Αρχειοθήκη ιστολογίου

Σάββατο 18 Αυγούστου 2018

Monitoring of patients with metastatic melanoma treated with immune checkpoint inhibitors using PET–CT

Abstract

Immune checkpoint inhibitors (ICI) have revolutionized therapy of metastatic melanoma. The first ICI was ipilimumab, a cytotoxic T lymphocyte-associated Ag 4 (CLTA-4) inhibitor with response rates of approximately 11% and disease control of 22%. The programmed cell death 1 (PD-1) inhibitors, such as pembrolizumab and nivolumab, led to longer progression-free survival and overall survival rates with fewer side effects. Molecular imaging techniques, such as positron emission tomography–computed tomography (PET–CT) with 2-deoxy-2-(18F)fluoro-d-glucose (18F-FDG) are in use for staging and therapy monitoring of metastatic melanoma. However, classical radiological imaging criteria such as RECIST and WHO are not appropriate for the assessment of ICI response. New immune-related criteria have been defined such as iRECIST or irRC, which refer to radiological imaging modalities. Until now only a few studies report on immunotherapy response assessment based on 18F-FDG PET–CT. The classical criteria used for therapy monitoring with 18F-FDG PET, such as the EORTC criteria, are not suitable for ICI monitoring. In this focussed review, we present different criteria proposed for ICI monitoring with 18F-FDG and their limitations. One goal is to early identify non-responders to tailor immunotherapy. Another question is pseudoprogression and how to interpret the 18F-FDG images for response assessment. Finally, the definition of 18F-FDG criteria which can be used to identify progress is crucial and discussed in the review. The recent presented PET-based immune-related criteria, the so-called PERCIMT (PET Response Evaluation Criteria for IMmunoTherapy) are presented. Furthermore, new tracers are discussed.



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Top Reviewers

Publication date: September–October 2018

Source: American Journal of Otolaryngology, Volume 39, Issue 5

Author(s):



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Effectiveness of voriconazole and corneal cross-linking on Phialophora verrucosa keratitis: a case report

We report a rare case of Phialophora verrucosa fungal keratitis, which required various types of treatment according to the intractable natural history of the disease.

https://ift.tt/2weSRSr

Synchronous double primary hepatic cancer consisting of hepatocellular carcinoma and cholangiolocellular carcinoma: a case report

The incidence of synchronous double primary hepatic cancers is extremely low. Cholangiolocellular carcinoma is also a rare disease.

https://ift.tt/2nQ3eIU

Tuberculous sacroiliitis with secondary psoas abscess in an older patient: a case report

Tuberculosis is the leading infectious cause of death worldwide. Among native Swiss people, tuberculosis is more common in older people than in younger people. Approximately 25–30% of reported cases of tubercu...

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Recurrent hypoglycemia secondary to metformin toxicity in the absence of co-ingestions: a case report

Metformin toxicity is well known to cause lactic acidosis. Multiple cases of hypoglycemia due to isolated metformin overdose have been reported. Increased glucose consumption secondary to anaerobic metabolism ...

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The changing aetiology of head and neck squamous cell cancer: A tale of three cancers?



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Analysis of gene copy number changes in head and neck cancer



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Decreasing cytokeratin 17 expression in head and neck cancer predicts nodal metastasis and poor prognosis: The first evidence



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Evaluation of an abutment‐level superpower sound processor for bone‐anchored hearing



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Assessing normal values for the FACE‐Q rhinoplasty module: An observational study



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Effects of sumatriptan nasal spray (Imigran) on human nasal mucosa



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Does otitis media in early childhood affect later behavioural development? Results from the Western Australian Pregnancy Cohort (Raine) Study



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A web‐based prediction score for head and neck cancer referrals



https://ift.tt/2Bj4ZI5

C‐reactive protein is an independent prognostic marker in patients with tongue carcinoma ‐ A retrospective study



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Hearing aids in patients with vestibular schwannoma: Interest of the auditory brainstem responses



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Reliable sonographic features for nodal thyroglobulin to diagnose recurrent lymph node metastasis from papillary thyroid carcinoma



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Patient‘s perspective on long‐term complications after superficial parotidectomy for benign lesions: Prospective analysis of a 2‐year follow‐up



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High sensitivity and negative predictive value of sentinel lymph node biopsy in a retrospective early stage oral cavity cancer cohort in the Northern Netherlands



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Oesophageal causes of dysphagia localised only to the pharynx: Implications for the suspected head and neck cancer pathway



https://ift.tt/2BmHSfA

Very long‐term Voice Handicap Index Voice Outcomes after Montgomery Thyroplasty: A cross‐sectional study



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A meta‐analysis on the surgical management of paraganglioma of the carotid body per Shamblin class



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Oropharyngeal squamous cell carcinoma induces an innate systemic inflammation, affected by the size of the tumour and the lymph node spread



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Hard onset therapy for functional hypoadduction and presbylaryngis: Our experience in 22 patients



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Use of an autologous bony crossbar graft for the management of caudal septal deviation: Our experience in twenty‐two patients



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Cochlear dead regions: Using the Threshold Equalising Noise (TEN) test to improve the assessment of potential cochlear implant candidates—The Oxford experience



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Multicenter clinical study proving antiseptic, bactericide and fungicide efficacy in a talc containing 17% sulfur in the treatment of patients with interdigital mycosis of the feet

Introduction: Set as an infection caused by fungi that use the keratin of skin, nails and hair as nutrients, the superficial mycosis develop under favorable conditions, such as heat and humidity, and stand out among the dermatologic diseases most prevalent in Brazil. One of the most common superficial mycoses is interdigital mycosis, characterized by flaking, cracks and itching between the toes, and the use of products with drying and antiseptic action is recommended to contribute to the decrease in the incidence of the disease.

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Pseudocellulitis and gemcitabine, a recently described entity: Case report and literature review

Case report: A 55-year-old woman presents with a dermatosis disseminated to the abdomen and left pelvic extremity, constituted by two erythematous and edematous plaques, with a diameter of 30 × 15 cm in the abdomen and 20 × 15 cm in the thigh, well circumscribed with "peau d'orange" appearance. The evolution was of sudden development 2 days before presenting to consultation, with mild pain and pruritus, without any previous treatment. Patient refered 2 previous similar episodes, presenting after administration of chemotherapy, with 2 cycles of clindamycin and remission of symptoms after 7 days.

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Chronic spontaneous urticaria treated with omalizumab (Xolair): A proposal of standardized tapering protocol before withdrawal to achieve the minimal effective dosage

Background: Chronic spontaneous urticaria (CSU) may represent a therapeutic challenge, although the recombinant humanized monoclonal antibody omalizumab has demonstrated a high effectiveness in the treatment of antihistamines-resistant CSU. There are no clear recommendations regarding the optimal duration of the treatment or the way to taper down the drug. The objective of our study was to describe our experience with a standardized tapering protocol of omalizumab before withdrawal.

https://ift.tt/2vTBreZ

Quality Improvement Project: Improving intake forms to make them more readable for patients in an urban clinic setting

In the landscape of increasing demands on physician and staff time, intake forms are frequently utilized to gather information before the start of the clinical encounter. These forms typically contain information on reason for visit, allergies, current medications, pertinent health history, abbreviated review of systems and important social history. We assessed a sample of the intake forms at our clinic and found that 63% of the time the forms were not filled out at all. A resident poll showed that 75% of residents felt the forms were not useful.

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Transdermal effectiveness of a lipid-based antimicrobial emulsion

A proprietary lipid-based emulsion (ML:8) with established antimicrobial efficacy was investigated. To model a clinical situation in which bacteria have penetrated the integumentary barrier, a reference strain of Staphylococcus aureus (NCTC 8255-4) was inoculated into the subdermal compartment of isolated sheets of pig skin mounted between two chamber-halves to permit separate access to surface and to subdermal compartments. The objective was to evaluate transdermal efficacy of a range of concentrations of ML:8 through porcine skin in vitro.

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Topical glycopyrronium tosylate (DRM04) for the treatment of primary axillary hyperhidrosis: Pooled results from the ATMOS-1 and ATMOS-2 phase 3 randomized controlled trials

Introduction: The impact of hyperhidrosis on quality of life is comparable to, or greater than, psoriasis or eczema. Glycopyrronium tosylate (GT; formerly DRM04) is a cholinergic receptor antagonist developed for topical application for the treatment of primary axillary hyperhidrosis. ATMOS-1 (NCT02530281) and ATMOS-2 (NCT02530294) were designed to assess the efficacy and safety of GT in patients with primary axillary hyperhidrosis.

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Tie-over bolsters versus quilting sutures for the closure of full-thickness skin grafts

Background: Full-thickness skin grafting is a well established and preferred technique in the reconstruction of various tissue defects and wounds. However, lack of uniformity in the procedure of closing and securing the grafts has led to a wide-range of different techniques.

https://ift.tt/2vW94Nd

The use of intralesional triamcinolone as treatment of primary cutaneous B-cell lymphomas

Primary cutaneous B-cell lymphomas (PCBCLs) are benign malignancies which rarely disseminate, with 5-year disease-specific survival ranging from 94% to 100%. They are commonly treated with excision, radiation, or chemotherapy, alone or in combination. Intralesional corticosteroid injection is an alternative that is cost-effective with minimal side-effects, although it is less-frequently utilized as a primary mode of treatment. The present study was undertaken to evaluate the experience of an academic medical center in using intralesional corticosteroid injection as first-line therapy for PCBCL.

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The rodent, the Hedgehog, and the man with nosocomephobia

A 71-year-old Caucasian gentleman presented in 2004 with a basal cell carcinoma (BCC) on his right cheek. A wide excision was arranged but was rescheduled and subsequently cancelled by the patient. He was noted to have a severe hospital phobia (nosocomephobia) related to childhood experiences concerning medical care of his parents. He declined all efforts to provide treatment and accepted the consequences. He represented 12 years later with a large tumor involving his right cheek, nose and sight threating eyelid involvement.

https://ift.tt/2vVZM3L

The Onychomycosis/Onychodystrophy Dermoscopy study (OMODO)—A comparative prospective study of onychoscopy features

Background: Onychomycosis (OM) and traumatic onychodystrophy (OD) are common causes of toenail dystrophy. Their treatment and prognosis differ, so early diagnosis is essential and questionable without mycology. Onychoscopy may prove useful in this setting. Although, few studies have addressed this issue and none directly compared OM and OD onychoscopic findings. We aimed to identify and describe onychoscopic patterns associated with OM and OD, proposing an onychoscopy-based algorithm to guide their differential.

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The association between periodontitis and interleukin-6 genetic polymorphism -174 G/C: A meta-analysis

Publication date: Available online 18 August 2018

Source: Archives of Oral Biology

Author(s): Bo Zhao, Ronghua Li

Abstract
Background

To evaluate the association between periodontitis and interleukin-6 (IL6) -174 G/C polymorphism by data synthesis and subgroup analysis.

Methods

Eighteen case-control studies from 16 articles with 1,616 cases and 1,511 controls were included in this meta-analysis by searching the public databases including PubMed, Embase and Web of Science databases by Jun 2018. Data syntheses were performed using Stata 9.0.

Results

There were inverse associations of IL6 -174 G/C polymorphism with both general periodontitis and overall periodontitis. In CC vs. GG inheritance model, whose effect was the most profound, the genetic polymorphism reduced the risks of general and overall periodontitis by 60% (95% CI = 0.25-0.65, P <  0.01) and 31% (95% CI = 0.38-0.97, P =  0.04) respectively. In addition, the G/C variation was likely to be protective against moderate (allele C vs. allele G: OR = 0.61, 95% CI = 0.43-0.87, P =  0.01; CC + GC vs. GG: OR = 0.57, 95% CI = 0.37-0.89, P =  0.01) and severe periodontitis (allele C vs. allele G: OR = 0.58, 95% CI = 0.41-0.84, P <  0.01; CC vs. GG: OR = 0.33, 95% CI = 0.13-0.82, P =  0.02) exclusively in Brazilian people. No reliable evidence was found regarding chronic periodontitis.

Conclusion

This meta-analysis suggests that IL6 -174 G/C polymorphism may be negatively associated with risk of periodontitis.



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Antagonistic effect of IL1 variants in Periodontitis and External Apical Root Resorption: evidence from a literature review

Publication date: Available online 18 August 2018

Source: Archives of Oral Biology

Author(s): Sónia Margarida Alves Pereira, Ana Carolina Jacob Melo, Elisabete Cristina Peres Resende, Fernando de Jesus Regateiro, Henriqueta Alexandra Mendes Breda Lobo Coimbra Silva

Abstract

External apical root resorption (EARR) induced by orthodontic treatment and chronic periodontitis (CP) are complex phenotypes dependent on the interaction of multiple genetic and non-genetic risk factors. Apart from different environmental triggers, these phenotypes are caused by antagonistic biological mechanisms involving local immunoinflammatory reaction and alveolar bone metabolism, for which IL1 have a prominent role. Whereas EARR benefits from bone remodelling, CP is characterized by osteolytic damaged. Our aim was to verify if these two phenotypes have opposite genetic profiles, considering the most frequently analysed polymorphisms for both diseases.

A review of the literature was performed searching for the association of rs1800587 from Interleukin-1 alpha (IL1A) gene and rs1143634 from interleukin-1 beta (IL1B) gene with EARR and CP. The electronic search included MEDLINE/PubMed, EBSCOhost, Cochrane and Web of Science databases. Twenty four articles met the inclusion and exclusion criteria. For IL1B polymorphism, two out of seven studies found a significant statistical association between EARR and CC genotype, whether for CP, there were eighth out of fifteen references describing a statistically significant associations with T allele. For IL1A variant, no significant association with EARR was described.

In conclusion, literature review suggests that for IL1B SNP rs1143634, EARR and CP have an opposite genetic profile. For IL1A SNP, our hypothesis could not be confirmed.



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Fusobacterium nucleatum promotes M2 polarization of macrophages in the microenvironment of colorectal tumours via a TLR4-dependent mechanism

Abstract

Fusobacterium nucleatum (Fn) has been shown to promote colorectal cancer (CRC) development by inhibiting host anti-tumour immunity. However, the impact of Fn infection on macrophage polarization and subsequent intestinal tumour formation as well as the underlying molecular pathways has not been investigated. We investigated the impact of Fn infection on macrophage polarization in human CRCs and cultured macrophages as well as the effects on macrophage phenotype and intestinal tumour formation in ApcMin/+ mice. We also examined whether macrophage-polarized activation challenged by Fn infection via a TLR4-dependent mechanism involved the IL-6/STAT3/c-MYC signalling cascade. Our data showed that macrophages are a major tumour-infiltrating immune cell type in human CRCs with Fn infection (P < 0.001). Fn infection increased M2 polarization of macrophages in vitro and in vivo, leading to intestinal tumour growth in ApcMin/+ mice. Moreover, Fn infection induced high expression of TLR4, IL-6, STAT3, p-STAT3, and c-MYC in cultured macrophages challenged with Fn, which was blocked by TAK-242 pre-treatment (P < 0.05). Interestingly, c-MYC protein was mainly co-localized with CD206+ M2 macrophages with Fn infection. In conclusion, we show that Fn infection increased M2 polarization of macrophages in vitro and in vivo. Furthermore, Fn infection enhanced colorectal tumour growth in a TLR4-dependent manner involving activation of the IL-6/p-STAT3/c-MYC signalling pathway. For the first time, our results indicate an immunosuppressive effect of Fn by promoting M2 polarization of macrophages through a TLR4-dependent mechanism, which may serve as a promising target for immunotherapy of Fn-related CRC.



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Assessment of facial analysis measurements by golden proportion

Publication date: Available online 18 August 2018

Source: Brazilian Journal of Otorhinolaryngology

Author(s): Kerem Sami Kaya, Bilge Türk, Mahmut Cankaya, Nurullah Seyhun, Berna Uslu Coşkun

Abstract
Introduction

The face is the most important factor affecting the physical appearance of a person. In facial aesthetics, there is a specific mathematical proportion, which is called golden proportion, used to measure and analyse facial aesthetic qualities in population.

Objectives

The aim of this study was to measure the facial soft tissue proportions which would help to constitute a standard for facial beauty and diagnose facial differences and anomalies and to compare these proportions to the golden proportion.

Methods

One hundred and thirty-three (133) Turkish patients 18–40 years of age (61 females, 72 males) were involved in the study. Analysis of the photographs was performed by the same physician, and a software programme was used (NIH Image, version 1.62). Facial proportions were measured and differences from the golden proportions were recorded and grouped as normal (1.6–1.699), short (<1.6) and long (>1.699).

Results

According to the facial analysis results, the trichion–gnathion/right zygoma–left zygoma was assessed: 33.1% of the patients were in normal facial morphology, 36.8% were in long facial morphology and 30.1% were in short facial morphology, according to this proportion. The trichion–gnathion/right zygoma–left zygoma proportion was significantly higher in males than females (p < 0.001). Statistically significant difference was noted in gender groups, according to the trichion–gnathion/right zygoma–left zygoma and the right lateral canthus–left lateral canthus/right cheilion–left cheilion proportions (p = 0.001, p = 0.028).

Conclusion

Facial proportion assessments in relation to the golden proportion showed that a statistically significant difference was observed between gender groups. Long facial morphology was observed more in males (51.4%); normal (41%) and short (39.3%) facial morphology were more common in females. The measurements and proportions for facial balance in our study population showed that the facial width and height proportions deviated from the golden proportion.

Resumo
Introdução

A face é o aspecto mais importante da aparência física de uma pessoa. Na estética facial, existe uma proporção matemática específica, que é chamada de proporção áurea. A proporção áurea é utilizada para medir e analisar as qualidades estéticas da face na população.

Objetivos

O objetivo deste estudo foi medir as proporções dos tecidos moles faciais que contribuem para o padrão da beleza facial auxiliando a percepção e diagnóstico das diferenças e anomalias faciais, e comparar essas proporções com a proporção áurea.

Método

Cento e trinta e três (133) pacientes turcos com 18 a 40 anos de idade (61 mulheres, 72 homens) foram incluídos no estudo. A análise das fotografias foi realizada pelo mesmo médico, e um programa de software foi utilizado (NIH Image, versão 1.62). As proporções faciais foram medidas e as diferenças das proporções áureas foram registradas e agrupadas como normais (1,6–1,699), curtas (<1,6) e longas (>1,699).

Resultados

De acordo com os resultados da análise facial, avaliou-se a proporção do tríquion-gnátio/zigoma direito-zigoma esquerdo, e 33,1% dos pacientes apresentaram morfologia facial normal, enquanto 36,8% tinham morfologia facial longa e 30,1% morfologia facial curta, segundo essa proporção. A proporção do tríquion-gnátio/zigoma direito-zigoma esquerdo, foi significantemente maior em homens do que em mulheres (p < 0,001). Uma diferença estatisticamente significante foi observada entre os sexos, de acordo com a proporção do tríquion-gnátio/zigoma direito-zigoma esquerdo e do canto lateral direito - canto lateral esquerdo/ângulo cantal direito- ângulo cantal esquerdo (p = 0,001, p = 0,028).

Conclusão

A avaliação da proporção facial em relação à proporção áurea mostrou que houve diferença estatisticamente significante entre os sexos. A morfologia facial longa foi mais observada no sexo masculino (51,4%), a morfologia facial normal (41%) e a curta (39,3%) foram mais comuns no sexo feminino. As medidas e proporções para o equilíbrio facial em nossa população estudada mostraram que as proporções de largura e altura faciais se desviaram da proporção áurea.



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Maternal exposure to farming environment protects offspring against allergic diseases by modulating the neonatal TLR-Tregs-Th axis

As the development of urbanization in China, the morbidity of allergic disease rise up prominently even in children, which may be partially associated with the excessively clean environment. It has been report...

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The Western (Buonfornello) necropolis (7th to 5th BC) of the Greek colony of Himera (Sicily, Italy): site‐specific discriminant functions for sex determination in the common burials resulting from the battle of Himera (ca. 480 BC)

International Journal of Osteoarchaeology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2Bl7glU

A case of non‐venereal treponematosis in a Pre‐Hispanic adult from Northeastern Argentina

International Journal of Osteoarchaeology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2Pk1YKj

Osteophageous Insect Damage on Human Bone from Je’reftheel, a Maya Mortuary Cave Site in West‐Central Belize

International Journal of Osteoarchaeology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2BnmpmS

Evidence for Differences in Activity Between Socioeconomic Groups at Kulubnarti, Nubia (550‐800 CE), from Osseous Modifications of the Proximal Femur

International Journal of Osteoarchaeology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2PhKQVH

Éruption lichénoïde cutanéo-muqueuse sous anti-PD-1

Publication date: Available online 17 August 2018

Source: Annales de Dermatologie et de Vénéréologie

Author(s): M. Amini-Adle, B. Balme, M. Locatelli-Sanchez, P.-J. Souquet, S. Dalle



https://ift.tt/2OLXuv4

Étude rétrospective d’une série de pemphigus paranéoplasiques

Publication date: Available online 17 August 2018

Source: Annales de Dermatologie et de Vénéréologie

Author(s): M. Fournet, P. Roblot, P. Levillain, G. Guillet, L. Machet, L. Misery

Résumé
Contexte

Le pemphigus paranéoplasique (PPN) est une maladie très rare et de mauvais pronostic associant un pemphigus, particulier par certains critères cliniques, immunologiques et histologiques, à une néoplasie.

Méthodes

Nous avons rétrospectivement analysé les dossiers de patients présentant un PPN dans la région Poitou-Charentes entre 2000 et 2015.

Résultats

Sept patients présentaient neuf néoplasies diagnostiquées de 4 mois avant à 25 mois après l'apparition des lésions cutanées (6/7) ou muqueuses (6/7) de pemphigus. Les lésions étaient cliniquement polymorphes. L'examen histologique révélait une acantholyse épidermique (7/7), des nécroses kératinocytaires (4/7) et une dermite lichénoïde d'interface (5/7). On mettait en évidence des dépôts d'IgG et de C3 intercellulaires ou le long de la jonction dermo-épidermique en immunofluorescence directe (IFD) (7/7), des anticorps anti-substance intercellulaire en immunofluorescence indirecte (IFI) sur vessie de rat (4/6), un immunotransfert reconnaissant les cibles antigéniques du PPN (2/4). La durée du suivi allait de 1 à 132 mois, la survie à 1 an était de 85,7 %.

Discussion

Les présentations cliniques et histopathologiques observées chez nos patients sont polymorphes, avec un chevauchement entre les manifestations cliniques et histologiques de PPN et de pemphigus classique. Le pronostic est meilleur dans notre série que dans la littérature. Les néoplasies associées sont diverses. Il semble exister des associations fortuites de pemphigus à des néoplasies, de meilleur pronostic que les véritables PPN. Un nouveau consensus pour les critères diagnostiques du PPN est nécessaire, qui aiderait les praticiens à diagnostiquer le PPN de manière plus homogène pour réaliser des études pronostiques ou des essais thérapeutiques.

Summary
Context

Paraneoplastic pemphigus (PNP) is a rare condition associated with poor prognosis. It associates polymorphic mucocutaneous manifestations with neoplasia. Diagnosis is difficult because of the various clinical and histological features involved and the lack of specificity of immunological examinations.

Methods

We retrospectively analyzed the records of patients presenting with PNP in the Poitou-Charentes region between 2000 and 2015.

Results

Seven patients were included. They presented 9 neoplasias (1 lymphoma, 1 melanoma, and 7 carcinomas) diagnosed from 4 months before to 25 months after the occurrence of cutaneous (6/7) and/or mucosal (6/7) polymorphic lesions. Histological examination revealed epidermal acantholysis (7/7), keratinocytic necrosis (4/7), and interface lichenoid dermatitis (5/7). Intercellular deposits of IgG and C3 or along the dermo-epidermal junction were detected with direct immunofluorescence (IF) (7/7). Four of 6 patients tested had positive indirect IF on rat bladder epithelium. Follow-up ranged from 1–132 months with a one-year survival of 85.7%.

Discussion

The clinical and histopathological presentations observed in our patients were polymorphic, with overlap between the clinical and histological features of PNP and classical pemphigus. Prognosis and survival appear better in our series than in the literature. It is possible that in some cases, the association of pemphigus with neoplasia was fortuitous, which might account for the better prognosis. A new consensus on the diagnostic criteria for PNP is needed to help practitioners to consensually diagnose it for prognostic or therapeutic trials.



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Nasal polyp fibroblasts modulate epithelial characteristics via Wnt signaling

International Forum of Allergy &Rhinology, EarlyView.


https://ift.tt/2Po2yHg

Operative time and cost variability for functional endoscopic sinus surgery

International Forum of Allergy &Rhinology, EarlyView.


https://ift.tt/2MVY9JY

Critical assessment of approaches for molecular docking to elucidate associations of HLA alleles with adverse drug reactions

Publication date: September 2018

Source: Molecular Immunology, Volume 101

Author(s): Kerry A. Ramsbottom, Daniel F. Carr, Andrew R. Jones, Daniel J. Rigden

Abstract

Adverse drug reactions have been linked with genetic polymorphisms in HLA genes in numerous different studies. HLA proteins have an essential role in the presentation of self and non-self peptides, as part of the adaptive immune response. Amongst the associated drugs-allele combinations, anti-HIV drug Abacavir has been shown to be associated with the HLA-B*57:01 allele, and anti-epilepsy drug Carbamazepine with B*15:02, in both cases likely following the altered peptide repertoire model of interaction. Under this model, the drug binds directly to the antigen presentation region, causing different self peptides to be presented, which trigger an unwanted immune response. There is growing interest in searching for evidence supporting this model for other ADRs using bioinformatics techniques. In this study, in silico docking was used to assess the utility and reliability of well-known docking programs when addressing these challenging HLA-drug situations. The overall aim was to address the uncertainty of docking programs giving different results by completing a detailed comparative study of docking software, grounded in the MHC-ligand experimental structural data – for Abacavir and to a lesser extent Carbamazepine - in order to assess their performance. Four docking programs: SwissDock, ROSIE, AutoDock Vina and AutoDockFR, were used to investigate if each software could accurately dock the Abacavir back into the crystal structure for the protein arising from the known risk allele, and if they were able to distinguish between the HLA-associated and non-HLA-associated (control) alleles. The impact of using homology models on the docking performance and how using different parameters, such as including receptor flexibility, affected the docking performance were also investigated to simulate the approach where a crystal structure for a given HLA allele may be unavailable. The programs that were best able to predict the binding position of Abacavir were then used to recreate the docking seen for Carbamazepine with B*15:02 and controls alleles.

It was found that the programs investigated were sometimes able to correctly predict the binding mode of Abacavir with B*57:01 but not always. Each of the software packages that were assessed could predict the binding of Abacavir and Carbamazepine within the correct sub-pocket and, with the exception of ROSIE, was able to correctly distinguish between risk and control alleles. We found that docking to homology models could produce poorer quality predictions, especially when sequence differences impact the architecture of predicted binding pockets. Caution must therefore be used as inaccurate structures may lead to erroneous docking predictions. Incorporating receptor flexibility was found to negatively affect the docking performance for the examples investigated. Taken together, our findings help characterise the potential but also the limitations of computational prediction of drug-HLA interactions. These docking techniques should therefore always be used with care and alongside other methods of investigation, in order to be able to draw strong conclusions from the given results.



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Zoon's plasma cell balanitis: clinical and dermoscopic features in pediatric patients

International Journal of Dermatology, EarlyView.


https://ift.tt/2nPNlSt

Recommendations for the use of telemedicine in severely under‐resourced settings: results from a pilot study in Niamey, Niger

International Journal of Dermatology, EarlyView.


https://ift.tt/2wf2f8V

Gastrointestinal prophylaxis in patients with autoimmune blistering disease treated with corticosteroids: an expert survey

International Journal of Dermatology, EarlyView.


https://ift.tt/2nOeyoG

A novel surgical technique: Crushed septal cartilage graft application in endonasal septoplasty

Publication date: Available online 17 August 2018

Source: Auris Nasus Larynx

Author(s): Vahit Mutlu

Abstract
Objective

Nowadays, different septoplasty procedures are applied for therapy of nasal septum deviation. However, various complications of the septoplasty procedures have been described. Several techniques have been developed to decrease the incidence of these complications by surgeons. We aimed to present the effectiveness of the crushed septal cartilage graft, which is a novel septoplasty technique.

Methods

Patients: Patients The study was performed based on the parameters of 500 patients who underwent surgery with crushed cartilage graft technique in our clinic between the dates 2013 and 2016.

Technique: This novel operation technique was performed under general anestesia. The NOSE (Nasal obstruction symptom evaluation) scale was applied to all patients in both the preoperative period and the 2nd month of the postoperative period, and then the both values were statistically compared. Additionally, all the patients were followed up for complications that may occur after the operation for a year.

Results

The study included 140 (28%) female and 360 (72%) male patients, which totally makes 500 patients. The average age of the participants was 35 ± 12.5. When compared to the preoperative NOSE scale values (P ˂ 0.001), the postoperative NOSE scale values were found to be significant. We watched intranasal infection and incrustation in 7(1.4%) patients in early postoperative period and the epistaxis in 3(0.6%) patients in late postoperative period. We did not see any postoperative complications apart from these two minor and insignificant complications during the follow-up along a year.

Conclusion

The crushed cartilage technique is a feasible, safe and effective alternative surgery technique to traditional septoplasty. What is more, complications of septoplasty can be prevented with the help of this novel surgical technique.



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(Invited thematic article) Prevalence and pathogenesis of osteopenia and osteoporosis in epidermolysis bullosa: An Evidence Based Review

Experimental Dermatology, Volume 0, Issue ja, -Not available-.


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Efficacy and safety of daylight photodynamic therapy after tailored pretreatment with ablative fractional laser or microdermabrasion: a randomized, side‐by‐side, single‐blind trial in patients with actinic keratosis and large area field cancerization

British Journal of Dermatology, Volume 0, Issue ja, -Not available-.


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Mosaic mutations in FGFR3 and FGFR2 are associated with naevoid acanthosis nigricans or RAVEN (round and velvety epidermal naevus)

British Journal of Dermatology, Volume 0, Issue ja, -Not available-.


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Tumor spontaneous regression in an elderly patient with Squamous Cell Carcinoma of the cranial vertex pre‐treated with cetuximab monotherapy

British Journal of Dermatology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2vUJLer

Xeroderma pigmentosum group D: Report of a novel combination of ERCC2 variations and its phenotype

The Journal of Dermatology, EarlyView.


https://ift.tt/2wkg9Xt

Development of Kasabach–Merritt phenomenon following vaccination: More than a coincidence?

The Journal of Dermatology, EarlyView.


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Subungual exostosis with postoperative recurrence followed by spontaneous regression

The Journal of Dermatology, EarlyView.


https://ift.tt/2wkfZiP

Reciprocal relationship between herpes zoster and cardiovascular diseases: A nationwide population‐based case–control study in Korea

The Journal of Dermatology, EarlyView.


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The Temporal Development of Dust Formation and Destruction in Nova Sagittarii 2015#2 (V5668 SGR): A Panchromatic Study

Gehrz, RD; Evans, A; Woodward, CE; Helton, LA; Banerjee, DPK; Srivastava, MK; Ashok, NM; ... Wagner, RM; + view all Gehrz, RD; Evans, A; Woodward, CE; Helton, LA; Banerjee, DPK; Srivastava, MK; Ashok, NM; Joshi, V; Eyres, SPS; Krautter, J; Kuin, NPM; Page, KL; Osborne, JP; Schwarz, GJ; Shenoy, DP; Shore, SN; Starrfield, SG; Wagner, RM; - view fewer (2018) The Temporal Development of Dust Formation and Destruction in Nova Sagittarii 2015#2 (V5668 SGR): A Panchromatic Study. The Astrophysical Journal , 858 (2) , Article 78. 10.3847/1538-4357/aaba81 . Green open access

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In situ X-ray imaging of defect and molten pool dynamics in laser additive manufacturing

Leung, CLA; Marussi, S; Atwood, RC; Towrie, M; Withers, PJ; Lee, PD; (2018) In situ X-ray imaging of defect and molten pool dynamics in laser additive manufacturing. Nature Communications , 9 , Article 1355. 10.1038/s41467-018-03734-7 . Green open access

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Training citizen translators: Design and delivery of bespoke training on the fundamentals of translation for New Zealand Red Cross

Federici, FM; Cadwell, P; (2018) Training citizen translators: Design and delivery of bespoke training on the fundamentals of translation for New Zealand Red Cross. Translation Spaces , 7 (1) pp. 20-43. 10.1075/ts.00002.fed . Green open access

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Synthesis of bioinspired collagen/alginate/fibrin based hydrogels for soft tissue engineering

Montalbano, G; Toumpaniari, S; Popov, A; Duan, P; Chen, J; Dalgarno, K; Scott, WE; Montalbano, G; Toumpaniari, S; Popov, A; Duan, P; Chen, J; Dalgarno, K; Scott, WE; Ferreira, AM; - view fewer (2018) Synthesis of bioinspired collagen/alginate/fibrin based hydrogels for soft tissue engineering. Materials Science and Engineering: C , 91 pp. 236-246. 10.1016/j.msec.2018.04.101 . Green open access

https://ift.tt/2vTYsyx

Mechanism of Ethanol Photooxidation on Single-Crystal Anatase TiO2(101)

Katsiev, K; Harrison, G; Alghamdi, H; Alsalik, Y; Wilson, A; Thornton, G; Idriss, H; (2017) Mechanism of Ethanol Photooxidation on Single-Crystal Anatase TiO2(101). The Journal of Physical Chemistry C , 121 (5) pp. 2940-2950. 10.1021/acs.jpcc.6b12776 . Green open access

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Revealing dendritic pattern formation in Ni, Fe and Co alloys using synchrotron tomography

Azeem, MA; Lee, PD; Phillion, AB; Karagadde, S; Rockett, P; Atwood, RC; Courtois, L; ... Dye, D; + view all Azeem, MA; Lee, PD; Phillion, AB; Karagadde, S; Rockett, P; Atwood, RC; Courtois, L; Rahman, KM; Dye, D; - view fewer (2017) Revealing dendritic pattern formation in Ni, Fe and Co alloys using synchrotron tomography. Acta Materialia , 128 pp. 241-248. 10.1016/j.actamat.2017.02.022 . Green open access

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Supporting pupils in school with social, emotional and mental health needs: a scoping review of the literature

Carroll, C; Hurry, J; (2018) Supporting pupils in school with social, emotional and mental health needs: a scoping review of the literature. Emotional and Behavioural Difficulties , 23 (3) pp. 310-325. 10.1080/13632752.2018.1452590 .

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Recognition of Dynamic Facial Affect in Substitute Maintained Opiate Users

Wellington, CE; (2013) Recognition of Dynamic Facial Affect in Substitute Maintained Opiate Users. Doctoral thesis (D.Clin.Psy), UCL (University College London).

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Low-background gamma spectroscopy at the Boulby Underground Laboratory

Scovell, PR; Meehan, E; Araújo, HM; Dobson, J; Ghag, C; Kraus, H; Kudryavtsev, VA; ... Yeoman, LM; + view all Scovell, PR; Meehan, E; Araújo, HM; Dobson, J; Ghag, C; Kraus, H; Kudryavtsev, VA; Liu, X-R; Majewski, P; Paling, SM; Preece, RM; Saakyan, R; Tomas, A; Toth, C; Yeoman, LM; - view fewer (2018) Low-background gamma spectroscopy at the Boulby Underground Laboratory. Astroparticle Physics , 97 pp. 160-173. 10.1016/j.astropartphys.2017.11.006 .

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