Meng-Ju Li

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.

Incidence of cancer in children aged 0–14 years in Taiwan, 1996–2010

Studies have found lower risk of childhood cancer among Asian children. We aim to characterize the recent incidence and incidence-trend of childhood cancer in Taiwan after the National Health Insurance program was launched in March 1995. Data were extracted from the Taiwan Cancer Registry, a population-based database established in 1979. Cases diagnosed at age 0-14 from 1996 to 2010 were analyzed and categorized according to the International Classification of Childhood Cancer, Third Edition (ICCC-3). In total, 8032 childhood cancer cases were included, with a microscopic verification rate of 93.9%. The overall age-standardized rate (ASR) of incidence adjusted to the 2000 World Standard Population is 125.0 cases/million, with a male-to-female ratio of 1.3. The top five cancer types (ICCC-3 subgroup[s]; ASR per million) are acute lymphoblastic leukemia (Ia, 30.3), acute myeloid leukemia (Ib; 9.4), non-Hodgkin lymphoma (IIb,c,e, 9.0), extracranial germ cell tumor (Xb,c; 8.3), and neuroblastoma (IVa; 7.8). The median age of diagnosis was 6 years for both genders. During the study period, the ASR of childhood cancer has been increasing at a rate of 1.2% per year (95% confidence interval, 0.6-1.7%). In contrast to Western countries, China, Japan, and Taiwan have lower incidence of childhood cancer; however, Taiwans incidence rates of childhood germ cell tumors and hepatic tumors are higher. In conclusion, this population-based study reveals that the incidence rate of childhood cancer in Taiwan is rising consistently. The high incidence of germ cell tumors warrants further investigation.

Synergistic antibacterial effects of localized heat and oxidative stress caused by hydroxyl radicals mediated by graphene/iron oxide-based nanocomposites.

UNLABELLED This work develops a composite system of reduced graphene oxide (rGO)-iron oxide nanoparticles (rGO-IONP) that can synergistically induce physical and chemical damage to methicillin-resistant Staphylococcus aureus (MRSA) that are present in subcutaneous abscesses. rGO-IONP was synthesized by the chemical deposition of Fe(2+)/Fe(3+) ions on nanosheets of rGO in aqueous ammonia. The antibacterial efficacy of the as-prepared rGO-IONP was evaluated in a mouse model with MRSA-infected subcutaneous abscesses. Upon exposure to a near-infrared laser in vitro, rGO-IONP synergistically generated localized heat and large amounts of hydroxyl radicals, which inactivated MRSA. The in vivo results reveal that combined treatment with localized heat and oxidative stress that is caused by hydroxyl radicals accelerated the healing of wounds associated with MRSA-infected abscesses. The above results demonstrate that an rGO-IONP nanocomposite system that can effectively inactivate multiple-drug-resistant bacteria in subcutaneous infections was successfully developed. FROM THE CLINICAL EDITOR The emergence of methicillin-resistant S. aureus (MRSA) has posed a significant problem in the clinical setting. Thus, it is imperative to develop new treatment strategies against this. In this study, the authors described the use of reduced graphene oxide (rGO)-iron oxide nanoparticles (rGO-IONP) to induce heat and chemical damage to MRSA. This approach may provide a platform the design of other treatment modalities against multiple-drug-resistant bacteria.

Diabetes mellitus in patients with thalassemia major

Diabetes mellitus is a major endocrinopathy for patients with thalassemia major. Although diabetes mellitus is multifactorial, iron loading is its primary cause and its management poses a clinical challenge. Detecting the pre‐diabetes stage is critical because clinical diabetes can potentially be reversed or prevented.

High-resolution melting analyses for genetic variants in ARID5B and IKZF1 with childhood acute lymphoblastic leukemia susceptibility loci in Taiwan

BACKGROUND Childhood acute lymphoblastic leukemia (ALL), a heterogeneous disease that includes multiple subtypes is defined by cell lineage and chromosome anomalies. Previous genome-wide association studies have reported several ARID5B and IKZF1 single nucleotide polymorphisms (SNPs) associated with the incidence of ALL. High-resolution melting (HRM) analysis is a rapid and convenient technique to detect SNPs; we thereby detected SNPs in ARID5B and IKZF1 genes. METHODS We enrolled 79 pediatric ALL patients and 80 healthy controls. Polymorphic variants of IKZF1 (rs6964823, rs4132601, and rs6944602) and ARID5B (rs7073837, rs10740055, and rs7089424) were detected by HRM, and SNPs were analyzed for association with childhood ALL. RESULTS The distribution of genotype rs7073837 in ARID5B significantly differed between ALL and controls (P=0.046), while those of IKZF1 (rs6964823, rs4132601, and rs6944602) and ARID5B (rs10740055 and rs7089424) did not. We analyzed the association for SNPs with B lineage ALL to find rs7073837 in ARID5B, conferring a higher risk for B lineage ALL (odds ratio, OR=1.70, 95% confidence interval, CI=1.01-2.87, P=0.049). CONCLUSION HRM is a practical method to detect SNPs in ARID5B and IKZF1 genes. We found that rs7073837 in ARID5B correlated with a risk for childhood B lineage ALL.

Treatment for childhood acute lymphoblastic leukemia in Taiwan: Taiwan Pediatric Oncology Group ALL-2002 study emphasizing optimal reinduction therapy and central nervous system preventive therapy without cranial radiation

Reinduction therapy has improved the outcomes in children with acute lymphoblastic leukemia (ALL). We sought to determine the optimal course(s) of reinduction therapy for standard‐risk (SR, or “low‐risk” in other groups) patients. Also, we evaluated outcomes using triple intrathecal therapy without cranial radiation (CrRT) for central nervous system (CNS) preventive therapy.

Disseminated candidemia refractory to caspofungin therapy in an infant with extremely low birth weight

Systemic fungal infections have high morbidity and mortality rates in neonates, especially neonates with an extremely low birth weight (ELBW). Here, we describe a 21-day-old ELBW female infant with an amphotericin B-unresponsive congenital Candida albicans infection that was treated with caspofungin. Blood sterilization was performed during the first episode, but a second episode of candidemia occurred after the discontinuation of caspofungin. Blood sterilization was again performed during the second round of caspofungin treatment, but fungal endocarditis and renal fungal balls still developed during the second episode. Caspofungin can be considered for invasive candidiasis in premature infants, especially in life-threatening situations. As for the focal lesions, more aggressive treatments other than just parenteral antibiotics should be considered. The literature regarding caspofungin therapy for neonatal candidiasis is also reviewed.

Successful extracorporeal membrane oxygenation support patients with malignancy and septic shock.

To the Editor: We read with interest the report of severe airway compromise secondary to a mediastinal malignancy managed with extracorporeal membrane oxygenation (ECMO) without intubation in two children [1], highlighting the use of ECMO as an alternate management strategy for this difficult situation. We recently cared for two patients with acute lymphoblastic leukemia (ALL) and profound septic shock who also survived with the support of venous-arterial (VA) ECMO. The first case was a 13-year-old female with T-ALL. Febrile neutropenia (white count: 1,440/ml) associated with positive blood cultures for Escherichia coli and Candida tropicalis developed during induction therapy. Despite administration of antibiotics, cefepime, amikin, and amphotericin-B, septic shock worsened, resulting in respiratory failure 8 days later. Ventilator support was provided with FiO2: 50%, PIP: 25 cm H2O, PEEP: 5 cm H2O, and MAP: 10 cm H2O. Antibiotics were changed to vancomycin, mepem, and caspofungin for broader spectrum coverage. Despite a high-dose infusion of inotropic agents (dopamine 20 mg/kg/min, norepinephrine 0.33 mg/kg/min, and epinephrine 0.2 mg/kg/min), the clinical condition of the patient deteriorated, exacerbated by increased metabolic acidosis (arterial blood gas pH: 7.19, CO2: 34.5 mm Hg, O2: 41.8 mm Hg, HCO3 : 13.3, BE: 13.3) and oliguria. V-A ECMO was implemented to provide circulatory support and hemofiltration was initiated due to renal failure. Following 3 days of ECMO support, blood pressure normalized. The patient was successfully weaned from the ventilator 3 days after the removal of ECMO. The second case involved a 21-year-old male diagnosed with pre-B ALL. The patient received peripheral blood stem-cell transplants from mismatched unrelated donor and engraftment was achieved. Six months post-transplant, the patient suffered from a urinary tract infection and cefazolin was prescribed; however, blood pressure dropped to 50/30 mm Hg 2 hr after admission, requiring the administration of high-dose inotropic agents. On the following day, the patient developed ventricular tachycardia (VT). Metabolic acidosis with desaturation was also noted (arterial blood gas pH: 7.11, CO2: 54.9 mm Hg, O2: 14.4 mm Hg, HCO3 : 17.7, BE: 11.2, and lactate: 8.9 mg/dl). DC shock was performed for the VT, but with no effect. Cardiopulmonary resuscitation was initiated; however, return of spontaneous circulation was not achieved. As a result, ECMO was implemented 38 min following the initiation of CPR. Under ECMO support, inotropic agents were tapered, resulting in a gradual increase in urine output. Cardiac function also improved with LVEF increasing from 24% to 48%. ECMO was removed after 5 days. The patient was extubated 8 days after removal from ECMO and discharged in stable condition. In critical situations, ECMO can provide cardiopulmonary support; however, experience implementing ECMO in malignant cases is somewhat limited and the benefits from such treatment are less than encouraging [2–6]. Children with cancer display a wide range of clinical manifestations and treatment should be tailored to each individual. When the condition is reversible (as with septic shock, respiratory failure, acute renal failure, and/or VT), ECMO may serve as a stopgap measure until conventional treatment takes effect. Within a well-conceived framework of technical support, ECMO shows considerable potential for expanded clinical application.

In situ depot comprising phase-change materials that can sustainably release a gasotransmitter H2S to treat diabetic wounds

Patients with diabetes mellitus are prone to develop refractory wounds. They exhibit reduced synthesis and levels of circulating hydrogen sulfide (H2S), which is an ephemeral gaseous molecule. Physiologically, H2S is an endogenous gasotransmitter with multiple biological functions. An emulsion method is utilized to prepare a microparticle system that comprises phase-change materials with a nearly constant temperature of phase transitions to encapsulate sodium hydrosulfide (NaHS), a highly water-labile H2S donor. An emulsion technique that can minimize the loss of water-labile active compounds during emulsification must be developed. The as-prepared microparticles (NaHS@MPs) provide an in situ depot for the sustained release of exogenous H2S under physiological conditions. The sustained release of H2S promotes several cell behaviors, including epidermal/endothelial cell proliferation and migration, as well as angiogenesis, by extending the activation of cellular ERK1/2 and p38, accelerating the healing of full-thickness wounds in diabetic mice. These experimental results reveal the strong potential of NaHS@MPs for the sustained release of H2S for the treatment of diabetic wounds.

Anomalous ascending aorta causing severe compression of the left bronchus in an infant with ventricular septal defect and pulmonary atresia

Tracheobronchial compression by cardiovascular structures complicates the course after surgery of congenital heart disease. A 2-month-old boy with ventricular septal defect, pulmonary atresia, and velocardiofacial syndrome had severe left main bronchus obstruction due to external compression by an anomalously oriented ascending aorta. The patient’s hypoxemic episodes necessitated extracorporeal membrane oxygenation. We inserted a stent in the left bronchus to open the airway, but the stent was crushed by the anomalous aorta. We later surgically rerouted the aorta and finally restored the patency of the left main bronchus. However, the patient died of fungemia, without being weaned from extracorporeal membrane oxygenation. We conclude that surgery is necessary instead of stent implantation to relieve the external compression of the left bronchus from a vessel with systemic arterial pressure.