IMPORTANCE Antibiotic therapy for acute uncomplicated appendicitis is effective in adult patients, but its application in pediatric patients remains controversial.OBJECTIVE To compare the safety and efficacy of antibiotic treatment vs appendectomy as the primary therapy for acute uncomplicated appendicitis in pediatric patients. DATA SOURCESThe PubMed, MEDLINE, EMBASE, and Cochrane Library databases and the Cochrane Controlled Trials Register for randomized clinical trials were searched through April 17, 2016. The search was limited to studies published in English. Search terms included appendicitis, antibiotics, appendectomy, randomized controlled trial, controlled clinical trial, randomized, placebo, drug therapy, randomly, and trial.STUDY SELECTION Randomized clinical trials and prospective clinical controlled trials comparing antibiotic therapy with appendectomy for acute uncomplicated appendicitis in pediatric patients (aged 5-18 years) were included in the meta-analysis. The outcomes included at least 2 of the following terms: success rate of antibiotic treatment and appendectomy, complications, readmissions, length of stay, total cost, and disability days.DATA EXTRACTION AND SYNTHESIS Data were independently extracted by 2 reviewers. The quality of the included studies was examined in accordance with the Cochrane guidelines and the Newcastle-Ottawa criteria. Data were pooled using a logistic fixed-effects model, and the subgroup pooled risk ratio with or without appendicolith was estimated. MAIN OUTCOMES AND MEASURESThe primary outcome was the success rate of treatment. The hypothesis was formulated before data collection.RESULTS A total of 527 articles were screened. In 5 unique studies, 404 unique patients with uncomplicated appendicitis (aged 5-15 years) were enrolled. Nonoperative treatment was successful in 152 of 168 patients (90.5%), with a Mantel-Haenszel fixed-effects risk ratio of 8.92 (95% CI, 2.67-29.79; heterogeneity, P = .99; I 2 = 0%). Subgroup analysis showed that the risk for treatment failure in patients with appendicolith increased, with a Mantel-Haenszel fixed-effects risk ratio of 10.43 (95% CI, 1.46-74.26; heterogeneity, P = .91; I 2 = 0%). CONCLUSIONS AND RELEVANCEThis meta-analysis shows that antibiotics as the initial treatment for pediatric patients with uncomplicated appendicitis may be feasible and effective without increasing the risk for complications. However, the failure rate, mainly caused by the presence of appendicolith, is higher than for appendectomy. Surgery is preferably suggested for uncomplicated appendicitis with appendicolith.

No abstract

Purpose Our previous study revealed that 90% (47 of 52; 95% CI: 0.79–0.96) of Chinese never-smokers with lung adenocarcinoma harbor known oncogenic driver mutations in just four genes: EGFR, ALK, HER2, and KRAS. Here, we examined the status of known driver mutations specifically in female never-smokers with lung adenocarcinoma. Experimental Design Tumors were genotyped for mutations in EGFR, KRAS, ALK, HER2, and BRAF. Data on age, stage, tumor differentiation, histological subtypes, and molecular alterations were recorded from 349 resected lung adenocarcinomas from female never-smokers. We further compared the clinicopathological parameters according to mutational status of these genes. Results Two hundred and sixty-six (76.2%) tumors harbored EGFR mutations, 16 (4.6%) HER2 mutations, 15 (4.3%) EML4-ALK fusions, seven (2.0%) KRAS mutations, and two (0.6%) BRAF mutations. In univariate analysis, patients harboring EGFR mutations were significantly older (p<0.001), whereas patients harboring HER2 mutations were significantly younger (p=0.036). Higher prevalence of KRAS (p=0.028) and HER2 (p=0.021) mutations was found in invasive mucinous adenocarcinoma (IMA). The frequency of EGFR mutations was positively correlated with acinar predominant tumors (p=0.002). Multivariate analysis revealed that older age at diagnosis (p=0.013) and acinar predominant subtype (p=0.005) were independent predictors of EGFR mutations. Independent predictors of HER2 mutations included younger age (p=0.030) and IMA (p=0.017). IMA (p=0.006) and poor differentiation (p=0.028) were independently associated with KRAS mutations. Conclusions The frequency of driver mutations in never-smoking female lung adenocarcinoma varies with histological subtypes and age at diagnosis. These data have implications for both clinical trial design and therapeutic strategies.

Prolongation of the QT interval of the ECG is associated with increased risk of torsades de pointes ventricular tachycardia. Ranolazine, a novel antianginal agent, is reported to decrease the delayed rectifier potassium current, I Kr , and to increase action potential duration (APD) and the QT interval. However, ranolazine is also reported to reduce late sodium current (late I Na) , a depolarizing current that contributes to prolongation of the plateau of the ventricular action potential. We hypothesized that ranolazine would decrease APD and the occurrence of arrhythmias when late I Na is increased. Therefore, we measured the effects of ranolazine alone and in the presence of anemone toxin (ATX)-II, whose action mimics the sodium channelopathy associated with long-QT3 syndrome, on epicardial monophasic action potentials and ECGs recorded from guinea pig isolated hearts. Ranolazine (0.1-50 M) prolonged monophasic APD at 90% repolarization (MAPD 90 ) by up to 22% but did not cause either early afterdepolarizations (EADs) or ventricular tachycardia (VT). ATX-II (1-20 nM) markedly increased APD and caused EADs and VT. Ranolazine (5-30 M) significantly attenuated increases in MAPD 90 and reduced episodes of EADs and VT produced by ATX-II. Ranolazine also attenuated the synergistic effect of MAPD 90 increase caused by combinations of ATX-II and blockers of I K [E-4031; 1-[2-(6-methyl-2-pyridyl)ethyl]-4-methylsulfonylaminobenzoyl)piperidine]. Thus, although ranolazine alone prolonged APD, it reduced APD and ventricular arrhythmias caused by agents that increased late I Na and decreased I K .Prolongation of the duration of the ventricular action potential (indicated on the surface electrocardiogram as an increase of the QT interval) due to inhibition of the rapid delayed-rectifier potassium current, I Kr , is caused by drugs from many therapeutic classes and is associated with an increased risk of ventricular tachyarrhythmias such as torsades de pointes (TdP) (Belardinelli et al., 2003). However, QT interval prolongation per se may not be proarrhythmic (Hondeghem et al., 2001). Ranolazine is a novel antianginal drug (Pepine and Wolff, 1999;Louis et al., 2002;Chaitman et al., 2004), and it prolongs the QT interval but is not known to increase the incidence of ventricular tachycardias (VTs) and may reduce the incidence of ischemia-related arrhythmias (Gralinski et al., 1996). At a cellular level, ranolazine has been found to reduce the peak outward current conducted by the delayed rectifier potassium channel I Kr with a potency (IC 50 value) of 11.5 M (Zygmunt et al., 2002) and to reduce the late inward sodium current (late I Na ) with an IC 50 of 5 to 21 M, depending on pacing frequency and membrane potential (Zygmunt et al., 2002;Song et al., 2004).Inhibitions of I Kr and late I Na by ranolazine would be expected to have opposite effects on the duration of the QT interval. Whereas inhibition of I Kr prolongs action potential duration (APD), inhibition of late I Na decreases APD. Thus, the effect of ranolazine o...