Effect of photon-initiated photoacoustic streaming, passive ultrasonic, and sonic irrigation techniques on dentinal tubule penetration of irrigation solution: a confocal microscopic study

Abstract

Objectives

The aim of this in vitro study was to evaluate the efficacy of different irrigation techniques including laser-activated irrigation using an erbium:yttrium-aluminum-garnet (Er:YAG) laser with a novel tip design (photon-induced photoacoustic streaming (PIPS)), Er:YAG laser with Preciso tip, sonic activation, and passive ultrasonic activation on the final irrigation solution penetration into dentinal tubules by using a laser scanning confocal microscope.

Material and methods

In this study, 65 extracted single-rooted human mandibular premolars were instrumented up to size 40 and randomly divided into 5 groups (n = 13) based on the activation technique of the final irrigation solution as follows: conventional irrigation (control group), sonic activation, passive ultrasonic activation, Er:YAG-PIPS tip activation, and Er:YAG-Preciso tip activation. In each group, 5 mL of 5% NaOCl labeled with fluorescent dye was used during the activation as the final irrigation solution. Specimens were sectioned at 2.5 and 8 mm from the apex and then examined under a confocal microscope to calculate the dentinal tubule penetration area. Data were analyzed using two-way analysis of variance (ANOVA) and Tukey's post hoc tests (P = 0.05).

Results

Both Er:YAG laser (Preciso/PIPS) activations exhibited a significantly higher penetration area than the other groups (P < 0.05). Additionally, passive ultrasonic activation had significantly higher penetration than the sonic activation group and the control group. Statistically significant differences were also found between each root canal third (coronal > middle > apical) (P < 0.001).

Conclusions

The results from the present study support the use of Er:YAG laser activation (Preciso/PIPS) to improve the effectiveness of the final irrigation procedure by increasing the irrigant penetration area into the dentinal tubules.

Clinical relevance

The activation of the irrigant and the creation of the streaming with the Er:YAG laser have a positive effect on the irrigant penetration.

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Treatment of medication-related osteonecrosis of the jaws (MRONJ) with ultrasonic piezoelectric bone surgery. A case series of 20 treated sites

Abstract

Purpose

There is no consensus on how to successfully treat medication-related osteonecrosis of the jaws (MRONJ). We report here on the application of piezoelectric bone surgery to treat MRONJ in combination with antibiotherapy and on its possible benefit.

Materiel and methods

A cohort of 18 consecutive patients has been treated for MRONJ; they involved 20 sites, 15 in the mandible, and five in the maxilla. Surgical removal of the necrotic areas and debridement was performed with a powerful piezoelectric surgery device (max 90 W) in combination with antibiotherapy.

Results

All patients healed and obtained a complete soft tissue closure within 1 month. No recurrence of the symptoms was observed during the present follow-up (10–54 months).

Conclusion

We hypothesize that healing of all treated sites might have resulted from the synergic effect of bone ablation, biofilm alteration, and antibiotic administration. Biofilm alteration might have permitted a better access of antibiotics to the involved germs. These encouraging results warrant further studies on the use of ultrasonic surgery to treat MRONJ patients in order to confirm or refute the hypothesized effect.

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Editorial board

Publication date: December 2016
Source:Revue de Stomatologie, de Chirurgie Maxillo-faciale et de Chirurgie Orale, Volume 117, Issue 6





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Calendrier des manifestations

Publication date: December 2016
Source:Revue de Stomatologie, de Chirurgie Maxillo-faciale et de Chirurgie Orale, Volume 117, Issue 6





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Erratum to: What is the best moment to apply phototherapy when associated to a strength training program? A randomized, double-blinded, placebo-controlled trial

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Beneficial effect of low-level laser therapy in acute lung injury after i-I/R is dependent on the secretion of IL-10 and independent of the TLR/MyD88 signaling

Abstract

The use of low-level laser for lung inflammation treatment has been evidenced in animal studies as well as clinical trials. The laser action mechanism seems to involve downregulation of neutrophil chemoattractants and transcription factors. Innate immune responses against microorganisms may be mediated by toll-like receptors (TLR). Intestinal ischemia and reperfusion (i-I/R) lead to bacterial product translocation, such as endotoxin, which consequently activates TLRs leading to intestinal and lung inflammation after gut trauma. Thus, the target of this study was to investigate the role of TLR activation in the laser (660 nm, 30 mW, 67.5 J/cm², 0.375 mW/cm², 5.4 J, 180 s, and spot size with 0.08 cm²) effect applied in contact with the skin on axillary lymph node in lung inflammation induced by i-I/R through a signaling adaptor protein known as myeloid differentiation factor 88 (MyD88). It is a quantitative, experimental, and laboratory research using the C57Bl/6 and MyD88^−/− mice (n = 6 mice for experimental group). Statistical differences were evaluated by ANOVA and the Tukey-Kramer multiple comparisons test to determine differences among groups. In order to understand how the absence of MyD88 can interfere in the laser effect on lung inflammation, MyD88^−/− mice were treated or not with laser and subjected to occlusion of the superior mesenteric artery (45 min) followed by intestinal reperfusion (4 h). In summary, the laser decreased the MPO activity and the lung vascular permeability, thickened the alveolar septa, reduced both the edema and the alveolar hemorrhage, as well as significantly decreased neutrophils infiltration in MyD88-deficient mice as well in wild-type mice. It noted a downregulation in chemokine IL-8 production as well as a cytokine IL-10 upregulation in these animals. The results also evidenced that in absence of IL-10, the laser effect is reversed. Based on these results, we suggest that the beneficial effect of laser in acute lung injury after i-I/R is dependent on the secretion of IL-10 and independent of the TLR/MyD88 signaling.

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Indoleamine 2,3-dioxygenase regulates T cell activity through Vav1/Rac pathway

Publication date: January 2017
Source:Molecular Immunology, Volume 81
Author(s): Runmei Li, Hui Li, Qian Sun, Liang Liu, Chen Zhang, Xiubao Ren
The immunoregulatory enzyme indoleamine 2,3-dioxygenase (IDO) suppresses T-cell responses and promotes immune tolerance in tumor resistance. A previous study determined that IDO inhibits Vav1 mRNA expression and the activation of Vav1 and its downstream targets in T cells in the guanine exchange factor (GEF)-independent pathway. The current study aims to determine whether IDO induces T-cell immunosuppression through Vav1/Rac signaling pathway, which is a GEF-dependent pathway. The correlation between Vav1 mRNA expressions in T cells of tumor infiltrating lymphocytes and the levels of IDO expression in lung cancer tissues from lung cancer patients was detected. HEK293 cells were stably transfected with human IDO (HEK293-IDO). T cells were isolated from human blood. HEK293-IDO cells were co-incubated with T cells in the presence or absence of an anti-CD3 antibody to activate T cell receptor (TCR) and/or 1-methyl-l-tryptophan (1-MT) to inhibit IDO activity. The early signaling proteins in T-cytoskeleton regulation through Vav1/Rac pathway of T cell were determined. A significant and negative correlation was observed between IDO and Vav1 expression in the tumor microenvironment. IDO, which was produced by HEK293-IDO cells, significantly inhibited the expression of Vav1, which resulted in defective F-actin reorganization. Thus, TCR signaling initiation was damaged. The effects on T-cells induced by the co-culture of HEK293-IDO cells with T cells were attenuated by 1-MT. Results indicate that the inhibitory effects of IDO on T cell immune responses may occur through the down-regulation of Vav1 protein expression and the suppression of Vav1/Rac cascade. These studies provide insight into the mechanisms of immune escape induced by IDO.



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Table of Contents

Publication date: January–February 2017
Source:American Journal of Otolaryngology, Volume 38, Issue 1





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Guidelines for Contributing Authors

Publication date: January–February 2017
Source:American Journal of Otolaryngology, Volume 38, Issue 1





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Editorial Board

Publication date: January–February 2017
Source:American Journal of Otolaryngology, Volume 38, Issue 1





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Third Molar Complications in the Elderly – A Matched-Pairs-Analysis

Publication date: Available online 5 December 2016
Source:Journal of Oral and Maxillofacial Surgery
Author(s): Frederik Baensch, Marcus S. Kriwalsky, Wiebke Kleffmann, Martin Kunkel
PurposeThe aim of this study was to evaluate the perioperative morbidity of third molar (3M) removal in elderly patients in an attempt to estimate the long-term future burden of 3M-related morbidity resulting from a consequent postponement of 3M surgery towards seniority.Patients and MethodsThe study-design was a retrospective matched pair analysis comparing patients age 65 and plus (Group A) to a control group (B) in adolescence and early adulthood (15-20 years). The age-group was the predictor variable in this study. The outcome variables were general health status as defined by the Modified Charlson- and ASA-Score, general surgical risks due to antithrombotic and/or antiresorptive medication and specific local surgical risks and complications.ResultsPatients in group A showed substantially more comorbidities as reflected in significant higher MCS and ASA Scores (p < 0.001). Older patients more frequent used antithrombotic agents (p < 0.001), had higher rates of ankylosis (p < 0.001) and nerve proximity (p < 0.001) and showed significantly more in intra- and postoperative complications (p < 0.001), thus, resulting in longer operations and a substantially longer hospital stay (p < 0.001).ConclusionWithin the limits of a non-epidemiological approach, our study figured out a substantially higher burden of morbidity and a significantly worse outcome of 3M surgery in senior adults compared to adolescent patients. Regarding the medical risks of an aging population, our data suggest a veritable burst of third molar associated morbidity, when the time of surgery is shifted to late adulthood.



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Fusobacterium necrophorum Pharyngitis Complicated by Lemierre’s Syndrome

We report the case of an 18-year-old woman who was referred to our outpatient clinic because of a 2-week history of sore throat, high fever, and neck tenderness unresponsive to a 7-day amoxicillin/clavulanic acid course. Infectious mononucleosis was initially suspected, but an extremely high value of procalcitonin and clinical deterioration suggested a bacterial sepsis, prompting the patient admission to our internal medicine ward. Blood cultures were positive for Fusobacterium necrophorum. CT scan detected a parapharyngeal abscess, a right internal jugular vein thrombosis, and multiple bilateral lung abscesses, suggesting the diagnosis of Lemierre's syndrome. The patient was treated with a 2-week course of metronidazole and meropenem with a gradual clinical recovery. She was thereafter discharged home with metronidazole and amoxicillin/clavulanic acid for 14 days and a 3-month course of enoxaparin, experiencing an uneventful recovery. The present case highlights the importance of taking into consideration the Lemierre's syndrome whenever a pharyngotonsillitis has a severe and unusual course.

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Quality of Life and Psycological Evaluation of Patients Affected by Head and Neck Cancer

Condition:   Quality of Life
Intervention:   Radiation: Head and Neck patients
Sponsor:   Michele Tedeschi
Recruiting - verified November 2016

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Study Assessing The "Best of" Radiotherapy vs the "Best of" Surgery in Patients With Oropharyngeal Carcinoma

Condition:   Oropharyngeal Cancer
Interventions:   Radiation: Intensity-Modulated Radiation Therapy;   Procedure: Trans Oral Surgery
Sponsors:   European Organisation for Research and Treatment of Cancer - EORTC;   Swiss Group for Clinical Cancer Research
Not yet recruiting - verified December 2016

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Identifying Intraoperative Nerve Monitoring in Thyroid Surgery Using Administrative Databases-Reply.

Identifying Intraoperative Nerve Monitoring in Thyroid Surgery Using Administrative Databases-Reply.

JAMA Otolaryngol Head Neck Surg. 2016 Dec 01;:

Authors: Al-Qurayshi Z, Randolph GW, Kandil E

PMID: 27918796 [PubMed - as supplied by publisher]

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Identifying Intraoperative Nerve Monitoring in Thyroid Surgery Using Administrative Databases.

Identifying Intraoperative Nerve Monitoring in Thyroid Surgery Using Administrative Databases.

JAMA Otolaryngol Head Neck Surg. 2016 Dec 01;:

Authors: Megwalu UC

PMID: 27918789 [PubMed - as supplied by publisher]

http://ift.tt/2gL6XF6

Slowly Growing Right-Sided Neck Mass With Progressive Dysphagia.

Slowly Growing Right-Sided Neck Mass With Progressive Dysphagia.

JAMA Otolaryngol Head Neck Surg. 2016 Dec 01;:

Authors: Lopez A, Papouchado B, Brumund KT

PMID: 27918788 [PubMed - as supplied by publisher]

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An Ovine Model for Exclusive Endoscopic Ear Surgery.

An Ovine Model for Exclusive Endoscopic Ear Surgery.

JAMA Otolaryngol Head Neck Surg. 2016 Dec 01;:

Authors: Anschuetz L, Bonali M, Ghirelli M, Mattioli F, Villari D, Caversaccio M, Presutti L

Abstract
Importance: With the international spread of exclusive transcanal endoscopic ear surgery, the need for a suitable and affordable surgical training model has grown during the past years.
Objective: To develop and validate an ex vivo animal model for exclusive endoscopic ear surgery.
Design, Setting, and Animal Models: In an experimental study, we compared ovine and human middle ear anatomy in 4 specimens and assessed the lamb as a model for endoscopic ear surgery. After confirming its suitability, we developed a surgical training program for canaloplasty, myringoplasty, and ossiculoplasty. From March 1 to May 31, 2016, the ex vivo model was tested, assessing the time needed for dissection and complications. Each experience was subjectively validated on a scale from 1 (very poor) to 10 (excellent).
Main Outcomes and Measures: Suitability of the lamb model for training in exclusive endoscopic ear surgery.
Results: We assessed the suitability of our novel lamb model on 20 ovine middle ears. All interventions could be performed in a satisfactory manner. The mean (SD) time required to perform canaloplasty was 29.7 (13.2) minutes, for middle ear dissection was 7.7 (2.6) minutes, for myringoplasty was 7.7 (4.3) minutes, and for ossiculoplasty was 10.4 (2.7) minutes. The time required for canaloplasty and tympano-meatal flap elevation during dissection decreased from 46.4 minutes in the first 5 cases to 16.2 minutes in the last 5 cases, representing an absolute difference of 30.2 minutes (95% CI, 22.28-38.12). Subjective ratings revealed excellent values for tissue quality (8.9 points of 10), overall satisfaction (8.3 points), and the learning experience (8.8 points).
Conclusions and Relevance: The ovine model is suitable for endoscopic ear surgery. We describe a novel, exclusively endoscopic approach in an ex vivo animal model for middle ear surgery. The proposed surgical program leads the trainee step by step through the main otologic procedures and is able to enhance his or her surgical skills.

PMID: 27918787 [PubMed - as supplied by publisher]

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Association Between Laryngeal Cancer and Asbestos Exposure: A Systematic Review.

Association Between Laryngeal Cancer and Asbestos Exposure: A Systematic Review.

JAMA Otolaryngol Head Neck Surg. 2016 Dec 01;:

Authors: Ferster AP, Schubart J, Kim Y, Goldenberg D

Abstract
Importance: It has been debated whether a link exists between laryngeal cancer and asbestos exposure. Prior systematic reviews have been conducted on this topic, but no updates have been performed on the most recent literature since 2000.
Objective: To provide an updated systematic review of the association between laryngeal cancer and asbestos exposure.
Evidence Acquisition: A search of electronic databases, including PubMed and the Cochrane Library, was performed for articles published between January 1, 2000, and April 30, 2016. Search terms, including laryngeal cancer and asbestos, were used to identify publications reviewing the risk of laryngeal cancer in association with asbestos exposure. Studies analyzing this association that were published in any language and translated reliably were included. Two independent reviewers assessed articles based on predetermined eligibility criteria. Each study was reviewed for quality using the Oxford Centre for Evidence-Based Medicine 2011 Levels of Evidence and assessed for their findings of support for or against a correlation between asbestos exposure and laryngeal cancer.
Findings: A total of 160 studies were retrieved from all databases, and 2 additional articles were identified by cross-references. Of the 162 articles screened, 15 articles comprising 438 376 study participants were included in this review. Of these 15 studies, 10 showed no correlation between asbestos exposure and laryngeal cancer. The remaining 5 studies claimed a correlation between asbestos exposure and incidence of laryngeal cancer, although only 1 accounted for smoking or alcohol exposure while 3 others did not, and 1 study included only 2 patients.
Conclusions and Relevance: Although asbestos is considered hazardous and carcinogenic, current evidence is lacking to support a correlation between asbestos exposure and laryngeal cancer. Few studies have been able to definitively conclude a causal association between asbestos exposure and laryngeal cancer, and those that found an association often did not account for the confounding factors of tobacco and alcohol exposure.

PMID: 27918783 [PubMed - as supplied by publisher]

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The Role of Adjuvant Chemotherapy in Surgically Managed, p16-Positive Oropharyngeal Squamous Cell Carcinoma.

The Role of Adjuvant Chemotherapy in Surgically Managed, p16-Positive Oropharyngeal Squamous Cell Carcinoma.

JAMA Otolaryngol Head Neck Surg. 2016 Dec 01;:

Authors: Skillington SA, Kallogjeri D, Lewis JS, Piccirillo JF

Abstract
Importance: Human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) has a favorable prognosis, and p16 immunohistochemistry is a surrogate marker of high-risk HPV infection and strong prognosticator. Given this favorable prognosis, treatment de-escalation for p16-positive OPSCC is now being considered with the goal of decreasing treatment-associated morbidity without compromising tumor control. The role of adjuvant chemotherapy in this setting is becoming increasingly unclear.
Objective: To compare survival between surgically managed patients with p16-positive OPSCC who received adjuvant chemoradiotherapy and patients who received adjuvant radiotherapy alone.
Design, Setting, and Participants: This was a cohort study of patients with OPSCC diagnosed from June 1996 to June 2010, with follow-up through December 2014, at a single tertiary referral center. One hundred ninety-five surgically managed, p16-positive patients without a history of head and neck cancer or distant metastasis at time of diagnosis were included.
Exposures: Patients were dichotomized into adjuvant radiotherapy and adjuvant chemoradiotherapy groups.
Main Outcomes and Measures: Overall survival was the primary outcome, and disease-free survival was the secondary outcome. Propensity-weighted multivariate Cox proportional hazards analysis was conducted to quantify the effect of adjuvant chemotherapy on survival.
Results: The study included 195 patients with p16-positive, surgically managed OPSCC. Median duration of follow-up was 87 months (interquartile range, 68-116 months). Ninety patients received adjunct chemoradiotherapy (mean age, 54.3 years), 88 patients received adjuvant radiotherapy (mean age, 56.4 years), and 17 patients received surgery alone. The 5-year overall survival rate for patients who received adjuvant chemoradiotherapy was 82% (95% CI, 73%-90%) and 84% (95% CI, 76%-91%) for patients who received adjuvant radiotherapy alone. The 5-year disease-free survival rate for patients who received adjuvant chemoradiotherapy was 79% (95% CI, 71%-88%) and 79% (95% CI, 70%-88%) for patients who received radiotherapy alone. After weighting cases by the inverse probability of receiving adjuvant chemotherapy and controlling for age, comorbidity, smoking, pathological T stage, and pathological N stage, the receipt of adjuvant chemotherapy was not significantly associated with disease-free survival (adjusted hazard ratio, 0.91; 95% CI, 0.59-1.42) but was associated with a statistically insignificant yet clinically meaningful increase in all-cause mortality (adjusted hazard ratio, 1.46; 95% CI, 0.91-2.33).
Conclusions and Relevance: Among patients with p16-positive OPSCC managed surgically with adjuvant radiotherapy, the addition of adjuvant chemotherapy provided no additional disease-free survival benefit and was associated with worse overall survival. These results should help inform future clinical trials aiming to deescalate treatment for p16-positive patients.

PMID: 27918781 [PubMed - as supplied by publisher]

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Acute Marjolin’s Ulcer in a Postauricular Scar after Mastoidectomy

Background. Marjolin's ulcer is a rare, aggressive cutaneous malignancy that arises primarily in burn scars but can occur in other types of scars. Squamous cell carcinoma is the most common variant, and while malignant degeneration usually takes a long time, it can develop acutely. Case Report. a 30-year-old man who developed Marjolin's ulcer acutely in a right postauricular scar after mastoidectomy and the incision and drainage of a mastoid abscess. To the best of our knowledge, this report is the first to describe a Marjolin's ulcer in a postauricular surgical scar. However, it has been reported in others areas in the head and neck. Conclusion. Marjolin's ulcer is most commonly observed after postburn scars, but it may be observed after any type of scars, as our patient developed an SCC with a postsurgical scar. Early diagnosis is essential, and a biopsy should be performed on any nonhealing wound or chronic wound that undergoes a sudden change. Tissue samples should be taken from both the centre and the margins of the wound.

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Acute septic arthritis of the temporomandibular joint derived from otitis media: a report and review of the English and Japanese literature

Abstract

Septic arthritis of the temporomandibular joint (SATMJ) is an extremely rare disease with characteristic features of preauricular pain, swelling, redness, and malocclusion. The present report describes a case of SATMJ derived from otitis media, which resulted in a good outcome. We also reviewed the English and Japanese literature with special interest in etiology. It is generally agreed that contiguous or distant infection and trauma are common etiological factors of SATMJ. So far, these etiological factors are mainly discussed based on hypotheses rather than sufficient evidence. Therefore, in many past cases, accurate causes were not identified. To our knowledge, our case is the third report of SATMJ following otitis media. In addition, this is the first case in which the pathogenic bacterium responsible for the otitis media was the definite cause of the SATMJ. Cases of SATMJ are sometimes misdiagnosed with otitis media, and SATMJ derived from otitis media is extremely rare. Dentists and otolaryngologists should collaborate for the management of this disease as needed.

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Presto lift—a facelift that preserves the retaining ligaments and SMAS tethering

Abstract

Background

Producing youthful facial appearance by face-lifting often comes along with an undesired loss of patient's individual phenotype. This may result from insufficient preservation of retaining ligaments, the "guardians of facial identify," and from severance of the intersegmental connections of the superficial musculo-aponeurotic system (SMAS), which tether, structure, and compartmentalize facial soft tissue into defined, relevant anatomical zones.

Methods

The technique reported here preserves most retaining ligaments. They serve to fix the facial soft tissue mass in loco. With the possible exception of the zygomatic-cutaneous ligament, they are only carefully distended. The SMAS intersegmental connections and the zygomatic SMAS border are preserved to retain effective points of facial tissue fixture. Aging-associated thinning and lengthening of the lower eyelid are reduced by midfacial-submalar preparation (Aston 1996). Subplatysmal preparation and disconnection of the cranial-platysmal border permits optimal modeling of neck structure.

Results

The combination of preservation of retaining ligaments and SMAS tethering ("PRESTO facelift") introduced here as a novel face-lifting technique conserves the individual esthetics of the patient by approaching her/his individual phenotype from decades ago. In addition, undesired outcomes of facelift surgery and common risks of facelift surgery are circumvented.

Conclusions

The PRESTO facelift technique generates optimal esthetic results that conserve a patient's personal facial identity, besides restoring a more youthful appearance and being rapid and safe.

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The role of aspirin desensitization in the management of aspirin-exacerbated respiratory disease.

Purpose of review: Aspirin-exacerbated respiratory disease (AERD) is a progressive inflammatory disease of the upper and lower airways characterized by marked eosinophilic nasal polyposis, asthma, and respiratory reactions to medications that inhibit the cyclooxygenase pathway. Aspirin desensitization has proven to be an effective tool in the management of this disease when used in a multidisciplinary setting. The purpose of this article is to review the current literature regarding AERD, aspirin desensitization, and share our opinion regarding the most optimal multidisciplinary approach to these complex patients. Recent findings: Numerous studies, including randomized, double-blind, placebo-controlled trials, have demonstrated the therapeutic effectiveness of aspirin desensitization with significant improvement in number of sinus infections per year, olfactory scores, nasal symptom scores, asthma symptom scores, sinus operations, hospitalizations, emergency room visits, and oral steroid use. Furthermore, the role of surgery is becoming increasingly important for recalcitrant sinus disease with recent studies showing comprehensive surgery as more beneficial to disease management. Summary: Aspirin desensitization is an effective therapeutic tool in the management of AERD. A multidisciplinary approach is critical between the otorhinolaryngologist and allergist to provide the most optimal care for this complex patient population. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.

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Posttreatment surveillance for sinonasal malignancy.

Purpose of review: Sinonasal neoplasms have a high rate of recurrence following treatment, and clinicians utilize a variety of surveillance techniques. Generally, surveillance modality and frequency of follow-up are determined by the guidelines for head and neck cancer as a broad category. However, recent studies have demonstrated that a more tailored approach to follow-up may be necessary. Recent findings: Endoscopy has low sensitivity in recurrence detection, especially in the asymptomatic patient. However, it is able to identify superficial recurrences that may be more amenable to repeat resection. Conversely, imaging [computed tomography (CT), MRI, and 18F-fluorodeoxyglucose-PET/CT] is useful in ruling out disease, but the inflammatory environment of the posttreatment sinonasal cavity leads to a high number of false positives. This is especially notable in PET/CT, which has worse specificity and positive predictive value in sinonasal malignancy than in head and neck malignancy overall, especially in the early posttreatment period. Little data are available on optimal timing and duration of follow-up, but tumor histology and aggressiveness should be considered when choosing a surveillance approach. Summary: Sinonasal malignancy surveillance strategies may warrant modifications of current protocols used for head and neck malignancy. This is due to a number of factors, including a greater diversity of sinonasal disorder and increased duration of posttreatment sinonasal inflammation. Clinicians should be aware of the performance parameters of commonly used surveillance techniques and adjust follow-up regimens based on this information. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.

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Polyps, asthma, and allergy: what's new.

Purpose of review: Although chronic rhinosinusitis with nasal polyps, asthma, and allergy share common inflammatory mechanisms, there is no evidence of cause-and-effect relationship. In this review, we present new studies investigating the complex immunology that links these diseases. Advances in new therapies as well as evidence regarding indication and timing of surgery, especially of more complex cases, are highlighted. Recent findings: New studies have endotyped patients in an effort to describe the exact inflammatory profile of each phenotype, whereas described cytokines seem to play a significant role in amplification of T2 inflammation, directly or via innate lymphoid cells. New mAbs that block specific cytokines of these pathways have been developed and seem to show reduced asthma severity as well as improved sinonasal outcomes. Moreover, it has been shown that operating early in the course of disease leads not only to bigger improvements in SNOT-22 outcomes but also to reduced asthma incidence postoperatively in refractory cases. Summary: Applying data from current studies in clinical practice, we could better manage refractory cases with asthma and polyps, both medically and surgically. Treatment has to be patient-centered, and this demands a multidisciplinary-team approach of the airway diseases. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.

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An update on endoscopic orbital decompression.

Purpose of review: Endoscopic orbital decompression is an ever-evolving surgical procedure with modifications as well as new indications for the procedure. The purpose of this review is to update the reader on optimizing patient selection, surgical timing, highlight the latest modifications to surgical technique and to evaluate surgical outcomes that can be achieved. Recent findings: Patient selection, disease pathology, and optimization of technology can lead to improved outcomes. Changes in technology continue to modify surgical techniques and surgical training, working towards decreased surgical complications with improved outcomes. Historically multiple approaches have been used for orbital decompression and this highlights that a balanced orbital decompression usually leads to the best outcome. Summary: Orbital decompression has evolved significantly since its inception over 100 years ago. Identifying the right patient, the ideal timing, and the indication for the procedure with utilization of technology can lead to improved outcomes and decreased complications. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.

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Caudal septum surgery techniques reviewed.

Purpose of review: The caudal septum has important functional and aesthetic implications. Deviations in this area can result in important nasal obstruction due not only to blockage of the nasal passage but also to compromise of the internal nasal valve. Cosmetically, alterations in the caudal septum can result in a twisted nasal tip, loss of projection, rotation, and imbalance in the ala-columellar relationship. Contemporary surgical options will be discussed showing how to preserve, reshape, and reinforce the caudal septum to obtain a final looking nose that is not only functional but also aesthetically pleasing. Recent findings: Recent publications have shown that cartilage preservation and remodeling techniques can be efficient in the treatment of the caudal septum. Adequate preoperative diagnosis must be made to be able to create a step-wise approach evolving from simple suturing techniques to more complex ones that require the use of grafts to reposition and keep the caudal septum in the midline with an adequate functional and cosmetic outcome. Summary: Adequate management of the caudal portion of the nasal septum is a challenge because of its importance in nasal function and cosmetic final results. There are many surgical options that can be used to correct and align this structure and there is no one single surgical technique that can be used in all cases. A step-wise approach is presented covering the different techniques used today evolving from simple to more complicated ones. The final surgical objective should be cosmetically pleasing noses that function appropriately. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.

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Postoperative care in endoscopic sinus surgery: a critical review.

Purpose of review: Chronic rhinosinusitis with and without nasal polyps is a common disease affecting people all over the world. Functional endoscopic sinus surgery (FESS) has become the gold standard treatment for medically refractive disease. Postoperative care is recommended by international leaders as an important part of the patient's management. This article is a critical review and discussion focusing on postoperative care, which is based on expert opinion, clinical studies, randomized controlled trials and meta-analysis studies. Recent findings: Postoperative care including nasal rinsing, topical corticosteroids, antibiotics and avoidance of nasal packing are unanimously considered to be the cornerstone of best practice following FESS. However, the effectiveness of in-office nasal debridement is still under debate. Summary: There is a lack of consensus regarding the necessity of performing in-office nasal debridement and the majority of clinicians carry out their postoperative care according to experience and their own preference. This is often determined by the extent of surgery performed, the severity of the postoperative inflammation, as well as being dependent on the patient's discomfort, the time constraints associated with postoperative care and the costs associated with additional appointments. Ideally, nasal debridement should be performed by the operating surgeon under endoscopic control both gently and atraumatically. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.

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An "ex vivo model" contributing to the diagnosis and evaluation of new drugs in cystic fibrosis.

Related Articles

An "ex vivo model" contributing to the diagnosis and evaluation of new drugs in cystic fibrosis.

Acta Otorhinolaryngol Ital. 2016 Nov 29;:

Authors: Di Lullo AM, Scorza M, Amato F, Comegna M, Raia V, Maiuri L, Ilardi G, Cantone E, Castaldo G, Iengo M

Abstract
Cystic fibrosis (CF) is an autosomal recessive disease caused by mutations in the cystic fibrosis transmembrane regulator (CFTR) gene. About 2000 mutations have been described so far. We setup an ex vivo model of human nasal epithelial cells (HNECs) to study CF patients testing the effect of novel mutations and molecular therapies. We performed the sampling (by brushing), followed by culture and analysis of HNECs using a series of molecular techniques. We performed 50 brushings from CF patients and controls. Using cultured cells, we: i) demonstrated the widely heterogeneous CFTR expression in patients and in controls; ii) defined the splicing effect of a CFTR mutation; iii) assessed the CFTR gating activity in patients bearing different mutations; iv) demonstrated that butyrate significantly enhances CFTR expression. Based on our data, we can conclude: 1) HNEC brushing is performed without anaesthesia and is well tolerated in all CF patients (children and adults); 2) HNECs can be preserved for up to 48 hours before culture allowings multicenter studies; 3) HNECs culture can be considered a suitable model to study the molecular effects of new CFTR gene mutations and/or uncertain meaning specific mutations of carriers; 4) an ex vivo model of HNECs may be used to evaluate, before human use, the effect of new drugs on patients' cells bearing specific CFTR mutations; 5) the methodology is adequate for a quantitative measurement, by fluorescence, of the CFTR gating activity of the HNECs from patients with different genotypes identifying: a) CF patients bearing two severe mutations with an activity < 10% (compared to controls - 100%); b) CF patients bearing at least a mild mutation with an activity of 10-20%; c) CF carriers (heterozygous subjects) with an activity between 40-70%.

PMID: 27897275 [PubMed - as supplied by publisher]

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Modelling tumour volume variations in head and neck cancer: magnetic resonance imaging contribution for patients undergoing induction chemotherapy.

Related Articles

Modelling tumour volume variations in head and neck cancer: magnetic resonance imaging contribution for patients undergoing induction chemotherapy.

Acta Otorhinolaryngol Ital. 2016 Nov 29;:

Authors: Dinapoli N, Tartaglione T, Bussu F, Autorino R, Miccichè F, Sciandra M, Visconti E, Colosimo C, Paludetti G, Valentini V

Abstract
Primary tumour volume evaluation has predictive value for estimating survival outcomes. Using volumetric data acquired by MRI in patients undergoing induction chemotherapy (IC) these outcomes were estimated before the radiotherapy course in head and neck cancer (HNC) patients. MRI performed before and after IC in 36 locally advanced HNC patients were analysed to measure primary tumour volume. The two volumes were correlated using the linear-log ratio (LLR) between the volume in the first MRI and the volume in the second. Cox's proportional hazards models (CPHM) were defined for loco-regional control (LRC), disease-free survival (DFS) and overall survival (OS). Strict evaluation of the influence of volume delineation uncertainties on prediction of final outcomes has been defined. LLR showed good predictive value for all survival outcomes in CPHM. Predictive models for LRC and DFS at 24 months showed optimal discrimination and prediction capability. Evaluation of primary tumour volume variations in HNC after IC provides an example of modelling that can be easily used even for other adaptive treatment approaches. A complete assessment of uncertainties in covariates required for running models is a prerequisite to create reliable clinically models.

PMID: 27897274 [PubMed - as supplied by publisher]

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Education of Patients with Atopic Dermatitis and Their Caregivers

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


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Atopic Dermatitis, Beyond the Skin Surface

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


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Attention-Deficit/Hyperactivity Disorder in Atopic Dermatitis: An Appraisal of the Current Literature

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


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Allergen immunotherapy: an updated review of safety.

Purpose of review: Allergen immunotherapy is the only modality that can modify the immune response upon exposure to aeroallergens and venom allergens. This review will update the allergist on recent studies evaluating safety of sublingual and subcutaneous allergen immunotherapy. Recent findings: Multiple clinical trials and retrospective studies have been published evaluating overall safety of these therapies. The risk of systemic reactions with subcutaneous immunotherapy remains quite low, but near-fatal and fatal anaphylaxis does occur, requiring physicians to be aware of potential risks for such events. Sublingual immunotherapy has a high incidence of local site application reactions, but severe anaphylactic events are very uncommon. Summary: Subcutaneous immunotherapy and sublingual immunotherapy are beneficial in treating allergic rhinitis and venom hypersensitivity but should be administered only by physicians familiar with potential risk factors and able to manage treatment-related local and systemic allergic reactions. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.

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Targeting IL-25 as a novel therapy in chronic rhinosinusitis with nasal polyps.

Purpose of review: Chronic rhinosinusitis with nasal polyps (CRSwNPs) is a heterogeneous inflammatory disorder with a poorly understood pathophysiology. Recent findings show that epithelial-derived cytokines, including thymic stromal lymphopoietin, IL-33, and IL-25, can exacerbate Th2 immune responses, ultimately leading to recalcitrant chronic rhinosinusitis and nasal polyp. Although IL-25 is increased in CRSwNP, the targeting of IL-25 as a therapeutic strategy remains largely unexplored. In this review, we outline the many recent advances in our understanding of the association between IL-25 and CRSwNP. Recent findings: Recently, we demonstrated that IL-25, produced primarily by sinonasal epithelial cells and infiltrating mast cells, plays an important role in the pathogenesis of CRSwNP in Asian patients. Furthermore, IL-25 and IL-25R are elevated in nasal polyps. This cytokine has roles in the pathogenesis of CRSwNP via modulating group 2 innate lymphoid cells (ILC2s). Similarly, ILC2 enrichment has been reported in CRSwNP patients, and a positive correlation has been shown between ILC2s and CRSwNP. Clinical trials blocking thymic stromal lymphopoietin and IL-33 pathways are ongoing using monoclonal antibodies, AMG157 and AMG282, against CRSwNP, respectively. Summary: Studies on the role played by IL-25 in the pathogenesis of CRSwNP are accumulating and suggest the possibility of a novel therapeutic strategy for treating CRSwNP. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://ift.tt/OBJ4xP Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.

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IgE and eosinophils as therapeutic targets in asthma.

Purpose of review: Asthma is a chronic inflammatory disorder characterized by reversible airflow obstruction, which is being more widely recognized as a broad-spectrum disease that encompasses multiple patient characteristics and pathophysiologic mechanisms. Suboptimal asthma control leads to increasing burden of healthcare costs and loss of productivity to society. Biologic therapies targeted at IgE and eosinophils can be used in poorly controlled allergic and eosinophilic asthma, respectively. The purpose of this review is to analyze the advancements in currently available biologic therapies targeted at IgE and eosinophils in asthma and to identify how these therapies may impact overall healthcare costs. Recent findings: Omalizumab is an anti-IgE antibody that is approved for use of poorly controlled moderate-to-severe asthma. Many studies have confirmed that omalizumab not only improves quality of life and symptom scores, but also decreases urgent care and emergency department visits and hospitalizations. Dupilumab is a biologic agent targeted at TH2 cytokines, but indirectly impacts IgE and is an important biologic agent for atopic disease. Mepolizumab, reslizumab, and benralizumab target IL-5, a key cytokine for eosinophils. For patients with poorly controlled eosinophilic asthma, these biologic agents improve asthma symptoms, reduce exacerbations, and reduce emergency visits and hospitalizations. Summary: Poorly controlled severe asthma affects a small portion of patients with asthma in the United States and yet it accounts for large portion of healthcare utilization. Biological therapies in poorly controlled severe persistent asthma have been identified to reduce healthcare utilization, including emergency visits and hospitalizations. Biologic agents have a clear beneficial role in the management of severe asthma, and further evaluations should be continued in identifying optimal patient characteristics for the various agents and overall benefit toward healthcare utilization and cost. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.

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Medical therapy, refractory chronic rhinosinusitis, and productivity costs.

Purpose of review: The purpose of this review is to address the most recent advances in the medical therapy for chronic rhinosinusitis (CRS), define recalcitrant and refractory CRS, and discuss the productivity costs associated with CRS. Recent findings: Recent studies evaluating anti-IL-4 receptor [alpha] antibodies and calcium channel blockers have demonstrated promising early results during management of CRS. Recent appropriateness criteria have been developed to assist clinicians with defining which patients have 'refractory' CRS and may be considered candidates for endoscopic sinus surgery. Productivity costs appear to be associated with disease severity and can be reduced with appropriate interventions. Summary: Topical corticosteroid therapy and high volume saline irrigation continue to be the cornerstone to medical therapy, whereas use of systemic corticosteroids and antibiotics depends on CRS phenotype and presence of acute exacerbation. More research is needed before routine use of novel immunomodulatory therapies such as anti-IL5, anti-IgE, anti-IL4, and calcium channel blockers. Clinicians should apply an appropriate definition for refractory CRS when discussing role of sinus surgery. Assessing the degree of work productivity impairment can assist in treatment decision-making and may help predict treatment outcomes. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.

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Rhinitis: adherence to treatment and new technologies.

Purpose of review: Nonadherence to treatment is a major issue in approximately 50% of patients suffering from chronic diseases. The availability of new technologies could represent a possible way to improve patients' engagement and adherence in a real-life setting. Research and technology tools made available or in process of being made available to patients with allergic diseases and their physicians could potentially improve the management of these disease in daily life by improving adherence. In this review, we sought to outline many of the recent advances in these technological approaches. Recent findings: Short Message Service (SMS) reminder, social networks, wearable devices, mobile applications (Apps), monitoring systems of inhaled device use, often presented as 'serious game' are changing the way of approaching to chronic disease, such as rhinitis, management. Summary: Studies of the role played by various technologies in improving adherence to treatment in rhinitis are still limited as compared with other diseases such as asthma, but the results are encouraging. Further studies in this area may lead to the discovery of novel management approaches that is easy to be integrated in patients' daily life. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.

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Near-fatal asthma: a heterogeneous clinical entity.

Purpose of review: The aims of the present review were to describe the heterogeneous nature of near-fatal asthma (NFA) and to summarize the distinctive phenotypes identified in this subtype of asthma. Recent findings: Clinical, physiological, and histological studies have shown a large number of triggers, pathological mechanisms, and risk factors associated with NFA. Based on the demographic and clinical characteristics of the patients, the circumstances surrounding the asthma exacerbation and some distinctive features of the disease, several clinical profiles of asthma patients with NFA have been described. Recent data show new associations between some gene expression patterns and fatal asthma, as well as with some biological markers related to inflammatory or immunologic mechanisms in the airways. Also, the use of statistical methods, such as cluster analysis, allowed identifying and confirming different phenotypes of life-threatening asthma patients. Summary: NFA is a heterogeneous clinical entity, in which different patients' clinical profiles may coexist [e.g. rapid-onset NFA, NFA in patients with dyspnea hypoperception or sensitized to certain pneumoallergens (Alternaria alternata, soybean), NFA related to the menstrual cycle, brittle asthma]. Knowledge of these phenotypes as well as adequate and specific management strategies can reduce morbidity and mortality in patients suffering from NFA. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.

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Dendritic cell subset expression in severe chronic rhinosinusitis with nasal polyps.

Purpose of review: Two main pillars are implicated in nasal polyposis development: a severe imbalance in immunomodulation and a mechanical dysfunction because of an abnormal remodeling process. Dendritic cells play a crucial role in the link between innate and adaptive immune response and orchestrating the T-cell response and are implicated in the severe inflammatory process found in nasal polypoid tissue. This review summarizes the existent knowledge about dendritic cells in nasal polyposis. Recent findings: Dendritic cells are found increased in nasal polyposis, regardless of subset. Of interest, plasmacytoid dendritic cells are decreased in patients with a more severe Th2 profile, suggesting an important role of the cytokines milieu in their functional response or that plasmacytoid dendritic cell could act mitigating the inflamed process found in polypoid tissue. Summary: Understanding the dendritic cell subset expression in different environments, as well as the effect of these subsets on T-cell differentiation will greatly improve the development of new therapies in nasal polyposis. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.

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Infantile Cortical Hyperostosis: Report of a Case with Observations on Clinical Manifestations, Radiology, and Pathology with a Late Follow-Up of Eight Years

Purpose. The purpose of our study was to investigate clinical manifestations, roentgen images, histopathological studies, and evolution of the disease in patient displaying infantile cortical hyperostosis. Methods. Roentgenograms were made to evaluate a neonatal patient presenting multiple soft-tissue swellings. The initial radiographs insinuated that the disease had been present for some time in utero. Bone puncture biopsy of the tibia for histopathological observation and diagnosis conclusions was performed. Results. The disease was demonstrated radiographically by massive cortical diaphyseal thickening and also extensive periosteal new bone formation surrounding several bones. Results in blood count were as follows: discrete anemia, moderate leukocytosis, and elevated sedimentation rate. Histological pattern of tissue removed from tibia showed lamellar cortical bones and hyperplasia. Biopsy studies disclosed no evidence of neoplasia as well as of bacterial infection. Comments. Clinical manifestations in a neonatal patient displaying infantile cortical hyperostosis have gradually decreased. Radiograph findings have demonstrated complete recovery of bones manifested by the disease. The pathologic findings are in accordance with previous microscopic examination summarized by the literature. Total patient cure, without sequels, could be demonstrated.

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International Forum of Allergy & Rhinology 2016 Reviewers

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Editorial

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Masthead - Editorial Board And Table of Contents

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Mathematical Modeling of Atopic Dermatitis Reveals “Double switch” Mechanisms Underlying Four Common Disease Phenotypes

Publication date: Available online 5 December 2016
Source:Journal of Allergy and Clinical Immunology
Author(s): Elisa Domínguez-Hüttinger, Panayiotis Christodoulides, Kosuke Miyauchi, Alan D. Irvine, Mariko Okada-Hatakeyama, Masato Kubo, Reiko J. Tanaka
BackgroundThe skin barrier acts as the first line of defense against constant exposure to biological, microbial, physical and chemical environmental stressors. Dynamic interplay between defects in the skin barrier, dysfunctional immune responses, and environmental stressors are major factors in the development of atopic dermatitis (AD). A systems-biology modeling approach can yield significant insights into these complex and dynamic processes through integration of prior biological data.ObjectiveTo develop a multi-scale mathematical model of AD pathogenesis that describes the dynamic interplay between the skin barrier, environmental stress and immune dysregulation, and use it to achieve a coherent mechanistic understanding of onset, progression and prevention of AD.MethodsWe mathematically investigated synergistic effects of known genetic and environmental risk factors on the dynamic onset and progression of the AD phenotype, from a mostly asymptomatic mild phenotype to a severe treatment-resistant form.ResultsOur model analysis identified a "double switch", with two concatenated bistable switches, as a key network motif that dictates AD pathogenesis: The first switch is responsible for the reversible onset of inflammation; The second switch is triggered by long-lasting or frequent activation of the first switch, causing the irreversible onset of systemic Th2 sensitization and worsening of AD symptoms.ConclusionsOur mathematical analysis of the bistable switch predicts that genetic risk factors lower the threshold of environmental stressors to trigger systemic Th2 sensitization. This analysis predicts and explains four common clinical AD phenotypes from a mild and reversible phenotype through to severe and recalcitrant disease and provides a mechanistic explanation for clinically-demonstrated preventive effects of emollient treatments against development of AD.

Graphical abstract

Teaser

Mathematical models that integrate biological data can help explain complex pathogenic processes in AD, offering a coherent explanation of mechanisms behind four common AD phenotypes and the dynamic onset, progression, and prevention of AD.


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Liver transplantation in patients with primary antibody deficiency

Publication date: Available online 6 December 2016
Source:Journal of Allergy and Clinical Immunology
Author(s): Silje F. Jørgensen, Magnhild Eide Macpherson, Kristian Bjøro, Tom Heming Karlsen, Henrik M. Reims, Krzysztof Grzyb, Bjarte Fosby, Børre Fevang, Pål Aukrust, Ingvild Nordøy

Teaser

Patients with primary antibody deficiency and liver failure should be considered for liver transplantation and not rejected because of their immunodeficiency alone. Improved anti-fungal prophylaxis may further improve their prognosis.


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Sacral Stress Fracture following the Bone Union of Lumbar Spondylolysis

While 22 articles have reported on sacral stress fractures, it is a rare injury and its etiology is not well known. We present the case of a 16-year-old male who presented with low back pain in 2015. He was a high school soccer player with a previous history of a bilateral L5 lumbar spondylolysis in 2014. The patient refrained from soccer and wore a brace for six months. Two months after restarting soccer, he again complained of low back pain. After 1 year, a lumbar spine computed tomography revealed the bone union of the spondylolysis. At his first visit to our hospital, his general and neurological conditions were normal and laboratory data were within the normal range. Sacral coronal magnetic resonance imaging (MRI) of the left sacral ala revealed an oblique lineal signal void surrounding bone marrow edema. Based on his symptoms, sports history, and MRI, he was diagnosed with a sacral stress fracture. He again refrained from soccer; his low back pain soon improved, and, after 1 year, the abnormal signal change had disappeared on sacral MRI. Recurrent low back pain case caused by a sacral stress fracture occurring after the bone union of lumbar spondylolysis is uncommon.

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A novel class of somatic mutations in blood detected preferentially in CD8+ cells

Publication date: Available online 5 December 2016
Source:Clinical Immunology
Author(s): Miko Valori, Lilja Jansson, Anna Kiviharju, Pekka Ellonen, Hanna Rajala, Shady Adnan Awad, Satu Mustjoki, Pentti J. Tienari
Somatic mutations have a central role in cancer but their role in other diseases such as autoimmune disorders is poorly understood. Earlier work has provided indirect evidence of rare somatic mutations in autoreactive T-lymphocytes in multiple sclerosis (MS) patients but such mutations have not been identified thus far. We analysed somatic mutations in blood in 16 patients with relapsing MS and 4 with other neurological autoimmune disease. To facilitate the detection of somatic mutations CD4+, CD8+, CD19+ and CD4−/CD8−/CD19− cell subpopulations were separated. We performed next-generation DNA sequencing targeting 986 immune-related genes. Somatic mutations were called by comparing the sequence data of each cell subpopulation to other subpopulations of the same patient and validated by amplicon sequencing. We found non-synonymous somatic mutations in 12 (60%) patients (10 MS, 1 myasthenia gravis, 1 narcolepsy). There were 27 mutations, all different and mostly novel (67%). They were discovered at subpopulation-wise allelic fractions of 0.2%–4.6% (median 0.95%). Multiple mutations were found in 8 patients. The mutations were enriched in CD8+ cells (85% of mutations). In follow-up after a median time of 2.3years, 96% of the mutations were still detectable. These results unravel a novel class of persistent somatic mutations, many of which were in genes that may play a role in autoimmunity (ATM, BTK, CD46, CD180, CLIP2, HMMR, IKFZF3, ITGB3, KIR3DL2, MAPK10, CD56/NCAM1, RBM6, RORA, RPA1 and STAT3). Whether some of this class of mutations plays a role in disease is currently unclear, but these results define an interesting hitherto unknown research target for future studies.



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Editorial Board

Publication date: December 2016
Source:Clinical Immunology, Volume 173





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