Oral burning with dysphagia and weight loss

Fibromyalgia is a disorder characterized by an abnormal pain regulation. Widespread pain, fatigue, and sleep disturbance are the prevalent symptoms. When unusual symptoms are overbearingly predominant at clinical presentation, the diagnosis becomes challenging. We report on the case of a patient with fibromyalgia, who presented with dysphagia, odynophagia, and glossodynia as prevalent symptoms. Difficulty in swallowing gradually developed over a month prior hospitalization, and worsened progressively so that nourishment and fluid intake were impeded. Because anemia with mild iron deficiency was found, esophagogastroduodenoscopy was performed, but no lesions were seen in the upper digestive tract. Levels of zinc and vitamin B12 were normal. Intense pain at pelvis and the inferior limbs, which was at a first glance referred to as osteoarthrosis, associated with oral symptoms and feeling of being in the clouds allowed us to diagnose fibromyalgia. Amitriptyline was used, with relief of symptoms. Although oropharyngeal symptoms were occasionally reported in fibromyalgia, they are often overlooked. The present case, therefore, testifies the need to consider the diagnosis of fibromyalgia when the patient presents with such symptoms that cannot be readily explained on other grounds

Novel perspectives on salt and interstitium: from hypertension to heart failure

Sodium (Na+) and water are closely linked in body fluid physiology by the concepts of osmosis and long-term balance. Our traditional understanding of fluid and electrolytes homeostasis has recently been challenged by suggestions of a systemic metabolic shift favouring water preservation when excess Na+ intake is excreted, and of skin as a depot for Na+ accumulation in multiple cardiovascular diseases and risk factors. In particular, a catabolic state would produce endogenous free water and facilitate its renal reabsorption independent of Na+, via urea generation and recycling: in the long term this could adversely impact cardiovascular risk, but has only been shown in preclinical settings. Similarly, the proposed water-independent nature of interstitial Na+ accumulation has the potential to induce local pathogenic changes to the surrounding structures, including the microvasculature, but lacks firm demonstration. The aims of this Thesis were therefore to investigate: 1) the impact of high Na+ intake on renal water-preserving mechanisms and metabolism in a real-life hypertensive population; 2) the nature, distribution and clinical correlates of tissue Na+ accumulation; 3) microvascular function, including capillary-interstitium fluid exchange and lymphatic drainage, in relation to interstitial Na+ accumulation. I herein retrospectively analysed clinical and biochemical blood and 24h-urinary data from consecutive patients with essential hypertension, collected at the time of screening for secondary causes, and found that kidneys can indeed dissociate Na+ and water handling (as estimated by their fractional excretions) when exposed to high Na+ intake. However, this comes at the cost of higher glomerular filtration rate, increased tubular energy expenditure, and protein catabolism at metabolomics signatures. By conducting a chemical analysis of multiple tissues from rodent models of salt sensitivity/salt loading and of skin from patients with hypertension or heart failure with preserved ejection fraction (HFpEF), I showed that tissue Na+ excess upon high Na+ intake is a systemic, rather than skin-specific, water-paralleled phenomenon reflecting the expansion of the extracellular compartment, and subclinical oedema in most cases. Despite the lack of any hypertonic interstitial Na+ accumulation to osmotically drag water out of vessels and facilitate the typical “congestion”, I also identified structural and molecular alterations in the skin blood and lymphatic microvasculature of patients with HFpEF, along with evidence of impaired lymphatic drainage of interstitial fluids upon pressure challenge. In summary, I confirmed the previous suggestions of a Na+-driven metabolic shift in a real-life population of hypertensive patients and largely expanded on the novel concepts of tissue Na+ accumulation. In particular, I disproved its water-independence in both experimental models and human subjects and suggested systemic isotonic Na+ excess as an important and likely prevalent determinant in the pathogenesis of hypertension and other cardiovascular diseases. The biophysical and molecular impact of this subclinical or clinically overt oedema on organ function, as well as the mechanisms of function and dysfunction of lymphatic vessels in the control of interstitial fluid in cardiovascular disease, need further exploration

Of snails, earthworms, and men: insights into strategies to preserve water

No abstract available

WAKE STRUCTURE AND DRAG OF VEHICLES WITH ROUNDED REAR EDGES

The wake structure at the rear of road vehicle is known to be of prime importance in aerodynamics performances [3]: about 30% of the total pressure drag derives from the rear end of the vehicle. While production vehicle present significant curvature at the rear end, most of fundamental aerodynamic analyses were carried out around simplified car models presenting sharp edges at the rear. Since recently, very few papers addressed the question of rear edges curvature in aerodynamics performances. Thacker et al. Showed that rounding the edge between the end of the roof and the rear slant suppressed the separation over the rear window and resulted in 10% drag reduction. Fuller et al.Studied the effect on spatial stability and intensity of the pillar vortex when rounding the side rear pillars. For both of these works, the analysis was focused on the flow behaviour over the rear window: the impact of the rear end rounding on the near wake topology was not discussed. The current study aims to understand how the use of rounded pillars with respect to sharp edges modifies the flow field (over the body surface and in the near wake) and hence the global drag. Moreover, an “academic” and an “industrial” model will be characterized to discuss the applicability of simplified models to simulate properly the sensitivity of pillars rounding

Aerodynamic performances of rounded fastback vehicle

Experimental and numerical analyzes were performed to investigate the aerodynamic performances of a realistic vehicle with a different afterbody rounding. This afterbody rounding resulted in a reduction to drag and lift at a yaw angle of zero, while the crosswind performances were degraded. Rounding the side pillars generated moderate changes to the drag and also caused important lift reductions. A minor effect on the drag force was found to result from the opposite drag effects on the slanted and vertical surfaces. The vorticity distribution in the near wake was also analyzed to understand the flow field modifications due to the afterbody rounding. Crosswind sensitivity was investigated to complete the analysis of the aerodynamic performances of the rounded edges models. Additional tests were conducted with geometry modifications as spoilers and underbody diffusers

Much Ado about N...atrium: modelling tissuesodium as a highly sensitive marker of subclinicaland localized oedema

Hypertonic Na+ accumulation in peripheral tissues is a recently described phenomenon: it has been associated with ageing, hypertension, diabetes, chronic kidney disease and heart failure, but its clinical meaning has yet to be determined. This concept conflicts with the classic physiological paradigm of constant balance between salt intake and excretion, and its water-independent nature is still a matter of debate. We developed a theoretical model explaining changes in the chemical composition of tissues as a function of extracellular volume fraction and excess extracellular fluid, i.e. oedema. The model suggests that the proportional increase in absolute Na+ content and concentration due to different degrees of oedema is higher than the parallel increase in water content, thus making Na+ a more sensitive index to detect this oedema. Our model would explain some of the recent findings of high tissue Na+ content in pathological conditions. More importantly, it prompts the reappraisal of tissue Na+ analysis from being a topic of niche interest to a potential diagnostic tool with broad applicability in the investigation of subclinical systemic and localized oedema

Supplemental Data and Methods: Subtyping of Primary Aldosteronism in the AVIS-2 Study: Assessment of Selectivity and Lateralisation

Context: Adrenal venous sampling (AVS) is the key test for subtyping primary aldosteronism (PA), but its interpretation varies widely across referral centers and this can adversely affect the management of PA patients. Objectives: To investigate in a real life study the rate of bilateral success, identification of unilateral aldosteronism and blood pressure outcomes in PA subtyped by AVS. Design and settings: in a retrospective analysis of the largest international registry of individual AVS data (AVIS-2 study) we investigated how different cut-off values of the selectivity (SI) and lateralization index (LI) affected rate of bilateral success, identification of unilateral aldosteronism and blood pressure outcomes. Results: AVIS-2 recruited 1625 individual AVS studies performed between 2000 and 2015 in 19 tertiary referral centers. Under unstimulated conditions, the rate of biochemically confirmed bilateral AVS success progressively decreased with increasing SI cut-offs; furthermore, with currently used LI cut-offs the rate of identified unilateral PA leading to adrenalectomy was as low as < 25%. A within-patient pairwise comparison of 402 AVS performed both under unstimulated and cosyntropin-stimulation conditions showed that cosyntropin increased the confirmed rate of bilateral selectivity for SI cutoffs ≥ 2.0, but with reduced lateralization rates (p < 0.001). Post-adrenalectomy outcomes were not improved by use of cosyntropin or more restrictive diagnostic criteria. Conclusion: Commonly used SI and LI cut-offs are associated with disappointingly low rates of biochemically defined AVS success and identified unilateral PA. Evidence-based protocols entailing less restrictive interpretative cut-offs might optimize the clinical use of this costly and invasive test

Quantitative Value of Aldosterone-Renin Ratio for Detection of Aldosterone-Producing Adenoma: The Aldosterone-Renin Ratio for Primary Aldosteronism (AQUARR) Study

Current guidelines recommend use of the aldosterone-renin ratio (ARR) for the case detection of primary aldosteronism followed by confirmatory tests to exclude false-positive results from further diagnostic workup. We investigated the hypothesis that this could be unnecessary in patients with a high ARR value if the quantitative information carried by the ARR is taken into due consideration

Drag and crosswind sensitivity of rounded fastback vehicle

Experimental and numerical analyzes were performed to investigate the aerodynamic performances of a realistic vehicle with a different afterbody rounding. This afterbody rounding resulted in a reduction to drag and lift at a yaw angle of zero, while the crosswind performances were degraded. Rounding the side pillars generated moderate changes to the drag and also caused important lift reductions. A minor effect on the drag force was found to result from the opposite drag effects on the slanted and vertical surfaces. The vorticity distribution in the near wake was also analyzed to understand the flow field modifications due to the afterbody rounding. Crosswind sensitivity was investigated to complete the analysis of the aerodynamic performances of the rounded edges models