the percentage of weight loss (P = 0.226) and SMI (P = 0.201 in men and 0.826 in women). Primary tumour size was associated with cachexia (adjusted odds ratio per 1 cm increase 1.28, 95% confidence interval 1.02-1.60, P = 0.034), whereas PCDM, fasting blood glucose, and levels of galectin-3 and S100A9 were not predictors of cachexia. CONCLUSIONS: Neither fasting blood glucose nor levels of galectin-3 and S100A9 were associated with cachexia-related parameters. Mediators of PCDM and hyperglycaemia do not directly mediate PC-induced cachexia.

Significant predictive factors of the severity and outcomes of the first attack of acute angioedema in children.

BACKGROUND: The initial episode of angioedema in children can be potential life-threatening due to the lack of prompt identification and treatment. We aimed to analyze the factors predicting the severity and outcomes of the first attack of acute angioedema in children. METHODS: This was a retrospective study with 406 children (< 18 years) who presented in the emergency department (ED) with an initial episode of acute angioedema and who had subsequent follow-up visits in the out-patient department from January 2008 to December 2014. The severity of the acute angioedema was categorized as severe (requiring hospital admission), moderate (requiring a stay in the short-term pediatric observation unit [POU]), or mild (discharged directly from the ED). The associations among the disease severity, patient demographics and clinical presentation were analyzed. RESULT: In total, 109 (26.8%) children had severe angioedema, and the majority of those children were male (65.1%). Most of the children were of preschool age (56.4%), and only 6.4% were adolescents. The co-occurrence of pyrexia or urticaria, etiologies of the angioedema related to medications or infections, the presence of respiratory symptoms, and a history of allergies (asthma, allergic rhinitis) were predictors of severe angioedema (all p < 0.05). Finally, the duration of angioedema was significantly shorter in children who had received short-term POU treatment (2.1 ± 1.1 days) than in those who discharged from ED directly (2.3 ± 1.4 days) and admitted to the hospital (3.5 ± 2.0 days) (p < 0.001). CONCLUSION: The co-occurrence of pyrexia or urticaria, etiologies related to medications or infections, the presence of respiratory symptoms, and a history of allergies were predictors of severe angioedema. More importantly, short-term POU observation and prompt treatment might be benefit for patients who did not require hospital admission.

Use High-Flow Nasal Cannula for Acute Respiratory Failure Patients in the Emergency Department: A Meta-Analysis Study.

OBJECTIVE: To evaluate the efficacy of high-flow nasal cannula (HFNC) therapy compared with conventional oxygen therapy (COT) or noninvasive ventilation (NIV) for the treatment of acute respiratory failure (ARF) in emergency departments (EDs). METHOD: We comprehensively searched 3 databases (PubMed, EMBASE, and the Cochrane Library) for articles published from database inception to 12 July 2019. This study included only randomized controlled trials (RCTs) that were conducted in EDs and compared HFNC therapy with COT or NIV. The primary outcome was the intubation rate. The secondary outcomes were the mortality rate, intensive care unit (ICU) admission rate, ED discharge rate, need for escalation, length of ED stay, length of hospital stay, and patient dyspnea and comfort scores. RESULT: Five RCTs (n = 775) were included. There was a decreasing trend regarding the application of HFNC therapy and the intubation rate, but the difference was not statistically significant (RR, 0.53; 95% CI, 0.26-1.09; p=0.08; I 2 = 0%). We found that compared with patients who underwent COT, those who underwent HFNC therapy had a reduced need for escalation (RR, 0.41; 95% CI, 0.22-0.78; p=0.006; I 2 = 0%), reduced dyspnea scores (MD -0.82, 95% CI -1.45 to -0.18), and improved comfort (SMD -0.76 SD, 95% CI -1.01 to -0.51). Compared with the COT group, the HFNC therapy group had a similar mortality rate (RR, 1.25; 95% CI, 0.79-1.99; p=0.34; I 2 = 0%), ICU admission rate (RR, 1.11; 95% CI, 0.58-2.12; p=0.76; I 2 = 0%), ED discharge rate (RR, 1.04; 95% CI, 0.63-1.72; p=0.87; I 2 = 0%), length of ED stay (MD 1.66, 95% CI -0.95 to 4.27), and hospital stay (MD 0.9, 95% CI -2.06 to 3.87). CONCLUSION: Administering HFNC therapy in ARF patients in EDs might decrease the intubation rate compared with COT. In addition, it can decrease the need for escalation, decrease the patient's dyspnea level, and increase the patient's comfort level compared with COT.

Galectin-3 and S100A9: Novel Diabetogenic Factors Mediating Pancreatic Cancer-Associated Diabetes.

OBJECTIVE: Pancreatic cancer-associated diabetes (PCDM) is a paraneoplastic phenomenon accounting for 1% of new-onset diabetes. We aimed to identify the mediators of PCDM and evaluate their usefulness in distinguishing PCDM from type 2 diabetes. RESEARCH DESIGN AND METHODS: Secreted proteins of MIA PaCa-2 cells were identified by proteomics, and those with ≥10-fold overexpression in transcriptome analysis were assessed by bioinformatics and glucose uptake assay to identify candidate factors. Expression of factors was compared between tumors with and without PCDM by immunohistochemistry. Serum levels were measured in a training set including PC with and without PCDM, type 2 diabetes, pancreatitis, other pancreatic/peripancreatic tumors, and control subjects (n = 50 each). Cutoff values for differentiation between PCDM and type 2 diabetes from the training set were validated in a test set (n = 41 each). RESULTS: Galectin-3 and S100A9 were overexpressed in tumors with PCDM and dose-dependently suppressed insulin-stimulated glucose uptake in C2C12 myotubes. In the training set, serum galectin-3 and S100A9 levels were exclusively increased in patients with PCDM and distinguished PCDM from type 2 diabetes (area under the curve [AUC] galectin-3: 0.73 [95% CI 0.64-0.83]; S100A9: 0.79 [95% CI 0.70-0.87]). Similar results were observed in the test set (AUC galectin-3: 0.83 [95% CI 0.74-0.92]; S100A9: 0.77 [95% CI 0.67-0.87]), with sensitivity and specificity 72.1% and 86.1%, respectively, for galectin-3 and 69.8% and 58.1% for S100A9 in differentiating between PCDM and type 2 diabetes. CONCLUSIONS: Galectin-3 and S100A9 are overexpressed in PCDM tumors and mediate insulin resistance. Galectin-3 and S100A9 distinguish PCDM from type 2 diabetes in subjects with new-onset diabetes.

Early Epinephrine Improves the Stabilization of Initial Post-resuscitation Hemodynamics in Children With Non-shockable Out-of-Hospital Cardiac Arrest.

Background: In children with non-shockable out-of-hospital cardiac arrest, early epinephrine (EE) might help to establish the return of spontaneous circulation (ROSC) and be associated with survival. In the present study, we aimed to analyze the effects of EE on outcomes and post-resuscitation hemodynamics in children with non-shockable OHCA. Methods: This was a retrospective analysis of data from 216 children (<19 years) who had suffered non-traumatic and non-shockable OHCA and received epinephrine for resuscitation (Jan 1, 2006-Dec 31, 2014). Demographics, pre-/in-hospital information, and the time to the first dose of epinephrine were recorded. Early post-resuscitation hemodynamics (the first hour after sustained ROSC), survival and good neurological outcomes (Pediatric Cerebral Performance Category Scales 1 or 2) were analyzed by the time to epinephrine-classified as early (EE): <15 min, intermediate (IE): 15-30 min, or late (LE): >30 min. Results: Twenty-eight (13.0%) children survived to discharge, but only 17 (7.9%) had good neurological outcomes. In all, 41 (18.9%) children received EE; in comparison to IE and LE, this was significantly associated with tachycardia (73.9%) in the post-resuscitation period (p < 0.05). Tachycardia (OR: 7.41, 95% CI: 1.96-29.31) and hypertension (OR: 6.03, 95% CI: 1.85-13.77) were significantly associated with EE after adjusting for confounding factors. EE was also significantly associated with better overall outcomes than ME and LE (any ROSC, sustained ROSC, survival to the intensive care unit, admission, survival to discharge and good neurological outcomes, all p < 0.05). Conclusions: EE helped to establish ROSC but was also associated with more tachycardia and hypertension in the early post-resuscitation period. In children with non-traumatic and non-shockable OHCA, EE was associated with a higher survival rate and better neurological outcomes than were ME and LE.

Demographics of Pediatric OHCA Survivors With Postdischarge Diseases: A National Population-Based Follow-Up Study.

Background: Postdischarge diseases (PDDs) have been reported for adult survivors of out-of-hospital cardiac arrest (OHCA). However, the detailed demographics of pediatric OHCA survivors with PDDs are not well-documented, and information regarding functional survivors is particularly limited. We aimed to report detailed information on the PDDs of survivors of traumatic and non-traumatic pediatric OHCA using a national healthcare database. Methods: We retrospectively obtained data from the Taiwan government healthcare database (2011-2015). Information on the demographics of traumatic and non-traumatic pediatric OHCA survivors (<20 years) was obtained and reported. The patients who survived to discharge (survivors) and those classified as functional survivors were followed up for 1 year for the analysis of newly diagnosed PDDs. The time from discharge to PDD diagnosis was also reported. Results: A total of 2,178 non-traumatic and 288 traumatic OHCA pediatric cases were included. Among the non-traumatic OHCA survivors (n = 374, survival rate = 17.2%), respiratory tract (n = 270, 72.2%), gastrointestinal (n = 187, 50.0%), and neurological diseases (n = 167, 49.1%) were the three most common PDD categories, and in these three categories, the majority of PDDs were atypical/influenza pneumonia, non-infective acute gastroenteritis, and generalized/status epilepsy, respectively. Among the traumatic OHCA survivors (n = 21, survival rate = 7.3%), respiratory tract diseases (n = 17, 81.0%) were the most common, followed by skin or soft tissue (n = 14, 66.7%) diseases. Most functional survivors still suffered from neurological and respiratory tract diseases. Most PDDs, except for skin or soft tissue diseases, were newly diagnosed within the first 3 months after discharge. Conclusions: Respiratory tract (pneumonia), neurological (epilepsy), and skin or soft tissue (dermatitis) diseases were very common among both non-traumatic and traumatic OHCA survivors. More importantly, most PDDs, except for skin or soft tissue diseases, were newly diagnosed within the first 3 months after discharge.

The Impact of Emergency Interventions and Patient Characteristics on the Risk of Heart Failure in Patients with Nontraumatic OHCA.

BACKGROUND: Since out-of-hospital cardiac arrest- (OHCA-) related dysfunction (ischemic/reperfusion injury and inflammatory response) might result in long-term impairment, we suspect that new-onset heart failure might be common in long-term survivors. However, these relationships had not been well addressed, and we aimed to analyze the impact of emergency interventions and patient characteristics on the risk of new-onset heart failure in patients with nontraumatic OHCA. METHODS: The Taiwanese government healthcare database contains data for 49,101 nontraumatic OHCA adult patients from 2011-2012, which were analyzed in this study. Nontraumatic OHCA patients who survived to the intensive care unit (ICU) were included as the study group (n = 7,321). Matched patients (n = 21,963) were recruited as a comparison group. Patients with any history of heart failure or cardiac arrest were not included in either group. All patients were followed-up for 6 months for the identification of new-onset heart failure. Adjustments were made for demographics, age, emergency interventions, and comorbidities as potential risk factors. RESULTS: In all, 3.84% (n = 281) of OHCA patients suffered new-onset heart failure, while only 1.24% (n = 272) of matched patients in the comparison group suffered new-onset heart failure. Strong risk factors for heart failure were age (60-75 years, HR: 11.4; 95% CI: 9-14.4), medical history (myocardial infarction, HR: 2.47; 95% CI: 2.05-2.98 and cardiomyopathy, HR: 2.94; 95% CI: 1.45-5.94), and comorbidities during hospitalization (ischemic heart disease, HR: 4.5; 95% CI: 3.46-5.86). Only extracorporeal membrane oxygenation (ECMO) decreased the risk of heart failure. Most (53.6%) heart failure events occurred within 60 days after OHCA. CONCLUSION: An age from 61 to 75 years, a history of myocardial infarction or cardiomyopathy, and ischemic heart disease or infection as comorbidities occurring during hospitalization were strong risk factors for new-onset heart failure in OHCA patients. However, ECMO could decrease this risk. More importantly, most heart failure events occurred within 60 days after OHCA.

A Novel, Optimized Method to Accelerate the Preparation of Injectable Poly-L-Lactic Acid by Sonication.

Current consensus for preparing injectable poly-L-lactic acid (PLLA) suggests adequate hydration (less than equal to 2-24 hours of reconstitution) of the lyophilized particles before injection, but the volume of reconstitution and the duration of hydration time varies. This study established a method to evaluate the distribution of PLLA particles after hydration and found that longer hydration time increased the effective portion (particles less than 60 µm) of PLLA products. Further investigation of the feasibility of reconstitution with sonication revealed that 2-hour hydration of PLLA powders with additional 5-minute-sonication could yield a comparable particle distribution with 48-hour-hydration of PLLA. Moreover, adding lidocaine into the diluent did not alter the distribution of PLLA particles. We proposed a new, feasible and efficient method of preparing PLLA injectable products: 2-hour hydration of the powders, sonication of the bottle or vial containing PLLA products for at least 5 minutes, and finalization with 1-2 mL of lidocaine immediately before injection. J Drugs Dermatol. 2018;17(8):894-898.

Defective antiviral responses of induced pluripotent stem cells to baculoviral vector transduction.

Genetic engineering of induced pluripotent stem cells (iPSCs) is important for their clinical applications, and baculovirus (BV) holds promise as a gene delivery vector. To explore the feasibility of using BV for iPSCs transduction, in this study we first examined how iPSCs responded to BV. We determined that BV transduced iPSCs efficiently, without inducing appreciable negative effects on cell proliferation, apoptosis, pluripotency, and differentiation. BV transduction slightly perturbed the transcription of 12 genes involved in the Toll-like receptor (TLR) signaling pathway, but at the protein level BV elicited no well-known cytokines (e.g., interleukin-6 [IL-6], tumor necrosis factor alpha [TNF-α], and beta interferon [IFN-ß]) except for IP-10. Molecular analyses revealed that iPSCs expressed no TLR1, -6, -8, or -9 and expressed merely low levels of TLR2, -3, and -4. In spite of evident expression of such RNA/DNA sensors as RIG-I and AIM2, iPSCs barely expressed MDA5 and DAI (DNA-dependent activator of IFN regulatory factor [IRF]). Importantly, BV transduction of iPSCs stimulated none of the aforementioned sensors or their downstream signaling mediators (IRF3 and NF-κB). These data together confirmed that iPSCs responded poorly to BV due to the impaired sensing and signaling system, thereby justifying the transduction of iPSCs with the baculoviral vector.

New approach to 2-quinolinones.

An efficient approach to 2-quinolinone derivatives 1 via Diels-Alder cyclization of exo-diene lactams 5 and dienophiles is reported.