Cutaneous squamous carcinoma in a patient with diabetic foot: an unusual evolution of a frequent complication

After basal cell carcinoma, the cutaneous squamous cell carcinoma (cSCC) is the second most frequent non-melanoma skin cancer worldwide, and, classically, arises from the upper coats of the epidermis of sun-exposed areas or from skin areas constantly exposed to a chronic inflammatory stimulus. The occurrence of cSCC seems to be linked to several factors, including exposure to sunlight (or other ultraviolet radiations), immunosuppression, chronic scarring conditions and some familial cancer syndromes. Although the majority of cSCCs are adequately eradicated by surgical excision, a subgroup of cSCC may be linked with an increased risk of recurrence, metastasis and death. The incidence of type 2 diabetes mellitus is constantly increasing worldwide. Importantly, diabetes mellitus is a strong risk factor for cancers (including cutaneous tumors) and is highly related with poor cancer outcomes. At present, in the literature, squamous cell carcinoma developing in association with diabetic foot ulcers has been already reported in some reports; however, additional data are needed to make the clinicians aware of this rare, although possible, complication. Therefore, we herein report an unusual case of an elderly man with T2DM and a positive oncological history, presenting a cSCC involving the skin overlying the first toe of left foot. The growing cSCC appeared approximately 3 years after the appearance of a diabetic ulcer

Early bronchopulmonary involvement in Crohn disease: a case report

BACKGROUND: Bronchopulmonary manifestations of Crohn disease have been rarely described in children, including both subclinical pulmonary involvement and severe lung disease. CASE PRESENTATION: A 6.5-year-old girl is described with early recurrent bronchopulmonary symptoms both at presentation and in the quiescent phase of Crohn disease. Pulmonary function tests (lung volumes and flows, bronchial reactivity and carbon monoxide diffusing capacity) were normal. Bronchoalveolar cytology showed increased (30%) lymphocyte counts and bronchial biopsy revealed thickening of basal membrane and active chronic inflammation. CONCLUSIONS: Clinical and histological findings in our young patient suggest involvement of both distal and central airways in an early phase of lung disease. The pathogenesis of Crohn disease-associated lung disorders is discussed with reference to the available literature. A low threshold for pulmonary evaluation seems to be advisable in all children with CD

Moving for a Better Life: Negotiating Fitting in and Belonging in Modern Diasporas

The paper focuses on the complexity of claiming and indexing fitting in and belonging in modern diasporas drawing on the narratives of young people (aged 15-26) who moved for the prospect of a better life. Successfully settling in a different context depends on being granted membership to the community and being accepted as one of us in at least some domains of human activity. This process is not straightforward and involves negotiating established hierarchies and positions of power. Dominant ideologies about the other are projected onto the newcomer, who is expected to fit in with the norms and ways of doing of the majority group and to display belonging. This paper focuses on the narratives of people from Greece and Italy who have either moved with their families or individually as young professionals. The narratives were collected through ethnographic interviews in a language chosen by the participants and fully transcribed and analysed following a critical interactional sociolinguistic approach. We pay special attention to the ways in which individuals position self and other. Our findings show that our participants narrate their lived experiences using binaries such as here and there, us and them, now and then in relation to belonging and fitting in. The participants claim intermediate, in-between positions and display strategies for claiming or resisting othering, while at the same time displaying fitting in with the broader, imagined context of the \u2018new\u2019 locus. We conclude the paper with the theoretical contribution of our work to socio- and applied linguistic studies and point to directions for further research

Association of CDK4 germline and BRAF somatic mutations in a patient with multiple primary melanomas and BRAF inhibitor resistance

Many genetic alterations, including predisposing or somatic mutations, may contribute toward the development of melanoma. Although CDKN2A and CDK4 are high-penetrance genes for melanoma, MC1R is a low-penetrance gene that has been associated most consistently with the disease. Moreover, BRAF is the most frequently somatically altered oncogene and is a validated therapeutic target in melanoma. This paper reports a case of multiple primary melanoma with germline CDK4 mutation, MC1R variant, and somatic BRAF mutation in nine out of 10 melanomas, indicating that a common pathogenesis, because of a predisposing genetic background, may be shared among distinct subsequent melanomas of probable clonal origin. After 3 months of targeted therapy with BRAF inhibitor, our patient developed resistance with rapid progression of the disease leading to death. This is the first case in which early resistance to BRAF inhibitor has been reported in a patient with CDK4 germline mutation

NRASQ61K mutated diffuse leptomeningeal melanomatosis in an adult patient with a brief review of the so-called "forme fruste" of neurocutaneous melanosis

Primary melanocytic tumors of central nervous system represent rare tumors arising from melanocytes of the leptomeninges. These neoplasms include focal forms like melanocytoma and primary malignant melanoma and diffuse forms like leptomeningeal melanocytosis and primary leptomeningeal melanomatosis. The clinical diagnosis remains challenging, with clinical and radiologic features overlapping with other more common diseases. Here we present a case of a 38\ua0years old male with primary diffuse leptomeningeal melanomatosis with presence of a NRASQ61K mutation without features of neurocutaneous melanosis

Lymphatic and blood vasculature in primary cutaneous melanomas of the scalp and neck

Background Scalp/neck melanomas have a poor prognosis, possibly because of a rich vascular supply that prompts tumor cells' dissemination. Methods We compared the accuracy of immunohistochemical (IHC) staining with morphology for the identification of lymphovascular invasion in 156 scalp/neck melanomas. We then analyzed the association of vessel invasion and density with pathological features and survival. Results IHC-detected lymphatic vessel invasion (LVI) and blood vessel invasion (BVI) were identified in 34.6% and 13.5% of cases, respectively. IHC increased the LVI/BVI detection compared to morphology (40.4% vs 16.6%; p &lt;.001). The degree of peritumoral and intratumoral blood vessel density (BVD) was greater than lymphatic vessel density (LVD). Ulceration was the only factor independently associated with intratumoral (p = .029) and peritumoral (p = .047) BVD. Tumor thickness was the only independent predictor of survival (p = .002). Conclusion IHC allows accurate assessment of lymphovascular invasion in scalp/neck melanomas. In these tumors, we observed a high incidence of BVI, which deserves further investigations.</br

Development and validation of a microRNA-based signature (MiROvaR) to predict early relapse or progression of epithelial ovarian cancer: a cohort study

Background Risk of relapse or progression remains high in the treatment of most patients with epithelial ovarian cancer, and development of a molecular predictor could be a valuable tool for stratification of patients by risk. We aimed to develop a microRNA (miRNA)-based molecular classifier that can predict risk of progression or relapse in patients with epithelial ovarian cancer. Methods We analysed miRNA expression profiles in three cohorts of samples collected at diagnosis. We used 179 samples from a Multicenter Italian Trial in Ovarian cancer trial (cohort OC179) to develop the model and 263 samples from two cancer centres (cohort OC263) and 452 samples from The Cancer Genome Atlas epithelial ovarian cancer series (cohort OC452) to validate the model. The primary clinical endpoint was progression-free survival, and we adapted a semi-supervised prediction method to the miRNA expression profile of OC179 to identify miRNAs that predict risk of progression. We assessed the independent prognostic role of the model using multivariable analysis with a Cox regression model. Findings We identified 35 miRNAs that predicted risk of progression or relapse and used them to create a prognostic model, the 35-miRNA-based predictor of Risk of Ovarian Cancer Relapse or progression (MiROvaR). MiROvaR was able to classify patients in OC179 into a high-risk group (89 patients; median progression-free survival 18 months [95% CI 15\u201322]) and a low-risk group (90 patients; median progression-free survival 38 months [24\u2013not estimable]; hazard ratio [HR] 1\ub785 [1\ub729\u20132\ub764], p=0\ub700082). MiROvaR was a significant predictor of progression in the two validation sets (OC263 HR 3\ub716, 95% CI 2\ub733\u20134\ub729, p&lt;0\ub70001; OC452 HR 1\ub739, 95% CI 1\ub711\u20131\ub774, p=0\ub70047) and maintained its independent prognostic effect when adjusted for relevant clinical covariates using multivariable analyses (OC179: adjusted HR 1\ub748, 95% CI 1\ub703\u20132\ub713, p=0\ub7036; OC263: adjusted HR 3\ub709 [2\ub724\u20134\ub728], p&lt;0\ub70001; and OC452: HR 1\ub741 [1\ub711\u20131\ub779], p=0\ub70047). Interpretation MiROvaR is a potential predictor of epithelial ovarian cancer progression and has prognostic value independent of relevant clinical covariates. MiROvaR warrants further investigation for the development of a clinical-grade prognostic assay. Funding AIRC and CARIPLO Foundation

In-flight polarization angle calibration for LiteBIRD: blind challenge and cosmological implications

International audienceWe present a demonstration of the in-flight polarization angle calibration for the JAXA/ISAS second strategic large class mission, LiteBIRD, and estimate its impact on the measurement of the tensor-to-scalar ratio parameter, r, using simulated data. We generate a set of simulated sky maps with CMB and polarized foreground emission, and inject instrumental noise and polarization angle offsets to the 22 (partially overlapping) LiteBIRD frequency channels. Our in-flight angle calibration relies on nulling the EB cross correlation of the polarized signal in each channel. This calibration step has been carried out by two independent groups with a blind analysis, allowing an accuracy of the order of a few arc-minutes to be reached on the estimate of the angle offsets. Both the corrected and uncorrected multi-frequency maps are propagated through the foreground cleaning step, with the goal of computing clean CMB maps. We employ two component separation algorithms, the Bayesian-Separation of Components and Residuals Estimate Tool (B-SeCRET), and the Needlet Internal Linear Combination (NILC). We find that the recovered CMB maps obtained with algorithms that do not make any assumptions about the foreground properties, such as NILC, are only mildly affected by the angle miscalibration. However, polarization angle offsets strongly bias results obtained with the parametric fitting method. Once the miscalibration angles are corrected by EB nulling prior to the component separation, both component separation algorithms result in an unbiased estimation of the r parameter. While this work is motivated by the conceptual design study for LiteBIRD, its framework can be broadly applied to any CMB polarization experiment. In particular, the combination of simulation plus blind analysis provides a robust forecast by taking into account not only detector sensitivity but also systematic effects