The Landscape of Actionable Molecular Alterations in Immunomarker-Defined Large-Cell Carcinoma of the Lung.

Introduction: Patients with pulmonary large-cell carcinoma (LCC) have poor prognosis and limited treatment options. The identification of clinically actionable molecular alterations helps to guide personalized cancer treatment decisions.

Patients And Methods: A consecutive cohort of 789 resected NSCLC cases were reviewed.

Mismatch repair deficiency is implicated in carcinoma arising from ovarian teratoma.

Malignant transformation of benign mature ovarian teratoma can result in a wide spectrum of cancer, including a variety of carcinoma, sarcoma, or melanoma. The role of mismatch repair defects in such malignant transformation is still elusive. In view of current immunotherapy, the role of mismatch repair deficiency can have significant implications on therapeutic strategy.

Botulinum Toxin Type A Versus Placebo for Idiopathic Clubfoot: A Two-Center, Double-Blind, Randomized Controlled Trial.

Background: Congenital idiopathic clubfoot is a condition that affects, on average, approximately 1 in 1,000 infants. One broadly adopted method of management, described by Ponseti, is the performance of a percutaneous complete tenotomy when hindfoot stall occurs. The use of onabotulinum toxin A (BTX-A) along with the manipulation and cast protocol described by Ponseti has been previously reported.

Exome and genome sequencing of nasopharynx cancer identifies NF-κB pathway activating mutations.

Nasopharyngeal carcinoma (NPC) is an aggressive head and neck cancer characterized by Epstein-Barr virus (EBV) infection and dense lymphocyte infiltration. The scarcity of NPC genomic data hinders the understanding of NPC biology, disease progression and rational therapy design. Here we performed whole-exome sequencing (WES) on 111 micro-dissected EBV-positive NPCs, with 15 cases subjected to further whole-genome sequencing (WGS), to determine its mutational landscape.

Improving education and coping of scoliosis patients undergoing surgery, and their families, using e-health.

Purpose: Healthcare providers have limited time to spend with scoliosis patients who are considering surgery and their families. The purpose of this study was to evaluate an e-health strategy to increase knowledge and coping in patients with scoliosis who are surgical candidates and their families.

Methods: We enrolled patients with scoliosis who were candidates for surgery and their families.

Therapeutic intervention for internalized stigma of severe mental illness: A systematic review and meta-analysis.

Objective: Internalized stigma can lead to pervasive negative effects among people with severe mental illness (SMI). Although prevalence of internalized stigma is high, there is a dearth of interventions and meanwhile a lack of evidence as to their effectiveness. This study aims at unraveling the existence of different therapeutic interventions and the effectiveness internalized stigma reduction in people with SMI via a systematic review and meta-analysis.

Profiling of Oncogenic Driver Events in Lung Adenocarcinoma Revealed MET Mutation as Independent Prognostic Factor.

Introduction: Oncogenic driver mutations activating receptor tyrosine kinase pathways are promising predictive markers for targeted treatment. We investigated the mutation profile of an updated driver events list on receptor tyrosine kinase/RAS/PI3K axis and the clinicopathologic implications in a cohort of never-smoker predominated Chinese lung adenocarcinoma.

Methods: We tested 154 lung adenocarcinomas and adenosquamous carcinomas for EGFR, KRAS, HER2, BRAF, PIK3CA, MET, NRAS, MAP2K1, and RIT1 mutations by polymerase chain reaction-direct sequencing.

Outcomes of infection following pediatric spinal fusion.

Background: Removal of instrumentation is often recommended as part of treatment for spinal infections, but studies have reported eradication of infection even with instrumentation retention by using serial débridements and adjuvant antibiotic pharmacotherapy. We sought to determine the effect of instrumentation retention or removal on outcomes in children with spinal infections.

Methods: We retrospectively reviewed the cases of patients who experienced early (< 3 mo) or late (≥ 3 mo) infected spinal fusions.

Outcomes of infection following pediatric spinal fusion.

Background: Removal of instrumentation is often recommended as part of treatment for spinal infections, but studies have reported eradication of infection even with instrumentation retention by using serial débridements and adjuvant antibiotic pharmacotherapy. We sought to determine the effect of instrumentation retention or removal on outcomes in children with spinal infections.

Methods: We retrospectively reviewed the cases of patients who experienced early (< 3 mo) or late (≥ 3 mo) infected spinal fusions.

Outcomes of bracing in juvenile idiopathic scoliosis until skeletal maturity or surgery.

Study Design: Retrospective comparative study.

Objective: To evaluate the outcome of bracing in patients with juvenile idiopathic scoliosis (JIS) at either skeletal maturity or time of scoliosis surgery.

Summary Of Background Data: JIS is generally thought to have poor outcomes with high rates of surgical fusion.

Reoperations after tarsal coalition resection: a population-based study.

Few studies have evaluated the incidence of subsequent operations after tarsal coalition resection. Using administrative databases, we followed up a cohort of patients who had undergone tarsal coalition resection to determine the rates and possible risk factors for subsequent resection or arthrodesis. Patients (aged 8 years or older) who had been treated from July 1994 to August 2009 in Canada were identified and included.

Characterization of rare transforming KRAS mutations in sporadic colorectal cancer.

KRAS mutational status has been shown to be a predictive biomarker of resistance to anti-EGFR monoclonal antibody (mAb) therapy in patients with metastatic colorectal cancer. We report the spectrum of KRAS mutation in 1506 patients with colorectal cancer and the identification and characterization of rare insertion mutations within the functional domain of KRAS. KRAS mutations are found in 44.

The epidemiology of paediatric supracondylar fracture fixation: a population-based study.

Introduction: The epidemiology of paediatric supracondylar fracture (SCF) fixation has not been evaluated at a population level. The purpose of this study was to: (1) determine the incidence density rate (IDR) of SCF fixation and (2) determine the rate of and risk factors for re-operation.

Methods: Using administrative databases, all patients who underwent SCF fixation (closed reduction percutaneous pinning (CRPP) or open reduction (OR)) in Ontario between April 2002 and March 2010 were identified.

Long-term functional outcomes of resected tarsal coalitions.

Background: There are few long-term studies evaluating tarsal coalition resections. The purpose of this study was to compare patient outcomes following resection of calcaneonavicular (CN) and talocalcaneal (TC) bars and to determine the relationship between the extent of a coalition and the outcome of resection.

Methods: Patients younger than 18 years receiving resection for symptomatic tarsal coalition (1991-2004 inclusive) were eligible to participate.

Detection of ALK rearrangement by immunohistochemistry in lung adenocarcinoma and the identification of a novel EML4-ALK variant.

Introduction: The echinoderm microtubule-associated protein-like 4 anaplastic lymphoma kinase (EML4-ALK) fusion gene has been identified as a potent oncogenic driver in non-small-cell lung cancer, in particular adenocarcinoma (ADC). It defines a unique subgroup of lung ADC, which may be responsive to ALK inhibitors. Detection of ALK rearrangement by fluorescence in situ hybridization (FISH) or reverse transcriptase polymerase chain reaction (RT-PCR) is considered to be the standard procedure, but each with its own limitation.

APOE genotype-function relationship: evidence of -491 A/T promoter polymorphism modifying transcription control but not type 2 diabetes risk.

Background: The apolipoprotein E gene (APOE) coding polymorphism modifies the risks of Alzheimer's disease, type 2 diabetes, and coronary heart disease. Aside from the coding variants, single nucleotide polymorphism (SNP) of the APOE promoter has also been shown to modify the risk of Alzheimer's disease.

Methodology/principal Findings: In this study we investigate the genotype-function relationship of APOE promoter polymorphism at molecular level and at physiological level: i.

T295M-associated Glut1 deficiency syndrome with normal erythrocyte 3-OMG uptake.

Purpose: Glucose transporter type 1 (Glut1) is expressed in vascular endothelial cells comprising blood-brain barrier. Glut1 deficiency syndrome is characterized by low cerebrospinal fluid (CSF) concentration of glucose with normoglycemia, infantile seizure, acquired microcephaly, developmental delay and ataxia. As Glut1 is also expressed in erythrocytes, the diagnosis is confirmed by a decreased uptake of 3-O-methylglucose (3-OMG) into erythrocytes.

Identification of potential CepR regulated genes using a cep box motif-based search of the Burkholderia cenocepacia genome.

Background: The Burkholderia cenocepacia CepIR quorum sensing system has been shown to positively and negatively regulate genes involved in siderophore production, protease expression, motility, biofilm formation and virulence. In this study, two approaches were used to identify genes regulated by the CepIR quorum sensing system. Transposon mutagenesis was used to create lacZ promoter fusions in a cepI mutant that were screened for differential expression in the presence of N-acylhomoserine lactones.