AHNS Series: Do you know your guidelines? Guideline recommendations for head and neck cancer of unknown primary site

Abstract

This article reviews the clinical practice guidelines for head and neck oncology focusing on the management of head and neck cancers of unknown primary (CUP). The primary purpose of this series is to raise awareness of the current guidelines in head and neck oncology by reviewing the recommendations and the evidence supporting such recommendations, particularly those published by the National Comprehensive Cancer Network (NCCN). We review the importance of a thorough history and physical examination, the impact of the American Joint Committee on Cancer (AJCC) eighth edition changes and the importance of immunohistochemistry, the timing and type of imaging, the role of panendoscopy and tonsillectomy (palatine and lingual), and the role of surgery, radiation, and chemotherapy in the primary management of these tumors.

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Clinical diagnosis and treatment outcomes for parapharyngeal space schwannomas: A single-institution review of 21 cases

Abstract

Background

Because the incidence of schwannoma arising from the parapharyngeal space (PPS) is very low, no studies have analyzed extirpation methods and postoperative neurological complications exclusively in PPS schwannomas.

Methods

The preoperative diagnosis and clinical outcomes of surgical treatment in 21 patients with PPS schwannoma who underwent surgery were investigated.

Results

Neurological deficit of the involved nerve developed in all patients regardless of the extirpation method used. However, the incidence of first bite syndrome in sympathetic chain schwannoma was significantly lower after intracapsular enucleation (40%) than after total resection (100%; P = .045). Furthermore, the incidence of postoperative complications unrelated to the involved nerve was lower after intracapsular enucleation (0%) than after total resection (42.9%; P = .055).

Conclusion

Although postoperative neurological deficit of the involved nerve was unavoidable in PPS schwannoma, intracapsular enucleation could be beneficial by reducing its severity and the incidence of complications unrelated to the involved nerve.

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Table of Contents

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Editorial Board

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Prevalence of type I sensitization to alpha-gal in forest service employees and hunters: Is the blood type an overlooked risk factor in epidemiological studies of the α-Gal syndrome?

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ABBV-085, an Antibody Drug Conjugate, in Subjects With Advanced Solid Tumors

Conditions:   Advanced Solid Tumors;   Undifferentiated Pleomorphic Sarcoma;   Squamous Cell Carcinoma of the Head and Neck;   Carcinoma of the Breast
Intervention:   Drug: ABBV-085
Sponsor:   AbbVie
Recruiting

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Clinicopathologic Predictive Factors of Cervical Lymph Node Metastasis in Differentiated Thyroid Cancer

Publication date: Available online 20 November 2017
Source:Acta Otorrinolaringológica Española
Author(s): Ronghao Sun, Hua Zhang, Kun Liu, Jinchuan Fan, Guojun Li, Xicheng Song, Chao Li
BackgroundCervical lymph node metastasis (LNM) has been proven to be a predictor for locoregional recurrence in differentiated thyroid carcinoma (DTC). Clinicopathological features could be effective predictive factors for central and lateral LNM of DTC, and provide references to surgeons for cervical neck dissection.MethodsRetrospective analysis of clinicopathological data was performed on 420 patients who underwent initial surgery from 2010 to 2015.ResultsThe incidence of central and lateral LNM was calculated. Of 420 patients, 247 (58.8%) exhibited central LNM, and 185 (44.1%) exhibited lateral LNM. There were 29 (6.9%) cases confirmed to have skip metastasis. Univariate and multivariate analysis revealed that tumour location, tumour size, multifocality, capsular invasion, affected lobes, and age were independent predictors of central LNM. Tumour location, capsular invasion, affected lobes, and tumour size were independent predictors of lateral LNM.ConclusionsOur findings suggest that tumour location, affected lobes, capsular invasion, age, tumour size and multifocality may be taken as predictive factors for cervical LNM of DTC. Meticulous perioperative evaluation of cervical LNM and prophylactic cervical lymph node dissection that aims to remove the occult lymph nodes may be an option for DTC with risk factors.



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Specific Organ Targeted Vestibular Physiotherapy: The Pivot in the Contemporary Management of Vertigo and Imbalance

Abstract

Introduction

Advancements in our understanding of vestibular physiology and how it is changes in different diseases have established that of the three therapeutic approaches to treat disorders of the vestibular system viz. pharmacotherapy, surgery and physical therapy, it is the later i.e., physical therapy which is the most efficacious modality in the management of balance disorders. The futility of vestibular sedatives in the correction of vestibular disorders and in the restoration of balance and the very limited role of surgery has now been recognised. Advancements in vestibulometry now enable us to localise any lesion in the vestibular system with utmost precision and also determine the exact cause of the balance disorder. The site of lesion and the specific organ that is defective can now be very precisely identified. Treatment modalities especially that for physical therapy hence have to be organ specific, and if possible, also disease specific.

Aims and Objectives

The study aims at evaluating the efficacy of physiotherapy in the management of balance disorders and also assesses the efficacy of organ targeted physical therapy, a new concept in restoring balance after vestibulometry has identified the offending organ.

Materials and Methods

The study was conducted in the specialised physical therapy unit for balance and gait disorder patients which is a part of Vertigo and Deafness Clinic in Kolkata, India. Special instruments for physical therapy devised by the first author were used for stimulation of specific sense organs in the vestibular labyrinth that were found to be defective in vestibulometry. Specially made Virtual reality programs were used in patients suffering from psychogenic balance disorders. The pre and post therapy status was evaluated by different standard scales to assess balance and dizziness.

Results

Very promising results were obtained. Organ targeted physiotherapy where defective sense organs were specifically stimulated showed remarkable improvement in different measures. Virtual reality exercises too showed very promising results in patients of psychogenic vertigo.

http://ift.tt/2mMCqLY

Specific Organ Targeted Vestibular Physiotherapy: The Pivot in the Contemporary Management of Vertigo and Imbalance

Abstract

Introduction

Advancements in our understanding of vestibular physiology and how it is changes in different diseases have established that of the three therapeutic approaches to treat disorders of the vestibular system viz. pharmacotherapy, surgery and physical therapy, it is the later i.e., physical therapy which is the most efficacious modality in the management of balance disorders. The futility of vestibular sedatives in the correction of vestibular disorders and in the restoration of balance and the very limited role of surgery has now been recognised. Advancements in vestibulometry now enable us to localise any lesion in the vestibular system with utmost precision and also determine the exact cause of the balance disorder. The site of lesion and the specific organ that is defective can now be very precisely identified. Treatment modalities especially that for physical therapy hence have to be organ specific, and if possible, also disease specific.

Aims and Objectives

The study aims at evaluating the efficacy of physiotherapy in the management of balance disorders and also assesses the efficacy of organ targeted physical therapy, a new concept in restoring balance after vestibulometry has identified the offending organ.

Materials and Methods

The study was conducted in the specialised physical therapy unit for balance and gait disorder patients which is a part of Vertigo and Deafness Clinic in Kolkata, India. Special instruments for physical therapy devised by the first author were used for stimulation of specific sense organs in the vestibular labyrinth that were found to be defective in vestibulometry. Specially made Virtual reality programs were used in patients suffering from psychogenic balance disorders. The pre and post therapy status was evaluated by different standard scales to assess balance and dizziness.

Results

Very promising results were obtained. Organ targeted physiotherapy where defective sense organs were specifically stimulated showed remarkable improvement in different measures. Virtual reality exercises too showed very promising results in patients of psychogenic vertigo.

http://ift.tt/2mMCqLY

Enhanced recovery in patients having free tissue transfer for head and neck cancer: does it make a difference?

Programmes for Enhanced Recovery after Surgery (ERAS) accelerate recovery, reduce morbidity, and shorten hospital stay in a wide range of surgical specialties. We established a standardised multimodal ERAS pathway for patients who were being treated by free tissue transfer for head and neck cancer to evaluate its benefit. Our primary outcome was duration of hospital stay, and secondary outcomes included complications, number of days to first mobilisation, and readmission rates. We compared 100 consecutive patients who followed the ERAS programme with a control group of 40 consecutive patients who had free tissue transfer before the ERAS programme was introduced.

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Are patients satisfied with the head and neck skin cancer service? An evaluation of outpatient services with a review of published reports

Scientific publications place much emphasis on postoperative outcomes such as recurrence, but little attention to patients' satisfaction. The purpose of this evaluation was to find out patients' reported outcomes after their initial consultation, treatment, and follow-up appointments for non-melanoma skin cancer of the head and neck. We used an adapted version of the European Organisation for Research and Treatment of Cancer (EORTC) validated questionnaire for patients' satisfaction to collect data prospectively from consenting patients between September and December 2015.

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Immunoresolvents signaling molecules at intersection between the brain and immune system

Jesmond Dalli | Charles N Serhan

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Laryngeal candidiasis: our experience from sixty biopsy specimens

Persistent throat symptoms, such as dysphonia, globus and throat pain, are highly prevalent and are a significant cause of morbidity¹. In a number of cases a clear cause of these symptoms is not identified and many patients are treated empirically with lifestyle advice and/or anti-reflux medication².

This article is protected by copyright. All rights reserved.

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Fetal Exposure to Maternal Pregnancy Complications and Respiratory Health in Childhood

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


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Innate Immune Activation by cGMP-AMP Nanoparticles Leads to Potent and Long-Acting Antiretroviral Response against HIV-1 [INFECTIOUS DISEASE AND HOST RESPONSE]

HIV-1 evades immune detection by the cGAS-STING cytosolic DNA-sensing pathway during acute infection. STING is a critical mediator of type I IFN production, and STING agonists such as cGMP-AMP (cGAMP) and other cyclic dinucleotides elicit potent immune and antitumor response. In this article, we show that administration of cGAMP, delivered by an ultra–pH-sensitive nanoparticle (NP; PC7A), in human PBMCs induces potent and long-acting antiretroviral response against several laboratory-adapted and clinical HIV-1 isolates. cGAMP-PC7A NP requires endocytosis for intracellular delivery and immune signaling activation. cGAMP-PC7A NP-induced protection is mediated through type I IFN signaling and requires monocytes in PBMCs. cGAMP-PC7A NPs also inhibit HIV-1 replication in HIV⁺ patient PBMCs after ex vivo reactivation. Because pattern recognition receptor agonists continue to show more clinical benefits than the traditional IFN therapy, our data present important evidence for potentially developing cGAMP or other STING agonists as a new class of immune-stimulating long-acting antiretroviral agents.

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Critical Functions of IRF4 in B and T Lymphocytes [PILLARS OF IMMUNOLOGY]

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In This Issue [IN THIS ISSUE]

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Pillars Article: Requirement for the Transcription Factor LSIRF/IRF4 for Mature B and T Lymphocyte Function. Science. 1997. 275: 540-543 [PILLARS OF IMMUNOLOGY]

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The Structural Basis for Complement Inhibition by Gigastasin, a Protease Inhibitor from the Giant Amazon Leech [MOLECULAR AND STRUCTURAL IMMUNOLOGY]

Complement is crucial to the immune response, but dysregulation of the system causes inflammatory disease. Complement is activated by three pathways: classical, lectin, and alternative. The classical and lectin pathways are initiated by the C1r/C1s (classical) and MASP-1/MASP-2 (lectin) proteases. Given the role of complement in disease, there is a requirement for inhibitors to control the initiating proteases. In this article, we show that a novel inhibitor, gigastasin, from the giant Amazon leech, potently inhibits C1s and MASP-2, whereas it is also a good inhibitor of MASP-1. Gigastasin is a poor inhibitor of C1r. The inhibitor blocks the active sites of C1s and MASP-2, as well as the anion-binding exosites of the enzymes via sulfotyrosine residues. Complement deposition assays revealed that gigastasin is an effective inhibitor of complement activation in vivo, especially for activation via the lectin pathway. These data suggest that the cumulative effects of inhibiting both MASP-2 and MASP-1 have a greater effect on the lectin pathway than the more potent inhibition of only C1s of the classical pathway.

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Galectin-1: A Jack-of-All-Trades in the Resolution of Acute and Chronic Inflammation [BRIEF REVIEWS]

Regulatory signals provide negative input to immunological networks promoting resolution of acute and chronic inflammation. Galectin-1 (Gal-1), a member of a family of evolutionarily conserved glycan-binding proteins, displays broad anti-inflammatory and proresolving activities by targeting multiple immune cell types. Within the innate immune compartment, Gal-1 acts as a resolution-associated molecular pattern by counteracting the synthesis of proinflammatory cytokines, inhibiting neutrophil trafficking, targeting eosinophil migration and survival, and suppressing mast cell degranulation. Likewise, this lectin controls T cell and B cell compartments by modulating receptor clustering and signaling, thus serving as a negative-regulatory checkpoint that reprograms cellular activation, differentiation, and survival. In this review, we discuss the central role of Gal-1 in regulatory programs operating during acute inflammation, autoimmune diseases, allergic inflammation, pregnancy, cancer, and infection. Therapeutic strategies aimed at targeting Gal-1–glycan interactions will contribute to overcome cancer immunosuppression and reinforce antimicrobial immunity, whereas stimulation of Gal-1–driven immunoregulatory circuits will help to mitigate exuberant inflammation.

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Complement Regulatory Protein Factor H Is a Soluble Prion Receptor That Potentiates Peripheral Prion Pathogenesis [INFECTIOUS DISEASE AND HOST RESPONSE]

Several complement proteins exacerbate prion disease, including C3, C1q, and CD21/35. These proteins of the complement cascade likely increase uptake, trafficking, and retention of prions in the lymphoreticular system, hallmark sites of early prion propagation. Complement regulatory protein factor H (fH) binds modified host proteins and lipids to prevent C3b deposition and, thus, autoimmune cell lysis. Previous reports show that fH binds various conformations of the cellular prion protein, leading us to question the role of fH in prion disease. In this article, we report that transgenic mice lacking Cfh alleles exhibit delayed peripheral prion accumulation, replication, and pathogenesis and onset of terminal disease in a gene-dose manner. We also report a biophysical interaction between purified fH and prion rods enriched from prion-diseased brain. fH also influences prion deposition in brains of infected mice. We conclude from these data and previous findings that the interplay between complement and prions likely involves a complex balance of prion sequestration and destruction via local tissue macrophages, prion trafficking by B and dendritic cells within the lymphoreticular system, intranodal prion replication by B and follicular dendritic cells, and potential prion strain selection by CD21/35 and fH. These findings reveal a novel role for complement-regulatory proteins in prion disease.

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Cutting Edge: Anti-TIM-3 Treatment Exacerbates Pulmonary Inflammation and Fibrosis in Mice [CUTTING EDGE]

Promising results of immune checkpoint inhibitors have indicated the use of immunotherapy against malignant tumors. However, they cause serious side effects, including autoimmune diseases and pneumonitis. T cell Ig and mucin domain (TIM)-3 is a new candidate immune checkpoint molecule; however, the potential toxicity associated with anti–TIM-3 treatment is unknown. In this study, we investigated the pathological contribution of anti–TIM-3 mAb in a bleomycin-induced lung inflammation and fibrosis model. Anti–TIM-3–treated mice showed more severe inflammation and peribronchiolar fibrosis compared with control IgG-treated mice. Anti–TIM-3 mAb was associated with increased numbers of myofibroblasts, collagen deposition, and TGF-β1 production in lungs. TIM-3 expression was only detected on alveolar macrophages that protect against fibrosis by apoptotic cell clearance. Treatment with anti–TIM-3 mAb inhibited the phagocytic ability of alveolar macrophages in vivo, resulting in the defective clearance of apoptotic cells in lungs. In summary, anti–TIM-3 mAb treatment might cause pneumonitis and it should be used with caution in clinical settings.

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Palmitate Conditions Macrophages for Enhanced Responses toward Inflammatory Stimuli via JNK Activation [INNATE IMMUNITY AND INFLAMMATION]

Obesity is associated with low-grade inflammation and elevated levels of circulating saturated fatty acids, which trigger inflammatory responses by engaging pattern recognition receptors in macrophages. Because tissue homeostasis is maintained through an adequate balance of pro- and anti-inflammatory macrophages, we assessed the transcriptional and functional profile of M-CSF–dependent monocyte-derived human macrophages exposed to concentrations of saturated fatty acids found in obese individuals. We report that palmitate (C16:0, 200 μM) significantly modulates the macrophage gene signature, lowers the expression of transcription factors that positively regulate IL-10 expression (MAFB, AhR), and promotes a proinflammatory state whose acquisition requires JNK activation. Unlike LPS, palmitate exposure does not activate STAT1, and its transcriptional effects can be distinguished from those triggered by LPS, as both agents oppositely regulate the expression of CCL19 and TRIB3. Besides, palmitate conditions macrophages for exacerbated proinflammatory responses (lower IL-10 and CCL2, higher TNF-α, IL-6, and IL-1β) toward pathogenic stimuli, a process also mediated by JNK activation. All of these effects of palmitate are fatty acid specific because oleate (C18:1, 200 μM) does not modify the macrophage transcriptional and functional profiles. Therefore, pathologic palmitate concentrations promote the acquisition of a specific polarization state in human macrophages and condition macrophages for enhanced responses toward inflammatory stimuli, with both effects being dependent on JNK activation. Our results provide further insight into the macrophage contribution to obesity-associated inflammation.

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Induction of Systemic Autoimmunity by a Xenobiotic Requires Endosomal TLR Trafficking and Signaling from the Late Endosome and Endolysosome but Not Type I IFN [AUTOIMMUNITY]

Type I IFN and nucleic acid–sensing TLRs are both strongly implicated in the pathogenesis of lupus, with most patients expressing IFN-induced genes in peripheral blood cells and with TLRs promoting type I IFNs and autoreactive B cells. About a third of systemic lupus erythematosus patients, however, lack the IFN signature, suggesting the possibility of type I IFN–independent mechanisms. In this study, we examined the role of type I IFN and TLR trafficking and signaling in xenobiotic systemic mercury-induced autoimmunity (HgIA). Strikingly, autoantibody production in HgIA was not dependent on the type I IFN receptor even in NZB mice that require type I IFN signaling for spontaneous disease, but was dependent on the endosomal TLR transporter UNC93B1 and the endosomal proton transporter, solute carrier family 15, member 4. HgIA also required the adaptor protein-3 complex, which transports TLRs from the early endosome to the late endolysosomal compartments. Examination of TLR signaling pathways implicated the canonical NF-B pathway and the proinflammatory cytokine IL-6 in autoantibody production, but not IFN regulatory factor 7. These findings identify HgIA as a novel type I IFN–independent model of systemic autoimmunity and implicate TLR-mediated NF-B proinflammatory signaling from the late endocytic pathway compartments in autoantibody generation.

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CK12a, a CCL19-like Chemokine That Orchestrates both Nasal and Systemic Antiviral Immune Responses in Rainbow Trout [MUCOSAL IMMUNOLOGY]

Chemokines and chemokine receptors have rapidly diversified in teleost fish but their immune functions remain unclear. We report in this study that CCL19, a chemokine known to control lymphocyte migration and compartmentalization of lymphoid tissues in mammals, diversified in salmonids leading to the presence of six CCL19-like genes named CK10a, CK10b, CK12a, CK12b, CK13a, and CK13b. Salmonid CCL19-like genes all contain the DCCL-conserved motif but share low amino acid sequence identity. CK12 (but not CK10 or CK13) is constitutively expressed at high levels in all four trout MALT. Nasal vaccination with a live attenuated virus results in sustained upregulation of CK12 (but not CK10 or CK13) expression in trout nasopharynx-associated lymphoid tissue. Recombinant His-tagged trout CK12a (rCK12a) is not chemotactic in vitro but it increases the width of the nasal lamina propria when delivered intranasally. rCK12a delivered intranasally or i.p. stimulates the expression of CD8α, granulysin, and IFN- in mucosal and systemic compartments and increases nasal CD8α⁺ cell numbers. rCK12a is able to stimulate proliferation of head kidney leukocytes from Ag-experienced trout but not naive controls, yet it does not confer protection against viral challenge. These results show that local nasal production of CK12a contributes to antiviral immune protection both locally and systemically via stimulation of CD8 cellular immune responses and highlight a conserved role for CK12 in the orchestration of mucosal and systemic immune responses against viral pathogens in vertebrates.

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Thymic-Specific Serine Protease Limits Central Tolerance and Exacerbates Experimental Autoimmune Encephalomyelitis [AUTOIMMUNITY]

The genetic predisposition to multiple sclerosis (MS) is most strongly conveyed by MHC class II haplotypes, possibly by shaping the autoimmune CD4 T cell repertoire. Whether Ag-processing enzymes contribute to MS susceptibility by editing the peptide repertoire presented by these MHC haplotypes is unclear. Thymus-specific serine protease (TSSP) is expressed by thymic epithelial cells and thymic dendritic cells (DCs) and, in these two stromal compartments, TSSP edits the peptide repertoire presented by class II molecules. We show in this article that TSSP increases experimental autoimmune encephalomyelitis severity by limiting central tolerance to myelin oligodendrocyte glycoprotein. The effect on experimental autoimmune encephalomyelitis severity was MHC class II allele dependent, because the lack of TSSP expression conferred protection in NOD mice but not in C57BL/6 mice. Importantly, although human thymic DCs express TSSP, individuals segregate into two groups having a high or 10-fold lower level of expression. Therefore, the level of TSSP expression by thymic DCs may modify the risk factors for MS conferred by some MHC class II haplotypes.

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IFN-{lambda}4 Attenuates Antiviral Responses by Enhancing Negative Regulation of IFN Signaling [INFECTIOUS DISEASE AND HOST RESPONSE]

Type III IFNs are important mediators of antiviral immunity. IFN-4 is a unique type III IFN because it is produced only in individuals who carry a dG allele of a genetic variant rs368234815-dG/TT. Counterintuitively, those individuals who can produce IFN-4, an antiviral cytokine, are also less likely to clear hepatitis C virus infection. In this study, we searched for unique functional properties of IFN-4 that might explain its negative effect on hepatitis C virus clearance. We used fresh primary human hepatocytes (PHHs) treated with recombinant type III IFNs or infected with Sendai virus to model acute viral infection and subsequently validated our findings in HepG2 cell line models. Endogenous IFN-4 protein was detectable only in Sendai virus–infected PHHs from individuals with the dG allele, where it was poorly secreted but highly functional, even at concentrations < 50 pg/ml. IFN-4 acted faster than other type III IFNs in inducing antiviral genes, as well as negative regulators of the IFN response, such as USP18 and SOCS1. Transient treatment of PHHs with IFN-4, but not IFN-3, caused a strong and sustained induction of SOCS1 and refractoriness to further stimulation with IFN-3. Our results suggest unique functional properties of IFN-4 that can be important in viral clearance and other clinical conditions.

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Transient BAFF Blockade Inhibits Type 1 Diabetes Development in Nonobese Diabetic Mice by Enriching Immunoregulatory B Lymphocytes Sensitive to Deletion by Anti-CD20 Cotherapy [AUTOIMMUNITY]

In NOD mice and also likely humans, B lymphocytes play an important role as APC-expanding autoreactive T cell responses ultimately causing type 1 diabetes (T1D). Currently, humans at high future T1D risk can only be identified at late prodromal stages of disease indicated by markers such as insulin autoantibodies. When commenced in already insulin autoantibody⁺ NOD mice, continuous BAFFR-Fc treatment alone or in combination with anti-CD20 (designated combo therapy) inhibited T1D development. Despite eliciting broader B lymphocyte depletion, continuous combo therapy afforded no greater T1D protection than did BAFFR-Fc alone. As previously observed, late disease stage–initiated anti-CD20 monotherapy did not inhibit T1D, and in this study was additionally found to be associated with development of drug-blocking Abs. Promisingly, NOD mice given transient late disease stage BAFFR-Fc monotherapy were rendered T1D resistant. However, combo treatment abrogated the protective effect of transient BAFFR-Fc monotherapy. NOD mice receiving transient BAFF blockade were characterized by an enrichment of regulatory B lymphocytes that inhibit T1D development through IL-10 production, but this population is sensitive to deletion by anti-CD20 treatment. B lymphocytes from transient BAFFR-Fc–treated mice suppressed T cell proliferation to a greater extent than did those from controls. Proportions of B lymphocytes expressing CD73, an ecto-enzyme operating in a pathway converting proinflammatory ATP to anti-inflammatory adenosine, were also temporarily increased by transient BAFFR-Fc treatment, but not anti-CD20 therapy. These collective studies indicate transient BAFFR-Fc–mediated B lymphocyte depletion elicits long-term T1D protection by enriching regulatory B lymphocytes that are deleted by anti-CD20 cotherapy.

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Factor H-IgG Chimeric Proteins as a Therapeutic Approach against the Gram-Positive Bacterial Pathogen Streptococcus pyogenes [INFECTIOUS DISEASE AND HOST RESPONSE]

Bacteria can cause life-threatening infections, such as pneumonia, meningitis, or sepsis. Antibiotic therapy is a mainstay of treatment, although antimicrobial resistance has drastically increased over the years. Unfortunately, safe and effective vaccines against most pathogens have not yet been approved, and thus developing alternative treatments is important. We analyzed the efficiency of factor H (FH)6-7/Fc, a novel antibacterial immunotherapeutic protein against the Gram-positive bacterium Streptococcus pyogenes. This protein is composed of two domains of complement inhibitor human FH (FH complement control protein modules 6 and 7) that bind to S. pyogenes, linked to the Fc region of IgG (FH6-7/Fc). FH6-7/Fc has previously been shown to enhance complement-dependent killing of, and facilitate bacterial clearance in, animal models of the Gram-negative pathogens Haemophilus influenzae and Neisseria meningitidis. We hypothesized that activation of complement by FH6-7/Fc on the surface of Gram-positive bacteria such as S. pyogenes will enable professional phagocytes to eliminate the pathogen. We found that FH6-7/Fc alleviated S. pyogenes–induced sepsis in a transgenic mouse model expressing human FH (S. pyogenes binds FH in a human-specific manner). Furthermore, FH6-7/Fc, which binds to protein H and selected M proteins, displaced FH from the bacterial surface, enhanced alternative pathway activation, and reduced bacterial blood burden by opsonophagocytosis in a C3-dependent manner in an ex vivo human whole-blood model. In conclusion, FH-Fc chimeric proteins could serve as adjunctive treatments against multidrug-resistant bacterial infections.

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Anti-CD20 Antibody Prevents Red Blood Cell Alloimmunization in a Mouse Model [IMMUNOTHERAPY AND VACCINES]

Alloimmunization against RBCs can cause life-threatening delayed hemolytic transfusion reactions. Anti-CD20 Ab has recently been used to prevent alloimmunization. However, its effects remain unclear, particularly in lymphoid organs. We investigated the impact of murine anti-CD20 Ab in the blood and spleen. We assessed protocols for preventing primary alloimmunization and for abolishing established alloimmunization. Prophylactic protocols prevented alloimmunization. However, anti-CD20 treatment could only limit the further amplification of established alloimmunization. Residual B cell subtype distribution was disrupted in the spleen, but adoptive transfer studies indicated that these cells were neither plasma nor memory cells. Anti-CD20 Ab had a major effect on alloreactive CD4⁺ T cells, increasing the expansion of this population and its CD40 expression, while lowering its CD134 expression, thereby confirming its role in alloimmunization. In conclusion, this study shows that anti-CD20 immunotherapy can prevent RBC Ab development. However, this immunotherapy is limited by the increase in alloreactive CD4⁺ T lymphocytes. Nevertheless, treatment with anti-CD20 Abs should be considered for patients requiring transfusion with a very high risk of alloimmunization and life-threatening complications.

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IL-17A-Induced PLET1 Expression Contributes to Tissue Repair and Colon Tumorigenesis [INNATE IMMUNITY AND INFLAMMATION]

This study identifies a novel mechanism linking IL-17A with colon tissue repair and tumor development. Abrogation of IL-17A signaling in mice attenuated tissue repair of dextran sulfate sodium (DSS)-induced damage in colon epithelium and markedly reduced tumor development in an azoxymethane/DSS model of colitis-associated cancer. A novel IL-17A target gene, PLET1 (a progenitor cell marker involved in wound healing), was highly induced in DSS-treated colon tissues and tumors in an IL-17RC–dependent manner. PLET1 expression was induced in LGR5⁺ colon epithelial cells after DSS treatment. LGR5⁺PLET1⁺ marks a highly proliferative cell population with enhanced expression of IL-17A target genes. PLET1 deficiency impaired tissue repair of DSS-induced damage in colon epithelium and reduced tumor formation in an azoxymethane/DSS model of colitis-associated cancer. Our results suggest that IL-17A–induced PLET1 expression contributes to tissue repair and colon tumorigenesis.

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{gamma}{delta} T Cells Are Required for the Induction of Sterile Immunity during Irradiated Sporozoite Vaccinations [IMMUNOTHERAPY AND VACCINES]

Whole-sporozoite vaccines confer sterilizing immunity to malaria-naive individuals by unknown mechanisms. In the first PfSPZ Vaccine trial ever in a malaria-endemic population, V2 T cells were significantly elevated and V9/V2 transcripts ranked as the most upregulated in vaccinees who were protected from Plasmodium falciparum infection. In a mouse model, absence of T cells during vaccination impaired protective CD8 T cell responses and ablated sterile protection. T cells were not required for circumsporozoite protein–specific Ab responses, and T cell depletion before infectious challenge did not ablate protection. T cells alone were insufficient to induce protection and required the presence of CD8α⁺ dendritic cells. In the absence of T cells, CD8α⁺ dendritic cells did not accumulate in the livers of vaccinated mice. Altogether, our results show that T cells were essential for the induction of sterile immunity during whole-organism vaccination.

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Orchestrating Role of Apoptosis Inhibitor of Macrophage in the Resolution of Acute Lung Injury [INNATE IMMUNITY AND INFLAMMATION]

Appropriate resolution of inflammation is known to be essential in tissue homeostasis. In this study, we evaluated the significance of a macrophage-derived soluble protein, apoptosis inhibitor of macrophage (AIM), in LPS-induced lung injury in mice. After oropharyngeal administration of LPS, the level of free-form serum AIM increased on days 2–4, accompanied by the resolution of inflammation, which was observed in the cellular profile of bronchoalveolar lavage fluid. In an experiment using wild-type (WT) and AIM^–/– mice, the resolution of inflammation was accelerated in AIM^–/– mice when compared with the WT mice, which was reversed when recombinant AIM protein was administered. The changes in the histopathological findings and inflammatory mediators followed similar trends, and the ratio of apoptotic cells was increased in AIM^–/– mice when compared with the WT mice. In vitro analysis showed that macrophage phagocytosis of apoptotic neutrophils was suppressed in the presence of AIM, indicating that anti-resolution property of AIM involves efferocytosis inhibition. In lipidomic analysis of lung tissues, the levels of several lipid mediators increased markedly when LPS was given to WT mice. However, in AIM^–/– mice, the concentrations of these lipid mediators were not significantly upregulated by LPS. These data reflect the significant role of AIM in lipid metabolism; it may suppress lipid metabolites at baseline, and then produce an inflammatory/pathologic pattern in the event of LPS-induced lung injury. Taken together, AIM may play an orchestrating role in the resolution process of inflammation by altering the profile of pulmonary lipid mediators in mice.

http://ift.tt/2zV5VAb

Listeria monocytogenes Replicate in Bone Marrow-Derived CD11c+ Cells but Not in Dendritic Cells Isolated from the Murine Gastrointestinal Tract [INFECTIOUS DISEASE AND HOST RESPONSE]

Recent fate-mapping studies and gene-expression profiles suggest that commonly used protocols to generate bone marrow–derived cultured dendritic cells yield a heterogeneous mixture, including some CD11c^hi cells that may not have a bona fide counterpart in vivo. In this study, we provide further evidence of the discordance between ex vivo–isolated and in vitro–cultured CD11c⁺ cells by analyzing an additional phenotype, the ability to support cytosolic growth of the facultative intracellular bacterial pathogen Listeria monocytogenes. Two days after foodborne infection of mice with GFP-expressing L. monocytogenes, a small percentage of CD103^neg and CD103⁺ conventional dendritic cells (cDC) in the intestinal lamina propria and mesenteric lymph nodes were GFP⁺. However, in vitro infection of the same subsets of cells harvested from naive mice resulted in inefficient invasion by the bacteria (<0.1% of the inoculum). The few intracellular bacteria detected survived for only a few hours. In contrast, cultured CD103^negCD11c⁺ cells induced by GM-CSF readily supported exponential growth of L. monocytogenes. Flt3 ligand–induced cultures yielded CD103⁺CD11c⁺ cells that more closely resembled cDC, with only a modest level of L. monocytogenes replication. For both culture protocols, the longer the cells were maintained in vitro, the more readily they supported intracellular growth. The results of this study suggest that cDC are not a niche for intracellular growth of L. monocytogenes during intestinal infection of mice.

http://ift.tt/2zTmqfX

Correction

Etzkorn JR, Sobanko JF, Elenitsas R, et al. Low recurrence rates for in situ and invasive melanomas using Mohs micrographic surgery with melanoma antigen recognized by T cells 1 (MART-1) immunostaining: Tissue processing methodology to optimize pathologic staging and margin assessment. J Am Acad Dermatol. 2015;72(5):840-50.

http://ift.tt/2zUJ8nR

Language-specific strategy for programming hearing aids — A double-blind randomized controlled crossover study

Voice-aligned compression (VAC) is a method used in Oticon's hearing aids to provide more comfortable hearing without sacrificing speech discrimination. The complex, non-linear compression curve for the VAC strategy is designed based on the frequency profile of certain spoken Western languages. We hypothesized that hearing aids could be further customized for Japanese-speaking users by modifying the compression curve using the frequency profile of spoken Japanese.

http://ift.tt/2zWq2xR

Pediatric type 1 cartilage tympanoplasty outcomes: A comparison of short and long term hearing results

Tympanoplasty is a commonly used procedure in children as in adults. The purposes of this study were to evaluate and report the long term results of type 1 cartilage tympanoplasty in pediatric population. Short term and long term hearing outcomes were compared according to age and perforation location.

http://ift.tt/2hDRFBs

Mannose-binding lectin deficiency associated with numerous paraspinal neurofibromas

Mannose-binding lectin (MBL) is a protein found in plasma that is part of the innate immune system and can activate the complement cascade.1 It is typically involved with antimicrobial and proinflammatory functions.2

http://ift.tt/2B7CRU0

The association of maternal prenatal vitamin D levels and child current wheeze

Wheezing is common in early childhood and is associated with subsequent asthma and decreased lung function.1 Prenatally, vitamin D influences immune system and lung development; a role in consequent child wheeze and asthma has been hypothesized.2,3 Previous research has reported associations between 25-dihydroxyvitamin D [25(OH)D] levels and respiratory or atopic outcomes potentially inconsistent by race.4 In this study we examine associations between maternal second trimester and delivery 25(OH)D levels and child current wheeze in the third year of life by maternal race.

http://ift.tt/2z5NZ2s

Hydroxychloroquine as a steroid-sparing agent in an infant with chronic urticaria

Hydroxychloroquine is an antimalarial drug frequently used to reduce inflammation in autoimmune and inflammatory conditions.1,2 In adults, hydroxychloroquine can be used as an alternative agent to treat antihistamine-refractory chronic spontaneous urticaria (CSU).3 It is unknown whether hydroxychloroquine is safe and effective for treating antihistamine-refractory CSU in children. We present the case of a 9-month-old male infant with 5 months of recurrent, unprovoked hives and swelling who was treated safely and successfully with hydroxychloroquine.

http://ift.tt/2B6rtrr

Schnitzler syndrome with IgG gammopathy and elevated IL-1β and IL-17 in skin biopsy

Schnitzler syndrome is a rare disorder known for chronic urticarial rash, systemic inflammation, and monoclonal gammopathy.1 Historically it has been associated with immunoglobulin M (IgM), but in the past 20 years new cases have been described that include variants with an immunoglobulin G (IgG) gammopathy. We report a case of Schnitzler syndrome associated with IgG gammopathy and increased expression of interleukin (IL)-1β and IL-17 by immunohistochemistry at skin biopsy examination.

http://ift.tt/2z8d2Sj

Advances in rhinitis—models and mechanisms

To summarize studies highlighting recent advances in rhinitis-related research in the past 2 years.

http://ift.tt/2B7CDME

Dexamethasone for inpatient childhood asthma exacerbations is as effective as short-acting corticosteroid treatment

Acute asthma exacerbations result in over 130,000 childhood hospitalizations in the United States annually.1 Systemic corticosteroids (SCS) are a fundamental component of exacerbation management and reduce relapse rates after hospital discharge.2 Use of prednisolone or other short-acting SCS during hospitalization may require continuation of this medication after hospital discharge, yet a recent study demonstrated that only about half of these prescriptions are filled within 3–7 days of discharge.

http://ift.tt/2z4zSu4

Visually Augmented Targeted Combination Light Therapy for Acne

A novel approach to using phototherapy for inflammatory acne was successful in this patient.
Journal of Medical Case Reports

http://ift.tt/2zSF7Ay

Endoscopic Evaluation of Duodenal Polyposis in Patients With Familial Adenomatous Polyposis (FAP)

Conditions:   Familial Adenomatous Polyposes;   Duodenal Polyposis;   Duodenal Cancer
Intervention:   Diagnostic Test: Esophagogastroduodenoscopy
Sponsor:   Copenhagen University Hospital, Hvidovre
Not yet recruiting

http://ift.tt/2hMseBc

A Study of Epacadostat and Nivolumab in Combination With Immune Therapies in Subjects With Advanced or Metastatic Malignancies (ECHO-208)

Condition:   Advanced or Metastatic Solid Tumors
Interventions:   Drug: Epacadostat;   Drug: Nivolumab;   Drug: Ipilimumab;   Drug: Lirilumab
Sponsor:   Incyte Corporation
Not yet recruiting

http://ift.tt/2jKBGG8

MRI of Esophagus Cancer

Conditions:   Esophagus Cancer;   Diagnoses Disease
Intervention:   Diagnostic Test: MRI
Sponsor:   Dromain Clarisse
Recruiting

http://ift.tt/2hSc09L

Muscle Dysfunction in Gastrointestinal or Hepatobiliary Cancer

Conditions:   Cancer;   Cancer of Pancreas;   Cancer of Liver;   Cancer of Esophagus;   Cancer of Stomach;   Cancer, Metastatic
Intervention:  
Sponsor:   Rigshospitalet, Denmark
Not yet recruiting

http://ift.tt/2hMh9Ah

Nivolumab for the Reversal of Squamous Dysplasia in High Risk Current and Former Smokers

Conditions:   Bronchial Dysplasia;   Tobacco Smoking;   History of Non-Small Cell Lung Cancer;   History of Head and Neck Cancer
Intervention:   Drug: Nivolumab
Sponsors:   University of Colorado, Denver;   Bristol-Myers Squibb
Not yet recruiting

http://ift.tt/2mL81h1

Reply to the Letter to the Editor: “Extracapsular dissection versus superficial parotidectomy in benign parotid gland tumors: The Vienna Medical School experience”

http://ift.tt/2AX9frP

Peroxisome proliferator activated receptor-gamma stimulation for prevention of 5-fluorouracil-induced oral mucositis in mice

Abstract

Background

Oral mucositis is a side effect of treatment regimens containing 5-fluorouracil (5-FU). The purpose of this study was to present our evaluation to see if rosiglitazone (RGZ) protected normal tissues from chemotherapy-induced oral mucositis.

Methods

C57BL/6J mice were treated with 5-FU for 5 days, with or without RGZ. Mice were euthanized after 5, 8, 11, or 15 days, and mucosal segments were collected.

Results

The RGZ did not affect the 5-FU-induced decrease in mouse body weight. The 5-FU caused loss of epithelial architecture, collagen fiber impairment, and inflammatory infiltration. The RGZ reduced leukocyte infiltration, preserved tissue structure, and dampened the 5-FU-induced expression of p53 and matrix metalloproteinase (Mmp)-2 after 5 days, and of Mmp-2 and interleukin (Il-1β after 15 days. The RGZ inhibited the 5-FU-induced increase of transforming growth factor-beta (TGF-β) and nuclear factor-kappa B (NF-κB) proteins and restored collagen protein levels.

Conclusion

The RGZ had a protective effect on oral mucosa damaged by chemotherapy. These data encourage the further study of RGZ for the prevention of 5-FU-induced mucositis in patients with cancer.

http://ift.tt/2iykL5Y

Free gracilis muscle transfer for smile reanimation after treatment for advanced parotid malignancy

Abstract

Background

The purpose of this study was to characterize the outcomes of free gracilis muscle transfer for delayed smile reanimation after radical parotidectomy.

Methods

A retrospective chart review of patients who underwent free gracilis muscle transfer for smile reanimation after radical parotidectomy between 2003 and 2016 was performed. Patient-reported quality of life (Facial Clinimetric Evaluation Scale [FaCE]), physician-reported facial function ("eFACE" facial grading scale), and oral commissure excursion were compared preoperatively and postoperatively.

Results

Twelve patients were identified with prior surgery and adjuvant therapy (radiotherapy in 6 cases and chemoradiotherapy in 6 cases). Significant postoperative improvements were demonstrated for ipsilateral commissure excursion with smile (preoperatively: −2.2 mm [SD 2.3 mm] vs postoperatively: 7.9 mm [SD 2.5 mm]; P = .002), with meaningful smile achieved in 11 of 12 cases (91.7%). The average duration of facial paralysis before intervention was 72 months (range 12-204 months).

Conclusion

Free gracilis muscle transfer is an option for dynamic smile reanimation in select patients who have undergone treatment for advanced parotid malignancy.

http://ift.tt/2AWh8xu

Intensity-modulated radiotherapy for elderly patients with nasopharyngeal carcinoma

Abstract

Background

The purpose of this study was to evaluate the clinical outcomes and patterns of failure after intensity-modulated radiotherapy (IMRT) for elderly patients with nasopharyngeal carcinoma (NPC).

Methods

Fifty-two patients treated with IMRT were eligible for study inclusion. Comorbidity was rated using the Adult Comorbidity Evaluation-27 (ACE-27) system.

Results

Twenty-six patients (50.0%) had an ACE-27 score of 1; and 6 (11.5%) had an ACE-27 score of 2. Eleven patients had died and 5 (45.5%) of them died of NPC. Two patients had developed local recurrence only, 1 had developed regional recurrence only, and 7 had developed distant metastasis only. The locoregional failure-free survival, distant failure-free survival, cancer-specific survival (CSS), and overall survival (OS) rates at 5 years were 92.6%, 83.7%, 84.9%, and 69.4%, respectively.

Conclusion

The results of treating elderly patients with NPC by IMRT were excellent. Distant metastasis remains the most difficult treatment challenge for elderly patients with NPC.

http://ift.tt/2izWw7r

Safety and effectiveness of endovascular embolization or stent-graft reconstruction for treatment of acute carotid blowout syndrome in patients with head and neck cancer: Case series and systematic review of observational studies

Abstract

Background

Indications for treatment and outcomes after endovascular management of carotid blowout syndrome for patients with head and neck cancer are not well defined. We investigated the safety and effectiveness of endovascular embolization and stent-graft reconstruction.

Methods

A literature review was performed for studies published between 2001 and 2015 with relevance to treatment outcomes. Our institutional database was examined to identify patients treated with endovascular techniques.

Results

A total of 266 patients were included. Rates of procedural stroke were higher after embolization of internal carotid artery (ICA)/common carotid artery (CCA) compared to stent graft (embolization 10.3%; stent graft 2.5%; P < .02). Stent graft of ICA/CCA was associated with higher rates of recurrent bleeding (embolization 9.1%; stent graft 31.9%; P < .01).

Conclusion

Both embolization and stent grafts are safe therapeutic options for acute carotid blowout syndrome. Embolization for ICA/CCA carotid blowout syndrome was associated with higher risks of procedural stroke and lower recurrent bleeding compared to stent grafts.

http://ift.tt/2AX9fbj

Letter to the Editor regarding “Extracapsular dissection versus superficial parotidectomy in benign parotid gland tumors: The Vienna Medical School experience”

http://ift.tt/2B72hkA

Circadian profiling reveals higher histamine plasma levels and lower diamine oxidase serum activities in 24% of patients with suspected histamine intolerance compared to food allergy and controls

Abstract

Background

Histamine intolerance is thought to trigger manifold clinical symptoms after ingesting histamine-rich food due to reduced activity of diamine oxidase (DAO). No study has hitherto systematically assessed daily fluctuations of histamine levels and DAO activities in symptomatic patients. The aim of the study was to investigate the presence of histamine intolerance, to therefore establish day profiles of histamine levels and DAO activities, and to compare the results between patients with suspected histamine intolerance, food allergy and healthy controls.

Methods

We determined day profiles of histamine plasma levels and DAO serum activities in 33 patients with suspected histamine intolerance, in 21 patients with proven food allergy and in 10 healthy control patients. Clinical symptoms, food intolerances and further clinical and laboratory-chemical parameters were evaluated.

Results

24% (8 of 33) suspected histamine intolerant patients showed elevated histamine levels during the day. That might be caused by constantly and significantly reduced DAO activities in these patients compared to food allergy and control patients. The remaining 25 patients presented normal histamine levels and DAO activities, but an increased prevalence of multiple food intolerances compared to the other subgroup of suspected histamine intolerants. There was no correlation between subjective complaints and serological histamine parameters in patients with suspected histamine intolerance.

Conclusions

We determined by daily profiling that decreased DAO activities correlated with elevated histamine levels in a subgroup of suspected histamine intolerants. This finding discriminates these patients from food intolerant individuals with similar clinical symptoms, and strongly suggests the presence of histamine intolerance.

This article is protected by copyright. All rights reserved.

http://ift.tt/2zjNbuW

Secondary erythromelalgia: a tryptophan dietary supplement-induced case associated with elevated 5-hydroxyindoleacetic acid (5HIAA) urinary levels

http://ift.tt/2hEuSp2

An extension of a multicenter, randomized, split-face clinical trial evaluating the efficacy and safety of chromophore gel-assisted blue light phototherapy for the treatment of acne

Abstract

A variety of laser/light-based devices have been reported to be effective for the treatment of acne, yet no long-term data on efficacy and safety have been published. A first 12-week clinical trial ("Main trial") recently demonstrated that the KLOX BioPhotonic System, an LED blue light device using photo-converter chromophores, can significantly improve moderate and severe facial acne vulgaris with an excellent safety profile. This Extension trial followed the Main trial, using the same BioPhotonic System, with the same dose and instructions for use, on patients having already completed treatment in the Main trial. Main objectives of this open-label long-term extension 12-week study were to evaluate the efficacy of the KLOX BioPhotonic System on the untreated hemiface during the Main trial, as well as the duration of response on the hemiface treated during the first 12-week Main trial. Despite their young age (mean age: 21.6 years) and their 12-week participation in the Main trial, 49 (54.4%) of the total number of patients who participated in the Main trial enrolled in this additional 12-week Extension trial. Baseline grading of acne was performed with the Investigator's Global Assessment (IGA) scale. For each patient, the hemiface randomly selected as a control during the Main trial received 6 weeks of treatment (twice weekly) and was then followed up for an additional 6 weeks. The first hemiface treated in the Main trial was consequently observed throughout the Extension trial, allowing for a further 12-week assessment of outcomes (total 24 weeks). In light of an additional 12 weeks of treatment on the contralateral face, the patient compliance rate was excellent, with 91.9% of the total number of patients receiving at least 80% of the treatments. Patients with a baseline IGA grade of 2 (mild) on the treated hemiface demonstrated a success rate of 58.3 and 66.7% at weeks 6 and 12, respectively. At these same time points, subjects with a baseline IGA grade of 3 (moderate) demonstrated a success rate of 81.8 and 90.0%. Patients with a baseline IGA grade of 4 (severe) demonstrated a success rate of 100% at both week 6 and week 12. When evaluating the originally treated hemifaces from the Main trial, the rate of return to baseline at 24 weeks was calculated to be 15.5%. This latter outcome confirmed the long duration of effect following treatment. The patient safety profile was also excellent, with very few related adverse events. The BioPhotonic System, which is comprised of LED blue light phototherapy and photo-converter chromophores, provides long-term efficacy and safety in the treatment of acne vulgaris, with a rate of compliance above what is generally observed in a young population of patients suffering from acne vulgaris, especially in light of sequential enrollment in a study treating one hemiface.

http://ift.tt/2zV6l9L

Regressed melanocytic nevi secondary to pembrolizumab therapy: an emerging melanocytic dermatologic effect from immune checkpoint antibody blockade

Abstract

Background

Immune checkpoint antibody blockade is an emerging therapeutic option for treating certain cancers including melanoma. This therapy is associated with dermatologic and systemic toxicities, some of which are more severe than others and may require withholding therapy.

Case reports

We report two patients with melanocytic nevi that regressed with pembrolizumab therapy. The first patient had stage IV BRAF K601E/L584F mutant melanoma that developed a regressed melanocytic nevus while being treated with pembrolizumab. The second patient had stage III BRAF V600R mutant melanoma that was treated with pembrolizumab and dabrafenib, and also developed a regressed melanocytic nevus. Both patients had good response to therapy and stable disease at 8 and 12 months of treatment, respectively.

Results

Regressed melanocytic nevi were observed in both patients treated with pembrolizumab for advance-stage melanoma. Immunohistochemical analysis of a regressed melanocytic nevus was associated with an inflammatory infiltrate rich in CD8+ T cells and CD163+, CD11c+ histiocytes.

Conclusion

Regressed melanocytic nevi are an emerging dermatologic effect from pembrolizumab therapy.

http://ift.tt/2hFtfHS

Syringe lubricant and adverse reactions

http://ift.tt/2zRjgJH

Autoantibodies to full body vascular cell junctions colocalize with MYZAP, ARVCF, desmoplakins I and II and p0071 in endemic pemphigus in Colombia, South America

Abstract

Background

We previously described a new variant of endemic pemphigus foliaceus in El Bagre, Colombia (El Bagre-EPF).

Methods

Here we aimed to investigate disease autoreactivity to vessels in all body organs/systems. We compared 57 patients and 57 controls from the endemic area, matched by demographics, age, sex, and work activity. We performed immunofluorescence, immunohistochemistry, confocal microscopy, immunoblotting, indirect immune electron microscopy studies, and autometallographic studies. We performed ultrasonography on large patient arteries, investigating for vascular anomalies. In addition, we reviewed autopsies on seven patients who died affected by El Bagre-EPF. We immunoadsorbed any positive vessel immunofluorescence with desmoglein (Dsg1), investigating for new autoantigens.

Results

Overall, 57/57 patients affected by El Bagre-EPF displayed autoantibodies to vessels in all the organs/systems of the body via all methods (P < 0.01). The autoreactivity was polyclonal, and the patient's antibodies colocalized with commercial antibodies to desmoplakins I and II, p0071, ARVCF, and MYZAP (all from Progen Biotechnik, Germany; P < 0.01; all present at cell junctions). Immunoadsorption with Dsg1 on positive vessel immunofluorescence showed that the immune response against the vessels was directed against non-Dsg1 antigen(s). Autometallographic studies showed deposits of metals and metalloids in vessel cell junctions and in erythrocytes of 85% of patients (P < 0.01).

Conclusions

Immune response to these vascular antigens is likely altering endothelial cells and vessel shapes, thus disturbing hemodynamic flow. The flow alterations likely lead to inflammation and may play a role in the atherogenesis often seen in these patients.

http://ift.tt/2hFYNxg

Anti-desmogleins autoantibodies detected by ELISA and blotting in bullous pemphigoid: what do they mean?

http://ift.tt/2zTpQj1

The “Duvic regimen” for erythrodermic flares secondary to Staphylococcus aureus in mycosis fungoides and Sézary syndrome

http://ift.tt/2hELw83

Polymorphous presentation of subcutaneous phaeohyphomycosis: a rare occurrence

http://ift.tt/2zTpOYr

Changing practices of hair relaxer use among black women in the United States

http://ift.tt/2hEuRBs

Human papillomavirus-associated cutaneous disease burden in human immunodeficiency virus (HIV)-positive patients: the role of human papillomavirus vaccination and a review of the literature

Abstract

Human papillomavirus (HPV) infection is related to the development of cutaneous squamous cell carcinoma, oropharyngeal carcinoma, and anogenital malignancies. Patients infected with human immunodeficiency virus (HIV) have impaired cell-mediated immunity, placing them at risk for more prolonged infection with a greater likelihood of disease expression. This presents important implications for screening and treatment of HPV in the HIV patient population. The use of prophylactic vaccines directed against HPV has been a promising clinical development, though the immunogenicity of these vaccines in the immunocompromised host and in patients with previously established HPV infections has not been well established. In this review, we describe the pathogenesis and epidemiology of HPV-related cutaneous malignancies in patients with HIV. We outline the current guidelines and recent advances in the field of HPV vaccination. It is our hope that increasing awareness of the HPV-related HIV comorbidities will lead to developments in preventative medicine capable of reducing the burden of these diseases. We recognize the importance of prevention as a primary defense against disease and hope that this article organizes and disseminates recent findings in the field of HPV-associated comorbidities in the HIV population.

http://ift.tt/2zTpNnl

Atomic force microscopy for biomechanical and structural analysis of human dermis: a complementary tool for medical diagnosis and therapy monitoring

Abstract

Skin mechanical properties are usually measured considering the entire skin thickness and very little is known about the mechanical behavior of individual skin layers. We propose atomic force microscopy (AFM) as a tool to quantify nanoscale changes in the biomechanical properties and ultrastructure of human papillary dermis exposed to different mechanical and physical stimuli. Samples from three human skin biopsies were studied: one stretched by obesity, one subjected to a high level of sun-exposure, and normal skin as control. Slices of the papillary dermis layer were harvested at controlled depths from each skin biopsy and 25 μm² areas of each slice were imaged and D-periodicity of collagen fibers measured by AFM, together with their stiffness. Standard histological analysis was also carried out in order to correlate biochemical properties and their distribution with stiffness and topography. We obtained similar stiffness values between the sample affected by obesity and the control sample at any depth level into the dermis, while the sun-exposed sample presented a significant lower stiffness. Additionally, all samples presented an increase in the stiffness at higher depths into the papillary dermis layer. Collagen fibers close to the epidermis of sample affected either by obesity and sun-exposure– the former even more than the latter – are thicker and present a larger D-period than those in the control sample. Our results open the possibility to use structural and mechanical analysis based on AFM as a complementary tool for medical diagnosis and therapy monitoring.

This article is protected by copyright. All rights reserved.

http://ift.tt/2hGOeKn

Interleukin-17 Alters the Biology of Many Cell Types Involved in the Genesis of Psoriasis, Systemic Inflammation, and Associated Comorbidities

Abstract

Psoriasis is a chronic, immune-mediated, systemic inflammatory disease that is defined by a characteristic skin reaction produced when elevated levels of inflammatory cytokines such as interleukin (IL)-17 alter the growth and differentiation of skin cells. The pathogenesis of comorbid conditions associated with psoriasis, including psoriatic arthritis, cardiovascular disease, obesity, metabolic syndrome, liver disorders, renal disease, and depression are also largely affected by inflammation. In this review, we examine the effect of IL-17 on the inflammatory pathways in a variety of different cell types, including keratinocytes, as well as epithelial cells of the colon, kidney, gut, and liver. Additionally, we investigate the role of IL-17 in mediating the psoriasis-associated comorbidities detailed above.

This article is protected by copyright. All rights reserved.

http://ift.tt/2zToEw3

Laudation for Dr. Alexander Berghaus

http://ift.tt/2j8FYTw

The Genetic Basis of Seborrheic Dermatitis: A Review

Abstract

Seborrheic Dermatitis (SD) is a common inflammatory skin disease that presents as itchy, flaking skin in the seborrheic areas. Various environmental and intrinsic factors have been identified as predisposing factors for SD, but its etiology remains poorly understood. Although it was recognized that genetic factors play a role in SD etiology, there have not been studies that systematically review the literature specifically for causal mutations or protein deficiencies in SD. In this review, we searched various databases for gene mutations and protein deficiencies that cause SD or SD-like phenotype in humans and experimental animals, and summarize 11 gene mutations or protein deficiencies that were described in the literature. Most of the encoded proteins play a role either in the immune response (ACT1, C5, IKBKG/NEMO, STK4, 2C TCR) or epidermal differentiation (ZNF750, MPZL3). Understanding the genetic basis of SD can impart knowledge of the pathobiology of the disease and help identify novel therapeutic targets.

This article is protected by copyright. All rights reserved.

http://ift.tt/2z56zre