A giant popliteal lipoblastoma in a 23-month-old girl: a case report

Lipoblastomas are rare benign tumors that arise from embryonic white fat and almost always occur in babies and children. Here, we report a case of a giant popliteal lipoblastoma in a 23-month-old Japanese girl...

http://ift.tt/2ilquvE

Clinical predictors of chronic rhinosinusitis: do the Canadian clinical practice guidelines for acute and chronic rhinosinusitis predict CT-confirmation of disease?

The diagnosis of chronic rhinosinusitis (CRS) based on clinical presentation alone remains challenging. To improve the accuracy of clinical diagnosis, the Canadian Rhinosinusitis Guidelines recommend the use o...

http://ift.tt/2iORfwh

A two-center, assessor-blinded, prospective trial evaluating the efficacy of a novel hypertonic draining cream for cellulite reduction: A Clinical and instrumental (Antera 3D CS) assessment

Summary

Introduction

Gynoid lipodystrophy, also known as cellulite, is a very common skin alteration representing mainly a cosmetic problem rather than a real disease. An effective treatment of cellulite has not been well established. The initial phase of cellulite is characterized by subdermal tissue edema with interstitial fluids retention. A new hypertonic topical product with draining action (HTC) containing NaCl 13%, escine, caffeine, and beta-sitosterol has been recently developed. A 28-day double-blind placebo-controlled study has shown that this cream is able to reduce thigh circumference and the thickness of adipose tissue. No data so far are available regarding an objective evaluation of skin appearance for a longer application period.

Study aim

To evaluate the clinical efficacy of 2-month HCT treatment with clinical and instrumental assessments.

Subjects and methods

In a prospective, 2-center, assessor-blinded trial 20 women (mean age 34 years) with cellulite of Grade I-III in severity were enrolled after their informed consent. HTC was applied once daily for 60 days. Primary outcomes of the trial were the evolution of thigh circumference measurements (assessed at baseline, after 1 and 2 months) and the computer-analysis of skin profilometry (ie, skin volumes) of a prespecified target area evaluated by means of Antera 3D CS digitalized images (assessed at baseline and at the end of the trial). Secondary outcome was the orange peel severity score (from 0 to 5) before and after pitch test.

Results

All subjects concluded the study period. Thigh circumference was reduced by −0.88 (right)/−1.2 cm (left) and by −1.8(right)/−2.1 (left) cm, after 30 and 60 days of treatment, respectively (P = .001, Wilcoxon test vs baseline). Antera 3D profilometry of the target zone showed a significant reduction in skin depression expressed in mm³ of −56% (from 59.7 to 26.73 mm³) after HTC application. Orange peel (no pitch test) mean (SD) score was 2.3 (1) at baseline, 2.0 (1) and 1.8 (0.8) after 1 and 2 months (P = .0031), respectively. After-pitch orange peel score was significantly reduced after treatment (from 3.3 to 2.2).

Conclusion

Once daily application of HTC for 2 months has confirmed its efficacy in the improvement of objective and subjective assessments of cellulite parameters.(Trial Number registration: ISRCTN15111614).

http://ift.tt/2zNlN4O

Immediate effect and safety of HIFU single treatment for male subcutaneous fat reduction

Summary

Background

The increasing search for procedures for fat reduction is related to dissatisfaction with body shape. High-intensity focused ultrasound (HIFU) has been proven effective in body sculpting when used noninvasively to reduce subcutaneous fat and improve body contour.

Aims

This study aimed to evaluate the immediate effect and safety of HIFU single treatment for male localized fat and body remodeling.

Patients/Methods

Twenty-four male subjects (18 to 59 years old) with BMI ≤ 30 kg/cm² and at least 2 cm of abdominal fat received a single HIFU treatment session. Individuals were subjected to abdominal measurements before and after procedure. In addition, biochemical analyses of blood samples were performed to assess possible inflammatory effects or oxidative stress induction by the treatment.

Results

High-intensity focused ultrasound was found to be an effective treatment in reducing localized adiposities in the abdominal region. A significant decrease (0.6%) was observed in infraumbilical circumference of subjects submitted to HIFU single treatment when compared with control subjects. The laboratory parameters did not present any appreciable changes.

Conclusion

This study further strengthens the current view that HIFU is an effective and safe tool for localized fat reduction.

http://ift.tt/2nsZ8Jn

Muscle fiber conduction velocity and EMG amplitude of the upper trapezius muscle in healthy subjects after low-level laser irradiation: a randomized, double-blind, placebo-controlled, crossover study

Abstract

Although low-level laser therapy (LLLT) is an important resource for the treatment of non-specific neck pain patients, the dose which presents the greatest therapeutic potential for the treatment of this pathology is still unclear. The present study aimed to evaluate the immediate effect of LLLT on the muscle fiber conduction velocity (MFCV) and electromyographic activity (EMG) of the upper trapezius (UT) muscle in healthy individuals. A total of 20 healthy subjects were enrolled in a randomized, double-blind, crossover study. Active LLLT (820 nm wavelength, 30 mW, energy total 18 J) or placebo LLLT (pLLLT) was delivered on the UT muscle. Each subject was subjected to a single session of active LLLT and pLLLT. Surface electromyography (sEMG) signal of the UT muscle was recorded during five different step contractions of shoulder elevation force (10–30% maximal voluntary contraction) pre- and post-LLLT irradiation. The values of MFCV and sEMG global amplitude (RMS_G) were used to calculate the effects of LLLT. The results showed no difference in the MFCV comparing the LLLT and pLLLT groups (F = 0.72 p = 0.39, η _p² = 0.004). However, a significant difference was observed in the RMS_G between the LLLT and pLLLT (F _1,2 = 16.66; P < 0.0001, η _p² = 0.09). Individuals who received active LLLT presented a significant decrease in RMS_G after laser application (F = 61.28; p < 0.0001, η _p² = 0.43). In conclusion, the 820 nm LLLT, with energy total of 18 J, did not alter the MFCV but significantly reduced the sEMG signal amplitude of the upper trapezius muscle in healthy subjects to a level of up to 30% of maximal voluntary contraction.

http://ift.tt/2kmjqmK

Is photobiomodulation (PBM) effective for the treatment of dentin hypersensitivity? A systematic review

Abstract

The present study aims to evaluate the current scientific data regarding the effectiveness of photobiomodulation (PBM) in the treatment of dentin hypersensitivity (DH) as an alternative method for pain control. A systematic review was conducted to assess the effectiveness of PBM as treatment for DH. A complete literature search was performed up to October 2016. Searches were conducted using Boolean operators and MeSH terms. References of all selected full-text articles and related reviews were scanned. A total of 280 articles were identified (241 articles were excluded by the title and abstract). Of the 39 articles selected for analysis, 36 were excluded because they presented one or more exclusion criteria. Therefore, three articles were qualified for inclusion in this systematic review. PBM may not lead to adverse effects provided that adequately controlled parameters are followed when treating DH. More consistent studies should be conducted in order to adequately observe the advantageous therapeutic effect of PBM.

http://ift.tt/2AsLsme

Subcutaneous granuloma annulare involving the scalp

Abstract

Subcutaneous granuloma annulare (SGA) is an uncommon subtype of granuloma annulare. There are few reports of this entity solely affecting the scalp. We report a case of biopsy-proven SGA in a 21-month-old boy with six asymptomatic, rock-hard scalp nodules.

http://ift.tt/2nrbQIm

CME Accreditation Page

http://ift.tt/2AXbEqk

Psychosocial Impact of Vascular Anomalies on Children and Their Families

Vascular anomalies are divided into tumors and malformations based on their clinical and cytologic attributes. Vascular malformations are further subcategorized as low-flow lymphatic, venous, capillary, or mixed lesions and as high-flow arteriovenous malformations. Treatment is reserved for vascular anomalies that are symptomatic or cosmetically disfiguring, and surgical and nonsurgical treatment options are widely varied with variable outcomes.

http://ift.tt/2A4Gld8

Forthcoming Issues

Otosclerosis and Stapes Surgery

http://ift.tt/2AXbxuU

Congenital Vascular Lesions of the Head and Neck

The number of physicians interested in the treatment of vascular anomalies has grown exponentially over the last several decades from a mere handful in the mid 1980s to several thousand today. Every year, hundreds of peer-reviewed articles are published in this field. Some of the most interesting articles have shed light on the underlying genetic and molecular bases of some of these conditions. This has led to the development of at least one group of medical therapies for some vascular lesions.

http://ift.tt/2A50YpM

Contents

Sujana S. Chandrasekhar

http://ift.tt/2AXbr6w

Orthognathic Considerations of Vascular Malformations

Vascular malformations affect the craniofacial skeleton in many ways, depending on the type of the lesion and its location. The lesions may exert a mass effect and cause thinning or thickening of the bone or cause expansion from direct bony infiltration. Orthognathic surgery can be used to correct any malocclusion or open bite deformities after the soft tissues are addressed.

http://ift.tt/2A50W18

Contributors

SUJANA S. CHANDRASEKHAR, MD

http://ift.tt/2AVPNjg

Multidisciplinary Approach to Vascular Anomalies Maximizes Outcomes

The birth of a child is a glorious and simultaneously nerve-wracking event in every family. If this is the 1 in 22 children born with a vascular lesion of the head and neck (which is visible in every picture and to every visitor), the parents' concerns multiply. Will my baby bleed? Will my baby stay deformed by this lesion? Is this the tip of the iceberg of other problems? Will my baby be forced to enter chronic medical/surgical care? These are some of the questions that race through the parents' brains, even as they marvel at the wondrousness of new life.

http://ift.tt/2A50OPc

Copyright

Elsevier

http://ift.tt/2AXbcs8

Classification and Pathology of Congenital and Perinatal Vascular Anomalies of the Head and Neck

Accurate histopathologic description in correlation with clinical and radiological evaluation is required for treatment of vascular anomalies, both neoplastic and malformative. It is important to examine current clinical, histologic, and immunophenotypical features that distinguish the major types of congenital and perinatal vascular anomalies affecting the head and neck. General discussions of pathogenesis and molecular diagnosis must also be taken into account. This article provides an overview of the features that distinguish the major types of congenital and perinatal vascular anomalies affecting the head and neck, and summarizes the diagnostic histopathologic criteria and nomenclature currently applied to these lesions.

http://ift.tt/2A50hga

Congenital Vascular Lesions of the Head and Neck

OTOLARYNGOLOGIC CLINICS OF NORTH AMERICA

http://ift.tt/2AVPDbE

Hereditary Hemorrhagic Telangiectasia

Hereditary hemorrhagic telangiectasia (HHT) describes the presenting manifestations of a disorder that is characterized by pathologic blood vessels. HHT is inherited as an autosomal dominant trait with variable penetrance. The abnormal vascular structures (dysplasias) can affect all the organs in the human body. The link between a physical stimulus and new lesion development has been established for mucosal trauma owing to nasal airflow turbulence, for ultraviolet exposure to the fingers, and for mechanical trauma to the dominant hand. The pressing question then is whether HHT treatment constitutes a stimulus that is sufficient to trigger new lesion development.

http://ift.tt/2A50C2q

Outcome Measurement for Vascular Malformations of the Head and Neck

Vascular malformations are congenital anomalies of the vascular and/or lymphatic system that affect the head and neck region. The most common treatment options are sclerotherapy, laser therapy, surgery, and embolization. Because vascular malformations are variable in type, size, extent, and location, it is a challenge to select methods for evaluation of treatment outcome. Without standardized outcome reporting, it is difficult to compare and combine scientific evidence to support therapeutic decision making. Standardized collection and reporting of outcome data are the first steps toward a fair comparison between treatments. This article describes outcome measurements for vascular malformations and initiatives to improve outcome reporting.

http://ift.tt/2AUMoRu

The Surgical Management of Infantile Hemangiomas

The surgical management of facial infantile hemangiomas presents a unique challenge. The aim of the surgeon should be to remove the hemangioma and to restore normal facial features. Each of the facial zones has its own special features and challenges. The surgeon should remember that the child started out with normal anatomy and that as the hemangioma proliferated, it displaced and thinned these normal structures and in many cases, expanded adjacent tissue. Hemangiomas do not as a rule, invade adjacent tissues as they proliferate. These facts will help in planning the various surgical approaches.

http://ift.tt/2A50uzY

The Management of Vascular Malformations of the Airway

Vascular malformations may affect nearly all aspects of the upper airway. Each type of malformation has a characteristic pattern of disease. These lesions may be focal or diffuse, and require directed management strategies. Physicians treating these entities should have a high level of suspicion to consider airway evaluation even in the absence of overt symptoms. However, cutaneous head and neck venous malformations or other lesions affecting the lips, oral cavity, or tongue can herald the presence of coexisting airway lesions. A multidisciplinary approach is critical in achieving comprehensive treatment.

http://ift.tt/2AVHB2t

Infantile Hemangiomas in the Head and Neck Region

Infantile hemangiomas (IHs) are benign vascular tumors of infancy most common in the region of the head and neck. Infantile hemangiomas are common; but they are extremely heterogeneous and cause a range of complications depending on their morphology, size, or location. Medical interventions for high-risk patients include topical and systemic therapies, including oral propranolol, which has revolutionized the management of IHs over the past recent years. In the following article, the authors aim to provide a review of the natural history, pathology, complications, syndromes, and medical management of infantile hemangioma.

http://ift.tt/2A57BZ7

Multidisciplinary Approach to the Management of Lymphatic Malformations of the Head and Neck

Lymphatic malformations (LMs) occur in 2.8 to 5 per 100,000 live births. Most involve the head and neck and they are equally common in men and women. They are developmental anomalies of unknown cause, although recent evidence suggests that an upregulation of the mammalian target of rapamycin (mTOR) pathway may be a causal factor leading to the overproduction of abnormal lymph vessels. These vessels are likely dilated lymphatic sacs sequestered from the lymphatic and venous systems. This overproduction results in the accumulation of lymph in dilated cystic spaces, which in turn results in the clinical features of an LM.

http://ift.tt/2AWNlZM

The Role of Surgery in the Management of Infantile Hemangiomas

Surgery for the management of infantile hemangiomas has become commonplace. Surgical technique articles are plentiful; however, little has been written about the timing of surgery. Knowledge of the biology of the tumors, data from developmental psychology, and the utility of facial reconstruction provide guidelines for timing of surgical intervention.

http://ift.tt/2A3j9fb

Congenital Vascular Tumors

Vascular tumors are benign neoplasms, which result from proliferating endothelial cells. These lesions present during infancy or childhood, may affect any location, and exhibit postnatal growth. Local complications include bleeding, tissue destruction, and pain whereas systemic sequelae include thrombocytopenia, congestive heart failure, and death. Vascular tumors should be differentiated from vascular malformations, which present at birth, have a quiescent endothelium, and grow in proportion to the child. Together, vascular tumors and malformations comprise the field of vascular anomalies.

http://ift.tt/2AYZhde

Etiology and Genetics of Congenital Vascular Lesions

The detection of somatic, activating genetic mutations to underlie development of vascular tumors and malformations led to a better understanding of their pathophysiology. Proteins encoded by the detected mutated genes activate the two major signaling pathways, also involved in cancer: the RAS/MAPK/ERK pathway and/or the PI3K/AKT/mTOR pathway. This gives a strong basis for studies to repurpose cancer therapeutics to patients with vascular tumors and malformations.

http://ift.tt/2A5bI7q

Usefulness of our proposed olfactory scoring system during endoscopic sinus surgery in patients with chronic rhinosinusitis

Abstract

Introduction

The primary aim of the current study was to examine the usefulness of our proposed olfactory scoring system in chronic rhinosinusitis (CRS) patients with olfactory disorders (n = 213) receiving endoscopic sinus surgery (ESS).

Materials and methods

Analyzed patients were divided into two groups: an eosinophilic CRS (ECRS) group (n = 153); and a non-ECRS group (n = 60). The T&T recognition threshold test was used to evaluate olfaction at baseline and at 3 and 12 months after ESS. Patients with mean recognition threshold < 2.0 at 3 or 12 months or with a decrease of ≥ 1.0 as compared with baseline were defined as showing clinical improvement. We scored mucosal conditions as normal (0 points), edema (1 point), and polyp (2 points) at the canopy of olfactory cleft (OC), middle and superior turbinates, superior nasal meatus, and sphenoethmoidal recess during ESS. The total score of OCs (SOCs) was calculated (range 0–20 points). We compared SOCs between ECRS and non-ECRS groups. Factors related to olfactory improvement were also investigated using uni- and multivariate analyses.

Results

SOCs in the ECRS and non-ECRS groups showed significant correlations with mean recognition thresholds at baseline and at 3 and 12 months. In the multivariate analysis for predicting improvement of mean recognition threshold, lower SOCs were significantly associated with olfactory improvement factors at 3 and 12 months postoperatively in the ECRS group.

Conclusion

SOCs appears promising for estimating olfactory prognosis after ESS in CRS patients.

http://ift.tt/2A1k3cd

Sialendoscopy in treating pediatric salivary gland disorders: a systematic review

Abstract

Objective

The primary aim of this study is to conduct a systematic review in order to evaluate the use of sialendoscopy in treating pediatric salivary gland disorders.

Methods

Eligible articles were identified through a comprehensive search of electronic databases. Using predefined inclusion criteria, published articles on sialendoscopy in children were selected and reviewed.

Results

17 articles including 323 pediatric patients and 424 salivary glands managed by sialendoscopy were identified. The most common salivary gland disorder affected was the parotid (83% of cases), followed by the submandibular gland (16.5% of cases). Juvenile recurrent parotitis (68.9%) was the most frequent diagnosis followed by sialolithiasis (14.7%). The most common complication was ductal perforation. During a pooled mean follow-up time of 18.3 months, recurrences were reported in 14.5% of patients mostly in patients diagnosed with juvenile recurrent parotitis.

Conclusion

Sialendoscopy is a minimally invasive diagnostic and therapeutic tool for inflammatory salivary gland disorders in pediatric patients. Based on the current review, sialendoscopy can be successfully implemented in cases of pediatric salivary gland disorders.

http://ift.tt/2AWvFgQ

Reply to the letter “Laryngopharyngeal reflux disease in the elderly”

http://ift.tt/2A3Cs8r

The outcome of cochlear implantation among children with genetic syndromes

Abstract

Objective

To assess the outcome and efficacy of cochlear implantation in children with genetic syndromes.

Method

Study design: case–control study.

Setting

A cochlear implantation tertiary referral center.

Patients

All pediatric cochlear implantation recipients with Waardenburg syndrome, Usher syndrome, Dandy–Walker syndrome, or albinism. A control group was appropriately matched to the syndromic group with regard to age at implantation and duration of device use.

Intervention

Cochlear implantation.

Main outcome measures

Subjects' auditory abilities, speech intelligibility, and pure tone thresholds were compared between the syndromic and non-syndromic group.

Results

A total of 25 subjects (13 syndromic and 12 non-syndromic) participated in the study. Neither auditory ability nor speech intelligibility scores differed significantly by group. The final PTA of both the groups showed normal-to-mild hearing loss: 26 dB HL in the syndromic group and 23 dB HL for the control group.

Conclusions

Cochlear implant recipients with genetic syndromes achieved similar levels auditory perception and speech intelligibility as their peers with a genetic syndrome. The presence of any of the genetic syndromes described herein should not be a contraindication to cochlear implant provision, as it would have a positive impact on the patients' sensory perception and lifestyle.

http://ift.tt/2AWnwJp

Prognostic value of the lymph node ratio in oropharyngeal carcinoma stratified for HPV-status

Abstract

Objective

Lymph node ratio (LNR) was shown to be a prognostic factor in laryngeal and oral cavity primaries. The purpose of this study was to investigate the impact of the lymph node ratio in oropharyngeal squamous cell carcinoma (OPSCC) with a high incidence of HPV-related disease. Therefore, the role of LNR was evaluated as an additional predictive parameter to the 8th edition of AJCC TNM staging system.

Methods

From December 2009 to August 2015, patients diagnosed with primary oropharyngeal squamous cell carcinoma were prospectively enrolled. After tumor resection with uni- or bilateral neck dissection, patients with ≥ 1 nodal metastasis (pN+) were eligible for a retrospective LNR analysis.

Results

137 patients underwent tumor resection with uni- or bilateral neck dissection. The proportion of HPV-associated disease was 42%. Most patients (n = 96; 70%) presented with involved neck nodes. In p16-positive OPSCC, the rate of pN + cases was significantly increased compared to p16-negative OPSCC (86% vs. 58%, p = 0.007). Patients with LNR ≤ 10% had a significant better overall survival (OS) and disease-specific survival (DSS). However, when stratified for p16-status, LNR ≤ 10% had a significant impact on OS only for HPV-associated tumors (p = 0.027), whereas LNR of ≤ 10% was not a significant predictor for better OS in p16-negative OPSCC (p = 0.143).

Conclusion

The LNR with a cut-off value of 10% serves as an additional prognostic parameter in HPV-related OPSCC and may help to improve risk stratification in combination with the revised AJCC 8th edition TNM classification.

http://ift.tt/2A3DLUQ

Reply to the Letter to the Editor concerning “Combined microscopic/endoscopic management of petrous apex lesions”

http://ift.tt/2AWnmSj

Repair of Occipital Bone Defects in Neurofibromatosis Type 1 by Means of CAD/CAM Prefabricated Titanium Plates

Cranial Maxillofac Trauma Reconstruction
DOI: 10.1055/s-0037-1608699

Certain skeletal defects may develop in neurofibromatosis type 1 (NF1), a common tumor-suppressor syndrome, such as cranial lesions confined to the lambdoid suture region. Here, we report on the repair of osseous defects of occipital bone in a NF1 patient with history of skull trauma and tumorous hemorrhage. Computer-aided design and computer-aided manufacturing (CAD/CAM)-assisted devices were applied to safely close the bone defects. The variable phenotype of NF1 in the occipital skull region is discussed and a brief review is presented on NF1-related therapies for tumors and malformations of the occipitoparietal skull region.
[...]

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

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

http://ift.tt/2ikI3fj

Metastasierung kutaner Plattenepithelkarzinome im HNO-Bereich

Laryngo-Rhino-Otol
DOI: 10.1055/s-0043-122745

Hintergrund Kutane Plattenepithelkarzinome können lymphogen sowohl nach intraparotideal, als auch nach zervikal metastasieren. Prognostisch scheinen sich gemäß mehreren Studien die beiden Metastasierungswege zu unterscheiden. Wir möchten mit klinikeigenen Daten das Metastasierungsverhalten hinsichtlich der Prognose untersuchen. Material und Methoden In die retrospektive Studie aufgenommen wurden 29 Kaukasier mit einem Plattenepithelkarzinom der Haut im Kopf-Halsbereich, welche sich zwischen 2004 und 2016 an unserer Hals-Nasen-Ohren-Klinik vorgestellt haben. Bei allen Patienten wurde eine Tumorresektion mit Neck dissection durchgeführt. Sowohl das präoperative Staging, wie auch die Nachsorge erfolgten mittels Ultraschall oder Computertomographie (konventionell oder PET Scan). Die Patienten wurden nach Metastasierungsverhalten eingeteilt und die entsprechenden Überlebensraten wurden ermittelt. Ergebnisse 11 Patienten hatten zervikale Metastasen, 4 Patienten parotideale Metastasen, 5 Patienten hatten beides. Bei 9 Patienten wurde eine prophylaktische Neck dissection bei cN0 durchgeführt. Ein lokoregionäres Tumorrezidiv trat in insgesamt 24 % der Fälle auf, davon waren alle mit einer zervikalen Metastasierung assoziiert. Die 5-Jahres Überlebensrate betrug in diesen Fällen 71 %. Im Gegensatz dazu betrug diese bei alleiniger parotidealer Metastasierung 100 %. Im Rahmen der prophylaktischen Neck dissection wurden in einem Fall okkulte Metastasen diagnostiziert. Schlussfolgerungen Eine zervikale Metastasierung geht im Gegensatz zu einer alleinigen parotidealen Metastasierung mit einer schlechteren Prognose einher. Die Überlebensrate nach chirurgischer Therapie, sowie gegebenenfalls zusätzlichen adjuvanten Radiotherapie ist insgesamt gut (79 %). Die Rolle einer prophylaktischen Neck dissection bei cN0 und entsprechenden Risikofaktoren ist nicht abschließend geklärt.
[...]

Georg Thieme Verlag KG Stuttgart · New York

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

http://ift.tt/2kkkqHL

IgG4-related disease presenting as hoarseness and postcricoid ulcer

Immunoglobulin G4–related disease (IgG4-RD) is an uncommon immune-mediated disorder with heterogeneous clinicopathologic features and variable disease manifestations.1 IgG4-RD is characterized by single-organ or multiorgan involvement, and tissue infiltration with IgG4 plasma cells and associated fibrosclerosis.2–5 Autoimmune pancreatitis represents the prototype of IgG4-RD, yet involvement of almost all organs has been reported.1–7 Elevated IgG4 serum concentration is noted in the majority of patients with IgG4-RD and is generally related to the more severe disease phenotype.

http://ift.tt/2iPyGbo

Hyalinizing clear cell carcinoma of salivary gland origin in the head and neck: clinical and histopathological analysis

Hyalinizing clear cell carcinoma (HCCC) is an extremely rare neoplasm of salivary gland origin with a low-grade indolent nature. It is difficult to distinguish from other malignant salivary gland tumours. Clinical outcomes following surgery are generally reported as good. The aim of this study was to further determine the features of HCCC. This study was approved by Medical ethics review of affiliated hospital of jiangsu university. Fourteen new cases of HCCC are reported. The clinical and histopathological data of these 14 cases were analysed alongside those of 141 cases identified in a systematic review of the literature (up to 2016).

http://ift.tt/2km2JYC

Diagnostic and treatment effects of sialendoscopy for patients with swelling of the parotid gland when sialoliths are undetected with computed tomography

Between August 2009 and May 2016, 74 patients underwent sialoendoscopic surgery. 32 patients had parotid gland disease and 9 patients had intermittent swelling of the parotid gland and sialoliths were not detected with CT imaging. 4 patients were diagnosed with idiopathic Stensen's duct stenosis. Sialendoscopy directly confirmed Stensen's duct stenosis in 2 patients. However, the sialendoscope was unable to be inserted in the other 2 patients, who had stenosis of the orifice of the Stensen's duct.

http://ift.tt/2A3UYxm

In This Issue [IN THIS ISSUE]

http://ift.tt/2A2lIyf

Development of a Novel CD4+ TCR Transgenic Line That Reveals a Dominant Role for CD8+ Dendritic Cells and CD40 Signaling in the Generation of Helper and CTL Responses to Blood-Stage Malaria [NOVEL IMMUNOLOGICAL METHODS]

We describe an MHC class II (I-A^b)–restricted TCR transgenic mouse line that produces CD4⁺ T cells specific for Plasmodium species. This line, termed PbT-II, was derived from a CD4⁺ T cell hybridoma generated to blood-stage Plasmodium berghei ANKA (PbA). PbT-II cells responded to all Plasmodium species and stages tested so far, including rodent (PbA, P. berghei NK65, Plasmodium chabaudi AS, and Plasmodium yoelii 17XNL) and human (Plasmodium falciparum) blood-stage parasites as well as irradiated PbA sporozoites. PbT-II cells can provide help for generation of Ab to P. chabaudi infection and can control this otherwise lethal infection in CD40L-deficient mice. PbT-II cells can also provide help for development of CD8⁺ T cell–mediated experimental cerebral malaria (ECM) during PbA infection. Using PbT-II CD4⁺ T cells and the previously described PbT-I CD8⁺ T cells, we determined the dendritic cell (DC) subsets responsible for immunity to PbA blood-stage infection. CD8⁺ DC (a subset of XCR1⁺ DC) were the major APC responsible for activation of both T cell subsets, although other DC also contributed to CD4⁺ T cell responses. Depletion of CD8⁺ DC at the beginning of infection prevented ECM development and impaired both Th1 and follicular Th cell responses; in contrast, late depletion did not affect ECM. This study describes a novel and versatile tool for examining CD4⁺ T cell immunity during malaria and provides evidence that CD4⁺ T cell help, acting via CD40L signaling, can promote immunity or pathology to blood-stage malaria largely through Ag presentation by CD8⁺ DC.

http://ift.tt/2A2l8k3

Glycogen Synthase Kinase-3 Modulates Cbl-b and Constrains T Cell Activation [IMMUNE REGULATION]

The decision between T cell activation and tolerance is governed by the spatial and temporal integration of diverse molecular signals and events occurring downstream of TCR and costimulatory or coinhibitory receptor engagement. The PI3K–protein kinase B (PKB; also known as Akt) signaling pathway is a central axis in mediating proximal signaling events of TCR and CD28 engagement in T cells. Perturbation of the PI3K–PKB pathway, or the loss of negative regulators of T cell activation, such as the E3 ubiquitin ligase Cbl-b, have been reported to lead to increased susceptibility to autoimmunity. In this study, we further examined the molecular pathway linking PKB and Cbl-b in murine models. Our data show that the protein kinase GSK-3, one of the first targets identified for PKB, catalyzes two previously unreported phosphorylation events at Ser⁴⁷⁶ and Ser⁴⁸⁰ of Cbl-b. GSK-3 inactivation by PKB abrogates phosphorylation of Cbl-b at these two sites and results in reduced Cbl-b protein levels. We further show that constitutive activation of PKB in vivo results in a loss of tolerance that is mediated through the downregulation of Cbl-b. Altogether, these data indicate that the PI3K–PKB–GSK-3 pathway is a novel regulatory axis that is important for controlling the decision between T cell activation and tolerance via Cbl-b.

http://ift.tt/2A2aMRk

Ubc9 Binds to ADAP and Is Required for Rap1 Membrane Recruitment, Rac1 Activation, and Integrin-Mediated T Cell Adhesion [MOLECULAR AND STRUCTURAL IMMUNOLOGY]

Although the immune adaptor adhesion and degranulation-promoting adaptor protein (ADAP) acts as a key mediator of integrin inside-out signaling leading to T cell adhesion, the regulation of this adaptor during integrin activation and clustering remains unclear. We now identify Ubc9, the sole small ubiquitin-related modifier E2 conjugase, as an essential regulator of ADAP where it is required for TCR-induced membrane recruitment of the small GTPase Rap1 and its effector protein RapL and for activation of the small GTPase Rac1 in T cell adhesion. We show that Ubc9 interacted directly with ADAP in vitro and in vivo, and the association was increased in response to anti-CD3 stimulation. The Ubc9-binding domain on ADAP was mapped to a nuclear localization sequence (aa 674–700) within ADAP. Knockdown of Ubc9 by short hairpin RNA or expression of the Ubc9-binding–deficient ADAP mutant significantly decreased TCR-induced integrin adhesion to ICAM-1 and fibronectin, as well as LFA-1 clustering, although it had little effect on the TCR proximal signaling responses and TCR-induced IL-2 transcription. Furthermore, downregulation of Ubc9 impaired TCR-mediated Rac1 activation and attenuated the membrane targeting of Rap1 and RapL, but not Rap1-interacting adaptor molecule. Taken together, our data demonstrate for the first time, to our knowledge, that Ubc9 acts as a functional binding partner of ADAP and plays a selective role in integrin-mediated T cell adhesion via modulation of Rap1-RapL membrane recruitment and Rac1 activation.

http://ift.tt/2A2laZd

Cutting Edge: c-Maf Is Required for Regulatory T Cells To Adopt ROR{gamma}t+ and Follicular Phenotypes [CUTTING EDGE]

Regulatory T cells (Tregs) adopt specialized phenotypes defined by coexpression of lineage-defining transcription factors, such as RORt, Bcl-6, or PPAR, alongside Foxp3. These Treg subsets have unique tissue distributions and diverse roles in maintaining organismal homeostasis. However, despite extensive functional characterization, the factors driving Treg specialization are largely unknown. In this article, we show that c-Maf is a critical transcription factor regulating this process in mice, essential for generation of both RORt⁺ Tregs and T follicular regulatory cells, but not for adipose-resident Tregs. c-Maf appears to function primarily in Treg specialization, because IL-10 production, expression of other effector molecules, and general immune homeostasis are not c-Maf dependent. As in other T cells, c-Maf is induced in Tregs by IL-6 and TGF-β, suggesting that a combination of inflammatory and tolerogenic signals promote c-Maf expression. Therefore, c-Maf is a novel regulator of Treg specialization, which may integrate disparate signals to facilitate environmental adaptation.

http://ift.tt/2AXk6FW

IgG1 Is Required for Optimal Protection after Immunization with the Purified Porin OmpD from Salmonella Typhimurium [IMMUNOTHERAPY AND VACCINES]

In mice, the IgG subclass induced after Ag encounter can reflect the nature of the Ag. Th2 Ags such as alum-precipitated proteins and helminths induce IgG1, whereas Th1 Ags, such as Salmonella Typhimurium, predominantly induce IgG2a. The contribution of different IgG isotypes to protection against bacteria such as S. Typhimurium is unclear, although as IgG2a is induced by natural infection, it is assumed this isotype is important. Previously, we have shown that purified S. Typhimurium porins including outer membrane protein OmpD, which induce both IgG1 and IgG2a in mice, provide protection to S. Typhimurium infection via Ab. In this study we report the unexpected finding that mice lacking IgG1, but not IgG2a, are substantially less protected after porin immunization than wild-type controls. IgG1-deficient mice produce more porin-specific IgG2a, resulting in total IgG levels that are similar to wild-type mice. The decreased protection in IgG1-deficient mice correlates with less efficient bacterial opsonization and uptake by macrophages, and this reflects the low binding of outer membrane protein OmpD–specific IgG2a to the bacterial surface. Thus, the Th2-associated isotype IgG1 can play a role in protection against Th1-associated organisms such as S. Typhimurium. Therefore, individual IgG subclasses to a single Ag can provide different levels of protection and the IgG isotype induced may need to be a consideration when designing vaccines and immunization strategies.

http://ift.tt/2A2lgjx

Cutting Edge: Processing of Oxidized Peptides in Macrophages Regulates T Cell Activation and Development of Autoimmune Arthritis [CUTTING EDGE]

APCs are known to produce NADPH oxidase (NOX) 2–derived reactive oxygen species; however, whether and how NOX2-mediated oxidation affects redox-sensitive immunogenic peptides remains elusive. In this study, we investigated a major immunogenic peptide in glucose-6-phosphate isomerase (G6PI), a potential autoantigen in rheumatoid arthritis, which can form internal disulfide bonds. Ag presentation assays showed that presentation of this G6PI peptide was more efficient in NOX2-deficient (Ncf1^m1J/m1J mutant) mice, compared with wild-type controls. IFN-–inducible lysosomal thiol reductase (GILT), which facilitates disulfide bond–containing Ag processing, was found to be upregulated in macrophages from Ncf1 mutant mice. Ncf1 mutant mice exhibited more severe G6PI peptide-induced arthritis, which was accompanied by the increased GILT expression in macrophages and enhanced Ag-specific T cell responses. Our results show that NOX2-dependent processing of the redox-sensitive autoantigens by APCs modify T cell activity and development of autoimmune arthritis.

http://ift.tt/2A164Df

Disruption of Thrombocyte and T Lymphocyte Development by a Mutation in ARPC1B [CLINICAL AND HUMAN IMMUNOLOGY]

Regulation of the actin cytoskeleton is crucial for normal development and function of the immune system, as evidenced by the severe immune abnormalities exhibited by patients bearing inactivating mutations in the Wiskott–Aldrich syndrome protein (WASP), a key regulator of actin dynamics. WASP exerts its effects on actin dynamics through a multisubunit complex termed Arp2/3. Despite the critical role played by Arp2/3 as an effector of WASP-mediated control over actin polymerization, mutations in protein components of the Arp2/3 complex had not previously been identified as a cause of immunodeficiency. Here, we describe two brothers with hematopoietic and immunologic symptoms reminiscent of Wiskott–Aldrich syndrome (WAS). However, these patients lacked mutations in any of the genes previously associated with WAS. Whole-exome sequencing revealed a homozygous 2 bp deletion, n.c.G623DEL-TC (p.V208VfsX20), in Arp2/3 complex component ARPC1B that causes a frame shift resulting in premature termination. Modeling of the disease in zebrafish revealed that ARPC1B plays a critical role in supporting T cell and thrombocyte development. Moreover, the defects in development caused by ARPC1B loss could be rescued by the intact human ARPC1B ortholog, but not by the p.V208VfsX20 variant identified in the patients. Moreover, we found that the expression of ARPC1B is restricted to hematopoietic cells, potentially explaining why a mutation in ARPC1B has now been observed as a cause of WAS, whereas mutations in other, more widely expressed, components of the Arp2/3 complex have not been observed.

http://ift.tt/2A3YkjP

Lung-Infiltrating Foxp3+ Regulatory T Cells Are Quantitatively and Qualitatively Different during Eosinophilic and Neutrophilic Allergic Airway Inflammation but Essential To Control the Inflammation [ALLERGY AND OTHER HYPERSENSITIVITIES]

Understanding functions of Foxp3⁺ regulatory T cells (Tregs) during allergic airway inflammation remains incomplete. In this study, we report that, during cockroach Ag–induced allergic airway inflammation, Foxp3⁺ Tregs are rapidly mobilized into the inflamed lung tissues. However, the level of Treg accumulation in the lung was different depending on the type of inflammation. During eosinophilic airway inflammation, ~30% of lung-infiltrating CD4 T cells express Foxp3, indicative of Tregs. On the contrary, only ~10% of infiltrating CD4 T cells express Foxp3 during neutrophilic airway inflammation. Despite the different accumulation, the lung inflammation and inflammatory T cell responses were aggravated following Treg depletion, regardless of the type of inflammation, suggesting regulatory roles for Tregs. Interestingly, however, the extent to which inflammatory responses are aggravated by Treg depletion was significantly greater during eosinophilic airway inflammation. Indeed, lung-infiltrating Tregs exhibit phenotypic and functional features associated with potent suppression. Our results demonstrate that Tregs are essential regulators of inflammation, regardless of the type of inflammation, although the mechanisms used by Tregs to control inflammation may be shaped by environmental cues available to them.

http://ift.tt/2AUY1b0

A Protective Function of IL-22BP in Ischemia Reperfusion and Acetaminophen-Induced Liver Injury [IMMUNE REGULATION]

Acute liver injury can be secondary to a variety of causes, including infections, intoxication, and ischemia. All of these insults induce hepatocyte death and subsequent inflammation, which can make acute liver injury a life-threatening event. IL-22 is a dual natured cytokine which has context-dependent protective and pathogenic properties during tissue damage. Accordingly, IL-22 was shown to promote liver regeneration upon acute liver damage. However, other studies suggest pathogenic properties of IL-22 during chronic liver injury. IL-22 binding protein (IL-22BP, IL-22Ra2) is a soluble inhibitor of IL-22 that regulates IL-22 activity. However, the significance of endogenous IL-22BP in acute liver injury is unknown. We hypothesized that IL-22BP may play a role in acute liver injury. To test this hypothesis, we used Il22bp-deficient mice and murine models of acute liver damage induced by ischemia reperfusion and N-acetyl-p-aminophenol (acetaminophen) administration. We found that Il22bp-deficient mice were more susceptible to acute liver damage in both models. We used Il22 x Il22bp double-deficient mice to show that this effect is indeed due to uncontrolled IL-22 activity. We could demonstrate mechanistically increased expression of Cxcl10 by hepatocytes, and consequently increased infiltration of inflammatory CD11b⁺Ly6C⁺ monocytes into the liver in Il22bp-deficient mice upon liver damage. Accordingly, neutralization of CXCL10 reversed the increased disease susceptibility of Il22bp-deficient mice. In conclusion, our data indicate that IL-22BP plays a protective role in acute liver damage, via controlling IL-22–induced Cxcl10 expression.

http://ift.tt/2A2lhnB

Endogenous Calcitriol Synthesis Controls the Humoral IgE Response in Mice [ALLERGY AND OTHER HYPERSENSITIVITIES]

The vitamin D receptor participates in the control of IgE class-switch recombination in B cells. The physiologic vitamin D receptor agonist, 1,25(OH)₂D₃ (calcitriol), is synthesized by the essential enzyme 25-hydroxyvitamin D₃-1α-hydroxylase (CYP27B1), which can be expressed by activated immune cells. The role of endogenous calcitriol synthesis for the regulation of IgE has not been proven. In this study, we investigated IgE-responses in Cyp27b1-knockout (KO) mice following sensitization to OVA or intestinal infection with Heligmosomoides polygyrus. Specific Igs and plasmablasts were determined by ELISA and ELISpot, Cyp27b1 expression was measured by quantitative PCR. The data show elevated specific IgE and IgG1 concentrations in the blood of OVA-sensitized Cyp27b1-KO mice compared with wild-type littermates (+898 and +219%). Accordingly, more OVA-specific IgG1-secreting cells are present in spleen and fewer in the bone marrow of Cyp27b1-KO mice. Ag-specific mechanisms are suggested as the leucopoiesis is in general unchanged and activated murine B and T lymphocytes express Cyp27b1. Accordingly, elevated specific IgE concentrations in the blood of sensitized T cell–specific Cyp27b1-KO mice support a lymphocyte-driven mechanism. In an independent IgE-inducing model, i.e., intestinal infection with H. polygyrus, we validated the increase of total and specific IgE concentrations of Cyp27b1-KO compared with wild-type mice, but not those of IgG1 or IgA. We conclude that endogenous calcitriol has an impact on the regulation of IgE in vivo. Our data provide genetic evidence supporting previous preclinical and clinical findings and suggest that vitamin D deficiency not only promotes bone diseases but also type I sensitization.

http://ift.tt/2A3I2I1

Serum IgA Immune Complexes Promote Proinflammatory Cytokine Production by Human Macrophages, Monocytes, and Kupffer Cells through Fc{alpha}RI-TLR Cross-Talk [INNATE IMMUNITY AND INFLAMMATION]

IgA is predominantly recognized to play an important role in host defense at mucosal sites, where it prevents invasion of pathogens by neutralization. Although it has recently become clear that IgA also mediates other immunological processes, little remains known about the potential of IgA to actively contribute to induction of inflammation, particularly in nonmucosal organs and tissues. In this article, we provide evidence that immune complex formation of serum IgA plays an important role in orchestration of inflammation in response to pathogens at various nonmucosal sites by eliciting proinflammatory cytokines by human macrophages, monocytes, and Kupffer cells. We show that opsonization of bacteria with serum IgA induced cross-talk between FcαRI and different TLRs, leading to cell type–specific amplification of proinflammatory cytokines, such as TNF-α, IL-1β, IL-6, and IL-23. Furthermore, we demonstrate that the increased protein production of cytokines was regulated at the level of gene transcription, which was dependent on activation of kinases Syk and PI3K. Taken together, these data demonstrate that the immunological function of IgA is substantially more extensive than previously considered and suggest that serum IgA–induced inflammation plays an important role in orchestrating host defense by different cell types in nonmucosal tissues, including the liver, skin, and peripheral blood.

http://ift.tt/2A29tSe

Mode of Tolerance Induction and Requirement for Aire Are Governed by the Cell Types That Express Self-Antigen and Those That Present Antigen [ANTIGEN RECOGNITION AND RESPONSES]

Aire controls the fate of autoreactive thymocytes (i.e., clonal deletion or development into regulatory T cells [Tregs]) through transcriptional control of the expression of tissue-restricted self-antigens (TRAs) from medullary thymic epithelial cells (mTECs) and bone marrow (BM)-derived cells. Although TRAs expressed by mTECs and BM-derived cells are suggested to complement each other to generate a full spectrum of TRAs, little is known about the relative contribution of TRAs from each component for establishment of self-tolerance. Furthermore, the precise role of Aire in specific types of Aire-expressing APCs remains elusive. We have approached these issues by generating two different types of transgenic mouse (Tg) model, which express a prefixed model self-antigen driven by the insulin promoter or the Aire promoter. In the insulin-promoter Tg model, mTECs alone were insufficient for clonal deletion, and BM-derived APCs were required for this action by utilizing Ag transferred from mTECs. In contrast, mTECs alone were able to induce Tregs, although at a much lower efficiency in the absence of BM-derived APCs. Importantly, lack of Aire in mTECs, but not in BM-derived APCs, impaired both clonal deletion and production of Tregs. In the Aire-promoter Tg model, both mTECs and BM-derived APCs could independently induce clonal deletion without Aire, and production of Tregs was impaired by the lack of Aire in mTECs, but not in BM-derived APCs. These results suggest that the fate of autoreactive thymocytes together with the requirement for Aire depend on the cell types that express self-antigens and the types of APCs involved in tolerance induction.

http://ift.tt/2AW1PJt

Gingival Tissue Inflammation Promotes Increased Matrix Metalloproteinase-12 Production by CD200Rlow Monocyte-Derived Cells in Periodontitis [CLINICAL AND HUMAN IMMUNOLOGY]

Irreversible tissue recession in chronic inflammatory diseases is associated with dysregulated immune activation and production of tissue degradative enzymes. In this study, we identified elevated levels of matrix metalloproteinase (MMP)-12 in gingival tissue of patients with the chronic inflammatory disease periodontitis (PD). The source of MMP12 was cells of monocyte origin as determined by the expression of CD14, CD68, and CD64. These MMP12-producing cells showed reduced surface levels of the coinhibitory molecule CD200R. Similarly, establishing a multicellular three-dimensional model of human oral mucosa with induced inflammation promoted MMP12 production and reduced CD200R surface expression by monocyte-derived cells. MMP12 production by monocyte-derived cells was induced by CSF2 rather than the cyclooxygenase-2 pathway, and treatment of monocyte-derived cells with a CD200R ligand reduced CSF2-induced MMP12 production. Further, MMP12-mediated degradation of the extracellular matrix proteins tropoelastin and fibronectin in the tissue model coincided with a loss of Ki-67, a protein strictly associated with cell proliferation. Reduced amounts of tropoelastin were confirmed in gingival tissue from PD patients. Thus, this novel association of the CD200/CD200R pathway with MMP12 production by monocyte-derived cells may play a key role in PD progression and will be important to take into consideration in the development of future strategies to diagnose, treat, and prevent PD.

http://ift.tt/2AUkgxQ

B Cells Drive Autoimmunity in Mice with CD28-Deficient Regulatory T Cells [AUTOIMMUNITY]

Follicular regulatory T (T_FR) cells are a newly defined regulatory T cell (Treg) subset that suppresses follicular helper T cell–mediated B cell responses in the germinal center reaction. The precise costimulatory signal requirements for proper T_FR cell differentiation and function are still not known. Using conditional knockout strategies of CD28, we previously demonstrated that loss of CD28 signaling in Tregs caused autoimmunity in mice (termed CD28-Treg mice), characterized by lymphadenopathy, accumulation of activated T cells, and cell-mediated inflammation of the skin and lung. In this study, we show that CD28 signaling is required for T_FR cell differentiation. Treg-specific deletion of CD28 caused a reduction in T_FR cell numbers and function, which resulted in increased germinal center B cells and Ab production. Moreover, residual CD28-deficient T_FR cells showed a diminished suppressive capacity as assessed by their ability to inhibit Ab responses in vitro. Surprisingly, genetic deletion of B cells in CD28-Treg mice prevented the development of lymphadenopathy and CD4⁺ T cell activation, and autoimmunity that mainly targeted skin and lung tissues. Thus, autoimmunity occurring in mice with CD28-deficient Tregs appears to be driven primarily by loss of T_FR cell differentiation and function with resulting B cell–driven inflammation.

http://ift.tt/2A2l5ET

Proinflammatory T Cell Status Associated with Early Life Adversity [CLINICAL AND HUMAN IMMUNOLOGY]

Early life adversity (ELA) has been associated with an increased risk for diseases in which the immune system plays a critical role. The ELA immune phenotype is characterized by inflammation, impaired cellular immunity, and immunosenescence. However, data on cell-specific immune effects are largely absent. Additionally, stress systems and health behaviors are altered in ELA, which may contribute to the generation of the ELA immune phenotype. The present investigation tested cell-specific immune differences in relationship to the ELA immune phenotype, altered stress parameters, and health behaviors in individuals with ELA (n = 42) and those without a history of ELA (control, n = 73). Relative number and activation status (CD25, CD69, HLA-DR, CD11a, CD11b) of monocytes, NK cells, B cells, T cells, and their main subsets were assessed by flow cytometry. ELA was associated with significantly reduced numbers of CD69⁺CD8⁺ T cells (p = 0.022), increased numbers of HLA-DR⁺ CD4 and HLA-DR⁺ CD8 T cells (p < 0.001), as well as increased numbers of CD25⁺CD8⁺ T cells (p = 0.036). ELA also showed a trend toward higher numbers of CCR4⁺CXCR3^–CCR6⁺ CD4 T cells. Taken together, our data suggest an elevated state of immune activation in ELA, in which particularly T cells are affected. Although several aspects of the ELA immune phenotype were related to increased activation markers, neither stress nor health-risk behaviors explained the observed group differences. Thus, the state of immune activation in ELA does not seem to be secondary to alterations in the stress system or health-risk behaviors, but rather a primary effect of early life programming on immune cells.

http://ift.tt/2AUs7M2

Broad Susceptibility of Nucleolar Proteins and Autoantigens to Complement C1 Protease Degradation [AUTOIMMUNITY]

Anti-nuclear autoantibodies, which frequently target the nucleoli, are pathogenic hallmarks of systemic lupus erythematosus (SLE). Although the causes of these Abs remain broad and ill-defined, a genetic deficiency in C1 complex (C1qC1r₂C1s₂) or C4 is able to induce these Abs. Considering a recent finding that, in dead cells, nucleoli were targeted by C1q and two nucleolar autoantigens were degraded by C1r/C1s proteases, we considered that C1 could help protect against antinuclear autoimmunity by broadly degrading nucleolar proteins or autoantigens. Nucleoli were isolated to homogeneity and structurally defined. After C1 treatment, cleaved nucleolar proteins were identified by proteomic two-dimensional fluorescence difference gel electrophoresis and mass spectrometry, and further verified by Western blotting using specific Abs. The extent of nucleolar autoantigen degradation upon C1 treatment was estimated using SLE patient autoantibodies. The isolated nucleoli were broadly reactive with SLE patient autoantibodies. These nucleoli lacked significant autoproteolysis, but many nucleolar proteins and autoantigens were degraded by C1 proteases; >20 nucleolar proteins were identified as C1 cleavable. These were further validated by Western blotting using specific Abs. The broad autoantigenicity of the nucleoli may attribute to their poor autoproteolysis, causing autologous immune stimulation upon necrotic exposure. However, C1q targets at these nucleoli to cause C1 protease activation and the cleavage of many nucleolar proteins or autoantigens. This may represent one important surveillance mechanism against antinuclear autoimmunity because C1 genetic deficiency causes anti-nuclear autoantibodies and SLE disease.

http://ift.tt/2AW1M0f

Regnase-1 and Roquin Nonredundantly Regulate Th1 Differentiation Causing Cardiac Inflammation and Fibrosis [IMMUNE REGULATION]

Regnase-1 and Roquin are RNA binding proteins that are essential for degradation of inflammatory mRNAs and maintenance of immune homeostasis. Although deficiency of either of the proteins leads to enhanced T cell activation, their functional relationship in T cells has yet to be clarified because of lethality upon mutation of both Regnase-1 and Roquin. By using a Regnase-1 conditional allele, we show that mutations of both Regnase-1 and Roquin in T cells leads to massive lymphocyte activation. In contrast, mutation of either Regnase-1 or Roquin affected T cell activation to a lesser extent than the double mutation, indicating that Regnase-1 and Roquin function nonredundantly in T cells. Interestingly, Regnase-1 and Roquin double-mutant mice suffered from severe inflammation and early formation of fibrosis, especially in the heart, along with the increased expression of Ifng, but not Il4 or Il17a. Consistently, mutation of both Regnase-1 and Roquin leads to a huge increase in the Th1, but not the Th2 or Th17, population in spleens compared with T cells with a single Regnase-1 or Roquin deficiency. Regnase-1 and Roquin are capable of repressing the expression of a group of mRNAs encoding factors involved in Th1 differentiation, such as Furin and Il12rb1, via their 3' untranslated regions. Moreover, Regnase-1 is capable of repressing Roquin mRNA. This cross-regulation may contribute to the synergistic control of T cell activation/polarization. Collectively, our results demonstrate that Regnase-1 and Roquin maintain T cell immune homeostasis and regulate Th1 polarization synergistically.

http://ift.tt/2AUs5DU

The Type 1 Diabetes-Resistance Locus Idd22 Controls Trafficking of Autoreactive CTLs into the Pancreatic Islets of NOD Mice [AUTOIMMUNITY]

Type 1 diabetes (T1D) has a strong genetic component. The insulin dependent diabetes (Idd)22 locus was identified in crosses of T1D-susceptible NOD mice with the strongly T1D-resistant ALR strain. The NODcALR-(D8Mit293-D8Mit137)/Mx (NOD-Idd22) recombinant congenic mouse strain was generated in which NOD mice carry the full Idd22 confidence interval. NOD-Idd22 mice exhibit almost complete protection from spontaneous T1D and a significant reduction in insulitis. Our goal was to unravel the mode of Idd22-based protection using in vivo and in vitro models. We determined that Idd22 did not impact immune cell diabetogenicity or β cell resistance to cytotoxicity in vitro. However, NOD-Idd22 mice were highly protected against adoptive transfer of T1D. Transferred CTLs trafficked to the pancreatic lymph node and proliferated to the same extent in NOD and NOD-Idd22 mice, yet the accumulation of pathogenic CTLs in the islets was significantly reduced in NOD-Idd22 mice, correlating with disease resistance. Pancreatic endothelial cells from NOD-Idd22 animals expressed lower levels of adhesion molecules, even in response to inflammatory stimuli. Lower adhesion molecule expression resulted in weaker adherence of T cells to NOD-Idd22 endothelium compared with NOD-derived endothelium. Taken together, these results provide evidence that Idd22 regulates the ability of β cell–autoreactive T cells to traffic into the pancreatic islets and may represent a new target for pharmaceutical intervention to potentially prevent T1D.

http://ift.tt/2A31uEC

TIM-3 Engagement Promotes Effector Memory T Cell Differentiation of Human Antigen-Specific CD8 T Cells by Activating mTORC1 [IMMUNE REGULATION]

T cell expression of TIM-3 following Ag encounter has been associated with a continuum of functional states ranging from effector memory T cells to exhaustion. We have designed an in vitro culture system to specifically address the impact of anti–TIM-3/TIM-3 engagement on human Ag-specific CD8 T cells during a normal response to Ag and found that anti–TIM-3 treatment enhances T cell function. In our in vitro T cell culture system, MART1-specific CD8 T cells were expanded from healthy donors using artificial APCs. To ensure that the T cells were the only source of TIM-3, cells were rechallenged with peptide-loaded artificial APCs in the presence of anti–TIM-3 Ab. In these conditions, anti–TIM-3 treatment promotes generation of effector T cells as shown by acquisition of an activated phenotype, increased cytokine production, enhanced proliferation, and a transcription program associated with T cell differentiation. Activation of mTORC1 has been previously demonstrated to enhance CD8 T cell effector function and differentiation. Anti–TIM-3 drives CD8 T cell differentiation through activation of the mTORC1 as evidenced by increased levels of phosphorylated S6 protein and rhebl1 transcript. Altogether these findings suggest that anti–TIM-3, together with Ag, drives differentiation in favor of effector T cells via the activation of mTOR pathway. To our knowledge, this is the first report demonstrating that TIM-3 engagement during Ag stimulation directly influences T cell differentiation through mTORC1.

http://ift.tt/2AUs3vM

Mer Receptor Tyrosine Kinase Signaling Prevents Self-Ligand Sensing and Aberrant Selection in Germinal Centers [AUTOIMMUNITY]

Mer tyrosine kinase (Mer) signaling maintains immune tolerance by clearing apoptotic cells (ACs) and inducing immunoregulatory signals. We previously showed that Mer-deficient mice (Mer^–/–) have increased germinal center (GC) responses, T cell activation, and AC accumulation within GCs. Accumulated ACs in GCs can undergo necrosis and release self-ligands, which may influence the outcome of a GC response and selection. In this study, we generated Mer^–/– mice with a global MyD88, TLR7, or TLR9 deficiency and cell type–specific MyD88 deficiency to study the functional correlation between Mer and TLRs in the development of GC responses and autoimmunity. We found that GC B cell–intrinsic sensing of self-RNA, but not self-DNA, released from dead cells accumulated in GCs drives enhanced GC responses in Mer^–/– mice. Although self-ligands directly affect GC B cell responses, the loss of Mer in dendritic cells promotes enhanced T cell activation and proinflammatory cytokine production. To study the impact of Mer deficiency on the development of autoimmunity, we generated autoimmune-prone B6.Sle1b mice deficient in Mer (Sle1b.Mer^–/–). We observed accelerated autoimmunity development even under conditions where Sle1b.Mer^–/– mice did not exhibit increased AC accumulation in GCs compared with B6.Sle1b mice, indicating that Mer immunoregulatory signaling in APCs regulates B cell selection and autoimmunity. We further found significant expansion, retention, and class-switching of autoreactive B cells in GCs under conditions where ACs accumulated in GCs of Sle1b.Mer^–/– mice. Altogether, both the phagocytic and immunomodulatory functions of Mer regulate GC responses to prevent the development of autoimmunity.

http://ift.tt/2AWegow

CD27-Mediated Regulatory T Cell Depletion and Effector T Cell Costimulation Both Contribute to Antitumor Efficacy [IMMUNOTHERAPY AND VACCINES]

CD27, a member of the TNFR superfamily, is constitutively expressed in most T cells and plays crucial roles in T cell effector functions. The costimulation and antitumor activity of CD27 agonistic Abs have been well documented in mouse models. Clinical testing of a human IgG1 anti-CD27 Ab, varlilumab (clone 1F5), is ongoing in cancer patients. In this study, we set out to further understand CD27 as an immunomodulatory target and to address the mechanism of antitumor efficacy using different IgG isotypes of 1F5 in human CD27-transgenic mice. 1F5mIgG1, the only isotype engaging inhibitory FcRIIB expressed in B cells, elicited the most potent and broad immune response, but terminal differentiation, exhaustion, and apoptosis in the activated effector T cells were inevitable. Accordingly, this isotype was the most effective in eradicating BCL1 lymphoma but had limited efficacy in s.c. tumors. Conversely, 1F5mIgG2a, which interacts with cells expressing activating FcRs, led to moderate immune activation, as well as to prominent reduction in the number and suppressive activity of regulatory T cells. These combined mechanisms imparted potent antitumor activity to 1F5mIgG2a, particularly against the s.c. tumors. 1F5hIgG1, varlilumab, showed balanced agonistic activity that was prominent at lower doses and depleting activity that was greater at higher doses. 1F5hIgG1 had good antitumor activity in all tumor models tested. Thus, both agonist and depleting properties contribute to the antitumor efficacy of CD27-targeted immunotherapy, and modulation of these activities in patients may be achieved by varying the dose and regimen.

http://ift.tt/2AUs0jA

Das Cochleaimplantat in der sozialgerichtlichen Rechtsprechung

Zusammenfassung

Hintergrund

Da sich die Indikation für eine CI-Versorgung erweitert hat („Single-Sided Deafness" [SSD], elektrisch akustische Stimulation [EAS], bilaterale Versorgung, Versorgung bei sehr langer Taubheit) und daher zunehmend mehr Patienten für eine solche Versorgung infrage kommen, kommt es auch immer öfter zu Auseinandersetzungen mit den Kostenträgern hinsichtlich der Frage, ob die Kosten für die Operation und die Nachsorgekosten durch die Krankenversicherungen getragen werden müssen.

Zielsetzung/Fragestellung

Dieser Artikel gibt einen Überblick über Urteile der deutschen Sozialgerichte. Es wurde untersucht, ob und in welchen Fällen es für den einzelnen Patienten empfehlenswert ist, den Klageweg zu beschreiten, und mit welcher Verfahrensdauer gerechnet werden muss.

Material und Methoden

Ausgewertet wurden die beiden größten kommerziellen juristischen Datenbanken sowie die durch die Sozialgerichtsbarkeit veröffentlichten Urteile. Als Suchparameter dienten verschiedene Kombinationen aus den Begriffen „Cochlear", „Cochlea", „Implant" und „Implantat". Drei Entscheidungen wurden durch direkte Anforderung beim entscheidenden Gericht erlangt, eine weitere in einem Artikel aufgeführt. Die besprochenen Entscheidungen ergingen im Zeitraum 2003 bis 2017.

Ergebnisse

Insgesamt wurden 12 Entscheidungen gefunden. Die Hauptsacheentscheidungen gingen bis auf einen Fall alle zugunsten der Patienten aus. Bei dem Verfahren, in dem die Klägerin nicht Recht bekam, handelte es sich um einen Ausnahmesachverhalt. Ein Kläger unterlag zwar im Verfahren auf einstweiligen Rechtsschutz, in der Hauptsache erkannte die Krankenversicherung seinen Anspruch auf eine CI-Versorgung jedoch an. Die Verfahren dauerten zwischen 1;8 Jahren und 9;5 Jahren.

Schlussfolgerung

Trotz des zeitlichen Aufwands lohnt sich die Beschreitung des Rechtswegs. Das grundsätzlich kostenfreie sozialgerichtliche Verfahren führt in den meisten Fällen dazu, dass die gesetzlichen Krankenversicherungen zur Tragung der Kosten für ein CI verpflichtet werden.

http://ift.tt/2AMnYZV

Zentrale und periphere Aspekte der Lärmschwerhörigkeit

Zusammenfassung

Lärm stellt in den entwickelten Industrieländern ein großes sozioökonomisches Problem dar. Für die Behandlung der durch die Lärmschwerhörigkeit auftretenden audiologischen Phänomene ist ein vertieftes Verständnis der zugrunde liegenden Schädigungsmechanismen peripherer und zentraler Anteile der Hörbahn notwendig. Die mechanische Schädigung, die Ischämie, die Exzitotoxizität sowie die auditorische Synaptopathie stellen die wesentlichen lärminduzierten Schädigungsprozesse in der Cochlea dar. Neben cochleären pathologischen Veränderungen treten jedoch auch zentralnervöse Schädigungen infolge der Lärmexposition auf. Aufgrund der Überstimulation kommt es sehr frühzeitig zum Zellverlust im Versorgungsgebiet des N. cochlearis. Der spätere Zellverlust in höheren auditorischen Kerngebieten ist im Gegensatz dazu auf die sensorische Deprivation zurückzuführen. Insgesamt wird dem strukturellen Verlust durch eine Modulation der Spontanaktivität im Sinne der Netzwerkhomöostase entgegenreguliert. Dennoch nimmt sehr wahrscheinlich die Verarbeitungsgüte durch die lärminduzierten neuroplastischen Veränderungen ab. Die Lärmschwerhörigkeit ist somit durch eine Reihe von peripheren und zentralen Veränderungen gekennzeichnet, die bisher nur teilweise einer Therapie zugänglich sind. Besonders im Hinblick auf die auditorische Synaptopathie und die zentralen Verarbeitungsdefizite werden neue therapeutische Ansätze benötigt, um audiologische Phänomene wie Tinnitus, Hyperakusis oder schlechtes Diskriminationsvermögen effektiv behandeln zu können.

http://ift.tt/2BHyGPb

Clinical predictors of chronic rhinosinusitis: do the Canadian clinical practice guidelines for acute and chronic rhinosinusitis predict CT-confirmation of disease?

Abstract

Background

The diagnosis of chronic rhinosinusitis (CRS) based on clinical presentation alone remains challenging. To improve the accuracy of clinical diagnosis, the Canadian Rhinosinusitis Guidelines recommend the use of specific symptom and endoscopic criteria. Our study objective was to determine whether symptom and endoscopic criteria, as defined by the Canadian Rhinosinusitis Guidelines, accurately predict CT-confirmed CRS diagnosis.

Methods

A retrospective cohort study of 126 patients who underwent CT sinuses based on clinical suspicion of possible CRS. The presence of symptom and endoscopic criteria, as defined by the Canadian Rhinosinusitis Guidelines, were compared between patients with and without a CT-confirmed CRS diagnosis using two-tailed Fisher's exact tests. Positive predictive values and likelihood ratios were determined for each symptom and endoscopic finding.

Results

Overall, 56.3% of patients had a CT-confirmed diagnosis of CRS. With the exception of nasal polyps, none of the symptom or endoscopic criteria had a statistically significant correlation with positive CT sinuses. For symptom criteria, positive predictive values ranged from 52.4% to 63.4%; likelihood ratios ranged from 0.85 to 1.34. For endoscopic criteria, positive predictive values and likelihood ratios were 71.4% and 1.94 (edema); 63.0% and 1.32 (discharge); and 92.9% and 10.1 (nasal polyps). 35.2% of patients with CT-confirmed CRS had normal endoscopic exams.

Conclusion

The Canadian Rhinosinusitis Guidelines' symptom and endoscopic criteria for CRS, with the exception of nasal polyps on endoscopy, do not accurately predict CT-confirmed disease. In addition, a normal endoscopic exam does not rule out CRS.

http://ift.tt/2zNvzDQ

Synergy of Pembrolizumab Anti-PD-1 Immunotherapy With Chemotherapy for Poorly Chemo-responsive Thyroid and Salivary Gland Tumors

Conditions:   Thyroid Cancer;   Salivary Gland Cancer
Interventions:   Drug: Pembrolizumab;   Drug: Docetaxel
Sponsor:   University of Chicago
Not yet recruiting

http://ift.tt/2iL8qP8

BRIDGE: Proactive Psychiatry Consultation and Case Management for Patients With Cancer

Conditions:   Cancer;   Severe Major Depression;   Schizophrenia;   Bipolar Disorder;   Lung Cancer;   Breast Cancer;   Head and Neck Cancer;   Gastrointestinal Cancer
Intervention:   Other: Proactive Psychiatry Consultation
Sponsors:   Massachusetts General Hospital;   Harvard Risk Management Foundation
Not yet recruiting

http://ift.tt/2ALAkl7

Primary Prevention of Concussion in Youth Ice Hockey Players

Condition:   Concussion
Interventions:   Other: Specific intervention;   Other: Control intervention
Sponsor:   Sport Injury Prevention Research Centre
Recruiting

http://ift.tt/2AL94mL

A Study to Evaluate the Safety, Tolerability, and Antitumor Activity of INCB001158 Plus Epacadostat, With or Without Pembrolizumab, in Advanced Solid Tumors

Condition:   Advanced or Metastatic Solid Tumors
Interventions:   Drug: INCB001158;   Drug: Epacadostat;   Drug: Pembrolizumab
Sponsor:   Incyte Corporation
Not yet recruiting

http://ift.tt/2iM3qdj

Combination of mAb-AR20.5, anti-PD-L1 and PolyICLC inhibits tumor progression and prolongs survival of MUC1.Tg mice challenged with pancreatic tumors

Abstract

A substantial body of evidence suggests the existence of MUC1-specific antibodies and cytotoxic T cell activities in pancreatic cancer patients. However, tumor-induced immunosuppression renders these responses ineffective. The current study explores a novel therapeutic combination wherein tumor-bearing hosts can be immunologically primed with their own antigen, through opsonization with a tumor antigen-targeted antibody, mAb-AR20.5. We evaluated the efficacy of immunization with this antibody in combination with PolyICLC and anti-PD-L1. The therapeutic combination of mAb-AR20.5 + anti-PD-L1 + PolyICLC induced rejection of human MUC1 expressing tumors and provided a long-lasting, MUC1-specific cellular immune response, which could be adoptively transferred and shown to provide protection against tumor challenge in human MUC1 transgenic (MUC.Tg) mice. Furthermore, antibody depletion studies revealed that CD8 cells were effectors for the MUC1-specific immune response generated by the mAb-AR20.5 + anti-PD-L1 + PolyICLC combination. Multichromatic flow cytometry data analysis demonstrated a significant increase over time in circulating, activated CD8 T cells, CD3⁺CD4⁻CD8⁻(DN) T cells, and mature dendritic cells in mAb-AR20.5 + anti-PD-L1 + PolyICLC combination-treated, tumor-bearing mice, as compared to saline-treated control counterparts. Our study provides a proof of principle that an effective and long-lasting anti-tumor cellular immunity can be achieved in pancreatic tumor-bearing hosts against their own antigen (MUC1), which can be further potentiated using a vaccine adjuvant and an immune checkpoint inhibitor.

http://ift.tt/2jLzuuk

Post-treatment neutrophil-to-lymphocyte ratio at week 6 is prognostic in patients with advanced non-small cell lung cancers treated with anti-PD-1 antibody

Abstract

We investigated inflammatory markers such as the neutrophil-to-lymphocyte ratio (NLR) that may predict the response to anti-PD-1 (programmed cell death protein 1) antibody therapy. Data from 54 patients with non-small cell lung cancer (NSCLC) treated with anti-PD-1 antibodies were retrospectively analyzed. The NLR was assessed at baseline and 6 weeks after the start of treatment (post-treatment). Eighteen of 54 patients (33.3%) had objective responses to treatment. Older age, absence of brain metastasis, low post-treatment NLR (< 5), and immune-related adverse events were significantly associated with response. Patients with a high post-treatment NLR (≥ 5) had significantly shorter progression-free survival (PFS) than those with a low post-treatment NLR (median, 1.3 vs. 6.1 months, p < 0.001). Multivariate analysis demonstrated that high post-treatment NLR [hazard ratio (HR) 15.1, 95% confidence interval (CI) 1.5–50.1, p < 0.001], liver metastasis (HR 4.9, 95% CI 1.9–12.4, p = 0.001), and brain metastasis (HR 3.2, 95% CI 1.3–8.2, p = 0.013) were independent prognostic factors of shorter PFS. Overall survival (OS) was significantly different in patients with high and low post-treatment NLRs (median, 2.1 vs. 14.0 months, p < 0.001). A high post-treatment NLR remained an independent prognostic factor for OS in multivariate analysis (HR 3.9, 95% CI 1.6–9.2, p = 0.003). The NLR at 6 weeks after treatment initiation was a prognostic marker in patients with advanced NSCLC treated with anti-PD-1 antibody. Further studies are warranted to evaluate the role of the 6-week NLR as a predictor in anti-PD-1 antibody treatment.

http://ift.tt/2BHLxRd

Relapsing Ipsilateral Vestibular Neuritis

In 2013, a 70-year-old male was admitted with an acute episode of vertigo, nausea, and vomiting with duration of one day. The patient's background included prehypertension, vitiligo, left ventricular hypertrophy, and Sjögren's syndrome. He denied any previous episode of vertigo or migraine manifestations. Neither hearing loss nor tinnitus or otorrhea was detected at the time of evaluation. No neurological symptoms were found. There was a left-beating spontaneous nystagmus Grade 3. The patient could stand still and walk on his own with some help without falling. Day 1 vHIT showed a significant reduction in VOR gain and refixation saccades after head impulses were delivered in the planes of the right anterior and horizontal semicircular canals. MRI showed no significant findings. He was treated with steroids. A vHIT performed 14 days later showed recovery of gains and no refixation saccades. In 2015, the patient had a new episode of acute vertigo. The clinical examination was similar, and the vHIT revealed a new drop of right superior and lateral canal gains. Cervical and ocular VEMPs were performed, and no significant asymmetry was detected. Serum PCR for herpes viruses resulted negative. Contrast MRI was performed without relevant brain findings.

http://ift.tt/2AMVjUV

A Rare Presentation of Rhinosporidiosis

Abstract

Rhinosporidiosis is a common condition seen in India specially in endemic areas and in low socio economic areas. Here we present with a rare presentation of cheek swelling caused by obstruction of stenson's duct with a short history of 5 months. Sialolith of parotid duct is uncommon presentation but not unheard of, the subsequent treatment and further histopathology of the ductoceol reveled the causative factor for the obstruction of parotid duct was Rhinosporidiosis which a very rare presentation with very few cases reported in literature. On further investigations it was found to be primary Rhinosporidiosis. Hence it is eminent that Rhinosporidiosis should also be kept in mind while looking for a cause for salivary duct obstruction specially in endemic areas.

http://ift.tt/2ATejBs

Incidentally Discovered Extranodal Marginal Zone B-Cell Lymphoma of Mucosa-Associated Lymphoid Tissue in the Colon

We present a case of colonic mucosa-associated lymphoid tissue (MALT) lymphoma in a 62-year-old woman diagnosed after a positive test for fecal occult blood.

http://ift.tt/2nsyYGs

A Rare Presentation of Rhinosporidiosis

Abstract

Rhinosporidiosis is a common condition seen in India specially in endemic areas and in low socio economic areas. Here we present with a rare presentation of cheek swelling caused by obstruction of stenson's duct with a short history of 5 months. Sialolith of parotid duct is uncommon presentation but not unheard of, the subsequent treatment and further histopathology of the ductoceol reveled the causative factor for the obstruction of parotid duct was Rhinosporidiosis which a very rare presentation with very few cases reported in literature. On further investigations it was found to be primary Rhinosporidiosis. Hence it is eminent that Rhinosporidiosis should also be kept in mind while looking for a cause for salivary duct obstruction specially in endemic areas.

http://ift.tt/2ATejBs

Areolar lymphocytoma in a child: A rare cutaneous presentation of borreliosis

Abstract

Lyme disease is a common tick-borne infection caused by Borrelia burgdorferi in the United States, where infection is most prevalent in the northeastern and mid-Atlantic states. Although classically associated with erythema migrans, Lyme disease caused by Borrelia species found in Europe may also present with other cutaneous findings. Here we report the case of a girl who was clinically diagnosed with Lyme disease based on her history of recent travel and the appearance of an areolar lymphocytoma; this was confirmed by testing. Testing for European Lyme disease does not follow the testing algorithm that the Centers for Disease Control and Prevention recommends and may be easily missed. Our case serves as an important reminder that common infections can have varying presentations depending on their region of acquisition and may require specialized testing for accurate diagnosis.

http://ift.tt/2A1nVdg

Excellent response to ustekinumab in a 9-year-old girl with severe psoriasis

Abstract

We report the case of a 9-year-old girl with severe plaque psoriasis refractory to multiple topical and systemic therapies. Physical examination revealed extensive, erythematous plaques with overlying thick scales that covered more than 80% of her body surface area, which included the face, scalp, trunk, and limbs. Because of the severity of the disease and lack of treatment response to other systemic therapies, she was treated with ustekinumab. Three weeks after ustekinumab was initiated, her psoriatic lesions fully cleared.

http://ift.tt/2AUjpgz

Acral-accentuated exanthem in an infant with parechovirus meningitis

Abstract

We report a case of an infant who had presented with fever and an acral-accentuated rash, for which his cerebrospinal fluid returned positive for parechovirus. He was treated symptomatically and discharged well, with no long-term complications.

http://ift.tt/2A1pfNt

The Immunoscore system predicts prognosis after liver metastasectomy in colorectal cancer liver metastases

Abstract

Background

The Immunoscore was initially established to evaluate the prognosis of stage I/II/III colorectal cancer patients. However, the feasibility of the Immunoscore for the prognosis of colorectal cancer liver metastases (CRCLM) has not been reported.

Methods

Liver metastases in 249 CRCLM patients were retrospectively analyzed. The Immunoscore was assessed according to the counts and densities of CD3+ and CD8+ T cells in the central- and peritumoral areas by immunohistochemistry. The prognostic role of the Immunoscore for relapse–free survival (RFS) and overall survival (OS) was analyzed with Kaplan–Meier curves and Cox multivariate models, and confirmed via an internal validation. Receiver operating characteristic (ROC) curves were plotted to compare the prognostic values of the Immunoscore and the clinical risk score (CRS) system.

Results

CRCLM patients with high Immunoscores (> 2) had significantly longer RFS [median RFS (95% confidence interval; 95% CI) 21.4 (7.8–35.1) vs. 8.7 (6.8–10.5) months, P < 0.001] and OS [median OS (95% CI): not reached vs. 28.7 (23.2–34.2) months, P < 0.001] than those with low Immunoscores (≤ 2). After stratification by CRS, the Immunoscore retained a statistically significant prognostic value for OS. The areas under the ROC curves (AUROCs) of the Immunoscore and the CRS system for RFS were 0.711 [95% CI 0.642–0.781] and 0.675[95% CI 0.601–0.749] (P = 0.492), whereas the AUROC of the Immunoscore system for OS was larger than that of the CRS system [0.759 (95% CI 0.699–0.818) vs. 0.660 (95% CI 0.592–0.727); P = 0.029].

Conclusions

The Immunoscore of liver metastases can be applied to predict the prognosis of CRCLM patients following liver resection.

http://ift.tt/2AnVvJo

New onset of psoriasis during nivolumab treatment for lung cancer

http://ift.tt/2jLQ64X

Successful treatment with i.v. immunoglobulin for localized cutaneous immunoglobulin light chain kappa-positive amyloidosis associated with dermatomyositis

http://ift.tt/2ihqA7r

Case of epidermolysis bullosa acquisita with concomitant anti-laminin-332 antibodies

Abstract

Subepidermal autoimmune blistering disease including bullous pemphigoid, pemphigoid gestationis, mucous membrane pemphigoid, anti-laminin-γ1 pemphigoid, linear immunoglobulin A bullous disease and epidermolysis bullosa acquisita (EBA), are all characterized by direct immunofluorescence microscopy or immunoglobulin deposition on the basement membrane zone. Among them, EBA is a rare acquired subepidermal autoimmune blistering disease of the skin and mucous membranes reactive with type VII collagen, a major component of the epidermal basement membrane zone. Anti-laminin-332-type mucous membrane pemphigoid has pathogenic autoantibodies against laminin-332, which is a basement membrane heterotrimeric protein composed of α3, β3 and γ2 laminin chains. We describe a 73-year-old Japanese man presenting with multiple, annular, tense blisters on the lower legs and oral lesions. Despite the severe clinical manifestations, the disease was successfully controlled by combination therapy of oral prednisolone and mizoribine. This case was confirmed to have autoantibodies to both type VII collagen and laminin-332 α3 chain by indirect immunofluorescence of 1 mol NaCl-split normal human skin, various immunoblot analyses and enzyme-linked immunosorbent assays. This case was a rare case of EBA with concomitant anti-laminin-332 antibodies.

http://ift.tt/2jJRyF2

Case of papuloerythroderma of Ofuji-like eruption during the course of bullous pemphigoid

http://ift.tt/2iiwKnz

The Development of the Genital Psoriasis Sexual Frequency Questionnaire (GenPs-SFQ) to Assess the Impact of Genital Psoriasis on Sexual Health

Abstract

Introduction

Patient-reported outcome measures (PROs) exist for psoriasis but not genital psoriasis (GenPs).

Methods

This cross-sectional, qualitative study in patients with moderate-to-severe GenPs was conducted to support development of a PRO for measuring the impact of GenPs on sexual activity and to establish content validity. The impacts of GenPs were identified in a literature review. Findings from the literature review were discussed with clinicians, and then patients with GenPs were interviewed.

Results

From the literature review, 52 articles, 44 abstracts, and 41 clinical trials met predefined search criteria. Of these, 11 concepts emerged as having theoretical support for use as measurable impacts of psoriasis symptoms on patients; these concepts included sexual functioning and general health-related quality of life (HRQoL). These concepts were confirmed and expanded upon by two clinicians who routinely care for patients with GenPs. Interviews were then conducted with GenPs patients (n = 20) to discuss the impact of GenPs on their HRQoL. Eighty percent of patients reported that GenPs impacted sexual frequency. The two-item GenPs Sexual Frequency Questionnaire (GenPs-SFQ) was developed to assess limitations on sexual activity frequency because of GenPs. Cognitive debriefing with an additional 50 patients with GenPs confirmed the utility and understandability of the GenPs-SFQ.

Conclusion

The GenPs-SFQ may have utility in clinical trials involving GenPs patients and in routine clinical practice.

Funding

Eli Lilly and Company.

Plain Language Summary

Plain language summary available for this article.

http://ift.tt/2kmb4LT

The Development of a Patient-Reported Outcome Measure for Assessment of Genital Psoriasis Symptoms: The Genital Psoriasis Symptoms Scale (GPSS)

Abstract

Introduction

Patient-reported outcome measures (PROs) specific for genital psoriasis (GenPs) have not been described.

Methods

In this cross-sectional, qualitative study in patients with moderate-to-severe GenPs, we sought to develop a PRO useful for GenPs symptom assessment. A literature review was performed to identify relevant psoriasis or GenPs symptoms and existing PROs that may be useful in the evaluation of symptom severity in GenPs patients. The literature review findings were discussed with clinicians, and then patients with GenPs.

Results

Relevant psoriasis or GenPs symptoms from the literature review included itch, pain, scaling, redness/erythema, and stinging/burning. The validity of these symptoms for GenPs and potentially relevant PROs was corroborated by clinical experts. After gap analysis, a draft symptom scale consisting of Numeric Rating Scale (NRS) items was constructed. We then conducted interviews with GenPs patients (n = 20) to support content validity and use of the draft symptom NRS items in routine practice and in clinical trials. Participants identified and confirmed relevant symptoms and evaluated the utility of the draft PRO. A new PRO was developed: the Genital Psoriasis Symptoms Scale (GPSS). Cognitive debriefing and cultural adaptation/translation interviews with a second group of patients confirmed cultural appropriateness of the GPSS.

Conclusion

The GPSS may be useful for assessing symptoms before, during, and after treatment in routine clinical practice and in clinical trials involving patients with GenPs.

Funding

Eli Lilly & Company.

Plain Language Summary

Plain language summary available for this article.

http://ift.tt/2BIkUMm