Update in the classification and the role of intra‐arterial stenting in the management of carotid body paragangliomas

Abstract

Background

To review the Shamblin classification of carotid body paragangliomas (CBPs) and the role of intra‐arterial stenting in their surgical management.

Methods

Retrospective case series of 20 patients with 28 CBPs that were surgically resected at our center. Intra‐arterial stenting was performed in Shamblin II and II classes.

Results

The mean follow‐up was 47.8 months. Five (17.9%) tumors were Shamblin class I, 15 (53.6%) were class II, and 8 (28.6%) were class III. Thirteen (68.4%) CBPs were associated with other paragangliomas. The internal carotid artery (ICA) was stented preoperatively in eight (28.6%) cases and occluded in four (14.3%) cases. The tumor extended to the jugular foramen in six cases (21.4%). Intraoperatively, there was an ICA injury in one case of Shamblin II CBP in the present era.

Conclusions

The proposed classification enables the clinician to plan the management of the ICA and the right approach. Stenting of the ICA gives a chance for complete tumor removal with arterial preservation.

http://bit.ly/2GuTxuS

Academic achievement of adolescents with asthma or atopic disease

Abstract

Background

Over a fifth of children and adolescents suffer with asthma or atopic disease. It is unclear whether asthma impacts academic performance in children and adolescents, and little is known about the association of eczema, food allergy or hay fever and academic performance.

Objective

To examine whether asthma, eczema, food allergy or hay fever impacts on adolescent academic performance and to assess the role of unmeasured confounding.

Methods

This study used the Childhood and Adolescent Twin Study of Sweden cohort born 1992‐1998. At age 9‐12 years, parents reported on their child's ever or current asthma, eczema, food allergy and hay fever status (n= 10963). At age 15, linked national patient and medication register information was used to create current and ever asthma definitions including severe and uncontrolled asthma for the same children. Academic outcomes in Grade 9 (age 15‐16 years) included: eligibility for high‐school (Grades 10‐12), and total mark of the best 16 subject units, retrieved from the Grade 9 academic register. Whole cohort analyses adjusted for known covariates were performed, and co‐twin control analyses to assess unmeasured confounders.

Results

There were no associations found for asthma or food allergy at 9‐12 years and academic outcomes in adolescence. In addition, at age 15, there were no statistically significant associations with current, ever, severe or uncontrolled asthma and academic outcomes. Eczema and hay fever at age 9‐12 years were found to be positively associated with academic outcomes, however, co‐twin control analyses did not support these findings, suggesting the main analyses may be subject to unmeasured confounding.

Conclusion and clinical relevance

Having asthma or an atopic disease during childhood or adolescence does not negatively impact on academic performance. This information can be used by clinicians when talking with children and parents about the implications of living with asthma or atopic disease.

This article is protected by copyright. All rights reserved.

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Answers to CME examination

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CME examination

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Answers to CME examination

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Reply to Wood et al.

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Issue Information ‐ TOC

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In this Issue: Graphical Abstracts

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Issue Information ‐ Cover and Editorial Board

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Pseudoankylosis Between Lateral Pterygoid Plates and Mandible: Report of one case

Publication date: Available online 16 February 2019

Source: Journal of Oral and Maxillofacial Surgery

Author(s): Mohammed Suliman Alsaleh, Hussam Ziad Alsalem, Mohammed Abdullah Assiri, Nasser Marje Almhidy

http://bit.ly/2TT0JDO

Comment on: “Does Accurate Positioning of the Temporomandibular Joint Titanium Condylar Prosthesis Prevent Complications?”

Publication date: Available online 15 February 2019

Source: Journal of Oral and Maxillofacial Surgery

Author(s): Salvatore Sembronio, Alessandro Tel, Massimo Robiony

http://bit.ly/2BD0wOi

Factors related to failure of autologous cranial reconstructions after decompressive craniectomy

Publication date: Available online 16 February 2019

Source: Journal of Cranio-Maxillofacial Surgery

Author(s): S.E.C.M. van de Vijfeijken, C. Groot, D.T. Ubbink, W.P. Vandertop, P.R.A.M. Depauw, E. Nout, A.G. Becking, A.G. Becking, L. Dubois, L.H.E. Karssemakers, D.M.J. Milstein, S.E.C.M. van de Vijfeijken, P.R.A.M. Depauw, F.W.A. Hoefnagels, W.P. Vandertop, C.J. Kleverlaan, T.J.A.G. Münker, T.J.J. Maal, E. Nout, M. Riool

Summary

Purpose

Cranioplasty is customary after decompressive craniectomy. Many different materials have been developed and used for this procedure. The ideal material does not yet exist, while complication rates in cranioplasties remain high. This study aimed to determine factors related to autologous bone flap failure.

Materials and Methods

In this two-center retrospective cohort study, 254 patients underwent autologous bone cranioplasty after initial decompressive craniectomy between 2004 and 2014. Medical records were reviewed regarding patient characteristics and factors potentially related to bone flap failure. Data were analyzed using univariable and multivariable regression analysis.

Results

Independent factors related to overall bone flap failure were: duration of hospitalization after decompressive craniectomy [OR: 1.012 (95%CI: 1.003–1.022); p=0.012], time interval between decompressive craniectomy and cranioplasty [OR: 1.018 (95%CI: 1.004–1.032); p=0.013], and follow-up duration [OR: 1.034 (95%CI: 1.020–1.047); p<0.001]. In patients with bone flap infection, neoplasm as initial diagnosis occurred significantly more often (29.2% vs. 7.8%; RD 6.5-42.5%) and duration of hospitalization after decompressive craniectomy tended to be longer (means 54 vs. 28 days, MD 26.2 days, 95%CI −8.6 to 60.9 days). Patients with bone flap resorption were significantly younger (35 vs. 43 years, MD 7.7 years, 95%CI 0.8-14.6 years) and their cranial defect size tended to be wider than in patients without bone flap resorption (mean circumference 39 vs. 37 cm; MD 2.4cm, 95% CI -0.43 to 5.2cm) and follow-up duration was significantly longer (44 vs. 14 months, MD 29 months, 95%CI 17-42 months).

Conclusion

A neoplasm as initial diagnosis, longer hospitalization after decompressive craniectomy, larger time interval between decompressive craniectomy and cranioplasty, and longer follow-up duration are associated with a higher risk of failure of autologous bone flaps for cranioplasty. Patients with these risk factors may be better served with an early recovery program after decompressive surgery or an alloplastic material for cranioplasty.

http://bit.ly/2GHKExf

Reconstruction of the temporomandibular joint: a comparison between prefabricated and customized alloplastic prosthetic total joint systems

Publication date: Available online 15 February 2019

Source: International Journal of Oral and Maxillofacial Surgery

Author(s): B.J. Siegmund, K. Winter, P. Meyer-Marcotty, J. Rustemeyer

Abstract

The implantation of an alloplastic total temporomandibular joint (TMJ) prosthesis is an innovative approach for the treatment of end-stage TMJ disorders. Two types of system exist: prefabricated (stock) and customized computer-aided design/computer-aided manufacturing (CAD/CAM) devices. A clinical study was performed to evaluate the effectiveness of these two designs. Twenty-eight patients treated between 2015 and 2017 were included and assigned to two groups: stock prostheses (group 1) and customized CAD/CAM prostheses (group 2). Clinical evaluations were performed at five time-points up to 6 months postoperative. Parameters included maximum interincisal opening, pain, diet, complications, and subjective well-being at the end of follow-up. Differences between pre-surgery and 6-month post-surgery values were highly significant (P < 0.001). No patient required a liquid diet at the end of treatment, and 66% of group 1 patients and 100% of group 2 patients reported improved well-being. Complications were observed in 32% of patients and included temporary paralysis of the facial nerve. In conclusion, clinical outcomes of stock and CAD/CAM prostheses suggested great improvements in mouth opening and reduction of pain as a result of the rehabilitation of TMJ function. Results showed comparable data for the two types of prosthesis design at 6 months postoperative.

http://bit.ly/2IhpBUG

Locally advanced mammary analogue secretory carcinoma of the parotid gland

Publication date: Available online 15 February 2019

Source: International Journal of Oral and Maxillofacial Surgery

Author(s): N. Tokuzen, H. Goda, K. Nakashiro

Abstract

Mammary analogue secretory carcinoma (MASC) has recently been recognized as a salivary gland tumour that is characterized by the ETV6–NTRK3 fusion gene. A case of locally advanced MASC of the parotid gland in a 67-year-old man is presented here. The patient visited the hospital due to a large right infra-auricular mass, which had been enlarging gradually over a period of 2 years. Contrast-enhanced computed tomography (CT) demonstrated a multilocular mass, 75 × 63 mm in size, containing a fluid component with non-uniform contrast effects in the interior portion. The mass had invaded the orbit, skull base, and parapharyngeal space. The patient had neither lymph node nor distant metastasis. The tumour showed tubular and ductal proliferation lined by a single layer of neoplastic cuboidal cells with clear foamy cytoplasm. Characteristic hobnail cells were observed. Expression of ETV6–NTRK3 fusion transcript in the tumour tissues was confirmed by RT-PCR. The final diagnosis was MASC (T4bN0M0, stage IVB). The patient received cetuximab together with radiotherapy at a total dose of 66 Gy. After treatment, CT showed a slightly reduced tumour volume, indicating stable disease. More than 56 months after treatment, the patient remains alive with no remarkable change in the tumour.

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Accuracy of custom-fitted temporomandibular joint alloplastic reconstruction and virtual surgical planning

Publication date: Available online 15 February 2019

Source: International Journal of Oral and Maxillofacial Surgery

Author(s): S. Sembronio, A. Tel, F. Costa, M. Isola, M. Robiony

Abstract

The purpose of this study was to evaluate the accuracy of temporomandibular joint (TMJ) custom-made replacements by means of virtual surgical planning.

The authors review 11 TMJ custom-made prostheses made of both mandibular and fossa components. Surgeries were virtually planned and patient-specific devices were designed together with surgical cutting and positional guides. Three-dimensional models for both preoperative planning and postoperative computed tomography scans were generated and overlapped in order to evaluate differences in measurements. Correlation between virtual preoperative and real postoperative prosthesis positioning was described by Lin's coefficient.

Results of statistical analysis showed an almost perfect concordance. Wilcoxon's matched-pairs test showed no statistically significant deviation between preoperative virtual surgical planning and postoperative results. Colour map analysis confirmed the correspondence between virtually planned positioning of the devices and postoperative results. All the prostheses were placed with great accuracy.

In conclusion, virtual surgical planning, surgical guides and patient-specific devices provide accuracy and precision in surgery for custom-made TMJ replacement.

http://bit.ly/2IfSYXu

Influence of mandibular setback surgery on three-dimensional pharyngeal airway changes

Publication date: Available online 15 February 2019

Source: International Journal of Oral and Maxillofacial Surgery

Author(s): S.-T. Lee, J.-H. Park, T.-G. Kwon

Abstract

The aim of this study was to investigate the factors influencing three-dimensional changes in pharyngeal airway space after mandibular setback surgery. Airway changes in 48 skeletal class III patients who had undergone mandibular setback surgery alone (n = 25, group 1) or with maxillary surgery (n = 23, group 2) were analyzed. Linear parameters, cross-sectional area, and volumes of the pharyngeal airway were evaluated before (T0), immediately after (T1), and 1 year after surgery (T2) by cone beam computed tomography. Although the reduced airway volume and cross-sectional area recovered slightly in the long term after surgery, the total pharyngeal airway volume (TPV) was significantly reduced compared to baseline, by 15% in group 1 and 12% in group 2. Regression analysis showed that maxillary posterior impaction in two-jaw surgery had a protective effect on preserving TPV. A change in body mass index from T0 to T2 was an important predictor of decreased TPV in one-jaw surgery patients. Maxillary posterior impaction can be a reliable option for compensating the pharyngeal airway reduction after mandibular setback surgery. Postoperative weight gain can increase the risk of postoperative pharyngeal airway reduction. Therefore, these factors need to be considered before and after mandibular setback surgery.

http://bit.ly/2GuKJ8a

Adenoid cystic carcinoma with high-grade transformation forming spindle cell component of the submandibular gland

Publication date: Available online 16 February 2019

Source: Auris Nasus Larynx

Author(s): Masaru Miyazaki, Mikiko Aoki, Kaori Koga, Makoto Hamasaki, Yoshikazu Sugiyama, Kensuke Midorikawa, Daisuke Hamatake, Michio Masaki, Yasushi Takamatsu, Akinori Iwasaki, Toshifumi Sakata, Toshitaka Nagao, Kazuki Nabeshima

Abstract

Adenoid cystic carcinoma (AdCC) with high-grade transformation (AdCC-HGT) is rare, and AdCC-HGT with spindle cell component is particularly rare. The patient was a 65-year-old man with a 5 cm sized swelling of the right submandibular gland. Submandibular sialoadenectomy was performed. Histopathological findings mainly showed conventional AdCC, and minorly showed two other components: (1) the pleomorphic component, a proliferation of atypical pleomorphic epithelial cells forming solid or small clusters and accompanied by necrosis; (2) the spindle cell component, containing atypical spindle cells invading the stroma. Postoperative chemoradiotherapy was performed. Multiple right lung nodular lesions were found on the contrast-enhanced chest CT one month after the surgery. Thoracoscopic pulmonary resection was performed. The lung tumors exhibited a proliferation of atypical spindle cells, accompanied by necrosis. We considered that the spindle cell component of the AdCC-HGT of the submandibular gland developed lung metastases. The patient died seven months after submandibular sialoadenectomy due to respiratory failure. Although rare, our case highlights the importance of recognising spindle cell components in conventional AdCC; even if the area is small, these high-grade transformation areas can metastasise and become prognostic factors.

http://bit.ly/2tqq38Q

HLA-A*32:01 is strongly associated with vancomycin-induced drug reaction with eosinophilia and systemic symptoms

Publication date: Available online 16 February 2019

Source: Journal of Allergy and Clinical Immunology

Author(s): Katherine C. Konvinse, Jason A. Trubiano, Rebecca Pavlos, Ian James, Christian M. Shaffer, Cosmin A. Bejan, Ryan J. Schutte, David A. Ostrov, Mark A. Pilkinton, Misha Rosenbach, Jeffrey P. Zwerner, Kristina B. Williams, Jack Bourke, Patricia Martinez, Francois Rwandamuriye, Abha Chopra, Mark Watson, Alec J. Redwood, Katie D. White, Simon A. Mallal

Abstract

Background

Vancomycin is a prevalent cause of the severe hypersensitivity syndrome drug reaction with eosinophilia and systemic symptoms (DRESS) which leads to significant morbidity and mortality and commonly occurs in the setting of combination antibiotic therapy which impacts future treatment choices. Variations in human leukocyte antigen (HLA) class I in particular have been associated with serious T-cell mediated adverse drug reactions which has led to preventive screening strategies for some drugs.

Objective

To determine if variation in the HLA region is associated with vancomycin-induced DRESS.

Methods

Probable vancomycin DRESS cases were matched 1:2 with tolerant controls based on sex, race, and age using BioVU, Vanderbilt's deidentified electronic health record database. Associations between DRESS and carriage of HLA class I and II alleles were assessed by conditional logistic regression. An extended sample set from BioVU was utilized to conduct a time-to-event analysis of those exposed to vancomycin with and without the identified HLA risk allele.

Results

Twenty-three individuals met inclusion criteria for vancomycin-associated DRESS. 19/23 (82.6%) cases carried HLA-A*32:01 compared to 0/46 (0%) of the matched vancomycin tolerant controls (p=1x10^-8) and 6.3% of the BioVU population (n=54,249) (p=2x10^-16). Time-to-event analysis of DRESS development during vancomycin treatment among the HLA-A*32:01 positive group indicated that 19.2% developed DRESS and did so within four weeks.

Conclusions

HLA-A*32:01 is strongly associated with vancomycin DRESS in a population of predominantly European ancestry. HLA-A*32:01 testing could improve antibiotic safety, help implicate vancomycin as the causal drug and preserve future treatment options with co-administered antibiotics.

Graphical abstract

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Treatments of Cold Urticaria: A Systematic Review

Publication date: Available online 15 February 2019

Source: Journal of Allergy and Clinical Immunology

Author(s): Kanokvalai Kulthanan, Saowalak Hunnangkul, Papapit Tuchinda, Leena Chularojanamontri, Puncharas Weerasubpong, Chanika Subchookul, Marcus Maurer

Abstract

Background

Several treatment options for cold urticaria (ColdU) have been studied and reported, but systematic reviews and meta-analyses are limited.

Objectives

To meta-analyze and review the efficacy and safety of ColdU treatments.

Methods

We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations. Suitable reports were identified by searching PubMed, Scopus, and Web of Science. Our systematic review included 16 studies, 9 of which met the eligibility criteria for the meta-analysis. We analyzed the effects of treatments on the critical temperature thresholds (CTTs) and critical stimulation time thresholds (CSTTs), as well as on the rates of complete response and adverse events.

Results

Our pooled meta-analyses showed that non-sedating, second-generation H₁-antihistamines (nsAHs) are effective in the treatment of ColdU, and that the updosing of nsAHs significantly reduced CTTs relative to their own standard doses and placebos. In 4 studies involving CSTT, the updosing of nsAHs also showed significantly better CSTTs than their own standard doses or placebos. Omalizumab resulted in a marked reduction of CTTs in H₁-AH-resistant patients. Of 118 adverse events in 8 studies, standard-dose nsAHs, updosed nsAHs, and omalizumab produced lower numbers of adverse events than first-generation AHs.

Conclusions

Our study showed that higher dosages of nsAHs were more effective than their own standard dosages in controlling ColdU symptoms. Increasing the dosages was not significantly associated with higher adverse event rates. Omalizumab at 150 and 300 mg every 4 weeks was shown to be effective for ColdU patients refractory to AHs.

http://bit.ly/2GuJZQd

Increased proportions of γδ T lymphocytes in atypical SCID associate with disease manifestations

Publication date: Available online 15 February 2019

Source: Clinical Immunology

Author(s): Inga Tometten, Kerstin Felgentreff, Manfred Hönig, Fabian Hauck, Michael H. Albert, Tim Niehues, Ruy Perez, Sujal Ghosh, Capucine Picard, Jan Stary, Renata Formankova, Austen Worth, Pere Soler-Palacín, Marina García-Prat, Luis M. Allende, Luis Ignacio Gonzalez-Granado, Polina Stepensky, Silvia Di Cesare, Alessia Scarselli, Caterina Cancrini

Abstract

Severe combined immunodeficiencies (SCID) comprise a group of genetic diseases characterized by abrogated development of T lymphocytes. In some case reports of atypical SCID patients elevated proportions of γδ T lymphocytes have been reported. However, it is unknown whether these γδ T cells modulate or reflect the patient's clinical phenotype. We investigated the frequency of elevated γδ T cell proportions and associations with clinical disease manifestations in a cohort of 76 atypical SCID patients. Increased proportions of γδ T lymphocytes were present in approximately 60% of these patients. Furthermore, we identified positive correlations between elevated proportions of γδ T cells and the occurrence of CMV infections and autoimmune cytopenias. We discuss that CMV infections might trigger an expansion of γδ T lymphocytes, which could drive the development of autoimmune cytopenias. We advocate that atypical SCID patients should be screened for elevated proportions of γδ T lymphocytes, CMV infection and autoimmune cytopenias.

http://bit.ly/2GuqEyW

Whole-exome sequencing identification of a novel splicing mutation of RUNX2 in a Chinese family with cleidocranial dysplasia

Publication date: Available online 15 February 2019

Source: Archives of Oral Biology

Author(s): Tingting Zhang, Wu Jing, Xiaoxue Zhao, Feifei Hou, Tengfei Ma, Huijuan Wang, Xu Zhang, Xiangyu Zhang

Abstract

Objectives

Cleidocranial dysplasia (CCD) is a congenital autosomal dominant skeletal disease characterized by multiple craniofacial and dental anomalies. Here, we investigated mutation of the runt-related transcription factor 2 (RUNX2) gene, which is considered responsible for most instances of CCD in patients, in a Chinese family with CCD.

Methods

Genomic DNA was extracted from the peripheral blood lymphocytes of all participants, and mutation analysis was performed using whole-exome and Sanger sequencing. Biophysical predictions of the altered protein were analyzed using various bioinformatics tools, and direct sequencing via reverse transcription polymerase chain reaction (PCR) was performed for functional analysis of the mutation. To determine the function of the mutated protein, expression of RUNX2 and integrin-binding sialoprotein (IBSP) was investigated via quantitative PCR.

Results

We identified a novel splicing mutation (c.581–9 T > G) in all affected members, with this RUNX2 mutation incorporating in a new splice site to replace the canonical splice site, thereby resulting in insertion of an 8-bp fragment within the terminal exon 5 splice-acceptor site and premature translation termination. qPCR results confirmed attenuated RUNX2 expression and IBSP overexpression in the peripheral blood lymphocytes of patients.

Conclusions

These results suggested that the newly identified splice-site mutation (c.581–9 T > G) in RUNX2 was responsible for CCD in this family through its alteration of RUNX2 activity and upregulated IBSP levels. These findings extend the mutational spectrum of the RUNX2 gene and might contribute to genetic diagnosis and counseling of families with CCD.

http://bit.ly/2SBexGF

Whole-exome sequencing identification of a novel splicing mutation of RUNX2 in a Chinese family with cleidocranial dysplasia

Publication date: Available online 15 February 2019

Source: Archives of Oral Biology

Author(s): Tingting Zhang, Wu Jing, Xiaoxue Zhao, Feifei Hou, Tengfei Ma, Huijuan Wang, Xu Zhang, Xiangyu Zhang

Abstract

Objectives

Cleidocranial dysplasia (CCD) is a congenital autosomal dominant skeletal disease characterized by multiple craniofacial and dental anomalies. Here, we investigated mutation of the runt-related transcription factor 2 (RUNX2) gene, which is considered responsible for most instances of CCD in patients, in a Chinese family with CCD.

Methods

Genomic DNA was extracted from the peripheral blood lymphocytes of all participants, and mutation analysis was performed using whole-exome and Sanger sequencing. Biophysical predictions of the altered protein were analyzed using various bioinformatics tools, and direct sequencing via reverse transcription polymerase chain reaction (PCR) was performed for functional analysis of the mutation. To determine the function of the mutated protein, expression of RUNX2 and integrin-binding sialoprotein (IBSP) was investigated via quantitative PCR.

Results

We identified a novel splicing mutation (c.581–9 T > G) in all affected members, with this RUNX2 mutation incorporating in a new splice site to replace the canonical splice site, thereby resulting in insertion of an 8-bp fragment within the terminal exon 5 splice-acceptor site and premature translation termination. qPCR results confirmed attenuated RUNX2 expression and IBSP overexpression in the peripheral blood lymphocytes of patients.

Conclusions

These results suggested that the newly identified splice-site mutation (c.581–9 T > G) in RUNX2 was responsible for CCD in this family through its alteration of RUNX2 activity and upregulated IBSP levels. These findings extend the mutational spectrum of the RUNX2 gene and might contribute to genetic diagnosis and counseling of families with CCD.

http://bit.ly/2SBexGF

Prurigo pigmentosa in a fair-skinned European woman: Dramatic improvement with doxycycline

Publication date: Available online 15 February 2019

Source: Annales de Dermatologie et de Vénéréologie

Author(s): J. Sanchez, A. Durlach, P. Bernard, B. Cribier, M. Viguier

Summary

Introduction

Prurigo pigmentosa is a rare inflammatory, pruriginous skin disease seen predominantly in young Asian women, with average age of onset in the mid-20s.

Observation

A 25-year-old fair-skinned European woman presented with a two-year history of pruriginous skin lesions recurring fortnightly. The initial lesions were inflammatory papules, which first emerged on the back of the neck before spreading to the shoulders, below the breasts and the back. The papules resolved leaving a reticular hyperpigmented network that gradually worsened after each episode. The clinical presentation and histopathological findings were consistent with a diagnosis of prurigo pigmentosa. Doxycycline 200 mg/day was initiated, with rapid resolution, absence of any further flare-ups and gradual regression of the reticular pigmentation.

Discussion

Prurigo pigmentosa is a skin disease of stereotypical presentation marked by frequent inflammatory flare-ups involving the trunk that are followed by periods of remission with residual hyperpigmentation. Herein we report a case observed in a fair-skinned French female subject. It is important that dermatologists are able to recognize it and distinguish it from other forms of pruriginous papular dermatosis, owing to the dramatic efficacy of tetracyclines in controlling the inflammatory flares and in reducing the adverse aesthetic impact of hyperpigmentation.

Résumé

Introduction

Le prurigo pigmentosa est une maladie cutanée inflammatoire rare, survenant habituellement chez des jeunes femmes asiatiques âgées de 20 à 30 ans.

Observation

Une jeune femme européenne à peau claire, âgée de 25 ans, développait depuis deux ans des lésions cutanées évoluant par poussées toutes les deux semaines. La poussée commençait par des lésions papuleuses inflammatoires très prurigineuses touchant essentiellement le dos. L'effacement des papules en fin de poussée laissait place à un réseau maculeux hyperpigmenté, de plus en plus marqué au fur et à mesure des poussées. La présentation clinique et l'histologie cutanée étaient compatibles avec le diagnostic de prurigo pigmentosa. Un traitement par doxycycline, 200 mg/j, s'accompagnait d'une amélioration très rapide, sans nouvelle poussée et avec régression progressive de l'hyperpigmentation.

Discussion

Le prurigo pigmentosa est une dermatose de présentation stéréotypée où alternent poussées de papules prurigineuses inflammatoires du tronc et phases de rémission avec hyperpigmentation séquellaire en réseau. Nous avons observé un cas survenant chez une jeune femme française à peau claire. Cette dermatose est importante à connaître et à isoler des autres dermatoses papuleuses prurigineuses en raison de la très grande efficacité des cyclines, qui permettent de mettre fin aux poussées inflammatoires et de réduire ainsi l'impact esthétique de la maladie lié à l'hyperpigmentation.

http://bit.ly/2BCRGQC

Les évolutions de la maladie VIH et de sa prise en charge ont modifié le rôle du dermatologue

Publication date: Available online 15 February 2019

Source: Annales de Dermatologie et de Vénéréologie

Author(s): S. Fouéré

http://bit.ly/2TTFGRQ

Editorial board

Publication date: February 2019

Source: Annales de Dermatologie et de Vénéréologie, Volume 146, Issue 2

Author(s):

http://bit.ly/2BE0DsB

Home environment of infants with risk indicators for hearing loss tends to be less stimulating

Publication date: Available online 16 February 2019

Source: International Journal of Pediatric Otorhinolaryngology

Author(s): Danielle Mendonça Araujo, Denise Castilho Cabrera Santos, Maria Cecília Marconi Pinheiro Lima

Abstract

Objective

To verify the home opportunities to the motor development offered to infants with and without risk indicators for hearing loss (RIHL).

Methods

Observational transversal study was done with infants between 8 and 10 months, being 77 with RIHL (Study Group-SG) and 77 without RIHL (Control Group-CG) The instrument used to characterize the sample and obtain information about the home affordances was the questionnaire Affordances in the Home Environment for the Motor Development - Infant Scale (AHEMD-IS). The results of the AHEMD-IS between the groups were compared using the Mann-Whitney and Chi-Squared tests. The significance test adopted for the study was 5%.

Results

Absolute values in the frequency of homes considered "moderately adequate" and "less than adequate" were greater in the SG in the most part of the categories, except the item Toys for Fine Motricity. It was possible to observe a statistically significant difference in the Total Score of the groups (p-value = 0.01346). Even with better results when compared with the SG, the number of homes of the CG group with affordances below expected is more than half of the sample.

Conclusions

It was possible to verify that home of infants with risk indicators for hearing loss have statistically less affordances when compared to the homes of infants without the indicators. The results alert us to the need of orientation to the infant's responsible/caretakers regarding to the importance of a favorable environment with stimulation of the infant motor development.

http://bit.ly/2TRuxAT

Annual hearing screening in girls with Turner Syndrome: results from the first three years in Glasgow

Publication date: Available online 15 February 2019

Source: International Journal of Pediatric Otorhinolaryngology

Author(s): Haytham Kubba, Kerrie McAllister, Karen Hunter, Avril Mason

Abstract

Background

Hearing loss is prevalent in girls with Turner Syndrome (TS). A number of cross-sectional studies have confirmed that conductive hearing loss due to middle ear disease and permanent, progressive sensorineural hearing loss are both very common and often unrecognised in TS. Hearing screening has been suggested by many authors and is recommended in some recent national audiology guidelines (every 3-5 years in an international consensus statement, every 1-2 years in the USA and every year in the UK). The effectiveness of such regular hearing screening has not been assessed before.

Study aims and methods

In January 2016 we began a programme of annual hearing screening for all girls attending the West of Scotland TS clinic. We have collected data on age, karyotype, ear and hearing symptoms, otoscopy findings, audiometric test results and subsequent outcomes for the first three years of our programme. Our aim is to assess whether this screening programme is an effective use of resources, with a worthwhile rate of detecting new otological problems and without an excessive additional workload for the audiology department.

Results

Twenty-six girls participated in the screening programme and 8 of these had no hearing issues or ear abnormalities at any time over the 3 years. Two girls had cholesteatoma, 4 had tympanic membrane retractions and/or perforations, and 9 had OME (of which 6 were transient and 3 persistent, with 2 of these requiring treatment). One cholesteatoma, one perforation and one persistent OME were already known about but all other diagnoses were new as a result of the screening programme. Five girls have persistent conductive hearing loss (plus another 6 who had a transient episode of conductive loss due to middle ear fluid) and 6 have some degree of sensorineural hearing loss (3 purely sensorineural, 3 mixed). At the time that a hearing loss was diagnosed, the parents had concerns about the hearing in 4 cases and no concerns in 12. Six girls have been fitted with hearing aids since we started the screening programme, each for different indications (sensorineural hearing loss in two cases, and one case each of persistent OME, post cholesteatoma surgery, tympanic membrane perforation and unilateral tympanic membrane retraction respectively). Two girls have had ear surgery as a result of referral from the programme (one for ventilation tubes, one for cholesteatoma).

Conclusions

The screening programme has picked up ear disease in 69% of girls with TS with only a small additional workload for the audiology department. The ongoing detection of new problems in the second and third years of the programme attests to the value of continued regular hearing screening for girls with TS.

http://bit.ly/2BypGgT

Childhood hearing loss: Impact on parents and family life

Publication date: Available online 15 February 2019

Source: International Journal of Pediatric Otorhinolaryngology

Author(s): Jesper Dammeyer, Anja Toft Hansen, Kathryn Crowe, Marc Marschark

Abstract

Background

Studies investigating the impact of having a child with hearing loss on the lives of parents and families have shown divergent results. Where some studies have reported that childhood hearing loss is associated with parental mental health problems, such as depression and stress, other studies report no impact on parental mental health and/or wellbeing.

Objective

The aim of this study was to examine the association between child-related variables—degree of hearing loss, additional disabilities, sign language abilities, cochlear implants (CI), externalizing and internalizing emotional and behavioral difficulties measured by the Strength and Difficulties Questionnaire (SDQ)—and parent-related variables—parents living together, parents' mental health, spouse activities without children, and parents' experience of the child as being a burden for the family.

Method

Data of 257 parents of children with hearing loss from a national survey were included.

Results

Only 18% of the children with hearing loss did not live with both parents, a figure significantly lower than that of the general population. The child variables of degree of hearing loss, having a CI or not, and sign language ability were not significantly associated with any of the parent variables investigated. The child having a disability in addition to hearing loss was found to be significantly associated with the frequency of spouses engaging in activities without children and reports that the child was a burden for the family. Both higher externalizing and internalizing scores on the SDQ were significantly associated with parental mental health problems, frequency of spouse activities without children, and the degree to which the child's difficulties were experienced as a burden for the family.

Conclusion

Children's hearing loss, per se, was found not to be significantly related to several key parent and family variables. However, children having additional disabilities and behavioral and emotional difficulties were significant with parent and family variables. This study thus underlines the need for further studies concerning relationships among factors related to childhood hearing loss and various family factors in order to better understand their impact on child development and family life.

http://bit.ly/2TRunJN

Survival outcomes after treatment of cancer of the oral cavity (1985–2015)

Publication date: March 2019

Source: Oral Oncology, Volume 90

Author(s): Daniella Karassawa Zanoni, Pablo H. Montero, Jocelyn C. Migliacci, Jatin P. Shah, Richard J. Wong, Ian Ganly, Snehal G. Patel

Abstract

Objectives

To present treatment results of oral squamous cell carcinoma (OSCC) at a tertiary cancer care center from 1985 to 2015.

Materials and methods

A total of 2082 patients were eligible for this study. Main outcomes measured were overall survival (OS) and disease specific survival (DSS). Prognostic variables were identified with bivariate analyses using Kaplan-Meier curves and log-rank testing for comparison. A p-value < 0.05 was considered statistically significant and significant factors were entered into multivariate analysis. Median age was 62 years (16–100), 56% were men, 66% reported a history of tobacco use and 71% of alcohol consumption. The most common subsite was tongue (51%). Seventy-three percent of patients had cT1-2 and 71% had clinically negative necks (cN0). Surgery alone was performed in 1348 patients (65%), adjuvant postoperative radiotherapy in 608 patients (29%) and postoperative chemoradiation in 126 patients (6%). Neck dissection was performed in 920 patients with cN0, and in 585 patients with a clinically involved neck. The median follow-up was 37.6 months (range 1–382).

Results

The 5-year OS and DSS were 64.4% and 79.3%, respectively. Age, comorbidities, margin status, vascular invasion, perineural invasion, AJCC 8th edition pT, and pN were independent prognostic factors of OS (p < 0.05). History of alcohol consumption, margin status, vascular invasion, perineural invasion, pT, and pN were independent prognostic factors of DSS (p < 0.05).

Conclusion

pN stage is the most powerful and consistent predictor of outcome in patients with OSCC treated with primary surgery and appropriate adjuvant therapy.

http://bit.ly/2V0ePUf

Can topical 5-fluorouracil be used as a viable treatment option for oral premalignant lesions and tumors?

Publication date: Available online 15 February 2019

Source: Oral Oncology

Author(s): Samapika Routray, Punit S. Dikhit, B.C. Rajani, Mohd. Musab Khan

http://bit.ly/2EdoHnO

Point of care ultrasonography in the allergy and immunology clinic

Publication date: Available online 16 February 2019

Source: Annals of Allergy, Asthma & Immunology

Author(s): Samira Jeimy, Andrew Wong-Pack, Shafaz Veetil, Harold Kim

http://bit.ly/2X5DvMR

Regarding clinical implications of magnetic resonance imaging in temporomandibular disorder patients presenting ear fullness

http://bit.ly/2GMo06K

In reference to management and follow‐up results of salivary fistulas treated with botulinum toxin

http://bit.ly/2tq9cmA

Surgery versus radiation for T1 glottic carcinoma: Second primary considerations

Although early glottic carcinoma is managed with radiation therapy (RT) or surgery, there is limited data on differences in second primary cancers of the larynx. We utilized the Surveillance, Epidemiology, and End Results (SEER) database to query T1 glottic carcinomas and assess the incidence of second primary laryngeal malignancies. Cumulative hazard for second primary laryngeal malignancies was compared with the log‐rank method. Among 844 surgical and 2,272 RT cases, observed‐to‐expected incidence ratios of laryngeal second primaries were 10.19 (5.89–16.55) and 6.87 (4.64–9.81) per 10 thousand person‐years, respectively. Mean person‐years at risk were comparable at 8.16 years (surgery) and 8.01 years (RT), and relative increased risk of laryngeal second primary was 20.95 (surgery) versus 14.09 (RT) per 10 thousand person‐years. Mean times to development of a second primary were also comparable (304 vs. 305 months, P = 0.898). Thus, second laryngeal primary development is analogous between cases treated with surgery alone versus RT. Continued discussion and investigation of surgery versus RT for early glottic squamous cell carcinoma will need to leverage these findings, along with ongoing investigation of voice and survival outcomes, to develop more well‐informed treatment algorithms. Laryngoscope, 2019

http://bit.ly/2GMpCgI

Clinicians vs. epidemiologists: Patch testing with methyldibromo glutaronitrile as a controversial issue

Abstract

The preservative methyldibromo glutaronitrile (MDBGN) (CAS 35691‐65‐7) is known since long as an important contact allergen mainly used in cosmetics (Review: [1]). MDBGN was banned EU‐wide from being used in leave‐on products in 2005, for rinse‐off products in 2008, and further restricted for non‐cosmetic (technical) applications in 2010. However, positive reactions in patch testing (PT) continued to occur.

This article is protected by copyright. All rights reserved.

http://bit.ly/2X4VbYS

Nested case‐control study investigating the diagnostic role of tissue eosinophilia in adverse cutaneous drug reactions

Abstract

Background

Although tissue‐eosinophilia has traditionally been considered diagnostically supportive of adverse cutaneous drug reactions (ACDRs), studies have suggested it is neither a sensitive nor a specific finding in drug eruptions (DEs).

Objectives

Determining whether skin‐tissue eosinophilia is a reliable indicator of ACDR.

Methods

A nested case‐control retrospective study conducted in a cohort of 170 patients at a single institution. Tissue eosinophilia (number of eosinophils per High Power Field (HPF)) was investigated in skin biopsies obtained from the following groups of patients who demonstrated: a)in vitro assay and telephone interview‐validated cutaneous drug reactions (True DE); b)initial clinical diagnosis of ACDR but drug etiology was excluded by in vitro assay and telephone interview (False DE); c)non drug‐associated cutaneous eruptions, skin tumors and nevi, randomly selected for evaluation (control).

Results

Significantly higher number of eosinophils per HPF was observed in the False DE compared to the True DE group (p=0.02). The False DE group demonstrated a higher number of eosinophils (p<0.001) while the True DE group eosinophils' number was not significantly higher as compared to control (p=0.2032).

Conclusions

Tissue eosinophilia is not a reliable indicator of ACDRs.

This article is protected by copyright. All rights reserved.

http://bit.ly/2S3FCNn

Comparison of efficacy of cold trypsinization versus warm trypsinization in preparation of autologous noncultured epidermal cell suspension for treatment of stable vitiligo

Abstract

Surgical modalities are the mainstay of treatment for medically resistant vitiligo. Among various techniques, non‐cultured epidermal cell suspension (NCES) has proven to be an effective and most accepted technique because of its advantage of treating large areas.

This article is protected by copyright. All rights reserved.

http://bit.ly/2X6ZmU4

Ultrasonography for early detection of non‐infectious necrotizing fasciitis secondary to cutaneous loxoscelism

Abstract

A 50‐year‐old woman consulted to the emergency department for painful erythematous swelling on her forearm hours after a spider bite. The patient had spent the evening cleaning the outside of her home, located in the periphery of an urban area, next to a ravine, on the western Mediterranean Basin, when she identified a spider on the dorsum of her forearm. She described it as a light‐brown coloured spider, with darker long legs, between 1 and 1,5 cm in size. Though she felt no pain she brushed off the spider and it scared away. Hours later she began feeling pain on that same forearm. She had no systemic symptoms. Physical examination revealed an erythematoedematous plaque on her forearm. Blood work revealed leukocytosis (13 x10⁹/L) and neutrophilia (81,3%). Cultures from blood and skin were taken. The patient was diagnosed with cellulitis versus suspected CL and admitted for intravenous antibiotic and non‐steroidal antiinflamatory therapy.

This article is protected by copyright. All rights reserved.

http://bit.ly/2S2tvQV

Psoriasis and skin pain: real‐life effectiveness of calcipotriol plus betamethasone dipropionate in aerosol foam formulation

Abstract

Background/objective

Although 40% of psoriasis patients reported skin pain, this symptom is often underestimated. A new formula of calcipotriol plus betamethasone dipropionate (Cal/BD) has been recently approved for psoriasis treatment. Therefore, we aimed to evaluate the efficacy of Cal/BD aerosol foam on skin pain of patients with plaque psoriasis.

Methods

A real‐life 4 weeks prospective, open study on Cal/BD aerosol foam (not compared to vehicle or emollient cream) was performed in adult psoriasis patients attending three Dermatology units located in Campania region, Italy, between March and October 2018. Inclusion criteria were a history of skin pain over the last week and psoriatic involvement of the palmar area. Before (t0) and after a course of once daily application of Cal/BD aerosol foam for 4 weeks (t1), the following items were evaluated: Psoriasis Area and Severity Index (PASI), Physician Global Assessment (PGA) index of target plaque on palmar region, subjective skin pain features through Pain Qualities Assessment Scale (PQAS) questionnaire, and skin pain threshold measured by pressure digital algometer at palmar psoriatic plaques.

Results

seventy‐five patients (43 male, mean age of 43.2 years) were enrolled. After 4 weeks of therapy with Cal/BD aerosol foam, a significant improvement in both PASI (mean: 6.5±2.1 at t0 vs 2.3±1.6 at t1) and palmar plaques PGA (mean: 3.6 at t0 vs 1.7 at t1) was observed (p<0.001). The mean intensity score of skin pain decreased from 7.6 to 1.3 (p<0.001); among skin pain qualities, intense, sensible, aching, and unpleasant showed the highest rate of reduction (t0‐t1: 6.3, 6.3, 6.1 and 5.8, respectively). Pain threshold of palmar skin lesions increased at t1.

Conclusions

our real‐life study suggested that Cal/BD aerosol foam may represent a valid topical anti‐psoriatic treatment, not only improving skin lesions, but also relieving cutaneous pain, thus contributing to ameliorate patients' quality of life.

This article is protected by copyright. All rights reserved.

http://bit.ly/2X6pHBJ

The fibroblast of radicular cyst facilitate osteoclastogenesis via the autocrine of Fibronectin containing extra domain A

Abstract

Objective

To investigate the alternative spliced isoforms of Fibronectin (FN) in the stroma of radicular cysts; and analyze the associations between these isoforms and the osteoclastogenic effects of fibroblasts.

Methods and materials

The specimens of radicular cysts were stained with immunohistochemistry, and the associations between each FN isoform and clinical parameters were assessed. The fibroblasts isolated from cysts or jaw bone were cultured to induce the Trap+MNCs. In the conditioned medium, the Fibronectin containing extra domain A (EDA+FN) were neutralized by antibody IST‐9, and the EDA exon of fibroblasts were knockout by CRISPR/Cas system, for assessing the osteolastogenic effects. The mRNA level of FN isoforms and the osteoclastogenesis related genes were analyzed by quantitive PCR.

Results

EDA+FN staining was positively associate with the size of the lesions (P<0.05). In contrast with the controls, the ratio of EDA+FN/total FN in the fibroblasts from radicular cysts was significantly higher (P<0.05), and positively associate with Trap+MNCs counting, it was consistent with increased expression of COX‐2, IL‐6, IL‐17 and the RANKL/OPG (P<0.05). The Trap+MNCs counting and osteoclastogenesis related genes were decreased by IST‐9 blocking and EDA exon knockout in fibroblasts, but the blockage of the interaction between EDA+FN and pre‐osteoclasts exhibited little effects on Trap+MNCs formation.

Conclusion

The microenvironment of the fibrous capsule of radicular cysts facilitate the splicing of EDA exon, it endues EDA+FN with autocrine effects on fibroblast itself, and increases the expression of osteoclastogenesis related genes, by which the osteoclastogenesis in radicular cysts could be initiated.

This article is protected by copyright. All rights reserved.

http://bit.ly/2X8npSS

Issue Information

http://bit.ly/2S6sRBF

Investigating the Nasal Cycle Using Unilateral Peak Nasal Inspiratory Flow and Acoustic Rhinometry Minimal Cross‐Sectional Area Measurements

Abstract

Objective

To plot the nasal cycle using unilateral peak nasal inspiratory flow (UPNIF) and unilateral minimal cross‐sectional area (UMCA) readings demonstrating a linear relationship in normal nasal function. Additionally, to determine how this changes in abnormal nasal function.

Design

A cross‐sectional study measuring UPNIF and UMCA in controls demonstrating normal nasal function and in patients with nasal obstruction.

Setting

Royal National Throat Nose and Ear Hospital, London.

Participants

39 participants, 26 controls and 13 patients, were recruited. Controls exhibited normal nasal function with SNOT‐22 <5. Patients nasal obstruction symptoms secondary to inflammation or structural abnormality with SNOT‐22 >9.

Main Outcome Measures and Results

Airflow rates and resistance values were derived from UPNIF and UMCA measurements respectively based on Poiseuille's laws. Ratios between right and left UPNIF and UMCA values were taken to adjust for confounding factors. The relationship of 1/Resistance Ratio and Airflow Rate Ratio demonstrated a linear of direct proportionality of strong correlation and statistical significance (correlation coefficient =0.76, p<<0.01). This suggests that data points from controls with a normal nasal cycle lie closely along the regressed line, while those lying significantly away were shown to belong to patients with nasal dysfunction. Olfactory dysfunction appears to be a sensitive discriminator in predicting this.

Conclusion

This study demonstrates the directly proportional relationship of 1/Resistance Ratio and Airflow Rate Ratio in normal nasal function. Furthermore, nasal pathology can be predicted if data points lie significantly outside these normal limits. Further studies are needed to validate exact normal and abnormal thresholds.

This article is protected by copyright. All rights reserved.

http://bit.ly/2S5I6er

“Cold turkey” or pharmacotherapy: Examination of tobacco cessation methods tried among smokers prior to developing head and neck cancer

Abstract

Background

Tobacco cessation methods employed by patients with head and neck cancer (HNSCC) are previously unstudied and have the potential to inform choice of cessation method and necessary abstinence support.

Methods

A total of 130 current smokers with HNSCC were queried regarding prior unsuccessful tobacco cessation techniques, product used (cold turkey, varenicline, and nicotine patch/gum), and maximum time abstained from smoking.

Results

One hundred six smokers retrospectively reported using one of the four main quit methods. Unassisted cessation ("cold turkey") was the most commonly used method (P < .001). A multiple ordinal logistic general estimating equation analysis revealed that cold turkey had increased odds [5.2 (95% confidence interval [CI]: 2.2, 11.8) and 4.3 (95% CI: 1.5, 12.9)] of achieving a longer quit duration than the nicotine patch or varenicline, respectively.

Conclusions

Among smokers developing HNSCC, previous cessation attempts were most commonly unassisted. This method was associated with longest abstinence periods. These data suggest insufficient support and education regarding behavioral and pharmacologic cessation therapies.

http://bit.ly/2EduhH6

Neuro-Oncology Diet and risk of glioma

Estimating survival for renal cell carcinoma patients with brain metastases: an update of the Renal Graded Prognostic Assessment tool Abstract Background Brain metastases are a common complication of renal cell carcinoma (RCC). Our group previously published the Renal Graded Prognostic Assessment (GPA) tool. In our prior RCC study (n = 286, 1985–2005), we found marked heterogeneity and variation in outcomes. In our recent update in a larger, more contemporary cohort, we identified additional significant prognostic factors. The purpose of this study is to update the original Renal-GPA based on the newly identified prognostic factors. Methods A multi-institutional retrospective institutional review board–approved database of 711 RCC patients with new brain metastases diagnosed from January 1, 2006 to December 31, 2015 was created. Clinical parameters and treatment were correlated with survival. A revised Renal GPA index was designed by weighting the most significant factors in proportion to their hazard ratios and assigning scores such that the patients with the best and worst prognoses would have a GPA of 4.0 and 0.0, respectively. Results The 4 most significant factors were Karnofsky performance status, number of brain metastases, extracranial metastases, and hemoglobin. The overall median survival was 12 months. Median survival for GPA groups 0–1.0, 1.5–2.0, 2.5–3, and 3.5–4.0 (% n = 25, 27, 30 and 17) was 4, 12, 17, and 35 months, respectively. Conclusion The updated Renal GPA is a user-friendly tool that will help clinicians and patients better understand prognosis, individualize clinical decision making and treatment selection, provide a means to compare retrospective literature, and provide more robust stratification of future clinical trials in this heterogeneous population. To simplify use of this tool in daily practice, a free online application is available at brainmetgpa.com. Phase I/II trial testing safety and immunogenicity of the multipeptide IMA950/poly-ICLC vaccine in newly diagnosed adult malignant astrocytoma patients Abstract Background Peptide vaccines offer the opportunity to elicit glioma-specific T cells with tumor killing ability. Using antigens eluted from the surface of glioblastoma samples, we designed a phase I/II study to test safety and immunogenicity of the IMA950 multipeptide vaccine adjuvanted with poly-ICLC in HLA-A2 + glioma patients. Methods Adult patients with newly diagnosed glioblastoma (n=16) and grade III astrocytoma (n=3) were treated with radiochemotherapy followed by IMA950/poly-ICLC vaccination. The first 6 patients received IMA950 (9 MHC class I and 2 MHC class II peptides) i.d. and poly-ICLC i.m. After protocol amendment, IMA950 and poly-ICLC were mixed and injected s.c. (n=7) or i.m. (n=6). Primary endpoints were safety and immunogenicity. Secondary endpoints were overall survival, progression-free survival at 6 and 9 months, and vaccine-specific peripheral CD4 and CD8 T cell responses. Results The IMA950/poly-ICLC vaccine was safe and well tolerated. Four patients presented cerebral edema with rapid recovery. For the first 6 patients, vaccine-induced CD8 T cell responses were restricted to a single peptide and CD4 responses were absent. After optimization of vaccine formulation, we observed multipeptide CD8 and sustained Th1 CD4 T cell responses. For the entire cohort, CD8 T cell responses to a single or multiple peptides were observed in 63.2% and 36.8% of patients, respectively. Median overall survival was 19 months for glioblastoma patients. Conclusion We provide, in a clinical trial, using cell surface-presented antigens, insights into optimization of vaccines generating effector T cells for glioma patients. Trial registration Clinicaltrials.gov NCT01920191. Recent Developments and Future Directions in Adult Lower-Grade Gliomas: Society for Neuro-Oncology (SNO) and European Association of Neuro-Oncology (EANO) Consensus Abstract The finding that most grade II and III gliomas harbor isocitrate dehydrogenase (IDH) mutations conveying a relatively favorable and fairly similar prognosis in both tumor grades highlights that these tumors represent a fundamentally different entity from IDH wild-type gliomas exemplified in most glioblastoma. Herein we review the most recent developments in molecular neuropathology leading to reclassification of these tumors based upon IDH and 1p/19q status, as well as the potential roles of methylation profiling and CDKN2A/B deletional analysis. We discuss the epidemiology, clinical manifestations, benefit of surgical resection, and neuroimaging features of lower-grade gliomas as they relate to molecular subtype, including advanced imaging techniques such as 2-hydroxyglutarate magnetic resonance spectroscopy and amino acid PET scanning. Recent, ongoing and planned studies of radiation therapy and both cytotoxic and targeted chemotherapies are summarized, including both small molecule and immunotherapy approaches specifically targeting the mutant IDH protein. Diet and risk of glioma: combined analysis of three large prospective studies in the UK and USA Abstract Background Available evidence on diet and glioma risk comes mainly from studies with retrospective collection of dietary data. To minimise possible differential dietary recall between those with and without glioma, we present findings from three large prospective studies. Methods Participants included 692,176 from (UK) Million Women Study, 470,780 from (US) NIH-AARP Study, and 99,148 from (US) PLCO Study. Cox regression yielded study-specific adjusted relative risks for glioma in relation to 15 food groups, 14 nutrients, and 3 dietary patterns, which were combined, weighted by inverse-variances of the relative risks. Separate analyses by <5 and ≥5 years follow-up assessed potential biases related to changes of diet before glioma diagnosis. Results The 1,262,104 participants, mean age 60.6 (SD5.5) at baseline, were followed for 15.4 million person-years (mean 12.2 years/participant), during which 2,313 incident gliomas occurred, at mean age 68.2 (SD6.4). Overall, there was weak evidence for increased glioma risks associated with increasing intakes of total fruit, citrus fruit, and fibre, and healthy dietary patterns, but these associations were generally null after excluding the first 5 years of follow-up. There was little evidence for heterogeneity of results by study or by sex. Conclusions The largest prospective evidence to date suggests little, if any, association between major food groups, nutrients, or common healthy dietary patterns, and glioma incidence. With the statistical power of this study and the comprehensive nature of the investigation here, it seems unlikely we have overlooked major effects of diet on risk of glioma that would be of public health concern.

Highlights from the Literature

Forthcoming Meetings Edited by Albert H. Kim and Jennie W. Taylor

Glioblastoma: a prognostic value of AMT-PET? See the article by John et al, pp. 264–273.

Old meet new—the path to combination treatments in pediatric low-grade gliomas See the article by Poore et al, pp. 252–263.

Disparities along the glioblastoma clinical trials landscape We read with interest the recent work by Vanderbeek et al1 regarding the current clinical trials landscape for glioblastoma (GBM) patients. An unexplored dimension of their analysis centers on disparities and demographic discrepancies between clinical trial participants and the broader GBM population. We therefore examined clinical trials with published results as highlighted by the authors, totaling 51 trials.1 While most of these trials reported details regarding patient age (48/51, 94%) and gender (47/51, 92%), only 14 trials (27%) provided information regarding ethnicity and/or race in either peer-reviewed publications or ClinicalTrials.gov. The rate of reporting ethnicity/race was particularly low among phase I/II studies (9/43, 21%) compared with phase III trials (5/8, 63%, chi-squared test P = 0.02).

Multimodal imaging-defined subregions in newly diagnosed glioblastoma: impact on overall survival Abstract Background Although glioblastomas are heterogeneous brain-infiltrating tumors, their treatment is mostly focused on the contrast-enhancing tumor mass. In this study, we combined conventional MRI, diffusion-weighted imaging (DWI), and amino acid PET to explore imaging-defined glioblastoma subregions and evaluate their potential prognostic value. Methods Contrast-enhanced T1, T2/fluid attenuated inversion recovery (FLAIR) MR images, apparent diffusion coefficient (ADC) maps from DWI, and alpha-[11C]-methyl-L-tryptophan (AMT)-PET images were analyzed in 30 patients with newly diagnosed glioblastoma. Five tumor subregions were identified based on a combination of MRI contrast enhancement, T2/FLAIR signal abnormalities, and AMT uptake on PET. ADC and AMT uptake tumor/contralateral normal cortex (T/N) ratios in these tumor subregions were correlated, and their prognostic value was determined. Results A total of 115 MRI/PET-defined subregions were analyzed. Most tumors showed not only a high-AMT uptake (T/N ratio > 1.65, N = 27) but also a low-uptake subregion (N = 21) within the contrast-enhancing tumor mass. High AMT uptake extending beyond contrast enhancement was also common (N = 25) and was associated with low ADC (r = −0.40, P = 0.05). Higher AMT uptake in the contrast-enhancing tumor subregions was strongly prognostic for overall survival (hazard ratio: 7.83; 95% CI: 1.98–31.02, P = 0.003), independent of clinical and molecular genetic prognostic variables. Nonresected high-AMT uptake subregions predicted the sites of tumor progression on posttreatment PET performed in 10 patients. Conclusions Glioblastomas show heterogeneous amino acid uptake with high-uptake regions often extending into non-enhancing brain with high cellularity; nonresection of these predict the site of posttreatment progression. High tryptophan uptake values in MRI contrast-enhancing tumor subregions are a strong, independent imaging marker for longer overall survival.

Supratotal resection in glioma: a systematic review Abstract Background Emerging evidence suggests survival benefit from resection beyond all MRI abnormalities present on T1-enhanced and T2‒fluid attenuated inversion recovery (FLAIR) modalities in glioma (supratotal resection); however, the quality of evidence is unclear. We addressed this question via systematic review of the literature. Methods EMBASE, MEDLINE, Scopus, and Web of Science databases were queried. Case studies, reviews or editorials, non-English, abstract-only, brain metastases, and descriptive works were excluded. All others were included. Results Three hundred and nine unique references yielded 41 studies for full-text review, with 7 included in the final analysis. Studies were mostly of Oxford Center for Evidence-Based Medicine Level 4 quality. A total of 88 patients underwent supratotal resection in a combined cohort of 492 patients (214 males and 278 females, age 18 to 82 years). Fifty-one supratotal resections were conducted on high-grade gliomas, and 37 on low-grade gliomas. Karnofsky performance status, overall survival, progression-free survival, neurological deficits postoperatively, and anaplastic transformation were the main measured outcomes. No randomized controlled trials were identified. Preliminary low-quality support was found for supratotal resection in increasing overall survival and progression-free survival for both low-grade and high-grade glioma. Conclusion The literature suggests insufficient evidence for carte blanche application of supratotal resection, particularly in lower-grade gliomas where neurological deficits can result in long-term disability. While the preliminary studies discussed here, containing data from only a few centers, have reported increased progression-free and overall survival, these claims require validation in prospective research studies involving larger patient populations with clearly defined appropriate outcome metrics in order to reduce potential bias.

Uncommon low-grade brain tumors Abstract The 2016 World Health Organization (WHO) classification of primary central nervous system (CNS) tumors includes numerous uncommon (representing ≤1% of tumors) low-grade (grades I–II) brain neoplasms with varying clinical behaviors and outcomes. Generally, gross tumor or maximal safe resection is the primary treatment. Adjuvant treatments, though their exact role is unknown, may be considered individually based on pathological subtypes and a proper assessment of risks and benefits. Targetable mutations such as BRAF (proto-oncogene B-Raf), TRAIL (tumor necrosis factor apoptosis inducing ligand), and PDGFR (platelet derived growth factor receptor) have promising roles in future management.

Outcomes following stereotactic radiosurgery for small to medium-sized brain metastases are exceptionally dependent upon tumor size and prescribed dose Abstract Background At our institution, we have historically treated brain metastasis (BM) ≤2 cm in eloquent brain with a radiosurgery (SRS) lower prescription dose (PD) to reduce the risk of radionecrosis (RN). We sought to evaluate the impact of this practice on outcomes. Methods We analyzed a prospective registry of BM patients treated with SRS between 2008 and 2017. Incidences of local failure (LF) and RN were determined and Cox regression was performed for univariate and multivariate analyses (MVAs). Results We evaluated 1533 BM ≤2 cm. Median radiographic follow-up post SRS was 12.7 months (1.4–100). Overall, the 2-year incidence of LF was lower for BM treated with PD ≥21 Gy (9.3%) compared with PD ≤15 Gy (19.5%) (sub–hazard ratio, 2.3; 95% CI: 1.4–3.7; P = 0.0006). The 2-year incidence of RN was not significantly higher for the group treated with PD ≥21 Gy (9.5%) compared with the PD ≤15 Gy group (7.5%) (P = 0.16). MVA demonstrated that PD (≤15 Gy) and tumor size (>1 cm) were significantly correlated (P < 0.05) with higher rates of LF and RN, respectively. For tumors ≤1 cm, when comparing PD ≤15 Gy with ≥21 Gy, the risks of LF and RN are equivalent. However, for lesions >1 cm, PD ≥21 Gy is associated with a lower incidence of LF without significantly increasing the risk of RN. Conclusion Our results indicate that rates of LF or RN following SRS for BM are strongly correlated with size and PD. Based on our results, we now, depending upon the clinical context, consider increasing PD to 21 Gy for BM in eloquent brain, excluding the brainstem.

Sex difference of mutation clonality in diffuse glioma evolution Abstract Background Sex differences in glioma incidence and outcome have been previously reported but remain poorly understood. Many sex differences that affect the cancer risk were thought to be associated with cancer evolution. Methods In this study, we used an integrated framework to infer the timing and clonal status of mutations in ~600 diffuse gliomas from The Cancer Genome Atlas (TCGA) including glioblastomas (GBMs) and low-grade gliomas (LGGs), and investigated the sex difference of mutation clonality. Results We observed higher overall and subclonal mutation burden in female patients with different grades of gliomas, which could be largely explained by the mutations of the X chromosome. Some well-established drivers were identified showing sex-biased clonality, such as CDH18 and ATRX. Focusing on glioma subtypes, we further found a higher subclonal mutation burden in females than males in the majority of glioma subtypes, and observed opposite clonal tendency of several drivers between male and female patients in a specific subtype. Moreover, analysis of clinically actionable genes revealed that mutations in genes of the mitogen-activated protein kinase (MAPK) signaling pathway were more likely to be clonal in female patients with GBM, whereas mutations in genes involved in the receptor tyrosine kinase signaling pathway were more likely to be clonal in male patients with LGG. Conclusions The patients with diffuse glioma showed sex-biased mutation clonality (eg, different subclonal mutation number and different clonal tendency of cancer genes), highlighting the need to consider sex as an important variable for improving glioma therapy and clinical care.

Rates of symptomatology are lower in recurrent sinonasal malignancy than in other recurrent cancers of the head and neck: a multi‐institutional study

Background

Sinonasal malignancies are a rare subset of head and neck tumors, and surveillance strategies after definitive tumor treatment are often generalized from those for overall head and neck cancer outcomes data. However, recent literature suggests that the posttreatment period in sinonasal cancer is fundamentally different and a more tailored surveillance approach may be beneficial. Although rates of symptomatology are high in head and neck cancer recurrence and patient‐driven follow‐up is common, rates of symptomatology are unknown in sinonasal cancer specifically.

Methods

Patients with recurrence of sinonasal malignancy were identified at 3 academic rhinology and skull base surgery centers. Demographic, tumor, and treatment data were collected. Rates of symptomatology at presentation were tabulated and examined in the context of several other variables.

Results

Fifty‐five patients had recurrence of sinonasal malignancy after definitive treatment. Fifty‐one percent of patients had no suspicious symptoms at the time of tumor recurrence, with an average time to recurrence of 33 months. Male patients and patients with stage IVA or lower disease were significantly more likely to be asymptomatic at the time of recurrence (p < 0.05).

Conclusion

Patients with sinonasal malignancy have a much lower rate of symptomatology during tumor recurrence than that observed in head and neck cancer overall. Furthermore, time to recurrence is substantially longer, as a majority of head and neck cancer recurrences occur in the first 12 months after treatment. These differences highlight the need for more tailored surveillance paradigms in asymptomatic patients with a history of a definitively treated sinonasal neoplasm.

http://bit.ly/2NaSBvO

Factors associated with readmission and mortality in adult patients with skin and soft tissue infections

Abstract

Background

Skin and soft tissue infections (SSTIs) are a common cause of consultation, and complicated cases require hospitalization. We describe factors that are related to readmission and/or mortality of hospitalized patients diagnosed with SSTIs.

Methods

Retrospective review of hospital‐admitted patients with a diagnosis of cellulitis, abscess, hidradenitis, fasciitis, and Fournier's gangrene. Cases from January 2002 to October 2015 were extracted from the diagnostic codification database of the Archives and Clinical Documentation Department.

Findings

We studied 1,482 episodes of hospitalized patients diagnosed with SSTIs. There were 187 (12.3%) readmissions, the most frequent diagnosis was cellulitis (72.7%), and the most commonly isolated microorganism was Staphylococcus aureus (25; 30.1%). Factors associated with readmissions were healthcare‐related infections (P = 0.002), prior antibiotic therapy (P < 0.001), ischemic heart disease (P = 0.01), chronic liver disease (P = 0.001), and diabetes mellitus (DM) (P = 0.006). The number of patients who died as a result of an infection was 34 (2.2%) and, in these patients, the most common diagnosis was also cellulitis (79.4%), which in 52.9% (P = 0.001) was community acquired. DM (P = 0.01), heart failure (P = 0.001), and chronic liver disease (P = 0.003) were the most frequent comorbidities. This group presented more complications (P < 0.005) such as endocarditis (P < 0.005), amputation (P = 0.018), severe sepsis (P < 0.005), and septic shock (P < 0.001).

Conclusions

Readmitted patients had healthcare‐related S. aureus infection, had received prior antibiotic therapy, and presented comorbid conditions such as ischemic heart disease, peripheral vascular disease, chronic liver disease, or DM. Comorbidities such as advanced age, DM, heart failure, and chronic liver disease were associated with complications and higher infection‐related mortality.

http://bit.ly/2STPo9l

A review of the etiologies, clinical characteristics, and treatment of canities

Abstract

Hair pigmentation is regulated by follicular melanogenesis, in which the process consists of melanin formation and transfer to keratinocytes in the hair shaft. Human hair follicles contain two types of melanin: the brown‐black eumelanin and yellow‐red pheomelanin. Eumelanin is commonly present in black and brown hair while pheomelanin is found in auburn and blonde hair. Hair follicle melanogenesis is under cyclical control and is concurrently coupled to hair growth. Many factors including intrinsic and extrinsic factors affect the follicular melanogenesis. Though many studies have been conducted to identify the pathogenesis and regulation of hair pigmentation, the etiology of canities and hair pigmentation is still unclear. The pathogenesis of canities or gray hair is believed to occur either from insufficient melanin formation due to melanocyte degeneration or a defect in melanosomal transfer. Canities is an aging sign which often interferes with one's socio‐cultural adjustment. On the other hand, premature canities correlate with diseases such as osteopenia and cardiovascular disease. Risk factors associated with canities are not only genetic but also external causes. For example, smoking, alcohol consumption, and stress are among the most common factors. Camouflage techniques are still used as the primary treatment of canities. Further treatments for canities are being developed to achieve the true reversal of hair pigmentation.

http://bit.ly/2N9lKrw

Relationship between dermoscopy and pathology in a case of clonal‐type pigmented Bowen's disease: Observation with vertical‐view dermoscopy

Abstract

Pigmented Bowen's disease (pBD) is a subtype of Bowen's disease, which presents clinically as a well‐circumscribed, hyperpigmented plaque. Its clinical manifestations are not fully characterized, and differential diagnoses include various pigmented skin lesions. Dermoscopy could be useful for the diagnosis, although nothing has been reported on the dermoscopic features of clonal‐type pBD. We herein report a first case of clonal‐type pBD on the sole and its dermoscopic features. Dermoscopy showed brown to blue‐gray dots/globules and focally anastomosing lines on the non‐weight‐bearing area, while the weight‐bearing area had a brown to blue‐gray fibrillar‐like pattern. To investigate the relationship between dermoscopy and histopathology, we focused on the melanin distribution in the horny layer of the epidermis, and used vertical dermoscopy observation. We investigated the relationship between dermoscopy and pathology by melanin depth estimation using a color lightness value.

http://bit.ly/2TMzmLL

Revival of favus in Japan caused by Trichophyton schoenleinii

Abstract

Favus is a type of dermatophytosis known to produce yellow scutula around hair follicles. Most cases of this disease worldwide are infections of Trichophyton schoenleinii. Favus has rarely been reported in Japan throughout the last four decades, and T. schoenleinii has not been clinically isolated in any case during the period. Here, we report a case of favus of vellus hair observed in a 63‐year‐old Japanese woman. Fungal culture showed negative; however, we detected fungal elements in the crust and hair bulbs by Grocott staining. Pathogenic fungi were identified as T. schoenleinii by polymerase chain reaction‐based DNA sequencing, targeting the internal transcribed spacer regions of the rRNA gene using the formalin‐fixed, paraffin‐embedded tissue sample. She was successfully treated with p.o. administration of terbinafine and topical application of luliconazole cream.

http://bit.ly/2BCBVcn

Practice‐Based Differences in Pediatric Discoid Lupus Erythematosus

Abstract

Background

Children with discoid lupus erythematosus (DLE) are at risk for disfigurement and progression to systemic lupus erythematosus (SLE). Consensus is lacking regarding optimal care of children with DLE.

Objectives

We compared practice patterns among pediatric dermatologists/rheumatologists treating pediatric DLE.

Methods

An online survey was sent to 292 pediatric rheumatologists in the Childhood Arthritis & Rheumatology Research Alliance (CARRA) and 200 pediatric dermatologists in the Pediatric Dermatology Research Alliance (PeDRA). Consensus was defined as >70% agreement.

Results

Survey response rates were 38% (dermatology, n = 76/200) and 21% (rheumatology, n = 60/292). Both specialties agreed that screening labs should include complete blood counts with differential, urinalysis, complements, erythrocyte sedimentation rate, antinuclear antibody and other autoantibodies, hepatic function, and renal function/electrolytes. Both specialties agreed that arthritis or nephritis should prompt intensified evaluation for SLE. No other patient features achieved consensus as disease‐modifying risk factors. Hydroxychloroquine was agreed upon as first‐line systemic therapy, but consensus was lacking for second or third‐line treatment.

Conclusions

We found few areas of consensus and significant practice differences between pediatric dermatologists/rheumatologists treating DLE. Knowledge gaps include risk factors for SLE, optimal screening and treatment of refractory skin disease.

This article is protected by copyright. All rights reserved.

http://bit.ly/2BzGHXN

Eczematous eruption during anti‐interleukin 17 treatment of psoriasis: an emerging condition

Abstract

Major advances in psoriasis pathogenesis gave rise to development of new effective drugs for its treatment. Particularly, biologic drugs revolutionized disease management. TNF‐α inhibitors represented the opening available biologic class since 2000. Thus, adverse cutaneous reactions to their use have been extensively investigated.

This article is protected by copyright. All rights reserved.

http://bit.ly/2TMUj9k

Efficacy of fractional CO2 laser with intralesional steroid compared with intralesional steroid alone in the treatment of keloids and hypertrophic scars

Summary

Background and objective

Keloids and hypertrophic scars (HTS) are abnormal fibrous reactions that persist for prolonged periods, rarely regress without treatment and recur after excision. Many modalities of treatment have been advocated but the success rates of these have been variable. The present study is an attempt to evaluate and compare the efficacy of combination of fractional CO₂ laser (FCL) and intralesional steroid (ILS) against ILS alone in the treatment of keloids and HTS.

Methods

Patients with keloids or HTS were divided into two groups of 25 each receiving four sessions of therapy. Group 1 (FCL + ILS) received combination of FCL and intralesional triamcinolone acetonide (TAC) 10 mg/mL. Group 2 (ILS only) received intralesional TAC 10 mg/mL alone. Pretreatment measurements and photographs were taken. Two unbiased qualified dermatologists made independent evaluation of the photographs using modified Manchester quartile score (MQS). The patient's satisfaction to treatment was graded on a scale of 1‐4. Statistical analysis was done using a statistical software.

Results

Statistically significant improvement was seen in height and length of the lesions. Overall appearance criteria of modified MQS showed an improvement of more than 50% in 43.3% of the lesions by the end of four sessions. Degree of hypertrophy showed more than 50% improvement in 40% of the lesions treated. Dyschromia showed more than 50% improvement in 33.4%. Texture showed the least improvement, with only 30% of lesions showing an improvement of more than 50%. The improvement of these parameters in ILS only group was significantly lower than the improvement seen in the FCL + ILS group.

Conclusion

Combination therapy with FCL and ILS was superior in efficacy when compared to ILS alone, in the treatment of keloids and HTS.

http://bit.ly/2S62JqD

Parry‐Romberg syndrome treatment with fat transfer and a new bleaching formula

Summary

Parry‐Romberg syndrome is a hemifacial atrophy which can be complicated by melasma. We present two cases of Parry‐Romberg syndrome, treated by fat transfer and bleaching of the skin using a modified "Kligman's formula." The atrophy, as well as the skin dyschromia, improved, and the results were stable.

http://bit.ly/2X6w9bZ

Efficacy of microneedling with topical vitamin C in the treatment of melasma

Summary

Background

Despite the wide therapeutic options available for the treatment of melasma, including many active topical medications, technologies with lights and peelings, clinical control of this disorder is extremely challenging.

Objectives

To evaluate the effect of microneedling with topical vitamin C in the treatment of melasma.

Methods

Thirty female patients with melasma received six sessions of microneedling with addition of topical vitamin C every two weeks. At each session, photos were taken and Melasma Area and Severity Index (MASI) score was calculated to assess the clinical improvement.

Results

Mean age of the eligible patients was 33.2 ± 5.77 years. About 50% of cases were of Fitzpatrick skin type III. All patients showed improvement at the end of the sessions. Mean MASI score in the first session was 8.61 ± 4.45 and there was a gradual decline in its value till it reached a mean of 5.75 ± 4.16 in the last session (P < 0.0001).

Conclusion

Microneedling with topical vitamin C is an effective and safe treatment option for epidermal melasma especially in Fitzpatrick skin phototypes I‐III.

http://bit.ly/2S2IWZe