Clinico‐pathological predictors of mismatch repair deficiency in sebaceous neoplasia: A large case series from a single Australian private pathology service

Abstract

Background/Objectives

Loss of expression of mismatch repair (MMR) proteins is frequently observed in sebaceous skin lesions and can be a herald for Lynch syndrome. The aim of this study was to identify clinico‐pathological predictors of MMR deficiency in sebaceous neoplasia that could aid dermatologists and pathologists in determining which sebaceous lesions should undergo MMR immunohistochemistry (IHC).

Methods

An audit of sebaceous skin lesions (excluding hyperplasia) where pathologist‐initiated MMR IHC was performed between January 2009 to December 2016 was undertaken from a single pathology practice identifying 928 lesions from 882 individuals. Lesions were further analysed for differences in gender, age at diagnosis, lesion type and anatomic location, stratified by MMR status.

Results

The 882 individuals (67.7% male) had a mean (SD) age of diagnosis of 68.4 ± 13.3 years. Nearly two‐thirds of the lesions were sebaceous adenomas, with 82.6% of all lesions occurring on the head and neck. MMR deficiency, observed in 282 of the 919 lesions (30.7%), was most common in sebaceous adenomas (210/282; 74.5%). MMR‐deficient lesions occurred predominantly on the trunk or limbs (64.7%), compared with 23.2% in head or neck (P < 0.001). Loss of MSH2 and MSH6 protein expression was most frequent pattern of loss (187/281; 66.5%). The highest AUC for discriminating MMR‐deficient sebaceous lesions from MMR‐proficient lesions was observed for the ROC curve based on subgroups defined by type and anatomic location of the sebaceous lesion (AUC = 0.68).

Conclusion

The best combination of measured clinico‐pathological features achieved only modest positive predictive values, sensitivity and specificity for identifying MMR‐deficient sebaceous skin lesions.

https://ift.tt/2AILtBf

Pigmentary Skin Disorders. Edited by P Kumarasinghe. Springer International Publishing, Cham, Switzerland, 2018. 297 pages. €110. ISBN 978‐3‐319‐70418‐0.

https://ift.tt/2QqDcMj

Current Microbiological Trends of Chronic Suppurative Otitis Media in a Tertiary Care Centre, Mysuru, India

Abstract

The aim of the study was to re- evaluate the current bacteriological profile of chronic suppurative otitis media and to know their antibiotic sensitivity pattern to commonly used antibiotics. To provide a guideline for empirical antibiotic therapy when culture facilities are not available. Observational study. Patients who presented to Ear, Nose and Throat department with chronic or recurrent ear discharge and on clinical examination found to have actively discharging ears were selected. Patients who did not receive antimicrobial therapy (topical or systemic) for the last 7 days were included. Out of the 106 ear swabs processed, bacterial growth was found in 100 samples (94.33%), while 6 samples (5.66%) showed no growth. The results revealed Pseudomonas aeruginosa as the most isolated bacteria (49%), followed by Staphylococcus aureus (18%). Antibiotic susceptibility—Pseudomonas aeruginosa was sensitive to Cefoperazone–Sulbactam (96%), Imipenem (82%), Piperacillin–Tazobactam (82%), Amikacin in 82% and Gentamicin (76%). It was found that Pseudomonas was sensitive to Ciprofloxacin in only 57% of the cases. Staphylococcus aureus isolates were sensitive to Vancomycin in 90%, Gentamicin in 81%, Clindamycin in 72%, and Erythromycin in 45%. It was found that 100% of the isolates were resistant to Ciprofloxacin. Our findings highlight the importance of continuous and periodic evaluation of microbiological pattern and antibiotic sensitivity of isolates in chronic suppurative otitis media patients to decrease the potential risk of complications by early institution of appropriate treatment.

https://ift.tt/2Sw65nJ

Current Microbiological Trends of Chronic Suppurative Otitis Media in a Tertiary Care Centre, Mysuru, India

Abstract

The aim of the study was to re- evaluate the current bacteriological profile of chronic suppurative otitis media and to know their antibiotic sensitivity pattern to commonly used antibiotics. To provide a guideline for empirical antibiotic therapy when culture facilities are not available. Observational study. Patients who presented to Ear, Nose and Throat department with chronic or recurrent ear discharge and on clinical examination found to have actively discharging ears were selected. Patients who did not receive antimicrobial therapy (topical or systemic) for the last 7 days were included. Out of the 106 ear swabs processed, bacterial growth was found in 100 samples (94.33%), while 6 samples (5.66%) showed no growth. The results revealed Pseudomonas aeruginosa as the most isolated bacteria (49%), followed by Staphylococcus aureus (18%). Antibiotic susceptibility—Pseudomonas aeruginosa was sensitive to Cefoperazone–Sulbactam (96%), Imipenem (82%), Piperacillin–Tazobactam (82%), Amikacin in 82% and Gentamicin (76%). It was found that Pseudomonas was sensitive to Ciprofloxacin in only 57% of the cases. Staphylococcus aureus isolates were sensitive to Vancomycin in 90%, Gentamicin in 81%, Clindamycin in 72%, and Erythromycin in 45%. It was found that 100% of the isolates were resistant to Ciprofloxacin. Our findings highlight the importance of continuous and periodic evaluation of microbiological pattern and antibiotic sensitivity of isolates in chronic suppurative otitis media patients to decrease the potential risk of complications by early institution of appropriate treatment.

https://ift.tt/2Sw65nJ

Effect of continuous positive airway pressure on endothelin-1 in patients with obstructive sleep apnea: a meta-analysis

Abstract

Purpose

Obstructive sleep apnea (OSA) is related to endothelin-1 (ET-1). Continuous positive airway pressure (CPAP) is an effective therapy for OSA. However, the effectiveness of CPAP on ET-1 levels in patients with OSA yielded contradictory results. We conducted a meta-analysis to assess the effect of CPAP on ET-1 levels in OSA.

Methods

The Embase, and Cochrane Library and PubMed were searched before March, 2018. The overall effects were measured by the standardized mean difference (SMD) with a 95% confidence interval (CI). Ten studies were included and the meta-analysis was conducted using Stata 14.0.

Results

10 studies involving 375 patients were included in the meta-analysis. The result showed that there was a significant reduction in ET-1 levels in OSA patients before and after CPAP therapy (SMD = − 0.74, 95% CI = − 1.30 to − 0.17, z = 2.56, p = 0.01). Further, subgroup analysis demonstrated that Apnea–Hypopnea Index (AHI), CPAP therapy duration, and sample size also affected CPAP therapy.

Conclusions

Our meta-analysis indicated that CPAP treatment among OSA patients was significantly was related to a decrease in ET-1 levels. Further prospective long-term studies with a larger number of patients are needed to evaluate and clarify this issue.

https://ift.tt/2AJQUzU

Temporal bone trauma effects on auditory anatomical structures in mastoid obliteration

Abstract

Purpose

The risk of temporal bone fractures in head trauma is not negligible, as injuries also depend on the resistance and integrity of head structures. The capacity of mastoid cells to absorb part of the impact kinetic energy of the temporal bone is diminished after open cavity mastoidectomy, even if the surgical procedure is followed by mastoid obliteration. The aim of our study was to evaluate the severity of lesions in auditory anatomical structures after a lateral impact on cadaveric temporal bones in which open cavity mastoidectomy followed by mastoid obliteration was performed, compared to cadaveric temporal bones with preserved mastoids.

Methods

The study was carried out on 20 cadaveric temporal bones, which were randomly assigned to two groups. In the study group, open cavity mastoidectomy followed by mastoid obliteration with heterologous materials was performed. All temporal bones were impacted laterally under the same conditions. Temporal bone fractures were evaluated by CT scan.

Results

External auditory canal fractures were six times more seen in the study group. Tympanic bone fractures were present in 80% of the samples in the study group and 10% in the control group (p = .005). Middle ear fractures were found in 70% of the samples in the study group and 10% in the control group (p = .02). Otic capsule violating fractures of the temporal bone were present only in the study group.

Conclusions

Mastoid obliteration with heterologous materials after open cavity mastoidectomy increases the risk of fracture, with the involvement of auditory anatomical structures.

https://ift.tt/2Ruo8dP

Clinical Thyroidology®High-Impact Articles

FREE ACCESS through December 11, 2018.
Read Now:

Vemurafenib Restores Radioiodine Uptake in Some Metastatic Thyroid Cancers
Jerome M. Hershman  

Randomized, Controlled Trials Show That Treatment of Subclinical Hypothyroidism Does Not Improve Quality of Life, Cognition, Blood Pressure, or BMI
Tim I.M. Korevaar 

Symptoms Strongly Drive the Consideration of Alternative Thyroid Hormone–Replacement Options in Patients with Hypothyroidism
Angela M. Leung 

Which Factors Predict the Outcome of Ablative Radioactive Iodine Treatment of Hyperthyroid Graves' Disease?
Jacques Orgiazzi 

 

The post Clinical Thyroidology^®High-Impact Articles appeared first on American Thyroid Association.

https://ift.tt/2QztXJq

The rhinologist's role in the management of rathke's cleft cysts

Purpose of review To review the recent literature regarding the growing role of rhinologists and otolaryngologists with neurosurgeons in the joint multidisciplinary team approach for managing patients with Rathke's cleft cysts (RCC). Recent findings The transnasal endoscopic approach to the skull base has become relatively mainstream for surgical treatment of RCCs. Suprasellar lesions, especially those that are purely suprasellar, are associated with higher recurrence rates, though an extended approach may improve dissection and access and therefore aid in lesion removal. Endoscopic cyst drainage is a well tolerated and effective way to treat RCC, and often avoids the postoperative endocrinopathies associated with complete cyst wall removal. Novel techniques have been described for maintaining tract patency, including the use of stents and flaps, in order to prevent cyst stenosis and reaccumulation. A frontier in skull base surgery is in applications for pediatric patients, and managing RCCs in this population surgically appears to be associated with positive outcomes overall. Summary Team-based endoscopic skull base surgery has spurred advances in our understanding of skull base disease, including RCCs. Optimal outcomes are most apparent when the experience and technique of both the endoscopist and neurosurgeon have developed jointly over time. Correspondence to Edward C. Kuan, MD, MBA, Department of Otolaryngology-Head & Neck Surgery, University of California, Irvine Medical Center, 101 The City Dr S, Bldg 56, Ste 500, Orange, CA 92868, USA.. Tel: +1 714 456 5753; fax: +1 714 456 5747; e-mail: eckuan@uci.edu Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2zGSMcV

Review and update on extracorporeal septoplasty

Purpose of review To examine the recent literature on extracorporeal septoplasty. Recent findings The literature suggests that extracorporeal septoplasty is an effective approach for both functional and cosmetic treatment of moderate to severe deformities of the caudal and dorsal septum. The procedure can be performed via an endonasal or external approach based on the nature of the deformity and the experience of the surgeon, although recent literature highlights various advantages of an external approach. The use of polydioxanone foil as a scaffold for septal reconstruction is widely accepted, and can enhance the technical performance of this technique. Although reported complication rates are low, tip deprojection and rotation have been observed in cases where extracorporeal septoplasty is performed without simultaneous rhinoplasty. Summary Extracorporeal septoplasty is a useful technique in the armamentarium of surgeons addressing deviations of the dorsal and caudal septum. Correspondence to Daniel G. Becker, Penn Medicine – Becker ENT, LLC 570 Egg Harbor Road, Suite B2, Sewell, NJ 08080, USA. Tel: +1 856 589 6673; fax: +1 856 589 3343; e-mail: dbecker@beckerent.com Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2Pe2NmP

Histopathologic analysis in the diagnosis and management of chronic rhinosinusitis

Purpose of review New research in the pathogenesis of chronic rhinosinusitis has shed light on an emerging classification system based on endotypes, which help to explain the individualized mechanism of disease in patients suffering from chronic rhinosinusitis with and without nasal polyps. The purpose of this review is to advocate the use of structured histopathologic analysis in the diagnosis and management of patients affected by chronic rhinosinusitis with and without polyps. Recent findings Numerous studies have demonstrated the role of inflammation in chronic rhinosinusitis and the ensuing histopatholgic changes. Few studies have implemented structured histopathologic analysis to guide diagnosis and treatment. Individualized therapy including biotherapeutics and comprehensive surgery has shown to improve outcomes in patients with refractory disease. Summary Structured histopathologic analysis can provide helpful information on the endotype of chronic rhinosinusitis. Routine use in clinical practice should be standardized especially in cases of chronic rhinosinusitis refractory to medical therapy and/or surgery. Correspondence to Dr Bobby A. Tajudeen, MD, Co-Director, Rush Sinus Program, Rush University Medical Center, 1611W. Harrison St., Suite 550, Chicago, IL 60612, USA. Tel: +312 942 9174; fax: +312 942 6653; e-mail: bobby_tajudeen@rush.edu Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2zFCVeH

Management of sphenoid lateral recess encephalocoeles

Purpose of review Sphenoid sinus lateral recess encephalocoeles (SSLRE) are rare occurrences and pose unique challenges due to limited surgical access for endoscopic endonasal repair and also the lack of consensus on optimal perioperative managements specifically in the spontaneous cases, which are also believed to be a variant of idiopathic intracranial hypertension (IIH). Endoscopic endonasal approaches have largely replaced the transcranial route and the techniques are continuously being refined to reduce the neurovascular morbidity and improve outcome. Recent findings Transpetrygoid is the most utilized approach with modifications suggested to limit bone removal, exposure and preservation of the neurovascular structures as dictated by the extent of the lateral recess. As more experience is gained, extended transphenoidal techniques were also successfully used for access. Lateral transorbital is a new approach to the lateral recess investigated in cadavers. IIH treatment is still controversial in the setting of SSLRE, but it appears rationale to evaluate, monitor and treat if necessary. Summary SSLRE management should be tailored to the specific anatomical variances and cause. Modifications of techniques have been described giving different options to access the lateral recess. Successful repair for spontaneous SSLRE may require treatment of IIH if present, but the long-term outcome is still unclear. Correspondence to Narayanan Prepageran, MBBS, MS, FRCS, Department of Otorhinolaryngology-Head and Neck Surgery, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia. Tel: +60 379 492062; e-mail: prepageran@yahoo.com Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2PhpwhU

Indications and endonasal treatment of petrous apex cholesterol granulomas

Purpose of review Lesions of the petrous apex of the temporal bone can be challenging to access and approaches laterally through the mastoid as well as medially through an endonasal approach are utilized to access this region while preserving function of adjacent structures. Cholesterol granulomas of the petrous apex requiring surgery are marsupialized to prevent expansion of the inflamed cyst and relieve associated clinical symptoms. The endonasal approach to the petrous apex has in the past been limited to lesions medial to the internal carotid artery. Recent findings Endoscopic approaches have been developed to expand the range of petrous apex lesions that are accessible endonasally. These endonasal corridors include a nasopharyngeal/transclival corridor, lateralization of the internal carotid artery to create an expanded medial window, a pterygopalatine infrapetrosal approach, and a contralateral maxillary approach, which allow improved access to the inferior and lateral petrous apex. Nasoseptal flaps may reduce the risk of postoperative stenosis of the drainage tract. Summary Endoscopic endonasal approaches can be used safely to address both medial and lateral/inferior petrous apex lesions. Morbidity of these procedures is low and use of a nasoseptal flap may limit restenosis of the drainage pathway. Correspondence to Michael A. Kohanski, MD, PhD, Division of Rhinology, Department of Otorhinolaryngology-Head and Neck Surgery, University of Pennsylvania Medical Center, 5th Floor Ravdin Building, 3400 Spruce Street, Philadelphia, PA 19104, USA. Tel: +1 215 614 0491; e-mail: Michael.Kohanski@uphs.upenn.edu Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2zGSLpn

Current indications for balloon sinuplasty

Purpose of review The purpose of the review is to evaluate the current indications and contraindications for balloon sinuplasty and review the clinical trials performed in this area. Recent findings The indications for balloon sinus dilatation are somewhat similar to those for endoscopic sinus surgery. Balloon sinus ostial dilation (BSD) has been found to be most effective in the treatment of recurrent acute sinusitis (RARS) and chronic rhinosinusitis without nasal polyposis (CRSsNP) that has been refractory to medical therapy. Multiple randomized clinical trials have demonstrated the efficacy of BSD in improving quality-of-life outcomes in patients with limited CRSsNP in both the clinic and operating room settings. However, because BSD merely dilates blocked sinusal ostia without removing tissue, it is typically restricted to addressing disorder involving the frontal, sphenoid, and maxillary sinuses. Individuals who have significant disease of the ethmoid sinus may have BSD adjunctively with endoscopic sinus surgery. BSD is unsuitable as a primary treatment modality in pansinus polyposis, widespread fungal sinusitis, connective tissue disorders at an advanced stage, or potential malignancy. A recent expert clinical consensus statement also concluded that BSD is not appropriate for treatment of patients with headache that do not meet the diagnostic criteria for CRS or RARS or patients who do not have both positive findings of sinus disease on computed tomography and sinonasal symptoms. Summary Balloon sinuplasty is an option in the treatment of sinusitis that has failed appropriate medical therapy. Evidence is best for limited disease in patients with CRSsNP affecting the frontal, sphenoid, and maxillary sinuses. Because BSD can be performed in the office setting, it can be a viable therapeutic alternative in patients with comorbidities who are unable to tolerate general anesthesia. Correspondence to Cemal Cingi, MD, Professor, Department of Otolaryngology, Head and Neck Surgery, University of Eskisehir Osmangazi, 26020 Eskisehir, Turkey. Tel: +90 532 2676616; e-mail: ccingi@gmail.com Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2PfJjhQ

Contemporary management of juvenile angiofibroma

Purpose of review To illustrate the latest developments and trends in the management of juvenile angiofibroma. Recent findings Endoscopic surgery is currently the primary management strategy for juvenile angiofibroma. Recent reports on the use of multiportal approaches have contributed to further extend its indications. Studies from different countries suggest that the lesion can display variable growth rates not only in relation to patient age. The same concept applies to residual lesions. For this reason, retreatment of persistent juvenile angiofibromas is indicated when serial imaging clearly shows that the lesion is growing. When redo surgery is potentially associated with high morbidity for the critical relationships of the lesion with adjacent structures, stereotactic or intensity-modulated radiation therapy can be an alternative. Early use of MRI in the postoperative course is a highly effective way to detect residual lesions. Summary Contemporary management of juvenile angiofibroma should primarily rely on endoscopic surgery to obtain radical tumor resection. Recent evidence on the behavior of residual postoperative juvenile angiofibroma and the development of conformal RT techniques have helped to clarify the role of watchful waiting and radiotherapy (RT) as alternatives to aggressive procedures in cases with critical extension of the lesion. Although radical excision is the primary therapeutic objective, the benign nature of juvenile angiofibroma and the reported tendency of small residual lesions to remain stable or involute, especially in postpubertal patients, should always be kept in mind to avoid unnecessary morbidity. Video abstract In the video, two of the authors describe the content of the review and present the main topics discussed in the article. https://ift.tt/2zCohVk. Correspondence to Giacomo Bertazzoni, MD, Unit of Otorhinolaryngology, University of Brescia, ASST Spedali Civili di Brescia, Piazzale Spedali Civili 1, 25123 Brescia, Italy. Tel: +39 030 3995322; e-mail: ilbertaz@gmail.com Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (https://ift.tt/2JRSqmn). Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2zE4EfF

Oncologic management of sinonasal undifferentiated carcinoma

Purpose of review This article reviews the latest treatment paradigms in sinonasal undifferentiated carcinoma (SNUC). Recent findings The aggressive biology and associated advanced presentation of SNUC make successful treatment a challenge shared across medical specialties. Still, studies reporting outcomes in SNUC indicate that an aggressive treatment strategy consisting of surgery, radiation and chemotherapy offers the best chance of prolonged survival. Summary Successful treatment of SNUC requires highly specialized care at tertiary cancer treatment facilities. A better understanding of the biology of the disease coupled with increasing outcome reporting will lead to optimized treatment regimens. Correspondence to Zara M. Patel, MD, Assistant Professor, Director of Endoscopic Skull Base Surgery, Rhinology - Sinus and Skull Base Surgery, Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, 801 Welch, Stanford, CA 94305, USA. Tel: +1 650 723 5651; e-mail: zmpatel@stanford.edu Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2PhOPR7

Endotypes of chronic rhinosinusitis

Purpose of review In contrast to the phenotypic classification of chronic rhinosinusitis (CRS), endotyping categorizes disease variants based on their underlying pathophysiologic mechanisms. Defining CRS endotypes may provide information on the risk for disease progression, recurrence and comorbid conditions, as well as identify suitable therapeutic targets. With the emergence of biologics, endotyping may enable personalized pharmacotherapy for recalcitrant CRS. The purpose of this review is to briefly summarize the pathophysiology and endotypes of CRS, and highlight the biologics that target mediators of CRS. Recent findings CRS is due to dysregulated immunologic responses to external stimuli, which induces inflammatory mediators. The linkage between innate lymphoid cells, adaptive CD4+ T helper and CD8 + cytotoxic T cells has led to proposed endotypes that are based around immune response deviation into type 1, type 2 and type 3 responses. Cluster analysis has attempted to define endotypes, accounting for clinical characteristics, molecular and cellular biomarkers, and treatment response. Biologics targeting epithelial-derived cytokines and immunoglobulin E, as well as mediators of type 1, type 2 and type 3 inflammation, are being investigated in CRS. Summary Although there have been significant advances made in the understanding of the pathomechanisms of CRS, there currently remains a lack of full characterization of CRS endotypes. Correspondence to Yvonne Chan, MD, FRCSC, MSc, HBSc, Division Head, Division of Rhinology, Department of Otolaryngology – Head and Neck Surgery, University of Toronto, Trillium Health Partners, 102-101 Queensway West, Mississauga, ON L5B 2P7, USA. Tel: +1 905 277 4312; e-mail: y.chan@utoronto.ca Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2zGDLYz

Open-neck organ preservation surgery for hypopharyngeal cancer: indications, techniques, limits, and outcomes

Purpose of review To appraise the practice and role of open-neck organ preserving surgery for hypopharyngeal squamous cell carcinoma and to update the current indications, techniques, limits, and outcomes. Recent findings The role of primary surgery for hypopharyngeal carcinoma has shifted over the past two decades to primary nonsurgical management with the use of induction or concurrent chemoradiotherapy. The preferred and most suitable tumours for open-neck surgery are the small-volume T stage diseases, with small to medium-volume neck metastases, however such patients are exceedingly rare. Nonetheless, more advanced tumours with cartilage invasion, vocal cord paralysis, or located at piriform apex and postcricoid area, previously unsuitable for open-neck organ preserving surgery, can now be excised and repaired, minimizing morbidity and improving quality of patients' life. Much of this surgical progress has been developed by innovative surgeons using free tissue transfer, accurate placement surgery, reconstruction of a neoglottis, and perfecting the pharyngoesophageal anastomosis. Current practice of open-neck organ preserving surgery for hypopharyngeal carcinoma has been mainly reported in Asia: Korea, Taiwan, Japan, and China. Summary There are some patients who are deemed unsuitable and/or unwilling for current treatment by nonsurgical approaches, and open-neck organ preserving laryngopharyngeal surgery may be a more suitable alternative than selecting a 'lesser or modified' chemo or bioradiotherapy regimen, resulting in a prolonged quantity and quality of life. Correspondence to Professor Patrick J. Bradley, MBA, FRCS, MD, 10 Chartwell Grove, Mapperley Plains, Nottingham NG3 5RD, UK. Tel: +44 115 9201611; e-mail: pjbradley@zoo.co.uk Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2PeQ0k0

Salivaomics in oral cancer

Purpose of review The goal of cancer screening is to detect tumor at an early stage, and early cancer detection is the hallmark of successful treatment. In addition to traditional tissue biopsy-based diagnostics, more reliable, inexpensive, and noninvasive methods are required for early diagnosis of cancer. In this review, we highlight some of the recent advancements in the field of salivary diagnostics in oral cancer. Recent findings 'Salivaomics' is a broad collection of technologies used to explore different types of molecules contained in saliva. Although many protein and mRNA salivary biomarkers have been identified that can detect oral squamous cell carcinoma (OSCC), none have so far been validated for current clinical use. As the heterogeneity in carcinogenesis and multifactorial cause for OSCC, the most reliable results are gathered with the use of multiple biomarker candidates to improve accuracy and sensitivity of the test used. This further requires sensitive technology to detect salivary biomarkers in low quantities. Summary Large scale studies that incorporate proteomic, transcriptomic, and additional 'omics,' need to be initiated to bring technology to clinical point-of-care applications. Correspondence to Katri Aro, MD, PhD, Department of Otorhinolaryngology – Head and Neck Surgery, Helsinki University Hospital, PO Box 263, FI-00029 HUS, Helsinki, Finland. Tel: +358 50 4272000; e-mail: katri.aro@hus.fi Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2zGDEw7

Chemically modified peanut extract shows increased safety while maintaining immunogenicity

Abstract

Background

Peanuts are most responsible for food‐induced anaphylaxis in adults in developed countries. An effective and safe immunotherapy is urgently needed. The aim of this study was to investigate the immunogenicity, allergenicity and immunotherapeutic efficacy of a well characterized chemically modified peanut extract (MPE) adsorbed to Al(OH)₃.

Methods

Peanut extract (PE) was modified by reduction and alkylation. Using sera of peanut allergic patients, competitive IgE‐binding assays and mediator release assays were performed. The immunogenicity of MPE was evaluated by measuring activation of human PE‐specific T‐cell lines and the induction of PE‐specific IgG in mice. The safety and efficacy of MPE adsorbed to Al(OH)₃ was tested in two mouse models by measuring allergic manifestations upon peanut challenge in peanut allergic mice.

Results

Compared to PE, the IgE‐binding and capacity to induce allergic symptoms of MPE was lower in all patients. PE and MPE displayed similar immunogenicity in vivo and in vitro. In mice sensitized to PE, the threshold for anaphylaxis (drop in BT) upon subcutaneous challenge with PE was 0.01 mg, while at 0.3 mg MPE no allergic reaction occurred. Anaphylaxis was not observed when PE and MPE were fully adsorbed to Al(OH)₃. Both PE and MPE + Al(OH)₃ showed to be efficacious in a model for immunotherapy.

Conclusion

In our studies an Al(OH)₃ adsorbed MPE showed reduced allergenicity compared to unmodified PE, while the efficacy of immunotherapy is maintained. The preclinical data presented in this study supports further development of modified peanut allergens for IT.

This article is protected by copyright. All rights reserved.

https://ift.tt/2RpHSiI

Much ado about Biologicals:Highlights of the Master Class on Biologicals, Prague, 2018

https://ift.tt/2KNb3th

The rhinologist's role in the management of rathke's cleft cysts

Purpose of review To review the recent literature regarding the growing role of rhinologists and otolaryngologists with neurosurgeons in the joint multidisciplinary team approach for managing patients with Rathke's cleft cysts (RCC). Recent findings The transnasal endoscopic approach to the skull base has become relatively mainstream for surgical treatment of RCCs. Suprasellar lesions, especially those that are purely suprasellar, are associated with higher recurrence rates, though an extended approach may improve dissection and access and therefore aid in lesion removal. Endoscopic cyst drainage is a well tolerated and effective way to treat RCC, and often avoids the postoperative endocrinopathies associated with complete cyst wall removal. Novel techniques have been described for maintaining tract patency, including the use of stents and flaps, in order to prevent cyst stenosis and reaccumulation. A frontier in skull base surgery is in applications for pediatric patients, and managing RCCs in this population surgically appears to be associated with positive outcomes overall. Summary Team-based endoscopic skull base surgery has spurred advances in our understanding of skull base disease, including RCCs. Optimal outcomes are most apparent when the experience and technique of both the endoscopist and neurosurgeon have developed jointly over time. Correspondence to Edward C. Kuan, MD, MBA, Department of Otolaryngology-Head & Neck Surgery, University of California, Irvine Medical Center, 101 The City Dr S, Bldg 56, Ste 500, Orange, CA 92868, USA.. Tel: +1 714 456 5753; fax: +1 714 456 5747; e-mail: eckuan@uci.edu Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2zGSMcV

Review and update on extracorporeal septoplasty

Purpose of review To examine the recent literature on extracorporeal septoplasty. Recent findings The literature suggests that extracorporeal septoplasty is an effective approach for both functional and cosmetic treatment of moderate to severe deformities of the caudal and dorsal septum. The procedure can be performed via an endonasal or external approach based on the nature of the deformity and the experience of the surgeon, although recent literature highlights various advantages of an external approach. The use of polydioxanone foil as a scaffold for septal reconstruction is widely accepted, and can enhance the technical performance of this technique. Although reported complication rates are low, tip deprojection and rotation have been observed in cases where extracorporeal septoplasty is performed without simultaneous rhinoplasty. Summary Extracorporeal septoplasty is a useful technique in the armamentarium of surgeons addressing deviations of the dorsal and caudal septum. Correspondence to Daniel G. Becker, Penn Medicine – Becker ENT, LLC 570 Egg Harbor Road, Suite B2, Sewell, NJ 08080, USA. Tel: +1 856 589 6673; fax: +1 856 589 3343; e-mail: dbecker@beckerent.com Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2Pe2NmP

Histopathologic analysis in the diagnosis and management of chronic rhinosinusitis

Purpose of review New research in the pathogenesis of chronic rhinosinusitis has shed light on an emerging classification system based on endotypes, which help to explain the individualized mechanism of disease in patients suffering from chronic rhinosinusitis with and without nasal polyps. The purpose of this review is to advocate the use of structured histopathologic analysis in the diagnosis and management of patients affected by chronic rhinosinusitis with and without polyps. Recent findings Numerous studies have demonstrated the role of inflammation in chronic rhinosinusitis and the ensuing histopatholgic changes. Few studies have implemented structured histopathologic analysis to guide diagnosis and treatment. Individualized therapy including biotherapeutics and comprehensive surgery has shown to improve outcomes in patients with refractory disease. Summary Structured histopathologic analysis can provide helpful information on the endotype of chronic rhinosinusitis. Routine use in clinical practice should be standardized especially in cases of chronic rhinosinusitis refractory to medical therapy and/or surgery. Correspondence to Dr Bobby A. Tajudeen, MD, Co-Director, Rush Sinus Program, Rush University Medical Center, 1611W. Harrison St., Suite 550, Chicago, IL 60612, USA. Tel: +312 942 9174; fax: +312 942 6653; e-mail: bobby_tajudeen@rush.edu Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2zFCVeH

Management of sphenoid lateral recess encephalocoeles

Purpose of review Sphenoid sinus lateral recess encephalocoeles (SSLRE) are rare occurrences and pose unique challenges due to limited surgical access for endoscopic endonasal repair and also the lack of consensus on optimal perioperative managements specifically in the spontaneous cases, which are also believed to be a variant of idiopathic intracranial hypertension (IIH). Endoscopic endonasal approaches have largely replaced the transcranial route and the techniques are continuously being refined to reduce the neurovascular morbidity and improve outcome. Recent findings Transpetrygoid is the most utilized approach with modifications suggested to limit bone removal, exposure and preservation of the neurovascular structures as dictated by the extent of the lateral recess. As more experience is gained, extended transphenoidal techniques were also successfully used for access. Lateral transorbital is a new approach to the lateral recess investigated in cadavers. IIH treatment is still controversial in the setting of SSLRE, but it appears rationale to evaluate, monitor and treat if necessary. Summary SSLRE management should be tailored to the specific anatomical variances and cause. Modifications of techniques have been described giving different options to access the lateral recess. Successful repair for spontaneous SSLRE may require treatment of IIH if present, but the long-term outcome is still unclear. Correspondence to Narayanan Prepageran, MBBS, MS, FRCS, Department of Otorhinolaryngology-Head and Neck Surgery, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia. Tel: +60 379 492062; e-mail: prepageran@yahoo.com Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Indications and endonasal treatment of petrous apex cholesterol granulomas

Purpose of review Lesions of the petrous apex of the temporal bone can be challenging to access and approaches laterally through the mastoid as well as medially through an endonasal approach are utilized to access this region while preserving function of adjacent structures. Cholesterol granulomas of the petrous apex requiring surgery are marsupialized to prevent expansion of the inflamed cyst and relieve associated clinical symptoms. The endonasal approach to the petrous apex has in the past been limited to lesions medial to the internal carotid artery. Recent findings Endoscopic approaches have been developed to expand the range of petrous apex lesions that are accessible endonasally. These endonasal corridors include a nasopharyngeal/transclival corridor, lateralization of the internal carotid artery to create an expanded medial window, a pterygopalatine infrapetrosal approach, and a contralateral maxillary approach, which allow improved access to the inferior and lateral petrous apex. Nasoseptal flaps may reduce the risk of postoperative stenosis of the drainage tract. Summary Endoscopic endonasal approaches can be used safely to address both medial and lateral/inferior petrous apex lesions. Morbidity of these procedures is low and use of a nasoseptal flap may limit restenosis of the drainage pathway. Correspondence to Michael A. Kohanski, MD, PhD, Division of Rhinology, Department of Otorhinolaryngology-Head and Neck Surgery, University of Pennsylvania Medical Center, 5th Floor Ravdin Building, 3400 Spruce Street, Philadelphia, PA 19104, USA. Tel: +1 215 614 0491; e-mail: Michael.Kohanski@uphs.upenn.edu Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2zGSLpn

Current indications for balloon sinuplasty

Purpose of review The purpose of the review is to evaluate the current indications and contraindications for balloon sinuplasty and review the clinical trials performed in this area. Recent findings The indications for balloon sinus dilatation are somewhat similar to those for endoscopic sinus surgery. Balloon sinus ostial dilation (BSD) has been found to be most effective in the treatment of recurrent acute sinusitis (RARS) and chronic rhinosinusitis without nasal polyposis (CRSsNP) that has been refractory to medical therapy. Multiple randomized clinical trials have demonstrated the efficacy of BSD in improving quality-of-life outcomes in patients with limited CRSsNP in both the clinic and operating room settings. However, because BSD merely dilates blocked sinusal ostia without removing tissue, it is typically restricted to addressing disorder involving the frontal, sphenoid, and maxillary sinuses. Individuals who have significant disease of the ethmoid sinus may have BSD adjunctively with endoscopic sinus surgery. BSD is unsuitable as a primary treatment modality in pansinus polyposis, widespread fungal sinusitis, connective tissue disorders at an advanced stage, or potential malignancy. A recent expert clinical consensus statement also concluded that BSD is not appropriate for treatment of patients with headache that do not meet the diagnostic criteria for CRS or RARS or patients who do not have both positive findings of sinus disease on computed tomography and sinonasal symptoms. Summary Balloon sinuplasty is an option in the treatment of sinusitis that has failed appropriate medical therapy. Evidence is best for limited disease in patients with CRSsNP affecting the frontal, sphenoid, and maxillary sinuses. Because BSD can be performed in the office setting, it can be a viable therapeutic alternative in patients with comorbidities who are unable to tolerate general anesthesia. Correspondence to Cemal Cingi, MD, Professor, Department of Otolaryngology, Head and Neck Surgery, University of Eskisehir Osmangazi, 26020 Eskisehir, Turkey. Tel: +90 532 2676616; e-mail: ccingi@gmail.com Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Contemporary management of juvenile angiofibroma

Purpose of review To illustrate the latest developments and trends in the management of juvenile angiofibroma. Recent findings Endoscopic surgery is currently the primary management strategy for juvenile angiofibroma. Recent reports on the use of multiportal approaches have contributed to further extend its indications. Studies from different countries suggest that the lesion can display variable growth rates not only in relation to patient age. The same concept applies to residual lesions. For this reason, retreatment of persistent juvenile angiofibromas is indicated when serial imaging clearly shows that the lesion is growing. When redo surgery is potentially associated with high morbidity for the critical relationships of the lesion with adjacent structures, stereotactic or intensity-modulated radiation therapy can be an alternative. Early use of MRI in the postoperative course is a highly effective way to detect residual lesions. Summary Contemporary management of juvenile angiofibroma should primarily rely on endoscopic surgery to obtain radical tumor resection. Recent evidence on the behavior of residual postoperative juvenile angiofibroma and the development of conformal RT techniques have helped to clarify the role of watchful waiting and radiotherapy (RT) as alternatives to aggressive procedures in cases with critical extension of the lesion. Although radical excision is the primary therapeutic objective, the benign nature of juvenile angiofibroma and the reported tendency of small residual lesions to remain stable or involute, especially in postpubertal patients, should always be kept in mind to avoid unnecessary morbidity. Video abstract In the video, two of the authors describe the content of the review and present the main topics discussed in the article. https://ift.tt/2zCohVk. Correspondence to Giacomo Bertazzoni, MD, Unit of Otorhinolaryngology, University of Brescia, ASST Spedali Civili di Brescia, Piazzale Spedali Civili 1, 25123 Brescia, Italy. Tel: +39 030 3995322; e-mail: ilbertaz@gmail.com Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (https://ift.tt/2JRSqmn). Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2zE4EfF

Oncologic management of sinonasal undifferentiated carcinoma

Purpose of review This article reviews the latest treatment paradigms in sinonasal undifferentiated carcinoma (SNUC). Recent findings The aggressive biology and associated advanced presentation of SNUC make successful treatment a challenge shared across medical specialties. Still, studies reporting outcomes in SNUC indicate that an aggressive treatment strategy consisting of surgery, radiation and chemotherapy offers the best chance of prolonged survival. Summary Successful treatment of SNUC requires highly specialized care at tertiary cancer treatment facilities. A better understanding of the biology of the disease coupled with increasing outcome reporting will lead to optimized treatment regimens. Correspondence to Zara M. Patel, MD, Assistant Professor, Director of Endoscopic Skull Base Surgery, Rhinology - Sinus and Skull Base Surgery, Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, 801 Welch, Stanford, CA 94305, USA. Tel: +1 650 723 5651; e-mail: zmpatel@stanford.edu Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2PhOPR7

Endotypes of chronic rhinosinusitis

Purpose of review In contrast to the phenotypic classification of chronic rhinosinusitis (CRS), endotyping categorizes disease variants based on their underlying pathophysiologic mechanisms. Defining CRS endotypes may provide information on the risk for disease progression, recurrence and comorbid conditions, as well as identify suitable therapeutic targets. With the emergence of biologics, endotyping may enable personalized pharmacotherapy for recalcitrant CRS. The purpose of this review is to briefly summarize the pathophysiology and endotypes of CRS, and highlight the biologics that target mediators of CRS. Recent findings CRS is due to dysregulated immunologic responses to external stimuli, which induces inflammatory mediators. The linkage between innate lymphoid cells, adaptive CD4+ T helper and CD8 + cytotoxic T cells has led to proposed endotypes that are based around immune response deviation into type 1, type 2 and type 3 responses. Cluster analysis has attempted to define endotypes, accounting for clinical characteristics, molecular and cellular biomarkers, and treatment response. Biologics targeting epithelial-derived cytokines and immunoglobulin E, as well as mediators of type 1, type 2 and type 3 inflammation, are being investigated in CRS. Summary Although there have been significant advances made in the understanding of the pathomechanisms of CRS, there currently remains a lack of full characterization of CRS endotypes. Correspondence to Yvonne Chan, MD, FRCSC, MSc, HBSc, Division Head, Division of Rhinology, Department of Otolaryngology – Head and Neck Surgery, University of Toronto, Trillium Health Partners, 102-101 Queensway West, Mississauga, ON L5B 2P7, USA. Tel: +1 905 277 4312; e-mail: y.chan@utoronto.ca Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2zGDLYz

Open-neck organ preservation surgery for hypopharyngeal cancer: indications, techniques, limits, and outcomes

Purpose of review To appraise the practice and role of open-neck organ preserving surgery for hypopharyngeal squamous cell carcinoma and to update the current indications, techniques, limits, and outcomes. Recent findings The role of primary surgery for hypopharyngeal carcinoma has shifted over the past two decades to primary nonsurgical management with the use of induction or concurrent chemoradiotherapy. The preferred and most suitable tumours for open-neck surgery are the small-volume T stage diseases, with small to medium-volume neck metastases, however such patients are exceedingly rare. Nonetheless, more advanced tumours with cartilage invasion, vocal cord paralysis, or located at piriform apex and postcricoid area, previously unsuitable for open-neck organ preserving surgery, can now be excised and repaired, minimizing morbidity and improving quality of patients' life. Much of this surgical progress has been developed by innovative surgeons using free tissue transfer, accurate placement surgery, reconstruction of a neoglottis, and perfecting the pharyngoesophageal anastomosis. Current practice of open-neck organ preserving surgery for hypopharyngeal carcinoma has been mainly reported in Asia: Korea, Taiwan, Japan, and China. Summary There are some patients who are deemed unsuitable and/or unwilling for current treatment by nonsurgical approaches, and open-neck organ preserving laryngopharyngeal surgery may be a more suitable alternative than selecting a 'lesser or modified' chemo or bioradiotherapy regimen, resulting in a prolonged quantity and quality of life. Correspondence to Professor Patrick J. Bradley, MBA, FRCS, MD, 10 Chartwell Grove, Mapperley Plains, Nottingham NG3 5RD, UK. Tel: +44 115 9201611; e-mail: pjbradley@zoo.co.uk Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2PeQ0k0

Salivaomics in oral cancer

Purpose of review The goal of cancer screening is to detect tumor at an early stage, and early cancer detection is the hallmark of successful treatment. In addition to traditional tissue biopsy-based diagnostics, more reliable, inexpensive, and noninvasive methods are required for early diagnosis of cancer. In this review, we highlight some of the recent advancements in the field of salivary diagnostics in oral cancer. Recent findings 'Salivaomics' is a broad collection of technologies used to explore different types of molecules contained in saliva. Although many protein and mRNA salivary biomarkers have been identified that can detect oral squamous cell carcinoma (OSCC), none have so far been validated for current clinical use. As the heterogeneity in carcinogenesis and multifactorial cause for OSCC, the most reliable results are gathered with the use of multiple biomarker candidates to improve accuracy and sensitivity of the test used. This further requires sensitive technology to detect salivary biomarkers in low quantities. Summary Large scale studies that incorporate proteomic, transcriptomic, and additional 'omics,' need to be initiated to bring technology to clinical point-of-care applications. Correspondence to Katri Aro, MD, PhD, Department of Otorhinolaryngology – Head and Neck Surgery, Helsinki University Hospital, PO Box 263, FI-00029 HUS, Helsinki, Finland. Tel: +358 50 4272000; e-mail: katri.aro@hus.fi Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2zGDEw7

VideoEndocrinology™ High-Impact Videos

VideoEndocrinology™
The Official Journal of: American Thyroid Association

FREE ACCESS through December 14, 2018.
Watch now:

Transoral Endoscopic Thyroidectomy Vestibular Approach: Technical Tips and Tricks
Gustavo G. Fernandez Ranvier, Patrick Neshiwat, William B. Inabnet III

Central Neck Dissection: The Five Key Steps
Nathaniel J. Walsh, Asif M. Talukder, David J. Terris 

Transoral and Submental Thyroidectomy
Yufei Chen, Kathryn H. Chomsky-Higgins, Iheoma Nwaogu, Carolyn D. Seib, Jessica E. Gosnell, Wen T. Shen, Quan-Yang Duh, Insoo Suh 

3D Anatomic Adrenal Modeling Aids Preoperative Planning in Cortical-Sparing Adrenalectomy
Janeil M. Mitchell, Michael J. Magnetta, Kelly L. McCoy, Sally E. Carty, Linwah Yip

The post VideoEndocrinology™ High-Impact Videos appeared first on American Thyroid Association.

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Rush desensitization with a single antigen induces subclinical activation of mast cells and protects against bystander challenge in dually sensitized mice

Abstract

Background

Rush desensitization can provide short‐term tolerance to individuals who are allergic to certain medications in instances where other therapeutic interventions are limited. While rush DS is typically successful in preventing adverse type I hypersensitivity reactions, the mechanism of allergic protection remains unknown. Given the rise in prevalence of individuals displaying multiple allergies, understanding the impact of rush DS on "bystander" allergens, or additional allergens to which an individual is sensitized, could help inform clinical recommendations.

Objective

To evaluate the effect of rush DS on bystander sensitization.

Materials and Methods

We used a murine model of rush DS, whereby BALB/c mice were sensitized to ovalbumin (OVA) and desensitized through repeated intraperitoneal injections of OVA. Using a local anaphylaxis assay, we measured ear swelling by Evans blue extravasation following intradermal challenge. In studies to measure the impact on bystander antigens, a modified protocol was used in which mice were dually sensitized to OVA and Keyhole limpet hemocyanin (KLH), and densensitized to either OVA or KLH prior to allergic challenge.

Results

The immunological effects of rush DS were independent of changes in Th1 and Th2 cytokine production and circulating OVA‐IgE levels. Instead, rush DS resulted in subclinical degranulation of mast cells prior to challenge. In our dual sensitization model, rush DS with a single antigen conferred protection against allergic challenge to a secondary antigen. Bystander protection required prior sensitization, as DS with an irrelevant antigen did not impact allergic responsiveness.

Conclusions and Clinical Relevance

We reveal that a key mechanism of rush DS protection against allergic responsiveness may be the subclinical degranulation of mast cells. Therefore, performing rush DS to a single antigen to which one is IgE‐sensitized may be sufficient to desensitize to multiple allergens. Future studies could lead to streamlined protocols of rush DS for patients with multiple allergies.

This article is protected by copyright. All rights reserved.

https://ift.tt/2FVch7a

An integrated framework using high‐dimensional mass cytometry and fluorescent flow cytometry identifies discrete B cell subsets in patients with red meat allergy

Abstract

Background

B cells play a critical role in the development and maintenance of food allergy by producing allergen‐specific IgE. Despite the importance of B cells in IgE‐mediated food allergy, the identity of sIgE‐producing human B cells and how IgE is regulated are poorly understood.

Objective

To identify the immunophenotypes of circulating B cells associated with the production of galactose‐alpha‐1,3‐galactose specific IgE production in patients with red meat allergy.

Methods

B cells in PBMC samples obtained from 19 adults with physician‐diagnosed red meat allergy and 20 non‐meat allergic healthy controls were assessed by mass cytometry along with a bioinformatics analysis pipeline to identify discrete B cell phenotypes that associated with serum sIgE. Fluorescent flow cytometry was then applied to sort purify discrete B cell subsets, and B cells were functionally evaluated on an individual cell level for the production of sIgE by ELISPOT.

Results

Discrete B cell phenotypes abundant in meat allergic subjects compared to non‐meat allergic controls were found in peripheral blood that do not share typical characteristics of classical isotype‐switched memory B cells that express high levels of CD27. These B cell subsets shared higher IgD and lower IgM expression levels coupled with CXCR4, CCR6 and CD25 expression. In vitro polyclonal stimulation of purified B cell subsets from meat allergic subjects demonstrated that these subsets were enriched for cells induced to secrete sIgE.

Conclusions and Clinical Relevance

Circulating B cells display increased abundance of discrete B cell subsets in meat allergic subjects. This observation, coupled with the capacity of individual B cell subsets to produce sIgE following activation, implicates these novel B cell phenotypes in promoting IgE in meat allergy.

This article is protected by copyright. All rights reserved.

https://ift.tt/2rjkzvf

Enhancement of lipid content and inflammatory cytokine secretion in SZ95 sebocytes by palmitic acid suggests a potential link between free fatty acids and acne aggravation

Abstract

A relationship between acne and free fatty acids (FFAs) has been suggested recently. However, the effects of FFAs on sebaceous glands are still largely unknown. At the same time, the role of FFAs during chronic inflammation is well established. Considering that FFAs are also a major component of sebum, it is likely that changes in FFA affect both the synthesis of sebum and the inflammatory response in sebaceous glands.

In this study, we examined a hypothesis that FFAs increase the production of sebum and induce inflammation in the sebaceous glands. We found that treatment of SZ95 sebocytes with exogenously applied palmitic acid (PA), a major saturated FFA, induced a significant increase in intracellular lipid levels. Moreover, PA treatment also increased the expression and secretion of the proinflammatory cytokines in SZ95 sebocytes. We also found that Toll‐like receptors were required for the inflammatory response triggered by PA.

The results of our study strengthen the notion about the link between acne and FFAs and suggest the mechanism underlying this relationship. Our results serve as a foundation for future work that will explore the association between FFA and acne and pave way to the development of novel treatment options for acne.

This article is protected by copyright. All rights reserved.

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Ultraviolet radiation, both UVA and UVB, influences the composition of the skin microbiome

Abstract

Background

Studies have begun to investigate the complex relationship between host and microorganisms in non‐infectious pathologies such as acne, atopic dermatitis, and psoriasis. Though the skin is exposed to environmental stressors such as ultraviolet radiation (UVR), no studies exist examining the effects of both UVA and UVB on the skin microbiome.

Objective

To test the effect of UVA and UVB on human skin microbiome.

Methods

To test whether UV will alter the cutaneous microbiome, participants were exposed to doses of UVA (22‐47 J/cm²) or UVB (100‐350 mJ/cm²) and samples were collected. DNA was isolated and sequenced to identify the microbial composition of each sample.

Results

There was vast intra‐ and inter‐subject variation at all time points and phylum and species‐level differences were identified. These included an increase in the phylum Cyanobacteria and a decrease in the family Lactobacillaceae and Pseudomonadaceae. The sensitivity of microbes to UVR and their re‐colonization potential following exposure differed in UVA vs UVB samples.

Limitations

The sample size was small, and the study was limited to males.

Conclusion

The results demonstrate that UVR has profound qualitative and quantitative influences on the composition of the skin microbiome, possibly effecting skin pathology in which UVR is a factor.

This article is protected by copyright. All rights reserved.

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Pigmented skin lesions displaying regression features: dermoscopy and reflectance confocal microscopy criteria for diagnosis

Abstract

Melanomas and nevi displaying regression features can be difficult to differentiate.

To describe reflectance confocal microscopy features in benign and malignant pigmented skin lesions characterized by regression features in dermoscopy.

Methods: Observational retrospective study. Inclusion criteria were presence of dermoscopic features of regression; availability of clinical, dermoscopic and RCM imaging; definite histopathologic diagnosis.

The study sample comprised 217 lesions; 108 (49.8%) melanomas and 109 were benign lesions, of which 102 (47.0%) nevi and 7 (3.2%) lichen planus like keratosis (lplk). Patients with melanoma were significantly older than those with benign lesions (61.9±15.4 vs. 46.1±14.8; p<0.001) and a higher proportion of melanomas displayed dermoscopic regression structures in more than 50% of lesion surface (n=83/108; 76.9%; p<0.001). On RCM examination, pagetoid cells were significantly more reported in melanoma group, than in benign lesions (86.1% vs. 59.6%; p<0.001) and were more frequently widespread distributed (65.6% vs. 20.0%; p<0.001) and both dendritic and roundish (36.6% vs. 15.4%; p<0.001) in shape. Aspecific architecture at the dermo‐epidermal junction (DEJ) was more commonly seen among melanomas than benign lesions (23.1% vs. 11.9%; p=0.002) with higher presence of dendritic and both dendritic and roundish atypical cells at the DEJ (28.7% vs. 18.3% and 19.4% vs. 3.7%; p<0.001, respectively). Focal pagetoid infiltration and ringed or clod patterns were more commonly seen in benign lesion.

In conclusion, the correct interpretation of regressing lesions remains a challenge, assessing carefully the extent and characteristics of architectural and cytologic atypia on RCM is an additional piece of the complex puzzle of melanoma diagnosis.

This article is protected by copyright. All rights reserved.

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Periodic patterns in Rodentia: development and evolution

Abstract

Mammalian periodic pigment patterns, such as spots and stripes, have long interested mathematicians and biologists because they arise from nonrandom developmental processes that are programmed to be spatially constrained, and can therefore be used as a model to understand how organized morphological structures develop. Despite such interest, the developmental and molecular processes underlying their formation remain poorly understood. Here, we argue that Arvicanthines, a clade of African rodents that naturally evolved a remarkable array of coat patterns, represent a tractable model system in which to dissect the mechanistic basis of pigment pattern formation. Indeed, we review recent insights into the process of stripe formation that were obtained using an Arvicanthine species, the African striped mouse (Rhabdomys pumilio), and discuss how these rodents can be used to probe deeply into our understanding of the factors that specify and implement positional information in the skin. By combining naturally evolved pigment pattern variation in rodents with classic and novel experimental approaches, we can substantially advance our understanding of the processes by which spatial patterns of cell differentiation are established during embryogenesis, a fundamental question in developmental biology.

This article is protected by copyright. All rights reserved.

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Inhibition of autophagy by chloroquine makes chemotherapy in nasopharyngeal carcinoma more efficient

Publication date: Available online 2 December 2018

Source: Auris Nasus Larynx

Author(s): Tomomi Aga, Kazuhira Endo, Akira Tsuji, Mitsuharu Aga, Makiko Moriyama-Kita, Takayoshi Ueno, Yosuke Nakanishi, Miyako Hatano, Satoru Kondo, Hisashi Sugimoto, Naohiro Wakisaka, Tomokazu Yoshizaki

Abstract

Objectives

A combination of platinum-based chemotherapy and radiotherapy is the standard treatment for nasopharyngeal carcinoma (NPC). However, the efficacy of chemotherapy has reached a plateau. Many autophagy studies suggest that autophagy can either promote or suppress to cancer progression. Thus, a role of autophagy in the acquisition of chemoradioresistance has recently been a notable event. Therefore, we examined the relationship between autophagy and chemotherapy in NPC.

Methods

The expression of Beclin 1 and microtubule-associated protein light chain 3 (LC3), a marker of autophagy, was determined by immunohistochemistry in the biopsy samples of patients with NPC before and after the first course of chemotherapy. Additionally, to investigate in the effect of autophagy suppression in chemotherapy, NPC cell line C666-1 cells were treated with cisplatin and/or chloroquine, an inhibitor of autophagy.

Results

The expression of Beclin 1 increased after chemotherapy in all patients. In NPC cell line C666-1, compared to cisplatin alone, combination therapy (cisplatin and chloroquine) reduced cell viability, and promoted cell apoptosis.

Conclusions

These results suggest that autophagy, represented by Beclin 1, is upregulated after chemotherapy in both in vitro and in vivo NPC studies. Inhibition of autophagy could therefore be new strategy for NPC treatment.

https://ift.tt/2zEEDgn

The human complement receptor type 2 (CR2)/CR1 fusion protein TT32, a novel targeted inhibitor of the classical and alternative pathway C3 convertases, prevents arthritis in active immunization and passive transfer mouse models

Publication date: January 2019

Source: Molecular Immunology, Volume 105

Author(s): Masha Fridkis-Hareli, Michael Storek, Eran Or, Richard Altman, Suresh Katti, Fang Sun, Tao Peng, Jeff Hunter, Krista Johnson, Yi Wang, Ante S. Lundberg, Gaurav Mehta, Nirmal K. Banda, V. MichaelHolers

Abstract

Complement activation in human diseases is characterized by the local covalent deposition of the long-lived C3 fragments iC3b/C3dg/C3d. Previously, TT30, a complement alternative pathway (AP)-selective inhibitor, was designed as a fusion protein linking the first four short consensus repeats (SCRs) of human complement receptor type 2 (CR2) with the first five SCRs of human factor H (fH). TT30 acts by utilizing CR2 SCR1–4 to bind the initially formed iC3b/C3dg/C3d fragments and delivering surface-targeted inhibition of AP C3 and C5 convertases through fH SCR 1-5. In order to combine classical (CP) and lectin (LP) pathway inhibitory abilities employing CR2-mediated targeting, TT32 was developed. TT32 is a CR2-CR1 fusion protein using the first ten SCRs of CR1, chosen because they contain both C3 and C5 convertase inhibitory activity through utilization of decay-acceleration and cofactor activity for both AP and CP. In Wieslab assays, TT32 showed potent inhibition of the CP and AP with IC₅₀ of 11 and 46 nM, respectively. The TT32 inhibitory activity is partially blocked with a molar excess of a competing anti-CR2 mAb, thus demonstrating the importance of the CR2 targeting. TT32 was studied in the type II (CII) collagen-induced arthritis (CIA), an active immunization model, and the CII antibody-induced arthritis (CAIA) passive transfer model. In CIA, injection of 2.0 mg TT32 at day 21 and 28 post disease induction, but not untargeted CR1 alone, resulted in a 51.5% decrease in clinical disease activity (CDA). In CAIA, treatment with TT32 resulted in a 47.4% decrease in CDA. Therefore, a complement inhibitor that targets both the AP and CP/LP C3/C5 convertases was shown to limit complement-mediated tissue damage and inflammation in disease models in which all three complement activation pathways are implicated.

https://ift.tt/2reESKi

Thyroid Function in Patients with Type 2 Diabetes Mellitus and Diabetic Nephropathy: A Single Center Study

Background. Diabetes mellitus is a common metabolic disease and the prevalence is increasing rapidly. Thyroid disorders including subclinical hypothyroidism (SCH) and low triiodothyronine (T3) syndrome are frequently observed in diabetic patients. We conducted a study to explore thyroid function in patients with type 2 diabetes mellitus (T2DM) and diabetic nephropathy (DN). Methods. We included 103 healthy volunteers, 100 T2DM patients without DN, and 139 with DN. Physical examinations including body mass index and blood pressure and laboratory measurements including renal function, thyroid function, and glycosylated hemoglobin were conducted. Results. Patients with DN had higher thyroid stimulating hormone (TSH) levels and lower free T3 (FT3) levels than those without DN (p

https://ift.tt/2BLYITe

Dynamic Tonsillar Prolapse Masquerading as Paradoxical Vocal Fold Movement Dysfunction

Publication date: Available online 2 December 2018

Source: International Journal of Pediatric Otorhinolaryngology

Author(s): Allison B.J. Tobey, Raymond C. Maguire

Abstract

Introduction

Paradoxical vocal fold movement dysfunction (PVFMD) is a disorder in which the vocal folds involuntarily adduct during inspiration resulting in stridor, cough, dysphonia and dyspnea. Diagnosis of PVFMD is difficult given the episodic nature of the disorder and the often-normal laryngeal exam in between episodes. Moreover, additional sources of obstruction have been identified as sources of Periodic Occurrence of Laryngeal Obstruction (POLO). Treatments can vary with site of obstruction.

Objective

To evaluate pediatric patients presenting to a Vocal Fold Dysfunction Center for evaluation of exertional, inspiratory, harsh breath sounds and dyspnea suggestive of PVFMD whom were found to have a dynamic obstruction of the upper airway due to adenotonsillar hypertrophy and prolapse.

Methods

Retrospective chart review of patients diagnosed with exertional dynamic tonsillar prolapse whom have undergone adenotonsillectomy. Clinical characteristics, spirometry, exam findings and response to adenotonsillectomy were recorded.

Results

Seven patients with exercise induced dyspnea and respiratory distress with whom underwent exercise spirometry then subsequent adenotonsillectomy were identified. Symptomatic co-morbidities were common and included: rhinitis (43%), reflux (29%), sleep disordered breathing (29%), asthma (14%), obesity (14%), prematurity (14%) and anxiety/post-traumatic stress disorder (PTSD) (14%). Preoperative use of bronchodilators or reflux medications was common. All patients were noted to have >50% oropharyngeal obstruction secondary to tonsillar hypertrophy and dynamic lateral pharyngeal collapse or tonsillar prolapse with inspiration. No exercise induced paradoxical vocal fold dysfunction was identified. All baseline and most exertion FVC, FEV1, FEV1/FVC and FEF 25-75% were normal. Four patients had flow volume loops suggestive of obstruction. All patients had symptomatic improvement after adenotonsillectomy.

Conclusions

Dynamic tonsillar prolapse can result in subjective exertional dyspnea and objective upper airway resistance mimicking PVFMD and treatment with adenotonsillectomy can greatly reduce symptoms.

https://ift.tt/2PfcDEX

Ankyloglossum Superius Syndrome Compromising a Neonatal Airway: Considerations in Congenital Oral Airway Obstructions

Publication date: Available online 1 December 2018

Source: International Journal of Pediatric Otorhinolaryngology

Author(s): Jason F. Ohlstein, Pablo L. Padilla, Rachel K. Garza, Brian D. Masel, Amr Abouleish, Harold S. Pine, Wasyl Szeremeta

Abstract

We report the case of a 37-week old newborn presenting on day 1 of life with an apparent congenital fusion of the tongue to the hard palate, consistent with Ankyloglossum Superius syndrome. Physical exam along with endoscopy showed apparent fusion of the floor of the mouth to the anterior hard palate displacing the tongue into the nasal cavity and obstructing the oral airway. The child was nasotracheally intubated and brought to the operating room for lysis of the fusion under binocular microscopy. We review the literature on this rare condition and provide an algorithm for evaluating the neonatal airway in the setting of congenital oral abnormalities.

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Maternal anaesthesia in open and fetoscopic surgery of foetal open spinal neural tube defects: A 6-year observational study

BACKGROUND Prenatal myelomeningocele repair by open surgery can improve the neurological prognosis of children with this condition. A shift towards a fetoscopic approach seems to reduce maternal risks and improve obstetric outcomes. OBJECTIVE The aim of this study was to report on the anaesthetic management of women undergoing prenatal open or fetoscopic surgery for neural tube defects. DESIGN A retrospective cohort study. SETTING Prenatal myelomeningocele repair research group, Vall d'Hebron University Hospital, Spain. INTERVENTION Intra-uterine foetal repairs of spina bifida between 2011 and 2016 were reviewed. Anaesthetic and vasoconstrictor drugs, fluid therapy, maternal haemodynamic changes during surgery, blood gas changes during CO2 insufflation for fetoscopic surgery, and maternal and foetal complications were noted. RESULTS Twenty-nine foetuses with a neural tube defect underwent surgery, seven (24.1%) with open and 22 (75.9%) with fetoscopic surgery. There were no significant differences in maternal doses of opioids or neuromuscular blocking agents. Open surgery was associated with higher dose of halogenated anaesthetic agents [maximum medium alveolar concentration (MAC) sevoflurane 1.90 vs. 1.50%, P = 0.01], higher need for intra-operative tocolytic drugs [five of seven (71.4%) and two of 22 (9.1%) required nitroglycerine, P = 0.001], higher volume of colloids (500 vs. 300 ml, P = 0.036) and more postoperative tocolytic drugs (three drugs in all seven cases (100%) of open and in one of 21 (4.76%) of fetoscopic surgery, P 

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Intra-operative tachycardia is not associated with a composite of myocardial injury and mortality after noncardiac surgery: A retrospective cohort analysis

BACKGROUND Myocardial injury after noncardiac surgery (MINS) is a major contributor to peri-operative morbidity and mortality with a reported incidence of about 8%. Tachycardia increases myocardial oxygen demand, and decreases oxygen supply, and is therefore a potential cause of MINS. OBJECTIVE We tested the hypothesis that there is an association between intra-operative area above a heart rate (HR) of 90 bpm and a composite of MINS and in-hospital all-cause mortality. DESIGN Retrospective analyses. SETTING Major tertiary care hospital, Cleveland, USA. PATIENTS Adults having elective or nonelective noncardiac surgery and scheduled troponin monitoring during the first 3 postoperative days between 2010 and 2015. MAIN OUTCOME MEASURES All-or-none composite of myocardial injury (MINS), defined by a peak postoperative generation 4 troponin T concentration at least 0.03 ng ml−1, and in-hospital all-cause mortality. RESULTS Among 2652 eligible patients, 123 (4.6%) experienced MINS within 7 days after surgery and 6 (0.2%) died before discharge. Intra-operative area above HR more than 90 bpm was not associated with the all-or-none composite of MINS and in-hospital mortality, with an estimated odds ratio (95% confidence interval) of 0.99 (0.97 to 1.01) per 1 h bpm increase in area above HR more than 90 bpm. Secondary outcomes were also unrelated to the composite, with estimated odds ratios (98.3% confidence interval) of 0.99 (0.98 to 1.00) for area above HR more than 80, 0.98 (0.92 to 1.04) for area above HR more than 100 bpm, and 0.96 (0.88 to 1.05) for maximum HR. CONCLUSION There was no apparent association between various measures of tachycardia and a composite of MINS and death, a result that contradicts previously reported associations between other measures of intra-operative tachycardia and MINS/mortality. Correspondence to Kurt Ruetzler, MD, Department of Outcomes Research, Anaesthesiology Institute, Cleveland Clinic, 9500 Euclid Avenue, P-77, Cleveland, OH 44195, USA Tel: +1 216 445 9857; fax: +1 216 444 6135; e-mail: kurt.ruetzler@reflex.at;web:www.or.org Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (https://ift.tt/2ylyqmW). © 2018 European Society of Anaesthesiology

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Group 2 innate lymphoid cells and eosinophilic chronic rhinosinusitis

Purpose of review Chronic rhinosinusitis (CRS) is a heterogeneous disease and is recently classified into two phenotypes, eosinophilic CRS (ECRS) and non-ECRS. ECRS is characterized by Th2-biased eosinophilic inflammation, and non-ECRS is characterized by Th1-biased neutrophilic inflammation. Group 2 innate lymphoid cells (ILC2s) rapidly produce large amounts of Th2 cytokines and exert critical roles in Th2-type immune responses. We summarize our current knowledge about the pathogenic roles of ILC2s in ECRS. Recent findings The prevalence of ILC2s is increased in nasal polyps, and it is positively correlated with the number of infiltrating eosinophils. Epithelium-derived cytokines (IL-33, IL-25, and thymic stromal lymphopoietin), cysteinyl leukotrienes, and prostaglandin D2 stimulate the production of Th2 cytokines from ILC2s, which drives eosinophilic inflammation in nasal mucosa. Regulation of ILC2s would be a novel therapeutic approach for the refractory and/or recurrent cases of ECRS. Summary Increased ILC2s play a pivotal role in the pathophysiology of ECRS by producing large amounts of Th2 cytokines, which lead to Th2-type eosinophilic inflammation in nasal polyps. Correspondence to Ichiro Tojima, MD, PhD, Department of Otorhinolaryngology, Shiga University of Medical Science, Seta-Tsukinowa, Otsu, Shiga 520-2192, Japan. Tel.: +81 77 548 2261;. fax: +81 77 548 2783; e-mail: itirotz@hotmail.com Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Obesity and adiposity indicators in asthma and allergic rhinitis in children

Purpose of review The prevalence of obesity and allergic diseases, such as asthma and allergic rhinitis, is increasing worldwide not only in adults, but also in children. Experimental and clinical studies have demonstrated the effect of obesity not only on asthma, but also on other allergic diseases. Recent findings Allergic diseases, such as asthma and allergic rhinitis, are common chronic inflammatory diseases of the airways. Obesity is an increasingly common pediatric disease and is a risk factor for the development of asthma in that obese patients with asthma tend to have more severe asthma that does not respond well to standard asthma therapy. On the contrary, children with asthma maybe at a high risk of obesity, suggesting that the relationship of asthma and obesity seems to be interrelated. The role of obesity on the development of allergic rhinitis is not well defined, whereas allergic rhinitis may have an impact on obesity. Summary Childhood obesity is often considered to be less serious than obesity in adults because of the greater risk of complications in obese adults. In this review, we discuss the allergic confounders of obesity and the impact of allergic diseases on obesity. Proper control of the BMI within the normal range in children with allergic diseases is important. Correspondence to Hanako Tajima, MD, PhD, Department of Pediatrics, Nippon Medical School, Musashi Kosugi Hospital, 1-396, Kosugi-cho, Nakahara-ku, Kawasaki City, Kanagawa 211-8533, Japan. Tel: +81 44 733 5181; fax: +81 44 711 8826; e-mail: s7047@nms.ac.jp Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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The role of surfactant protein-A in sinusitis

Purpose of review Surfactant protein-A (SP-A) is a collectin protein expressed in airway epithelia that is critical in the modulation of both innate and adaptive immunity against inhaled pathogens. In this review, we highlight associations of altered SP-A function in asthma and chronic rhinosinusitis, and its potential role as a targeted therapy for sinusitis. Recent findings SP-A has been shown to bind and opsonize inhaled pathogens, thereby clearing bacteria through phagocytosis. We have recently identified that SP-A levels are increased in response to Pseudomonas aeruginosa, a common bacterial pathogen in chronic rhinosinusitis. Moreover, SP-A has also been shown to modulate epithelial inflammatory mediators and play a role in eosinophil-mediated airway disease. The development of a transgenic murine model expressing human genetic variants of SP-A2 have suggested that the human surfactant protein-A2 223K variant significantly increases eosinophil degranulation, suggesting a genotype-phenotype correlation in human airway disease. Summary SP-A is important in both the innate and adaptive host defense mechanisms in the upper and lower airways. Although research in this field in sinusitis is nascent, initial work suggests that aberrant SP-A regulation may be one etiologic factor in the development of bacterial and eosinophilic-associated sinusitis. Correspondence to Eugene H. Chang, MD, FACS, Associate Professor, Otolaryngology Director, Rhinology, 1501 N. Campbell Avenue PO Box 245074 Tucson, AZ 85724, USA. Tel: +520 626-6673; fax: +520 626-6995; e-mail: echang@oto.arizona.edu Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Preventing the development of asthma: stopping the allergic march

Purpose of review: To describe important precipitants of asthma and allergic disease, to highlight the links between these triggers and modifications within the immune system, and to examine innovative research regarding asthma prevention with focus on attenuating the atopic march. Recent findings: Allergen avoidance, allergen immunotherapy, IgE antagonists, prevention and treatment of respiratory infections, as well as management of gastrointestinal and respiratory dysbiosis have been considered as strategies in asthma prevention. Antenatal vitamin D supplementation in expectant mothers and aggressive control of atopic dermatitis to prevent the development of other allergic conditions were carefully studied as well. Summary: Asthma is a major cause of morbidity and lost productivity. Despite the tremendous burden of this disease, the scientific community is still struggling to find an effective means of prevention. The contribution of genetics to the development of atopy cannot be altered, but environmental changes as well as pharmacotherapy have been studied as modifiable risk factors. Many trials to date have been effective only for subjects with certain characteristics. This is likely because asthma is a heterogenous condition, with a variety of triggers and clinical phenotypes. Thus far, a universally effective prevention strategy has eluded us. However, if an intervention can be found to prevent asthma and the allergic march, it will greatly improve quality of life for millions of sufferers and decrease healthcare expenditures. Correspondence to Wanda Phipatanakul, MD, MS, Division of Immunology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA. Tel: +1 617 355 6117; e-mail: Wanda.Phipatanakul@childrens.harvard.edu Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Role of IL-35 in sublingual allergen immunotherapy

Purpose of review Sublingual allergen immunotherapy (SLIT), a disease-modifying treatment for allergic rhinitis, can induce long-term clinical benefits which are mediated by immune responses that include generation of regulatory B (Breg) and T (Treg) cells. The newest member of the IL-12 superfamily, IL-35, is an anti-inflammatory cytokine known to be produced by Breg and Treg cells. Limited studies are available on the role of IL-35 on allergic rhinitis and during SLIT. This review summarizes recent findings relevant to the topic of IL-35 and their role in SLIT. Recent findings Recombinant IL-35 protein can induce the generation of IL-35-producing Breg and Treg cells with immunosuppressive capacity. Levels of IL-35 and IL-35-inducible Treg (iTR35) cells are dysregulated in allergic rhinitis patients, which can be restored with SLIT. Mechanism of IL-35-mediated tolerance to allergens includes suppressions of T cell proliferation, Th2 cytokine production, and B cell production of IgE antibodies. Summary Emerging evidence supports a potential role for IL-35 and iTR35 cells in tolerance maintenance during SLIT. A better understanding for the role of IL-35 and iTR35 cells could provide new avenues for the development of clinical biomarker to assess efficacy of allergen immunotherapy and novel therapeutic strategies for allergic rhinitis. Correspondence to Mohamed H. Shamji, PhD, Immunomodulation and Tolerance Group, Allergy and Clinical Immunology, Inflammation, Repair and Development, National Heart and Lung Institute, Imperial College London, 1st Floor, Room 111, Sir Alexander Fleming Building, South Kensington Campus, London SW7 2AZ, United Kingdom. Tel: +44 0 7872850369; 44 0 20 75941673; e-mail: m.shamji@imperial.ac.uk Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Impact of occupational exposure on human microbiota

Purpose of review Recent evidence suggests that environmental exposures change the adult human microbiome. Here, we review recent evidence on the impact of the work microbiome and work-related chemical, metal and particulate exposures on the human microbiome. Recent findings Prior literature on occupational microbial exposures has focused mainly on the respiratory effects of endotoxin, but a recent study suggests that not all endotoxin is the same; endotoxin from some species is proinflammatory, whereas endotoxin from other species is anti-inflammatory. Work with animals can change the adult human microbiome, likely through colonization. Early studies in military personnel and animal models of gulf war illness show that military exposures change the gut microbiome and increase gut permeability. Heavy metal and particulate matter exposure, which are often elevated in occupational settings, also change the gut microbiome. Summary An emerging body of literature shows that work-related exposures can change the human microbiome. The health effects of these changes are currently not well studied. If work exposures lead to disease through alterations in the human microbiome, exposure cessation without addressing changes to the human microbiome may be ineffective for disease prevention and treatment. Correspondence to Peggy S. Lai, MD, MPH, Division of Pulmonary and Critical Care Medicine, Massachusetts General Hospital, 55 Fruit Street, Bulfinch 148, Boston, MA 02114, USA. E-mail: pslai@hsph.harvard.edu Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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