Σφακιανάκης Αλέξανδρος
ΩτοΡινοΛαρυγγολόγος
Αναπαύσεως 5 Άγιος Νικόλαος
Κρήτη 72100
00302841026182
00306932607174
alsfakia@gmail.com

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Τρίτη 24 Μαΐου 2016

Kisspeptin Responsiveness Signals Emergence of Reproductive Endocrine Activity: Implications for Human Puberty.

Kisspeptin Responsiveness Signals Emergence of Reproductive Endocrine Activity: Implications for Human Puberty.

J Clin Endocrinol Metab. 2016 May 23;:jc20161545

Authors: Lippincott MF, Chan YM, Delaney A, Morales DR, Butler JP, Seminara SB

Abstract
CONTEXT: Some patients with idiopathic hypogonadotropic hypogonadism (IHH) undergo spontaneous activation of their hypothalamic-pituitary-gonadal axis resulting in normalization of steroidogenesis and/or gametogenesis, a phenomenon termed reversal.
OBJECTIVE: To assess the responsiveness of the GnRH neuronal network to exogenous kisspeptin administration in IHH patients who have undergone reversal.
PARTICIPANTS: Six men with congenital IHH and evidence for reversal.
INTERVENTION: Subjects underwent q10 min blood sampling to measure GnRH-induced LH secretion at baseline and in response to intravenous boluses of kisspeptin (0.24 - 2.4 nmol/kg) and GnRH (75 ng/kg).
RESULTS: Individuals with sustained reversal of their hypogonadotropism (spontaneous LH pulses) responded to exogenous kisspeptin with a GnRH-induced LH pulse. Individuals who had reversal but then subsequently suffered relapse of their IHH (loss of spontaneous LH pulsatility) did not respond to kisspeptin.
CONCLUSIONS: The ability of kisspeptin to stimulate a GnRH-induced LH pulse correlates with the presence of endogenous LH pulses. This data suggests that reversal of hypogonadotropism, and by extension, sexual maturation, may be due to the acquisition of kisspeptin responsiveness.

PMID: 27214398 [PubMed - as supplied by publisher]



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The present and the future of the RAS pathway: From function and genomics to inhibition.

The present and the future of the RAS pathway: From function and genomics to inhibition.

Cancer Biol Ther. 2016 May 21;:0

Authors: Gil-Bazo I, Sweet-Cordero A, Vicent S

Abstract
This meeting report summarizes the highlights of the II International Frontiers in Oncology meeting "The present and future of the RAS pathway: from function and genomics to inhibition" (RAS Frontiers) organized by the Center for Applied Medical Research (CIMA; Pamplona, SPAIN), the Clinic of the University of Navarra (CUN; Pamplona, SPAIN) and the Stanford Cancer Institute (SCI; Stanford University, CA, USA) in Pamplona (October 5-7, 2015). The RAS Frontiers meeting gathered together scientists from all over the world and featured the latest advances in the study of the RAS pathway covering aspects from basic research to translational and clinical investigation. Among the topics presented were novel mouse models that recapitulate human carcinogenesis and serve as preclinical platforms for drug testing, cutting-edge approaches for the identification of novel vulnerabilities and regulators of the RAS pathway, as well as current inhibitory strategies for the treatment of human RAS-driven cancers.

PMID: 27212457 [PubMed - as supplied by publisher]



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Can dental panoramic radiographic findings serve as indicators for the development of medication-related osteonecrosis of the jaw?

Can dental panoramic radiographic findings serve as indicators for the development of medication-related osteonecrosis of the jaw?

Dentomaxillofac Radiol. 2016 May 23;:20160065

Authors: Klingelhöffer C, Klingelhöffer M, Müller S, Ettl T, Wahlmann U

Abstract
OBJECTIVES: The purpose of this case-control study was to find a correlation between certain imaging findings in dental panoramic radiographs and the risk for developing a medication-related osteonecrosis of the jaw (MRONJ) in patients taking antiresorptive therapy (AT).
METHODS: Randomized and blinded dental panoramic radiographs of 60 patients undergoing antiresorptive drug treatment (36 patients with MRONJ, 24 patients without MRONJ) and of 60 patients without AT were analyzed by 3 experts for the following signs: sequestrum, osteosclerosis, difference in sclerosing of alveolar process and body of mandible, visible alveolar socket, enhancement and loss of lamina dura, enhancement of the oblique ridge, enhancement of the mandibular canal, proliferative periostitis and osteolytic processes at the cortex.
RESULTS: Signs were seen significantly more often in patients undergoing AT than in the control group (CG) (osteosclerosis p-value = 0.019, visible alveolar socket p-value = 0.001, enhancement of lamina dura p-value < 0.001, enhancement of the mandibular canal p-value = 0.025, proliferative periostitis p-value = 0.05 and osteolytic processes at the cortex p-value < 0.001). While there is no significant difference between the CG and the group of patients with AT without manifest MRONJ for any sign, the significance increases when taking the group of patients under AT with manifest MRONJ into consideration. In addition, if medication was administered for malignant reasons, the signs visible alveolar socket, enhancement of the lamina dura and the enhancement of the mandibular canal were seen significantly more often.
CONCLUSIONS: The radiographic findings mentioned above are not indicators for the development of MRONJ, as they are seen only in patients with manifest osteonecrosis. However, these findings could be important to assess the dimension and potency of a MRONJ.

PMID: 27213837 [PubMed - as supplied by publisher]



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Characterization, Quantification and Compound-specific Isotopic Analysis of Pyrogenic Carbon Using Benzene Polycarboxylic Acids (BPCA).

Characterization, Quantification and Compound-specific Isotopic Analysis of Pyrogenic Carbon Using Benzene Polycarboxylic Acids (BPCA).

J Vis Exp. 2016;(111)

Authors: Wiedemeier DB, Lang SQ, Gierga M, Abiven S, Bernasconi SM, Früh-Green GL, Hajdas I, Hanke UM, Hilf MD, McIntyre CP, Scheider MP, Smittenberg RH, Wacker L, Wiesenberg GL, Schmidt MW

Abstract
Fire-derived, pyrogenic carbon (PyC), sometimes called black carbon (BC), is the carbonaceous solid residue of biomass and fossil fuel combustion, such as char and soot. PyC is ubiquitous in the environment due to its long persistence, and its abundance might even increase with the projected increase in global wildfire activity and the continued burning of fossil fuel. PyC is also increasingly produced from the industrial pyrolysis of organic wastes, which yields charred soil amendments (biochar). Moreover, the emergence of nanotechnology may also result in the release of PyC-like compounds to the environment. It is thus a high priority to reliably detect, characterize and quantify these charred materials in order to investigate their environmental properties and to understand their role in the carbon cycle. Here, we present the benzene polycarboxylic acid (BPCA) method, which allows the simultaneous assessment of PyC's characteristics, quantity and isotopic composition ((13)C and (14)C) on a molecular level. The method is applicable to a very wide range of environmental sample materials and detects PyC over a broad range of the combustion continuum, i.e., it is sensitive to slightly charred biomass as well as high temperature chars and soot. The BPCA protocol presented here is simple to employ, highly reproducible, as well as easily extendable and modifiable to specific requirements. It thus provides a versatile tool for the investigation of PyC in various disciplines, ranging from archeology and environmental forensics to biochar and carbon cycling research.

PMID: 27214064 [PubMed - as supplied by publisher]



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The Monoiodoacetate Model of Osteoarthritis Pain in the Mouse.

The Monoiodoacetate Model of Osteoarthritis Pain in the Mouse.

J Vis Exp. 2016;(111)

Authors: Pitcher T, Sousa-Valente J, Malcangio M

Abstract
A major symptom of patients with osteoarthritis (OA) is pain that is triggered by peripheral as well as central changes within the pain pathways. The current treatments for OA pain such as NSAIDS or opiates are neither sufficiently effective nor devoid of detrimental side effects. Animal models of OA are being developed to improve our understanding of OA-related pain mechanisms and define novel pharmacological targets for therapy. Currently available models of OA in rodents include surgical and chemical interventions into one knee joint. The monoiodoacetate (MIA) model has become a standard for modelling joint disruption in OA in both rats and mice. The model, which is easier to perform in the rat, involves injection of MIA into a knee joint that induces rapid pain-like responses in the ipsilateral limb, the level of which can be controlled by injection of different doses. Intra-articular injection of MIA disrupts chondrocyte glycolysis by inhibiting glyceraldehyde-3-phosphatase dehydrogenase and results in chondrocyte death, neovascularization, subchondral bone necrosis and collapse, as well as inflammation. The morphological changes of the articular cartilage and bone disruption are reflective of some aspects of patient pathology. Along with joint damage, MIA injection induces referred mechanical sensitivity in the ipsilateral hind paw and weight bearing deficits that are measurable and quantifiable. These behavioral changes resemble some of the symptoms reported by the patient population, thereby validating the MIA injection in the knee as a useful and relevant pre-clinical model of OA pain. The aim of this article is to describe the methodology of intra-articular injections of MIA and the behavioral recordings of the associated development of hypersensitivity with a mind to highlight the necessary steps to give consistent and reliable recordings.

PMID: 27214709 [PubMed - as supplied by publisher]



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Generation of ESC-derived Mouse Airway Epithelial Cells Using Decellularized Lung Scaffolds.

Generation of ESC-derived Mouse Airway Epithelial Cells Using Decellularized Lung Scaffolds.

J Vis Exp. 2016;(111)

Authors: Shojaie S, Lee J, Wang J, Ackerley C, Post M

Abstract
Lung lineage differentiation requires integration of complex environmental cues that include growth factor signaling, cell-cell interactions and cell-matrix interactions. Due to this complexity, recapitulation of lung development in vitro to promote differentiation of stem cells to lung epithelial cells has been challenging. In this protocol, decellularized lung scaffolds are used to mimic the 3-dimensional environment of the lung and generate stem cell-derived airway epithelial cells. Mouse embryonic stem cell are first differentiated to the endoderm lineage using an embryoid body (EB) culture method with activin A. Endoderm cells are then seeded onto decellularized scaffolds and cultured at air-liquid interface for up to 21 days. This technique promotes differentiation of seeded cells to functional airway epithelial cells (ciliated cells, club cells, and basal cells) without additional growth factor supplementation. This culture setup is defined, serum-free, inexpensive, and reproducible. Although there is limited contamination from non-lung endoderm lineages in culture, this protocol only generates airway epithelial populations and does not give rise to alveolar epithelial cells. Airway epithelia generated with this protocol can be used to study cell-matrix interactions during lung organogenesis and for disease modeling or drug-discovery platforms of airway-related pathologies such as cystic fibrosis.

PMID: 27214388 [PubMed - as supplied by publisher]



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High Resolution Quantification of Crystalline Cellulose Accumulation in Arabidopsis Roots to Monitor Tissue-specific Cell Wall Modifications.

High Resolution Quantification of Crystalline Cellulose Accumulation in Arabidopsis Roots to Monitor Tissue-specific Cell Wall Modifications.

J Vis Exp. 2016;(111)

Authors: Fridman Y, Holland N, Elbaum R, Savaldi-Goldstein S

Abstract
Plant cells are surrounded by a cell wall, the composition of which determines their final size and shape. The cell wall is composed of a complex matrix containing polysaccharides that include cellulose microfibrils that form both crystalline structures and cellulose chains of amorphous organization. The orientation of the cellulose fibers and their concentrations dictate the mechanical properties of the cell. Several methods are used to determine the levels of crystalline cellulose, each bringing both advantages and limitations. Some can distinguish the proportion of crystalline regions within the total cellulose. However, they are limited to whole-organ analyses that are deficient in spatiotemporal information. Others relying on live imaging, are limited by the use of imprecise dyes. Here, we report a sensitive polarized light-based system for specific quantification of relative light retardance, representing crystalline cellulose accumulation in cross sections of Arabidopsis thaliana roots. In this method, the cellular resolution and anatomical data are maintained, enabling direct comparisons between the different tissues composing the growing root. This approach opens a new analytical dimension, shedding light on the link between cell wall composition, cellular behavior and whole-organ growth.

PMID: 27214583 [PubMed - as supplied by publisher]



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Substantiating Appropriate Motion Capture Techniques for the Assessment of Nordic Walking Gait and Posture in Older Adults.

Substantiating Appropriate Motion Capture Techniques for the Assessment of Nordic Walking Gait and Posture in Older Adults.

J Vis Exp. 2016;(111)

Authors: Dalton CM, Nantel J

Abstract
Nordic walking (NW) has become a safe and simple form of exercise in recent years, and in studying this gait pattern, various data collection techniques have been employed, each with positives and negatives. The aim was to determine the effect of NW on older adult gait and posture and to determine optimal use of different data collection systems in both short and long duration analysis. Gait and posture during NW and normal walking were assessed in 17 healthy older adults (age: 69 ± 7.3). Participants performed two trials of 6 Minute Walk Tests (6MWT) (1 with poles (WP) and 1 without poles (NP)) and 6 trials of a 5m walk (3 WP and 3 NP). Motion was recorded using two systems, a 6-sensor accelerometry system and an 8-camera 3-dimensional motion capture system, in order to quantify spatial-temporal, kinematic, and kinetic parameters. With both systems, participants demonstrated increased stride length and double support and decreased gait speed and cadence WP compared to NP (p <0.05). Also, with motion capture, larger single support time was found WP (p <0.05). With 3-D capture, smaller hip power generation and moments of force were found at heel contact and pre-swing as well as smaller knee power absorption at heel contact, pre-swing, and terminal swing WP compared to NP, when assessed over one cycle (p <0.05). Also, WP yielded smaller moments of force at heel contact and terminal swing along with larger moments at mid-stance of a gait cycle (p <0.05). No changes were found for posture. NW seems appropriate for promoting a normal gait pattern in older adults. Three-dimensional motion capture should primarily be used during short duration gait analysis (i.e. single gait cycle), while accelerometry systems should be primarily employed in instances requiring longer duration analysis such as during the 6MWT.

PMID: 27214263 [PubMed - as supplied by publisher]



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Microinjection for Transgenesis and Genome Editing in Threespine Sticklebacks.

Microinjection for Transgenesis and Genome Editing in Threespine Sticklebacks.

J Vis Exp. 2016;(111)

Authors: Erickson PA, Ellis NA, Miller CT

Abstract
The threespine stickleback fish has emerged as a powerful system to study the genetic basis of a wide variety of morphological, physiological, and behavioral phenotypes. The remarkably diverse phenotypes that have evolved as marine populations adapt to countless freshwater environments, combined with the ability to cross marine and freshwater forms, provide a rare vertebrate system in which genetics can be used to map genomic regions controlling evolved traits. Excellent genomic resources are now available, facilitating molecular genetic dissection of evolved changes. While mapping experiments generate lists of interesting candidate genes, functional genetic manipulations are required to test the roles of these genes. Gene regulation can be studied with transgenic reporter plasmids and BACs integrated into the genome using the Tol2 transposase system. Functions of specific candidate genes and cis-regulatory elements can be assessed by inducing targeted mutations with TALEN and CRISPR/Cas9 genome editing reagents. All methods require introducing nucleic acids into fertilized one-cell stickleback embryos, a task made challenging by the thick chorion of stickleback embryos and the relatively small and thin blastomere. Here, a detailed protocol for microinjection of nucleic acids into stickleback embryos is described for transgenic and genome editing applications to study gene expression and function, as well as techniques to assess the success of transgenesis and recover stable lines.

PMID: 27214565 [PubMed - as supplied by publisher]



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Targeting Biofilm Associated Staphylococcus aureus Using Resazurin Based Drug-susceptibility Assay.

Targeting Biofilm Associated Staphylococcus aureus Using Resazurin Based Drug-susceptibility Assay.

J Vis Exp. 2016;(111)

Authors: Dalecki AG, Crawford CL, Wolschendorf F

Abstract
Most pathogenic bacteria are able to form biofilms during infection, but due to the difficulty of manipulating and assessing biofilms, the vast majority of laboratory work is conducted with planktonic cells. Here, we describe a peg plate biofilm assay as performed with Staphylococcus aureus. Bacterial biofilms are grown on pegs attached to a 96-well microtiter plate lid, washed through gentle submersion in buffer, and placed in a drug challenge plate. After subsequent incubation they are again washed and moved to a final recovery plate, in which the fluorescent dye resazurin serves as a viability indicator. This assay offers greatly increased ease-of-use, reliability, and reproducibility, as well as a wealth of data when conducted as a kinetic read. Moreover, this assay can be adapted to a medium-throughput drug screening approach by which an endpoint fluorescent readout is taken instead, offering a path for drug discovery efforts.

PMID: 27214174 [PubMed - as supplied by publisher]



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Submental Artery Perforator Island Flap Without Including Digastric Muscle

 in the Reconstruction of Lower Face and Intraoral Defects.: Purpose: For reconstruction of intraoral and lower face defects, it is important to use flaps that prevent reliable and pliable soft tissue and it is possible to use aesthetically most compatible with recipient site. In this study, the authors aimed to present their clinical experiences and results of lower face and intraoral defects reconstructions with submental artery island perforator flap without including the digastric muscle to have a thinner and useful flap.

Methods: Six patients with lower face and intraoral defects that were reconstructed using the submental artery island flap between November 2013 and February 2015 were retrospectively analyzed. Patient demographics, age, sex, defect etiologies, and complications were assessed.

Surgical Technique: Hand Doppler examination was performed and submental artery marked preoperatively. The superior border of the flap was designed at least 1 cm away from the mandibular border to avoid injury to the marginal mandibular nerve and prevent lip eversion. After the identification of the submental artery via the retrograde dissection, the anterior belly of the digastric muscle was not included the flap to prevent a thinner flap. After the dissection, the island flap was transferred to the defect site through a subcutaneous tunnel. The donor sites were closed primarily.

Results: A partially flap necrosis was occurred in 1 patient due to hematome in the tunnel around the pedicle. The wound healed uneventfully with conservative management. In the remaining patients there were no complications.

Conclusion: The submental artery perforator island flap without including the digastric muscle is a reliable and suitable option for the medium-sized defects in the lower face and intraoral defects.

(C) 2016 by Mutaz B. Habal, MD.




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The Reconstruction of Lower Face and Intraoral Defects

The Use of Submental Artery Perforator Island Flap Without Including Digastric Muscle in the Reconstruction of Lower Face and Intraoral Defects.: Purpose: For reconstruction of intraoral and lower face defects, it is important to use flaps that prevent reliable and pliable soft tissue and it is possible to use aesthetically most compatible with recipient site. In this study, the authors aimed to present their clinical experiences and results of lower face and intraoral defects reconstructions with submental artery island perforator flap without including the digastric muscle to have a thinner and useful flap.

Methods: Six patients with lower face and intraoral defects that were reconstructed using the submental artery island flap between November 2013 and February 2015 were retrospectively analyzed. Patient demographics, age, sex, defect etiologies, and complications were assessed.

Surgical Technique: Hand Doppler examination was performed and submental artery marked preoperatively. The superior border of the flap was designed at least 1 cm away from the mandibular border to avoid injury to the marginal mandibular nerve and prevent lip eversion. After the identification of the submental artery via the retrograde dissection, the anterior belly of the digastric muscle was not included the flap to prevent a thinner flap. After the dissection, the island flap was transferred to the defect site through a subcutaneous tunnel. The donor sites were closed primarily.

Results: A partially flap necrosis was occurred in 1 patient due to hematome in the tunnel around the pedicle. The wound healed uneventfully with conservative management. In the remaining patients there were no complications.

Conclusion: The submental artery perforator island flap without including the digastric muscle is a reliable and suitable option for the medium-sized defects in the lower face and intraoral defects.

(C) 2016 by Mutaz B. Habal, MD.




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The 5q deletion size in myeloid malignancies is correlated to additional chromosomal aberrations and to TP53 mutations

Abstract

Deletions in the long arm of chromosome 5 (del(5q)) are recurrent abnormalities in myeloid malignancies. We analyzed del(5q) and accompanying molecular mutations in MDS, MPN and MDS/MPN cases. A high del(5q) frequency was revealed in MDS (1869/11398 cases; 16%), followed by MDS/MPN (37/1107; 3%) and MPN (97/6373; 2%). To investigate potential associations of the del(5q) size with the respective phenotypes, we applied array CGH analyses in selected cohorts of 61 MDS, 22 MDS/MPN and 23 MPN cases. The size varied between 16-119 Mb with no differences between the entities. However, MPN and MDS/MPN cases with del(5q) sole showed a significantly smaller del(5q) than cases with additional aberrations. Sequence analyses of 27 genes revealed ≥1 mutation in 91% of patients. The highest mutation frequencies in the total cohort were observed for TP53 (31%), JAK2 (23%) and DNMT3A (18%). The molecular mutation patterns in the del(5q) cohorts were different between the entities but resembled known patterns of cohorts not selected for del(5q). Further, TP53 mutations were significantly more frequent in cases with a larger deletion size (p=0.003). The results suggest a correlation of large del(5q) with TP53 mutations and with additional chromosomal aberrations possibly contributing to more severe courses of these cases. This article is protected by copyright. All rights reserved.



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Cytogenetic and Molecular Profile of Endometrial Stromal Sarcoma

Abstract

Recent cytogenetic and molecular investigations have improved our understanding of endometrial stromal tumors, including sarcomas (ESS), and helped redefine their classification into more pathogenetically meaningful categories. Since much more can be gained through such studies, we add information on another 22 ESS examined by karyotyping, PCR analysis, expression array analysis, and transcriptome sequencing. In spite of the known preference for certain pathogenetic pathways, we found considerable genetic heterogeneity in high-grade (HG) as well as in low-grade (LG) ESS. Not all HG tumors showed a YWHAE-NUTM chimeric transcript and as many as six LGESS showed no hitherto known ESS-related fusions. Among the transcripts identified by transcriptome sequencing and verified by Sanger sequencing, new variants of ZC3H7-BCOR and its reciprocal BCOR-ZC3H7 were identified as was involvement of the CREBBP and MLLT4 genes (both well known leukemia-related genes) in two new fusions. FISH analysis identified a known EPC1-PHF1 fusion which led to the identification of a new variant at the molecular level. The fact that around 70 genes were found differentially expressed, by microarray analysis, when comparing LGESS showing ESS-related fusions with LGESS without such transcripts, underscores the biochemical importance of the observed genetic heterogeneity and hints that new subgroups/entities in LGESS still remain undiscovered. This article is protected by copyright. All rights reserved.



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Copy Number Changes of Clinically Actionable Genes in Melanoma, Non-Small Cell Lung Cancer and Colorectal Cancer – A Survey Across 822 Routine Diagnostic Cases

Abstract

Targeted deep massive parallel sequencing has been implemented in routine molecular diagnostics for high-throughput genetic profiling of formalin-fixed paraffin-embedded (FFPE) cancer samples. This approach is widely used to interrogate simple somatic mutations but experience with the analysis of copy number variations (CNV) is limited. Here, we retrospectively analyzed CNV in 822 cancer cases (135 melanoma, 468 non-small cell lung cancers (NSCLC), 219 colorectal cancers (CRC)). We observed a decreasing frequency of CNV in clinically actionable genes from melanoma to NSCLC to CRC. The overall cohort displayed 168 (20%) amplifications in 17 druggable targets. The majority of BRAF mutant melanomas (57%) showed co-occurring CNV in other genes, mainly affecting CDKN2A. Subsets showed clustered deletions in ABL1, NOTCH1, RET or STK11, GNA11, and JAK3. Most NRAS mutant melanomas (77%) harbored CNVs in other genes with CDKN2A and FGFR3 being most frequently affected. Five BRAF/NRASwt tumors had co-amplifications of KDR, KIT, PDGFRA and another six mutated KIT. Among NSCLC, we identified 14 EGFRamp (with ten EGFRmut) and eight KRASamp (with seven KRASmut). KRASmut tumors displayed frequent amplifications of MYC (n=10) and MDM2 (n=5). Fifteen KRAS/EGFR/BRAFwt tumors had MET mutations/amplifications. In CRC, amplified IGF2 was most prevalent (n=13) followed by MYC (n=9). Two cases showed amplified KRAS wildtype alleles. Five KRAS mutant tumors showed either amplifications of NRAS (n=2) or EGFR (n=3). In conclusion we demonstrate that our approach i) facilitates detection of CNV, ii) enables detection of known CNV patterns, and iii) uncovers new CNV of clinically actionable genes in FFPE tissue samples across cancers. This article is protected by copyright. All rights reserved.



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Secondary EWSR1 Gene Abnormalities in SMARCB1-Deficient Tumors with 22q11-12 Regional Deletions: Potential Pitfalls in Interpreting EWSR1 FISH Results

ABSTRACT

SMARCB1 inactivation occurs in a variety of tumors, being caused by various genetic mechanisms. Since SMARCB1 and EWSR1 genes are located close to each other on at the chromosome 22, larger SMARCB1 deletions may encompass the EWSR1 locus. Herein, we report four cases with SMARCB1-deletions showing concurrent EWSR1 gene abnormalities by FISH, which lead initially to misinterpretations as EWSR1-rearranged tumors. Our study group included various morphologies: a poorly differentiated chordoma, an extrarenal rhabdoid tumor, a myoepithelial carcinoma, and a proximal-type epithelioid sarcoma. All cases showed loss of SMARCB1 (INI1) by immunohistochemistry and displayed characteristic histologic features for the diagnoses. The SMARCB1 FISH revealed homozygous or heterozygous deletions in three and one case, respectively. The co-hybridized EWSR1 probes demonstrated either unbalanced split signals or heterozygous deletion in two cases each. The former suggested bona fide rearrangement, while the latter resembled an unbalanced translocation. However, all the FISH patterns were quite complex and distinct from the simple and uniform split signals seen in typical EWSR1 rearrangements. We conclude that in the context of 22q11-12 regional alterations present in SMARCB1-deleted tumors, simultaneous EWSR1 involvement may be misinterpreted as equivalent to EWSR1 rearrangement. A detailed clinicopathologic correlation and supplementing the EWSR1 FISH assay with complementary methodology is mandatory for correct diagnosis. This article is protected by copyright. All rights reserved.



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Aplasia Cutis Congenita Associated With Aplasia of the Superficial Temporal Artery.

Aplasia Cutis Congenita Associated With Aplasia of the Superficial Temporal Artery.: Aplasia cutis congenita with or without congenital anomalies is a rare congenital disorder most commonly involving the skin of the scalp, as well as the skull and dura.

The etiology is uncertain, and several theories, including vascular accident intrauterine period, vascular anomaly, intrauterine infection, teratogen, and aminiotic adhesion, have been proposed. One theory is that lesions of the scalp are usually caused by vascular anomalies.

The authors report on a patient with aplasia cutis congenita presenting with a huge skin and skull defect combined with aplasia of the superficial temporal artery, which was thought to be the etiology.

(C) 2016 by Mutaz B. Habal, MD.




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Endoscopic Versus Microscopic Transsphenoidal Surgery in Pituitary Adenoma.

Outcomes and Complications of 

This retrospective study aimed to define outcomes and complications of endoscopic versus microscopic transsphenoidal surgery in pituitary adenoma. Data of 94 patients who underwent transsphenoidal endoscopic (n = 45) or microscopic surgery (n = 49) between June 2000 and June 2014 for pituitary adenoma, performed at Katip Celebi University Hospital, were retrospectively analyzed. The patients' symptomatology, type of adenoma, radiologic findings, surgical outcomes, and preoperative and postoperative complications were investigated. The total subtotal resection rate was 73.4% (69 patients) and partial resection rate was 26.6% (25 patients). Total subtotal resection rate was 77.6% (38 patients) in the microscopic group and 68.9% (31 patients) in the endoscopic group. Total resection was seen more often in the endoscopic group than in the microscopic group, with no significant difference between the groups. Four patients (8.2%) in the microscopic group had postoperative cerebrospinal fluid leak compared with 3 patients (6.7%) in the endoscopic group. Two patients (2.1%) had hematoma, with 1 patient each in the endoscopic and microscopic group. Panhypopituitarism development rate was higher in the endoscopic group (no significant difference between the 2 groups). One patient (2%) developed blindness in the microscopic group and 1 (2.2%) had meningitis in the endoscopic group. Based on this study, the total resection rate was higher in the microscopic group than in the endoscopic group. However, outcomes and complication rate did not differ significantly between the 2 surgical techniques. Both techniques have advantages and disadvantages. Prospective randomized controlled trials should be conducted to compare the 2 surgical methods.

(C) 2016 by Mutaz B. Habal, MD.




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Headache Attributed to Fibrous Dysplasia of the Ethmoid Bone

 Mimicking Menstrual Migraine Without Aura.: The authors experienced a patient of fibrous dysplasia originating from the ethmoid bone which presented with severe headache with some features suggestive of menstrual migraine without aura. Fibrous dysplasia originating from the ethmoid bone is a rare disease entity, but may cause severe headache that can be misdiagnosed as "menstrual migraine" because of similar symptoms in female patients. Because the primary objective of surgery is symptomatic relief, conservative transnasal endoscopic approach may be considered an alternative to more invasive external surgical techniques in carefully selected patients, especially originating from the nasal cavity and paranasal sinuses.

(C) 2016 by Mutaz B. Habal, MD.




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Calcification in Craniopharyngiomas

Preliminary Study on Composition and Microstructure of Calcification in Craniopharyngiomas

Abstract

To analyze the element composition and microstructure of calcification in craniopharyngiomas and to explore the differences among differing degrees of calcification, 50 consecutive patients with craniopharyngioma were selected. X-ray diffraction analysis and energy-dispersive X-ray spectroscopy analysis were performed on the calcified plaques isolated from the tumor specimens. All calcified plaques were constituted of hydroxyapatite crystals and some amorphous materials. The main elements for the analysis were calcium, phosphate, carbon, and oxygen. There were significant differences among groups of differing degrees of calcification in the percentage composition of calcium, phosphorus, and carbon (P < 0.05), in which the element content of calcium and phosphorus had a positive correlation with the extent of calcification (rp = 0.745 and 0.778, respectively, P < 0.01), while the element content of carbon had a negative correlation with the extent of calcification (rp =-0.526, P
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(C) 2016 by Mutaz B. Habal, MD.
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Guided Self-Generation of Vascularized Neo-Bone

 for Autologous Reconstruction of Large Mandibular Defects.: Reconstruction of large mandibular defects is complex and challenging. The authors aimed to individually self-generate a large vascularized bone construct for autologous transplantation without the use of exogenous additives based on the concept of guided self-generation. Using computer-aided design and manufacturing a large size goat mandibular bone was reconstructed in 3 dimensions. Its negative mold printed from hydroxylapatite was temporarily embedded into the costal periosteum along with a contralateral demineralized bone matrix scaffold as control. After 3 months, a mandibular bone construct was obtained and used for autologous transplantation. Osteogenesis and angiogenesis were assessed by real-time imaging, histology, and biomechanical tests during neo-bone formation and up to 6 months after transplantation surgery. A total of 20 animals received implantation of a mandibular bone negative mold along with a contralateral demineralized bone matrix scaffold. Resulting negative mold mandibular bone constructs showed anatomically, histologically, and functionally similar characteristics compared with native controls. Only 1 goat presented partial fibrosis during construct generation with subsequent absorbtion after reconstruction. The absence of exogenous cells, growth factors, and scaffolds facilitated direct translation of this novel concept into clinical application. Further studies are needed to determine functional long-term outcomes and possible extensions to other tissues and organs.

(C) 2016 by Mutaz B. Habal, MD.




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Oxidized Regenerated Cellulose and a Free Fascia Lata Graft.

Endoscopic Repair of the Injured Internal Carotid Artery Utilizing Oxidized Regenerated Cellulose and a Free Fascia Lata Graft.: Objective: To introduce appropriate surgical procedures for the endoscopic repair of the internal carotid artery (ICA) injury.

Methods: Two patients with ICA injury during the endoscopic endonasal approach surgery were reviewed.

Results: Internal carotid artery injury during the endonasal skull-base approach was a rare complication. Once ICA injury occurred, 2 large bore suctions were placed immediately for drainage and the bleeding point was located. Then, an oxidized regenerated cellulose was quickly pressed onto the bleeding point and was held there to stop the bleeding. Afterward, a free graft of fascia lata was inserted and the free fat graft was compressed for repair. Absorbable packing materials were used for nasal packing.

Conclusions: Endoscopic repair utilizing oxidized regenerated cellulose and a free fascia lata graft is a safe and feasible surgical option for ICA injury.

(C) 2016 by Mutaz B. Habal, MD.




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Delayed Facial Nerve Palsy

 After Open Reduction of an Isolated Zygomaticomaxillary Complex Fracture.: Facial nerve paralysis is a devastating complication which can occur after a variety of otolaryngic procedures, including facial trauma repair. The frontal and marginal branches are most often placed at risk. However, facial nerve paralysis is not typically described as a risk in most uncomplicated facial trauma repairs of the zygomaticomaxillary complex (ZMC). In particular, buccal branch injury has not been described in a delayed setting following repair of the ZMC. The authors present a patient of delayed buccal branch paralysis following a simple ZMC repair which has not been previously reported.

The diagnosis, clinical course, and management strategies for delayed facial nerve paralysis in the setting of a ZMC repair are discussed. This rare complication after facial trauma repair should be discussed with patients as a possible complication.

(C) 2016 by Mutaz B. Habal, MD.




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Novel Rigid External Distraction Device Improves Stability and Controls the Vector During Midfacial Advancement.

Novel Rigid External Distraction Device Improves Stability and Controls the Vector During Midfacial Advancement.: The major limitation of the rigid external devices currently used for midfacial distraction after subcranial Le Fort III osteotomies is the ductile wire that connects the midface to the device, which makes it difficult to control the vector and force during distraction. The authors describe a novel external appliance that addresses this and other problems of contemporary devices, and application of a custom cranial template that facilitates precise placement of the device to achieve the planned vector of distraction.

(C) 2016 by Mutaz B. Habal, MD.




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A Double-Lobe Flap Design Combined Nasolabial Advancement and Infraorbital Rotation for Reconstruction of Infraorbital Defect.

A Double-Lobe Flap Design Combined Nasolabial Advancement and Infraorbital Rotation for Reconstruction of Infraorbital Defect.: Various adjacent flaps have been designed to close infraorbital defect, and each of them is trying to get an aesthetic outcome and meanwhile circumvent eyelid retraction, ectropion, and functional disability. Here, the authors report an adjacent double-lobe flap, which took advantage of nasolabial advancement and infraorbital rotation of the 2 lobes, combinatorially closed a pentagon infraorbital defect by removal of 2 small skin paddles as donor sites, and finally yielded an acceptable aesthetic and functional outcome. This flap may be a new option for closure of polygon infraorbital defects.

(C) 2016 by Mutaz B. Habal, MD.




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Ketofol for Procedural Sedation and Analgesia in Closed Reduction of Nasal Fracture.

Two Different Concentrations of 



Objectives: Ketofol is a mixture of propofol and ketamine in various concentrations. It is accepted as a suitable combination in procedural sedation and analgesia. The mixture of propofol and ketamine with different respiratory and hemodynamic effects may result in fewer dose-related side effects and a probable synergistic effect. This study was designed to compare the adverse effects and quality of analgesia of 2 different intravenous concentrations of ketofol in patients undergoing closed reduction of the nose.

Methods: This randomized double-blinded study was conducted on 100 patients who underwent closed reduction of nose. The patients were divided into 2 groups of 50, and received either a combination of propofol/ketamine (1:1) (Group I) or propofol/ketamine (3:1) (Group II). Hemodynamic changes, including systolic blood pressure, diastolic blood pressure, heart rate and O2sat, and side effects such as hallucination, vomiting, coughing and apnea, were recorded.

Results: Data analysis showed that the demographic characteristics (age, height, and weight) were similar in 2 groups, and there were no significant differences between the 2 groups. There was no significant hemodynamic change between both groups. However, there was a decrease in hallucination and vomiting in the group that received higher concentration of ketofol (ketamine/propofol of 1:3).

Conclusion: There was no significant hemodynamic change between both groups that received concentrations of 1:1 and 3:1 propofol /ketamine. However, there was a reduction in hallucination, vomiting, and recovery duration in the group that received higher concentration of propofol. In conclusion, increasing the concentration of propofol can be useful with fewer side effects and lower duration of recovery.

(C) 2016 by Mutaz B. Habal, MD.




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Laryngeal Chondroma as Complication of Endotracheal Entubation

Laryngeal Chondroma: An Unusual Complication Endotracheal Entubation.: Introduction: Laryngeal cartilaginous framework tumors are very rare. Chondroma and chondrosarcoma are the most common types of these tumors.

Patient Presentation: A 27-year-old man with a history of intubation presented with exercise-induced dyspnea. A computed tomography scan of larynx showed a rounded and circumscribed mass without infiltration of the adjacent structures which obstructs 75% of airway. Histopathological investigation of the mass revealed the chondroma of the larynx. The patients' history of intubation trauma with the subsequent progressive onset of clinical symptoms demonstrates the relationship between these 2 entities.

Conclusion: Clinicians should consider laryngeal chondroma in the differential diagnosis of dyspnea after endotracheal intubation.

(C) 2016 by Mutaz B. Habal, MD.




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Secretory Cell Differentiation of the Human Airway Epithelium

JAG1-Mediated Notch Signaling Regulates 

Abstract

Basal cells (BC) are the stem/progenitor cells of the human airway epithelium capable of differentiating into secretory and ciliated cells. Notch signaling activation increases BC differentiation into secretory cells, but the role of individual Notch ligands in regulating this process in the human airway epithelium is largely unknown. The objective of this study was to define the role of the Notch ligand JAG1 in regulating human BC differentiation. JAG1 over-expression in BC increased secretory cell differentiation, with no effect on ciliated cell differentiation. Conversely, knockdown of JAG1 decreased expression of secretory cell genes. These data demonstrate JAG1-mediated Notch signaling regulates differentiation of BC into secretory cells.



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Positional OSA (POSA),Apnea hypopnea index (AHI) ≥5,Supine AHI,Ulnar nerve entrapment at elbow

Ulnar nerve entrapment at elbow in obstructive sleep apnea patients: a randomized controlled trial:

Abstract



Purpose

Obstructive sleep apnea (OSA) is a highly prevalent disease. For diagnostic and therapeutic purposes, OSA has been divided into several subgroups. Positional OSA (POSA), the most frequent subgroup (56 %), is described as overall apnea hypopnea index (AHI) ≥5 and supine AHI at least twice as high when compared to non-supine AHI. We aimed to investigate the frequency of ulnar nerve entrapment neuropathy at the elbow (UNEE) in OSA patients without clinical signs and symptoms of ulnar neuropathy and intended to find if sleeping position in OSA had an impact on UNEE development.




Methods

Fifty POSA, 48 non-positional OSA (NPOSA) patients, and 45 healthy controls without diabetes mellitus, hypothyroidism, rheumatic diseases, and cervical radiculopathy underwent nerve conduction studies.




Results

We found that UNEE was highly frequent in OSA patients (42.9 %) and significantly more frequent in moderate to severe POSA patients than mild POSA patients (65.4 vs. 33.3 %, p < 0.05). Furthermore, when compared to non-positional ones, UNEE was significantly more frequent in moderate to severe POSA patients (65.4 vs. 36.4 %, p < 0.05).




Conclusions

Our results showed that the severity of OSA in positional patients was correlated with increased frequency of UNEE. OSA patients should be informed about the predisposition of UNEE and questioned for the symptoms in periodical controls. POSA patients should be alerted about the additional effect of sleeping position on UNEE and the necessity of OSA treatment should be emphasized.



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The systematic physical examination in patients with obstructive sleep disorders

Inter-examiner agreement of the systematic physical examination in patients with obstructive sleep disorders:

Abstract



Purpose

The goal of this study was to investigate the agreement between examiners who were or were not trained in the physical examination of the upper airway (UA) and the craniofacial skeleton of individuals with obstructive sleep disorders (OSD).




Method

A systematic assessment of the UA and craniofacial skeleton was performed on 55 individuals with OSD. The participants were consecutively assessed by three otorhinolaryngologists who specialized in sleep medicine for at least 1 year (trained examiners) and two doctors who were attending a residency program in otorhinolaryngology (untrained examiners).




Results

When analyzing all of the parameters assessed, the concordance was better in the trained group (k = 0.694, which is considered "good") compared to the untrained group (k = 0.475, "fair") (p < 0.001). The inter-examiner agreement was also better in the trained compared to the untrained group, as follows: craniofacial (k = 0.643 vs. 0.349), nasal (k = 0.657 vs. 0.614), and pharyngeal (k = 0.729 vs. 0.276) abnormalities (p < 0.05).




Conclusion

The overall concordance of the physical examination of the UA and craniofacial skeleton was "good" among the trained specialists and "fair" among examiners without appropriate training, despite its subjectivity.



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The systematic physical examination in patients with obstructive sleep disorders

Inter-examiner agreement of the systematic physical examination in patients with obstructive sleep disorders:

Abstract



Purpose

The goal of this study was to investigate the agreement between examiners who were or were not trained in the physical examination of the upper airway (UA) and the craniofacial skeleton of individuals with obstructive sleep disorders (OSD).




Method

A systematic assessment of the UA and craniofacial skeleton was performed on 55 individuals with OSD. The participants were consecutively assessed by three otorhinolaryngologists who specialized in sleep medicine for at least 1 year (trained examiners) and two doctors who were attending a residency program in otorhinolaryngology (untrained examiners).




Results

When analyzing all of the parameters assessed, the concordance was better in the trained group (k = 0.694, which is considered "good") compared to the untrained group (k = 0.475, "fair") (p < 0.001). The inter-examiner agreement was also better in the trained compared to the untrained group, as follows: craniofacial (k = 0.643 vs. 0.349), nasal (k = 0.657 vs. 0.614), and pharyngeal (k = 0.729 vs. 0.276) abnormalities (p < 0.05).




Conclusion

The overall concordance of the physical examination of the UA and craniofacial skeleton was "good" among the trained specialists and "fair" among examiners without appropriate training, despite its subjectivity.



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The carbapenems and tigecycline were active against Enterobacteriaceae. Agents with activity against A. baumannii complex and P. aeruginosa are limited. The carbapenems, tigecycline, linezolid, and vancomycin were active against Gram-positive organisms.

Antimicrobial Susceptibility among European Gram-Negative and Gram-Positive Isolates Collected as Part of the Tigecycline Evaluation and Surveillance Trial (2004-2014): Background: European centers (n = 226) involved in the Tigecycline Evaluation and Surveillance Trial (TEST, 2004-2014) submitted data and bacterial isolates. Methods: Minimal inhibitory concentrations and susceptibility were determined using Clinical and Laboratory Standards Institute methods and European Committee on Antimicrobial Susceptibility Testing breakpoints. Results: The rates of the following resistant pathogens increased from 2004 to 2014: extended-spectrum β-lactamase (ESBL)-positive Escherichia coli (from 8.9 to 16.9%), multidrug-resistant Acinetobacter baumannii complex (from 15.4 to 48.5%), and ESBL-positive Klebsiella pneumoniae (from 17.2 to 23.7%). The rate of methicillin-resistant Staphylococcus aureus was 27.5% in 2004 and 28.9% in 2014. Resistance to the carbapenems (imipenem and meropenem) was 37.4 and 14.5% for A. baumannii complex and Pseudomonas aeruginosa, respectively. Carbapenem resistance was ≤4.3% among the Enterobacteriaceae and 0.2% against Streptococcus pneumoniae. The resistance to tigecycline ranged between 7.4% against ESBL-producing K. pneumoniae and 0.0% against S. aureus.



Conclusions:



The carbapenems and tigecycline were active against Enterobacteriaceae. 

Agents with activity against A. baumannii complex and P. aeruginosa are limited. 

The carbapenems, tigecycline, linezolid, and vancomycin were active against Gram-positive organisms.



Chemotherapy 2017;62:1-11




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Antimicrobial Susceptibility,The Tigecycline Evaluation and Surveillance Trial (TEST)

Antimicrobial Susceptibility among European Gram-Negative and Gram-Positive Isolates Collected as Part of the Tigecycline Evaluation and Surveillance Trial (2004-2014): Background: European centers (n = 226) involved in the Tigecycline Evaluation and Surveillance Trial (TEST, 2004-2014) submitted data and bacterial isolates. Methods: Minimal inhibitory concentrations and susceptibility were determined using Clinical and Laboratory Standards Institute methods and European Committee on Antimicrobial Susceptibility Testing breakpoints. Results: The rates of the following resistant pathogens increased from 2004 to 2014: extended-spectrum β-lactamase (ESBL)-positive Escherichia coli (from 8.9 to 16.9%), multidrug-resistant Acinetobacter baumannii complex (from 15.4 to 48.5%), and ESBL-positive Klebsiella pneumoniae (from 17.2 to 23.7%). The rate of methicillin-resistant Staphylococcus aureus was 27.5% in 2004 and 28.9% in 2014. Resistance to the carbapenems (imipenem and meropenem) was 37.4 and 14.5% for A. baumannii complex and Pseudomonas aeruginosa, respectively. Carbapenem resistance was ≤4.3% among the Enterobacteriaceae and 0.2% against Streptococcus pneumoniae. The resistance to tigecycline ranged between 7.4% against ESBL-producing K. pneumoniae and 0.0% against S. aureus.Conclusions: The carbapenems and tigecycline were active against Enterobacteriaceae. Agents with activity against A. baumannii complex and P. aeruginosa are limited. The carbapenems, tigecycline, linezolid, and vancomycin were active against Gram-positive organisms.

Chemotherapy 2017;62:1-11




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Sideline Neurological Evaluation

 a Detailed Approach to the Sideline, In-Game Neurological Assessment of Contact Sport Athletes:

Abstract

Contact sport holds inherent risk of traumatic injury to participant athletes. Neurologic injury, from trauma, portends significant potential for morbidity and mortality. The in-game sideline presents a challenging setting for injury evaluation. Athletic trainers and team physicians should understand general principles of the neurologic evaluation and apply a systematic approach that allows an organized evaluation of and differential diagnosis of neurologic injury. Athlete welfare demands an immediate, accurate diagnosis followed by targeted management. Management provides appropriate referral, timely treatment, and appropriate return-to-play decision. Management begins with recognition.



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Primary and Secondary Headache Disorders

Spreading Depression in 

Abstract



Purpose of Review

Spreading depression (SD) is a wave of simultaneous and near-complete depolarization of virtually all cells in brain tissue associated with a transient "depression" of all spontaneous or evoked electrical activity in the brain. SD is widely accepted as the pathophysiological event underlying migraine aura and may play a role in headache pathogenesis in secondary headache disorders such as ischemic stroke, subarachnoid or intracerebral hemorrhage, traumatic brain injury, and epilepsy. Here, we provide an overview of the pathogenic mechanisms and propose plausible hypotheses on the involvement of SD in primary and secondary headache disorders.




Recent Findings

SD can activate downstream trigeminovascular nociceptive pathways to explain the cephalgia in migraine, and possibly in secondary headache disorders as well. In healthy, well-nourished tissue (such as migraine), the intense transmembrane ionic shifts, the cell swelling, and the metabolic and hemodynamic responses associated with SD do not cause tissue injury; however, when SD occurs in metabolically compromised tissue (e.g., in ischemic stroke, intracranial hemorrhage, or traumatic brain injury), it can lead to irreversible depolarization, injury, and neuronal death. Recent non-invasive technologies to detect SDs in human brain injury may aid in the investigation of SD in headache disorders in which invasive recordings are not possible.




Summary

SD explains migraine aura and progression of neurological deficits associated with other neurological disorders. Studying the nature of SD in headache disorders might provide pathophysiological insights for disease and lead to targeted therapies in the era of precision medicine.



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Stress and Primary Headache

Review of the Research and Clinical Management:

Abstract

This review begins with a discussion of the nature of stress and then presents the functional model of primary headache as a framework for conceptualizing the complex relationship between stress and headaches. Research is reviewed on stress as a trigger of headaches and how stress can play a role in the developmental and psychosocial context of headaches. Clinical management of headaches from a stress perspective is considered both at the level of trials of behavioral interventions that broadly fit into the stress management category and the additional strategies that might be useful for individual cases based on the research demonstrating associations between stress and headaches. The review concludes by suggesting that although some researchers have questioned whether stress can trigger headaches, overall, the literature is still supportive of such a link. Advances in methodology are discussed, the recent emphasis on protective factors is welcomed, and directions for future research suggested.



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King LT-D supraglottic airway

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KING LT-D™: Disposable Supraglottic Airways

King Systems is one of the industry's leading manufacturers and distributors of disposal supraglottic airways. The King LT-D, a versatile airway management tool, is an alternative to tracheal intubation or mask ventilation. It is easy to insert and is strategically designed to minimize airway trauma. This sterile, single-use supraglottic airway provides a patent airway for superior patient ventilation.

Benefits of the KING LT-D Disposable Supraglottic Airways

Simple

  • Seals in the esophagus and oropharynx to provide positive pressure ventilation
  • Single inflation port
  • Color-coded full range of sizes

Disposable

  • No risk of cross-contamination


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Alternative airway placement

Rogue Capno Waves: Confirm and monitor alternative airway placement:





A 56-year-old male collapsed at a restaurant and received several minutes of dispatcher-assisted CPR. A civilian responding to a mobile phone alerting system retrieved an AED from an adjacent business and administered one shock prior to arrival of EMS.

Initial assessment revealed the morbidly obese patient had a pulse and blood pressure but was unresponsive and apneic. Bag-valve-mask ventilations were difficult due to the patient's size, so the ALS transport crew elected to intubate. After two unsuccessful oral endotracheal intubation attempts, a King LT-D supraglottic airway was inserted and manual ventilation was continued.

Consistent with protocol, waveform capnography was attached; the following tracing was obtained.





The ALS providers believed the supraglottic airway was placed properly. They theorized that the zero value ETCO2 and absence of a discernable capnography waveform resulted from the use of monitoring equipment designed for endotracheal tubes with an alternative (supraglottic) airway.

In fact, the supraglottic airway was not in place; the patient shortly thereafter became bradycardic, rearrested and subsequently died.

Comparing waveforms from different airway adjuncts


There are some studies that compare ETCO2 waveforms and measurements obtained from endotracheally intubated patients to those using supraglottic or other alternative airways. In the mid 1990s, supraglottic airways began to gain popularity as an alternative to endotracheal intubation for short duration surgical procedures requiring general anesthesia.

In that era, multiple papers were published comparing capnography waveforms and values obtained from multiple types of airways and using a wide variety of ventilation modes. It was during that same period when comparisons were made using nasal cannula derived end-tidal values.

Those studies established two findings unequivocally. First, ETCO2 values obtained from measurements made in-line with any airway device, including bag-valve-mask devices and nasal cannulas, are equivalent to those obtained from an endotracheal tube. Second, waveforms obtained from any airway device, including BVMs and nasal cannulas, are identical to those obtained from an endotracheal tube.

The implications of these earlier and innumerable studies from the anesthesia world were significant. Capnography was a safe and reliable means of assessing the adequacy of ventilation in endotracheally intubated patients, of patients being ventilated with all types of airways and of patients being ventilated with no airway adjuncts at all.

Research studies also demonstrated that capnographic waveforms could be used with alternative airways to evaluate a wide variety of conditions such as cuff leaks, ventilator dyssychrony, bronchospasm, air trapping and low cardiac output with equal efficacy regardless of the type of airway they were attached to. These findings should not be lost on EMS.

There are no differences


While there remain some questions about proper sampling and use of capnography in certain high-flow gas therapies such as jet ventilation in neonates and high-flow nasal cannula therapy for adults, neither of these therapies are currently used by EMS.

Continuous waveform capnography is an EMS standard of care and must be used to monitor placement and adequacy of ventilation with any artificial airway. The voluminous anesthesia and prehospital literature tells us that the waveforms and values obtained from any alternative airway will be identical to those obtained from an endotracheal tube.

There are no differences. If you place supraglottic airways and fail to see a four-phase capnographic waveform, the airway is not in place and ventilation is not occurring.

The incidence of misplaced supraglottic airways may not be low nor is the number of ALS providers who mistakenly attribute lack of a clearly observable capnography waveform to use of an alternative airway. An abstract presented in January by Vithalani et al, reported a 13.9 percent incidence of unrecognized misplaced King airways by paramedics in a large urban 911 EMS system.

ETCO2 is irrefutable indication of airway placement and ventilation


There are many reasons why an alternative airway may not be properly placed, some related to operator error and some to variations in patient anatomy.

Regardless of why, the absence of a clearly discernable four-phase capnography waveform and the presence of measureable CO2 is a clear and irrefutable indication that the airway is not in place and ventilation is not occurring.

Finally, EMS providers should use capnography waveforms obtained during ventilation — regardless of the type of airway in place — to assess the effectiveness of ventilation and troubleshoot airway and ventilatory issues such as cuff leaks, air trapping, airway resistance and dyssychrony.

References reviewed:

  1. Gottschalk A, Mirza N, Weinstein GS, Edwards MW.  Capnography during jet ventilation for laryngoscopy.  Anesth Analg. 1997;85:155-159.
  2. Chhibber AK, Kolano JW, Roberts WA.  Relationship between end-tidal and arterial carbon dioxide with laryngeal mask airways and endotracheal tubes in children.  Anesth Analg.  1996;82:247-250.
  3. Chhibber AK, Fickling K, Kolano JW, Roberts WA.  Comparison of end-tidal and arterial carbon dioxide in infants using laryngeal mask airway and endotracheal tube.  Anesth Analg.  1997;84:51-53.
  4. Fukuda K, Ichinohe T, Kaneko Y.  Is measurement of end-tidal CO2 through a nasal cannula reliable?  Anesth Prog.  1997;44:23-26. 
  5. Lee JS, Nam SB, Chang CH, Han DW, Lee YW, Shin CS.  Relationship between arterial and end-tidal carbon dioxide pressures during anesthesia using a laryngeal tube.  Acta Anaesthesiologica Scandinavica.  2005;49: 759-762. 
  6. Casati A, Fanelli G, Cappelleri G, Albertin A, Anelati D, Magistris L, Torri G. Arterial to end-tidal carbon dioxide tension difference in anaesthetized adults mechanically ventilated via a laryngeal mask or a cuffed oropharyngeal airway.  Eur J Anaesthesiol. 1999;16:534-538.
  7. Freeman JF, Ciarallo C, Rappaport L, Mandt M, Bajaj L.  Use of capnographs to assess quality of pediatric ventilation with 3 different airway modalities.
  8. Vithalani VD, Richmond N, Davis SQ, Hejl L, Howerton D,  Gleason W, Emergency Physicians Advisory Board, MedStar Mobile Healthcare.  Unrecognized failed airway management using a blind-insertion supraglottic device.  Abstracts for the 2016 NAEMSP Scientific Assembly.  Prehospital Emergency Care. 2016;20:144. 




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Nissen Fundoplication for Laryngopharyngeal Reflux

 After Patient Selection Using Dual pH, Full Column Impedance Testing: A Pilot Study: Objectives:

Prior studies demonstrate inconsistent diagnostic strategies for laryngopharyngeal reflux disease (LPR) patients who are offered laparoscopic Nissen fundoplication (Nissen). Superior symptom resolution outcomes are demonstrated in patients with accompanying typical gastroesophageal reflux (GERD) symptoms. This study aims to evaluate the efficacy of selecting patients with LPR complaints for Nissen using full column, dual pH impedance catheters (multichannel intraluminal impedance catheters [MII]).

Methods:

All patients who underwent Nissen for management of LPR symptoms refractory to at least 3 months of twice daily (BID) proton pump inhibitor (PPI) therapy with reflux symptom index (RSI) of 13 or higher and who had demonstrable reflux on MII were included. Pre- and (minimum) 16 week post-Nissen RSI scores as well as LPR-specific complaints were collected.

Results:

Eleven patients met criteria. Nine subjects (5 female, 4 male) had complete data. All 9 (100%) achieved improvement in RSI. The average pre-Nissen RSI was 31.7, and average post-Nissen RSI was 10 (P < .001). Six (67%) subjects dropped below an RSI of 13. Seven subjects (78%) had resolution of their primary LPR symptom, and 6 (67%) subjects had resolution of all LPR symptoms.

Conclusions:

Patients with LPR who are selected using dual pH and full column impedance are likely to demonstrate improvement in RSI following Nissen.



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Detection of Helicobacter pylori by Real-Time PCR for 16s rRNA

 in Stools of NonInfected Healthy Children, Using ELISA Antigen Stool Test as the Gold Standard:

Abstract

Background

We previously detected Helicobacter pylori infection by stool antigen ELISA assay in 33-41% of asymptomatic Chilean children between 2–3 years of age, of which 11–20% had a transient infection and 21–22% a persistent infection. A total of 88% of ELISA-positive samples were also rtPCR positive, while 37/133 (33%) of ELISA-negative stool samples were rtPCR positive. The significance of a ELISA-negative/rtPCR-positive sample requires clarification. We aimed to determine whether rtPCR is able to detect persistent infections not detected by ELISA.

Materials and Methods

We selected 36 children with an ELISA-negative/rtPCR-positive stool sample, of which 25 were never H. pylori infected according to ELISA, and 11 had a transient infection with an ELISA-positive sample before or after the discordant sample. At least two additional consecutive ELISA-negative samples per child were tested in duplicate by rtPCR for the 16s rRNA gene.

Results

A total of 14 of 78 (17.9%) rtPCR reactions were positive, but only 4/78 (5.1%) were positive in both duplicates, representing a total of 3/36 (8.3%) children with an additional rtPCR-positive sample, only one of whom was persistently negative by ELISA. One child with a transient infection had two positive rtPCR reactions despite negative ELISA samples.

Conclusions

In H. pylori noninfected or transiently infected children, as determined by stool ELISA, additional ELISA-negative/rtPCR-positive stool samples were found in 8.3% of children, but a possible persistent infection was only identified in 2.7% of children. Thus, the characterization of infection dynamics in children is not being misrepresented by application of stool ELISA. Furthermore, rtPCR does not significantly improve dynamic characterization.


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Does Dehiscence of the Facial Nerve Canal Affect Tympanoplasty Results?.

This study aimed to evaluate the prevalence of facial nerve canal dehiscence in tympanoplasty patients and its influence on the need for revision surgery and on hearing results and anatomical outcomes. Patients who underwent tympanoplasty with/without mastoidectomy at Ankara University Otolaryngology Department from 2006 through 2013 with a minimum follow-up period of 6 months were reviewed retrospectively in this original study. Patients were divided into those with and without cholesteatoma. Numbers and frequencies of dehiscence were recorded according to disease type, the need for revision surgery, and hearing results and anatomical outcomes. Study subjects included 206 patients, of whom 15 (7.3%) had dehiscence. The prevalence of dehiscence was significantly high in the patients with cholesteatoma (13/50 patients) compared with those without (2/156 patients). The dehiscence frequency was significantly high in cholesteatoma (42.8%), as well as overall (14.7%), revision-surgery patients. Hearing results (P

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Outcomes and Complications of Endoscopic Versus Microscopic Transsphenoidal Surgery in Pituitary Adenoma.

This retrospective study aimed to define outcomes and complications of endoscopic versus microscopic transsphenoidal surgery in pituitary adenoma. Data of 94 patients who underwent transsphenoidal endoscopic (n = 45) or microscopic surgery (n = 49) between June 2000 and June 2014 for pituitary adenoma, performed at Katip Celebi University Hospital, were retrospectively analyzed. The patients' symptomatology, type of adenoma, radiologic findings, surgical outcomes, and preoperative and postoperative complications were investigated. The total subtotal resection rate was 73.4% (69 patients) and partial resection rate was 26.6% (25 patients). Total subtotal resection rate was 77.6% (38 patients) in the microscopic group and 68.9% (31 patients) in the endoscopic group. Total resection was seen more often in the endoscopic group than in the microscopic group, with no significant difference between the groups. Four patients (8.2%) in the microscopic group had postoperative cerebrospinal fluid leak compared with 3 patients (6.7%) in the endoscopic group. Two patients (2.1%) had hematoma, with 1 patient each in the endoscopic and microscopic group. Panhypopituitarism development rate was higher in the endoscopic group (no significant difference between the 2 groups). One patient (2%) developed blindness in the microscopic group and 1 (2.2%) had meningitis in the endoscopic group. Based on this study, the total resection rate was higher in the microscopic group than in the endoscopic group. However, outcomes and complication rate did not differ significantly between the 2 surgical techniques. Both techniques have advantages and disadvantages. Prospective randomized controlled trials should be conducted to compare the 2 surgical methods. (C) 2016 by Mutaz B. Habal, MD.

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Two Different Concentrations of Ketofol for Procedural Sedation and Analgesia in Closed Reduction of Nasal Fracture.

Objectives: Ketofol is a mixture of propofol and ketamine in various concentrations. It is accepted as a suitable combination in procedural sedation and analgesia. The mixture of propofol and ketamine with different respiratory and hemodynamic effects may result in fewer dose-related side effects and a probable synergistic effect. This study was designed to compare the adverse effects and quality of analgesia of 2 different intravenous concentrations of ketofol in patients undergoing closed reduction of the nose. Methods: This randomized double-blinded study was conducted on 100 patients who underwent closed reduction of nose. The patients were divided into 2 groups of 50, and received either a combination of propofol/ketamine (1:1) (Group I) or propofol/ketamine (3:1) (Group II). Hemodynamic changes, including systolic blood pressure, diastolic blood pressure, heart rate and O2sat, and side effects such as hallucination, vomiting, coughing and apnea, were recorded. Results: Data analysis showed that the demographic characteristics (age, height, and weight) were similar in 2 groups, and there were no significant differences between the 2 groups. There was no significant hemodynamic change between both groups. However, there was a decrease in hallucination and vomiting in the group that received higher concentration of ketofol (ketamine/propofol of 1:3). Conclusion: There was no significant hemodynamic change between both groups that received concentrations of 1:1 and 3:1 propofol /ketamine. However, there was a reduction in hallucination, vomiting, and recovery duration in the group that received higher concentration of propofol. In conclusion, increasing the concentration of propofol can be useful with fewer side effects and lower duration of recovery. (C) 2016 by Mutaz B. Habal, MD.

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Laryngeal Chondroma: An Unusual Complication Endotracheal Entubation.

Introduction: Laryngeal cartilaginous framework tumors are very rare. Chondroma and chondrosarcoma are the most common types of these tumors. Patient Presentation: A 27-year-old man with a history of intubation presented with exercise-induced dyspnea. A computed tomography scan of larynx showed a rounded and circumscribed mass without infiltration of the adjacent structures which obstructs 75% of airway. Histopathological investigation of the mass revealed the chondroma of the larynx. The patients' history of intubation trauma with the subsequent progressive onset of clinical symptoms demonstrates the relationship between these 2 entities. Conclusion: Clinicians should consider laryngeal chondroma in the differential diagnosis of dyspnea after endotracheal intubation. (C) 2016 by Mutaz B. Habal, MD.

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A Double-Lobe Flap Design Combined Nasolabial Advancement and Infraorbital Rotation for Reconstruction of Infraorbital Defect.

Various adjacent flaps have been designed to close infraorbital defect, and each of them is trying to get an aesthetic outcome and meanwhile circumvent eyelid retraction, ectropion, and functional disability. Here, the authors report an adjacent double-lobe flap, which took advantage of nasolabial advancement and infraorbital rotation of the 2 lobes, combinatorially closed a pentagon infraorbital defect by removal of 2 small skin paddles as donor sites, and finally yielded an acceptable aesthetic and functional outcome. This flap may be a new option for closure of polygon infraorbital defects. (C) 2016 by Mutaz B. Habal, MD.

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The Use of Submental Artery Perforator Island Flap Without Including Digastric Muscle in the Reconstruction of Lower Face and Intraoral Defects.

Purpose: For reconstruction of intraoral and lower face defects, it is important to use flaps that prevent reliable and pliable soft tissue and it is possible to use aesthetically most compatible with recipient site. In this study, the authors aimed to present their clinical experiences and results of lower face and intraoral defects reconstructions with submental artery island perforator flap without including the digastric muscle to have a thinner and useful flap. Methods: Six patients with lower face and intraoral defects that were reconstructed using the submental artery island flap between November 2013 and February 2015 were retrospectively analyzed. Patient demographics, age, sex, defect etiologies, and complications were assessed. Surgical Technique: Hand Doppler examination was performed and submental artery marked preoperatively. The superior border of the flap was designed at least 1 cm away from the mandibular border to avoid injury to the marginal mandibular nerve and prevent lip eversion. After the identification of the submental artery via the retrograde dissection, the anterior belly of the digastric muscle was not included the flap to prevent a thinner flap. After the dissection, the island flap was transferred to the defect site through a subcutaneous tunnel. The donor sites were closed primarily. Results: A partially flap necrosis was occurred in 1 patient due to hematome in the tunnel around the pedicle. The wound healed uneventfully with conservative management. In the remaining patients there were no complications. Conclusion: The submental artery perforator island flap without including the digastric muscle is a reliable and suitable option for the medium-sized defects in the lower face and intraoral defects. (C) 2016 by Mutaz B. Habal, MD.

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Novel Rigid External Distraction Device Improves Stability and Controls the Vector During Midfacial Advancement.

The major limitation of the rigid external devices currently used for midfacial distraction after subcranial Le Fort III osteotomies is the ductile wire that connects the midface to the device, which makes it difficult to control the vector and force during distraction. The authors describe a novel external appliance that addresses this and other problems of contemporary devices, and application of a custom cranial template that facilitates precise placement of the device to achieve the planned vector of distraction. (C) 2016 by Mutaz B. Habal, MD.

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Guided Self-Generation of Vascularized Neo-Bone for Autologous Reconstruction of Large Mandibular Defects.

Reconstruction of large mandibular defects is complex and challenging. The authors aimed to individually self-generate a large vascularized bone construct for autologous transplantation without the use of exogenous additives based on the concept of guided self-generation. Using computer-aided design and manufacturing a large size goat mandibular bone was reconstructed in 3 dimensions. Its negative mold printed from hydroxylapatite was temporarily embedded into the costal periosteum along with a contralateral demineralized bone matrix scaffold as control. After 3 months, a mandibular bone construct was obtained and used for autologous transplantation. Osteogenesis and angiogenesis were assessed by real-time imaging, histology, and biomechanical tests during neo-bone formation and up to 6 months after transplantation surgery. A total of 20 animals received implantation of a mandibular bone negative mold along with a contralateral demineralized bone matrix scaffold. Resulting negative mold mandibular bone constructs showed anatomically, histologically, and functionally similar characteristics compared with native controls. Only 1 goat presented partial fibrosis during construct generation with subsequent absorbtion after reconstruction. The absence of exogenous cells, growth factors, and scaffolds facilitated direct translation of this novel concept into clinical application. Further studies are needed to determine functional long-term outcomes and possible extensions to other tissues and organs. (C) 2016 by Mutaz B. Habal, MD.

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Delayed Facial Nerve Palsy After Open Reduction of an Isolated Zygomaticomaxillary Complex Fracture.

Facial nerve paralysis is a devastating complication which can occur after a variety of otolaryngic procedures, including facial trauma repair. The frontal and marginal branches are most often placed at risk. However, facial nerve paralysis is not typically described as a risk in most uncomplicated facial trauma repairs of the zygomaticomaxillary complex (ZMC). In particular, buccal branch injury has not been described in a delayed setting following repair of the ZMC. The authors present a patient of delayed buccal branch paralysis following a simple ZMC repair which has not been previously reported. The diagnosis, clinical course, and management strategies for delayed facial nerve paralysis in the setting of a ZMC repair are discussed. This rare complication after facial trauma repair should be discussed with patients as a possible complication. (C) 2016 by Mutaz B. Habal, MD.

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Headache Attributed to Fibrous Dysplasia of the Ethmoid Bone Mimicking Menstrual Migraine Without Aura.

The authors experienced a patient of fibrous dysplasia originating from the ethmoid bone which presented with severe headache with some features suggestive of menstrual migraine without aura. Fibrous dysplasia originating from the ethmoid bone is a rare disease entity, but may cause severe headache that can be misdiagnosed as "menstrual migraine" because of similar symptoms in female patients. Because the primary objective of surgery is symptomatic relief, conservative transnasal endoscopic approach may be considered an alternative to more invasive external surgical techniques in carefully selected patients, especially originating from the nasal cavity and paranasal sinuses. (C) 2016 by Mutaz B. Habal, MD.

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