Lingual abscess is a rare disorder, and current knowledge regarding clinical manifestations and treatment modalities has not been well established. This study presented 6 cases of lingual abscess patients between January 2012 and December 2017. There were three men and three women. Median age was 54 years. Odynophagia and local pain were the common presenting symptoms. Local trauma was the main predisposing factor of anterior abscess, while lingual tonsillitis or infected thyroglossal cyst was the predisposing factor of posterior abscess. An impending airway obstruction was identified in two patients, requiring tracheostomy. All patients achieved an excellent outcome with a combination of surgical drainage and proper antibiotics as well as using proper investigation for detecting unusual areas of lingual abscess. According to the data from the study's results and review of the relevant literature, an abscess located at the anterior two-thirds of the tongue is easy to diagnose while the posterior one-third of the tongue abscess is relative difficulty. Using contrast-enhanced computed tomography increases diagnostic accuracy, especially on the tongue base and deep space infection. The management strategies include (1) protecting the airway, (2) draining the abscess by needle aspiration or surgery, and (3) administering antibiotics early. Our series showed a superiority of surgical drainage when the patients present with marked tissue edema, deep loculated infection, and airway obstruction.
https://ift.tt/2Pbir7g
Τρίτη 6 Νοεμβρίου 2018
Lingual Abscess: Predisposing Factors, Pathophysiology, Clinical Manifestations, Diagnosis, and Management
Microscopic approach for repairing nasal septal perforations using bilateral advancement flaps
Abstract
Background
Septal perforations consist in an anatomic defect of the mucosal, cartilaginous and/or bone tissues of the nasal septum. A huge variety of approaches and techniques for nasal perforation repair have been reported.
Methodology/principal
Between January 2008 and January 2017, 38 patients were treated for nasal septal perforation in Department of Otorhinolaryngology Head and Neck Surgery, Fundación Jiménez Díaz University Hospital, Madrid, Spain. A novel approach is presented based on microscope. Septal perforation closure was performed with endonasal bilateral advancement flaps-established technique and autologous cartilage and muscle temporal fascia grafts. We performed a retrospective review of closure rates and complications.
Results
A postoperative follow-up of at least 12 months was performed in 37 patients. The mean size of perforation was 1.33 cm. After the withdrawal of the silicone splints, perforations were completely closed in all cases. However, during the follow-up, four patients resulted in a reperforation, so our closure rate was 89.19%. For all cases, symptoms related to septal defect were solved. Only one case was reported of local infections that was resolved with antibiotics in a few days.
Conclusions
Microscopic approach of septal perforation closure using bilateral advancement flaps can be an affordable technique with a high percent of success and low rate of complications.
https://ift.tt/2qx6WIw
Impact of age on elderly patients with oral cancer
Abstract
Introduction
In this study we have tried to analyze the impact of age on various clinico-pathological parameters, treatment completion and subsequent survival in older patients.
Materials and methods
This is a retrospective analysis of 140 elderly (> 65 years) patients of oral cancer operated between January 2012 and December 2013. The patients were divided into two groups based upon their age that ≤ 70 years and > 70 years.Association of distribution of various clinico-pathological factors between different groups was assessed by using Chi-square test. Survival analysis was done using Kaplan Meir analysis. Univariate and multivariate analysis were performed.
Results
The two groups had similar distribution of various clinico-pathological factors. Disease free survival for the group ≤ 70 and > 70 years was 37.6 months and 36.4 months (p < 0.594). 13.5% and 7.8% patients > 70 years and ≤ 70 years were either advised or received sub-optimal adjuvant therapy (p < 0.002).
Conclusion
There is no difference distribution of various clinico-pathological factors and survival in patients of oral cancer ≤ 70 and > 70 years of age. Age did not affect survival. Majority of patients could complete the adjuvant therapy advised. Still, significantly more number of patients > 70 years could not receive/complete appropriate adjuvant therapy. Thus treatment needs to be tailored keeping in mind the individual's performance status and the co-morbidities.
https://ift.tt/2yUYoA6
Tranexamic acid and post-tonsillectomy hemorrhage: propensity score and instrumental variable analyses
Abstract
Purpose
Although post-tonsillectomy hemorrhage occurs rarely, it can be life-threatening. Previous studies showed that tranexamic acid (TXA) had insignificant association with the rate of post-tonsillectomy hemorrhage, but those findings were limited by small sample sizes. The purpose of this study was to examine the effectiveness of TXA in preventing post-tonsillectomy hemorrhage using nationwide database.
Methods
Data of a retrospective cohort of 117,598 patients from 750 hospitals, who had undergone tonsillectomy between 2010 and 2016, were drawn from the Diagnosis Procedure Combination database in Japan and studied.
Results
Propensity score-matched analysis showed no significant differences in proportions of reoperation or blood transfusion after tonsillectomy between the treatment (TXA from the day of tonsillectomy) and control groups (1.50% vs. 1.47%, p = 0.64). Instrumental variable analysis also showed no significant differences (odds ratio, 0.98; 95% confidence interval, 0.86–1.13; p = 0.82). Higher proportions of reoperation or blood transfusion were significantly associated with male sex, older age, emergency hospitalization, prolonged anesthesia, and medium hospital volume (annual number of tonsillectomies).
Conclusions
Administration of TXA from the day of tonsillectomy is not associated with reduction in reoperation or blood transfusion rates.
https://ift.tt/2JK2Tl8
Hemorrhage within the tympanic membrane without perforation
Hemotympanum refers to both the presence of blood in the middle ear cavity and to ecchymosis of the tympanic membrane (TM), and a systematic study of intra-TM (iTM) hemorrhage without bleeding in the middle ea...
https://ift.tt/2qykO5e
In vivo Raman spectroscopic characteristics of different sites of the oral mucosa in healthy volunteers
Abstract
Objectives
Investigate the biochemistry of in vivo healthy oral tissues through Raman spectroscopy. We aimed to characterize the biochemical features of healthy condition in oral subsites (buccal mucosa, lip, tongue, and gingiva) of healthy subjects. More specifically, we investigated Raman spectral characteristics and biochemical content of in vivo healthy tissues on Brazilian population. This characterization can be used to better define normal tissue and improve the detection of oral premalignant conditions in future studies.
Materials and methods
For spectroscopic analysis a Raman spectrometer (Kaiser Optical Systems imaging spectrograph Holospec, f / 1.8i-NIR) coupled with a laser 785 nm, 60 mW was used. Raman measurements were obtained by means of an optical fiber (EMVision fiber optic probe) coupled between the laser and the spectrometer. Three spectra per site were acquired from the lip, buccal mucosa, tongue, and gingiva of ten healthy volunteers. This resulted in 30 spectra per oral sub-site and in total 120 spectra.
Results
We report detailed biochemical information on these subsites and their relative composition based on deconvolution studies of their spectra. Finally, we also report classification efficiency of 61, 83, 41, and 93% for buccal, gingiva, lip, and tongue respectively after applying multivariate statistical tools.
Conclusions
We quantitated the contribution of various biochemicals in terms of percentage, and this will enable comparison not only across anatomical sites but also across studies. Raman spectroscopy can rapidly probe tissue biochemistry of healthy oral regions. Moreover, the study suggests the possibility of using Raman spectroscopy combined with signal processing and multivariate analysis methods to differentiate the oral sites in healthy conditions and compare with pathological conditions in future studies.
Clinical relevance
The spectral characterization of the healthy condition of oral tissues by a noninvasive, label-free, and real-time analytical techniques is important to create a spectral reference for future diagnosis of pathological conditions.
https://ift.tt/2AQyrmg
Osteomyelitis des Gesichtsschädels
Laryngo-Rhino-Otol
DOI: 10.1055/a-0762-3967
© Georg Thieme Verlag KG Stuttgart · New York
Article in Thieme eJournals:
Table of contents | Full text
https://ift.tt/2QqznmL
Recurrent respiratory papillomatosis: update 2018
Purpose of review Recurrent respiratory papillomatosis (RRP) is the most common as well as the costliest benign airway neoplasm in the United States [Ivancic et al. (2018). Laryngoscope Investig Otolaryngol 3:22; Derkay (1995). Arch Otolaryngol Head Neck Surg 121:1386]. In addition, it is potentially deadly, with risk of airway obstruction as well as a 3–7% risk of malignant conversion [Schraff et al. (2004). Arch Otolaryngol Head Neck Surg 130:1039]. This review highlights exciting advancements over the past 1–2 years in scientific understanding of the pathophysiology, epidemiology, natural history, prevention, and treatment of this difficult disease. Recent findings Recent studies have yielded the following findings: The primary quality of life reduction that patients perceive is voice-related; the membranous vocal folds are the most frequently involved anatomic subsite in adult-onset RRP; there may be a correlation between laryngopharyngeal reflux, herpes simplex virus type 2, and adult-onset RRP; there has been a decline in RRP incidence in Australia following the implementation of a national vaccination program; addition of educational audiovisual aids assists in vaccine acceptance rates; preventive vaccination can be used as treatment for pediatric as well as adult RRP patients with demonstrable effects on antibody titers and reoperation rates; calreticulin-linked DNA vaccines show promise in reducing the growth rate of human papilloma virus (HPV)11 E6/E7-expressing tumors in mice; injection of bevacizumab is associated with no adverse tissue affects; systemic bevacizumab is effective as a treatment for severe uncontrolled disease; pegylated interferon treatment is effective in select severe pediatric RRP disease; and finally, increased rates of programed death 1 T-lymphocyte infiltration and programed death-ligand 1 expression are seen on both papilloma and infiltrating immune cells. Summary RRP is declining in incidence but remains a challenging disease to treat with great costs to patients, families, and the healthcare system. As the disease continues to be better understood, new frontiers are opening in treatment, particularly for severe or poorly controlled disease. Until the disease can be eradicated, it remains a vital area of research to help prevent new cases and treat afflicted patients.https://ift.tt/2RG46N8
Current approaches to instrumental assessment of swallowing in children
Purpose of the review This article reviews recent developments in the instrumental assessment of swallowing in children with a specific focus on research published between January 2017 and June 2018. Recent findings Instrumental swallowing assessments reported in the time period included: videofluoroscopic study of swallowing, digital cervical auscultation, dynamic ultrasound, high-resolution impedance manometry, nasal airflow thermistry and respiratory inductance plethysmography. Several studies were found exploring tools to objectively quantify videofluoroscopic study of swallowing data; swallowing from the mouth through to stomach was addressed including approaches to analysing mastication as well as evaluating oesophageal motility disorders. Summary Even though a vast range of instrumentation were studied, lack of clarity on clinical feasibility and objective measures that facilitate medical decision-making in practice mean further research is required to provide guidance on implementation. Promising novel approaches to aid the quantification of swallowing physiology from the mouth, pharynx and through to the oesophagus are emerging.https://ift.tt/2SOlz7k
Techniques for evaluation and management of tongue-base obstruction in pediatric obstructive sleep apnea
Purpose of review Tongue-base obstruction (TBO) is a common cause of persistent obstructive sleep apnea (OSA) after tonsillectomy and adenoidectomy in children. This review discusses available diagnostic modalities and surgical treatment options for the management of TBO. Recent findings Recently, a systematic review that included nine studies using drug-induced sleep endoscopy (DISE) in the evaluation of children with persistent OSA after tonsillectomy and adenoidectomy identified the tongue-base as the most common site of obstruction. Summary TBO is a common and correctable cause of persistent OSA in children. Diagnostic modalities include awake flexible laryngoscopy, plain neck films, DISE, and cine MRI. Because DISE and cine MRI are performed in a sleep-like state, they are fairly reliable in identifying the site of obstruction. As continuous positive airway pressure is often poorly tolerated in the pediatric population, there is considerable interest in surgical options for TBO. Depending on the location and the severity of the obstruction, interventions such as lingual tonsillectomy, posterior midline glossectomy, tongue suspension suture, epiglottopexy, hypoglossal nerve stimulation, tongue–lip adhesion, and hyoid suspension may play a role in management.https://ift.tt/2RHTSMf
Velopharyngeal incompetence: role in paediatric swallowing deficits
Purpose of review The purpose of this manuscript is to highlight the latest advances in diagnosis and management of velopharyngeal incompetence (VPI) as it pertains to swallowing deficits in children. This is timely and relevant as otolaryngologists are often amongst the first to diagnose and treat VPI. Although nasal regurgitation of a bolus is frequently transient, persistent problems can be associated with other swallowing problems and other significant medical problems. Furthermore, velopharyngeal incompetence has implications for speech production. Recent findings Persistent VPI associated with a swallowing deficit can be an isolated anomaly with or without a cleft palate or submucous cleft palate. VPI may be secondary to a cranial neuropathy, esophageal abnormality or associated with another airway anomaly, any of which may further contribute to dysphagia. Findings of additional anomalies may be suggestive of a syndrome. Workup should explore these potential causes. When velopharyngeal incompetence is associated with dysphagia, fiberoptic endoscopic evaluation of swallow (FEES) and videofluoroscopic swallow study (VFSS) can be helpful in diagnosis and management. The advantages and disadvantages of FEES and VFSS have been well delineated over the past few years. Similarly, nasopharyngoscopy and fluoroscopy are increasingly used in diagnosis and management of VPI that is associated with hypernasal resonance disorders. Summary Concurrent medical diagnoses or syndrome manifestations are often associated with or contribute significantly to the cause of dysphagia in children with VPI. As VPI can be a sign of brainstem vagal neuropathy, the clinician should investigate by imaging the CNS if other correlative symptoms of dysphagia and examination findings are present. Endoscopy is advocated for evaluation of vocal fold function. Fluoroscopy is best for further assessment of airway protection or safety of swallow. And, whenever indicated, additional workup is recommended to determine an underlying cause of the swallowing disorder.https://ift.tt/2SS5Sfd
Recurrent laryngeal nerve reinnervation: is this the standard of care for pediatric unilateral vocal cord paralysis?
Purpose of review Ansa to recurrent laryngeal nerve reinnervation, otherwise known as a nonselective laryngeal reinnervation (NSLR), is growing in popularity for the management of pediatric unilateral neuronal vocal fold movement impairment (VFMI). In this chapter, we will review the current treatment options for neuronal VFMI and role that NSLR plays in the treatment algorithm. Recent findings In 2018, Bouhabel and Hartnick published a survey of fellowship trained pediatric otolaryngologists and found an increasing comfort level with NSLR. Respondents felt that NSLR resulted in favorable subjective and objective postsurgical voice outcomes. Furthermore, NSLR may decrease the risk of aspiration in children with neuronal VFMI. Although NSLR appears to work, the voice results are not perfect for all children. Further work is being done to understand which preoperative variables, such as age, time from injury, and preop laryngeal electromyography, may predict a better voice outcome. Summary A variety of treatment options exist for unilateral neuronal VFMI. Recent data and developments demonstrate the effectiveness of reinnervation as a potential first-line surgical intervention in children with unilateral neuronal VFMI.https://ift.tt/2RHTPA3
Swallowing function in advanced age
Purpose of review To present current literature regarding swallowing function in advanced age, including healthy ageing, dysphagia and trends in multidisciplinary team service delivery. Recent findings Normative studies support swallowing efficiency but greater variability in healthy advanced age, through to 100 years old. Deviations from normative data and symptoms of dysphagia leading to aspiration or nutritional risk, imply swallowing disorder, rather than simply the ageing process. Quantitative and qualitative studies are emerging that promote management of swallow dysfunction for an ageing society, including innovative assessment, home treatment, swallowing exercise and optimized mealtimes. Summary Current literature on swallowing function in advanced age provides multidisciplinary perspectives and initiatives, with clear commitment to improving quality of life for older adults. The diversity of the older population and serious consequences of swallowing difficulties calls for routine screening tools for swallowing impairment and malnutrition risk. Representation of 'oldest old' in future normative studies is essential to guide swallowing management in adults over 85 years old.https://ift.tt/2SMJT9A
IgG4-related disease in the head and neck
Purpose of review To summarize current evidence regarding the pathophysiology, diagnostic criteria, and management of IgG4 disease in the head and neck. Recent findings The anti-CD20 antibody, rituximab is being used increasingly as a primary treatment modality in cases with a definitive diagnosis. Despite the favorable prognosis, it is now recognized that the incidence of cancer development within 3 years of diagnosis is higher than that of the general population. Summary IgG4-related disease is a sclerosing, chronic inflammatory disease, that is benign, and usually occurs in middle-aged to elderly individuals. Definitive diagnosis of IgG4-related disease requires radiological confirmation of enlargement of the affected organ, elevated serum IgG4 levels, and characteristic histopathological findings. Treatment is primarily with systemic corticosteroids or the monoclonal anti-CD20 antibody rituximab, surgical excision, or a combination of treatment modalities. Prognosis is good with complete remission in up to 90% of patients.https://ift.tt/2RHTJIH
Cervical osteophytosis and spine posture: contribution to swallow disorders and symptoms
Purpose of review The article reviews the effects of cervical osteophytosis and spine posture on swallowing, and how they can cause dysphagia. Recent findings Cerivical osteophytosis which is a bony overgrowth of the cervical spines, it affects the swallowing through different mechanisms, including direct mechanical compression of the pharynx and esophagus, disturbances of normal epiglottic tilt over the inlet of the larynx by the osteophytes at C3–C4 level, inflammatory reactions in the tissues around the esophagus and cricopharyngeal spasm. Also, cervical spine posture in normal individuals could affect the swallowing mechanism by disturbance of the sphincteric action of the larynx and upper esophageal sphincter. Summary Cervical osteophytosis and abnormal cervical curvature may be overlooked by the Otolaryngologists as causes of swallowing disorders. The diagnosis is usually confirmed by radiologic study for the cervical spine. Cervical abnormality should be kept in mind while we are investigating patients with swallowing problem, and postural modification may help in treatment of such cases.https://ift.tt/2SRPVWH
Update on sinus disease in children with cystic fibrosis: advances in treatment modalities, microbiology, and health-related quality-of-life instruments
Purpose of review There is a lack of consensus with regards to the diagnosis and treatment of sinus disease in children with cystic fibrosis. Here, we review literature from the past 18 months in order to highlight the way forward in this contentious field. Recent findings Most of the literature (from the past 18 months) on sinus disease in pediatric cystic fibrosis focused on treatment approaches, bacteriology and immunology, and health-related quality-of-life (HRQOL) instruments. Quality studies have demonstrated that functional endoscopic sinus surgery (FESS) is as safe in children with or without cystic fibrosis; that the microbiology of the paranasal sinus in children with cystic fibrosis is different than that of their lungs; and, that HRQOL instruments may prove useful in determining sinonasal disease severity in children with cystic fibrosis. Summary Medical and surgical approaches appear to be viable in the treatment of sinonasal disease in pediatric cystic fibrosis; the microbiology and immunology of pediatric cystic fibrosis is proving more complex and nuanced than initially believed; and, HRQOL instruments show promise in reconciling differences between observable and clinically relevant sinus disease in pediatric cystic fibrosis patients.https://ift.tt/2RHTCgf
High-resolution manometry: what about the pharynx?
Purpose of review High-resolution pharyngeal manometry (HRPM) is a well tolerated, catheter-based, method for recording the pressures and bolus flow generated by the pharyngeal muscles during swallowing. Despite a body of published evidence and a critical mass of investigators in the field, there is a lack of consensus surrounding what biomechanical phenomena to measure. The purpose of this review is to provide some insights into the information on swallowing physiology that can be gathered using HRPM. Recent findings HRPM literature has focused on measuring biomechanical phenomena that may be relevant to measure in relation to dysphagia research. This review focuses on the measurement of pharyngeal luminal occlusive forces, intrabolus distension pressure, bolus presence and bolus flow timing as key features of pharyngeal swallowing that require measurement and allow for derivation of the Swallow Risk Index, a global measure of swallow function indicative of swallowing functional reserve. Summary HRPM allows objective derivation of measures of swallow function that may have value for diagnosis and research in relation to swallowing disorders. HRPM has demonstrated clinical applicability in specific patient populations and offers unique advantages that compliment current assessment methods.https://ift.tt/2SS50re
Vocal fold nodules in children
Purpose of review Vocal nodules are a common presentation in children, representing the most common cause of dysphonia. Recent findings Children with siblings, ADHD, and of male sex are most likely to be affected. Female children, however, tend to have more likely progression into adolescence. Quality-of-life indices can aid in screening for vocal nodules whereas stroboscopy, and possibly, ultrasound are required for definitive diagnosis. Summary Management has not significantly changed over time and should begin with conservative behavioral and environmental modifications along with voice therapy in those more severely impacted. Though immediate outcomes vary somewhat depending on management direction, the overall prognosis seems to be good even with lack of intervention. It is most critical to ensure a definitive diagnosis, and offer management therapies that are appropriate for the level of impact the vocal nodules have on communication and voice production in the child.https://ift.tt/2RHTu0f
Laryngopharyngeal reflux disease: clinical presentation, diagnosis and therapeutic challenges in 2018
Purpose of review To review the recent literature on presentation, diagnosis and treatment of laryngopharyngeal reflux. Recent findings Patients with laryngopharyngeal reflux have a higher risk for gastroesophageal reflux and respiratory-related diseases. Many symptoms and findings are underestimated, contributing to the inconclusive results of many therapeutic trials. Additionally, little significance is given to nonacid and mixed refluxates, although a significant prevalence. The association between symptoms, signs, impedance-pH studies and pepsin detection could be the most accurate way for a clear diagnosis. 'Reflux profiling' is also important for the administration of a personalized treatment based on diet, proton pump inhibitors, alginate, magaldrate and other second-line drugs. There are only a handful of studies focusing on the addition of alginate or magaldrate to the treatment of laryngopharyngeal reflux, although their contribution has extensively been demonstrated. Summary Diagnosis remains controversial despite improvement in impedance and availability of pepsin detection in daily practice. With recent studies exhibiting a significant prevalence of nonacid or mixed refluxes, the addition of alginate or magaldrate to proton pump inhibitors should be considered. Future studies are needed to assess these new therapeutic schemes in moderate and severe laryngopharyngeal reflux.https://ift.tt/2SRejYn
Tympanostomy tube otorrhea in children: prevention and treatment
Purpose of review One in two children treated with tympanostomy tubes, experience episodes of otorrhea whilst their tubes are in place. In this review, we present the results of the most recent publications on prevention and treatment of tympanostomy tube otorrhea (TTO). Recent findings Recent systematic reviews on water precautions for children with tympanostomy tubes support the American Academy of Otolaryngology – Head and Neck Surgery guideline recommendation against such preventive measures as there is no evidence that it protects against TTO. Studies on tympanostomy tube design and material suggest that silicone tubes have a lower TTO risk and that biofilms appear to be mainly located in the perpendicular junction of the T-tubes and the round rims of the Paparella-type tubes. Another study shows that the biofilm-component DNAB-II protein is present in otorrhea of half of children with TTO. Targeting this protein could lead to a collapse of the biofilm structure and as such a potential new treatment for chronic TTO. New systematic reviews show that antibiotic eardrops are the most effective first-line treatment of acute TTO and suggest that an antibiotic–corticosteroid combination is more effective than antibiotic only. Although in many countries, quinolone eardrops are the preferred choice because of being non-ototoxic, one study found a higher risk of persistent perforation after tube extrusion in children treated with quinolone eardrops as compared with children treated with aminoglycoside eardrops. Summary Recent evidence confirms that water precautions for children with tympanostomy tubes are not effective in preventing TTO. Antibiotic–corticosteroid eardrops are the most effective treatment of acute TTO.https://ift.tt/2RHTo8T
Prospective evaluation of psychological burden in patients with oral cancer
The high morbidity and mortality that is associated with oral cancer places a huge psychological burden on patients. The purpose of this prospective study was to evaluate levels of depression, anxiety, and stress, at three time points using DASS-21 (Depression, Anxiety and Stress Scale-21). We also compared DASS-21 with HADS (Hospital Anxiety and Depression Scale). A total of 111 patients were enrolled and 75 of them completed the questionnaires at diagnosis, one month after treatment, and three months after discharge.
https://ift.tt/2PePK9B
Probiotics as treatment for food allergies among pediatric patients: a meta-analysis
The burden of disease of food allergy is increasing worldwide. The standard of management is allergen avoidance and symptomatic treatment. Probiotics have been proposed to be beneficial for treatment and preve...
https://ift.tt/2F3TeqD
Revision Parathyroidectomy Using 4D CT for Localization
Finding a tiny tumor in a field of scar or localizing an ectopic parathyroid before primary surgery is like searching...https://ift.tt/2PMh924
Otologist-Neurotologist Joins Memorial Hermann and UTHealth
Aniruddha ("Alok") Patki, MD, has joined the Department of Otolaryngology-Head and Neck Surgery as assistant professor of otology-neurotology at McGovern...https://ift.tt/2RCyZ4R
Meet Amy Martin, MSN, APRN, ACNP-BC, CCRN, Newest Member of the ORL Team
Amy Martin chose nursing as a career when she was 8 years old, dressed as a pumpkin. "It was Halloween...https://ift.tt/2D6uZph
Two ORL Specialists Named Super Doctors Rising Stars
William Yao, MD, and Kunal Jain, MD, were named by their peers as Super Doctors Rising Stars® in Texas. Following...https://ift.tt/2PhyxMZ
Differenzialdiagnostik von Lipödem und Lymphödem
Zusammenfassung
Das Lipödem ist eine Erkrankung des subkutanen Fettgewebes der Extremitäten, die nahezu ausschließlich Frauen im postpubertären Alter betrifft. Charakteristisch ist die Kombination aus disfigurierender Fettgewebshypertrophie der proximalen Extremitäten, zunehmender Schmerzhaftigkeit und Hämatomneigung. Lymphödeme können primär oder sekundär bei beiden Geschlechtern auftreten. Typisch ist das Missverhältnis von Lymphlast und Kapazität der lymphatischen Gefäße. Stets sind die distalen Abschnitte des Körpers stärker betroffen als die proximalen. Zu Beginn ist das Lymphödem schmerzlos, im fortgeschrittenen Stadium kann ein Spannungsschmerz hinzutreten. Die Kombination beider Erkrankungen ist beschrieben, jedoch ist das Lipödem nicht als Ursache eines Lymphödems anzusehen, ganz im Gegenteil zur zentralen Adipositas. Diese erhöht das Risiko für Lymphödeme beträchtlich. Die Differenzierung der Diagnosen ist für eine sinnvolle Therapieplanung essenziell.
https://ift.tt/2PhybG9
Epidemiologie des nichtkleinzelligen Lungenkarzinoms in Deutschland
Zusammenfassung
Bei etwa 80 % der bösartigen Lungentumoren handelt es sich um nichtkleinzellige Lungenkarzinome (NSCLC). Im Jahr 2014 wurden in Deutschland rund 43.000 Neuerkrankungen am NSCLS diagnostiziert, davon etwas mehr als ein Drittel bei Frauen (15.000). Adeno- und Plattenepithelkarzinome sind die beiden am häufigsten vorkommenden Subtypen. Der Anteil der Adenokarzinome steigt in den letzten Jahren bei beiden Geschlechtern an − ein Trend, der auch international beobachtet werden kann. Als wichtigster Risikofaktor gilt das Tabakrauchen, wobei Adenokarzinome häufiger bei Nichtrauchern auftreten als andere histologische Subtypen. Daher spielen hier wahrscheinlich andere Risikofaktoren wie Radon- oder Feinstaubbelastung − relativ gesehen − eine größere Rolle. Zwischen den Subtypen des NSCLS finden sich teilweise deutliche Unterschiede in der Verteilung der Tumorstadien und in den Überlebensraten.
https://ift.tt/2PDboUz
Lebensqualität von Überlebenden eines nichtkleinzelligen Lungenkarzinoms
Zusammenfassung
Hintergrund
Eine Erkrankung an nichtkleinzelligem Lungenkarzinom (NSCLC) bringt eine Vielzahl von körperlichen, psychischen und sozialen Belastungen mit sich. Diese können auch noch lange Zeit nach der Erkrankung Auswirkungen auf die Lebensqualität der Betroffenen haben.
Ziel
Es erfolgt eine Beschreibung von Faktoren, die mit der Lebensqualität von NSCLC-Überlebenden assoziiert sind sowie eine Übersicht über erforderliche Bestandteile der Nachsorge und Möglichkeiten von Survivorship-Care-Plänen.
Methoden
Ein narratives Literaturreview wurde auf der Basis einer PubMed-Recherche durchgeführt.
Ergebnisse
NSCLC-Überlebende haben häufig persistierende Symptome und psychosoziale Auswirkungen der Erkrankung und Therapie. Besonders häufig beeinträchtigte Bereiche der Lebensqualität sind die körperliche und Rollenfunktion. Faktoren, die sich auf die Lebensqualität auswirken umfassen u. a. physische Symptome (Atemnot, Fatigue, Schmerzen, Husten, Schlafstörungen), Therapie, Rezidive/Zweittumoren, Komorbiditäten, psychische Belastung (Ängstlichkeit, Depressivität) sowie soziodemografische Faktoren (Alter, Geschlecht, Alleinleben). Eine patientenzentrierte Nachsorgeplanung sollte möglichst frühzeitig den Zugang zu supportiven Therapien, palliativmedizinischer Intervention, psychosozialer Unterstützung, Unterstützung zur Lebensstiländerung und regelmäßigen Nachsorgeuntersuchungen sicherstellen. Eine besondere Bedeutung kommt der Entwicklung und Implementierung von Survivorship-Care-Plänen zu, die darauf abzielen, die Versorgungskontinuität zu gewährleisten sowie Langzeiteffekten und Spätfolgen vorzubeugen oder diese zu lindern.
Schlussfolgerung
NSCLC-Überlebende haben vielfältige Einschränkungen der Lebensqualität. Patientenzentrierte, strukturierte Versorgungsmodelle könnten einen wichtigen Beitrag zur langfristigen Erhaltung ihrer Lebensqualität leisten.
https://ift.tt/2RyGiL0
Psychoonkologische Versorgung von Hirntumorpatienten
Zusammenfassung
Hintergrund
Die Diagnose Hirntumor löst nicht nur beim Betroffenen selbst, sondern auch bei den Angehörigen existenzielle Ängste und größte Unsicherheit aus und ist eine enorme Herausforderung für alle Beteiligten.
Ziel
Psychoonkologische Screeningverfahren und Ergebnisse werden diskutiert sowie Interventionen für Hirntumorpatienten vorgestellt.
Material und Methoden
Nach einer Literaturrecherche und Diskussion der besonderen Belastung von Hirntumorpatienten und ihren Angehörigen werden psychoonkologische Interventionsmöglichkeiten vorgestellt.
Ergebnisse
Die Mehrheit der Patienten fühlt sich zu Erkrankungsbeginn überschwellig belastet. Im längerfristigen Krankheitsverlauf treten bei ca. 20 % Depressionen auf, wobei Patienten mit psychiatrischen Vorerkrankungen häufiger betroffen sind. Als psychoonkologische Screeningverfahren können die Hospital Anxiety and Depression Scale (HADS) oder das Distress-Thermometer (DT) eingesetzt werden. Bei überschwelligen Werten in der HADS oder DT ≥ 5 und emotionale Probleme ≥2 sollte ein psychoonkologisches Gespräch erfolgen. Insbesondere DKG-zertifizierten neuroonkologischen Tumorzentren halten ein psychoonkologisches Gesprächsangebot für Patienten und Angehörige vor. Die Angebote sollten zeitnah und niederschwellig sein, um die psychosozialen Belastungen zu reduzieren, die Lebensqualität zu erhöhen und subsyndromale Krankheitssymptome zu erkennen.
Diskussion
Spezifische Interventionen für Hirntumorpatienten gibt es bislang kaum. Wirksame psychoonkologische Interventionen sind Psychoedukation, psychotherapeutische Gespräche und Entspannungsverfahren. Zusätzlich sollten die Betroffenen zu körperlicher Aktivität und kultureller und gesellschaftlicher Teilhabe ermutigt werden.
https://ift.tt/2PO0s6E
Neue Aspekte in der Therapie von Schilddrüsenkarzinomen
Zusammenfassung
Während die chirurgische Therapie beim Schilddrüsenkarzinom v. a. in frühen Stadien eine wichtige Rolle einnimmt, wird im palliativen Setting ein multimodaler Ansatz verfolgt, der neben der klassischen Chemotherapie v. a. die Therapie mit Tyrosinkinaseinhibitoren beinhaltet. Es erfolgt eine Analyse der auf dem ASCO-Kongress 2018 präsentierten Studien zum Schilddrüsenkarzinom. Es wurden v. a. Studien zur Therapie des radiojodrefraktären differenzierten Schilddrüsenkarzinoms, des anaplastischen Schilddrüsenkarzinoms sowie zur Immuntherapie ausgewählt und analysiert. Klinisch und präklinisch relevante Studien werden in diesem Review vorgestellt und kritisch interpretiert.
https://ift.tt/2SJQMsp
Highlights der ASCO Jahrestagung 2018 zur Immuntherapie von Kopf-Hals-Tumoren
Zusammenfassung
Hintergrund
In der Kopf-Hals-Onkologie gewinnen immuntherapeutische Konzepte an Bedeutung und wurden bei dem diesjährigen amerikanischen Krebskongress in relevanter Anzahl präsentiert.
Ziel der Arbeit
In dieser Arbeit sollen die interessantesten Studien und Studienergebnisse der Immuntherapie von Kopf-Hals-Tumoren zusammengefasst werden.
Material und Methoden
Alle ASCO Abstracts und Präsentationen zur Immuntherapie von Kopf-Halstumoren wurden beurteilt und die interessantesten Studien aufgearbeitet.
Ergebnisse
Auch wenn unmittelbar praxisverändernde Ergebnisse großer Phase-III-Studien ausblieben, wurden einige nennenswerte Ansätze und neue Erkenntnisse für die Immuntherapie von Kopf-Hals-Tumoren präsentiert. Neoadjuvante Immuntherapiestudien, Ergebnisse zur Immuntherapie im Alter, zum prognostischen Einfluss immunvermittelter Nebenwirkungen und neue Immuntherapiekombinationen werden hier zusammengefasst.
Schlussfolgerung
Die Rolle der Immuntherapie erreicht in der Behandlung von Kopf-Hals-Tumoren einen zunehmenden Stellenwert. Viele wegweisende Studien befinden sich derzeit in der Durchführung, Auswertung oder Planung.
https://ift.tt/2zvZQbo
MERRF syndrome (Myoclonic Epilepsy with Ragged Red Fibres) presenting with cervicothoracic lipomatosis
Publication date: Available online 5 November 2018
Source: European Annals of Otorhinolaryngology, Head and Neck Diseases
Author(s): F. Carré, R. Hervochon, C. Foirest, F. Tankéré
Abstract
Introduction
Patients with MERRF syndrome (Myoclonic Epilepsy with Ragged Red Fibres) usually present with encephalomyopathy. However, progressive, recurrent cervicothoracic lipomatosis may be rarely observed.
Case report
The authors report 4 cases of MERRF syndrome associated with lipomatosis. In 3 patients, the diagnosis of MERRF syndrome was established on the basis of the clinical features of the lipomas and clinical interview revealing a personal or family history of lipomas and myopathy.
Discussion
In the presence of extensive spinal lipomatosis, the presence of other clinical signs of MERRF syndrome in the patient or the patient's family must be investigated. A diagnosis of MERRF syndrome can guide appropriate genetic counselling.
https://ift.tt/2AO43Jj
Associated Injuries are Frequent and Severe Among Geriatric Patients with Zygomatico-Orbital Fractures
Publication date: Available online 5 November 2018
Source: Journal of Oral and Maxillofacial Surgery
Author(s): Miika Toivari, Johanna Snäll, Anna Liisa Suominen, Satu Apajalahti Consultant, Christian Lindqvist, Hanna Thorén
Abstract
Purpose
Associated injuries (AIs) are hypothesized to be frequent in geriatric zygomatico-orbital (ZMO) fractures. The study aim was to determine the relationship between ZMO fractures and AIs in geriatric patients in comparison to younger adults.
Materials and methods
A retrospective case-control study was carried out on geriatric patients aged 65 years or more (n = 93) and younger adults aged 20 to 30 years (n = 68) diagnosed with pure unilateral ZMO fractures. The main exposure was age, the primary outcome was AI outside the face, and secondary outcomes were the type and severity of AI, ocular injuries, restriction of mandible movement, and ZMO buttress asymmetry. The confounding variables were gender, trauma mechanism, type of ZMO fracture, and dislocation. Statistical analyses included x2 tests, risk evaluation with 2 x 2 tables, and logistic regression analysis.
Results
AIs outside the face, and particularly brain injuries, were significantly more frequent among the elderly patients than the controls (P < .001). The significant predictors of AIs outside the face were a fall from height (66.7%), MVAs (66.7%), and the absence of ZMO dislocation (59.5%) (P < .001). The adjusted risk of brain injury was 2.5-fold in the absence of dislocation. The geriatric patients had an over five-fold higher risk of brain injuries compared to the younger controls (P = .003).
Conclusions
AIs in general, and particularly brain injuries, are frequent in geriatric ZMO fractures. Intracranial injuries should be rolled out, particularly in geriatric patients diagnosed with a non-dislocated ZMO fracture.
https://ift.tt/2Qi7HR4
Salvage Chemoradiation Therapy for Recurrence After Radical Surgery or Palliative Surgery in Esophageal Cancer Patients
Interventions: Radiation: Involved field irradiation; Radiation: Elective field irradiation; Drug: Paclitaxel; Drug: Lobaplatin; Drug: PEG-rhG-CSF
Sponsors: Chinese Academy of Medical Sciences; The First Affiliated Hospital with Nanjing Medical University; Tianjin Medical University Cancer Institute and Hospital; Anyang Cancer Hospital; Fujian Cancer Hospital; Beijing Cancer Hospital; Hebei Medical University Fourth Hospital
Recruiting
https://ift.tt/2PPJPHL
SHR-1316 in Combination With Chemotherapy in Patients With Esophageal Squamous Cell Cancer
Interventions: Drug: Irinotecan liposome; Drug: SHR-1316; Drug: Fluorouracil
Sponsor: Jiangsu HengRui Medicine Co., Ltd.
Recruiting
https://ift.tt/2RAyM2b
Study of the Efficacy of Lenvatinib Combined With Denosumab in the Treatment of Patients With Predominant Bone Metastatic Radioiodine Refractory Differentiated Thyroid Carcinomas
Intervention: Drug: Lenvatinib + Denosumab
Sponsor: Centre Leon Berard
Not yet recruiting
https://ift.tt/2PGmKHm
Stretching of the Diaphragm and Cervical Impulse Technique and Its Possible Spirometric Changes
Interventions: Procedure: Stretching the diaphragm muscle; Procedure: Impulse technique in rotation of cervical level 3 and 4; Procedure: Combined technique of diaphragm muscle stretch and cervical rotation impulse technique level 3 and 4
Sponsor: Cardenal Herrera University
Not yet recruiting
https://ift.tt/2RFe1Tc
Lidocaine to Prevent Cough and Hemodynamic Changes in Tracheal Extubation
Interventions: Drug: Lidocaine; Drug: Saline Solution
Sponsor: Hospital Fernandez
Not yet recruiting
https://ift.tt/2PHjCuz
The characteristics and pivotal roles of triggering receptor expressed on myeloid cells-1 in autoimmune diseases
Publication date: Available online 5 November 2018
Source: Autoimmunity Reviews
Author(s): Sheng Gao, Yongdong Yi, Guojun Xia, Chengyang Yu, Chenmin Ye, Fuyang Tu, Leibin Shen, Wenqian Wang, Chunyan Hua
Abstract
Triggering receptor expressed on myeloid cells-1 (TREM-1) engagement can directly trigger inflammation or amplify an inflammatory response by synergizing with TLRs or NLRs. Autoimmune diseases are a family of chronic systemic inflammatory disorders. The pivotal role of TREM-1 in inflammation makes it important to explore its immunological effects in autoimmune diseases. In this review, we summarize the structural and functional characteristics of TREM-1. Particularly, we discuss recent findings on TREM-1 pathway regulation in various autoimmune diseases, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), inflammatory bowel disease (IBD), type 1 diabetes (T1D), and psoriasis. This receptor may potentially be manipulated to alter the inflammatory response to chronic inflammation and possible therapies are explored in this review.
https://ift.tt/2D68LDK
Target Therapy in SLE
Publication date: Available online 5 November 2018
Source: Autoimmunity Reviews
Author(s): Matthias Schneider
Abstract
The intention of this paper is to review actual developments in target therapy in SLE. Target therapy includes both the objective of intervention and the aim of treatment. The objective should be linked to the pathophysiologic process of SLE; the aim has to be in any case an improved outcome.
The current therapeutic in SLE is guided mostly by secondary prevention. In SLE, besides a BASIC concept with antimalarials, bone and sun protection, vaccination and cardiovascular risk minimising, treatment waits for new manifestations to be started to prevent secondarily damage. With the new treatment target remission, treatment should aim at ensuring long-term survival, preventing organ damage and optimizing health-related quality-of-life by controlling disease activity and minimising comorbidities and drug toxicity. First examples show that some patients are in remission and that those patients have a better outcome. But for treat-to-target a strategy needs to be developed that needs to be evaluated.
https://ift.tt/2Pf0EvS
Dampness and mold hypersensitivity syndrome and vaccination as risk factors for chronic fatigue syndrome
Publication date: Available online 5 November 2018
Source: Autoimmunity Reviews
Author(s): Tamara Tuuminen, Tiina Jääskeläinen, Kirsi Vaali, Olli Polo
https://ift.tt/2D3nFdY
Adrenal Insufficiency in Systematic Lupus Erythematosus (SLE) and Antiphospholipid Syndrome (APS): A Systematic Review
Publication date: Available online 5 November 2018
Source: Autoimmunity Reviews
Author(s): Keum Hwa Lee, HyunJeong Lee, Cheol-hun Lee, Jin Yeong Kim, Jong Min Kim, Se Seung Kim, Seungmin Jeong, In Sung Hwang, Namsoo Kim, Na Eun Kim, Soogeun Shin, Dongkwan Shin, Joo Sang Song, Dong Hyun Shin, Jung Dong Kim, Jeehoon Kim, Yong Seok Lee, Hansung Kang, Dong Ha Kim, So Hyun Moon
Abstract
Background: Adrenal insufficiency (AI) is associated with high morbidity and mortality. The aim of this systematic review was to enhance diagnostic approaches and summarize therapeutic strategies in the management of AI in patients with an underlying prior disease history.
Methods: A literature search of PubMed and EMBASE databases was performed and 91 publications containing 105 cases were included for the final analysis.
Results: The following frequency of clinical signs and symptoms was noted: abdominal pain (39.04%) was the leading symptom, followed by fever (33.33%), vomiting (23.81%), and nausea (19.05%). Antiphospholipid syndrome (APS) was present in 73%, systematic lupus erythematosus (SLE) in 17% of the patients, while 2% had a diagnosis of both, SLE and APS. ACTH stimulation test (ACTHst) was performed in 18% of cases and 76.6% of them were unresponsive towards stimulation. Variable treatment approaches were used: hydrocortisone was most commonly used (38.09%), followed by fludrocortisone (26.67%), prednisolone (20.00%) and volume replacement treatment (11.43%), respectively.
Conclusions: This analysis highlights the importance of an early diagnosis and initiation of therapeutic management when AI is suspected. In line, signs and symptoms related to autoimmune diseases in patients with AI should be reviewed crtitically.
https://ift.tt/2P9niWy
Liver-Associated Immune Abnormalities
Publication date: Available online 5 November 2018
Source: Autoimmunity Reviews
Author(s): Eyal Grunebaum, Yaron Avitzur
Abstract
In recent years, the cross talk between the liver and the immune system is being uncovered, in part by studying liver involvement in primary immune deficiencies (PID) and in part by investigating the alterations of the immune system following orthotic liver transplantation (OLT). Here we review some of the reciprocal interactions between the liver and the immune system. Patients with PID, particularly those involving inherited defects in T and B cells or innate immunity are prone to infections and inflammatory responses that often involve the liver. Omenn's syndrome, familial hemophagocytic lymphohistiocytosis, AIRE, FOXP3 and CD25 deficiencies, common variable immunodeficiency, CD40 ligand deficiency, chronic granulomatous disease and autoimmune lymphoproliferative syndrome are some of the notable PID associated with typical hepatobiliary abnormalities. Knowledge gained from studying these PID together with laboratory and histological evaluations can assist in managing PID-associated liver dysfunction. The liver itself also has important effects on the immune system, as evident from the growing experience with patients surviving OLT. Up to 40% of pediatric patients who receive OLT suffer from post transplantation allergy, autoimmunity, and immune-mediated disorders (PTAA). PTAA is more common after liver and heart transplantations than kidney transplantations. Potential contributing factors for the increased frequency of PTAA after OLT include the age of the patients, the prolonged use of tacrolimus and the reduced regulatory immune function with a shift towards a TH2 immune response. Better understanding of the mechanisms leading to the development of PTAA after OLT will also improve the management of these conditions.
https://ift.tt/2D9w8g3
Arthritis in primary Sjögren's syndrome: Characteristics, outcome and treatment from French multicenter retrospective study
Publication date: Available online 5 November 2018
Source: Autoimmunity Reviews
Author(s): Adrien Mirouse, Raphaèle Seror, Eric Vicaut, Xavier Mariette, Maxime Dougados, Anne-Laure Fauchais, Alban Deroux, Azeddine Dellal, Nathalie Costedoat-Chalumeau, Guillaume Denis, Jérémie Sellam, Jean-Benoît Arlet, Christian Lavigne, Geoffrey Urbanski, Dominique Fischer-Dumont, Abdou Diallo, Olivier Fain, Arsène Mékinian, on behalf of Club Rhumatismes Inflammation and SNFMI
Abstract
Objective
To describe the characteristics and the outcome of primary Sjögren Syndrome (pSS) associated arthritis and to compare the efficacy of different therapeutic regimen.
Methods
We conducted a retrospective study using Club Rhumatisme and Inflammation (CRI) and French Internal Medicine Society (SNFMI) networks. All patients with a diagnosis of pSS and at least one episode of clinical and/or echographic synovitis were included. Patients with synovitis (cases) were compared to pSS patients without synovitis (controls).
Results
57 patients (93% women) were included with a median age of 54 years [45–63]. Patients with synovitis had more frequently lymph node enlargement (12.3% vs. 1.8%, p = .007) and a higher ESSDAI score (8 [[6], [7], [8], [9], [10], [11], [12]] vs. 2 [[1], [2], [3], [4]], p < .0001). There was no difference concerning CRP levels, rheumatoid factor and cyclic citrullinated peptide (CCP)-antibodies positivity. Among 57 patients with synovitis, 101 various treatment courses have been used during the follow-up of 40 [22.5–77] months. First treatment course consisted in steroids alone (3.5%), steroids in association (79%) with hydroxychloroquine (HCQ) (49%), methotrexate (MTX) (35%), rituximab (RTX) (5.3%) or other immunosuppressive drugs (7%). HCQ, MTX, and RTX were associated with a significant reduction of tender and swollen joint count, and a significant steroids-sparing effect. No difference could be shown for the joint response between these treatment regimens.
Conclusion
pSS articular manifestations may include synovitis which could mimic rheumatoid arthritis but differ by the absence of structural damage. Even if the use of HCQ, MTX, and RTX seem to be effective for joint involvement, the best regimen remains to be determined.
https://ift.tt/2PhY7kY
VALIDATION and meta-analysis of kappa index biomarker in multiple sclerosis diagnosis
Publication date: Available online 5 November 2018
Source: Autoimmunity Reviews
Author(s): Paloma Menéndez-Valladares, Maria Isabel García-Sánchez, Myriam Adorna Martínez, Jose Luis García De Veas Silva, Carmen Bermudo Guitarte, Guillermo Izquierdo Ayuso
Abstract
The importance of studying the cerebrospinal fluid (CSF) in Multiple Sclerosis (MS) is included in the last McDonald criteria (2018). The study of oligoclonal IgG bands (OCGB) assay is strongly recommended in some situations in which MS diagnosis is uncertain. New biomarkers are developed during the last years. Kappa free light chains (FLC) can predict conversion to MS in patients with Clinically Isolated Syndrome (CIS).
The aim of this work is to validate the clinical usefulness of the kappa index, and to establish the actual state of knowledge for kappa index as a biomarker of conversion in CIS patients by a meta-analysis. Kappa index seems more relevant than the mere concentration of kappa FLC in CSF.
In the validation study, 334 patients were included; in which 100 were CIS patients. Patients were divided in two groups according kappa index cut-off of 10.62: group 1 (kappa index>10.62); group 2 (kappa index<10.62). In group 1 more patients had positive OCGB, IgG index>0.56 and fulfilled magnetic resonance imaging (MRI) criteria. In contrast, in group 2, more patients showed negative OCGB, IgG index<0.56 and did not fulfilled MRI criteria. While 67.6% of patients from group 1 converted to MS, only 12.5% of patients from group 2 converted to MS. An HR of 6.02 was obtained in the Kaplan-Meier analysis.
In the meta-analysis, 8 studies were finally included. The SROC curve revealed a high diagnostic performance for the kappa index as a MS diagnostic biomarker. Despite heterogeneity found between studies, the global OR revealed a good discriminatory capacity of kappa index.
In conclusion, kappa index has a great clinical sensitivity and specificity as a support in MS diagnosis. High kappa index increase the probability of CIS to MS conversion. A correct sample processing in the preanalytical stage is key to obtain right results and to allow establishing comparison between laboratories.
https://ift.tt/2D4C7Tg
X chromosome and female bias in systemic lupus erythematosus: Focus on population-based evidence
Publication date: Available online 5 November 2018
Source: Autoimmunity Reviews
Author(s): Dongsheng Di, Hui Yuan, Linlin Zhang, Xiaoxiao Wu, Haifeng Pan, Dongqing Ye, Ruixue Leng
https://ift.tt/2D1Pi7r
Hemorrhage within the tympanic membrane without perforation
Abstract
Background
Hemotympanum refers to both the presence of blood in the middle ear cavity and to ecchymosis of the tympanic membrane (TM), and a systematic study of intra-TM (iTM) hemorrhage without bleeding in the middle ear cavity has not been conducted. The goals of our study were to analyze the causes of iTM hemorrhage without TM perforation or bleeding in the middle ear cavity, and to demonstrate the clinical characteristics of the disease.
Methods
This Case series study included five patients with iTM hemorrhage between August 2014 and August 2017. An iTM hemorrhage was diagnosed when otoendoscopic examination demonstrated minor bleeding behind the intact TM, a hemorrhage was observed between the TM annulus and the epidermal layer, and temporal bone computed tomography revealed thickening of the TM without soft tissue density within the tympanic cavity or temporal bone fracture. Initial symptoms, and serial findings of otoendoscopy and pure tone audiometry (PTA) were investigated.
Results
iTM hemorrhage developed due to blunt head trauma in two patients, descent barotrauma during scuba diving in two patients, and spontaneous epistaxis in one patient. Otalgia and ear fullness were the most common symptoms, but PTA showed no or minimal conductive hearing loss in all patients.
Conclusions
An iTM hemorrhage may develop after blunt head trauma, barotrauma due to scuba diving, or spontaneous epistaxis; otological symptoms included otalgia, tinnitus, and aural fullness. An iTM hemorrhage resolved spontaneously without specific treatment, usually within 1 month.
https://ift.tt/2zvJ2kR
Clinical features of laryngeal myasthenia gravis: A case series
Publication date: Available online 5 November 2018
Source: American Journal of Otolaryngology
Author(s): XiangLi Yang, Liu Niu, ChunWei Yang, Lin Wang, JiXiang Liu, GuoYing He
Abstract
Background
Myasthenia gravis (MG) is an autoimmune disease. Dysarthria, dysphagia, and difficulty swallowing as exclusive initial and primary complaints in MG (laryngeal MG) are rare and seldom reported.
Methods
Here we review and analyze the largest series of laryngeal MG patients.
Results
A total of 30 patients with laryngeal MG as primary manifestation were found in 20 case reports/series. Dysarthria was the most frequent primary symptom (14/30), followed by dysphagia (11/30), slurred speech (4/30) and dysphonia (1/30). Sixty-three percent visited the otolaryngology department first. Only 23.33% of patients were diagnosed with MG at the first clinic visit. Forty-five percent laryngeal MG patients were acetylcholine receptor (AChR) antibody positive, 52.9% showed decremental response in the repetitive nerve stimulation (RNS) test, and 92.6% were positive in the neostigmine/edrophonium test. Fluctuating weakness was examined in 16 of 30 patients and observed in 14/16 patients.
Conclusion
Laryngeal MG is a rare and possibly under-diagnosed condition. The patients can present with dysarthria, dysphagia, or difficulty swallowing. Fluctuation in severity of disease by neostigmine/edrophonium test is a typical feature for MG patients. AChR antibody and RNS tests should be included to evaluate the pathologic changes in the neuromuscular junction.
https://ift.tt/2D5xeJu
Sonographische Analyse des Schluckakts im zervikalen Ösophagusabschnitt
Zusammenfassung
Hintergrund und Fragestellung
Die Dysphagie ist ein häufig in verschiedenen Fachbereichen von Patienten benanntes Symptom, bei dem sich die Frage nach der anzustrebenden Diagnostik stellt. Neben der HNO-ärztlichen Spiegeluntersuchung stehen die derzeitigen Goldstandards Videofluoroskopie und fiberoptisch-endoskopische Evaluation des Schluckens (FEES) zur Verfügung. Häufig kommt im klinischen Alltag der Ultraschall zum Einsatz, dessen Anwendungsmöglichkeit im Hinblick auf die Schluckdiagnostik zu hinterfragen ist.
Material und Methoden
Zwischen April 2012 und Februar 2014 wurden 81 Probanden (zwischen 19 und 66 Jahren) ohne Hinweise auf eine Schluckstörung sonographisch untersucht. Es wurden die Darstellbarkeit anatomisch am Schluckakt beteiligter Strukturen überprüft und unter Verwendung verschiedener Substanzen (Speichel, Wasser und Götterspeise) Schluckvideos im zervikalen Ösophagusbereich aufgezeichnet und ausgewertet. Im Rahmen einer Pilotstudie wurde die Untersuchung an 3 dysphagischen Patienten erprobt.
Ergebnisse
Der Zungengrund, die intralaryngealen Strukturen, die Halswirbelsäule und die Schilddrüsen waren sehr gut darstellbar. In besonderer Weise gelang die sonographische Darstellung des zervikalen Ösophagusabschnitts. Dieser konnte mit einer Länge von 5,78 ± 1,66 cm eingesehen werden, der Durchmesser betrug 0,88 ± 0,10 cm. Am schlechtesten ließ sich der Sinus piriformis sonographisch beurteilen. Er war in 39,5 % der Fälle nicht einsehbar. In der Odds Ratio war die Darstellbarkeit des Sinus piriformis 5,6-fach höher bei Normalgewichtigen und 11,3-fach höher bei einem Alter unter 25 Jahren. Bei der Untersuchung jener Patienten, welche eine Schluckstörung aufwiesen, konnten 3 verschiedene Krankheitsbilder (ein M. Forestier, eine Ösophagusstenose und eine Motoneuronenerkrankung) als Ursache für die Beschwerden ermittelt werden.
Schlussfolgerung
Die Sonographie zeigte eine sehr gute Darstellbarkeit des Schluckakts mit Beurteilungsmöglichkeit des zervikalen Ösophagus. Der HNO-Arzt sollte bei der Verfügbarkeit des Ultraschalls an diese Diagnostikmöglichkeit denken, welche die wiederholte Beurteilung im zervikalen Abschnitt ermöglicht und die bisherigen Verfahren sinnvoll ergänzen kann.
https://ift.tt/2Pia1va
IgE blockade during food allergen ingestion enhances the induction of inhibitory IgG antibodies
Publication date: Available online 4 November 2018
Source: Annals of Allergy, Asthma & Immunology
Author(s): Amanda J. Stranks, Samantha C. Minnicozzi, Samuel J. Miller, Oliver T. Burton, Stephanie L. Logsdon, Jonathan M. Spergel, Kari C. Nadeau, Jacqueline A. Pongracic, Dale T. Umetsu, Rima Rachid, Andrew J. MacGinnitie, Lynda Schneider, Hans C. Oettgen
https://ift.tt/2QnFad1
Dual functionality of lamprey VLRB C-terminus (LC) for multimerization and cell surface display
Publication date: December 2018
Source: Molecular Immunology, Volume 104
Author(s): Jung Seok Lee, Jaesung Kim, Se Pyeong Im, Si Won Kim, Jae Wook Jung, Jassy Mary S. Lazarte, Jeong Ho Lee, Kim D. Thompson, Tae Sung Jung
Abstract
Lamprey, one of the living representatives of jawless vertebrates, uses variable lymphocyte receptors B (VLRB) for antigen recognition, rather than immunoglobulin (Ig) based receptors as used by higher vertebrates. The C-terminus of lamprey VLRB (LC) possess a glycosylphosphatidylinositol (GPI) signal sequence and seven cysteine residues providing dual functionality of the VLRB antibody in the form of a humoral agglutinin and cell membrane receptors. Here, we show that the LC can be either secreted or be membrane anchored as a heterologous fused protein in a multimeric form comprising of eight or ten monomeric units. Using serially truncated LC variants, we showed that the LC, in which the last three amino acid "RKR" were deleted, referred to as LC7, was the most suitable domain for multimeric construction, whereas, the intact LC is more tailored for applications involving membrane anchorage. We show that an antibody specific for viral hemorrhagic septicemia virus (VHSV) (VLR43), displayed on HEK-293F cells using a PiggyBac (PB) transposase system, exhibited a dose-dependent reaction with its antigen, verifying that the LC can be applied in antibody display technology. Therefore, the present report provides valuable insight into the structure of the lamprey VLRB and highlights its potential use as a novel fusion partner for multimerization and membrane anchorage of chimeric proteins.
https://ift.tt/2DpLT3g
Acidic pH promotes oxidation-induced dissociation of C-reactive protein
Publication date: December 2018
Source: Molecular Immunology, Volume 104
Author(s): Shuo-Lei Li, Jun-Rui Feng, Hai-Hong Zhou, Chun-Miao Zhang, Guang-Bo Lv, Yu-Bo Tan, Zhong-Bo Ge, Ming-Yu Wang
Abstract
Background
Circulating levels of the systemic inflammation marker C-reactive protein (CRP) have been associated with increased risk and poor outcomes of many diseases, such as cardiovascular events and cancer. Accumulating evidence has indicated that the conformational rearrangement of human pentameric CRP (pCRP) to monomeric CRP (mCRP) is a prerequisite for participation in the pathogenesis. Therefore, determining the mechanism of the dissociation of pCRP into pro-inflammatory mCRP under physiological/pathological circumstances has been intriguing.
Methods
The effects of oxidative and acidic stress occurring in inflammation on pCRP were examined by electrophoresis, electron microscopy, protein fluorescence, neoepitope expression and endothelial cell responses.
Results
Reactive oxygen species (ROS) generated by the copper-hydrogen peroxide system could rapidly induce the dissociation of CRP at mild acidic pH within four hours, but not at physiological pH of 7.4. Meanwhile, mannitol, a ROS scavenger, could not protect against dissociation, which implied that local ROS from accessible histidine residues may be crucially beneficial to the formation of mCRP in a redox-balanced microenvironment. Furthermore, mCRP generated by ROS could be reduced by DTT, which indicated the exposure of functional motif aa35-47, and showed potent proinflammatory actions on endothelial cells, comparable to mCRP generated by urea.
Conclusion
dissociation of pCRP to mCRP could be rapidly induced by ROS from copper- hydrogen peroxide system in dependence on mildly acidic stress regardless of a redox-balanced microenvironment.
https://ift.tt/2qxzmT0
Corrigendum to “Immune modulatory properties of 6-gingerol and resveratrol in Atlantic salmon macrophages” [Mol. Immunol. 95 (2018) 10–19]
Publication date: Available online 5 November 2018
Source: Molecular Immunology
Author(s): Nicole C. Smith, Sherri L. Christian, Richard G. Taylor, Javier Santander, Matthew L. Rise
https://ift.tt/2QoQkhI
Thirdhand smoke component can exacerbate a mouse asthma model through mast cells
Publication date: November 2018
Source: Journal of Allergy and Clinical Immunology, Volume 142, Issue 5
Author(s): Mang Yu, Kaori Mukai, Mindy Tsai, Stephen J. Galli
Background
Thirdhand smoke (THS) represents the accumulation of secondhand smoke on indoor surfaces and in dust, which, over time, can become more toxic than secondhand smoke. Although it is well known that children of smokers are at increased risk for asthma or asthma exacerbation if the disease is already present, how exposure to THS can influence the development or exacerbation of asthma remains unknown.
Objective
We investigated whether epicutaneous exposure to an important component of THS, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), can influence asthma pathology in a mouse model elicited by means of repeated intranasal challenge with cockroach antigen (CRA).
Methods
Wild-type mice, α7 nicotinic acetylcholine receptor (nAChR)– or mast cell (MC)–deficient mice, and mice with MCs that lacked α7 nAChRs or were the host's sole source of α7 nAChRs were subjected to epicutaneous NNK exposure, intranasal CRA challenge, or both, and the severity of features of asthma pathology, including airway hyperreactivity, airway inflammation, and airway remodeling, was assessed.
Results
We found that α7 nAChRs were required to observe adverse effects of epicutaneous NNK exposure on multiple features of CRA-induced asthma pathology. Moreover, MC expression of α7 nAChRs contributed significantly to the ability of epicutaneous NNK exposure to exacerbate airway hyperreactivity to methacholine, airway inflammation, and airway remodeling in this model.
Conclusion
Our results show that skin exposure to NNK, a component of THS, can exacerbate multiple features of a CRA-induced model of asthma in mice and define MCs as key contributors to these adverse effects of NNK.
https://ift.tt/2PEYgOE
Neutrophils drive type I interferon production and autoantibodies in patients with Wiskott-Aldrich syndrome
Publication date: November 2018
Source: Journal of Allergy and Clinical Immunology, Volume 142, Issue 5
Author(s): Karla E. Cervantes-Luevano, Nicoletta Caronni, Maria C. Castiello, Elena Fontana, Giulia M. Piperno, Asma Naseem, Paolo Uva, Marita Bosticardo, Genni E. Marcovecchio, Luigi D. Notarangelo, Maria P. Cicalese, Alessandro Aiuti, Anna Villa, Federica Benvenuti
Background
Wiskott-Aldrich syndrome (WAS) is a rare primary immunodeficiency caused by mutations in Wiskott-Aldrich syndrome protein (WASp), a key regulator of cytoskeletal dynamics in hematopoietic cells. A high proportion of patients experience autoimmunity caused by a breakdown in T- and B-cell tolerance. Moreover, excessive production of type I interferon (IFN-I) by plasmacytoid dendritic cells (pDCs) contributes to autoimmune signs; however, the factors that trigger excessive innate activation have not been defined.
Objective
Neutrophil extracellular traps (NETs) emerged as major initiating factors in patients with diseases such as systemic lupus erythematosus and rheumatoid arthritis. In this study we explored the possible involvement of aberrant neutrophil functions in patients with WAS.
Methods
We evaluated the expression of a set of granulocyte genes associated with NETs in a cohort of patients with WAS and the presence of NET inducers in sera. Using a mouse model of WAS, we analyzed NET release by WASp-null neutrophils and evaluated the composition and homeostasis of neutrophils in vivo. By using depletion experiments, we assessed the effect of neutrophils in promoting inflammation and reactivity against autoantigens.
Results
Transcripts of genes encoding neutrophil enzymes and antimicrobial peptides were increased in granulocytes of patients with WAS, and serum-soluble factors triggered NET release. WASp-null neutrophils showed increased spontaneous NETosis, induced IFN-I production by pDCs, and activated B cells through B-cell activating factor. Consistently, their depletion abolished constitutive pDC activation, normalized circulating IFN-I levels, and, importantly, abolished production of autoantibodies directed against double-stranded DNA, nucleosomes, and myeloperoxidase.
Conclusions
These findings reveal that neutrophils are involved in the pathogenic loop that causes excessive activation of innate cells and autoreactive B cells, thus identifying novel mechanisms that contribute to the autoimmunity of WAS.
Graphical abstract
https://ift.tt/2Rxta8I
Mutations affecting the actin regulator WD repeat–containing protein 1 lead to aberrant lymphoid immunity
Publication date: November 2018
Source: Journal of Allergy and Clinical Immunology, Volume 142, Issue 5
Author(s): Laurène Pfajfer, Nina K. Mair, Raúl Jiménez-Heredia, Ferah Genel, Nesrin Gulez, Ömür Ardeniz, Birgit Hoeger, Sevgi Köstel Bal, Christoph Madritsch, Artem Kalinichenko, Rico Chandra Ardy, Bengü Gerçeker, Javier Rey-Barroso, Hanna Ijspeert, Stuart G. Tangye, Ingrid Simonitsch-Klupp, Johannes B. Huppa, Mirjam van der Burg, Loïc Dupré, Kaan Boztug
Background
The actin-interacting protein WD repeat–containing protein 1 (WDR1) promotes cofilin-dependent actin filament turnover. Biallelic WDR1 mutations have been identified recently in an immunodeficiency/autoinflammatory syndrome with aberrant morphology and function of myeloid cells.
Objective
Given the pleiotropic expression of WDR1, here we investigated to what extent it might control the lymphoid arm of the immune system in human subjects.
Methods
Histologic and detailed immunologic analyses were performed to elucidate the role of WDR1 in the development and function of B and T lymphocytes.
Results
Here we identified novel homozygous and compound heterozygous WDR1 missense mutations in 6 patients belonging to 3 kindreds who presented with respiratory tract infections, skin ulceration, and stomatitis. In addition to defective adhesion and motility of neutrophils and monocytes, WDR1 deficiency was associated with aberrant T-cell activation and B-cell development. T lymphocytes appeared to develop normally in the patients, except for the follicular helper T-cell subset. However, peripheral T cells from the patients accumulated atypical actin structures at the immunologic synapse and displayed reduced calcium flux and mildly impaired proliferation on T-cell receptor stimulation. WDR1 deficiency was associated with even more severe abnormalities of the B-cell compartment, including peripheral B-cell lymphopenia, paucity of B-cell progenitors in the bone marrow, lack of switched memory B cells, reduced clonal diversity, abnormal B-cell spreading, and increased apoptosis on B-cell receptor/Toll-like receptor stimulation.
Conclusion
Our study identifies a novel role for WDR1 in adaptive immunity, highlighting WDR1 as a central regulator of actin turnover during formation of the B-cell and T-cell immunologic synapses.
Graphical abstract
https://ift.tt/2PFEz9o
CD40 ligand deficiency causes functional defects of peripheral neutrophils that are improved by exogenous IFN-γ
Publication date: November 2018
Source: Journal of Allergy and Clinical Immunology, Volume 142, Issue 5
Author(s): Otavio Cabral-Marques, Tabata Takahashi França, Ashraf Al-Sbiei, Lena Friederike Schimke, Taj Ali Khan, Claudia Feriotti, Tania Alves da Costa, Osvaldo Reis Junior, Cristina Worm Weber, Janaíra Fernandes Ferreira, Fabiola Scancetti Tavares, Claudia Valente, Regina Sumiko Watanabe Di Gesu, Asif Iqbal, Gabriela Riemekasten, Gustavo Pessini Amarante-Mendes, José Alexandre Marzagão Barbuto, Beatriz Tavares Costa-Carvalho, Paulo Vitor Soeiro Pereira, Maria J. Fernandez-Cabezudo
Background
Patients with X-linked hyper-IgM syndrome caused by CD40 ligand (CD40L) deficiency often present with episodic, cyclic, or chronic neutropenia, suggesting abnormal neutrophil development in the absence of CD40L-CD40 interaction. However, even when not neutropenic and despite immunoglobulin replacement therapy, CD40L-deficient patients are susceptible to life-threatening infections caused by opportunistic pathogens, suggesting impaired phagocyte function and the need for novel therapeutic approaches.
Objectives
We sought to analyze whether peripheral neutrophils from CD40L-deficient patients display functional defects and to explore the in vitro effects of recombinant human IFN-γ (rhIFN-γ) on neutrophil function.
Methods
We investigated the microbicidal activity, respiratory burst, and transcriptome profile of neutrophils from CD40L-deficient patients. In addition, we evaluated whether the lack of CD40L in mice also affects neutrophil function.
Results
Neutrophils from CD40L-deficient patients exhibited defective respiratory burst and microbicidal activity, which were improved in vitro by rhIFN-γ but not soluble CD40L. Moreover, neutrophils from patients showed reduced CD16 protein expression and a dysregulated transcriptome suggestive of impaired differentiation. Similar to CD40L-deficient patients, CD40L knockout mice were found to have impaired neutrophil responses. In parallel, we demonstrated that soluble CD40L induces the promyelocytic cell line HL-60 to proliferate and mature by regulating the expression of genes of the same Gene Ontology categories (eg, cell differentiation) when compared with those dysregulated in peripheral blood neutrophils from CD40L-deficient patients.
Conclusion
Our data suggest a nonredundant role of CD40L-CD40 interaction in neutrophil development and function that could be improved in vitro by rhIFN-γ, indicating a potential novel therapeutic application for this cytokine.
https://ift.tt/2RBcL3e
Protein corona–mediated targeting of nanocarriers to B cells allows redirection of allergic immune responses
Publication date: November 2018
Source: Journal of Allergy and Clinical Immunology, Volume 142, Issue 5
Author(s): Limei Shen, Stefan Tenzer, Wiebke Storck, Dominika Hobernik, Verena Katherina Raker, Karl Fischer, Sandra Decker, Andrzej Dzionek, Susanne Krauthäuser, Mustafa Diken, Alexej Nikolaev, Joachim Maxeiner, Petra Schuster, Cinja Kappel, Admar Verschoor, Hansjörg Schild, Stephan Grabbe, Matthias Bros
Background
Nanoparticle (NP)–based vaccines are attractive immunotherapy tools because of their capability to codeliver antigen and adjuvant to antigen-presenting cells. Their cellular distribution and serum protein interaction ("protein corona") after systemic administration and their effect on the functional properties of NPs is poorly understood.
Objectives
We analyzed the relevance of the protein corona on cell type–selective uptake of dextran-coated NPs and determined the outcome of vaccination with NPs that codeliver antigen and adjuvant in disease models of allergy.
Methods
The role of protein corona constituents for cellular binding/uptake of dextran-coated ferrous nanoparticles (DEX-NPs) was analyzed both in vitro and in vivo. DEX-NPs conjugated with the model antigen ovalbumin (OVA) and immunostimulatory CpG-rich oligodeoxynucleotides were administered to monitor the induction of cellular and humoral immune responses. Therapeutic effects of this DEX-NP vaccine in mouse models of OVA-induced anaphylaxis and allergic asthma were assessed.
Results
DEX-NPs triggered lectin-induced complement activation, yielding deposition of activated complement factor 3 on the DEX-NP surface. In the spleen DEX-NPs targeted predominantly B cells through complement receptors 1 and 2. The DEX-NP vaccine elicited much stronger OVA-specific IgG2a production than coadministered soluble OVA plus CpG oligodeoxynucleotides. B-cell binding of the DEX-NP vaccine was critical for IgG2a production. Treatment of OVA-sensitized mice with the DEX-NP vaccine prevented induction of anaphylactic shock and allergic asthma accompanied by IgE inhibition.
Conclusions
Opsonization of lectin-coated NPs by activated complement components results in selective B-cell targeting. The intrinsic B-cell targeting property of lectin-coated NPs can be exploited for treatment of allergic immune responses.
https://ift.tt/2PFEySS
Basophils from allergic patients are neither hyperresponsive to activation signals nor hyporesponsive to inhibition signals
Publication date: November 2018
Source: Journal of Allergy and Clinical Immunology, Volume 142, Issue 5
Author(s): Lydie Cassard, Katia Sperber, Tan-Phuc Buivan, Aurélie Cotillard, Raphaëlle Bourdet-Sicard, Matthew L. Albert, Estelle Mottez, Jérôme Laurent, Marie-Thérèse Guinnepain, Marc Daëron
Background
Basophil activation contributes to inflammatory reactions, especially in allergy. It is controlled, both positively and negatively, by several mechanisms. High-affinity IgE receptors (FcεRI) generate a mixture of activation and inhibition signals when aggregated, the ratio of which depends on the concentration of allergen recognized by receptor-bound IgE. Low-affinity IgG receptors (FcγRIIA/B) generate inhibition signals when coengaged with FcεRI by allergen-antibody immune complexes. Commensal and probiotic bacteria, such as Lactobacillus paracasei, generate inhibition signals through still unclear mechanisms.
Objective
We sought to investigate whether mechanisms that control, both positively and negatively, basophil activation, which were unraveled and studied in basophils from healthy donors, are functional in allergic patients.
Methods
FcεRI and FcγRIIA/B expression, FcεRI-dependent activation, FcεRI-dependent inhibition, and FcγRIIB-dependent inhibition were examined in blood basophils incubated overnight with or without L paracasei and challenged under 10 experimental conditions. Basophils from healthy donors were compared with basophils from patients who consulted an allergology outpatient clinic over a period of 3 months with respiratory allergy, anaphylaxis antecedents, chronic urticaria, and/or atopic dermatitis.
Results
Patients' basophils expressed neither more FcεRI nor less FcγRIIB than basophils from healthy donors. They were neither hyperreactive to positive regulation nor hyporeactive to negative regulation, irrespective of the receptors or mechanisms involved and the allergic manifestations of the patients.
Conclusion
Regulatory mechanisms that control basophil activation are fully functional in allergic patients. Intrinsic defects in these mechanisms do not explain allergic manifestations. Based on these mechanisms, immune checkpoint modifiers can be developed as novel therapeutic tools for allergy.
https://ift.tt/2RE6Fir
Intestinal IFN-γ–producing type 1 regulatory T cells coexpress CCR5 and programmed cell death protein 1 and downregulate IL-10 in the inflamed guts of patients with inflammatory bowel disease
Publication date: November 2018
Source: Journal of Allergy and Clinical Immunology, Volume 142, Issue 5
Author(s): Johanna Sophie Alfen, Paola Larghi, Federica Facciotti, Nicola Gagliani, Roberto Bosotti, Moira Paroni, Stefano Maglie, Paola Gruarin, Chiara Maria Vasco, Valeria Ranzani, Cristina Frusteri, Andrea Iseppon, Monica Moro, Maria Cristina Crosti, Stefano Gatti, Massimiliano Pagani, Flavio Caprioli, Sergio Abrignani, Richard A. Flavell, Jens Geginat
Background
IL-10 is an anti-inflammatory cytokine required for intestinal immune homeostasis. It mediates suppression of T-cell responses by type 1 regulatory T (TR1) cells but is also produced by CD25+ regulatory T (Treg) cells.
Objective
We aimed to identify and characterize human intestinal TR1 cells and to investigate whether they are a relevant cellular source of IL-10 in patients with inflammatory bowel diseases (IBDs).
Methods
CD4+ T cells isolated from the intestinal lamina propria of human subjects and mice were analyzed for phenotype, cytokine production, and suppressive capacities. Intracellular IL-10 expression by CD4+ T-cell subsets in the inflamed guts of patients with IBD (Crohn disease or ulcerative colitis) was compared with that in cells from noninflamed control subjects. Finally, the effects of proinflammatory cytokines on T-cell IL-10 expression were analyzed, and IL-1β and IL-23 responsiveness was assessed.
Results
Intestinal TR1 cells could be identified by coexpression of CCR5 and programmed cell death protein 1 (PD-1) in human subjects and mice. CCR5+PD-1+ TR1 cells expressed IFN-γ and efficiently suppressed T-cell proliferation and transfer colitis. Intestinal IFN-γ+ TR1 cells, but not IL-7 receptor–positive TH cells or CD25+ Treg cells, showed lower IL-10 expression in patients with IBDs. TR1 cells were responsive to IL-23, and IFN-γ+ TR1 cells downregulated IL-10 with IL-1β and IL-23. Conversely, CD25+ Treg cells expressed higher levels of IL-1 receptor but showed stable IL-10 expression.
Conclusions
We provide the first ex vivo characterization of human intestinal TR1 cells. Selective downregulation of IL-10 by IFN-γ+ TR1 cells in response to proinflammatory cytokines is likely to drive excessive intestinal inflammation in patients with IBDs.
Graphical abstract
https://ift.tt/2PDg50z
An unexpected protective role of low-affinity allergen-specific IgG through the inhibitory receptor FcγRIIb
Publication date: November 2018
Source: Journal of Allergy and Clinical Immunology, Volume 142, Issue 5
Author(s): Lisha Zha, Fabiana M.S. Leoratti, Lichun He, Mona O. Mohsen, Mark Cragg, Federico Storni, Monique Vogel, Martin F. Bachmann
Background
Induction of allergen-specific IgG antibodies is a critical parameter for successful allergen-specific immunotherapy. IgG antibodies can inhibit IgE-mediated mast cell activation through direct allergen neutralization or through the inhibitory receptor FcγRIIb. The affinity of IgE antibodies to the allergen has been shown to be critical for cellular activation.
Objective
Here we addressed the question of affinity thresholds of allergen-specific IgG antibodies for inhibition of mast cell activation using 2 different mAbs against the major cat allergen Fel d 1 both in vitro and in vivo in mice.
Methods
Sequences of the 2 high-affinity mAbs were back-mutated to germline, resulting in low-affinity (10−7 mol/L) antibodies of the exact same specificity.
Results
Using these newly generated recombinant antibodies, we demonstrate that low-affinity antibodies are still able to inhibit mast cell activation through FcγRIIb but do not neutralize the allergen.
Conclusion
Antibody affinity dictates the mechanism of mast cell inhibition, and IgG antibodies triggering the inhibitory FcγRIIb pathway can show a broader cross-reactivity pattern than previously thought. This indicates that allergen-specific immunotherapy generates a larger protective umbrella of inhibitory IgG antibodies than previously appreciated.
Graphical abstract
https://ift.tt/2RE6uns
Glucagon-like peptide 1 signaling inhibits allergen-induced lung IL-33 release and reduces group 2 innate lymphoid cell cytokine production in vivo
Publication date: November 2018
Source: Journal of Allergy and Clinical Immunology, Volume 142, Issue 5
Author(s): Shinji Toki, Kasia Goleniewska, Sara Reiss, Jian Zhang, Melissa H. Bloodworth, Matthew T. Stier, Weisong Zhou, Dawn C. Newcomb, Lorraine B. Ware, Gregg D. Stanwood, Aurelio Galli, Kelli L. Boyd, Kevin D. Niswender, R. Stokes Peebles
Background
IL-33 is one of the most consistently associated gene candidates for asthma identified by using a genome-wide association study. Studies in mice and in human cells have confirmed the importance of IL-33 in inducing type 2 cytokine production from both group 2 innate lymphoid cells (ILC2s) and TH2 cells. However, there are no pharmacologic agents known to inhibit IL-33 release from airway cells.
Objective
We sought to determine the effect of glucagon-like peptide 1 receptor (GLP-1R) signaling on aeroallergen-induced airway IL-33 production and release and on innate type 2 airway inflammation.
Methods
BALB/c mice were challenged intranasally with Alternaria extract for 4 consecutive days. GLP-1R agonist or vehicle was administered starting either 2 days before the first Alternaria extract challenge or 1 day after the first Alternaria extract challenge.
Results
GLP-1R agonist treatment starting 2 days before the first Alternaria extract challenge decreased IL-33 release in the bronchoalveolar lavage fluid and dual oxidase 1 (Duox1) mRNA expression 1 hour after the first Alternaria extract challenge and IL-33 expression in lung epithelial cells 24 hours after the last Alternaria extract challenge. Furthermore, GLP-1R agonist significantly decreased the number of ILC2s expressing IL-5 and IL-13, lung protein expression of type 2 cytokines and chemokines, the number of perivascular eosinophils, mucus production, and airway responsiveness compared with vehicle treatment. GLP-1R agonist treatment starting 1 day after the first Alternaria extract challenge also significantly decreased eosinophilia and type 2 cytokine and chemokine expression in the airway after 4 days of Alternaria extract challenge.
Conclusion
These results reveal that GLP-1R signaling might be a therapy to reduce IL-33 release and inhibit the ILC2 response to protease-containing aeroallergens, such as Alternaria.
Graphical abstract
https://ift.tt/2PCR7hV
IL-25 enhances TH17 cell–mediated contact dermatitis by promoting IL-1β production by dermal dendritic cells
Publication date: November 2018
Source: Journal of Allergy and Clinical Immunology, Volume 142, Issue 5
Author(s): Hajime Suto, Aya Nambu, Hideaki Morita, Sachiko Yamaguchi, Takafumi Numata, Takamichi Yoshizaki, Eri Shimura, Ken Arae, Yousuke Asada, Kenichiro Motomura, Mari Kaneko, Takaya Abe, Akira Matsuda, Yoichiro Iwakura, Ko Okumura, Hirohisa Saito, Kenji Matsumoto, Katsuko Sudo, Susumu Nakae
Background
In addition to thymic stromal lymphopoietin and IL-33, IL-25 is known to induce TH2 cytokine production by various cell types, including TH2 cells, TH9 cells, invariant natural killer T cells, and group 2 innate lymphoid cells, involved in TH2-type immune responses. Because both TH2-type and TH17-type cells/cytokines are crucial for contact hypersensitivity (CHS), IL-25 can contribute to this by enhancing TH2-type immune responses. However, the precise role of IL-25 in the pathogenesis of fluorescein isothiocyanate–induced CHS is poorly understood.
Objective
We investigated the contribution of IL-25 to CHS using Il25−/− mice.
Methods
CHS was evaluated by means of measurement of ear skin thickness in mice after fluorescein isothiocyanate painting. Skin dendritic cell (DC) migration, hapten-specific TH cell differentiation, and detection of IL-1β–producing cells were determined by using flow cytometry, ELISA, and immunohistochemistry, respectively.
Results
In contrast to thymic stromal lymphopoietin, we found that IL-25 was not essential for skin DC migration or hapten-specific TH cell differentiation in the sensitization phase of CHS. Unexpectedly, mast cell– and non–immune cell–derived IL-25 was important for hapten-specific TH17 cell–mediated rather than TH2 cell–mediated inflammation in the elicitation phase of CHS by enhancing TH17-related, but not TH2-related, cytokines in the skin. In particular, IL-1β produced by dermal DCs in response to IL-25 was crucial for hapten-specific TH17 cell activation, contributing to induction of local inflammation in the elicitation phase of CHS.
Conclusion
Our results identify a novel IL-25 inflammatory pathway involved in induction of TH17 cell–mediated, but not TH2 cell–mediated, CHS. IL-25 neutralization can be a potential approach for treatment of CHS.
Graphical abstract
https://ift.tt/2RF14c2
Systems biology and in vitro validation identifies family with sequence similarity 129 member A (FAM129A) as an asthma steroid response modulator
Publication date: November 2018
Source: Journal of Allergy and Clinical Immunology, Volume 142, Issue 5
Author(s): Michael J. McGeachie, George L. Clemmer, Boris Hayete, Heming Xing, Karl Runge, Ann Chen Wu, Xiaofeng Jiang, Quan Lu, Bruce Church, Iya Khalil, Kelan Tantisira, Scott Weiss
Background
Variation in response to the most commonly used class of asthma controller medication, inhaled corticosteroids, presents a serious challenge in asthma management, particularly for steroid-resistant patients with little or no response to treatment.
Objective
We applied a systems biology approach to primary clinical and genomic data to identify and validate genes that modulate steroid response in asthmatic children.
Methods
We selected 104 inhaled corticosteroid–treated asthmatic non-Hispanic white children and determined a steroid responsiveness endophenotype (SRE) using observations of 6 clinical measures over 4 years. We modeled each subject's cellular steroid response using data from a previously published study of immortalized lymphoblastoid cell lines under dexamethasone (DEX) and sham treatment. We integrated SRE with immortalized lymphoblastoid cell line DEX responses and genotypes to build a genome-scale network using the Reverse Engineering, Forward Simulation modeling framework, identifying 7 genes modulating SRE.
Results
Three of these genes were functionally validated by using a stable nuclear factor κ-light-chain-enhancer of activated B cells luciferase reporter in A549 human lung epithelial cells, IL-1β cytokine stimulation, and DEX treatment. By using small interfering RNA transfection, knockdown of family with sequence similarity 129 member A (FAM129A) produced a reduction in steroid treatment response (P < .001).
Conclusion
With this systems-based approach, we have shown that FAM129A is associated with variation in clinical asthma steroid responsiveness and that FAM129A modulates steroid responsiveness in lung epithelial cells.
https://ift.tt/2PEt6qJ
A functional splice variant associated with decreased asthma risk abolishes the ability of gasdermin B to induce epithelial cell pyroptosis
Publication date: November 2018
Source: Journal of Allergy and Clinical Immunology, Volume 142, Issue 5
Author(s): Ronald A. Panganiban, Maoyun Sun, Amber Dahlin, Hae-Ryung Park, Mengyuan Kan, Blanca E. Himes, Jennifer A. Mitchel, Carlos Iribarren, Eric Jorgenson, Scott H. Randell, Elliot Israel, Kelan Tantisira, Stephanie Shore, Jin-Ah Park, Scott T. Weiss, Ann Chen Wu, Quan Lu
Background
Genetic variants in the chromosomal region 17q21 are consistently associated with asthma. However, mechanistic studies have not yet linked any of the associated variants to a function that could influence asthma, and as a result, the identity of the asthma gene(s) remains elusive.
Objectives
We sought to identify and characterize functional variants in the 17q21 locus.
Methods
We used the Exome Aggregation Consortium browser to identify coding (amino acid–changing) variants in the 17q21 locus. We obtained asthma association measures for these variants in both the Genetic Epidemiology Research in Adult Health and Aging (GERA) cohort (16,274 cases and 38,269 matched controls) and the EVE Consortium study (5,303 asthma cases and 12,560 individuals). Gene expression and protein localization were determined by quantitative RT-PCR and fluorescence immunostaining, respectively. Molecular and cellular studies were performed to determine the functional effects of coding variants.
Results
Two coding variants (rs2305480 and rs11078928) of the gasdermin B (GSDMB) gene in the 17q21 locus were associated with lower asthma risk in both GERA (odds ratio, 0.92; P = 1.01 × 10−6) and EVE (odds ratio, 0.85; joint PEVE = 1.31 × 10−13). In GERA, rs11078928 had a minor allele frequency (MAF) of 0.45 in unaffected (nonasthmatic) controls and 0.43 in asthma cases. For European Americans in EVE, the MAF of rs2305480 was 0.45 for controls and 0.39 for cases; for all EVE subjects, the MAF was 0.32 for controls and 0.27 for cases. GSDMB is highly expressed in differentiated airway epithelial cells, including the ciliated cells. We found that, when the GSDMB protein is cleaved by inflammatory caspase-1 to release its N-terminal fragment, potent pyroptotic cell death is induced. The splice variant rs11078928 deletes the entire exon 6, which encodes 13 amino acids in the critical N-terminus, and abolishes the pyroptotic activity of the GSDMB protein.
Conclusions
Our study identified a functional asthma variant in the GSDMB gene of the 17q21 locus and implicates GSDMB-mediated epithelial cell pyroptosis in pathogenesis.
Graphical abstract
https://ift.tt/2RD95hk