Effects of HLA status and HER2 status on outcomes in breast cancer patients at risk for recurrence – Implications for vaccine trial design

Publication date: Available online 17 July 2018

Source: Clinical Immunology

Author(s): O. Jackson Doreen, Trappey A. Francois, Clifton G. Travis, J. Vreeland Timothy, M. Peace Kaitlin, F. Hale Diane, K. Litton Jennifer, L. Murray James, A. Perez Sonia, Papamichail Michael, A. Mittendorf Elizabeth, E. Peoples George

Abstract

Immunotherapy, using peptide-based cancer vaccines is being studied to assess its potential in breast cancer. Trials of HLA-restricted peptide vaccines have been difficult to enroll given HLA subtype restrictions. It is necessary to determine the prognostic significance of HLA-status in breast cancer if patients who are ineligible to receive a vaccine due to their HLA-status are used as controls. The impact of targeted tumor associated antigen expression, when it effects eligibility is also important. We examined control patients from two randomized phase II trials that tested HER2-peptide vaccines to determine the effect of HLA-A2 status and HER2 expression on disease-free survival. The analysis showed that HLA-A2-status does not affect disease-free survival, regardless of HER2 expression suggesting that HLA-A2 negative patients can be used as control patients. Additionally, HER2 over-expression was associated with a better disease-free survival in this population, underscoring the need for additional therapies in HER2 low-expressing breast cancer.

ClinicalTrials.gov Identifier: NCT00524277

https://ift.tt/2NmWDjK

Systemic lupus erythematosus-myasthenia gravis overlap syndrome: Presentation and treatment depend on prior thymectomy

Publication date: Available online 17 July 2018

Source: Clinical Immunology

Author(s): Scott Brian Minchenberg, Geeta Chaparala, Zachary Oaks, Katalin Banki, Andras Perl

Abstract

In this study, we investigated four patients who met the diagnostic criteria for overlapping systemic lupus erythematosus (SLE) and myasthenia gravis (MG) but responded differently to treatment. All patients were acetylcholine receptor (AChR) and antinuclear antibody positive at the time of SLE diagnosis. Two patients presented with SLE who have been effectively treated with cholinesterase inhibitors for MG. These patients developed SLE with photosensitivity, rash, and arthritis post thymectomy, which had been performed 29 years and 40 years earlier, respectively. Two other patients were found to have AChR antibodies and MG in the context on new-onset SLE. These subjects were responsive to hydroxychloroquine and immunosuppression but failed cholinesterase inhibitors. The evolution of these cases is relevant for the role of thymus in lupus pathogenesis during aging and for treatment selection in SLE-MG overlap patients.

https://ift.tt/2NZisag

Accidental food allergy reactions: Products and undeclared ingredients

Publication date: Available online 17 July 2018

Source: Journal of Allergy and Clinical Immunology

Author(s): W. Marty Blom, Anouska D. Michelsen-Huisman, Harmieke van Os-Medendorp, Gert van Duijn, Mary-lène de Zeeuw-Brouwer, Astrid Versluis, Jacqueline J.M. Castenmiller, Hubert P.J.M. Noteborn, Astrid G. Kruizinga, André C. Knulst, Geert F. Houben

Background

Accidental allergic reactions to food are frequent and can be severe and even fatal.

Objective

We sought to analyze the culprit food products and levels of unexpected allergens in accidental reactions.

Methods

A prospective cohort study was conducted in adults (n = 157) with a physician-confirmed diagnosis of food allergy. During a 1-year follow-up, 73 patients reported accidental allergic reactions and the culprit food products. Food samples received (n = 51) were analyzed for a wide range of suspected noningredient allergens, and risk was quantified.

Results

A very diverse range of food products was responsible for the unexpected allergic reactions. Thirty-seven percent (19/51) of products analyzed had 1 to 4 culprit allergens identified that were not supposed to be present according to the ingredient declaration. Concentrations varied from 1 to 5000 mg of protein of the allergenic food per kilogram of food product and were greatest for peanut, milk, and sesame. Milk proteins posed the highest estimated risk for objective allergic reactions. The intake of culprit allergens by patients varied considerably. For those cases in which culprit allergens were detected, the intake of at least 1 allergen exceeded the reference dose or a culprit allergen with a yet unknown reference dose was present. Both patient neglect of precautionary allergen labeling statements and omission of using a precautionary allergen labeling statement by food manufacturers seem to contribute to accidental reactions.

Conclusion

A wide range of food products are causing accidental reactions in patients with food allergy. Eight different allergens not declared on the ingredient lists were detected in the culprit food products, all of which were representative of allergens regulated in the European Union.

Graphical abstract

https://ift.tt/2JwL9rq

Pilomatricome : corrélation dermatopathologie-dermatoscopie

Publication date: Available online 17 July 2018

Source: Annales de Dermatologie et de Vénéréologie

Author(s): P. Huet, G. Barnéon, B. Cribier

https://ift.tt/2NqJVAx

Femtosecond laser settings for optimal bracket bonding to zirconia

Abstract

Bonding orthodontic brackets to ceramic materials is a challenging procedure; femtosecond (FS) laser conditioning could provide improved results, but the ideal settings for effective bracket-zirconia bonding have never been established. This study aimed to analyze the differences in surface roughness and shear bond strength (SBS) produced by different femtosecond laser settings and establish a protocol to prepare zirconia surfaces for optimal adhesion to metal orthodontic brackets. One hundred eighty zirconia samples were assigned to six groups according to surface treatment: (1) control; (2) air-particle abrasion (APA); (3) FS laser irradiation (300 mW output power, 60 μm inter-groove distance); (4) FS laser irradiation (200 mW, 100 μm); (5) FS laser irradiation (40 mW, 60 μm); and (6) FS laser irradiation (200 mW, 60 μm). Surface roughness was measured. Orthodontic brackets were bonded to the zirconia specimens, and SBS was measured. SBS in groups 3 and 6 was significantly higher than the other groups (5.92 ± 1.12 MPa and 5.68 ± 0.94 MPa). No significant differences were found between groups 1, 2, 4, and 5 (3.87 ± 0.77 MPa, 4.25 ± 0.51 MPa, 3.74 ± 0.10 MPa, and 3.91 ± 0.53 MPa). Surface roughness was significantly greater for FS laser than for control and APA groups (p = 1.28 × 10⁻⁸). FS laser at 200 mW, 60 μm can be recommended as the ideal settings for treating zirconia surfaces, producing good SBS and more economical energy use.

https://ift.tt/2zO3roK

Ethmoid tumor and oncogenic osteomalacia: Case report and review of the literature

Publication date: Available online 17 July 2018

Source: European Annals of Otorhinolaryngology, Head and Neck Diseases

Author(s): A. Villepelet, O. Casiraghi, S. Temam, A. Moya-Plana

Abstract

Introduction

Oncogenic osteomalacia is a very rare disease usually caused by a phosphaturic mesenchymal tumor, particularly the "mixed connective tissue type", secreting FGF-23 hormone.

Objective

The authors report a case of ethmoid tumor associated with oncogenic osteomalacia and discuss management based on a review of the literature.

Case summary

A 41-year-old woman with multiple fractures causing major disability was diagnosed with early-onset osteoporosis. CT scan followed by MRI, performed due to the concomitant presence of nasal obstruction, showed a right ethmoid tumor in contact with the dura mater and periorbital tissues, but with no signs of invasion. Endoscopic resection was performed with reconstruction of the defect of the cribriform plate by a nasoseptal flap. Nasal and bone symptoms subsequently resolved. Histological examination revealed a phosphaturic mesenchymal tumor.

Discussion

Twelve cases of mesenchymal tumor of the ethmoid sinus associated with oncogenic osteomalacia have been reported to date. FGF-23 assay and whole-body MRI with STIR sequence are useful for the diagnosis. A very favorable outcome is observed after surgical treatment in the majority of cases.

https://ift.tt/2moY2ej

Skewed X-chromosome inactivation and next-generation sequencing to identify a novel SMPX variants associated with X-linked hearing loss in a Chinese family

Publication date: Available online 17 July 2018

Source: International Journal of Pediatric Otorhinolaryngology

Author(s): Song Gao, Yi Jiang, Guojian Wang, Yongyi Yuan, Shasha Huang, Xue Gao, Xiaohong Li, Dejun Zhang, Jian Wu, Xiaowen Ji, Tao Deng, Ligang Wang, Dongyang Kang, Pu Dai

Abstract

Objective

Hereditary nonsyndromic hearing loss is extremely heterogeneous and an X-linked form accounts for 1∼5% of all cases. The aim of this study was to identify the pathogenic variants in a nonsyndromic X-linked dominant hearing loss family, and explain the reason of different hearing phenotype in hearing between the two sisters with the same variant.

Methods

Targeted gene capture and next-generation sequencing were used to study the genetic cause. What's more, methylation differences among the androgen receptor genes were used to investigate whether the different hearing levels of the two sisters is related to X-chromosome inactivation (Xi).

Results

We identified SMPX c.29insA (p.Asn10Lysfs*3) as the novel variant causing deafness. The skewed X-chromosome inactivation was relevant to the hearing difference between the two sisters.

Conclusion

Targeted gene capture and NGS is an efficient way to identify pathogenic variants in genes. Analysis of X-chromosome inactivation is beneficial to the diagnosis and genetic counseling of X-linked dominant hearing loss families.

https://ift.tt/2uIxnNn