Ching-Chia Wang

Survey of outcome of CPR in pediatric in-hospital cardiac arrest in a medical center in Taiwan

PURPOSE OF THE STUDY While the outcomes of cardiopulmonary resuscitation (CPR) for pediatric in-hospital cardiac arrest (IHCA) are reported for many regions, none is reported for Asian countries. We report the outcomes of CPR for pediatric IHCA in a tertiary medical center in Taiwan and also identify prognostic factors associated with poor outcome. METHODS Data were retrieved retrospectively from 2000 to 2003 and prospectively from 2004 to 2006 from our web-based registry system. We evaluated patients younger than 18 years of age who had IHCA and received CPR. The primary outcome was survival to hospital discharge, and the secondary outcomes were sustained return of spontaneous circulation (ROSC), and favorable neurological outcomes as assessed by pediatric cerebral performance categories (PCPC). RESULTS We identified 316 patients and the overall hospital survival was 20.9% and 16.1% had favorable neurological outcomes. Sixty-four patients ever supported with ECMO. We further analyzed 252 patients who underwent conventional CPR only and most had cardiac disease (133/252, 52.8%). The second most common preexisting condition was hematologic or oncologic disease (43/252, 17.1%). Of the 252 patients, 153 (60.7%) achieved sustained ROSC, 50 (19.8%) survived to discharge, and 39 patients (15.5%) had favorable neurological outcomes. CPR during off-work hours resulted in inferior chances of reaching sustained ROSC. Multivariate analysis showed that long CPR duration, hematology/oncology patients, and pre-arrest vasoactive drug infusion were significantly associated with decreased hospital survival (p<0.05). CONCLUSIONS Outcomes of CPR for pediatric patients with IHCA in Taiwan were comparable to corresponding reports in Western countries, but more hematology/oncology patients were included. Long CPR duration, hematologic or oncologic underlying diseases, and vasoactive agent infusion prior IHCA were associated with poor outcomes. The concept of palliative care should be proposed to families of terminally ill cancer patients in order to avoid unnecessary patient suffering. Also, establishing a balanced duty system in the future might increase chances of sustained ROSC.

Eleven years of experience with extracorporeal cardiopulmonary resuscitation for paediatric patients with in-hospital cardiac arrest.

PURPOSE The study aims to describe 11 years of experience with extracorporeal cardiopulmonary resuscitation (ECPR) for in-hospital paediatric cardiac arrest in a university affiliated tertiary care hospital. METHODS Paediatric patients who received extracorporeal membrane oxygenation (ECMO) during active extracorporeal cardiopulmonary resuscitation (ECPR) at our centre from 1999 to 2009 were included in this retrospective study. The results from three different cohorts (1999-2001, 2002-2005 and 2006-2009) were compared. Survival rates and neurological outcomes were analysed. Favourable neurological outcome was defined as paediatric cerebral performance categories (PCPC) 1, 2 and 3. RESULTS We identified 54 ECPR events. The survival rate to hospital discharge was 46% (25/54), and 21 (84%) of the survivors had favourable neurological outcomes. The duration of CPR was 39±17 min in the survivors and 52±45 min in the non-survivors (p=NS). The patients with pure cardiac causes of cardiac arrest had a survival rate similar to patients with non-cardiac causes (47% (18/38) vs. 44% (7/16), p=NS). The non-survivors had higher serum lactate levels prior to ECPR (13.4±6.4 vs. 8.8±5.1 mmol/L, p<0.01) and more renal failure after ECPR (66% (19/29) vs. 20% (5/25), p<0.01). The patients resuscitated between 2006 and 2009 had shorter durations of CPR (34±13 vs. 78±76 min, p=0.032) and higher rates of survival (55% (16/29) vs. 0% (0/8), p=0.017) than those resuscitated between 1999 and 2002. CONCLUSIONS In our single-centre experience with ECPR for paediatric in-hospital cardiac arrest, the duration of CPR has become shorter and outcomes have improved in recent years. Higher pre-ECPR lactate levels and the presence of post-ECPR renal failure were associated with increased mortality. The presence of non-cardiac causes of cardiac arrest did not preclude successful ECPR outcomes. The duration of CPR was not significantly associated with poor outcomes in this study.

Adenovirus Serotype 3 and 7 Infection with Acute Respiratory Failure in Children in Taiwan, 2010–2011

Objective Increased incidence of adenovirus infection in children was noticed since September 2010 in Taiwan and severe cases requiring intensive care were noted later. We did this study to find the clinical characteristics and risk factors associated with severe adenovirus infection. Patients and Methods We collected cases of severe adenovirus infection between November 2010 and June 2011 to analyze their clinical characteristics in two medical centers in northern Taiwan. Severe adenovirus infection was defined as laboratory-confirmed adenovirus cases with required intensive care. Hexon gene sequencing was performed for molecular genotyping. Results 45 patients were included, 22 cases (49%) were infected with serotype 7, 19 (42%) with serotype 3, and 4 with serotype 2. The median age (range) was 2.75 years (0.08–15.43 years); 87% were below 5 years. Male to female ratio was 1.65 (28 to 17). Of these patients, 56% had underlying neurological diseases, 50% experienced fever higher than 40°C and 69% suffered fever longer than one week. The clinical diagnosis included pneumonia in 40 (89%) patients, bronchopneumonia in 5 (11%), and encephalitis in 7 (16%). At least 22 patients had pleural effusion. They had complications of respiratory failure (53%), acute respiratory distress syndrome (24%), hypotension (40%), and 6 (13%) patients needed extracorporeal membranous oxygenation. Ten (22%) patients died, all with underlying major systemic diseases and 7 (70%) infected with serotype 7. Conclusions Adenovirus serotype 7 and 3 can cause severe disease–even death–in children, especially those with underlying neurological diseases. Patients infected with adenovirus serotype 7 tended to have a higher case-fatality rate.

Quercetin attenuates renal ischemia/reperfusion injury via an activation of AMP-activated protein kinase-regulated autophagy pathway

Renal ischemia/reperfusion (I/R) is a major cause of acute renal failure. Quercetin, a flavonoid antioxidant, presents in many kinds of food. The molecular mechanism of quercetin on renal protection during I/R is still unclear. Here, we investigated the role of AMP-activated protein kinase (AMPK)-regulated autophagy in renal protection by quercetin. To investigate whether quercetin protects renal cells from I/R-induced cell injury, an in vitro model of I/R and an in vivo I/R model were used. Cell apoptosis was determined by propidium iodide/annexin V staining. Western blotting and immunofluorescence were used to determine the autophagy. AMPK expression was inhibited with appropriate short hairpin RNA (shRNA). In cultured renal tubular cell I/R model, quercetin decreased the cell injury, up-regulated the AMPK phosphorylation, down-regulated the mammalian target of rapamycin (mTOR) phosphorylation and activated autophagy during I/R. Knockdown of AMPK by shRNA transfection decreased the quercetin-induced autophagy but did not affect the mTOR phosphorylation. In I/R mouse model, quercetin decreased the increased serum creatinine level and altered renal histological score. Quercetin also increased AMPK phosphorylation, inhibited the mTOR phosphorylation and activated autophagy in the kidneys of I/R mice. These results suggest that quercetin activates an AMPK-regulated autophagy signaling pathway, which offers a protective effect in renal I/R injury.

Advanced Glycation End-Products Induce Apoptosis in Pancreatic Islet Endothelial Cells via NF-κB-Activated Cyclooxygenase-2/Prostaglandin E2 Up-Regulation

Microvascular complications eventually affect nearly all patients with diabetes. Advanced glycation end-products (AGEs) resulting from hyperglycemia are a complex and heterogeneous group of compounds that accumulate in the plasma and tissues in diabetic patients. They are responsible for both endothelial dysfunction and diabetic vasculopathy. The aim of this study was to investigate the cytotoxicity of AGEs on pancreatic islet microvascular endothelial cells. The mechanism underlying the apoptotic effect of AGEs in pancreatic islet endothelial cell line MS1 was explored. The results showed that AGEs significantly decreased MS1 cell viability and induced MS1 cell apoptosis in a dose-dependent manner. AGEs dose-dependently increased the expressions of cleaved caspase-3, and cleaved poly (ADP-ribose) polymerase in MS1 cells. Treatment of MS1 cells with AGEs also resulted in increased nuclear factor (NF)-κB-p65 phosphorylation and cyclooxygenase (COX)-2 expression. However, AGEs did not affect the expressions of endoplasmic reticulum (ER) stress-related molecules in MS1 cells. Pretreatment with NS398 (a COX-2 inhibitor) to inhibit prostaglandin E2 (PGE2) production reversed the induction of cleaved caspase-3, cleaved PARP, and MS1 cell viability. Moreover, AGEs significantly increased the receptor for AGEs (RAGE) protein expression in MS1 cells, which could be reversed by RAGE neutralizing antibody. RAGE Neutralizing antibody could also reverse the induction of cleaved caspase-3 and cleaved PARP and decreased cell viability induced by AGEs. These results implicate the involvement of NF-κB-activated COX-2/PGE2 up-regulation in AGEs/RAGE-induced islet endothelial cell apoptosis and cytotoxicity. These findings may provide insight into the pathological processes within the pancreatic islet microvasculature induced by AGEs accumulation.

Long-term follow-up of a girl with Maroteaux-Lamy syndrome after bone marrow transplantation

BackgroundMucopolysaccharidosis type VI (MPS VI or Maroteaux-Lamy syndrome) is a rare autosomal recessive genetic disorder. We treated a 10-year-old girl with Maroteaux-Lamy syndrome successfully with bone marrow transplantation (BMT).MethodsThe patient had reconstitution with bone marrow from her HLA-matched brother. One month after BMT, arylsulfatase activity of the recipient’s leukocytes became normal. No graft-versushost disease (GVHD) was observed. Arylsulfatase B activity was maintained and the urinary excretion of glycosaminoglycans (GAGs) became normal.ResultsThe clinical response of the patient was slow but persistent during 12 years after BMT. Improved motor function included walking alone for a long distance without aid, riding a bicycle, taking a bath by herself, etc. Besides, few infections occurred. Exertional dyspnea, severe snoring, and vertigo were much improved.ConclusionsEarly intervention is recommended for BMT. Allogeneic BMT may provide a better life quality as illustrated in the present case.

Advanced glycation end-products induced VEGF production and inflammatory responses in human synoviocytes via RAGE-NF-κB pathway activation †

Aging and diabetes are known to be the major cause to affect the progression of osteoarthritis (OA). Advanced glycation end products (AGEs) have been observed to accumulate in various organs especially in joint tissue and do damage to the joint tissue during aging and diabetes. Synovial angiogenesis and inflammation are observed across the full range of OA severity. The signaling pathway of AGEs on vascular endothelial growth factor (VEGF) production and inflammatory responses in synoviocytes are still unclear. Here, we investigated the role of receptor for AGEs (RAGE) and the signaling pathway involved in AGEs‐induced VEGF production and inflammatory responses in human synoviocytes. Human synoviocytes were cultured and treated with AGEs (25–100 µg/ml). AGEs significantly induced the protein expressions of cyclooxygenase‐2 (COX‐2) and VEGF and the productions of prostaglandin‐E2 (PGE2), VEGF, interleukin‐6 (IL‐6), and metalloproteinase‐13 (MMP‐13) in human synoviocytes in a dose‐dependent manner. Moreover, AGEs markedly activated the phosphorylations of IκB kinase (IKK)α/β, IκBα, and nuclear factor (NF)‐κB‐p65 proteins in human synoviocytes in a time‐dependent manner. Treatment with neutralizing antibody for RAGE statistically significantly decreased the AGEs‐induced increase in COX‐2, VEGF, PGE2, IL‐6, and MMP13 and AGEs‐activated NF‐κB pathway activation. Taken together, these findings indicate that AGEs are capable of inducing VEGF production and inflammatory responses via RAGE‐NF‐κB pathway activation in human synoviocytes.

PPARγ is involved in the hyperglycemia‐induced inflammatory responses and collagen degradation in human chondrocytes and diabetic mouse cartilages

Diabetic hyperglycemia has been suggested to play a role in osteoarthritis. Peroxisome proliferator‐activated receptor‐γ (PPARγ) was implicated in several pathological conditions including diabetes and inflammation. The detailed effects and mechanisms of hyperglycemia on cartilage damage still need to be clarified. Here, we investigated the role of PPARγ in hyperglycemia‐triggered chondrocyte/cartilage damages using a human chondrocyte culture model and a diabetic mouse model. Human chondrocytes were cultured and treated with high concentration of glucose (30 mM) to mimic hyperglycemia in the presence or absence of pioglitazone, a PPARγ agonist. Streptozotocin (STZ) was used to induce mouse diabetes. Our data showed that high glucose induced the protein expressions of cyclooxygenase‐2 (COX‐2) and production of prostaglandin‐E2 (PGE2), interleukin‐6 (IL‐6), and metalloproteinase‐13 (MMP‐13), but decreased the protein expression of collagen II and PPARγ in human chondrocytes. These alterations in high glucose‐treated human chondrocytes could be reversed by pioglitazone in a dose‐dependent manner. Moreover, pioglitazone administration could also significantly reverse the hyperglycemia, formation of AGEs, productions of IL‐6 and MMP‐13, and cartilage damage in STZ‐induced diabetic mice. Taken together, these findings suggest that hyperglycemia down‐regulates PPARγ expression and induces inflammatory and catabolic responses in human chondrocytes and diabetic mouse cartilages.

Arsenic Exposure and Glucose Intolerance/Insulin Resistance in Estrogen-Deficient Female Mice.

Background Epidemiological studies have reported that the prevalence of diabetes in women > 40 years of age, especially those in the postmenopausal phase, was higher than in men in areas with high levels of arsenic in drinking water. The detailed effect of arsenic on glucose metabolism/homeostasis in the postmenopausal condition is still unclear. Objectives We investigated the effects of arsenic at doses relevant to human exposure from drinking water on blood glucose regulation in estrogen-deficient female mice. Methods Adult female mice who underwent ovariectomy or sham surgery were exposed to drinking water contaminated with arsenic trioxide (0.05 or 0.5 ppm) in the presence or absence of 17β-estradiol supplementation for 2–6 weeks. Assays related to glucose metabolism were performed. Results Exposure of sham mice to arsenic significantly increased blood glucose, decreased plasma insulin, and impaired glucose tolerance, but did not induce insulin resistance. Blood glucose and insulin were higher, and glucose intolerance, insulin intolerance, and insulin resistance were increased in arsenic-treated ovariectomized mice compared with arsenic-treated sham mice. Furthermore, liver phosphoenolpyruvate carboxykinase (PEPCK) mRNA expression was increased and liver glycogen content was decreased in arsenic-treated ovariectomized mice compared with arsenic-treated sham mice. Glucose-stimulated insulin secretion in islets isolated from arsenic-treated ovariectomized mice was also significantly decreased. Arsenic treatment significantly decreased plasma adiponectin levels in sham and ovariectomized mice. Altered glucose metabolism/homeostasis in arsenic-treated ovariectomized mice was reversed by 17β-estradiol supplementation. Conclusions Our findings suggest that estrogen deficiency plays an important role in arsenic-altered glucose metabolism/homeostasis in females. Citation Huang CF, Yang CY, Chan DC, Wang CC, Huang KH, Wu CC, Tsai KS, Yang RS, Liu SH. 2015. Arsenic exposure and glucose intolerance/insulin resistance in estrogen-deficient female mice. Environ Health Perspect 123:1138–1144; http://dx.doi.org/10.1289/ehp.1408663

Outcome of pulmonary and aortic stenosis in Williams-Beuren syndrome in an Asian cohort.

Aims: To define the cardiovascular anomalies and the long‐term outcomes in an Asian cohort with Williams‐Beuren syndrome (WBS).