Aesthetic reconstruction of retroauricular keloid: Creating a keystone flap from the mastoid-helix area

Abstract

Advances in aesthetic rhinoplasty using conchal cartilage grafts have led to a high occurrence of retroauricular keloids. The purpose of this study is to introduce our surgical experiences using a keystone flap in retroauricular keloids following conchal cartilage grafts. The present study is a retrospective review of patients with pathologically confirmed retroauricular keloids following conchal cartilage grafts. These cases were surgically excised and we covered the defect with a keystone flap followed by one-time steroid injection at postoperative day 14 and silicone gel sheeting application for 3 months. Treatment outcome was recorded as recurrence or non-recurrence. In all patients, a follow-up period of minimum 12 months was required. Of these patients, 90.0% had successful treatment of their auricular keloids, whereas 10.0% had recurrences. The postoperative course was uneventful. In conclusion, our aesthetic reconstruction using a keystone flap created from the mastoid-helix area is a useful treatment strategy in terms of retroauricular keloids following conchal cartilage grafts.

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Computerbasierte Testung neurokognitiver Aspekte im Rahmen der audiologischen Diagnostik

Laryngo-Rhino-Otol
DOI: 10.1055/s-0043-124972

Hintergrund Im Hinblick auf den demographischen Wandel der Gesellschaft gewinnen in der Hörrehabilitation neurokognitive Fähigkeiten immer mehr an Bedeutung. Fragestellung Ziel der Studie war es zu untersuchen, inwiefern eine neurokognitive Testung mittels PC-gestützter Aufgaben zur Evaluation der unterschiedlichen Bereiche der Kognition auch für ältere Patienten mit und ohne Hörstörung geeignet ist und wie sich diese in den klinischen Alltag des HNO-Arztes integrieren lässt. Patientenbeschreibung 171 Patienten ≥ 50 Jahren mit und ohne eine beidseitige Hörbeeinträchtigung wurden eingeschlossen: n = 90 im Alter zwischen 50 und 64 Jahren (57,0 ± 4,5) und 81 Ältere ab 65 (72,5 ± 5,4). Methode Eine computerbasierte Testung mit rein visuellen Instruktionen beinhaltete neben der Aufmerksamkeit, der Verarbeitungsgeschwindigkeit, dem Kurz- und Langzeitgedächtnis auch exekutive Funktionen. Zuvor erfolgte ein Probedurchgang unter Anleitung einer geschulten Mitarbeiterin. Ergebnisse Auch wenn die Testung unabhängig von Alter oder Hörstatus in allen Fällen eigenständig möglich war, benötigten Hörgeschädigte 15 Minuten länger zur Durchführung und beurteilten diese als anstrengender als Hörgesunde (71 % versus 63 %). Patienten mittleren Alters sahen die Durchführbarkeit für Menschen des höheren Lebensalters mit 30 % signifikant (p = 0,02) kritischer als die betroffene Altersgruppe selbst (10 %). Schlussfolgerung Eine umfassende kognitive Testung älterer Schwerhöriger mit computerbasierten Aufgaben lässt sich problemlos in den klinischen HNO Alltag integrieren und könnte eine wertvolle Ergänzung der audiologischen Diagnostik im Hinblick auf eine bestmögliche Hörrehabilitation darstellen.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

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Inherited thrombotic thrombocytopenic purpura mimicking immune thrombocytopenic purpura during pregnancy: a case report

Thrombotic thrombocytopenic purpura is a very rare hereditary blood deficiency disorder of ADAMTS13 (von Willebrand factor-cleaving protease) and a life-threatening thrombotic microangiopathy characterized by ...

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Reassessment of Differentiated Thyroid Cancer Patients Using the Eighth TNM/AJCC Classification System: A Comparative Study

Thyroid , Vol. 0, No. 0.


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Effect of Diabetes Sleep Education for T2DM Who Sleep After Midnight: A Pilot Study from China

Metabolic Syndrome and Related Disorders , Vol. 0, No. 0.


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The Association Between Sleeping Time and Metabolic Syndrome Features, Among Older Adults Living in Mediterranean Region: The MEDIS Study

Metabolic Syndrome and Related Disorders , Vol. 0, No. 0.


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Clinical study to evaluate the performance of a noninvasive focused ultrasound device for thigh fat and circumference reduction compared to control

Summary

Background and objectives

An FDA-cleared focused ultrasound device (UltraShape, Syneron Candela^®, Yokneam, Israel) for noninvasive abdominal fat reduction produces localized mechanical cellular membrane disruption in adipocytes. This study seeks to determine the safety and efficacy of this device for use on the thighs.

Study designs/Materials and methods

Fourteen women aged 33-60 were selected to receive 3 biweekly treatments to one thigh with the other thigh serving as an internal control. The subjects had a BMI range of 18-30 kg/m² and a weight range of 54-83 kg. After the third treatment, patients were followed at 4, 8, and 16 weeks. Fat thickness was measured by both caliper and ultrasound. In addition, thigh circumference and the patient's weight were measured. Pain, edema, erythema, and adverse events as well as investigator and patient overall satisfaction were recorded at all visits.

Results

In comparison with the control, there was a statistically significant average reduction in fat thickness measured by calipers at all time points with a 22.20% (P = .0165) improvement in 16 weeks. By ultrasound, there was a 19.23% (4.03 mm P = .0051) reduction in fat thickness at 16 weeks with statistically significant improvement at the other follow-up visits. At 16 weeks, thigh circumference improved, on average, 2.8 cm (P = .0059) at the midline. 90.0% of the subjects were satisfied with the results at 16 weeks, and the investigator was 100% satisfied. No adverse events were reported; no edema was observed in any subject. All subjects experienced mild erythema. All reported zero pain on a 0-10 scale.

Conclusion

Focused ultrasound is safe, effective, and well tolerated to improve the circumference and fat thickness of the thighs without significant side effects. There were no significant adverse events. Investigators and subjects were highly satisfied with the results.

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Antibody Immunodominance: The Key to Understanding Influenza Virus Antigenic Drift

Viral Immunology , Vol. 0, No. 0.


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Preventing Peanut Allergy

Pediatric Allergy, Immunology, and Pulmonology , Vol. 0, No. 0.


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The p38-MK2/3 Module Is Critical for IL-33-Induced Signaling and Cytokine Production in Dendritic Cells [MOLECULAR AND STRUCTURAL IMMUNOLOGY]

IL-33 is an IL-1 cytokine superfamily member. Binding of IL-33 to the IL-33R induces activation of the canonical NF-B signaling and activation of MAPKs. In bone marrow–derived dendritic cells, IL-33 induces the production of IL-6, IL-13, and TNF-α. However, the signaling pathways resulting in IL-33–induced effector functions of dendritic cells are unknown. In this article, we show that the IL-33–induced cytokine production is only partly dependent on p65. Thereby, p65 mediates the production of IL-6, but not of IL-13, whereas the p38–Mapk-activated protein kinases 2/3 (MK2/3) signaling module mediates the IL-13, but not the IL-6, production. In addition, GM-CSF, which is critical for the differentiation and proliferation of bone marrow–derived dendritic cells, potentiates the p65-dependent IL-6 and the p38-MK2/3–dependent IL-13 production. Furthermore, we found that effective TNF-α production is only induced in the presence of GM-CSF and IL-33 via the p38-MK2/3 signaling module. Taken together, we found that the p38-MK2/3 signaling module is essential to mediate IL-33–induced cytokine production in dendritic cells.

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Intestinal Inflammation-Mediated Clearance of Amebic Parasites Is Dependent on IFN-{gamma} [INFECTIOUS DISEASE AND HOST RESPONSE]

Intestinal amebiasis is a major cause of diarrhea. However, research on host–amebae interactions has been hampered owing to a lack of appropriate animal models. Recently, a mouse model of intestinal amebiasis was established, and using it, we reported that Entamoeba moshkovskii colonized the intestine in a manner similar to that of the pathogenic Entamoeba histolytica. In this study, we evaluated the protective mechanisms present against amebae using this model. CBA/J mice infected with E. histolytica had a persistent infection without apparent symptoms. In contrast, E. moshkovskii–infected mice rapidly expelled the ameba, which was associated with weight loss, diarrhea, and intestinal damage characterized by apoptosis of intestinal epithelial cells (IECs). Expression of NKG2D on intestinal intraepithelial lymphocytes (IELs) and IFN-–producing cells in Peyer's patches were significantly induced after infection with E. moshkovskii but not with E. histolytica. IFN-–deficient mice infected with E. moshkovskii showed no obvious symptoms. Notably, none of these mice expelled E. moshkovskii, indicating that IFN- is responsible not only for intestinal symptoms but also for the expulsion of amebae. Furthermore, apoptosis of IECs and expression of NKG2D on IELs observed in E. moshkovskii–infected mice did not occur in the absence of IFN-. In vivo blocking of NKG2D in mice infected with E. moshkovskii enabled ameba to survive longer and remarkably reduced apoptotic IECs. Our results clearly demonstrate a novel protective mechanism exerted by IFN- against intestinal amebae, including induction of cytotoxicity of IELs toward IECs.

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Human NK Cells Downregulate Zap70 and Syk in Response to Prolonged Activation or DNA Damage [INNATE IMMUNITY AND INFLAMMATION]

The extent of NK cell activity during the innate immune response affects downstream immune functions and, ultimately, the outcome of infectious or malignant disease. However, the mechanisms that terminate human NK cell responses have yet to be defined. When activation receptors expressed on NK cell surfaces bind to ligands on diseased cells, they initiate a signal that is propagated by a number of intracellular kinases, including Zap70 and Syk, eventually leading to NK cell activation. We assayed Zap70 and Syk content in NK cells from healthy human donors and identified a subset of NK cells with unusually low levels of these two kinases. We found that this Zap70^lowSyk^low subset consisted of NK cells expressing a range of surface markers, including CD56^hi and CD56^low NK cells. Upon in vitro stimulation with target cells, Zap70^lowSyk^low NK cells failed to produce IFN- and lysed target cells at one third the capacity of Zap70^hiSyk^hi NK cells. We determined two independent in vitro conditions that induce the Zap70^lowSyk^low phenotype in NK cells: continuous stimulation with activation beads and DNA damage. The expression of inhibitory receptors, including NKG2A and inhibitory killer Ig-like receptors (KIRs), was negatively correlated with the Zap70^lowSyk^low phenotype. Moreover, expression of multiple KIRs reduced the likelihood of Zap70 downregulation during continuous activation, regardless of whether NK cells had been educated through KIR–HLA interactions in vivo. Our findings show that human NK cells are able to terminate their functional activity without the aid of other immune cells through the downregulation of activation kinases.

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Identification of a Multipotent Progenitor Population in the Spleen That Is Regulated by NR4A1 [IMMUNE SYSTEM DEVELOPMENT]

The developmental fate of hematopoietic stem and progenitor cells is influenced by their physiological context. Although most hematopoietic stem and progenitor cells are found in the bone marrow of the adult, some are found in other tissues, including the spleen. The extent to which the fate of stem cells is determined by the tissue in which they reside is not clear. In this study, we identify a new progenitor population, which is enriched in the mouse spleen, defined by cKit⁺CD71^lowCD24^high expression. This previously uncharacterized population generates exclusively myeloid lineage cells, including erythrocytes, platelets, monocytes, and neutrophils. These multipotent progenitors of the spleen (MPPS) develop from MPP2, a myeloid-biased subset of hematopoietic progenitors. We find that NR4A1, a transcription factor expressed by myeloid-biased long term-hematopoietic stem cells, guides the lineage specification of MPPS. In vitro, NR4A1 expression regulates the potential of MPPS to differentiate into erythroid cells. MPPS that express NR4A1 differentiate into a variety of myeloid lineages, whereas those that do not express NR4A1 primarily develop into erythroid cells. Similarly, in vivo, after adoptive transfer, Nr4a1-deficient MPPS contribute more to erythrocyte and platelet populations than do wild-type MPPS. Finally, unmanipulated Nr4a1^–/– mice harbor significantly higher numbers of erythroid progenitors in the spleen compared with wild-type mice. Together, our data show that NR4A1 expression by MPPS limits erythropoiesis and megakaryopoeisis, permitting development to other myeloid lineages. This effect is specific to the spleen, revealing a unique molecular pathway that regulates myeloid bias in an extramedullary niche.

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Memory T Cell Proliferation before Hepatitis C Virus Therapy Predicts Antiviral Immune Responses and Treatment Success [INFECTIOUS DISEASE AND HOST RESPONSE]

The contribution of the host immune system to the efficacy of new anti-hepatitis C virus (HCV) drugs is unclear. We undertook a longitudinal prospective study of 33 individuals with chronic HCV treated with combination pegylated IFN-α, ribavirin, and telaprevir/boceprevir. We characterized innate and adaptive immune cells to determine whether kinetics of the host response could predict sustained virologic response (SVR). We show that characteristics of the host immune system present before treatment were correlated with successful therapy. Augmentation of adaptive immune responses during therapy was more impressive among those achieving SVR. Most importantly, active memory T cell proliferation before therapy predicted SVR and was associated with the magnitude of the HCV-specific responses at week 12 after treatment start. After therapy initiation, the most important correlate of success was minimal monocyte activation, as predicted by previous in vitro work. In addition, subjects achieving SVR had increasing expression of the transcription factor T-bet, a driver of Th1 differentiation and cytotoxic effector cell maturation. These results show that host immune features present before treatment initiation predict SVR and eventual development of a higher frequency of functional virus-specific cells in blood. Such host characteristics may also be required for successful vaccine-mediated protection.

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The STAT3-IL-10-IL-6 Pathway Is a Novel Regulator of Macrophage Efferocytosis and Phenotypic Conversion in Sterile Liver Injury [INNATE IMMUNITY AND INFLAMMATION]

The disposal of apoptotic bodies by professional phagocytes is crucial to effective inflammation resolution. Our ability to improve the disposal of apoptotic bodies by professional phagocytes is impaired by a limited understanding of the molecular mechanisms that regulate the engulfment and digestion of the efferocytic cargo. Macrophages are professional phagocytes necessary for liver inflammation, fibrosis, and resolution, switching their phenotype from proinflammatory to restorative. Using sterile liver injury models, we show that the STAT3–IL-10–IL-6 axis is a positive regulator of macrophage efferocytosis, survival, and phenotypic conversion, directly linking debris engulfment to tissue repair.

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Extracellular Lactate: A Novel Measure of T Cell Proliferation [NOVEL IMMUNOLOGICAL METHODS]

Following activation, T cells rapidly divide and acquire effector functions. This energetically demanding process depends upon the ability of T cells to undergo metabolic remodeling from oxidative phosphorylation to aerobic glycolysis, during which glucose is converted into lactate and released extracellularly. In this article, we demonstrate that extracellular lactate can be used to dynamically assess human T cell responses in vitro. Extracellular lactate levels strongly correlated with T cell proliferation, and measuring lactate compared favorably with traditional methods for determining T cell responses (i.e., [³H]thymidine incorporation and the use of cell proliferation dyes). Furthermore, we demonstrate the usefulness of measuring lactate as a read-out in conventional suppression assays and high-throughput peptide-screening assays. Extracellular lactate was stably produced over 7 d, and results were reproducibly performed over several freeze–thaw cycles. We conclude that the use of extracellular lactate measurements can be a sensitive, safe, stable, and easy-to-implement research tool for measuring T cell responses and cellular metabolic changes in vitro.

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In This Issue [IN THIS ISSUE]

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Dendritic Cells on the Way to Glory [PILLARS OF IMMUNOLOGY]

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Pillars Article: Efficient presentation of soluble antigen by cultured human dendritic cells is maintained by granulocyte/macrophage colony-stimulating factor plus interleukin 4 and downregulated by tumor necrosis factor {alpha}. J. Exp. Med. 1994. 179:1109-1118 [PILLARS OF IMMUNOLOGY]

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The Hypoxia-Adenosine Link during Intestinal Inflammation [BRIEF REVIEWS]

Intestinal inflammation is a key element in inflammatory bowel disease and is related to a combination of factors, including genetics, mucosal barrier dysfunction, bacteria translocation, deleterious host–microbe interactions, and dysregulated immune responses. Over the past decade, it has been appreciated that these inflammatory lesions are associated with profound tissue hypoxia. Interestingly, an endogenous adaptive response under the control of hypoxia signaling is enhancement in adenosine signaling, which impacts these different endpoints, including promoting barrier function and encouraging anti-inflammatory activity. In this review, we discuss the hypoxia–adenosine link in inflammatory bowel disease, intestinal ischemia/reperfusion injury, and colon cancer. In addition, we provide a summary of clinical implications of hypoxia and adenosine signaling in intestinal inflammation and disease.

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Cutting Edge: Low-Affinity TCRs Support Regulatory T Cell Function in Autoimmunity [CUTTING EDGE]

Regulatory T cells (Tregs) use a distinct TCR repertoire and are more self-reactive compared with conventional T cells. However, the extent to which TCR affinity regulates the function of self-reactive Tregs is largely unknown. In this study, we used a two-TCR model to assess the role of TCR affinity in Treg function during autoimmunity. We observed that high- and low-affinity Tregs were recruited to the pancreas and contributed to protection from autoimmune diabetes. Interestingly, high-affinity cells preferentially upregulated the TCR-dependent Treg functional mediators IL-10, TIGIT, GITR, and CTLA4, whereas low-affinity cells displayed increased transcripts for Areg and Ebi3, suggesting distinct functional profiles. The results of this study suggest mechanistically distinct and potentially nonredundant roles for high- and low-affinity Tregs in controlling autoimmunity.

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Type 2 Cysteinyl Leukotriene Receptors Drive IL-33-Dependent Type 2 Immunopathology and Aspirin Sensitivity [ALLERGY AND OTHER HYPERSENSITIVITIES]

Cysteinyl leukotrienes (cysLTs) facilitate mucosal type 2 immunopathology by incompletely understood mechanisms. Aspirin-exacerbated respiratory disease, a severe asthma subtype, is characterized by exaggerated eosinophilic respiratory inflammation and reactions to aspirin, each involving the marked overproduction of cysLTs. Here we demonstrate that the type 2 cysLT receptor (CysLT₂R), which is not targeted by available drugs, is required in two different models to amplify eosinophilic airway inflammation via induced expression of IL-33 by lung epithelial cells. Endogenously generated cysLTs induced eosinophilia and expanded group 2 innate lymphoid cells (ILC2s) in aspirin-exacerbated respiratory disease–like Ptges^–/– mice. These responses were mitigated by deletions of either Cysltr2 or leukotriene C₄ synthase (Ltc4s). Administrations of either LTC₄ (the parent cysLT) or the selective CysLT₂R agonist N-methyl LTC₄ to allergen sensitized wild-type mice markedly boosted ILC2 expansion and IL-5/IL-13 generation in a CysLT₂R-dependent manner. Expansion of ILC2s and IL-5/IL-13 generation reflected CysLT₂R-dependent production of IL-33 by alveolar type 2 cells, which engaged in a bilateral feed-forward loop with ILC2s. Deletion of Cysltr1 blunted LTC₄-induced ILC2 expansion and eosinophilia but did not alter IL-33 induction. Pharmacological blockade of CysLT₂R prior to inhalation challenge of Ptges^–/– mice with aspirin blocked IL-33–dependent mast cell activation, mediator release, and changes in lung function. Thus, CysLT₂R signaling, IL-33–dependent ILC2 expansion, and IL-33–driven mast cell activation are necessary for induction of type 2 immunopathology and aspirin sensitivity. CysLT₂R-targeted drugs may interrupt these processes.

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Inhibition of the Deubiquitinase Usp14 Diminishes Direct MHC Class I Antigen Presentation [ANTIGEN RECOGNITION AND RESPONSES]

Infected or transformed cells must present peptides derived from endogenous proteins on MHC class I molecules to be recognized and targeted for elimination by Ag-specific cytotoxic T cells. In the first step of peptide generation, proteins are degraded by the proteasome. In this study, we investigated the role of the ubiquitin-specific protease 14 (Usp14), a proteasome-associated deubiquitinase, in direct Ag presentation using a ligand-stabilized model protein expressed as a self-antigen. Chemical inhibition of Usp14 diminished direct presentation of the model antigenic peptide, and the effect was especially pronounced when presentation was restricted to the defective ribosomal product (DRiP) form of the protein. Additionally, presentation specifically from DRiP Ags was diminished by expression of a catalytically inactive form of Usp14. Usp14 inhibition did not appreciably alter protein synthesis and only partially delayed protein degradation as measured by a slight increase in the half-life of the model protein when its degradation was induced. Taken together, these data indicate that functional Usp14 enhances direct Ag presentation, preferentially of DRiP-derived peptides, suggesting that the processing of DRiPs is in some ways different from other forms of Ag.

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B Cell-Intrinsic MyD88 Signaling Promotes Initial Cell Proliferation and Differentiation To Enhance the Germinal Center Response to a Virus-like Particle [ANTIGEN RECOGNITION AND RESPONSES]

Although TLR signaling in B cells has been implicated in the germinal center (GC) responses during viral infections and autoimmune diseases, the underlying mechanism is unclear. Bacterial phage Qβ-derived virus-like particle (Qβ-VLP) contains TLR ligands, which can enhance Qβ-VLP-induced Ab response, including GC response, through TLR/MyD88 signaling in B cells. In this study, by examining Ag-specific B cell response to Qβ-VLP, we found that lack of B cell MyD88 from the beginning of the immune response led to a more severe defect in the GC scale than abolishing MyD88 at later time points of the immune response. Consistently, B cell–intrinsic MyD88 signaling significantly enhanced the initial proliferation of Ag-specific B cells, which was accompanied with a dramatic increase of plasma cell generation and induction of Bcl-6⁺ GC B cell precursors. In addition, B cell–intrinsic MyD88 signaling promoted strong T-bet expression independent of IFN- and led to the preferential isotype switching to IgG2a/c. Thus, by promoting the initial Ag-specific B cell proliferation and differentiation, B cell–intrinsic MyD88 signaling enhanced both T-independent and T-dependent Ab responses elicited by Qβ-VLP. This finding will provide additional insight into the role of TLR signaling in antiviral immunity, autoimmune diseases, and vaccine design.

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Murine Red Blood Cells Lack Ligands for B Cell Siglecs, Allowing Strong Activation by Erythrocyte Surface Antigens [ANTIGEN RECOGNITION AND RESPONSES]

CD22 and sialic acid–binding Ig-like lectin (Siglec)-G are members of the Siglec family of inhibitory coreceptors expressed on B cells that participate in enforcement of peripheral B cell tolerance. We have shown previously that when a BCR engages its cognate Ag on a cell surface that also expresses Siglec ligands, B cell Siglecs are recruited to the immunological synapse, resulting in suppression of BCR signaling and B cell apoptosis. Because all cells display sialic acids, and CD22 and Siglec-G have distinct, yet overlapping, specificities for sialic acid–containing glycan ligands, any cell could, in principle, invoke this tolerogenic mechanism for cell surface Ags. However, we show in this article that C57BL/6J mouse RBCs are essentially devoid of CD22 and Siglec-G ligands. As a consequence, RBCs that display a cell surface Ag, membrane-bound hen egg lysozyme, strongly activate Ag-specific B cells. We reasoned that de novo introduction of CD22 ligands in RBCs should abolish B cell activation toward its cognate Ag on the surface of RBCs. Accordingly, we used a glyco-engineering approach wherein synthetic CD22 ligands linked to lipids are inserted into the membrane of RBCs. Indeed, insertion of CD22 ligands into the RBC cell surface strongly inhibited B cell activation, cytokine secretion, and proliferation. These results demonstrate that the lack of Siglec ligands on the surface of murine RBCs permits B cell responses to erythrocyte Ags and show that Siglec-mediated B cell tolerance is restricted to cell types that express glycan ligands for the B cell Siglecs.

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Antibody-Mediated Neutralization of uPA Proteolytic Function Reduces Disease Progression in Mouse Arthritis Models [AUTOIMMUNITY]

Genetic absence of the urokinase-type plasminogen activator (uPA) reduces arthritis progression in the collagen-induced arthritis (CIA) mouse model to an extent just shy of disease abrogation, but this remarkable observation has not been translated into therapeutic intervention. Our aim was to test the potential in mice of an Ab that blocks the proteolytic capacity of uPA in the CIA model and the delayed-type hypersensitivity arthritis model. A second aim was to determine the cellular origins of uPA and the uPA receptor (uPAR) in joint tissue from patients with rheumatoid arthritis. A mAb that neutralizes mouse uPA significantly reduced arthritis progression in the CIA and delayed-type hypersensitivity arthritis models. In the CIA model, the impact of anti-uPA treatment was on par with the effect of blocking TNF-α by etanercept. A pharmacokinetics evaluation of the therapeutic Ab revealed target-mediated drug disposition consistent with a high turnover of endogenous uPA. The cellular expression patterns of uPA and uPAR were characterized by double immunofluorescence in the inflamed synovium from patients with rheumatoid arthritis and compared with synovium from healthy donors. The arthritic synovium showed expression of uPA and uPAR in neutrophils, macrophages, and a fraction of endothelial cells, whereas there was little or no expression in synovium from healthy donors. The data from animal models and human material provide preclinical proof-of-principle that validates uPA as a novel therapeutic target in rheumatic diseases.

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GM-CSF Promotes Chronic Disability in Experimental Autoimmune Encephalomyelitis by Altering the Composition of Central Nervous System-Infiltrating Cells, but Is Dispensable for Disease Induction [AUTOIMMUNITY]

GM-CSF has been portrayed as a critical cytokine in the pathogenesis of experimental autoimmune encephalomyelitis (EAE) and, ostensibly, in multiple sclerosis. C57BL/6 mice deficient in GM-CSF are resistant to EAE induced by immunization with myelin oligodendrocyte glycoprotein (MOG)_35–55. The mechanism of action of GM-CSF in EAE is poorly understood. In this study, we show that GM-CSF augments the accumulation of MOG_35–55-specific T cells in the skin draining lymph nodes of primed mice, but it is not required for the development of encephalitogenic T cells. Abrogation of GM-CSF receptor signaling in adoptive transfer recipients of MOG_35–55-specific T cells did not alter the incidence of EAE or the trajectory of its initial clinical course, but it limited the extent of chronic CNS tissue damage and neurologic disability. The attenuated clinical course was associated with a relative dearth of MOG_35–55-specific T cells, myeloid dendritic cells, and neutrophils, as well as an abundance of B cells, within CNS infiltrates. Our data indicate that GM-CSF drives chronic tissue damage and disability in EAE via pleiotropic pathways, but it is dispensable during early lesion formation and the onset of neurologic deficits.

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Production of IL-17 by MAIT Cells Is Increased in Multiple Sclerosis and Is Associated with IL-7 Receptor Expression [AUTOIMMUNITY]

Multiple sclerosis (MS) is a T cell–driven inflammatory disease of the CNS. Research on T cell subsets involved in MS pathogenesis has mainly focused on classical CD4⁺ T cells, especially Th17 cells, as they produce the proinflammatory, MS-associated cytokine IL-17. However, the abundant unconventional mucosal-associated invariant T (MAIT) cells are also able to produce IL-17. MAIT cells are characterized by high CD161 expression and a semi-invariant Vα7.2 TCR, with which they recognize bacterial and yeast Ags derived from the riboflavin (vitamin B2) metabolism. In this study, we characterized MAIT cells from the peripheral blood of MS patients in comparison with healthy individuals with respect to their type-17 differentiation. We found a specific increase of IL-17⁺ MAIT cells as well as an increased expression of retinoic acid–related orphan receptor (ROR)t and CCR6 in MAIT cells from MS patients, whereas the expression of T cell activation markers HLA-DR and CD38 was not different. IL-17 production by MAIT cells furthermore correlated with the surface expression level of the IL-7 receptor α-chain (CD127), which was significantly increased on MAIT cells from MS patients in comparison with healthy individuals. In summary, our findings indicate an augmented type-17 differentiation of MAIT cells in MS patients associated with their IL-7 receptor surface expression, implicating a proinflammatory role of these unconventional T cells in MS immunopathology.

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Select Clr-g Expression on Activated Dendritic Cells Facilitates Cognate Interaction with a Minor Subset of Splenic NK Cells Expressing the Inhibitory Nkrp1g Receptor [IMMUNE REGULATION]

Natural killer gene complex–encoded immunomodulatory C-type lectin-like receptors include members of the NKRP1 and C-type lectin-like 2 (CLEC2) gene families, which constitute genetically linked receptor-ligand pairs and are thought to allow for NK cell–mediated immunosurveillance of stressed or infected tissues. The mouse C-type lectin-like receptor Nkrp1g was previously shown to form several receptor-ligand pairs with the CLEC2 proteins Clr-d, Clr-f, and Clr-g, respectively. However, the physiological expression of Nkrp1g and its CLEC2 ligands as well as their functional relevance remained poorly understood. Recently, we demonstrated a gut-restricted expression of Clr-f on intestinal epithelial cells that is spatially matched by Nkrp1g on subsets of intraepithelial lymphocytes. In this study, we investigated expression and ligand interaction of Nkrp1g in the splenic compartment, and found an exclusive expression on a small subset of NK cells that upregulates Nkrp1g after cytokine exposure. Whereas transcripts of Clr-d and Clr-f are virtually absent from the spleen, Clr-g transcripts were abundantly detected throughout different leukocyte populations and hematopoietic cell lines. However, a newly generated anti–Clr-g mAb detected only residual Clr-g surface expression on splenic monocytes, whereas many hematopoietic cell lines brightly display Clr-g. Clr-g surface expression was strongly upregulated on splenic CD8α⁺ conventional dendritic cells (DCs) and plasmacytoid DCs upon TLR-mediated activation and detectable by Nkrp1g, which dampens NK cell effector functions upon Clr-g engagement. Hence, different to the intestinal tract, in the spleen, Nkrp1g is selectively expressed by a subset of NK cells, thereby potentially allowing for an inhibitory engagement with Clr-g-expressing activated DCs during immune responses.

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Novel TCR-Mediated Mechanisms of Notch Activation and Signaling [IMMUNE REGULATION]

The Notch receptor is an evolutionarily highly conserved transmembrane protein that is essential to a wide spectrum of cellular systems. Notch signaling is especially important to T cell development, and its deregulation leads to leukemia. Although not well characterized, it continues to play an integral role in peripheral T cells, in which a unique mode of Notch activation can occur. In contrast to canonical Notch activation initiated by adjacent ligand-expressing cells, TCR stimulation is sufficient to induce Notch signaling. However, the interactions between these two pathways have not been defined. In this article, we show that Notch activation occurs in peripheral T cells within a few hours post–TCR stimulation and is required for optimal T cell activation. Using a panel of inhibitors against components of the TCR signaling cascade, we demonstrate that Notch activation is facilitated through initiation of protein kinase C–induced ADAM activity. Moreover, our data suggest that internalization of Notch via endocytosis plays a role in this process. Although ligand-mediated Notch stimulation relies on mechanical pulling forces that disrupt the autoinhibitory domain of Notch, we hypothesized that, in T cells in the absence of ligands, these conformational changes are induced through chemical adjustments in the endosome, causing alleviation of autoinhibition and receptor activation. Thus, T cells may have evolved a unique method of Notch receptor activation, which is described for the first time, to our knowledge, in this article.

http://ift.tt/2DwN5lH

Human M2 Macrophages Limit NK Cell Effector Functions through Secretion of TGF-{beta} and Engagement of CD85j [IMMUNE REGULATION]

NK cells play important roles during immunosurveillance against tumors and viruses as they trigger cytotoxicity against susceptible cells and secrete proinflammatory cytokines such as IFN-. In addition, upon activation, macrophages can become proinflammatory (M1) or anti-inflammatory (M2) cells. Although the consequences of the cross-talk between M1 and NK cells are known, the outcome of the cross-talk between M2 and NK cells remains ill-defined. Therefore, in the current work, we investigated the outcome and the underlying mechanisms of the interaction between resting or stimulated human NK cells with M1 or M2. We observed a lower percentage of activated NK cells that produced less IFN- upon coculture with M2. Also, CD56^dim NK cells cocultured with M2 displayed lower degranulation and cytotoxic activity than NK cells cocultured with M1. Soluble TGF-β and M2-driven upregulation of CD85j (ILT-2) on NK cells accounted for the diminished IFN- production by CD56^bright NK cells, whereas M2-driven upregulation of CD85j on NK cells accounted for the generation of hyporesponsive CD56^dim NK cells with limited degranulation and cytotoxic capacity. Accordingly, M2 expressed higher amounts of HLA-G, the main ligand for CD85j, than M1. Hyporesponsiveness to degranulation in NK cells was not restored at least for several hours upon removal of M2. Therefore, alternatively activated macrophages restrain NK cell activation and effector functions through different mechanisms, leading to NK cells that display diminished IFN- production and at least a transiently impaired degranulation ability. These results unravel an inhibitory circuit of possible relevance in pathological situations.

http://ift.tt/2n0qP8M

Deficiency of the AIM2-ASC Signal Uncovers the STING-Driven Overreactive Response of Type I IFN and Reciprocal Depression of Protective IFN-{gamma} Immunity in Mycobacterial Infection [IMMUNE REGULATION]

The nucleic acids of Mycobacterium tuberculosis can be detected by intracellular DNA sensors, such as cyclic GMP-AMP synthase and absent in melanoma 2 (AIM2), which results in the release of type I IFN and the proinflammatory cytokine IL-1β. However, whether cross-talk occurs between AIM2–IL-1β and cyclic GMP-AMP synthase–type I IFN signaling upon M. tuberculosis infection in vivo is unclear. In this article, we demonstrate that mycobacterial infection of AIM2^–/– mice reciprocally induces overreactive IFN-β and depressive IFN- responses, leading to higher infection burdens and more severe pathology. We also describe the underlying mechanism whereby activated apoptosis-associated speck-like protein interacts with a key adaptor, known as stimulator of IFN genes (STING), and inhibits the interaction between STING and downstream TANK-binding kinase 1 in bone marrow–derived macrophages and bone marrow–derived dendritic cells, consequently reducing the induction of type I IFN. Of note, apoptosis-associated speck-like protein expression is inversely correlated with IFN-β levels in PBMCs from tuberculosis patients. These data demonstrate that the AIM2–IL-1β signaling pathway negatively regulates the STING–type I IFN signaling pathway by impeding the association between STING and TANK-binding kinase 1, which protects the host from M. tuberculosis infection. This finding has potential clinical significance.

http://ift.tt/2Dyv2Mg

IL-4-Induced Gene 1: A Negative Immune Checkpoint Controlling B Cell Differentiation and Activation [IMMUNE REGULATION]

Emerging data highlight the crucial role of enzymes involved in amino acid metabolism in immune cell biology. IL-4–induced gene-1 (IL4I1), a secreted l-phenylalanine oxidase expressed by APCs, has been detected in B cells, yet its immunoregulatory role has only been explored on T cells. In this study, we show that IL4I1 regulates multiple steps in B cell physiology. Indeed, IL4I1 knockout mice exhibit an accelerated B cell egress from the bone marrow, resulting in the accumulation of peripheral follicular B cells. They also present a higher serum level of natural Igs and self-reactive Abs. We also demonstrate that IL4I1 produced by B cells themselves controls the germinal center reaction, plasma cell differentiation, and specific Ab production in response to T dependent Ags, SRBC, and NP-KLH. In vitro, IL4I1-deficient B cells proliferate more efficiently than their wild-type counterparts in response to BCR cross-linking. Moreover, the absence of IL4I1 increases activation of the Syk-Akt-S6kinase signaling pathway and calcium mobilization, and inhibits SHP-1 activity upon BCR engagement, thus supporting that IL4I1 negatively controls BCR-dependent activation. Overall, our study reveals a new perspective on IL4I1 as a key regulator of B cell biology.

http://ift.tt/2n0OZQp

EZH2 Represses the B Cell Transcriptional Program and Regulates Antibody-Secreting Cell Metabolism and Antibody Production [IMMUNE REGULATION]

Epigenetic remodeling is required during B cell differentiation. However, little is known about the direct functions of epigenetic enzymes in Ab-secreting cells (ASC) in vivo. In this study, we examined ASC differentiation independent of T cell help and germinal center reactions using mice with inducible or B cell–specific deletions of Ezh2. Following stimulation with influenza virus or LPS, Ezh2-deficient ASC poorly proliferated and inappropriately maintained expression of inflammatory pathways, B cell–lineage transcription factors, and Blimp-1–repressed genes, leading to fewer and less functional ASC. In the absence of EZH2, genes that normally gained histone H3 lysine 27 trimethylation were dysregulated and exhibited increased chromatin accessibility. Furthermore, EZH2 was also required for maximal Ab secretion by ASC, in part due to reduced mitochondrial respiration, impaired glucose metabolism, and poor expression of the unfolded-protein response pathway. Together, these data demonstrate that EZH2 is essential in facilitating epigenetic changes that regulate ASC fate, function, and metabolism.

http://ift.tt/2Dw0Zo7

A Cellular MicroRNA Facilitates Regulatory T Lymphocyte Development by Targeting the FOXP3 Promoter TATA-Box Motif [IMMUNE SYSTEM DEVELOPMENT]

The CD4⁺CD25⁺FOXP3⁺ regulatory T cells (Tregs) mediate immunological self-tolerance and suppress various immune responses. FOXP3 is a key transcriptional factor for the generation and development of Tregs. Its expression is regulated by various cytokines including TGF-β, IL-2, and IL-10. It is important to further identify the regulatory factors for Tregs. Given that many microRNAs (miRNAs) could specifically interact with the core promoter region and specifically enhance the transcription of many target genes, we searched for any possible miRNA(s) targeting the core promoter region of the FOXP3 gene. We found that miR-4281, an miRNA specifically expressed in hominids, can potently and specifically upregulate FOXP3 expression by directly interacting with the TATA-box motif in the human FOXP3 promoter. Consequently, miR-4281 significantly accelerated the differentiation of human naive cells to induced Tregs (iTregs) that possess immune suppressor functions and weaken the development of graft-versus-host disease in a humanized mouse model. Interestingly, iTregs induced by the combination of TGF-β, IL-2, and chemically synthesized miR-4281 were more stable and functional than those induced by TGF-β and IL-2 alone. Moreover, we found that the IL-2/STAT5 signal transduction upregulates FOXP3 expression not only through the classical pathway, but also by enhancing the expression of the miR-4281 precursor gene (SNCB) and, correspondingly, miR-4281. This study reveals a novel mechanism regulating FOXP3 expression and human iTreg development and, therefore, offers a new therapeutic target to manipulate immunosuppressive system.

http://ift.tt/2n2LQj4

Newly Generated CD4+ T Cells Acquire Metabolic Quiescence after Thymic Egress [IMMUNE SYSTEM DEVELOPMENT]

Mature naive T cells circulate through the secondary lymphoid organs in an actively enforced quiescent state. Impaired cell survival and cell functions could be found when T cells have defects in quiescence. One of the key features of T cell quiescence is low basal metabolic activity. It remains unclear at which developmental stage T cells acquire this metabolic quiescence. We compared mitochondria among CD4 single-positive (SP) T cells in the thymus, CD4⁺ recent thymic emigrants (RTEs), and mature naive T cells in the periphery. The results demonstrate that RTEs and naive T cells had reduced mitochondrial content and mitochondrial reactive oxygen species when compared with SP thymocytes. This downregulation of mitochondria requires T cell egress from the thymus and occurs early after young T cells enter the circulation. Autophagic clearance of mitochondria, but not mitochondria biogenesis or fission/fusion, contributes to mitochondrial downregulation in RTEs. The enhanced apoptosis signal-regulating kinase 1/MAPKs and reduced mechanistic target of rapamycin activities in RTEs relative to SP thymocytes may be involved in this mitochondrial reduction. These results indicate that the gain of metabolic quiescence is one of the important maturation processes during SP–RTE transition. Together with functional maturation, it promotes the survival and full responsiveness to activating stimuli in young T cells.

http://ift.tt/2DyqIMM

Comparative study on the incision healing of the palatal mucosa by using Er:YAG laser or traditional scalpel in the SD rats

Abstract

The aim of this study was to compare the histology of wound healing following incisions with the scalpel or the Er:YAG laser in the palatal mucosa of SD rats. Two types of wounds were performed with the stainless steel scalpel or the Er:YAG laser in the palatal mucosa of SD rats, while the adjacent untreated palatal mucosa was chosen as control. Rats were sacrificed on day 1, day 3, day 7, and day 30 post-surgery. Biopsy samples from each wound were examined and the expression of IL-1ß and TGF-ß1 was determined by enzyme-linked immunosorbent assay (ELISA). The early postoperative incision of the scalpel group had obvious bleeding and swelling, while the laser wound mainly covered the surface of white pseudomembrane. The infiltration of neutrophils and lymphocytes in the stroma of the scalpel incision was more than that of the laser group. Compared to the laser group, 1 and 3 days after operation, the TGF-β1 content of the scalpel group were significantly increased (P = 0.032 and 0.019). Seven days after operation, the TGF-β1 content of two groups was decreased. TGF-β1 expression of control group was obviously increased (P > 0.05); 1, 3, and 7 days after operation, the traditional scalpel amount of IL-1β expression was significantly higher than that of control group (P = 0.000, 0.000, and 0.001). Postoperative day 1, IL-1β expression of laser group and control group had no significant difference (P = 0.572). Three days after operation, IL-1β expression of laser incision was increased and was significantly higher than that in control group (P = 0.032), however lower than the scalpel group (P = 0.03). Seven days after operation, the IL-1β expression of two groups had no significant difference (P = 0.333); however, the IL-1β expression of two groups were significantly higher than that of the control group (P = 0.02 and 0.001). Compared to the traditional scalpel, the incision of Er:YAG laser has smaller inflammation reaction, more pseudomembrane coverage, and minimal damage of the mucoperiosteal tissue.

http://ift.tt/2G5joFX

Stevens–Johnson syndrome/toxic epidermal necrolysis and erythema multiforme drug-related hospitalisations in a national administrative database

Stevens–Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) and erythema multiforme (EM) are immunologically-mediated dermatological disorders commonly triggered by drug exposure and/or other external agents...

http://ift.tt/2BkpmiN

Does hyperthyroidism worsen prognosis of thyroid carcinoma? A retrospective analysis on 2820 consecutive thyroidectomies

Hyperthyroidism is associated with high incidence of thyroid carcinoma; furthermore, tumors arisen in hyperthyroid tissue show an aggressive behavior. Thyroid Stimulating Hormone (TSH) and Thyroid-stimulating ...

http://ift.tt/2n52lwb

An automated A-value measurement tool for accurate cochlear duct length estimation

There has been renewed interest in the cochlear duct length (CDL) for preoperative cochlear implant electrode selection and postoperative generation of patient-specific frequency maps. The CDL can be estimated...

http://ift.tt/2BlazEl

Use of medial upper arm free flap in oral cavity reconstruction: a preliminary study

The medial upper arm has previously been proposed as a potential free flap donor site, but the clinical application of such flaps in head and neck reconstruction has not been popular. The preliminary results of the clinical application of medial upper arm free flaps in oral cavity reconstruction are reported here. Five patients with oral cancer underwent surgical resection and neck dissection, with simultaneous reconstruction using a medial upper arm free flap. Functional outcomes were investigated using the University of Washington Quality of Life Questionnaire.

http://ift.tt/2BlDMz6

Seltene Ursache einer supraklavikulären Schwellung

http://ift.tt/2rqGO5G

3D accuracy of implant positions in template-guided implant placement as a function of the remaining teeth and the surgical procedure: a retrospective study

Abstract

Objective

The aim of this study was to investigate differences between the virtually planned and clinically achieved implant positions in completely template-guided implantations as a function of the type of edentulous space, the residual natural dentition, and the surgical implementation.

Materials and methods

Fifty-six patient cases with a total of 122 implants were evaluated retrospectively. The implantations were completely template-based. The data of the planned implant positions were overlaid with the actual clinical implant positions, followed by measurements of the 3D deviations in terms of coronal (x_c) and apical distance, height (x_h), and angulation (ang) and statistical analysis.

Results

The mean x_c was 1.2 mm (SD 0.7 mm); the mean x_a was 1.8 mm (SD 0.9 mm), the mean x_h was 0.8 mm (SD 0.7 mm); and the mean ang was 4.8° (SD 3.1). The type of edentulous space and the jaw (maxilla/mandible) had no significant effect on the results in terms of implant positions. The presence of an adjacent natural tooth at the time of implantation had a significant influence on x_h (p = 0.04) and ang (p = 0.05). No significant differences were found regarding the surgical approach for any of the parameters examined.

Conclusion

The results of our study are in the same range as those of other studies. Template-guided implantation offers a high degree of accuracy even in the presence of different configurations of the residual dentition or different surgical approaches. A clinical benefit is therefore present, especially from a prosthetic point of view.

Clinical relevance

The clinically achievable accuracy can be described as sufficient for further prosthetic treatment, given the intrinsic and methodological tolerances, making prosthetic rehabilitation safe and predictable.

http://ift.tt/2G3YRlc

In response to socioeconomic disparities and comorbidities, not race, affect salivary gland malignancy survival outcomes

http://ift.tt/2DpGTYS

Early-injection laryngoplasty may lower risk of thyroplasty: A systematic review and meta-analysis

Objective

To determine whether injection laryngoplasty within 6 months following the onset of unilateral vocal fold paralysis (UVFP) decreases the rate of permanent thyroplasty in adults.

Data Sources

Search strategies created by a medical librarian were implemented in multiple online research databases.

Review Methods

Inclusion and exclusion criteria were designed to capture randomized clinical trials and cohort studies examining adults with UVFP who received injection laryngoplasty early in the course of treatment, within 6 months of onset, or who were observed. The primary outcome was the rate of thyroplasty. The Newcastle-Ottawa scale was used to assess quality of included cohort studies. Random effects meta-analysis was used to calculate an overall relative risk (RR). Heterogeneity was evaluated with the I² statistic.

Results

The search strategy resulted in 1,177 studies, of which four cohort studies remained for meta-analysis after applying inclusion and exclusion criteria. All studies were rated as 9 of 9 on the Newcastle-Ottawa scale. Meta-analysis of 275 patients with UVFP revealed that the overall pooled RR of undergoing thyroplasty in those receiving an early injection was 0.25 (95% confidence interval 0.14–0.45) compared to conservative management (late or no injection). The I² overall was 62.4%.

Conclusion

Otolaryngologists should offer injection laryngoplasty to patients with a diagnosis of UVFP within 6 months of diagnosis (recommendation based on grade C evidence with a preponderance of benefit over harm). Laryngoscope, 2018

http://ift.tt/2DXsyDX

Innervation status in chronic vocal fold paralysis and implications for laryngeal reinnervation

Objective

Treatment options for symptomatic unilateral vocal fold paralysis (VFP) include vocal fold augmentation, laryngeal framework surgery, and laryngeal reinnervation. Laryngeal reinnervation (LR) has been suggested to provide "tone" to the paralyzed VF. This implies a loss of tone as a result of denervation without reinnervation. We performed laryngeal electromyography (LEMG) in patients with chronic VFP to understand the innervation status associated with a chronically paralyzed vocal fold.

Study Design

Retrospective review of LEMG data in adult patients with chronic VFP from January 2009 to December 2014.

Methods

LEMG was performed at least 6 months after-onset of VFP. Qualitative LEMG, quantitative LEMG, and adductory synkinesis testing were performed, and the parameters were collected.

Results

Twenty-seven vocal folds were studied (23 unilateral VFP and 2 bilateral VFP). Average age was 59 ± 17 years. The median duration from recurrent laryngeal nerve injury to LEMG was 8.5 months (range 6–90 months). The majority of patients, 24 of 27 (89%), had motor unit potentials during phonation tasks on LEMG, and only 3 of 27 (11%) patients were electrically silent. Quantitative LEMG showed 287.8 mean turns per second (normal ≥ 400). Motor unit configuration was normal in 12 of 27 (44%), polyphasic in 12 of 27 (44%), and absent in the electrically silent patients. Adductory synkinesis was found in 6 of 20 (30%) patients.

Conclusion

Chronic vocal fold paralysis is infrequently associated with absent motor-unit recruitment, indicating some degree of preserved innervation and/or reinnervation in these patients. LEMG should be part of the routine workup for chronic VFP prior to consideration of LR.

Level of Evidence

4. Laryngoscope, 2018

http://ift.tt/2DpGKEO

Perception and duration of pain after office-based vocal fold injection augmentation

Objectives/Hypothesis

In-office laryngology procedures are important in the treatment of voice and swallowing disorders. Patient tolerance determines which procedures can be performed without sedation or formal anesthesia. This study examines pain perception during and after in-office vocal fold injection augmentation.

Study Design

Prospective cohort study.

Methods

Patients scheduled for office-based vocal fold injection augmentation were prospectively enrolled at an academic voice center. The short-form McGill Pain Questionnaire was administered before, during, and after the procedure and on postprocedure days 1, 3, and 7. Pre- and postprocedure vital signs were recorded and heart rate was continuously monitored. Telephone questionnaires were completed on postprocedure days 1 and 3.

Results

Forty-five patients consented to participate in our study (24 males, mean age 61 years). Most patients experienced mild to moderate pain with increasing heart rate during the procedure. Pain remained or increased 20 minutes after the procedure and improved but persisted for 1 day. Sensory and affective discomfort was endorsed by the majority. A minority of patients experienced bruising and changes in swallowing with diet modification for 3 days after the procedure. Sixteen percent had discomfort after 1 week.

Conclusions

This is the first prospective study examining patient perception of pain during and after in-office injection augmentation using a validated scale and pain descriptors with extended follow-up. The results may offer guidance for patient counseling, consent, and treatment to improve tolerance and success.

Level of Evidence

4. Laryngoscope, 2018

http://ift.tt/2DX4z7Q

Programmed death ligand-1 expression as immunotherapeutic target in sinonasal cancer

Abstract

Background

Sinonasal cancer carries a poor prognosis, especially in recurrent stages, and it is a disease with very limited treatment options.

Methods

The expression of programmed death ligand-1 (PD-L1) as a marker for immunotherapy was evaluated in 53 sinonasal squamous cell carcinoma (SCC) and 126 intestinal-type adenocarcinoma (ITAC) samples. Results were correlated to clinicopathological characteristics and follow-up data.

Results

Membranous PD-L1 staining of tumor cells was observed in 34% (18/53) of the sinonasal SCC samples and in 17% (22/126) of the ITAC samples. The PD-L1 positivity on infiltrating immune cells occurred in 45% (24/53) of the sinonasal SCC samples and in 33% (41/126) of the ITAC samples. Expression of PD-L1 showed no correlation to clinicopathological parameters and was not an independent risk factor for survival.

Conclusion

The PD-L1 positivity does not seem to have prognostic value. However, a proportion of patients with sinonasal SCC and ITAC may benefit from therapy with immune checkpoint inhibitors that recently have been approved for clinical application in head and neck cancer.

http://ift.tt/2Dr40ly

Targeting of miR-31/96/182 to the Numb gene during head and neck oncogenesis

Abstract

Background

MicroRNAs (miRNAs) play crucial roles in head and neck squamous cell carcinoma (HNSCC). This study investigates whether miR-31, miR-96, and miR-182 are involved in targeting Numb during HNSCC.

Methods

The expression of miR-31/96/182 in tumor tissues was analyzed. Reporter assay, knockdown, expression, and oncogenic analysis were carried out in cell lines.

Results

Upregulation of miR-31/96/182 was detected in tumor tissues. In addition, advanced tumors showed higher expression levels of these miRNAs. The expression of these miRNAs was upregulated after treatment with areca ingredients (P < .01 or P < .001). These miRNAs directly targeted the 3′ untranslated region (UTR) sequence of the Numb gene. An increased migration and invasion of HNSCC cells was associated with the exogenous expression of miR-31/96/182 (P < .01 or P < .001), and this was reverted by expression of Numb.

Conclusion

This study provides new evidence demonstrating that there is frequent and concordant upregulation of miR-31, miR-96, and miR-182 during HNSCC and these miRNAs co-target Numb.

http://ift.tt/2E0KyNS

Multicenter assessment of exclusive endoscopic endonasal approach for the treatment of 53 olfactory neuroblastomas

Abstract

Background

Given the particularities of olfactory neuroblastoma (ONB) and the lack of studies on the subject, a multicenter collaborative study was conducted to assess treatment strategy.

Methods

Fifty-three patients with ONB were included from the French Rare Head and Neck Cancer Expert Network (REFCOR) database: 16T1, 8T2, 19T3, and 10T4. All cases were treated endoscopically with skull base removal and repair in 26 cases (49%) and without external craniotomy.

Results

The overall survival (OS) and disease-free survival (DFS) rates at 5 years were 87% and 71%, respectively, with mean follow-up of 45.4 ± 26.5 months. The complication rate was 18.8% with 4 cases of meningitis. Pathological analysis showed positive margins in 26.8%, notably on the dura-mater and periorbita, without impairment of OS or DFS. Forty-eight patients received adjuvant radiotherapy on T ± N. Ten patients had a recurrence (18.9%). Six patients died of their disease. Prophylactic neck irradiation seemed to reduce the recurrence rate.

Conclusion

Exclusively endoscopic treatment proved efficient and reliable in a large controlled series.

http://ift.tt/2Dr3YtW

Neutrophil-to-lymphocyte ratio in head and neck cancer prognosis: A systematic review and meta-analysis

Abstract

Background

Hematologic markers, such as the neutrophil-to-lymphocyte ratio (NLR), characterize the inflammatory response to cancer and are associated with poorer survival in various malignancies. We evaluate the effect of pretreatment NLR on overall survival (OS) in patients with head and neck squamous cell carcinoma (HNSCC).

Methods

Using multiple databases, a systematic search for articles evaluating the effect of NLR on OS in patients with HNSCC was performed. An inverse variation, random-effects model was used to analyze the data.

Results

A total of 24 of 241 articles, including 6479 patients, were analyzed. The combined hazard ratio for OS in patients with an elevated NLR (range 2.04-5) was 1.78 (confidence interval [CI] 1.53-2.07; P < .0001). The hazard ratios for site-specific cancer: oral cavity 1.56 CI 1.23-1.98 (P < .001), nasopharynx 1.66 CI 1.35-2.04 (P < .001), larynx 1.55 CI 1.26-1.92 (P < .001), and hypopharynx 2.36 CI 1.54-3.61 (P < .001).

Conclusion

An elevated NLR is predictive of poorer OS in patients with HNSCC.

http://ift.tt/2DZj5Mj

Effect of time to simulation and treatment for patients with oropharyngeal cancer receiving definitive radiotherapy in the era of risk stratification using smoking and human papillomavirus status

Abstract

Background

The effect of increasing time to definitive radiotherapy (RT) for patients with oropharyngeal squamous cell carcinoma (SCC) is unknown.

Methods

Nodal tumor volumes at staging and simulation were compared for patients with oropharyngeal SCC. Time from staging to initiation of RT was tabulated. The primary endpoint of interest was nodal progression at simulation.

Results

Increasing time to simulation was associated with nodal progression in 144 patients (r = 0.474; P < .001). Patients with human papillomavirus (HPV)-associated oropharyngeal SCC were more likely to have nodal progression (50% vs 26%; P = .008). A threshold of 32 days was associated (sensitivity 77.9% and specificity 60.2%) with nodal progression (P < .001). Increasing time from staging to treatment initiation was associated with a greater risk of distant failure (hazard ratio [HR] 4.157; 95% confidence interval [CI] 1.170-14.764) but not progression-free survival (PFS; P = .179) or overall survival (OS; P = .474).

Conclusion

Increasing time before RT for patients with oropharyngeal SCC is associated with nodal progression and increased hazard of distant failure, although not PFS or OS in our population.

http://ift.tt/2Dr3ST6

Role of dental hardware in oral cavity squamous cell carcinoma in the low-risk nonsmoker nondrinker population

Abstract

Background

Oral cavity squamous cell carcinoma (SCC) arising in nonsmokers and nondrinkers remains poorly characterized. We hypothesized that these patients had prior exposure to metallic dental hardware.

Methods

We utilized a questionnaire querying the lifetime oral health status of 54 patients. Demographics and extensive oral health history were collected.

Results

The majority of patients (74%) had prior exposure to metallic dental hardware. The younger population with almost exclusively oral tongue cancer had a high prevalence of metallic orthodontic braces (40%) within 15 years before diagnosis. In the 51+ year age group, 82% had crowns, dental implants, and/or dentures with metallic elements.

Conclusion

Exposure to metallic dental hardware has increased in the past few decades given the rise of orthodontic braces and older adults retaining more teeth. Although this study does not prove a causal relationship between oral cavity SCC and dental hardware, this is a step toward identifying and investigating their role.

http://ift.tt/2DZAwN0

Robotic surgery for submandibular gland resection through a trans-hairline approach: The first human series and comparison with applicable approaches

Abstract

Background

Many submandibular gland diseases are treated by surgical intervention. Transcervical surgery results in an obvious cervical scar, whereas the retroauricular approach leaves a scar in the postauricular area. Therefore, robotic submandibular gland resection through a trans-hairline approach is developed to improve postoperative aesthetic outcomes.

Methods

From 2012 to 2017, 24 consecutive patients who met the inclusion criteria and had received submandibular gland resection through the trans-hairline robotic surgery were analyzed.

Results

All surgical procedures were successfully performed without conversion and appreciable complications. The incision was completely concealed within the hairs. Treatments of submandibular gland benign or malignant tumors were completed without any positive margins or disease recurrence.

Conclusion

This study demonstrated the feasibility and safety of the trans-hairline approach for robotic submandibular gland resection in the first human series. The procedure is applicable to many submandibular gland diseases with complete disease control, and has aesthetic advantages over other robotic surgical approaches.

http://ift.tt/2Dr3MLe

Novel method to save the parathyroid gland during thyroidectomy: Subcapsular saline injection

Abstract

Background

Saving the parathyroid gland during thyroidectomy remains challenging. Subcapsular saline injection (SCASI) was developed in February 2015. Its ability to spare the parathyroid gland was assessed.

Methods

All consecutive patients who underwent total thyroidectomy with or without neck lymph node dissection in 2013-2015 were included in this retrospective cohort study. Patients were divided into the SCASI and non-SCASI groups. Serum parathyroid hormone (PTH) levels were measured on day 1 and 6 months after surgery. Transient and permanent hypoparathyroidism were defined as day 1 and 6 month PTH < 10.0 and <15.0 pg/mL, respectively.

Results

The groups (both had 98 patients each) did not differ in demographics, tumor size, operation extent, pathology, thyroiditis rate, and incidental parathyroid gland excision rate. Compared with non-SCASI patients, patients who underwent the SCASI method exhibited transient hypoparathyroidism (35.7% vs 19.4%, P < .001) and permanent hypoparathyroidism (4.1% vs 0%, P = .043) significantly less frequently.

Conclusion

The procedure of SCASI effectively spared the parathyroid gland during thyroidectomy.

http://ift.tt/2E1s1RD

Evaluation of margins in head and neck squamous cell carcinoma from the surgeon's perspective

Abstract

Background

The surgeon's evaluation of resection status based on frozen section analysis during operation and pathological examination of resected specimens often differ. For this study, we recapitulated the surgeon's perspective during an operation, accordingly classified the evaluation of margins by the surgeon, and analyzed its impact on the outcome compared with the pathological results.

Methods

This was a retrospective analysis. As data sources, paper-based and digital patient files, as well as the Munich Cancer Registry database were used.

Results

Three hundred ninety-six cases were included in this analysis. Only the evaluation of margins by the surgeon influenced local control, and the pathological results influenced disease-free survival (DFS). Surprisingly, margins of >5 mm of normal tissue to cancer growth led to local control and overall survival (OS) significantly worse than 1 to 5-mm resections.

Conclusion

The evaluation of margins by the surgeon is of significant importance for local control and OS. It is largely based on frozen section analysis, which, therefore, should be used whenever possible.

http://ift.tt/2DrMjSZ

Generic quality of life in persons with hearing loss: a systematic literature review

Abstract

Background

To the best of our knowledge, no empirically based consensus has been reached as to if, and to what extent, persons with hearing loss (HL) have reduced generic Quality of life (QoL). There seems to be limited knowledge regarding to what extent a hearing aid (HA) would improve QoL. The main aim of the present study was to review studies about the relationship between HL and QoL. A supporting aim was to study the association between distress and HL.

Methods

Literature databases (Cinahl, Pub Med and Web of Science) were searched to identify relevant journal articles published in the period from January 2000 to March 17, 2016. We performed a primary search pertaining to the relationship between HL, HA and QoL (search number one) followed by a supporting search pertaining to the relationship between distress/mood/anxiety and HL (search number two). After checking for duplications and screening the titles of the papers, we read the abstracts of the remaining papers. The most relevant papers were read thoroughly, leaving us with the journal articles that met the inclusion criteria.

Results

Twenty journal articles were included in the present review: 13 were found in the primary search (HL and QoL), and seven in the supporting search (HL and distress). The literature yields equivocal findings regarding the association between generic QoL and HL. A strong association between distress and HL was shown, where distressed persons tend to have a lowered generic QoL. It is suggested that QoL is lowered among HL patients. Some studies suggest an increased generic QoL following the use of HA, especially during the first few months after initiation of treatment. Other studies suggest that HA use is one of several possible factors that contribute to improve generic QoL.

Conclusions

The majority of the studies suggest that HL is associated with reduced generic QoL. Using hearing aids seem to improve general QoL at follow-up within the first year. HL is a risk factor for distress. Further research is needed to explore the relationship between HL and generic QoL, in addition to the importance of influencing variables on this relationship.

http://ift.tt/2mXRGTW

An automated A-value measurement tool for accurate cochlear duct length estimation

Abstract

Background

There has been renewed interest in the cochlear duct length (CDL) for preoperative cochlear implant electrode selection and postoperative generation of patient-specific frequency maps. The CDL can be estimated by measuring the A-value, which is defined as the length between the round window and the furthest point on the basal turn. Unfortunately, there is significant intra- and inter-observer variability when these measurements are made clinically. The objective of this study was to develop an automated A-value measurement algorithm to improve accuracy and eliminate observer variability.

Method

Clinical and micro-CT images of 20 cadaveric cochleae specimens were acquired. The micro-CT of one sample was chosen as the atlas, and A-value fiducials were placed onto that image. Image registration (rigid affine and non-rigid B-spline) was applied between the atlas and the 19 remaining clinical CT images. The registration transform was applied to the A-value fiducials, and the A-value was then automatically calculated for each specimen. High resolution micro-CT images of the same 19 specimens were used to measure the gold standard A-values for comparison against the manual and automated methods.

Results

The registration algorithm had excellent qualitative overlap between the atlas and target images. The automated method eliminated the observer variability and the systematic underestimation by experts. Manual measurement of the A-value on clinical CT had a mean error of 9.5 ± 4.3% compared to micro-CT, and this improved to an error of 2.7 ± 2.1% using the automated algorithm. Both the automated and manual methods correlated significantly with the gold standard micro-CT A-values (r = 0.70, p < 0.01 and r = 0.69, p < 0.01, respectively).

Conclusion

An automated A-value measurement tool using atlas-based registration methods was successfully developed and validated. The automated method eliminated the observer variability and improved accuracy as compared to manual measurements by experts. This open-source tool has the potential to benefit cochlear implant recipients in the future.

http://ift.tt/2F1O6hY

Does hyperthyroidism worsen prognosis of thyroid carcinoma? A retrospective analysis on 2820 consecutive thyroidectomies

Abstract

Background

Hyperthyroidism is associated with high incidence of thyroid carcinoma; furthermore, tumors arisen in hyperthyroid tissue show an aggressive behavior. Thyroid Stimulating Hormone (TSH) and Thyroid-stimulating antibodies, present in Graves's disease, seem to play a key role in carcinogenesis and tumoral growth.

Methods

We retrospectively reviewed our series of patients who underwent thyroidectomy for thyroid carcinoma. We compared pathological features and surgical outcomes of hyperthyroid versus euthyroid patients.

Results

From 2007 to 2015, 909 thyroidectomies were performed at our institution for thyroid cancer: 87 patients were hyperthyroid and 822 euthyroid. We observed, in hyperthyroid patients, a higher rate of transient hypoparathyroidism (28.1% vs 13.2%; p < 0.01) and of node metastases (12.6% vs 6.1%; p = 0.03); also local recurrence rate was higher (5.7% vs 2.5%) even if not statistically significant (p = 0.17). Five-year disease free survival rate was significant lower in the same group (89.1% vs 96.6%; p = 0.03).

Conclusion

Thyroid cancers in hyperthyroid patients have an aggressive behavior, with high incidence of local invasion and a worse prognosis than euthyroid patients. All hyperthyroid patients should undergo a careful evaluation with ultrasound and scintigraphy; in case of suspicious nodules, an aggressive approach, including thyroidectomy and lymphectomy, is justified. In patients with toxic adenoma, thyroid cancer is uncommon, thus a loboisthmectomy can be safely performed.

Trial registration number

Research registry n. 2670 registered 19 June 2017 (retrospectively registered).

http://ift.tt/2DzSiIB

Identification of T-cell epitopes from benzylpenicillin conjugated to human serum albumin and implication in penicillin allergy

Abstract

Background

There is in vitro evidence that T-cells from allergic patients react to benzylpenicillin-human serum albumin (BP-HSA) bioconjugates. Our group has recently shown the existence of naïve CD4⁺ T lymphocytes recognizing BP-HSA in healthy donors. However, BP-haptenated peptides from HSA participating in the immunization of allergic patients have never been identified. The purpose of the present study is to identify immunodominant BP-haptenated peptides from HSA involved in immunization of patients to BP and to refine the frequency calculation of naïve CD4⁺ T-cells recognizing BP.

Methods

Co-cultures were established with CD4⁺ T-cell from non-allergic donors and mature autologous dendritic cells (DCs) loaded with BP-HSA or BP-haptenated peptides from HSA. The CD4⁺ T-cell response specific for BP-HSA or for individual BP-haptenated peptides was measured using an interferon-γ (IFN-γ) ELISpot assay. Frequency of BP-specific CD4⁺ T-cell was then calculated using the Poisson distribution. BP-HSA and BP-haptenated peptides recognition by allergic patients was evaluated on peripheral blood mononuclear cells (PBMCs) using a lymphocyte transformation test (LTT).

Results

Results showed that BP-HSA and BP-haptenated peptides were recognized by naïve T-cells from 15/16 and 13/14 tested healthy donors respectively. Most donors responded to 3 peptides with BP covalently bound on lysines 159, 212 and 525. Two of these benzylpenicilloylated peptides (lysines 159 and 525) were also found to induce PBMCs proliferation in patients with allergic reaction to penicillins.

Conclusion

This study identifies and characterizes for the first time the BP-haptenated peptides from HSA involved in the immunization of patients to penicillins.

This article is protected by copyright. All rights reserved.

http://ift.tt/2G3Jmd3

Clostridium perfringens Septicemia and a Bleeding Ulcer of a Jejunal Interposition: A Case Report and Short Review of the Literature

Introduction. We report a case of Clostridium perfringens septicemia in a patient presenting with a bleeding ulcer of a jejunal interposition. Case Presentation. An 81-year-old female patient was acutely admitted to our hospital due to hematemesis and melena. She had a history of metastatic gastrointestinal stromal tumor, for which she was receiving second line treatment with sunitinib. She had also undergone a Merendino procedure 4 years prior to presentation. The patient underwent emergency gastroscopy, which revealed a bleeding ulcer in the jejunal interposition. Despite initial endoscopic control of the bleeding and transfusion of blood products, the hemoglobin level continued to drop, and the patient was treated for an assumed hemolytic transfusion reaction. The patient died 3 days following admission, and the results of blood cultures later confirmed a Clostridium perfringens septicemia. The postmortem examination revealed a diffuse spread of Clostridium perfringens to multiple organs. Conclusion. This case is a reminder of the importance of considering septicemia, particularly in association with Clostridium perfringens, as a potential cause of hemolysis. It also demonstrates the extent of organ involvement in a case of diffuse clostridial myonecrosis.

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Assessment of the efficacy of a new complex antisensitive skin cream

Summary

Background

Sensitive skin is frequently complaint in dermatology consultation with cutaneous manifestations such as stinging, redness, dryness, and burning sensation that affect the quality of life. Its pathogenesis is mainly related to dysfunction of neurosensory, skin barrier, and also immune activity. The treatment is generally based on continuous and topical therapy by nonirritating complex.

Objective

To evaluate the antisensitive function of a new complex cream composed by Yunnan Portulaca oleracea extract, Prinsepia utilis oil, beta-glucan, and sodium hyaluronate extracted from mushroom.

Methods

A randomized double-blind and self-control study was conducted on 20 selected volunteers with sensitive skin. Subjects applied the test cream to 1 side of the face, and the control cream (tolerance-extreme cream) to the other side of the face, twice daily over 28 days. Evaluations were performed at baseline and at 28 days. Expert clinical grading of facial skin including dryness, roughness, desquamation, and erythema was assessed. Subject self-assessment questionnaires, digital photography and noninvasive bioinstrumentation of hydration, transepidermal water loss, lipid index, skin texture, and wettability were also included in the study.

Results

Products were well tolerated. For all parameters studied, no significant difference was observed between test and control creams. Results showed that test cream provided a statistically significant improvement in clinical grading scores for dryness, roughness, and erythema at 28 days compared to baseline. In addition, statistically significant improvement of skin hydration and texture parameters (eg, smoothness and roughness) was demonstrated. Volunteers' questionnaire revealed self-perceived benefits consistent with expert visual grading.

Conclusion

This study confirmed the effectiveness and tolerance of the new complex cream in subjects with sensitive skin. The test cream could serve as a daily care moisturizer for face.

http://ift.tt/2n05Yn1

Analysis of images for detection of oral epithelial dysplasia: A review

Publication date: March 2018
Source:Oral Oncology, Volume 78
Author(s): Reetoja Nag, Raunak Kumar Das
This paper provides a review of various image analysis approaches that have been previously used for recognition of dysplasia in images of the epithelium of the oral cavity. This domain has become especially admissible with the uncovering of the importance of image analysis which can probably be an aid to subjective diagnosis by histopathologists. Oral malignancy is a rampant form of cancer found among people of the Indian subcontinent due to various deleterious habits like consumption of tobacco, areca nut, betel leaf etc. Oral Submucous Fibrosis, a precancer, whose pathological category falls between normal epithelium and epithelial dysplasia, is caused because of these habits and can ultimately lead to oral cancer. Hence early detection of this condition is necessary. Image analysis methods for this purpose have an enormous potential which can also reduce the heavy workload of pathologists and to refine the criterion of interpretation. This paper starts with a critique of statistics of oral carcinoma in India and distribution of cancer in intra-oral sites and moves on to its causes and diagnostic approaches including causative agents, problems in curative approach and importance of image analysis in cancer detection. The various image analysis methods to appraise the cytological and architectural changes accompanied by Oral Epithelial Dysplasia in the images of the oral epithelial region have been described in relation to 2005 WHO Classification System and it was found that in future, analysis of images based on the mentioned methods has the potential in better interpretation and diagnosis of oral carcinoma.



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Does volumetric measurement serve as an imaging biomarker for tumor aggressiveness of ameloblastomas?

Publication date: March 2018
Source:Oral Oncology, Volume 78
Author(s): Ali-Farid Safi, Martin Kauke, Marco Timmer, Andrea Grandoch, Hans-Joachim Nickenig, Elif Gültekin, Reinhard Büttner, Matthias Kreppel, Joachim Zöller




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Influence of anemia and BMI on prognosis of laryngeal squamous cell carcinoma: Development of an updated prognostic model

Publication date: March 2018
Source:Oral Oncology, Volume 78
Author(s): R.J.L.M. te Riele, E.A.C. Dronkers, M.H. van den Brink, M.J. De Herdt, A. Sewnaik, J.A. Hardillo, R.J. Baatenburg de Jong
Objectiveevaluating the impact of anemia and body mass index (BMI) on survival, and development of a prognostic model for overall survival for patients with laryngeal squamous cell carcinoma (LSCC).Materials and methodsA retrospective cohort study was performed including all consecutive patients with LSCC diagnosed and treated at the Erasmus Medical Center between January 2006 and December 2013. Patient- and tumor-specific data were collected using data from the Netherlands Comprehensive Cancer Organization and supplemented with data from patient records available in the Erasmus MC. All comorbidities were scored at the time of diagnosis.Resultsin total 788 patients were included. Mean follow-up time was 50 months (SD: ±30), during which 298 patients (37.8%) died. In both univariate and multivariate analysis BMI and anemia were significant predictors for overall survival. Multivariate analysis was performed using known predictors such as age, TNM-stage and comorbidity (ACE-27). The hazard ratio of anemia was 1.41 (95% CI: 1.05–1.90) and of BMI was 0.97 (95% CI: 0.94–0.99). BMI had an inverse association with overall survival in both univariate and multivariate survival analysis. Updating and validating an existing prognostic model with addition of anemia and BMI enhanced the performance of the prognostic model (C-statistic) from 0.77 (95% CI: 0.74–0.79) to 0.79 (95% CI: 0.77–0.82).Conclusionanemia and BMI are predictors of overall survival for LSCC, independent of other known predictors of overall survival. Adding anemia and BMI to an existing prognostic model provides better prediction of overall survival.



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Three-dimensional printing of patient-specific surgical plates in head and neck reconstruction: A prospective pilot study

Publication date: March 2018
Source:Oral Oncology, Volume 78
Author(s): Wei-fa Yang, Wing Shan Choi, Yiu Yan Leung, Justin Paul Curtin, Ruxu Du, Chun-yu Zhang, Xian-shuai Chen, Yu-xiong Su
BackgroundSurgical plates have been extensively used in head and neck reconstruction and conventional plates are mass-produced with universal configurations. To overcome disadvantages of conventional surgical plates, we have been exploring patient-specific surgical plates using the three-dimensional (3D) printing technology. We hypothesized that the application of 3D-printed patient-specific surgical plates in head and neck reconstruction is feasible, safe and precise.MethodsWe are conducting a prospective clinical trial to assess the feasibility, safety and accuracy of applying 3D-printed patient-specific surgical plates in head and neck reconstruction. The primary endpoint was the intraoperative success rate. Secondary endpoints included the incidence and severity of postoperative adverse events within six months postoperatively. The accuracy of surgical outcomes was also explored by comparing the planned and final positions of the maxilla, mandible and grafted bone segments.ResultsFrom December 2016 to October 2017, ten patients were enrolled and underwent head and neck reconstruction using 3D-printed patient-specific surgical plates. The patient-specific surgical plates adapted to bone surface precisely and no plate-bending was performed. The intraoperative success rate was 100%. The average follow-up period was 6.5 months. No major adverse events were observed. The mean absolute distance deviation of integral mandible or maxilla was 1.40 ± 0.63 mm, which showed a high accuracy of reconstruction.ConclusionsThe 3D printing of patient-specific surgical plates could be effective in head and neck reconstruction. Surgical procedures were simplified. The precise jaw reconstruction was achieved with high accuracy. Long-term results with a larger sample size are warranted to support a final conclusion.The study protocol has been registered in ClinicalTrials.gov with a No. of NCT03057223.



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Effect of adjuvant radiotherapy treatment center volume on overall survival

Publication date: March 2018
Source:Oral Oncology, Volume 78
Author(s): Ramez Philips, Daniel Martin, Antoine Eskander, Jeffrey Schord, Nicole Brown, Songzhu Zhao, Guy Brock, Bhavna Kumar, Ricardo Carrau, Enver Ozer, Amit Agrawal, Stephen Y. Kang, James W. Rocco, David Schuller, Syed Ali, Dukagjin Blakaj, Aashish Bhatt, John Grecula, Theodoros Teknos, Virginia Diavolitsis, Matthew Old
Objectivesto examine the impact of radiotherapy center volume on overall survival in patients with oral cavity and oropharyngeal squamous cell carcinoma getting adjuvant radiation therapy after receiving surgery at a high-volume center.Materials and Methodsa retrospective study was conducted on patients with oral cavity squamous cell carcinoma or oropharyngeal squamous cell carcinoma treated surgically at a tertiary institution from 2000 to 2012 who received adjuvant radiotherapy. The outcome variable was overall survival and the independent variable was location of adjuvant radiation therapy: high-volume center (HVC) versus low-volume center (LVC). Cox proportional hazards models were used to assess associations between predictors of death. Variables that were found to be significant at the α = 0.10 were included in a multivariable model.Results336 patients met inclusion criteria. One-hundred thirty-nine patients received adjuvant radiation therapy at HVC and 197 patients received adjuvant radiation therapy at LVC. A univariate Cox proportional hazards model identified the variables location, age, marital status, subsite, T stage, extracapsular extension, and smoking status to include in a multivariable model. Age, subsite, T stage, and extracapsular extension were independent predictors of overall survival (p < .05). Location (p = .55), marital status (p = .29), and smoking status (p = .22) were not statistically significant predictors of survival.ConclusionAfter surgery at a HVC, the volume of adjuvant radiation therapy center was not significantly associated with overall survival. Significant predictors of survival included age, subsite, T stage, and extracapsular extension.



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Real time indocyanin green near infrared lymphangiography for the reduction of drainage volume after neck dissection

Publication date: March 2018
Source:Oral Oncology, Volume 78
Author(s): Jimmy Yu Wai Chan, Stanley Thian Sze Wong, William Ignace Wei
BackgroundTo investigate the role of indocyanine green (ICG) lymphangiography in the reduction of drainage after neck dissection.MethodsPatients with oral cavity squamous cell carcinoma were randomized into Group A (study group) and Group B (control). In the study group, upon the completion of neck dissection, a total of 2.5 mg of ICG was injected submucosally at the four quadrants around the tumour. Another 2.5 mg of ICG was injected subdermally in the groin bilaterally. The neck was screened using Near Infrared fluorescence. The presence of lymphatic leakage was noted and plicated with silk stitches. The total drainage volume of post-operative day 1, day 2 and the total accumulated volume until drain removal was measured.ResultsTwenty-two patients (Group A, n = 12; Group B, n = 10) were recruited. All patients in Group A had at least one site of lymphatic leakage identified. One patient in Group B developed chylous fistula and was excluded from analysis. The mean total drain output for day 1 and 2 after surgery, as well as the mean total output before drain removal, were significantly lower in Group A (22.4 ml vs. 86.2 ml [p = .02]; 14.2 ml vs. 72.8 ml [p = .02]; and 58.4 ml vs. 392 ml [p = .01], respectively), allowing earlier drain removal (2.2 days vs. 7.2 days, p = .02).ConclusionsIntra-operative ICG lymphangiography is useful in the reduction of drainage volume after neck dissection for caners in the head and neck region.



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Patterns of care and impact of prognostic factors in the outcome of NUT midline carcinoma: a systematic review and individual patient data analysis of 119 cases

Abstract

Introduction

NUT midline carcinoma is a rare tumour occurring in young adults which is frequently misdiagnosed as poorly differentiated squamous cell carcinoma or germ cell tumour. Though considered highly aggressive, there is limited information about the clinical behaviour of such patients. We intended to perform this review of published literature to assess the demographic profile, pattern of care and assess survival outcomes.

Methods

Two authors independently searched PubMed and Google search for eligible studies from 1950 till July 1 2017 published in English language using MESH terms NUT midline carcinoma; NUT midline carcinoma and radiotherapy and translocation 15:19 tumour.

Results

Data of 119 patients were retrieved from 64 publications for statistical analysis. Median age of the entire cohort was 23 years (range 0–68 years). The analysis revealed equal incidence in males and females (60:58). The present analysis revealed that the most common location is the lung (n = 42) followed by head and neck (n = 40). Median OS for the entire cohort was only 5 months with 1 and 5 year OS for the entire cohort was 24.99 and 7.09% respectively. Radiotherapy and chemotherapy inclusion in primary treatment had a significant impact on overall survival on univariate analysis while surgery did not affect survival significantly. No impact on overall survival was found based on type of molecular translocation, i.e., NUT–BRD4, NUT–BRD3 or other variants. Inadequate data were available for identify impact of BET inhibitors and HiDAc on PFS and OS.

Conclusion

NUT midline carcinoma has dismal prognosis. Radiotherapy and chemotherapy improves survival, but do not provide long term control except in anecdotal cases. Further research is needed to improve outcomes in future.

http://ift.tt/2G1IlSV

British Association of Dermatologists’ guidelines for the investigation and management of generalized pruritus in adults without an underlying dermatosis, 2018

Summary

Pruritus (or itch) is a common and distressing symptom of many skin diseases, systemic illnesses and psychological disorders. Itch is perhaps the commonest presenting symptom of skin disorders. In any two week period, 8 to 9% of the population suffer from significant pruritus. The focus of this guideline is not itchy rashes, but rather the situation where itch is present without rash. The guidelines also do not cover itch in children, in pregnancy, nor do they detail the science of the cause of itch. The study group consist mostly of dermatologists (skin specialists) from a number of hospitals in the U.K., but a number of other hospital doctors, a nurse and a general practitioner (GP) are also part of the team. There may be an underlying cause of pruritus, such as blood disorders, iron deficiency or excess, kidney problems, liver problems, cancer, infections, medications, behavioural factors, dry skin or any combination of these with old age. This can be significant in 20 to 30% of cases of itchy skin without rash. There remain a small number of individuals with itch and no apparent underlying cause or rash. It is always important to look for an underlying causative condition, as the most effective management of pruritus without rash depends on the treatment of any underlying disease. The management of itch appears to be very situation specific, even if the underlying cause cannot be treated. The management of true pruritus of unknown cause is different again.

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脂溢性皮炎在中老年人群中的发病率及决定因素:鹿特丹研究

Summary

脂溢性皮炎是一种常见的皮肤病,见于头皮、面部及胸部,主要表现为炎症和脂性鳞屑。虽然尚不清楚脂溢性皮炎的病因,但研究者认为马拉色氏酵母菌的过度生长是脂溢性皮炎的部分原因。若干其他因素也与此类疾病有关;年龄、性别、肥胖、肤色、压力、沮丧、教育程度、高血压、气候、皮肤干燥、饮酒以及吸烟等因素都与脂溢性皮炎有关,但相关性证据通常并无定论。该研究旨在确定与脂溢性皮炎有关的生活方式及生理因素。该研究中的数据来自针对荷兰中老年人群开展的鹿特丹研究,旨在研究这些之前报告的因素。研究依据在于,了解决定因素可以在脂溢性皮炎的病理生理学方面提供新的见解,以便采取预防策略和/或新的治疗方案。在鹿特丹研究中,5,498 位参与者进行了全身皮肤检查,其中 788 位罹患脂溢性皮炎。作者发现,男性、肤色浅、冬季以及全身干燥皮肤可增加脂溢性皮炎发病率,其他因素则与脂溢性皮炎无关。此外,作者分析了研究性别差异能否通过激素差异来解释,但他们发现激素与脂溢性皮炎之间并无关联。在已发现的关联中,干燥皮肤似乎最容易带来影响。因此,增强皮肤屏障可以作为脂溢性皮炎治疗中的一个目标。

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Novel clinical and molecular findings in Spanish patients with nevoid basal cell carcinoma syndrome

Summary

Nevoid basal cell carcinoma syndrome (NBCCS), also known as Gorlin Syndrome, affects only 1 in 56 000 people. It is usually inherited from a parent with the condition and affects both males and females equally (autosomal dominant inheritance). People with NBCCS may show characteristic features such as extra fingers or toes, irregular ribs, an unusually shaped face and large head. Tumours sometimes develop, particularly jaw cysts and basal cell carcinomas (BCCs) of the skin from which the syndrome is named. NBCCS is caused by mistakes (mutations) in a gene called PTCH1 located on the long arm of chromosome 9. PTCH1 acts as a brake on a set of chemical processes in cells called the Hedgehog (HH)/GLI signalling pathway. In NBCCS, mutations inactivate PTCH1 allowing excessive Hedgehog signalling. This loss of control results in the abnormal bones and tumours. Within an affected family, people with the same genetic mutation can have very different abnormalities. This group from Spain studied 22 unrelated Spanish people with NBCCS to see if they could discern any relationship between specific clinical abnormalities and specific genetic mutations. BCCs were very common, occurring in 96% of patients with 43% having more than 50; 77% had jaw cysts. Two abnormalities had not previously been recognised in NBCCS: double uterus and a benign nerve tumour. They found 19 PTCH1 mutations that had not previously been reported. However, they could not find any pattern relating the type of mutation to the clinical abnormalities. Presumably other factors besides the PTCH1 mutation causes the clinical features.

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A new era in holistic care: bridging the gap between dermatologists and oncologists for the treatment of malignant melanoma

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Morphological characteristics and human papillomavirus genotype predict the treatment response in cutaneous warts

Summary

Skin warts are highly prevalent in both children and adults. They are caused by a virus called 'human papilloma virus' (HPV). Only around half of skin warts disappear after treatment. This study was performed to predict the type of HPV in warts and more importantly, to predict which warts are likely to disappear after treatment. Therefore, features both of patients and their warts were studied. A new standard tool for warts (the CWARTS diagnostic tool) was used to score the appearance of the wart and 23 different virus types were tested. The treatments that were used were monochloroacetic acid, cryotherapy or a combination of cryotherapy and salicylic acid. In total, 311 warts of 159 patients were studied. Black dots in a wart suggested presence of HPV. If warts contained HPV2, HPV27 or HPV57 they responded less often to most treatments. However this did not apply to warts located on the hands or body if they were treated with cryotherapy. Warts that show callus or are deeper located on the skin were less responsive to cryotherapy. To summarize, the appearance of warts and the type of HPV they contain influence the chance of healing. Therefore, in the future it might be important for medics to take this into account when choosing a treatment option for common and plantar warts.

http://ift.tt/2n0aIc9

Advances in the diagnosis of pigmented skin lesions

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The views of children and young people on the use of silk garments for the treatment of eczema: a nested qualitative study within the CLOTHing for the relief of Eczema Symptoms (CLOTHES) randomized controlled trial

Summary

This study reports on a trial from the U.K. to find out if specialised silk clothing improved eczema in children. Eczema is a common skin condition. It affects around one in five children and can cause sore and itchy skin, poor sleep and reduced quality of life. As part of this work the researchers wanted to find out what the children who wore the garments in the study thought of them. They invited 18 children aged between five and 15 years to take part, meeting in small groups and using stories and play to help the children tell the researchers about the garments. All the children and young people had high hopes that the garments would make their skin much better. They expected the garments to feel soft and smooth and were disappointed when they were not like this. They reported that they mostly wore them at night as it was embarrassing to wear them during the day. Some said that the garments were see through. Garments tended to go grey and start to fall apart when they had been worn and washed. A few children found that the garments made their skin more comfortable and helped them sleep better. They were disappointed that the miracle cure they hoped for did not happen. It is important and possible to involve children in studies like this so we can understand what they think about possible treatments for eczema.

http://ift.tt/2rvBTjB

Efficacy and adverse events of oral isotretinoin for acne: a systematic review

Summary

Acne vulgaris, usually just referred to as acne, is the most common skin disease. It causes red spots, pus-filled spots and blackheads and can vary in severity from mild to severe. Because it can be very visible, it can cause anxiety, reduced self-esteem and stigma. In cases of more severe acne that hasn't improved with other treatments, a powerful drug taken orally (by mouth) called isotretinoin can be prescribed by doctors. This study, from Canada, reviewed evidence from randomized controlled trials (RCTs) to assess the efficacy and safety of isotretinoin. RCTs are studies in which a number of patients are randomly allocated to two or more test groups, one of which will be a 'control' group (who typically receive either no treatment, standard care or a placebo), while the other groups will receive the specific treatments being tested. The different groups of patients are then monitored in the exact same way, allowing for direct comparison between different treatments. Eleven trials were identified, involving a total of 760 patients - mostly males. Across all trials, isotretinoin reduced acne lesion counts (number of spots), and always by a greater amount than controls, which were either placebo, oral antibiotics, or another control type. The frequency of adverse events, meaning unwanted side effects, was twice as high with isotretinoin (751 events) compared to control (388 events). More than half of all adverse events related to skin dryness. Adverse events caused 12 of the 760 participants to withdrawal from trials, due to the development of Stevens-Johnson Syndrome, cheilitis, xerosis, acne flare, photophobia, elevated liver enzymes, decreased appetite, headaches and depressed mood. This review suggests that isotretinoin is effective in reducing acne lesion counts, but adverse events are common.

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Image Gallery: A case of malignant syphilis in an HIV-infected patient mimicking fungal infection

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Corrigenda

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通过电子皮镜观察到在后天性痣亚型中常见 BRAF 和 NRAS 突变,表现出组成型 MAPK 通路活化

Summary

大多数人的皮肤上都有几个褐斑,我们称之为黑素细胞痣或痣。痣对人体无害,但偶尔可能转化为潜在致死性肿瘤,也就是恶性黑色素瘤。在放大镜(电子皮镜)下,皮肤科专家通过外观确定了不同类型的痣。广义上:"球状"痣在早年出现,并且可能转化为黑色素瘤;"网状"痣在成年期出现,并且可能与未长痣部位出现的黑色素瘤有关;带"外围球状体"(PG) 的网状痣会生长,但非恶性。良性痣及癌性痣(恶性黑色素瘤)中都可能出现 BRAF 和 NRAS 基因突变(变异)。这些基因是在肿瘤形成中起重要作用的 MAPK 通路的成分。为说明这些基因的作用,这些来自澳大利亚的研究人员探讨了电子皮镜下外观与良性痣中的 NRAS 和 BRAF 突变之间的关系。他们通过电子皮镜检查了 27 人的 40 个后天性(非先天性)痣,然后去痣以进行分析。在显微镜下,研究人员观察到大多数网状痣中的细胞结构无序,但这种情况在球状痣以及 PG 痣中很少见。研究人员使用了一种能够检测单细胞突变的新型高灵敏度方法("微滴式数字 PCR"),他们发现大多数球状痣以及所有 PG 痣都出现 BRAF 突变,网状痣则出现 BRAF 或 NRAS 突变。研究人员得出结论,所有痣具有 MAPK 基因突变,证明 MAPK 通路在黑素细胞痣及黑色素瘤的形成中起基础性作用。

http://ift.tt/2mZV1Sr