First and second waves of coronavirus disease-19: A comparative study in hospitalized patients in Reus, Spain.

Many countries have seen a two-wave pattern in reported cases of coronavirus disease-19 during the 2020 pandemic, with a first wave during spring followed by the current second wave in late summer and autumn. Empirical data show that the characteristics of the effects of the virus do vary between the two periods. Differences in age range and severity of the disease have been reported, although the comparative characteristics of the two waves still remain largely unknown. Those characteristics are compared in this study using data from two equal periods of 3 and a half months. The first period, between 15th March and 30th June, corresponding to the entire first wave, and the second, between 1st July and 15th October, corresponding to part of the second wave, still present at the time of writing this article. Two hundred and four patients were hospitalized during the first period, and 264 during the second period. Patients in the second wave were younger and the duration of hospitalization and case fatality rate were lower than those in the first wave. In the second wave, there were more children, and pregnant and post-partum women. The most frequent signs and symptoms in both waves were fever, dyspnea, pneumonia, and cough, and the most relevant comorbidities were cardiovascular diseases, type 2 diabetes mellitus, and chronic neurological diseases. Patients from the second wave more frequently presented renal and gastrointestinal symptoms, were more often treated with non-invasive mechanical ventilation and corticoids, and less often with invasive mechanical ventilation, conventional oxygen therapy and anticoagulants. Several differences in mortality risk factors were also observed. These results might help to understand the characteristics of the second wave and the behaviour and danger of SARS-CoV-2 in the Mediterranean area and in Western Europe. Further studies are needed to confirm our findings.

Hemodynamic effects of blood clots trapped by an inferior vena cava filter.

The alteration of blood flow around an OPTEASE inferior vena cava filter with one or two blood clots attached was investigated by means of computational fluid dynamics. We used a patient-specific vein wall geometry, and we generated different clot models with shapes adapted to the filter and vein wall geometries. A total of eight geometries, with one or two clots and a total clot volume of 0.5 or 1 cm3 , were considered. A non-Newtonian model for blood viscosity was adopted and the possible development of turbulence was accounted for by means of a three-equation model. Two blood flow rates were considered for each case, representative for rest and exercise conditions. In exercise conditions, flow unsteadiness and even turbulence was detected in some cases. Pressure and wall shear stress (WSS) distributions were modified in all cases. Clots attached to the filter downstream basket considerably increased averaged WSS values by up to almost 50%. In all the cases a flow recirculation region appeared downstream of the clot. The degree of flow stagnation in these regions, an indicator of propensity to thrombogenesis, was estimated in terms of mean residence times and mean blood viscosity. High levels of flow stagnation were detected in rest conditions in the wake of those clots that were placed upstream from the filter. Our results suggest that one downstream placed big clot, showing a higher tendency to induce flow instabilities and turbulence, might be more harmful than two small clots placed in tandem.

A comparative CFD study of four inferior vena cava filters.

Computational fluid dynamics was used to simulate the flow of blood within an inferior vena cava (IVC) geometry model that was reconstructed from computed tomography images obtained from a real patient. The main novelty of the present work is that we simulated the implantation of 4 different filter models in this realistic IVC geometry. We considered different blood flow rates in the range between Vin =20 and Vin =80 cm3 /s, and all simulations were performed with both the Newtonian and a non-Newtonian model for the blood viscosity. We compared the hemodynamics performance of the different filter models, and we paid a special attention to the total drag force, Fd , exerted by the blood flow on the filter surface. This force is the sum of 2 contributions: the viscous skin friction force, which was found to be roughly proportional to the filter surface area, and the pressure force, which depended on the particular filter geometry design. The Fd force is relevant because it must be balanced by the total force exerted by the filter hooks/struts on the IVC wall at the attachment locations. For the highest Vin value investigated, the variation in Fd among filters was from 116 to 308 dyne. We also showed how the present results can be extrapolated to obtain good estimates of the drag forces if the blood viscosity levels change, ie, if the patient with a filter implanted is treated with anticoagulant therapy.

Effects of walking in deep venous thrombosis: a new integrated solid and fluid mechanics model.

Deep venous thrombosis (DVT) is a common disease. Large thrombi in venous vessels cause bad blood circulation and pain; and when a blood clot detaches from a vein wall, it causes an embolism whose consequences range from mild to fatal. Walking is recommended to DVT patients as a therapeutical complement. In this study the mechanical effects of walking on a specific patient of DVT were simulated by means of an unprecedented integration of 3 elements: a real geometry, a biomechanical model of body tissues, and a computational fluid dynamics study. A set of computed tomography images of a patient's leg with a thrombus in the popliteal vein was employed to reconstruct a geometry model. Then a biomechanical model was used to compute the new deformed geometry of the vein as a function of the fiber stretch level of the semimembranosus muscle. Finally, a computational fluid dynamics study was performed to compute the blood flow and the wall shear stress (WSS) at the vein and thrombus walls. Calculations showed that either a lengthening or shortening of the semimembranosus muscle led to a decrease of WSS levels up to 10%. Notwithstanding, changes in blood viscosity properties or blood flow rate may easily have a greater impact in WSS.

Effect of anticoagulant treatment in deep vein thrombosis: A patient-specific computational fluid dynamics study.

A methodology that might help physicians to establish a diagnostic and treatment tailored for each specific patient with a pathological thrombus is presented. A realistic model for the geometry of a popliteal vein with a thrombus just above the knee was reconstructed from in vivo computed tomography images acquired from one specific patient and then it was used to perform computational fluid dynamics (CFD) simulations. The wall shear stress (WSS) response to the administration of anticoagulant drugs and the influence of viscosity on the shape of the velocity distribution were investigated. Both a Newtonian and a non-Newtonian viscosity model were implemented for different blood flow rates in the range 3-7 cm(3)/s. The effect of anticoagulants on the blood was simulated by setting three different levels of viscosity in the Newtonian model (µ/µ∞=0.60, 0.80 and 1 with µ∞=3.45×10(-3) Pas). A reduction of µ by a given amount always led to a more modest reduction, typically by a factor of two, of the resulting WSS levels. Moreover, for a given flow rate the calculation with the non-Newtonian viscosity model yielded WSS levels between 20% and 40% larger than those obtained in the corresponding Newtonian fluid simulation. It was also found that blood moves slowly in the region between the thrombus and the vein wall, a fact that will favor the growth of the thrombotic mass. Both the mean WSS levels and the degree of sluggishness of the blood flow can be described by functions of the Reynolds number.

Calculation of human femoral vein wall parameters in vivo from clinical data for specific patient.

A common problem in the elaboration of biomechanical models is determining the properties and characteristics (measures) of the physical behavior of in vivo tissues in the human body. Correct estimates must be made of the tissue's physical properties and its surroundings. We suggest a method to compute the constitutive modeling of venous tissue, for every specific patient, from clinically registered ultrasounds images. The vein is modeled as a hyperelastic, incompressible, thin-walled cylinder and the membrane stresses are computed using strain energy. The approach is based on a strain-energy function suggested by Holzapfel capturing the characteristic nonlinear anisotropic responses of femoral veins with its collagen fibers.

Plasma fatty acid binding protein 4 is associated with atherogenic dyslipidemia in diabetes.

The aim of this study was to evaluate the impact of adipocyte fatty acid binding protein 4 (FABP4) on the lipid profile in type 2 diabetic subjects. Plasma levels of FABP4 and adiponectin and an extensive lipid profile were analyzed in 169 type 2 diabetic subjects and 105 controls. Type 2 diabetic subjects were categorized according the presence of atherogenic dyslipidemia. Univariate statistical analyses, partial correlation tests, and binary logistic regression models were applied. In type 2 diabetic subjects, FABP4 was positively correlated with plasma triglycerides (P = 0.007), apolipoprotein C-III (apoC-III) (P = 0.009), and all the components of triglyceride-rich lipoproteins, including VLDL triglycerides (P = 0.002), VLDL-cholesterol (P = 0.001), and VLDL apoB (P = 0.001). FABP4 was inversely correlated with apoA-I (P = 0.038), HDL-cholesterol (P = 0.002), and HDL apoA-I (P = 0.010) in type 2 diabetic subjects. These correlations are not significantly affected by age, gender, body mass index, adiponectin, insulin, or any pharmacological treatment. The associations are even stronger when the FABP4/adiponectin ratio is considered. None of these associations were observed in controls. High FABP4 and low adiponectin levels are independent predictors of atherogenic dyslipidemia. In conclusion, FABP4 plasma concentrations hold strong potential for development as a clinical biomarker for atherogenic dyslipidemia, independent of obesity and insulin resistance, in type 2 diabetic subjects.

Oxidized to non-oxidized lipoprotein ratios are associated with arteriosclerosis and the metabolic syndrome in diabetic patients.

BACKGROUND AND AIM: Type 2 diabetic patients have a greater prevalence of the metabolic syndrome, oxidative stress and accelerated atherosclerosis, compared to non-diabetics. We examined the association between biomarkers of lipid peroxidation and the presence of atherosclerosis and the metabolic syndrome in diabetic patients. METHODS AND RESULTS: We studied oxidized LDL (OxLDL), OxLDL/LDL, OxLDL/HDL, lipoperoxides, autoantibodies against OxLDL (OxLDL-Ab), diene formation of LDL (lag phase), vitamin E, vitamin E/cholesterol and PON1 polymorphisms (-108C>T, 55T>A, and 192A>G) in 166 non-smoking type 2 diabetic patients, 119 fulfilling the criteria for the metabolic syndrome, 73 with atherosclerosis and 93 without atherosclerosis. Patients with macrovascular disease had higher values of OxLDL/LDL (11%; P=0.016), OxLDL/HDL (18%; P=0.024) and OxLDL-Ab (12%; P=0.046). OxLDL/LDL and OxLDL/HDL were correlated with the number of components of the metabolic syndrome (P<0.001). PON1 polymorphisms were not associated to LDL oxidation markers, only PON1 (-108TT) was weakly associated with higher OxLDL-Ab concentrations (22%; P=0.040) in patients with atherosclerosis. CONCLUSION: OxLDL/LDL, OxLDL/HDL and OxLDL-Ab are the most useful clinical parameters of lipoprotein oxidation for discriminating the presence of macrovascular disease in diabetic patients. The presence of the metabolic syndrome in these patients is also associated with an increase in the oxidized lipoprotein ratios.

Plasma fatty acid-binding protein 4 increases with renal dysfunction in type 2 diabetic patients without microalbuminuria.

BACKGROUND: Fatty acid-binding protein 4 (FABP4) has been linked to metabolic syndrome development, diabetes, and arteriosclerosis, but the role of FABP4 in target organ damage has not been assessed. We evaluated whether plasma FABP4 is associated with renal dysfunction in type 2 diabetic patients. METHODS: In 263 individuals (161 type 2 diabetic patients and 102 healthy nondiabetic controls), we analyzed the correlation between FABP4 and creatinine or glomerular filtration index (MDRD-GFR) regarding the presence or absence of microalbuminuria. Patients with severe chronic kidney disease (MDRD-GFR <30 mL/min/1.73 m(2)) or albuminuria were not included. RESULTS: FABP4 concentrations were higher in diabetic patients with MDRD-GFR <60 mL/min/1.73 m(2) (P <0.001). We observed a significant, direct correlation between FABP4 and creatinine (r = 0.446, P <0.001) and an inverse correlation between FABP4 and MDRD-GFR (r = -0.511, P <0.001) in type 2 diabetic patients, but not in nondiabetic individuals. These correlations were sustained when only those patients without microalbuminuria were analyzed (r = 0.414, P <0.001 and r = -0.510, P <0.001, respectively). Type 2 diabetic patients with FABP4 in the highest tertile compared with those in the lower tertiles had increased adjusted odds ratios for moderate renal dysfunction [7.5 (95%CI 1.8-30.7), P = 0.005 and 15.3 (3.1-76.4), P = 0.001; respectively], independent of microalbuminuria. CONCLUSIONS: High FABP4 plasma concentrations are associated with high plasma creatinine and low MDRD-GFR in patients with type 2 diabetes even in the absence of microalbuminuria or clinically relevant alterations of creatinine and MDRD-GFR values. FABP4 concentrations should be taken into consideration as an early marker of kidney damage in patients with type 2 diabetes.