Percutaneous endoscopic gastrostomy in children

PurposePercutaneous endoscopic gastrostomy (PEG) can improve nutritional status and reduce the amount of time needed to feed neurologically impaired children. We evaluated the characteristics, complications, and outcomes of neurologically impaired children treated with PEG.MethodsWe retrospectively reviewed the records of 32 neurologically impaired children who underwent PEG between March 2002 and August 2008 at our medical center. Forty-two PEG procedures comprising 32 PEG insertions and 10 PEG exchanges, were performed. The mean follow-up time was 12.2 (6.6) months.ResultsMean patient age was 9.4 (4.5) years. The main indications for PEG insertion were swallowing difficulty with GI bleeding due to nasogastric tube placement and/or the presence of gastroesophageal reflux disease (GERD). The overall rate of complications was 47%, with early complications evident in 25% of patients and late complications in 22%. The late complications included one gastro-colic fistula, two cases of aggravated GERD, and four instances of wound infection. Among the 15 patients with histological evidence of GERD before PEG, 13 (87%) had less severe GERD, experienced no new aspiration events, and showed increased body weight after PEG treatment.ConclusionPEG is a safe, effective, and relatively simple technique affording long-term enteral nutritional support in neurologically impaired children. Following PEG treatment, the body weight of most patients increased and the levels of vomiting, GI bleeding, and aspiration fell. We suggest that PEG with post-procedural observation be considered for enteral nutritional support of neurologically impaired children

Reference values for respiratory system impedance using impulse oscillometry in healthy preschool children

PurposeThe normal values for lung resistance and lung capacity of children, as determined by impulse oscillometry (IOS), are different for children of different ethnicities. However, reference values there is no available reference value for Korean preschool children have yet to be determined. The aim of the present study was to determine the normal ranges of IOS parameters in Korean preschool children.MethodsA total of 133 healthy Korean preschool children were selected from 639 children (aged 3 to 6 years) who attended kindergarten in Seongnam, Gyeonggi province, Korea. Healthy children were defined according to the European Respiratory Society (ERS) criteria. All subjects underwent lung function tests using IOS. The relationships between IOS value (respiratory resistance (Rrs) and reactance (Xrs) at 5 and 10 Hz and resonance frequency (RF)) and age, height, and weight were analyzed by simple linear and multiple linear regression analyses.ResultsThe IOS success rate was 89.5%, yielding data on 119 children. Linear regression identified height as the best predictor of Rrs and Xrs. Using stepwise multiple linear regressions based on age, height, and weight, we determined regression equations and coefficients of determination (R2) for boys (Rrs5=1.934-0.009×Height, R2=12.1%; Xrs5=0.774+0.006×Height-0.002×Age, R2=20.2% and for girls (Rrs5=2.201-0.012×Height, R2=18.2%; Xrs5=-0.674+0.004×Height, R2=10.5%).ConclusionThis study provides reference values for IOS measurements of normal Korean preschool children. These provide a basis for the diagnosis and monitoring of preschool children with a variety of respiratory diseases

Application and optimisation of the Comparison on Extreme Laboratory Tests (CERT) algorithm for detection of adverse drug reactions: Transferability across national boundaries.

PURPOSE: The Singapore regulatory agency for health products (Health Sciences Authority), in performing active surveillance of medicines and their potential harms, is open to new methods to achieve this goal. Laboratory tests are a potential source of data for this purpose. We have examined the performance of the Comparison on Extreme Laboratory Tests (CERT) algorithm, developed by Ajou University, Korea, as a potential tool for adverse drug reaction detection based on the electronic medical records of the Singapore health care system. METHODS: We implemented the original CERT algorithm, comparing extreme laboratory results pre- and post-drug exposure, and 5 variations thereof using 4.5 years of National University Hospital (NUH) electronic medical record data (31 869 588 laboratory tests, 6 699 591 drug dispensings from 272 328 hospitalizations). We investigated 6 drugs from the original CERT paper and an additional 47 drugs. We benchmarked results against a reference standard that we created from UpToDate 2015. RESULTS: The original CERT algorithm applied to all 53 drugs and 44 laboratory abnormalities yielded a positive predictive value (PPV) and sensitivity of 50.3% and 54.1%, respectively. By raising the minimum number of cases for each drug-laboratory abnormality pair from 2 to 400, the PPV and sensitivity increased to 53.9% and 67.2%, respectively. This post hoc variation, named CERT400, performed particularly well for drug-induced hepatic and renal toxicities. DISCUSSION: We have demonstrated that the CERT algorithm can be applied across national boundaries. One modification (CERT400) was able to identify adverse drug reaction signals from laboratory data with reasonable PPV and sensitivity, which indicates potential utility as a supplementary pharmacovigilance tool

Efficacy and Safety of Ceritinib 450 mg/day with Food and 750 mg/day in Fasted State in Treatment-Naïve Patients with ALK+ Non-Small Cell Lung Cancer: Results from the ASCEND-8 Asian Subgroup Analysis

PURPOSE: Previous report from the ASCEND-8 trial showed consistent efficacy with less gastrointestinal (GI) toxicity in patients with anaplastic lymphoma kinase-rearranged (ALK+) advanced/metastatic non-small cell lung cancer (NSCLC) treated with ceritinib 450-mg with food compared with 750-mg fasted. In this subgroup analysis, we report outcomes in Asian patients of the ASCEND-8 trial. MATERIALS AND METHODS: Key efficacy endpoints were blinded independent review committee (BIRC)-assessed overall response rate (ORR) and duration of response (DOR) evaluated per Response Evaluation Criteria in Solid Tumors v1.1. Other efficacy endpoints were investigator-assessed ORR and DOR; BIRC- and investigator-assessed progression-free survival (PFS) and disease control rate; overall survival (OS). Safety was evaluated by frequency and severity of adverse events. RESULTS: At final data cutoff (6 March 2020), 198 treatment-naïve patients were included in efficacy analysis, of which 74 (37%) comprised the Asian subset; 450-mg fed (n=29), 600-mg fed (n=19), and 750-mg fasted (n=26). Baseline characteristics were mostly comparable across study arms. At baseline, more patients in 450-mg fed arm (44.8%) had brain metastases than in 750-mg fasted arm (26.9%). Per BIRC, patients in the 450-mg fed arm had a numerically higher ORR, 24-month DOR rate and 24-month PFS rate than the 750-mg fasted arm. The 36-month OS rate was 93.1% in 450-mg fed arm and 70.9% in 750-mg fasted arm. Any-grade GI toxicity occurred in 82.8% and 96.2% of patients in the 450-mg fed and 750-mg fasted arms, respectively. CONCLUSION: Asian patients with ALK+ advanced/metastatic NSCLC treated with ceritinib 450-mg fed showed numerically higher efficacy and lower GI toxicity than 750-mg fasted patients.Y

Hippo Pathway-independent Restriction of TAZ and YAP by Angiomotin*

The Hippo pathway restricts the activity of transcriptional co-activators TAZ and YAP by phosphorylating them for cytoplasmic sequestration or degradation. In this report, we describe an independent mechanism for the cell to restrict the activity of TAZ and YAP through interaction with angiomotin (Amot) and angiomotin-like 1 (AmotL1). Amot and AmotL1 were robustly co-immunoprecipitated with FLAG-tagged TAZ, and their interaction is dependent on the WW domain of TAZ and the PPXY motif in the N terminus of Amot. Amot and AmotL1 also interact with YAP via the first WW domain of YAP. Overexpression of Amot and AmotL1 caused cytoplasmic retention of TAZ and suppressed its transcriptional outcome such as the expression of CTGF and Cyr61. Hippo refractory TAZ mutant (S89A) is also negatively regulated by Amot and AmotL1. HEK293 cells express the highest level of Amot and AmotL1 among nine cell lines examined, and silencing the expression of endogenous Amot increased the expression of CTGF and Cyr61 either at basal levels or upon overexpression of exogenous S89A. These results reveal a novel mechanism to restrict the activity of TAZ and YAP through physical interaction with Amot and AmotL1