Children with a button battery impaction present with nonspecific symptoms that may account for a delay in medical care. We conducted a retrospective study of the clinical presentation, management, and complications associated with button battery ingestion in thepediatric aerodigestive tract and to evaluate the associated longterm morbidity. We reviewed the medical records of 23 patients who were treated for button battery impaction at our tertiary care children's hospitalfrom Jan. 1,2000,. through July 31,2013. This population was made up of 14boys and 9 girls, aged 7 days to 12 years (mean: 4 yr). Patients were divided into three groups based on the site of impaction; there were 9 impactions in the esophagus and 7 each in thenasal cavity andstomach. We compiled information on thetypeandsizeofeach battery, theduration of the impaction, presenting symptoms, treatment, and outcomes. The mean duration of battery impaction was 40.6, 30.7, and 21.0 hours in the esophagus, nasal cavity, andstomach, respectively. We wereable toidentify the specific type of battery in 13 cases; 11 of these cases (85%) involved a 3-V 20-mm lithium ionbattery, including all cases of esophageal impaction in which the type of battery was identified. The most common presenting signs and symptoms were vomiting (n =7 (30%j), difficultyfeeding (n = 5 [22%]), cough (n = 5), and bloody
BackgroundMyeloid-derived suppressor cells (MDSC) and M2 monocytes/macrophages are two types of suppressive myeloid antigen presenting cells that have been shown to promote tumor progression and correlate with poor prognosis in cancer patients. Tumor antigen specific monoclonal antibodies (mAb) have emerged as important agents for cancer therapy. In addition to the direct inhibition of tumor growth, the Fc portions of the therapeutic mAbs, such as the IgG1 portion of the anti-epidermal growth factor receptor (EGFR) mAb cetuximab, might interact with the Fc-gamma receptors (FcγR) on myeloid cells and modulate their suppressive activity.MethodsPatients with locally advanced head and neck squamous cell carcinoma (HNSCC) on the UPCI 08–013 NCT01218048 trial were treated with single-agent cetuximab before surgery. Blood were collected pre- and post-cetuximab treatment to analyze frequency of monocytic MDSC (CD11b+CD14+HLA-DRlo/-), granulocytic MDSC (LIN−CD11b+CD15+) and CD11b+CD14+HLA-DRhi monocytes by flow cytometry. Besides, CD11b+CD14+HLA-DRhi monocytes were sorted for qPCR analysis of IL-10 and IL-12B transcripts. MDSC were generated in vitro with or without coated hIgG1 and tested for suppressive activity in mixed leukocyte reaction (MLR). Naïve monocytes from HNSCC patients co-cultured with tumor cell lines in the presence of cetuximab or hIgG1 were analyzed for M1/2 surface markers and cytokines.ResultsWe observed significantly increased monocytic MDSC in non-responders and decreased granulocytic MDSC in responders after cetuximab treatment. In addition, circulating CD11b+CD14+HLA-DRhi monocytes of cetuximab responders displayed attenuated M2 polarization, with decreased CD163+ expression and IL-10 transcripts after cetuximab treatment. This beneficial effect appeared to be FcγR dependent, since CD16 ligation reproduced the reversal of suppressive activity of MDSC in vitro. CD14+ naïve monocytes from the co-cultures of tumor cells, cetuximab and HNSCC patient PBMC or purified monocytes were skewed to an M1-like phenotype, with increased expression of HLA-DR, CD86 and production of IL-12 p70. Likewise, reduced M2 features (expression of CD163 and production of IL-10) were found after crosslinking CD16 on the surface of monocytes to cetuximab-coated tumor cells.ConclusionOur studies demonstrate a novel function of cetuximab in ameliorating suppressive phenotypes of FcγR bearing myeloid cells in cancer patients, which is associated with better clinical outcome of cetuximab-treated patients.Clinical trial registry#NCT01218048. Registered 7 October 2010.Electronic supplementary materialThe online version of this article (doi:10.1186/s40425-015-0097-6) contains supplementary material, which is available to authorized users.
Alternative splicing generates a vast diversity of protein isoforms from a limited number of protein-coding genes, with many of the isoforms possessing unique, and even contrasting, functions. Fluorescence-based splicing reporters have the potential to facilitate studies of alternative splicing at the single-cell level and can provide valuable information on phenotypic transitions in almost real time. Fibroblast growth factor receptor 2 (FGFR2) pre-mRNA is alternatively spliced to form the epithelial-specific and mesenchymal-specific IIIb and IIIc isoforms, respectively, which are useful markers of epithelial-mesenchymal transitions (EMT). We have used our knowledge of FGFR2 splicing regulation to develop a fluorescence-based reporter system to visualize exon IIIc regulation in vitro and in vivo. Here we show the application of this reporter system to the study of EMT in vitro in cell culture and in vivo in transgenic mice harboring these splicing constructs. In explant studies, the reporters revealed that FGFR2 isoform switching is not required for keratinocyte migration during cutaneous wound closure. Our results demonstrate the value of the splicing reporters as tools to study phenotypic transitions and cell fates at single cell resolution. Moreover, our data suggest that keratinocytes migrate efficiently in the absence of a complete EMT.
Objectives (1) To describe the presentation, management, and outcomes associated with pediatric esophageal food impaction (EFI) at a single tertiary care institution. (2) To identify the key clinical features of pediatric EFI that are associated with a diagnosis of eosinophilic esophagitis (EoE). Study Design Case series with chart review. Setting Tertiary care children's hospital. Subjects and Methods Thirty-five children <18 years of age presenting with EFI between November 1, 2006, and October 31, 2013, were included. Presenting symptoms, medical history, biopsy results, endoscopic findings, and underlying etiology were examined. Fisher exact test, t tests, and logistic regression were used to compare between patients with and without EoE. Results Thirty-five patients had isolated EFI and were included in the study. EoE accounted for 74% (n = 26) of pediatric EFI, with the remaining cases being attributed to neurologic impairment (n = 5, 15%), prior surgeries (n = 1, 3%), reflux esophagitis (n = 1, 3%), or unknown etiologies (n = 2, 6%). EFI was the initial manifestation of EoE in 81% (n = 21) of patients. The most common presenting symptoms were dysphagia (n = 34), choking (n = 26), and vomiting (n = 23). Linear furrowing was the only endoscopic finding that was significantly associated with EoE ( P < .001). Conclusion Most esophageal food impactions in the pediatric population are associated with an underlying diagnosis of EoE and are often the initial manifestation of the disease. EoE must be considered in all pediatric patients with EFI; esophageal biopsies should be strongly considered in these patients at the time of endoscopic management of the EFI.
Objective Ablations of locally advanced or recurrent head and neck cancer commonly result in large composite orofacial defects. Chimeric flaps represent a unique surgical option for these defects, as they provide diverse tissue types from a single donor site. The purpose of the study was to consolidate the literature on chimeric flaps with regard to postoperative complication rates to help inform surgical decision making. Data Sources The librarian created search strategies with a combination of keywords and controlled vocabulary in Ovid Medline (1946), Embase (1947), Scopus (1823), Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, and Clinicaltrails.gov (1997). Review Methods Candidate articles were independently reviewed by 2 authors familiar with the subject material, and inclusion/exclusion criteria were uniformly applied for article selection. Articles were considered eligible if they included patients who received a single chimeric flap for reconstruction of head and neck defects and if they provided data on complication rates. Results A total of 521 chimeric flaps were included in the study. The major complication rate was 22.6%, while the minor complication rate was 14.0%. There were 7 flap deaths noted in the series. Median operative time and harvest time were 15.0 and 2.5 hours, respectively. Conclusion Chimeric flaps represent a viable option for reconstruction of complex head and neck defects and have complication rates similar to those of double free flaps and single free flaps with locoregional flap while only modestly increasing total operative time.
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