A case of facial burn due to the misuse of garlic face mask for acne

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Clinical translation and regulatory aspects of CAR/TCR-based adoptive cell therapies—the German Cancer Consortium approach

Abstract

Adoptive transfer of T cells genetically modified by TCRs or CARs represents a highly attractive novel therapeutic strategy to treat malignant diseases. Various approaches for the development of such gene therapy medicinal products (GTMPs) have been initiated by scientists in recent years. To date, however, the number of clinical trials commenced in Germany and Europe is still low. Several hurdles may contribute to the delay in clinical translation of these therapeutic innovations including the significant complexity of manufacture and non-clinical testing of these novel medicinal products, the limited knowledge about the intricate regulatory requirements of the academic developers as well as limitations of funds for clinical testing. A suitable good manufacturing practice (GMP) environment is a key prerequisite and platform for the development, validation, and manufacture of such cell-based therapies, but may also represent a bottleneck for clinical translation. The German Cancer Consortium (DKTK) and the Paul-Ehrlich-Institut (PEI) have initiated joint efforts of researchers and regulators to facilitate and advance early phase, academia-driven clinical trials. Starting with a workshop held in 2016, stakeholders from academia and regulatory authorities in Germany have entered into continuing discussions on a diversity of scientific, manufacturing, and regulatory aspects, as well as the benefits and risks of clinical application of CAR/TCR-based cell therapies. This review summarizes the current state of discussions of this cooperative approach providing a basis for further policy-making and suitable modification of processes.

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A systematic review of pyoderma gangrenosum with pulmonmary involvement: clinical presentation, diagnosis, and management

Abstract

Pyoderma gangrenosum (PG) is a neutrophilic dermatosis that often has extracutaneous manifestations, with lung involvement being the most common (1, 2). In this systematic review we have summarized the clinical presentation, predisposing factors, and treatment of PG patients with pulmonary involvement and compared them to classic neutrophilic disorders. Using the search terms "pulmonary, lung, respiratory, bronchi, or bronchopulmonary" AND "pyoderma gangrenosum" a systematic review was conducted using PubMed and Web of Science.

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Basal cell carcinoma of the scrotum: an important but easily overlooked entity

Abstract

Basal cell carcinoma (BCC) is the most common skin cancer worldwide [1]. In Germany, 82/100.000 inhabitants are yearly diagnosed with BCC [2]. Since chronic exposure to UV-light is the major risk factor for the development of BCC, the tumor is rarely seen in non-sun-exposed anatomical sites such as the genital area [1]. So far, only a few case reports or small case series have been published about BCC in this location, the pathogenic mechanisms underlying the development of scrotal BCCs are unknown.

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Progeria: case report and new drugs perspectives

Abstract

Hutchinson-Gilford progeria syndrome (HGPS) is one of the rarest human diseases, an autosomal dominant premature aging disorder ¹. Its incidence is 1-4 per 8 million newborns ². There are aging-associated symptoms, including lack of subcutaneous fat, hair loss, joint contractures, progressive cardiovascular disease resembling atherosclerosis, and death due to heart attacks and strokes in childhood.

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A fifth subtype of Kaposi's sarcoma, classic Kaposi's sarcoma in men who have sex with men: a cohort study in Paris

Abstract

Background

Classic Kaposi's sarcoma (CKS) occurs predominantly among elderly men and is associated with KSHV (Kaposi's Sarcoma-Associated Herpesvirus). In low endemic countries, KSHV infects predominantly men having sex with men (MSM).

Objectives

To describe a cohort of classic Kaposi sarcoma in a low endemic area for KSHV, to highlight the features of CKS in MSM and identify prognostic factors.

Methods

Retrospective single-center study of CKS cases. We compared MSM to heterosexual patients. Then, we divided the patients into two subgroups, those requiring a systemic treatment and the others, and we performed univariate and multivariate analysis to determine aggressiveness of CKS.

Results

Between 2006 and 2015, seventy-four patients were included. Mean age at diagnosis was 68.9 years, sex ratio (M/F) was 6.4 and 28% were MSM; MSM patients were younger (p=0.02), less often originated from endemic areas (p<0.0001). KS was less severe (p=0.04), required more often a local treatment than a systemic one (p=0.03). On multivariate analysis, CD4 T cell count> 500/mm³ at baseline was associated with a reduced risk of severe evolution.

Conclusion

First CKS cohort in low endemic zone. We describe a fifth subtype of KS: KS in MSM. The CD4 T-cell count was found to correlate with prognosis.

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Hypertrichosis of the pinnae in a patient using panitumumab

Abstract

Various subgroups of epidermal growth factor receptor inhibitors (EGFRIs) are increasingly being used in the treatment of several cancers. However, as a generalized class effect, they are frequently associated with a wide spectrum of dermatological adverse reactions affecting skin, hair and nail of varying severity.A 53-year-old male with metastatic rectal cancer receiving every two weeks infusions of panitumumab, a human monoclonal antibody targeting EGFR, presented with a generalized acneiform papulopustular eruption (Grade 3 according to the Common Terminology Criteria for Adverse Events version 4.03).

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Reversed actinic damage in two children with xeroderma pigmentosum treated with topical imiquimod

Abstract

Xeroderma pigmentosum (XP) is a group of genetic diseases with high incidence of ultraviolet-related skin cancers that usually appear in childhood. Treatment options for skin cancer in XP include surgery, electrocoagulation, topical 5-fluorouracil or imiquimod 5% cream¹. Oral retinoids have been used for skin cancer prevention, alone or in combination with topical imiquimod, with good response².

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Diagnostic approach to subcutaneous nodules in patients with neuroendocrine tumors treated with depot somatostatin analogs: a cross-sectional study

Abstract

Background

The presence of cutaneous nodules in patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs) receiving depot somatostatin analogs (SSAs) is a diagnostic challenge as differential diagnosis between injection site reactions and metastases is essential.

Objective

To characterize the clinical, radiological, cytological and histopathological features of subcutaneous nodules in patients with GEP-NETs treated with SSAs.

Materials and Methods

Retrospective, cross-sectional study of patients with GEP-NETs treated with SSAs in whom subcutaneous nodules were detected on routine abdominal CT scans. High resolution and color Doppler ultrasonography was performed. Those patients with inconclusive radiological studies went through fine-needle aspiration cytology (FNAC) and/or biopsy.

Results

Twelve patients (5 males, 7 females) were included (6 midgut carcinoid NETs, 6 pancreatic NETs). Three patients received intramuscular depot octreotide, 7 subcutaneous lanreotide, and 2 both treatments. CT scan findings were nonspecific. Sonography revealed a hyperechoic pattern in recent injections, and a hypoechoic pattern with a characteristic hyperechoic peripheral rim in long-term injections (more than 3 months after injection). On color Doppler sonography, nodules showed no signs of intralesional vascularity. Fine-needle aspiration cytology (FNAC) was performed in 5 patients, revealing a characteristic acellular proteinaceous material. Biopsy in 4 patients showed different reactional infiltrates around the acellular material.

Conclusions

High resolution and color Doppler ultrasonography may be very useful for the differential diagnosis of subcutaneous nodules in patients with GEP-NETs treated with SSAs. FNAC and a biopsy are useful tests for confirmation of the diagnosis in patients with inconclusive findings. We propose a management algorithm.

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Atopic Dermatitis and Alcohol Use: A Meta-Analysis and Systematic Review

Abstract

While several maternal exposures have been associated with an increased risk of atopic dermatitis (AD) in offspring, the effect of alcohol use during pregnancy on the risk of AD in offspring is unclear. Furthermore, it is unclear whether adults with AD have an increased alcohol use, though other poor health behaviors have been associated with AD including smoking and physical inactivity as well as psychiatric disease. In this systematic review and meta-analysis, the association between alcohol use and AD were investigated in two ways: 1) whether alcohol use (drinkers versus abstainers) during pregnancy is associated with AD in offspring, and 2) whether AD is associated with increased alcohol use. The medical databases Pubmed, Embase and Web of Science were searched and data extraction was done by two independent reviewers. Eighteen studies were included in the qualitative analysis (comparing alcohol drinkers to abstainers) and 12 studies were included in the quantitative analysis. There was a positive association between alcohol use during pregnancy and development of AD in offspring (pooled odds ratio [OR] 1.16; 95% confidence interval [CI] 1.09-1.24). However, there was no consistent association between AD in adults and adolescents and alcohol use (pooled OR 1.06; 95% CI 0.92-1.23). There is a need for future well-designed prospective studies to firmly establish the association between alcohol use and AD.

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Effect of finish line design on stress distribution in bilayer and monolithic zirconia crowns: a three-dimensional finite element analysis study

This study evaluated the influence of different finish line designs and abutment materials on the stress distribution of bilayer and monolithic zirconia crowns using three-dimensional finite element analysis (FEA). Three-dimensional models of two types of zirconia premolars – a yttria-stabilized zirconia framework with veneering ceramic and a monolithic zirconia ceramic – were used in the analysis. Cylindrical models with the finish line design of the crown abutments were prepared with three types of margin curvature radius (CR): CR = 0 (CR0; shoulder margin), CR = 0.5 (CR0.5; rounded shoulder margin), and CR = 1.0 (CR1.0; deep chamfer margin). Two abutment materials (dentin and brass) were analyzed. In the FEA model, 1 N was loaded perpendicular to the occlusal surface at the center of the crown, and linear static analysis was performed. For all crowns, stress was localized to the occlusal loading area as well as to the axial walls of the proximal region. The lowest maximum principal stress values were observed when the dentin abutment with CR0.5 was used under a monolithic zirconia crown. These results suggest that the rounded shoulder margin and deep chamfer margin, in combination with a monolithic zirconia crown, potentially have optimal geometry to minimize occlusal stress.

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Recurrent Syncope, a Clue in Amyloid Cardiomyopathy

Infiltrative cardiomyopathies include a variety of disorders that lead to myocardial thickening resulting in a constellation of clinical manifestations and eventually heart failure that could be the first clue to reach the diagnosis. Among the more described infiltrative diseases of the heart is amyloid cardiomyopathy. The disease usually presents with subtle, nonspecific symptoms. Herein, we illustrate a case of recurrent syncope as the initial presenting symptom for systemic amyloid with polyneuropathy and cardiomyopathy as a cause of syncope. The article illustrates the role of advanced cardiac imaging in the diagnosis of the disease with a focused literature review. We also highlight the role of early, shared decision-making between patient, family, and medical team in the management of cardiac amyloidosis.

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Epstein–Barr virus strain heterogeneity impairs human T-cell immunity

Abstract

The Epstein–Barr virus (EBV) establishes lifelong infections in > 90% of the human population. Although contained as asymptomatic infection by the immune system in most individuals, EBV is associated with the pathogenesis of approximately 1.5% of all cancers in humans. Some of these EBV-associated tumors have been successfully treated by the infusion of virus-specific T-cell lines. Recent sequence analyses of a large number of viral isolates suggested that distinct EBV strains have evolved in different parts of the world. Here, we assessed the impact of such sequence variations on EBV-specific T-cell immunity. With the exceptions of EBNA2 and the EBNA3 family of proteins, an overall low protein sequence disparity of about 1% was noted between Asian viral isolates, including the newly characterized M81 strain, and the prototypic EBV type 1 and type 2 strains. However, when T-cell epitopes including their flanking regions were compared, a substantial proportion was found to be polymorphic in different EBV strains. Importantly, CD4+ and CD8+ T-cell clones specific for viral epitopes from one strain often showed diminished recognition of the corresponding epitopes in other strains. In addition, T-cell recognition of a conserved epitope was affected by amino acid exchanges within the epitope flanking region. Moreover, the CD8+ T-cell response against polymorphic epitopes varied between donors and often ignored antigen variants. These results demonstrate that viral strain heterogeneity may impair antiviral T-cell immunity and suggest that immunotherapeutic approaches against EBV should preferably target broad sets of conserved epitopes including their flanking regions.

http://ift.tt/2DG2SuG

Clinical value of 18FDG PET/CT in screening for distant metastases in head and neck squamous cell carcinoma

Abstract

Objectives

The detection of distant metastases is of major importance in management of head and neck squamous cell carcinoma patients.

Design

All patients underwent 18FDG PET/CT for the detection of distant metastases.

Setting

Retrospective single center study.

Participants

Head and neck squamous cell carcinoma patients with high risk factors for distant metastases.

Main outcome measures

Accuracy of 18FDG PET/CT for the detection of distant metastases using clinical development of distant metastases and a minimal follow-up of twelve months as reference standard. Comparison of overall survival between patients diagnosed with distant metastases during initial screening and patients diagnosed with distant metastases during follow-up.

Results

In 23 (12%) of the 190 patients 18FDG PET/CT detected distant metastases at screening. Sensitivity and negative predictive value were 46.2% (95% CI 32.6 – 59.7) and 82.6% (95% CI 76.8 – 88.5). No difference in median overall survival from the time of distant metastases detection was found between patients diagnosed with DM during work-up or during follow up.

Conclusions

In head and neck squamous cell carcinoma patients with high risk factors 18FDG PET/CT has a high negative predictive value for the detection of distant metastases and should be used in daily clinical practice, although the sensitivity is limited when long term follow-up is used as reference standard.

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Correlation between septal body size and inferior turbinate hypertrophy on computed tomography scans in fifty patients: A radiological analysis

Abstract

The septal body contains expansile tissue that may behave in a similar manner to the inferior turbinate. It is situated in the nasal valve region and, like the inferior turbinate, can cause changes in the nasal cross-sectional area and resistance to airflow.

Septal body hypertrophy combined with inferior turbinate hypertrophy may result in changes to nasal cross-sectional area and resistance to airflow.

Septal body hypertrophy is likely to accompany inferior turbinate hypertrophy.

Septal body thickness demonstrated significant positive correlation with the widths of the anterior turbinate medial mucosa and middle turbinate lateral mucosa. Septal body length demonstrated significant correlation with the widths of the anterior turbinate lateral mucosa and posterior turbinate lateral mucosa.

Septal body hypertrophy is significantly associated with inferior turbinate hypertrophy and narrowed internal nasal valve area. These results indicate that clinicians should check for concomitant septal body hypertrophy in patients with inferior turbinate hypertrophy.

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