OtoRhinoLaryngology News: 09/02/17

Σάββατο 2 Σεπτεμβρίου 2017

Combination therapy of PKCζ and COX-2 inhibitors synergistically suppress melanoma metastasis

Metastatic malignant melanoma is one of the most aggressive malignancies and its treatment remains challenging. Recent studies demonstrate that the melanoma metastasis has correlations with the heightened acti...

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NLRP3 inflammasome activation promotes inflammation-induced carcinogenesis in head and neck squamous cell carcinoma

NLRP3 inflammasome acts as a danger signal sensor that triggers and coordinates the inflammatory response. However, the roles of NLRP3 inflammasome in the tumorigenesis and development of cancer stem cells (CS...

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Cervical disc arthroplasty for the treatment of adjacent segment disease: a systematic review of clinical evidence

Publication date: Available online 2 September 2017
Source:Clinical Neurology and Neurosurgery
Author(s): Ting-kui Wu, Hao Liu, Ning Ning, Ying Hong, Ming-dan Deng, Bei-yu Wang, Xin Rong, Yang Meng, Hua Chen
The safety and efficacy of cervical disc arthroplasty (CDA) performed adjacent to previous fusion for the treatment of adjacent segment disease (ASD) remains unknown. This systematic review summarizes clinical evidence on the outcomes of CDA performed adjacent to previous cervical fusion. A systematic search of PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), Medline and Embase for literature published through March 2017 was conducted. All the studies on CDA for the treatment of ASD after cervical fusion surgery were included. Two independent reviewers searched and assessed the literature according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PRISMA). A total of 5 studies were identified. The overall quality of evidence was low. All included studies demonstrated that clinical outcomes reflected by several assessment scales improved after arthroplasty. Cervical lordosis range of motion (ROM) after arthroplasty remained and was even enhanced postoperatively. The rate of complications and subsequent surgeries was low. There is a dearth of information regarding the outcomes of CDA for the treatment of ASD in the literature. In general, CDA may be a safe and effective surgical procedure to treat ASD, but this conclusion needs to be confirmed by future long-term, prospective clinical trials.

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Expanding our research horizons

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RNA sequencing and pathway analysis identify tumor necrosis factor alpha driven small proline-rich protein dysregulation in chronic rhinosinusitis

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Promotion of olfactory receptor neuron differentiation of olfactory neuroepithelial cells by using chitosan solution

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Sinus bacteriology in patients with cystic fibrosis or primary ciliary dyskinesia: A systematic review

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An update on the epidemiology of aspirin-exacerbated respiratory disease

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Immunoglobulin G4 sinusitis in association with aspirin-exacerbated respiratory disease

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Outcomes of sinonasal squamous cell carcinoma with and without association of inverted papilloma: A multi-institutional analysis

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Quality-of-life outcomes in patients who underwent subcutaneous immunotherapy and sublingual immunotherapy in a real-world clinical setting

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The effect of olfactory training on the odor threshold in patients with traumatic anosmia

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Erratum

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The effect of closed septorhinoplasty on nasal functions and on external and internal nasal valves: A prospective study

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Primary endoscopic endonasal dacryocystorhinostomy for pediatric nasolacrimal duct obstruction: A systematic review

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Long-term olfactory outcome after nasoseptal flap reconstructions in midline skull base surgery

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Draf III frontal sinus surgery: “How I do it”

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Utility of intraoperative frozen sections in surgical decision making for acute invasive fungal rhinosinusitis

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MiR-210-3p inhibits the tumor growth and metastasis of bladder cancer via targeting fibroblast growth factor receptor-like 1.

MiR-210-3p inhibits the tumor growth and metastasis of bladder cancer via targeting fibroblast growth factor receptor-like 1.

Am J Cancer Res. 2017;7(8):1738-1753

Authors: Yang X, Shi L, Yi C, Yang Y, Chang L, Song D

Abstract
Current evidence indicates that microRNAs are widely down-regulated in various tumors including colorectal carcinoma, liver cancer and lung cancer, and function as tumor suppressors through inhibiting cancer cell growth, invasion and migration. Here, we demonstrated that miR-210-3p level was significantly reduced in the bladder cancer compared to paratumor tissues, and attempt to reveal the regulatory role of miR-210-3p in bladder cancer progression. Exogenous overexpression of miR-210-3p inhibited the proliferation, migration and invasion of bladder cancer cells in vitro. In addition, the nude mouse xenograft model showed that miR-210-3p over-expressing inhibited bladder cancer growth and liver metastasis whereas silencing miR-210-3p caused an opposite outcome, which is mainly regulated by targeting fibroblast growth factor receptor-like 1 (FGFRL1). We also demonstrated that the expression of FGFRL1 in bladder cancer specimens were negatively correlated with miR-210-3p level, and FGFRL1 overexpression rescued the cell proliferation and invasion inhibited by ectopic expression of miR-210-3p. Moreover, knockdown of FGFRL1 was able to mimic the cell growth and metastasis effects induced by miR-210-3p over-expressing in bladder cancer cells. Together, these results indicate that miR-210-3p plays an important role in the regulation of bladder cancer growth and metastasis in vitro and in vivo through targeting FGFRL1.

PMID: 28861329 [PubMed]

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Targeting MYC sensitizes malignant mesothelioma cells to PAK blockage-induced cytotoxicity.

Targeting MYC sensitizes malignant mesothelioma cells to PAK blockage-induced cytotoxicity.

Am J Cancer Res. 2017;7(8):1724-1737

Authors: Tan Y, Sementino E, Chernoff J, Testa JR

Abstract
Clinical management of malignant mesothelioma (MM) is very challenging due to marked resistance of this tumor to chemotherapy. Various mechanisms lead to a less than ideal drug concentration inside of MM cells, diminishing cytotoxicity. Consequently, single cytotoxic drugs achieve very modest response rates in MM patients, and combination regimens using standard and novel therapies have achieved only limited improvement in overall survival. Here, we demonstrate that MYC has either proliferative or pro-survival effects in MM cells during normal or stressed conditions, respectively. A MYC inhibitor 10058-F4 reduced MM cell proliferation via down regulation of cyclin D. Under serum starvation conditions, MM cells became quiescent, and the addition of MYC inhibitors triggered apoptosis in the resting MM cells. We also found that high concentrations of the PAK inhibitor PF3758309 killed MM cells, but the drug had only cytostatic effects at lower concentrations. These quiescent cells underwent apoptosis upon pharmacological inhibition of MYC. A novel MYC inhibitor KJ-Pyr-9 and a newer PAK inhibitor, FRAX597, also demonstrated marked cytotoxic cooperativity. Collectively, these findings demonstrate that targeting of MYC can sensitize MM cells and provide rationale for inhibition of MYC and PAK as a novel combinatory regimen for the treatment of this otherwise therapy-resistant, clinically incurable malignancy.

PMID: 28861328 [PubMed]

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A human recombinant IL-7/HGFβ hybrid cytokine enhances antitumor immunity in mice.

A human recombinant IL-7/HGFβ hybrid cytokine enhances antitumor immunity in mice.

Am J Cancer Res. 2017;7(8):1714-1723

Authors: Han F, Hu R, Su M, Yu Y, Yang H, Lai L

Abstract
We purified a hybrid cytokine that contains interleukin-7 (IL-7) and the beta-chain of hepatocyte growth factor (HGFβ) from a unique long-term murine bone marrow culture system. We have cloned and expressed the human form of IL-7/HGFβ in which the IL-7 and HGFβ genes are connected by a flexible linker to produce a single-chain recombinant human IL-7/HGFβ protein (hrIL-7/HGFβ). To determine whether hrIL-7/HGFβ has antitumor activity, we injected this hybrid cytokine into melanoma and colon cancer animal models, and then assessed the local tumor growth and tumor metastasis. We show here that in vivo administration of hrIL-7/HGFβ significantly inhibited the growth and metastasis of malignant melanoma and colon cancer in mice. The antitumor activity was involved in a marked increase in the number of tumor-infiltrating CD4(+) and CD8(+) T cells and activated dendritic cells. The immunological mechanism by which hrIL-7/HGFβ inhibits tumor growth was confirmed by its inability to inhibit tumor growth in vitro and in immunodeficient mice. Furthermore, immune cells from hrIL-7/HGFβ-treated cancer-bearing mice can be adoptively transferred into naïve mice to resist same tumor cell challenge. Therefore, hrIL-7/HGFβ has potential applications in the treatment of cancer patients.

PMID: 28861327 [PubMed]

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LncRNA SNHG5 regulates imatinib resistance in chronic myeloid leukemia via acting as a CeRNA against MiR-205-5p.

LncRNA SNHG5 regulates imatinib resistance in chronic myeloid leukemia via acting as a CeRNA against MiR-205-5p.

Am J Cancer Res. 2017;7(8):1704-1713

Authors: He B, Bai Y, Kang W, Zhang X, Jiang X

Abstract
Imatinib resistance has become a major obstacle for the treatment of chronic myeloid leukemia (CML). The present study aimed to investigate the effects of the long non-coding RNA, SNHG5 on imatinib resistance in CML and explored the underlying mechanisms. The quantitative real-time PCR results showed that SNHG5 and ABCC2 expressions were up-regulated in the isolated peripheral blood cells of the CML patients when compared with healthy controls, and SNHG5 expression levels was positively correlated with ABCC2 in CML patients. In vitro studies showed that the expressions of SNHG5 and ABCC2 were up-regulated in imatinib resistant cells (K562-R) when compared to K562 cells. Bioinformatics analysis showed the interaction between SNHG5 and miR-205-5p, which was further confirmed by luciferase reporter assay and RNA immune-precipitation in K562 cells. Overexpression of SNHG5 suppressed the expression of miR-205-5p and the expression of SNHG5 was negatively correlated with the miR-205-5p expression in CML patients. In addition, ABCC2 was predicted as a downstream target of miR-205-5p, which was further confirmed by the luciferase reporter assay in K562-R cells, and overexpression of miR-205-5p suppressed the expression of ABCC2 in K562-R cells. In vitro functional assay showed that overexpression of SNHG5 in K562 cells increased imatinib resistance and knock-down of SNHG5 reduced the imatinib resistance in K562-R cells. Further experiments showed that SNHG5 promotes imatinib resistance through regulating ABCC2. Taken together, SNHG5 promotes imatinib resistance in CML via acting as a competing endogenous RNA against miR-205-5p.

PMID: 28861326 [PubMed]

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The efficacy of combination therapy with oncolytic herpes simplex virus HF10 and dacarbazine in a mouse melanoma model.

The efficacy of combination therapy with oncolytic herpes simplex virus HF10 and dacarbazine in a mouse melanoma model.

Am J Cancer Res. 2017;7(8):1693-1703

Authors: Tanaka R, Goshima F, Esaki S, Sato Y, Murata T, Nishiyama Y, Watanabe D, Kimura H

Abstract
Advanced melanoma has long been treated with chemotherapy using cytotoxic agents like dacarbazine (DTIC), but overall survival rates with these drugs have been generally low. Recently, immunoregulatory monoclonal antibodies and molecularly targeted therapy with a BRAF inhibitor and/or a MEK inhibitor, have been used to treat malignant melanoma and have improved the survival rate of patients with advanced melanoma. However, high prices of these drugs are problematic. In this study, we evaluated the oncolytic efficacy of HF10, an attenuated, replication-competent HSV, with DTIC in immunocompetent mice model of malignant melanoma. For in vitro studies, cytotoxicity assays were conducted in clone M3 mouse melanoma cells. For the in vivo studies, subcutaneous melanoma models were prepared in DBA/2 mice with clone M3 cells, and then HF10 was intratumorally inoculated with/without intraperitoneal DTIC injection. The efficacy of the therapies was evaluated by survival, growth of subcutaneous tumor, and histopathological and immunological analyses. Both HF10 infection and DTIC treatment showed cytotoxic effects in melanoma cells, but combination treatment with HF10 and DTIC showed a rapid and strong cytotoxic effect compared with monotherapy. In the subcutaneous melanoma model, intratumoral HF10 inoculation significantly inhibited tumor growth. HF10 also inhibited the growth of non-inoculated contralateral tumors when it was injected into the ipsilateral tumors of mice. In histologic and immunohistochemical analysis, tumor lysis and inflammatory cell infiltration were observed after intratumoral HF10 inoculation. When mice were treated with HF10 and DTIC, the combination therapy induced a robust systemic anti-tumor immune response and prolonged survival. IFN-γ secretion from splenocytes of the HF10-DTIC combination therapy group showed more IFN-γ secretion than did the other groups. These data showed the efficacy of HF10 and DTIC combination therapy in a mouse melanoma model.

PMID: 28861325 [PubMed]

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MicroRNA-1179 inhibits glioblastoma cell proliferation and cell cycle progression via directly targeting E2F transcription factor 5.

MicroRNA-1179 inhibits glioblastoma cell proliferation and cell cycle progression via directly targeting E2F transcription factor 5.

Am J Cancer Res. 2017;7(8):1680-1692

Authors: Xu X, Cai N, Zhi T, Bao Z, Wang D, Liu Y, Jiang K, Fan L, Ji J, Liu N

Abstract
Glioblastoma multiforme (GBM) is an extraordinary aggressive disease that requires more effective therapeutic options. In the past few years, many microRNAs (miRNAs) have been demonstrated to have important roles in promoting GBM progression. However, little is known about the role of miR-1179 in GBM. In the present study, we found that miR-1179 was significantly downregulated in glioma tissues and cell lines. Functional experiments showed that introduction of miR-1179 dramatically suppressed GBM cell proliferation and cell cycle progression. Importantly, treatment of miR-1179 strongly inhibited tumor growth in a subcutaneous GBM model. Further studies showed that E2F transcription factor 5 (E2F5), a key transcription factor that controls cell cycle transition, was a direct target of miR-1179. Silencing of E2F5 inhibited the proliferative ability of GBM cells and induces cell cycle arrest, which were consistent with the effects of miR-1179 overexpression. More importantly, reintroduction of E2F5 into GBM cells reversed the tumor-suppressive function of miR-1179. Finally, we demonstrated that miR-1179 expression was negatively correlated with E2F5 messenger RNA (mRNA) levels in high-grade gliomas. Our findings provide new insights into the role of miR-1179 in the progression of GBM, and implicate the potential application of miR-1179 in GBM therapy.

PMID: 28861324 [PubMed]

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POU2F1 promotes growth and metastasis of hepatocellular carcinoma through the FAT1 signaling pathway.

POU2F1 promotes growth and metastasis of hepatocellular carcinoma through the FAT1 signaling pathway.

Am J Cancer Res. 2017;7(8):1665-1679

Authors: Zhu HY, Cao GY, Wang SP, Chen Y, Liu GD, Gao YJ, Hu JP

Abstract
Increasing evidence suggests that POU domain class 2 transcription factor 1 (POU2F1) participates in carcinogenesis and cancer progression via promotion of cell proliferation and metastasis; however, the functional role of POU2F1 in hepatocellular carcinoma (HCC) is largely unknown. In this study, we determined that POU2F1 was significantly up-regulated in HCC tumor tissue and cell lines. We demonstrated that POU2F1 over-expression promoted HCC cell proliferation, colony formation, migration, and invasion, while silencing of POU2F1 inhibited these malignant phenotypes. In vivo experiments indicated that knockdown of POU2F1 inhibited HCC cell metastasis and xenograft growth, whereas ectopic expression of POU2F1 promoted these cellular functions. Microarray analysis suggests that FAT atypical cadherin 1 (FAT1) can function downstream of POU2F1. Functionally, we demonstrated that POU2F1 knockdown induced growth suppression and metastasis inhibition of HCC cells and inactivated the FAT1 pathway, indicating that POU2F1 is a potential novel therapeutic target in HCC.

PMID: 28861323 [PubMed]

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14-3-3ζ loss impedes oncogene-induced mammary tumorigenesis and metastasis by attenuating oncogenic signaling.

14-3-3ζ loss impedes oncogene-induced mammary tumorigenesis and metastasis by attenuating oncogenic signaling.

Am J Cancer Res. 2017;7(8):1654-1664

Authors: Joshi S, Yang J, Wang Q, Li P, Wang H, Zhang Q, Xiong Y, Pickering BF, Parker-Thornburg J, Behringer RR, Yu D

Abstract
The 14-3-3ζ protein belongs to the 14-3-3 family of regulatory eukaryotic proteins that modulate signaling by binding to wide variety of signaling molecules. 14-3-3ζ expression is amplified in over 40% breast cancer patients and is associated with a poor prognosis. Various in vitro and xenograft models have suggested that attenuating 14-3-3ζ expression may provide therapeutic benefits but there has been no study looking at tumor onset and metastasis in breast cancer mouse models with a targeted deletion of 14-3-3ζ. We generated a 14-3-3ζ knockout mouse model to characterize the role of 14-3-3ζ in breast cancer progression. Crossing 14-3-3ζ-/- mice with MMTV-PyMT and MMTV-Neu transgenic mice revealed that loss of 14-3-3ζ prolonged tumor latency and reduced lung metastasis as compared to MMTV-PyMT and MMTV-Neu mice. Mechanistically, loss of 14-3-3ζ suppressed tumor proliferation and angiogenesis and promoted apoptosis by suppressing the Akt and Erk pathway and upregulated the expression of the tumor suppressor p53. Our results provide evidence showing that attenuating 14-3-3ζ expression/activity in mammary tumors can provide a therapeutic benefit.

PMID: 28861322 [PubMed]

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FoxC1 promotes epithelial-mesenchymal transition through PBX1 dependent transactivation of ZEB2 in esophageal cancer.

FoxC1 promotes epithelial-mesenchymal transition through PBX1 dependent transactivation of ZEB2 in esophageal cancer.

Am J Cancer Res. 2017;7(8):1642-1653

Authors: Zhu X, Wei L, Bai Y, Wu S, Han S

Abstract
Esophageal cancer (EC) was one of the most lethal malignancies worldwide with intricate mechanisms. Here we reported that Forkhead box C1 (FoxC1), a member of the forkhead family transcription factors, was up-regulated in EC tissues and cell lines in comparison with controls. FoxC1 levels were negatively correlated with tumor stage, lymph node metastasis and survival status of EC patients. Knockdown of FoxC1 inhibited the proliferation, colony formation and epithelial-mesenchymal transition (EMT) of EC cells, while overexpression of FoxC1 promoted these biological behaviors. Mechanically, serial deletion and chromatin immunoprecipitation assays showed that ZEB2, a well-reported transcriptional suppressor of E-cadherin, was a direct transcriptional target of FoxC1. Moreover, FoxC1 was recruited to the ZEB2 promoter by its interaction with the pioneer transcription factor pre-B-cell leukemia homeobox 1 (PBX1). Importantly, significant correlation between levels of FoxC1 and ZEB2 was observed in EC tissues and the two proteins could be used as prognostic biomarkers together. Hence, our results revealed a critical role of FoxC1 in the EMT process of EC and uncovered a novel mechanism for the regulation of ZEB2-E-cadherin axis in EC.

PMID: 28861321 [PubMed]

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CS1 (SLAMF7, CD319) is an effective immunotherapeutic target for multiple myeloma.

CS1 (SLAMF7, CD319) is an effective immunotherapeutic target for multiple myeloma.

Am J Cancer Res. 2017;7(8):1637-1641

Authors: Malaer JD, Mathew PA

Abstract
CS1 (also known as CD319, CRACC and SLAMF7) was identified as an NK cell receptor regulating immune functions. It is also expressed on B cells, T cells, Dendritic cells, NK-T cells, and monocytes. CS1 is overexpressed in multiple myeloma and makes it a target for immunotherapy. A humanized anti-CS1 antibody, Elotuzumab or Empliciti has shown promising results in clinical studies. This review focuses on the biology of CS1 in NK and other hematopoietic cells and multiple myeloma. Anti-CS1 mAb can activate natural cytotoxicity of NK cells as well as enhance ADCC (antibody-dependent cell-mediated cytotoxicity) and thus makes an effective target for immunotherapy of MM.

PMID: 28861320 [PubMed]

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Steroid hormone receptors as prognostic markers in breast cancer.

Steroid hormone receptors as prognostic markers in breast cancer.

Am J Cancer Res. 2017;7(8):1617-1636

Authors: Louie MC, Sevigny MB

Abstract
Despite the existence of many promising anti-cancer therapies, not all breast cancers are equally treatable, due partly to the fact that focus has been primarily on a few select breast cancer biomarkers- notably ERα, PR and HER2. In cases like triple negative breast cancer (ERα(-), PR(-), and HER2(-)), there is a complete lack of available biomarkers for prognosis and therapeutic purposes. The goal of this review is to determine if other steroid receptors, like ERβ and AR, could play a prognostic and/or therapeutic role. Data from various in vitro, in vivo, and clinical breast cancer studies were examined to analyze the presence and function of ERβ, PR, and AR in the presence and absence of ERα. Additionally, we focused on studies that examined how expression of the various steroid receptor isoforms affects breast cancer progression. Our findings suggest that while we have a solid understanding of how these receptors work individually, how they interact and behave in the presence and absence of other receptors requires further research. Furthermore, there is an incomplete understanding of how the various steroid receptor isoforms interact and impact receptor function and breast cancer progression, partly due to the difficulty in detecting all the various isoforms. More large-scale clinical studies must be made to analyze systematically the expression of steroid hormone receptors and their respective isoforms in breast cancer patients in order to determine how these receptors interact with each other and in turn affect cancer progression.

PMID: 28861319 [PubMed]

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Self Made Xeno-pericardial Aortic Tubes to Treat Native and Aortic Graft Infections

Publication date: Available online 2 September 2017
Source:European Journal of Vascular and Endovascular Surgery
Author(s): Salome Weiss, Eva-Luca Tobler, Hendrik von Tengg-Kobligk, Vladimir Makaloski, Daniel Becker, Thierry P. Carrel, Jürg Schmidli, Thomas R. Wyss
ObjectivesThe most appropriate material for reconstruction of the aorta for native or graft infection remains a matter for debate. This study examines the mid-term outcome of patients and graft durability after in situ aortic reconstruction with self made bovine pericardial tube grafts.MethodsThis was a retrospective analysis of all patients who underwent in situ aortic reconstruction using self made bovine pericardial tube grafts between January 2008 and December 2015 at a tertiary referral centre. Peri-operative and mid-term outcomes including mortality and re-infection were analysed at the end of January 2017. Available follow-up imaging was reviewed to assess graft durability.ResultsBovine pericardial aortic tube grafts were used in 35 patients (86% male) with a median age of 69 years (range 38–84) to reconstruct the ascending aorta or the aortic arch (7), the descending (7), the thoraco-abdominal (7), or the abdominal (14) aorta. Twelve patients (34%) were treated for infection of the native aorta and 23 (66%) for prosthetic graft infection. Twenty-two patients (63%) underwent emergency surgery. Thirty day mortality was 31% (n = 11). Additionally, six patients died during follow-up after a median of 33 months (range 3–70). For the remaining patients, mean follow-up was 48 months (± 26) with a mean Follow-Up Index of 0.98 ± 0.08. There were no readmissions or re-operations for re-infection or graft related complications. Follow-up imaging showed no signs of graft degeneration after a median of 15 months (range 3–68).ConclusionsSurgical treatment of native and aortic graft or endograft infection remains high risk. Self made bovine pericardial tube grafts for in situ reconstruction are a promising option offering many advantages. Despite high early mortality rates, early radiological and mid-term clinical results are good. Definitive eradication of the infection seems feasible after in situ insertion of xeno-pericardial material for aortic repair.

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Outcome after Turndown for Elective Abdominal Aortic Aneurysm Surgery

Publication date: Available online 2 September 2017
Source:European Journal of Vascular and Endovascular Surgery
Author(s): Joshua D. Whittaker, Lewis Meecham, Virginia Summerour, Sheirin Khalil, Georgia Layton, Marianne Yousif, Adrian Jennings, Micheal Wall, Jeremy Newman
ObjectivesThe aim was to assess the survival of patients who had been turned down for repair of an abdominal aortic aneurysm (AAA) and to examine the factors influencing this.MethodsThis was a retrospective observational study of a prospectively maintained database of all patients turned down for AAA intervention by the Black Country Vascular Network multidisciplinary team (MDT) from January 2013 to December 2015. Data on AAA size, cardiopulmonary exercise testing (CPET) and cause of death were recorded.ResultsThere were 112 patients. The median age at turndown was 83.9 years (IQR 10.2 years). The median AAA size at turndown was 63 mm (IQR 16.7 mm). The median follow-up time after turndown was 324 days (IQR 537.5 days). Sixty-four patients (57.1%) were deceased after 2 years, with a median survival time of 462 days (IQR 579 days). Patients who died had a significantly larger AAA dimension (median 65 mm, IQR 18.5 mm) than those surviving to date (median 59 mm, IQR 10 mm, p = .004). Using Cox regression analysis, the probability of 1 year survival in the whole population was 0.614. The probability of 2 year survival was 0.388. When accounting for age, gender, AAA dimension, and British Aneurysm Repair risk score, no factors had significant influence over survival. Of the 64 deceased patients, 30 had an accessible cause of death: 36.7% of these were due to ruptured AAAs. There was no significant difference in AAA size between those dying of ruptures and those dying of other causes (p = .225, mean 74 mm and 67 mm respectively).ConclusionsBeing turned down for AAA repair carries a significant short-term risk of mortality. Those turned down for repair carried significant levels of comorbid disease but no factors considered were found to be independently predictive of the length of survival.

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How to Write a High Quality Multiple Choice Question (MCQ): A Guide for Clinicians

Publication date: Available online 1 September 2017
Source:European Journal of Vascular and Endovascular Surgery
Author(s): P.A. Coughlin, C.R. Featherstone
Despite the variety of assessment tools available, multiple choice questions (MCQs) still play an integral part in examinations at both a national and speciality board level. MCQs have a number of methodological advantages yet their strength is related to the quality of the question posed. Specifically, there has been a move towards the MCQ testing a taxonomically higher order concept of integration-interpretation and problem solving. This paper focuses on question development and the potential pitfalls to avoid.

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The effect of light-emitting diode (590/830 nm)−based low-level laser therapy on posttraumatic edema of facial bone fracture patients

Posttraumatic edema in facial bone fracture patients may interfere with the operation field and delay the schedule. Thus, swiftly reducing the edema alleviates patient discomfort and advances the operation date. Ice packing and compression bandages are often used for such a purpose, but such methods are often inconvenient for the face. In this study, we aim to analyze the effect of light-emitting diode (LED) (590/830 nm)−based low-level laser therapy (LLLT) in posttraumatic edema in facial bone fracture patients.

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Utility of intraoperative frozen sections in surgical decision making for acute invasive fungal rhinosinusitis.

Utility of intraoperative frozen sections in surgical decision making for acute invasive fungal rhinosinusitis.

Am J Rhinol Allergy. 2017 Sep 01;31(5):341

Authors: Amedee RG

PMID: 28859714 [PubMed - in process]

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Draf III frontal sinus surgery: "How I do it".

Draf III frontal sinus surgery: "How I do it".

Am J Rhinol Allergy. 2017 Sep 01;31(5):338-340

Authors: Carney AS

Abstract
BACKGROUND: The Draf III approach to the frontal sinus can be used during revision endoscopic sinus surgery for chronic rhinosinusitis and to provide access for tumor resection, mucoceles, and repair of cerebrospinal fluid leaks.
OBJECTIVE: To describe a simple and safe way to perform a Draf III approach by using the "outside-in" approach.
METHODS: By using a 0° endoscope and a single 15°, 5-mm, coarse diamond burr, the main steps of the procedure are the following: (1) elevation of the mucosal flaps and creation of the septal window, (2) drilling out the frontal beak, (3) creation of neo-ostium and removal of the interfrontal septum, (4) joining the neo-ostium with the frontal recesses, (5) smoothing off the cavity and lowering of the "frontal T," and (6) use of mucosal flaps and grafts to cover exposed bone.
CONCLUSION: This approach is a quick and easy way to perform a Draf III, and reduces operative time and minimizes complications.

PMID: 28859713 [PubMed - in process]

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Primary endoscopic endonasal dacryocystorhinostomy for pediatric nasolacrimal duct obstruction: A systematic review.

Primary endoscopic endonasal dacryocystorhinostomy for pediatric nasolacrimal duct obstruction: A systematic review.

Am J Rhinol Allergy. 2017 Sep 01;31(5):328-333

Authors: Saniasiaya J, Abdullah B, Husain S, Wang Y, Wan Mohammad Z

Abstract
BACKGROUND: Epiphora secondary to nasolacrimal duct obstruction is common in the pediatric age group. The mainstay treatment among these young patients has been conservative. Once epiphora becomes recalcitrant, however, an external or an endonasal approach is considered.
OBJECTIVE: Endoscopic dacryocystorhinostomy (EDCR) entails creating an opening from the lacrimal sac directly into the nasal cavity to counteract nasolacrimal duct obstruction. We reviewed the literature to determine the effectiveness and the safety of primary EDCR to treat pediatric nasolacrimal duct obstruction.
METHOD: A literature search was conducted by using a number of medical literature data bases for the period from 1995 to 2016. The following search words were used either individually or in combination: epiphora, nasolacrimal duct obstruction, endoscopic dacryocystorhinostomy, powered endoscopic dacryocystorhinostomy, laser-assisted endoscopic dacryocystorhinostomy, children, congenital, acquired, presaccal obstruction, and postsaccal obstruction. In addition, a few articles were identified based on the experience and information provided by the senior authors (B.A., S.H., D.Y.W.). The search was conducted over a 1-month period (January 2017). Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and the Cochrane Handbook for Systematic Reviews of Interventions were followed when possible.
RESULTS: Only 10 original clinical research articles were selected based on our objectives and selection criteria. All the studies were at level of evidence III: nonrandomized and noncomparative prospective or retrospective case series. Altogether, 313 patients with ages that ranged from 4 months to 18 years were enrolled. A total of 352 EDCRs were performed that were either single sided (n = 313) or bilateral (n = 39). The most common causes of the obstruction were classified as congenital, followed by idiopathic, and then acquired. A meta-analysis was not performed because of the heterogeneity of the patient groups and variability of the methods used to measure outcomes.
CONCLUSION: Analysis of the results indicated that EDCR was an effective, safe therapeutic approach to treating nasolacrimal duct obstruction in pediatric patients. It should be considered as an alternative procedure to external dacryocystorhinostomy after a failed conservative treatment.

PMID: 28859711 [PubMed - in process]

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The effect of closed septorhinoplasty on nasal functions and on external and internal nasal valves: A prospective study.

The effect of closed septorhinoplasty on nasal functions and on external and internal nasal valves: A prospective study.

Am J Rhinol Allergy. 2017 Sep 01;31(5):323-327

Authors: Pecorari G, Riva G, Bianchi FA, Cavallo G, Revello F, Bironzo M, Verzè L, Garzaro M, Ramieri G

Abstract
BACKGROUND: Because nasal function and shape are so closely intertwined, quantitative assessments can better define their relationship and how they are affected by septorhinoplasty.
OBJECTIVE: The aim of this prospective study was to perform an analysis of the nasal airflow resistances and a three-dimensional (3D) evaluation of the soft-tissue changes after closed septorhinoplasty.
METHODS: Before surgery (T0) and 6 months after closed septorhinoplasty (T1), 30 patients underwent symptoms evaluation by means of the Italian version of the Nasal Obstruction Symptom Evaluation scale, endoscopic fiberoptic nasal examination, and visual analog scale for subjective assessment of nasal obstruction. Nasal airflow resistances were investigated with active anterior active rhinomanometry. A 3D laser scanner was used to evaluate facial soft-tissues, with specific nasal points and angles.
RESULTS: Subjective nasal obstruction decreased. Anterior active rhinomanometry demonstrated a reduction in total inspiratory and expiratory resistances between T0 and T1 but without statistical significance. The significance was still absent after decongestion, excluding turbinate hypertrophy as a cause of failed objective amelioration of nasal resistance. Facial laser scanning showed statistically significant reduction of the superior nasal width and superior alar angle, and a weak negative correlation between the superior alar angle and nasal resistances.
CONCLUSION: The absence of objective reduction of nasal airflow resistances could be the result of concurrent surgery on nasal septum and nasal valve. In particular, the ameliorating effect on nasal airflow resistances is counterbalanced by the worsening effect of the narrowing of nasal valve.

PMID: 28859710 [PubMed - in process]

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Erratum.

Erratum.

Am J Rhinol Allergy. 2017 Sep 01;31(5):322

Authors:

PMID: 28859709 [PubMed - in process]

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The effect of olfactory training on the odor threshold in patients with traumatic anosmia.

The effect of olfactory training on the odor threshold in patients with traumatic anosmia.

Am J Rhinol Allergy. 2017 Sep 01;31(5):317-322

Authors: Jiang RS, Twu CW, Liang KL

Abstract
BACKGROUND: Olfactory training is a novel intervention that has been used to treat olfactory dysfunction. This study attempted to investigate the effect of olfactory training in patients with traumatic anosmia.
METHODS: Patients with a clear history of anosmia after experiencing a head injury and whose phenyl ethyl alcohol (PEA) odor detection thresholds were -1 after steroid and zinc treatment were included. The patients were randomly divided into two groups, with patients in one group given a bottle of PEA and those in another group given a bottle of mineral oil for 3-month olfactory training. All the patients were followed up with a PEA threshold test and the traditional Chinese version of the University of Pennsylvania Smell Identification Test (UPSIT-TC). Magnetic resonance imaging was performed to measure the volume of the olfactory bulbs. Any patient whose PEA threshold result was below -1.01 or whose UPSIT-TC score increased four or more points was considered to have shown improvement in their olfactory function.
RESULTS: Forty-two patients received PEA olfactory training, whereas 39 received olfactory training with mineral oil. The improvement of PEA thresholds function was observed in 10 patients within the PEA group and in 2 patients in the mineral oil group. The frequency of improvement of threshold within the PEA group was significantly higher than that of the mineral oil group. Neither olfactory bulb volume nor UPSIT-TC score was significantly different between the two groups.
CONCLUSION: Our results showed that olfactory training with PEA can improve PEA odor threshold levels in patients with traumatic anosmia.

PMID: 28859708 [PubMed - in process]

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Quality-of-life outcomes in patients who underwent subcutaneous immunotherapy and sublingual immunotherapy in a real-world clinical setting.

Quality-of-life outcomes in patients who underwent subcutaneous immunotherapy and sublingual immunotherapy in a real-world clinical setting.

Am J Rhinol Allergy. 2017 Sep 01;31(5):310-316

Authors: Schwanke T, Carragee E, Bremberg M, Reisacher WR

Abstract
OBJECTIVE: To compare changes in quality of life (QOL) that resulted from sublingual immunotherapy (SLIT) and subcutaneous immunotherapy (SCIT) in a real-world clinical setting.
BACKGROUND: SLIT is established as a viable alternative to SCIT for the treatment of allergic rhinitis. Although comparative trials are increasingly available, few studies have examined QOL outcomes between these two treatments.
METHODS: One hundred and five participants who underwent immunotherapy for airborne allergies were enrolled in this prospective, single-center study. Forty participants completed the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) at initiation of therapy, after 6 months, and after 1 year of therapy. Only patients with complete time points were included in the ultimate analysis. Twenty-nine of these participants underwent SCIT and 11 underwent SLIT. The effects of age, sex, and asthma history were also examined.
RESULTS: The participants in both groups demonstrated improvements in QOL regarding allergic rhinoconjunctivitis over the study period. However, the change in the RQLQ score from both baseline to 6 months and baseline to 1 year was only statistically significant in the SCIT group (p = 0.002, 6 months and 1 year). The participants in the SCIT group also demonstrated statistically significant improvement from baseline to 1 year in the specific domains of practical and emotional functioning, nasal symptoms, non-nasal/eye symptoms, and sleep. After 1 year, both SCIT and SLIT demonstrated a minimally important difference from baseline in the overall RQLQ score. Age <35 years in the SCIT group had a significant positive impact on QOL improvement (p = 0.038).
CONCLUSION: Although improvements in QOL were noted in both groups, changes in overall scores and the majority of domains only achieved statistical significance in the SCIT group. A small study population and difficulties adhering to immunotherapy dosing schedules in the SLIT group may be contributing factors.

PMID: 28859707 [PubMed - in process]

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Outcomes of sinonasal squamous cell carcinoma with and without association of inverted papilloma: A multi-institutional analysis.

Outcomes of sinonasal squamous cell carcinoma with and without association of inverted papilloma: A multi-institutional analysis.

Am J Rhinol Allergy. 2017 Sep 01;31(5):305-309

Authors: Lobo BC, D'Anza B, Farlow JL, Tang D, Woodard TD, Ting JY, Sindwani R

Abstract
INTRODUCTION: Sinonasal squamous cell carcinoma (SCC) accounts for <1% of all malignancies but represents 70% of sinonasal cancer. Up to 10% of SCCs are associated with inverted papilloma (IPSCC). Studies that compare patients, treatment, and outcomes of SCC and IPSCC are absent in the literature.
METHODS: A retrospective review of patients with SCC and those with IPSCC at Cleveland Clinic and Indiana University from 1995 to 2015. The records were analyzed for demographics, tumor characteristics, treatment, and outcomes.
RESULTS: The study comprised 117 patients with SCC, of whom, 29 had IPSCC. The mean age at diagnosis was similar: 63 and 64 years for patients with SCC and patients with IPSCC, respectively; with female patients representing 36% and 34%, respectively (p > 0.99).Smokers represented 64% of the patients with SCC and 55% of patients with IPSCC (p = 0.3); excessive alcohol intake was noted in 16% of the patients with SCC and 21% of the patients with IPSCC (p = 0.56).The maxillary sinus was most commonly involved, followed by the nasal cavity (51% versus 35% SCC, 45% versus 38% IPSCC). Frontal ethmoid and sphenoid sinuses contained primary tumors only in patients with SCC. Upfront treatment was surgery in 84% of patients with SCC and 97% of patients with IPSCC (p = 0.18); 68 and 55% received radiation, respectively, and 25 and 21% received chemotherapy, respectively.Overall survival averaged 5.5 and 3.4 years for patients with SCC and patients with IPSCC, respectively (p = 0.12); disease-free survival was 4.8 and 2.9 years, respectively (p = 0.18). Nodal metastasis was more likely in patients with SCC (18 versus 0%; p = 0.02). When divided into high- and low-stage disease: more common nodal metastases were demonstrated in high-stage SCC than in low-stage disease (p = 0.03). Overall survival was decreased between high- and low-grade disease but not when subdivided between SCC and IPSCC.
CONCLUSION: Although SCC with and without IP association are considered different diseases, their demographics and outcomes seem similar. Nodal metastasis was noted to be higher in the SCC cohort, which may indicate different tumor biology. Further study is warranted.

PMID: 28859706 [PubMed - in process]

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Immunoglobulin G4 sinusitis in association with aspirin-exacerbated respiratory disease.

Immunoglobulin G4 sinusitis in association with aspirin-exacerbated respiratory disease.

Am J Rhinol Allergy. 2017 Sep 01;31(5):302-304

Authors: Johal K, Welch K, Peters A

Abstract
BACKGROUND: Immunoglobulin G4 (IgG4) related disease is a systemic inflammatory disease characterized by tumor-like tissue infiltration with IgG4 positive (IgG4+) plasma cells. Aspirin-exacerbated respiratory disease (AERD) is defined as asthma, chronic rhinosinusitis with nasal polyposis, and hypersensitivity to cyclooxygenase-1 inhibitors.
OBJECTIVE: We described a case of a non-smoking 61-year-old male with prior NSAID sensitivity who presented with a 1-year history of left eye proptosis associated with chronic nasal symptoms, ultimately identified as concurrent AERD and IgG4 sinusitis.
METHODS: The patient was evaluated in the clinic and diagnosed by using clinical, radiographic, and surgical biopsy findings.
RESULTS: Although initial concern was greatest for malignancy, a biopsy specimen confirmed the presence of a dense lymphoplasmacytic infiltrate and storiform fibrosis, associated with increased IgG4+ plasma cells. Therefore, IgG4-related disease (RD) was identified in this patient with AERD.
CONCLUSION: Shared type II inflammation may be responsible for the coexistence of IgG4-RD and AERD as observed in our patient. Health care workers must be cognizant of the simultaneous presentation of both IgG4-RD and AERD.

PMID: 28859705 [PubMed - in process]

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An update on the epidemiology of aspirin-exacerbated respiratory disease.

An update on the epidemiology of aspirin-exacerbated respiratory disease.

Am J Rhinol Allergy. 2017 Sep 01;31(5):299-301

Authors: White AA

Abstract
BACKGROUND: Aspirin-exacerbated respiratory disease (AERD) is a disorder of nasal polyposis, asthma, and hypersensitivity respiratory reactions when on systemic cyclooxygenase 1 blockade.
METHODS: AERD warrants specific evaluation as an endotype of asthma and chronic sinus disease due to unique therapeutic opportunities. Currently, aspirin therapy is uniquely beneficial as an anti-inflammatory therapy in AERD, with multiple additional therapies currently in early to late clinical studies, which might also show exceptional benefit in AERD.
RESULTS: Yet, given the lack of a simple diagnostic test, opportunities to identify patients with AERD are still frequently neglected.
CONCLUSION: Identifying the prevalence and population characteristics necessary to determine appropriate candidates in whom to perform diagnostic aspirin challenge remains critically important and was the purpose of this article.

PMID: 28859704 [PubMed - in process]

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Sinus bacteriology in patients with cystic fibrosis or primary ciliary dyskinesia: A systematic review.

Sinus bacteriology in patients with cystic fibrosis or primary ciliary dyskinesia: A systematic review.

Am J Rhinol Allergy. 2017 Sep 01;31(5):293-298

Authors: Møller ME, Alanin MC, Grønhøj C, Aanæs K, Høiby N, von Buchwald C

Abstract
BACKGROUND: A correlation exists between the microbial flora of the upper and lower airways in patients with cystic fibrosis (CF) or with primary ciliary dyskinesia (PCD). The sinuses can function as a bacterial reservoir where gram-negative bacteria adapt to the airways and repeatedly are aspirated to and colonize the lungs according to the theory of the united (unified) airways. Whereas the pattern of bacterial flora in the lower airways has been extensively studied, the upper airways have drawn limited attention.
OBJECTIVE: Our aim was to review the literature that reported bacterial flora in the sinuses and nasal cavities of patients with CF or PCD.
METHODS: A number of medical literature data bases were systematically searched between January 1960 and July 2016. We applied the following inclusion criteria: a minimum of one case of PCD (or Kartagener syndrome) or CF, and microbiology analyses from the nose or paranasal sinuses.
RESULTS: We included 46 studies (1823 patients) from 16 countries. Staphylococcus aureus was found in 30% of the noses and sinuses of patients with CF. Other common bacteria found included Pseudomonas aeruginosa, coagulase negative staphylococci, and Haemophilus influenzae. In PCD, H. influenzae was the most common bacteria (28%), followed by Streptococcus pneumoniae and P. aeruginosa. If studies that included nonsurgical swab and blowing samples were excluded, then P. aeruginosa was the most common bacterium in patients with CF (34%) and in patients with PCD (50%), followed by S. aureus and H. influenza.
CONCLUSION: S. aureus, P. aeruginosa, coagulase negative staphylococci, and H. influenzae dominated in the upper airways of patients with CF. In patients with PCD, H. influenzae, S. pneumoniae, and P. aeruginosa dominated. When studies that included swab and blowing samples were excluded, P. aeruginosa was the most common bacterium in both groups. Direct comparisons among the studies were restricted due to very heterogeneous methods, and a better standardization of procedures and outcomes is needed.

PMID: 28859703 [PubMed - in process]

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Promotion of olfactory receptor neuron differentiation of olfactory neuroepithelial cells by using chitosan solution.

Promotion of olfactory receptor neuron differentiation of olfactory neuroepithelial cells by using chitosan solution.

Am J Rhinol Allergy. 2017 Sep 01;31(5):289-292

Authors: Li ST, Young TH, Lin CF, Huang TW

Abstract
BACKGROUND: Olfactory dysfunction significantly influences patients' quality of life. Chitosan has been reported to support neuron and Schwann cell growth and even leads to orient axonal growth. However, researchers have yet to explore whether chitosan solution can promote differentiation of olfactory receptor neurons of the olfactory neuroepithelium and be used for treating olfactory dysfunction.
OBJECTIVE: To evaluate the effect of chitosan solution on the differentiation of olfactory neuroepithelial cells.
METHOD: Olfactory neuroepithelial cells were isolated from embryonic day 17 of Wistar rats and then cultured with and without soluble chitosan for 9 days. The concentration of chitosan solution was set at 0.1 mg/mL. The effects of treatment were assessed by immunocytochemistry and Western blot after culturing.
RESULTS: The morphologic analysis indicated that olfactory neuroepithelial cells treated with chitosan exhibited bipolar shape with asymmetric processes. In addition, from days 3 to 9, the expression level of βIII tubulin gradually reduced, but the expression level of olfactory marker protein significantly rose at day 9 in the chitosan groups (p < 0.05). Importantly, chitosan-treated olfactory neuroepithelial cells expressed more signal transduction apparatuses, olfactory neuron specific-G protein and adenylate cyclase 3, than those without chitosan treatment at day 9. Western blot analysis also further confirmed the results (p < 0.05).
CONCLUSION: Experimental results revealed that soluble chitosan promoted differentiation of olfactory neuroepithelial cells based on its role in olfactory receptor neuron differentiation, neurite outgrowth, and signal transduction apparatus expressions.

PMID: 28859702 [PubMed - in process]

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RNA sequencing and pathway analysis identify tumor necrosis factor alpha driven small proline-rich protein dysregulation in chronic rhinosinusitis.

RNA sequencing and pathway analysis identify tumor necrosis factor alpha driven small proline-rich protein dysregulation in chronic rhinosinusitis.

Am J Rhinol Allergy. 2017 Sep 01;31(5):283-288

Authors: Ramakrishnan VR, Gonzalez JR, Cooper SE, Barham HP, Anderson CB, Larson ED, Cool CD, Diller JD, Jones K, Kinnamon SC

Abstract
BACKGROUND: Chronic rhinosinusitis (CRS) is a heterogeneous inflammatory disorder in which many pathways contribute to end-organ disease. Small proline-rich proteins (SPRR) are polypeptides that have recently been shown to contribute to epithelial biomechanical properties relevant in T-helper type 2 inflammation. There is evidence that genetic polymorphism in SPRR genes may predict the development of asthma in children with atopy and, correlatively, that expression of SPRRs is increased under allergic conditions, which leads to epithelial barrier dysfunction in atopic disease.
METHODS: RNAs from uncinate tissue specimens from patients with CRS and control subjects were compared by RNA sequencing by using Ingenuity Pathway Analysis (n = 4 each), and quantitative polymerase chain reaction (PCR) (n = 15). A separate cohort of archived sinus tissue was examined by immunohistochemistry (n = 19).
RESULTS: A statistically significant increase of SPRR expression in CRS sinus tissue was identified that was not a result of atopic presence. SPRR1 and SPRR2A expressions were markedly increased in patients with CRS (p < 0.01) on RNA sequencing, with confirmation by using real-time PCR. Immunohistochemistry of archived surgical samples demonstrated staining of SPRR proteins within squamous epithelium of both groups. Pathway analysis indicated tumor necrosis factor (TNF) alpha as a master regulator of the SPRR gene products.
CONCLUSION: Expression of SPRR1 and of SPRR2A is increased in mucosal samples from patients with CRS and appeared as a downstream result of TNF alpha modulation, which possibly resulted in epithelial barrier dysfunction.

PMID: 28859701 [PubMed - in process]

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Expanding our research horizons.

Expanding our research horizons.

Am J Rhinol Allergy. 2017 Sep 01;31(5):281-282

Authors: Laidlaw TM

PMID: 28859700 [PubMed - in process]

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Long-term effects of tDCS on fatigue, mood and cognition in multiple sclerosis

Fatigue is frequently reported by multiple sclerosis (MS) patients and remains one of their most debilitating and difficult to manage symptoms. It constitutes a great challenge to MS caregivers especially in face of the modest efficacy and numerous side effects of available medications. Apart from fatigue, cognitive and psychiatric manifestations could affect around 65% and 95% of MS patients, respectively (Chalah and Ayache, 2017).

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The Medial Plantar Sensory Response: A Sensitive Marker of Acute Inflammatory Demyelinating Polyneuropathy

Acute Inflammatory Demyelinating Polyneuropathy (AIDP) is an acute neuropathy characterized by ascending motor weakness that is often heralded by sensory symptoms. Diagnosis is confirmed by nerve conduction studies (NCS) that demonstrate the presence of widespread demyelination changes in motor nerves (Hadden et al., 1998). Sensory nerve involvement is early and often follows a typical pattern, the sural sparing pattern (Al-Shekhlee et al., 2007). This pattern is widely accepted as a specific marker of AIDP and is particularly useful when motor changes are not yet apparent (Hiew et al., 2016).

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Prefrontal cortical responses in children with prenatal alcohol-related neurodevelopmental impairment: A functional near-infrared spectroscopy study

Fetal Alcohol Spectrum Disorders (FASDS) is a term that refers to a cluster of physical and neurobehavioral abnormalities, including facial dysmorphology, growth retardation, and disruption to brain development, that have been investigated for over four decades in human and animal model studies of prenatal alcohol exposure (PAE) (Riley et al., 2011). Although public health awareness and prevention efforts have increased as a result of these findings, recent estimates of the prevalence of Fetal Alcohol Syndrome (FAS), the most severe FASD condition, have ranged from .6 to .9 percent of live births with the full range of FASDs estimated to fall between 2.4 to 4.8 percent (May et al., 2014).

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Electrophysiological correlates of performance monitoring in binge drinking: Impaired error-related but preserved feedback processing

Binge drinking is an alcohol consumption pattern characterized by alternations between intense alcohol intakes and abstinence periods (Courtney and Polich, 2009). Despite the lack of consensus regarding its definition, this habit is now widespread in young people in Western countries (e.g., Kanny et al., 2013). As a matter of fact, binge drinking is no longer considered as a recreational and occasional alcohol consumption activity, but rather as a risky behavior with major cognitive consequences (e.g., in memory or attentional processes; Hartley et al., 2004; Heffernan and O'Neill, 2012).

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A pitfall in magnetic stimulation for measuring central motor conduction time

An interesting electrophysiological study of patients with Hirayama disease using magnetic stimulation is published in the current issue of Clinical Neurophysiology. Zheng et al. (2017) measured two types of central motor conduction time (CMCT) in patients with Hirayama disease: one is CMCT using the F-wave technique (CMCTF) and another is CMCT using magnetic motor root stimulation (CMCTM) (Rossini et al. 2015). The authors compared CMCTF and CMCTM, and they showed that CMCTM was abnormally prolonged compared with CMCTF.

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S195 Physiological properties of the seizure onset zone and brain connectivity: Insights gained from callosotomy procedures

Rapidly propagating frontal lobe seizures that are difficult to lateralize may do so after corpus callosotomy. We performed callosotomy using laser interstitial thermal therapy (LITT) in three patients who were undergoing stereoelectroencephalography (SEEG) and examined both the electrocorticogram electrophysiology and neuroimaging connectivity measures.

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Is the 3-Dimensional Strut Plate an Adequate Fixation Technique for Mandibular Symphysis Fractures?

Publication date: Available online 1 September 2017
Source:Journal of Oral and Maxillofacial Surgery
Author(s): Andrew T. Meram, Sergio Olate, Celso F. Palmieri
PurposeTo present a series of cases of mandibular symphysis fractures treated at our institution with a 3-dimensional strut plate. The aim of this study is to confirm the stability of this fixation technique, and discuss its advantages, disadvantages, and potential complications.MethodsThe investigators designed and implemented a retrospective cohort study composed of patients operated on by the same surgeon at our institution between July 2012 and April 2014 who had suffered a mandible fracture with a symphysis component. Patients were evaluated to identify aspects of occlusion, fracture mobility, postoperative infection, and the need for hardware removal.ResultsThe sample was composed of 12 subjects who met inclusion criteria. This required the fracture be linear and non-comminuted, there be sufficient distance from the mental foramina, a maximum of 5 days between the trauma and the surgery, and a minimum postoperative period of 3 months. The mean age of the sample was 33.4 years; and 8.3% of the patients enrolled were female (1/12). Ten subjects did well. Two subjects developed surgical site infection, one of whom had nonunion as well requiring additional fixation.ConclusionThe results of this study suggest a 3-dimensional strut plate applied to symphysis fractures provides adequate fracture stabilization with a risk of complications that is comparable to more traditional fixation methods. In addition, there exists an added advantage of minimal manipulation and adaptation that may hasten overall operating time.

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News and Announcements

Publication date: Available online 2 September 2017
Source:Journal of Oral and Maxillofacial Surgery

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Does Fixation Method Affect Stability of Sagittal Split Osteotomy and Condylar Position?

Publication date: Available online 31 August 2017
Source:Journal of Oral and Maxillofacial Surgery
Author(s): Reza Tabrizi, Fereydoun Pourdanesh, Hassan Mirmohammad Sadeghi, Sholeh Shahidi, Behnaz Poorian
PurposeFixation methods are important for condylar position and stability in sagittal split osteotomy (SSO) procedures. The aim of this study was to compare changes of the condylar position and stability following SSOs for mandibular setback in plate fixation with monocortical screw and bicortical screws.Materials and MethodsIn this retrospective cohort study, patients who underwent mandibular setback were studied in two groups. In group 1, fixation was done via miniplate with four monocortical screws and in group 2, this was done via 3 bicortical screws. Cone beam computed tomography (CBCT) scans were taken before and immediately after SSOs and one year later. Condylar position was evaluated linearly (mediolateral movement in the coronal view) and angularly (condylar axis with Frankfort plane in the coronal view). Stability of the mandible was determined at the B point horizontally and vertically.ResultsForty-eight patients were studied in two equal groups. A significant difference for the mediolateral changes of the condyle before and after osteotomies was detected between the two groups (P=0.003). There was no difference between the two groups for angular changes of the condyle before and after SSOs in the coronal view (P=0.45). Analysis of the data did not reveal any differences for vertical relapse at the B point (P=0.47) or horizontal relapse between the two groups (P=0.21).ConclusionAccording to this study, bicortical screw fixation may be associated with more condylar displacement. However, we could not find significant differences in surgical stability between miniplate fixation with monocortical screws or bicortical screw fixation after one year of follow-up.

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Follicular Lymphoma with Hyaline-vascular Castleman-like Features Analysis of 6 Cases and Review of the Literature

Publication date: Available online 2 September 2017
Source:Human Pathology
Author(s): Sergio Pina-Oviedo, Roberto N. Miranda, Pei Lin, John T. Manning, L. Jeffrey Medeiros
Follicular lymphoma (FL) with features reminiscent of hyaline-vascular Castleman disease (CD) is an unusual morphologic variant that may create diagnostic difficulties. To our knowledge, only 5 cases of this variant have been reported. We describe the clinicopathologic features of 6 cases including 2 men and 4 women with a median age of 63years (range, 41–77). Morphologically, all lymph node biopsy specimens showed at least a focal area of conventional FL; 4 cases showed neoplastic follicles with hyalinized blood vessels penetrating into germinal centers (lollipop-like lesions); 4 cases had interfollicular areas with increased vascular stroma, 2 cases showed small neoplastic follicles with prominent, onion skin-like mantle zones, and 1 case showed two or more germinal centers within follicles (twinning). The small neoplastic follicles were more cellular than lymphocyte-deplete follicles of true hyaline-vascular CD and the interface between germinal centers and mantle zones was ill-defined. No cases showed dysplastic follicular dendritic cells. Immunohistochemistry for BCL-2 was positive in all 6 cases. Flow cytometry immunophenotypic analysis showed a monotypic B-cell population in 2 of 3 cases assessed. Conventional cytogenetic or FISH studies performed in 2 cases showed t(14;18)(q32;q21) or IGH-BCL2 supporting the diagnosis of FL. The cases presented here add clinicopathologic data to the few cases of FL with hyaline-vascular CD-like features reported previously in the literature. Distinguishing this variant of FL from hyaline-vascular CD is important given the differences in treatment and prognosis of patients with each disease.

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Frequency and Pathological Characteristics of Drug-Induced Liver Injury in a Tertiary Medical Center

Publication date: Available online 2 September 2017
Source:Human Pathology
Author(s): Mark Ettel, Gabriel Acosta Gonzalez, Shweta Gera, Ogechukwu Eze, Samuel Sigal, James S Park, Ruliang Xu
Drug-induced liver injury (DILI) accounts for approximately 10% of acute hepatitis cases. DILI can arise as idiosyncratic or intrinsic injury from hundreds of drugs, herbals, and nutritional supplements and is essential to recognize as one of the differential diagnoses of hepatitis in a liver biopsy. The purpose of this study is to investigate the frequency and pathological characteristics of DILI related to the variety of hepatotoxic agents. We searched our pathology database for all patients with hepatitis diagnosed on liver biopsy from January 2012 to May 2016, and selected patients with a diagnosis of DILI. Electronic medical records were reviewed for patient medication list, history of herbal medicine or supplement use, and pre-biopsy liver function test (LFT) results. Clinical and pathologic correlation was used to determine the causative or related agents for DILI. We then assessed histopathologic features of liver injury and categorized biopsy findings as primarily bile duct injury, lobular/portal hepatitis, or mixed changes. 604 total liver biopsies for hepatitis or liver injury were identified, of which 70 cases (11.6%) carried the diagnosis of DILI confirmed by clinical correlation. The most common etiologies associated with DILI were supplements and herbal products (31.4%), antimicrobials (14.3%), chemotherapeutics (11.4%), antilipidemics (7.1%) and immunomodulatory agents (7.1%). LFT results positively correlated with histological findings. Nutritional/herbal supplements have emerged as one of the major hepatotoxicity agents. DILI can manifest as predominantly hepatitis, bile duct injury or combination. Histological pattern recognition in the liver biopsy may help identify specific hepatotoxic agents causing DILI.

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Mutation of NRAS is a Rare Genetic Event in Ovarian Low-Grade Serous Carcinoma

Publication date: Available online 2 September 2017
Source:Human Pathology
Author(s): Deyin Xing, Yohan Suryo Rahmanto, Felix Zeppernick, Charlotte G. Hannibal, Susanne K. Kjaer, Russell Vang, Ie-Ming Shih, Tian-Li Wang
Activating mutations involving the members of the RAS signaling pathway, including KRAS, NRAS, and BRAF, have been reported in ovarian low-grade serous carcinoma and its precursor lesion, serous borderline tumor (SBT). Whether additional genetic alterations in the RAS oncogene family accumulate during the progression of serous borderline tumor (SBT) to invasive low grade serous carcinoma (LGSC) remains largely unknown. While mutations of KRAS and BRAF occur at a very early stage of progression, even preceding the development of SBT, additional driving events, such as NRAS mutations, have been postulated to facilitate progression. In this study, we analyzed NRAS exon 3 mutational status in 98 cases that were diagnosed with SBT/atypical proliferative serous tumor (SBT/APST), non-invasive LGSC (niLGSC), or invasive LGSC (iLGSC). Of the latter, NRAS Q61R (CAA to CGA) mutations were detected in only 2 of 56 (3.6%) cases. The same mutation was not detected in any of the SBT/APSTs or niLGSCs. Mutational analysis for hotspots in KRAS and BRAF demonstrated a wildtype pattern of KRAS and BRAF in one of the NRAS-mutated cases. Interestingly, another LGSC case with NRAS mutation harbored a concurrent BRAF V600L mutation. These findings indicate that, although recurrent NRAS mutations are present, their low prevalence indicates that NRAS plays a limited role in the development of LGSC. Further studies to identify other oncogenic drivers of LGSC progression is warranted.

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Pulmonary interstitial glycogenosis associated with a spectrum of neonatal pulmonary disorders

Publication date: Available online 2 September 2017
Source:Human Pathology
Author(s): Ernest Cutz, Rose Chami, Sharon Dell, Jacob Langer, David Manson
Primary or isolated pulmonary interstitial glycogenosis (PIG) is a rare disease presenting as tachypnea and hypoxemia during the perinatal period. A diffuse interstitial infiltrate with focal hyperinflation is visible on chest imaging. The biopsy findings include diffuse expansion of the interstitium by spindle-shaped cells with pale cytoplasm that, on electron microscopy (EM), are poorly differentiated mesenchymal cells containing abundant monoparticulate glycogen. This glycogenosis appears to be a transient abnormality, usually with a favorable prognosis. Recently, cases of PIG, some associated with other pulmonary or systemic abnormalities, have been described. The clinical significance and potential role of PIG changes remain unknown. We report 28 cases of PIG associated with a spectrum of pediatric pulmonary and cardiovascular disorders, including arterial hypertensive changes with and without abnormal alveolar development (n=9), congenital heart disease (CHD; n=4), hyperplasia of pulmonary neuroendocrine cells resembling neuroendocrine hyperplasia of infancy (NEHI, n=5), congenital pulmonary airway malformation (n=5), congenital lobar emphysema (n=4), and Noonan syndrome (n=1). In all cases, PIG was confirmed by positive periodic acid–Schiff (PAS) staining, immunopositivity for vimentin, and EM. Although some patients improved with age, seven died of respiratory failure or complications of CHD, suggesting that PIG may be clinically significant when associated with other severe disorders. The association of PIG with a spectrum of mostly congenital lung disorders supports its origin as a developmental abnormality of interstitial fibroblast differentiation rather than a nonspecific reactive process.

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Immunophenotypic Comparison of Testicular Sclerosing Sertoli Cell Tumors and Sertoli Cell Tumors Not Otherwise Specified

Publication date: Available online 2 September 2017
Source:Human Pathology
Author(s): Hector Mesa, Chen Zhang, Juan C. Manivel, Thomas M. Ulbright
Testicular Sertoli cell tumors (SCT) are rare and most fall into the category of SCT-not otherwise specified (SCT-NOS). Only a few additional types of SCT are recognized. Sclerosing SCT (S-SCT), originally described in 1991, comprises a small fraction of SCTs and was considered a specific entity until the 2016 revision of the World Health Organization classification of non-germ cell tumors, where it was classified as a morphologic variant of SCT-NOS. In a recent study, differences in expression of PAX2/PAX8, inhibin, androgen receptor and S100 protein between SCT-NOS and S-SCT were noted in a small number of cases. In this interinstitutional study, we compared the expression of these markers and β-catenin in 11 cases each of SCT-NOS and S-SCT to determine if differences exist that could justify keeping a separate classification of these neoplasms. PAX2/PAX8 cocktail was the only marker that was significantly overexpressed in S-SCT. Expression of androgen receptors was strong in S-SCT and variable in SCT-NOS, but did not reach statistical significance. Expression of β-catenin was common in both, while inhibin was infrequent. The available material was insufficient for a conclusive evaluation of S100 protein expression. Overall, our results support the inclusion of S-SCT as a morphologic variant of SCT-NOS. Expression of PAX2/PAX8 in S-SCT may reflect an overactive epithelial to mesenchymal transition as has been shown in experimental models of acute and chronic seminiferous tubular injury and might be related to the process generating the stroma in these tumors.

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Histone deacetylases inhibition: a potential diagnostic and therapeutic target for cancers—reply

Publication date: Available online 2 September 2017
Source:Human Pathology
Author(s): Daniel Neureiter, Tobias Kiesslich

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The effect of light-emitting diode (590/830 nm)−based low-level laser therapy on posttraumatic edema of facial bone fracture patients

Publication date: Available online 2 September 2017
Source:Journal of Cranio-Maxillofacial Surgery
Author(s): Woo Yeol Baek, Il Hwan Byun, In Sik Yun, Jae Yoon Kim, Tai Suk Roh, Dae Hyun Lew, Young Seok Kim
PurposePosttraumatic edema in facial bone fracture patients may interfere with the operation field and delay the schedule. Thus, swiftly reducing the edema alleviates patient discomfort and advances the operation date. Ice packing and compression bandages are often used for such a purpose, but such methods are often inconvenient for the face. In this study, we aim to analyze the effect of light-emitting diode (LED) (590/830 nm)−based low-level laser therapy (LLLT) in posttraumatic edema in facial bone fracture patients.Materials and MethodsWe conducted a prospective cohort study of 40 patients who were admitted to a single institution for facial bone fracture. The patients were divided into two groups of 20 each, treated either with LLLT or with sham treatment light. We used an LLLT device that consists of planar LED-based arrays with double wavelengths 590 nm and 830 nm. The patients were treated with either true or sham light from posttraumatic day 1 to 5, twice a day. After each treatment, the volume of a patient's face was measured with a 3-dimensional camera. We analyzed and compared the changes in facial edema. The Wilcoxon rank sum test was conducted for statistical comparison of the two groups, and significance was set to the level of p < 0.05.ResultsThe sex ratio and mean age of the two groups were of little difference. The fracture sites included the nasal bone, orbital wall, zygomaticomaxillary bone, mandible, and frontal sinus. Mechanisms of injury included fall, assault, traffic accident, sports, and gunshot. The total operation rate of both groups was equal to 85%. Our analysis showed a 16.5% reduction of edema in the LLLT group and 7.3% in the sham light group. The edema reduction was statistically significantly greater in the LLLT group than in the sham light group (p < 0.047).ConclusionLED-based LLLT is recently receiving attention worldwide for its cost-effectiveness and large coverage area compared to traditional laser therapy. Recent studies support its effectiveness in various areas such as wound healing, skin rejuvenation, and pain alleviation. In this study, we treated facial bone fracture patients with LED-based LLLT, and showed its effectiveness in reducing posttraumatic edema.

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The effect of light-emitting diode (590/830 nm)−based low-level laser therapy on posttraumatic edema of facial bone fracture patients

Spatial distribution of osteopontin, CD44v6 and podoplanin in the lining epithelium of odontogenic keratocyst, and their biological relevance

Publication date: Available online 1 September 2017
Source:Annals of Diagnostic Pathology
Author(s): Khamisah Awang Kechik, Chong Huat Siar
Background and aimsThe odontogenic keratocyst (OKC) remains the most challenging jaw cyst to treat because of its locally-aggressive behaviour and high recurrence potential. Emerging evidence suggests that osteopontin, its receptors CD44v6 and integrin αv, and podoplanin, have a role in the local invasiveness of this cyst. However the spatial distribution characteristics of these pro-invasive markers in the lining epithelium of OKC, and their association with the clinicopathologic parameters of OKC are largely unexplored. This study sought to address these issues in comparison with dentigerous cysts (DCs) and radicular cysts (RCs) and to evaluate their biological relevance.MethodsA sample consisting of 20 OKC cases, 10 DCs and 10 RCs was subjected to immunohistochemical staining for osteopontin, CD44v6 and integrin αv, and podoplanin, and semiquantitative analysis was performed.ResultsAll factors (except integrin αv) were detected heterogeneously in the constitutive layers of the lining epithelium in all three cyst types. Key observations were significant upregulation of CD44v6 and podoplanin in OKC compared to DCs and RCs, suggesting that these protein molecules may play crucial roles in promoting local invasiveness in OKC (P<0.05). Osteopontin underexpression and distribution patterns were indistinctive among all three cysts indicating its limited role as pro-invasive factor. Clinical parameters showed no significant correlations with all protein factors investigated.ConclusionsPresent findings suggest that an osteopontin^low CD44v6^high and podoplanin^high immunoprofile most probably represent epithelial signatures of OKC and are markers of local invasiveness in this cyst.

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Development of a tool to aid the radiologic technologist using augmented reality and computer vision

Abstract

This technical innovation describes the development of a novel device to aid technologists in reducing exposure variation and repeat imaging in computed and digital radiography. The device consists of a color video and depth camera in combination with proprietary software and user interface. A monitor in the x-ray control room displays the position of the patient in real time with respect to automatic exposure control chambers and image receptor area. The thickness of the body part of interest is automatically displayed along with a motion indicator for the examined body part. The aim is to provide an automatic measurement of patient thickness to set the x-ray technique and to assist the technologist in detecting errors in positioning and motion before the patient is exposed. The device has the potential to reduce the incidence of repeat imaging by addressing problems technologists encounter daily during the acquisition of radiographs.

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Carbon-ion radiotherapy for non-small cell lung cancer with interstitial lung disease: a retrospective analysis

Lung cancer is frequently complicated by interstitial lung disease (ILD). Treatment protocols for lung cancer patients with ILD have not been established; surgery, chemotherapy, and radiotherapy can all cause ...

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PRELIM II(EDI BOARD)

Publication date: September 2017
Source:Neuroscience Research, Volume 122

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The roles of cortical astrocytes in chronic pain and other brain pathologies

Publication date: Available online 1 September 2017
Source:Neuroscience Research
Author(s): Kei Eto, Sun Kwang Kim, Ikuko Takeda, Junichi Nabekura
Astrocytes are the most abundant cell type in the brain. Several decades ago, they were considered to be only support cells in the central nervous system. Recent studies using advanced technologies have clarified that astrocytes play more active roles in regulating neuronal function and remodeling synaptic structures by releasing molecules called gliotransmitters. In addition to various physiological functions, astrocytes are activated under disease conditions, such as chronic pain, releasing molecules that in turn cause reorganization of the central nervous system microstructure and disrupt behavior in pathological conditions. In the present review, we summarize cortical astrocyte function in chronic pain and other neurological disorders and discuss the role of astrocytes in brain pathologies.

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Autophagy and mitophagy elements are increased in body fluids of multiple sclerosis-affected individuals

Background

Multiple sclerosis (MS) is a chronic multifaceted demyelinating and neurodegenerative disease of the central nervous system (CNS) of presumed autoimmune origin.1

Patients with MS are characterised by a spatial and temporal dissemination of neurological sign and symptoms, by the presence of multifocal lesions in the periventricular white matter on MRI scans and by an immunoglobulin synthesis within the CNS.1 Further diagnostic tools are desirable, and the use of blood and cerebrospinal fluid (CSF) biomarkers may contribute to the comprehension of the disease's pathogenesis and progression.

Autophagy is an evolutionarily conserved and genetically controlled cellular process where intracellular components are sequestered within double-membrane vesicles (autophagosomes), which then fuse with lysosomes where the material is degraded.2 Autophagy also occurs as mitophagy, which is responsible for the removal of aberrant, aged and wasted mitochondria. Interestingly, autophagic/mitophagic pathways have been found deregulated in various human diseases. In particular, it...

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Sleep patterns in Parkinsons disease: direct recordings from the subthalamic nucleus

Sleep is a fundamental homeostatic process, and disorders of sleep can greatly affect quality of life. Parkinson's disease (PD) is highly comorbid for a spectrum of sleep disorders and deep brain stimulation (DBS) of the subthalamic nucleus (STN) has been reported to improve sleep architecture in PD. We studied local field potential (LFP) recordings in PD subjects undergoing STN-DBS over the course of a full-night's sleep. We examined the changes in oscillatory activity recorded from STN between ultradian sleep states to determine whether sleep-stage dependent spectral patterns might reflect underlying dysfunction. For this study, PD (n=10) subjects were assessed with concurrent polysomnography and LFP recordings from the DBS electrodes, for an average of 7.5 hours in 'off' dopaminergic medication state. Across subjects, we found conserved spectral patterns among the canonical frequency bands (delta 0–3 Hz, theta 3–7 Hz, alpha 7–13 Hz, beta 13–30 Hz, gamma 30–90 Hz and high frequency 90–350 Hz) that were associated with specific sleep cycles: delta (0–3 Hz) activity during non-rapid eye movement (NREM) associated stages was greater than during Awake, whereas beta (13–30 Hz) activity during NREM states was lower than Awake and rapid eye movement (REM). In addition, all frequency bands were significantly different between NREM states and REM. However, each individual subject exhibited a unique mosaic of spectral interrelationships between frequency bands. Our work suggests that LFP recordings from human STN differentiate between sleep cycle states, and sleep-state specific spectral mosaics may provide insight into mechanisms underlying sleep pathophysiology.

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Associations d’hormonothérapie et de radiothérapie pour le cancer de prostate

Publication date: Available online 1 September 2017
Source:Cancer/Radiothérapie
Author(s): C. Hennequin, I. Fumagalli, V. Martin, L. Quero
L'association d'une radiothérapie et d'une hormonothérapie est devenue le standard de traitement des cancers de prostate localisé à haut risque du fait de deux groupes d'essais randomisés : plusieurs essais ont démontré le bénéfice de l'association en comparaison de la radiothérapie exclusive : ces essais ont maintenant plus de dix ans de recul et montrent un bénéfice de survie globale. Trois essais plus récents ont comparé à l'association une hormonothérapie seule : là aussi un bénéfice en survie a été mis en évidence pour l'association. Des questions se posent encore sur la durée optimale de l'hormonothérapie, en particulier au vu des effets secondaires de celle-ci. Les patients atteints de cancer de pronostic intermédiaire semblent bénéficier d'une hormonothérapie courte alors que ceux atteints d'un cancer de score de Gleason 8 – 10 tireraient bénéfice d'une hormonothérapie longue. Les modalités précises de la radiothérapie sont également en cours d'évaluation.Combination of radiotherapy and androgen deprivation is now considered as the standard of care for patients with a localized prostate cancer but poor prognosis factors. Two groups of randomized trials have led to this recommendation: some have compared radiotherapy alone versus hormonal treatment and radiotherapy: these trials demonstrated, now with a long follow-up, an improvement in 10-year survival for the combined treatment. Three recent trials compared androgen deprivation alone or combined with radiotherapy; a benefit in survival was also demonstrated in favour of the combination. Some questions remained concerning the optimal duration of hormonal treatment, in view of its potential side effects. Patients in the intermediate prognostic groups could receive a short-term androgen deprivation, but those with a high Gleason score must be treated with a long-term hormonal treatment. Modalities of radiotherapy, regarding volumes and dose must also be précised in the next years.

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Mise en place de l’audit patient traceur au sein d’un centre privé de radiothérapie

Publication date: Available online 1 September 2017
Source:Cancer/Radiothérapie
Author(s): S. Nardin, N. Pinto, R.-J. Bensadoun
L'audit du patient traceur est une méthode d'évaluation introduite par la Haute autorité de santé (HAS) dans la certification V2014. Celle-ci est non obligatoire dans les centres privés de radiothérapie. Dans notre démarche d'amélioration continue de la qualité et afin d'améliorer la prise en charge de nos patients, la direction de notre établissement a décidé d'utiliser cette méthode afin d'évaluer ses pratiques et d'impliquer les professionnels au cœur de la démarche.The "tracer patient" audit is an evaluation method introduced by the French health authority in the V2014 certification. This is not mandatory in private radiotherapy centres. In our continuous quality improvement approach and in order to improve the management of patient care, the management of our radiation therapy centre has decided to use this method to evaluate our medical practice and to engage healthcare professionals at the core of this approach.

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Assessing hypoxia risk during air travel after a severe asthma exacerbation in children

Publication date: Available online 1 September 2017
Source:Annals of Allergy, Asthma & Immunology
Author(s): Jose Antonio Peña-Zarza, Borja Osona, Sebastian Sailer, Jose Antonio Gil-Sanchez, Joan Figuerola Mulet

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Nasal interleukin 25 as a novel biomarker for patients with chronic rhinosinusitis with nasal polyps and airway hypersensitiveness

Publication date: Available online 1 September 2017
Source:Annals of Allergy, Asthma & Immunology
Author(s): Fenghong Chen, Haiyu Hong, Yueqi Sun, Xianting Hu, Jia Zhang, Geng Xu, Weidong Zhao, Huabin Li, Jianbo Shi
BackgroundChronic rhinosinusitis with nasal polyps (CRSwNP) is a chronic inflammatory disease of the upper airway and is tightly linked with airway hyperresponsiveness (AHR) and asthma. However, the surrogate biomarkers for indicating AHR and asthma in patients with CRSwNP remain elusive.ObjectiveTo investigate the surrogate biomarkers for indicating AHR and asthma in patients with CRSwNP.MethodsIn this study, sinonasal tissues were collected from 42 patients with CRSwNP (asthma, n = 17; asymptomatic AHR, n = 11; non-AHR, n = 14), 11 patients with chronic rhinosinusitis without nasal polyps (CRSsNP), and 13 controls. The protein and messenger RNA levels of interleukin (IL) 25 and other cytokines in nasal polyp (NP) and control sinonasal tissues were determined by quantitative real-time polymerase chain reaction and multiplex immunoassay, respectively. Multivariate logistic regression and receiver operating characteristic curve analysis were performed to assess the clinical relevance of IL-25.ResultsWe found that the protein and messenger RNA levels of IL-25 were significantly increased in NP tissues compared with the control sinonasal tissues from patients with CRSwNP, patients with CRSsNP, and controls. Multivariate logistic regression revealed that the nasal IL-25 protein level and nasal and blood eosinophil counts were independent risk factors for AHR in patients with CRSwNP. According to receiver operating characteristic curve analysis, nasal tissue IL-25 had a sensitivity of 91.4% and a specificity of 62.8% (area under the curve, 0.845) at the cutoff level of 5 pg/μL for indicating AHR in this CRSwNP cohort.ConclusionOur findings indicated that IL-25 was significantly increased in NP tissues and may be considered as the molecular indicator for AHR in patients with CRSwNP.Trial RegistrationClinicalTrials.gov Identifier: NCT02110654.

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Long-term results of a phase II study of gemcitabine and cisplatin chemotherapy combined with intensity-modulated radiotherapy in locoregionally advanced nasopharyngeal carcinoma

Publication date: October 2017
Source:Oral Oncology, Volume 73
Author(s): Mingyao Wu, Dan Ou, Xiayun He, Chaosu Hu

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Chemotherapy in head and neck osteosarcoma: Adjuvant chemotherapy improves overall survival

Publication date: October 2017
Source:Oral Oncology, Volume 73
Author(s): YiMing Chen, Sandhya Gokavarapu, QingCheng Shen, Feng Liu, Wei Cao, YueHua Ling, Tong Ji
BackgroundOsteosarcoma is an aggressive bone malignancy presenting uncommonly in head and neck sites. Surgery is mainstay in treatment. However; trials show an improved survival with addition of chemotherapy in the treatment of extremity osteosarcoma. The head and neck osteosarcomas(HNOs) were excluded in these trials because of atypical presentation and disease course. Further; sufficient numbers were not possible for a trial. We present the largest retrospective study from single institute investigating the role of chemotherapy in the management of HNOs.Patients and methodsThe retrospective cohort of HNOs treated from 2007 to 2015 of a tertiary hospital were charted. The therapeutic and prognostic factors were analyzed for overall survival(OS), disease free survival(DFS), local control(LC) and metastasis(MT) in univariate and multivariate analysis. The minimum and median period of follow up was 12months and 56.04months respectively.ResultsThere was a total of 157 patients definitively treated with surgery in the time period. 7 patients had positive margins and all were maxillary or skull base tumors. The multivariate cox regression showed significance of tumor site(p=0.034), margin status (p=0.006), chemotherapy(p=0.025), histological subtype(p=0.012) as predictors of overall survival. The margin status(p=0.002), Radiotherapy(p=0.005) were significant predictors for local recurrence. The age and histology subtype(p=0.058) were borderline significant predictors of metastasis(p=0.065). The KM method for OS of different chemotherapy groups(p=0.013), and survival with and without chemotherapy(p=0.007) was significant. The OS was significantly better with adjuvant chemotherapy among various treatment plans(p=0.034).ConclusionAdjuvant chemotherapy improved OS while adjuvant radiotherapy improved local control of HNOs.

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Pre-diagnostic dynamic HPV16 IgG seropositivity and risk of oropharyngeal cancer

Publication date: October 2017
Source:Oral Oncology, Volume 73
Author(s): Karen S. Anderson, Garrick Wallstrom, Hilde Langseth, Marshall Posner, Julia N. Cheng, Rizwan Alam, Diego Chowell, Ingegerd E. Furre, Jon Mork
ObjectiveThe aim of this study was to determine the association of HPV16 antibodies (Abs) and oropharyngeal cancer (OPC) risk in sera obtained prior to clinical diagnosis.MethodsWe identified 92 participants with incident OPC and 460 matched controls from the Janus Serum Bank Cohort in Norway. Archived tumor specimens were requested for a subset of the cases. Serum samples were collected from cases, on average, 9.3years before diagnosis (range, 0.1–14.9years). Ten cases had serum samples from multiple time points. IgG seropositivity to 8 HPV16 antigens was determined, and a logistic regression classifier of a panel of all early-antigen (EA) Abs for the predictive diagnosis of OPC was applied.ResultsHPV16 EA seropositivity was present in 25.0% of patients with OPC and 7.6% of controls (odds ratio (OR), 4.1; 95% CI, 2.3–7.2, p<0.0001). Abs to E2 were strongly associated with cases 0–2years pre- diagnosis (OR, 150.1; 95% CI, 27.4–1040.0, p<0.0001), and the probability of seropositivity was inversely associated with time to diagnosis (OR, 0.7 per additional year; 95% CI, 0.6–0.9, p=0.0002). Abs to E2 were also strongly associated with tumor HPV status (OR, 35.6; 95% CI, 8.7–200.0, p<0.0001). A positive score on the binary classifier was associated with an overall OR of 15.8 (95% CI, 5.6–53.4) compared with controls (p<0.05), and was strongly associated with tumor HPV status (OR, 27.4; 95% CI, 8.6–99.6, p<0.001).ConclusionsHPV16 Abs are detectable years prior to diagnosis of OPC, and the probability of seropositivity increases closer to diagnosis.

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A randomized, open-label, Phase III clinical trial of nivolumab vs. therapy of investigator’s choice in recurrent squamous cell carcinoma of the head and neck: A subanalysis of Asian patients versus the global population in checkmate 141

Publication date: October 2017
Source:Oral Oncology, Volume 73
Author(s): Naomi Kiyota, Yasuhisa Hasegawa, Shunji Takahashi, Tomoya Yokota, Chia-Jui Yen, Shigemichi Iwae, Yasushi Shimizu, Ruey-Long Hong, Masahiro Goto, Jin-Hyoung Kang, Wing Sum Kenneth Li, Robert L. Ferris, Maura Gillison, Yoshinobu Namba, Manish Monga, Mark Lynch, Makoto Tahara
ObjectivesTo assess efficacy and safety of nivolumab versus investigator's choice of therapy (IC) in Asian patients with platinum-refractory recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN).Materials and methodsThirty-four patients from Japan, Taiwan, Hong Kong, and Korea received nivolumab 3mg/kg (n=23) every 2weeks or IC (n=11), as part of a global trial (n=361), until intolerable toxicity or disease progression. The primary endpoint was overall survival (OS).ResultsMedian OS was 9.5months (95% confidence interval [CI] 9.1–NR) with nivolumab and 6.2months (95% CI 2.6–NR) with IC. Seven (30.4%) patients receiving nivolumab and six (54.5%) receiving IC died. The hazard ratio (HR) for risk of death (nivolumab vs. IC) was 0.50 (95% CI 0.17–1.48). Median progression-free survival was 1.9months (95% CI 1.6–7.5) with nivolumab and 1.8months (95% CI 0.4–6.1) with IC (HR 0.57 [95% CI 0.25–1.33]). Objective response rates (complete+partial responses) were 26.1% (6/23 patients; 95% CI 10.2–48.4) for nivolumab and 0% (0/11 patients; 95% CI 0.0–28.5) for IC. Sixteen (69.6%) nivolumab-treated patients and 10 (90.9%) patients receiving IC had a treatment-related adverse event, most commonly decreased appetite (21.7%), pruritus, rash, and fatigue (17.4% each) with nivolumab, and nausea, stomatitis, and decreased appetite (27.3% each) with IC.ConclusionNivolumab demonstrated a survival advantage compared with conventional treatments in Asian patients with platinum-refractory recurrent or metastatic SCCHN, and was well tolerated.Clinical trial registration NCT02105636.

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A frailty index from common clinical and laboratory tests predicts increased risk of death across the life course

Abstract

A frailty index (FI) based entirely on common clinical and laboratory tests might offer scientific advantages in understanding ageing and pragmatic advantages in screening. Our main objective was to compare an FI based on common laboratory tests with an FI based on self-reported data; we additionally investigated if the combination of subclinical deficits with clinical ones increased the ability of the FI to predict mortality. In this secondary analysis of the 2003–2004 and 2005–2006 National Health and Nutrition Examination Survey data, 8888 individuals aged 20+ were evaluated. Three FIs were constructed: a 36-item FI using self-reported questionnaire data (FI-Self-report); a 32-item FI using data from laboratory test values plus pulse and blood pressure measures (FI-Lab); and a 68-item FI that combined all items from each index (FI-Combined). The mean FI-Lab score was 0.15 ± 0.09, the FI-Self-report was 0.11 ± 0.11 and FI-Combined was 0.13 ± 0.08. Each index showed some typical FI characteristics (skewed distribution with long right tail, non-linear increase with age). Even so, there were fewer people with low frailty levels and a slower increase with age for the FI-Lab compared to the FI-Self-report. Higher frailty level was associated with higher risk of death, although it was strongest at older ages. Both FI-Lab and FI-Self-report remained significant in a combined model predicting death. The FI-Lab was feasible and valid, demonstrating that even subclinical deficit accumulation increased mortality risk. This suggests that deficit accumulation, from the subcellular to the clinically visible is a useful construct that may advance our understanding of the ageing process.

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Αρχειοθήκη ιστολογίου

Σάββατο 2 Σεπτεμβρίου 2017

Abstract

Abstract