Evaluation of risk stratification strategies in pediatric patients with febrile neutropenia

ObjectiveTo evaluate the performance of risk stratification protocols for febrile neutropenia specific to the pediatric population.MethodsRetrospective study of a cohort of pediatric patients undergoing cancer treatment with episodes of neutropenia due to chemotherapy and fever, treated at the emergency department of a tertiary cancer hospital from January 2015 to June 2017. Patients who were bone marrow transplant recipients and patients with neutropenia due to causes other than chemotherapy were excluded. Six protocols were applied to all patients: Rackoff, Alexander, Santolaya, Rondinelli, Ammann 2003, and Ammann 2010. The following outcomes were assessed: microbiological infection, death, ICU admission, and need for more than two antibiotics. The performance of each protocol was analyzed for sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and receiver operator characteristic (ROC) curve.ResultsThis study evaluated 199 episodes of febrile neutropenia in 118 patients. Microbiological infection was identified in 70 samples from 45 distinct episodes (22.6%), 30 patients used more than two antibiotics during treatment (15%), eight required ICU admission (4%), and one patient died (0.8%). Three protocols achieved high sensitivity indices and NPV regarding the outcomes of death and ICU admission: Alexander, Rackoff, and Ammann 2010; however, Rackoff showed higher sensitivity (0.82) and NPV (0.9) in relation to the microbiological infection outcome.ConclusionThe Rackoff risk rating showed the best performance in relation to microbiological infection, death, and ICU admission, making it eligible for prospective evaluation.     

Recent developments in the analysis of avermectin and milbemycin residues in food safety and the environment

A review of the developments on the analysis of residues of avermectins and milbemycins (both macrocyclic lactones) is presented. The macrocyclic lactones (MLs) are an important class of chemicals, which are used worldwide as veterinary drugs and as crop protection agents. As a result, residues of MLs are important from both a food safety and environmental perspective. A review of the developments in ML residues in food was carried out in detail in 2006. As a result, this paper covers recent developments in the area of food analysis, which are mainly multi-residue assays based on liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). A brief coverage of HPLC fluorescence (HPLC-FLD) based methods is included for completeness. The paper will carry out a comprehensive review of ML residues in environmental samples. These additional sections are reflective of the growing number of research papers published on LC-MS/MS and environmental applications in recent years.     

Comprehensive genetic analysis of OEIS complex reveals no evidence for a recurrent microdeletion or duplication

Omphalocele-exstrophy of the bladder-imperforate anus-spinal defects (OEIS) complex, or cloacal exstrophy (EC), is a rare constellation of malformations in humans involving the urogenital, gastrointestinal, and skeletal systems, and less commonly the central nervous system. Although OEIS complex is well-recognized in the clinical setting, there remains a significant lack of understanding of this condition at both the developmental and the genetic level. While most cases are sporadic, familial cases have been reported, suggesting that one or more specific genes may play a significant role in this condition. Several developmental mechanisms have been proposed to explain the etiology of OEIS complex, and it is generally considered to be a defect early in caudal mesoderm development and ventral body wall closure. The goal of this study was to identify genetic aberrations in 13 patients with OEIS/EC using a combination of candidate gene analysis and microarray studies. Analysis of 14 candidate genes in combination with either high resolution SNP or oligonucleotide microarray did not reveal any disease-causing mutations, although novel variants were identified in five patients. To our knowledge, this is the most comprehensive genetic analysis of patients with OEIS complex to date. We conclude that OEIS is a complex disorder from an etiological perspective, likely involving a combination of genetic and environmental predispositions. Based on our data, OEIS complex is unlikely to be caused by a recurrent chromosomal aberration.     

改善高危急性淋巴细胞白血病的预后:将新发现应用于临床

高危急性淋巴细胞白血病(acute lymphoblastie leukemia,ALL)是儿科肿瘤学的最大挑战之一.复发ALL是导致青少年死亡的首要原因,由于药物毒性限制了现有化疗方案强度的增加,故进一步改善预后需要开发直接针对合理靶标的治疗方法.这篇综述聚焦美国儿科血液和肿瘤学会2010年年会中提出的高危和复发ALL在生物学和治疗方面的进展.大样本研究结果 证实,一些与复发相关的高危因素包括:年龄较大、T系细胞表型和治疗早期微小残留病(minimal residual disease,MRD)持续呈阳性.由于抢救治疗的疗效仍旧很差,所以需要新的治疗方法.以往的观点认为BCR-ABL1阳性(Ph+),则ALL预后很差,但是最近的研究显示,酪氨酸激酶抑制剂(tyrosine kinase inhibitors,TKIs)的使用,可极大改善治疗效果.高分辨率基因组分析对遗传学改变和基因表达的研究,彻底改变了对ALL遗传学基础的理解,并且发现了与不良预后相关的一些改变,包括淋巴系转录因子基因IKZF1(IKAROS)突变、Janus激酶激活突变和淋巴系细胞因子受体基因CRLF2重排.这些数据显示,高危ALL的遗传学基础是多因素的,还提供了潜在的治疗选择--直接抑制JAK通路.     

Acquired progressive ataxia and palatal tremor: importance of MRI evidence of hemosiderin deposition and vascular malformations

Oculopalatal tremor is frequently accompanied by progressive ataxia. In symptomatic oculopalatal tremor the ataxia frequently is delayed in onset. Progressive ataxia is a defining clinical feature of superficial siderosis. We report 5 cases with palatal tremor and ataxia. Four cases had evidence of intraparenchymal hemosiderin deposition on T2-gradient-echo imaging. Three cases had a brainstem vascular malformation. In two cases the hemosiderin deposition was likely due to prior trauma. The significance of these associations and possible similarities between ataxia related to superficial siderosis and ataxia and intraparenchymal hemosiderin is discussed.     

Use of respiratory biofeedback and CLAWS for increased navigator efficiency for imaging the thoracic aorta

A novel technique to guide a subjects' breathing pattern using a respiratory biofeedback (rBF) “game” to improve respiratory efficiency is presented. The continuously adaptive windowing strategy, a fully automatic and highly efficient free‐breathing navigator gated technique, is used to acquire the data as it ensures that all potential navigator acceptance windows are possible. This enables the rBF to be fully adaptable to a subject's respiratory pattern. Images of the thoracic aorta acquired using balanced steady‐state free precession with continuously adaptive windowing strategy respiratory motion control, with and without rBF, were compared in 10 healthy subjects. Total scan time was reduced by using rBF. The mean scan time was reduced from 7 min 44 s (463 cardiac cycles, ±127cc) without rBF to 5 min 43 s (380 cardiac cycles, ±118cc) with the use of rBF (P < 0.05). Respiratory efficiency was increased from 45% without rBF to 56% with rBF (P < 0.01). Image quality was the same for both techniques (P = ns). In conclusion, rBF significantly improved respiratory efficiency and reduced acquisition duration without affecting image quality. Magn Reson Med, 2011. © 2011 Wiley Periodicals, Inc.     

U.S. Food and Drug Administration Approval Summary: Erlotinib for the First‐Line Treatment of Metastatic Non‐Small Cell Lung Cancer With Epidermal Growth Factor Receptor Exon 19 Deletions or Exon 21 (L858R) Substitution Mutations

On May 14, 2013, the U.S. Food and Drug Administration approved erlotinib (Tarceva, Astellas Pharma Inc., Northbrook, IL, http://www.us.astellas.com /) for the first‐line treatment of patients with metastatic non‐small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) substitution mutations. This indication for erlotinib was approved concurrently with the cobas EGFR Mutation Test (Roche Molecular Systems, Inc., Basel, Switzerland, http://www.molecular.roche.com), a companion diagnostic test for patient selection. The approval was based on clinically important improvements in progression‐free survival (PFS) and objective response rate (ORR) and an acceptable toxicity profile demonstrated in a multicenter, open label trial enrolling 174 patients with metastatic NSCLC whose tumors had EGFR mutations as determined by a laboratory‐developed test. Patients were randomized (1:1) to receive erlotinib (150 mg/day) or platinum‐based doublet chemotherapy. The primary endpoint was investigator‐assessed PFS. Secondary endpoints included overall survival (OS) and ORR. Superior PFS (hazard ratio [HR] 0.34; 95% confidence interval [CI]: 0.23, 0.49; p < .001) and ORR (65% vs. 16%) were observed in the erlotinib arm. Median PFS was 10.4 months and 5.2 months in the erlotinib and chemotherapy arms, respectively. There was no difference in OS (HR 0.93; 95% CI: 0.64, 1.35) with median OS of 22.9 months and 19.5 months in the erlotinib and chemotherapy arms, respectively. The most frequent (≥30%) adverse reactions in the erlotinib‐treated patients were rash, diarrhea, asthenia, cough, dyspnea, and decreased appetite. The most frequent (≥5%) grade 3 and 4 adverse reactions were rash and diarrhea.