A rare case of an aldosterone secreting metastatic adrenocortical carcinoma and papillary thyroid carcinoma in a 31-year-old male

We report a rare synchronous presentation of adrenocortical carcinoma (ACC) and papillary thyroid carcinoma (PTC). A 31-year-old male first presented with a large left adrenal mass that was identified during the workup for refractory hypertension due to hyperaldosteronism. The mass was removed surgically with pathology showing ACC. The patient was then treated with adjuvant radiation therapy and mitotane chemotherapy. Four months post ACC resection, metastatic ACC to the right upper lung and PTC in the left lobe of the thyroid were found in surveillance imaging. He subsequently developed pulmonary, contralateral adrenal and brain metastases from his ACC. Li Fraumeni syndrome and Multiple Endocrine Neoplasia Type I (MEN I) were considered, but testing of both P53 and menin genes showed no mutation. We also performed a review of the literature and found three similar cases, however gene mutation analysis was not performed.

Skin autofluorescence is increased in patients with carotid artery stenosis and peripheral artery disease

Advanced glycation end products (AGEs) have a pivotal role in atherosclerosis. We evaluated skin autofluorescence (SAF), a non-invasive measurement of tissue AGE accumulation, in patients with carotid artery stenosis with and without coexisting peripheral artery occlusive disease (PAOD). SAF was measured using the AGE Reader™ in 56 patients with carotid artery stenosis and in 56 age- and sex-matched healthy controls without diabetes, renal dysfunction or known atherosclerotic disease. SAF was higher in patients with carotid artery stenosis compared to the control group: mean 2.81 versus 2.46 (P = 0.002), but especially in the younger age group of 50–60 years old: mean 2.82 versus 1.94 (P = 0.000). Patients with carotid artery stenosis and PAOD proved to have an even higher SAF than patients with carotid artery stenosis only: mean 3.28 versus 2.66 (P = 0.003). Backward linear regression analysis showed that age, smoking, diabetes mellitus, renal function and the presence of PAOD were the determinants of SAF, but carotid artery stenosis was not. SAF is increased in patients with carotid artery stenosis and PAOD. The univariate and multivariate associations of SAF with age, smoking, diabetes, renal insufficiency and PAOD suggest that increased SAF can be seen as an indicator of widespread atherosclerosis

Spatial Language Processing in the Blind: Evidence for a Supramodal Representation and Cortical Reorganization

Neuropsychological and imaging studies have shown that the left supramarginal gyrus (SMG) is specifically involved in processing spatial terms (e.g. above, left of), which locate places and objects in the world. The current fMRI study focused on the nature and specificity of representing spatial language in the left SMG by combining behavioral and neuronal activation data in blind and sighted individuals. Data from the blind provide an elegant way to test the supramodal representation hypothesis, i.e. abstract codes representing spatial relations yielding no activation differences between blind and sighted. Indeed, the left SMG was activated during spatial language processing in both blind and sighted individuals implying a supramodal representation of spatial and other dimensional relations which does not require visual experience to develop. However, in the absence of vision functional reorganization of the visual cortex is known to take place. An important consideration with respect to our finding is the amount of functional reorganization during language processing in our blind participants. Therefore, the participants also performed a verb generation task. We observed that only in the blind occipital areas were activated during covert language generation. Additionally, in the first task there was functional reorganization observed for processing language with a high linguistic load. As the visual cortex was not specifically active for spatial contents in the first task, and no reorganization was observed in the SMG, the latter finding further supports the notion that the left SMG is the main node for a supramodal representation of verbal spatial relations

Co-expression of CD147 (EMMPRIN), CD44v3-10, MDR1 and monocarboxylate transporters is associated with prostate cancer drug resistance and progression

Background: The aim of this study is to seek an association between markers of metastatic potential, drug resistance-related protein and monocarboxylate transporters in prostate cancer (CaP). Methods: We evaluated the expression of invasive markers (CD147, CD44v3-10), drug-resistance protein (MDR1) and monocarboxylate transporters (MCT1 and MCT4) in CaP metastatic cell lines and CaP tissue microarrays (n=140) by immunostaining. The co-expression of CD147 and CD44v3-10 with that of MDR1, MCT1 and MCT4 in CaP cell lines was evaluated using confocal microscopy. The relationship between the expression of CD147 and CD44v3-10 and the sensitivity (IC50) to docetaxel in CaP cell lines was assessed using MTT assay. The relationship between expression of CD44v3-10, MDR1 and MCT4 and various clinicopathological CaP progression parameters was examined. Results: CD147 and CD44v3-10 were co-expressed with MDR1, MCT1 and MCT4 in primary and metastatic CaP cells. Both CD147 and CD44v3-10 expression levels were inversely related to docetaxel sensitivity (IC50) in metastatic CaP cell lines. Overexpression of CD44v3-10, MDR1 and MCT4 was found in most primary CaP tissues, and was significantly associated with CaP progression. Conclusions: Our results suggest that the overexpression of CD147, CD44v3-10, MDR1 and MCT4 is associated with CaP progression. Expression of both CD147 and CD44v3-10 is correlated with drug resistance during CaP metastasis and could be a useful potential therapeutic target in advanced disease

Cardiovasc Diabetol

BACKGROUND: Advanced glycation end-products play a role in diabetic vascular complications. Their optical properties allow to estimate their accumulation in tissues by measuring the skin autofluorescence (SAF). We searched for an association between SAF and major adverse cardiovascular events (MACE) incidence in subjects with Type 1 Diabetes (T1D) during a 7 year follow-up. METHODS: During year 2009, 232 subjects with T1D were included. SAF measurement, clinical [age, sex, body mass index (BMI), comorbidities] and biological data (HbA1C, blood lipids, renal parameters) were recorded. MACE (myocardial infarction, stroke, lower extremity amputation or a revascularization procedure) were registered at visits in the center or by phone call to general practitioners until 2016. RESULTS: The participants were mainly men (59.5%), 51.5 +/- 16.7 years old, with BMI 25.0 +/- 4.1 kg/m(2), diabetes duration 21.5 +/- 13.6 years, HbA1C 7.6 +/- 1.1%. LDL cholesterol was 1.04 +/- 0.29 g/L, estimated Glomerular Filtration Rates (CKD-EPI): 86.3 +/- 26.6 ml/min/1.73 m(2). Among these subjects, 25.1% were smokers, 45.3% had arterial hypertension, 15.9% had elevated AER (>/= 30 mg/24 h), and 9.9% subjects had a history of previous MACE. From 2009 to 2016, 22 patients had at least one new MACE: 6 myocardial infarctions, 1 lower limb amputation, 15 revascularization procedures. Their SAF was 2.63 +/- 0.73 arbitrary units (AU) vs 2.08 +/- 0.54 for other patients (p = 0.002). Using Cox-model, after adjustment for age (as the scale time), sex, diabetes duration, BMI, hypertension, smoking status, albumin excretion rates, statin treatment and a previous history of MACE, higher baseline levels of SAF were significantly associated with an increased risk of MACE during follow-up (HR = 4.13 [1.30-13.07]; p = 0.02 for 1 AU of SAF) and Kaplan-Meier curve follow-up showed significantly more frequent MACE in group with SAF upper the median (p = 0.001). CONCLUSION: A high SAF predicts MACE in patients with T1D

Skin fluorescence as a clinical tool for non-invasive assessment of advanced glycation and long-term complications of diabetes

Glycation is important in the development of complications of diabetes mellitus and may have a central role in the well-described glycaemic memory effect in developing these complications. Skin fluorescence has emerged over the last decade as a non-invasive method for assessing accumulation of advanced glycation endproducts. Skin fluorescence is independently related to micro- and macrovascular complications in both type 1 and type 2 diabetes mellitus and is associated with mortality in type 2 diabetes. The relation between skin fluorescence and cardiovascular disease also extends to other conditions with increased tissue AGE levels, such as renal failure. Besides cardiovascular complications, skin fluorescence has been associated, more recently, with other prevalent conditions in diabetes, such as brain atrophy and depression. Furthermore, skin fluorescence is related to past long-term glycaemic control and clinical markers of cardiovascular disease. This review will discuss the technique of skin fluorescence, its validation as a marker of tissue AGE accumulation, and its use as a clinical tool for the prediction of long-term complications in diabetes mellitus

Plasma lipid profiles discriminate bacterial from viral infection in febrile children

Fever is the most common reason that children present to Emergency Departments. Clinical signs and symptoms suggestive of bacterial infection are often non-specific, and there is no definitive test for the accurate diagnosis of infection. The 'omics' approaches to identifying biomarkers from the host-response to bacterial infection are promising. In this study, lipidomic analysis was carried out with plasma samples obtained from febrile children with confirmed bacterial infection (n = 20) and confirmed viral infection (n = 20). We show for the first time that bacterial and viral infection produces distinct profile in the host lipidome. Some species of glycerophosphoinositol, sphingomyelin, lysophosphatidylcholine and cholesterol sulfate were higher in the confirmed virus infected group, while some species of fatty acids, glycerophosphocholine, glycerophosphoserine, lactosylceramide and bilirubin were lower in the confirmed virus infected group when compared with confirmed bacterial infected group. A combination of three lipids achieved an area under the receiver operating characteristic (ROC) curve of 0.911 (95% CI 0.81 to 0.98). This pilot study demonstrates the potential of metabolic biomarkers to assist clinicians in distinguishing bacterial from viral infection in febrile children, to facilitate effective clinical management and to the limit inappropriate use of antibiotics