Roux-en-Y gastric bypass, but not sleeve gastrectomy, decreases plasma PCSK9 levels in morbidly obese patients.

AIM: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a master regulator of low-density lipoprotein cholesterol (LDL-C) metabolism, acting as an endogenous inhibitor of the LDL receptor. While it has been shown that bariatric surgery differentially affects plasma LDL-C levels, little is known of its effects on plasma PCSK9 concentrations. Therefore, the present study aimed to: (i) investigate the effect of sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) on plasma PCSK9 concentrations; and (ii) correlate baseline or postoperative plasma PCSK9 concentration variations with anthropometric and metabolic parameters. METHODS: Fasting plasma PCSK9 levels were measured by ELISA in morbidly obese patients before and 6 months after bariatric surgery. Patients were recruited from three prospective cohorts (in Nantes and Colombes in France, and Antwerp in Belgium). RESULTS: A total of 156 patients (34SG, 122RYGB) were included. Plasma PCSK9, LDL-C and non-high-density lipoprotein cholesterol (non-HDL-C) levels were significantly reduced after RYGB (-19.6%, -16.6% and -19.5%, respectively; P<0.0001), but not after SG. In all patients, postoperative PCSK9 change was positively correlated with fasting plasma glucose (FPG; r=0.22, P=0.007), HOMA-IR (r=0.24, P=0.005), total cholesterol (r=0.17, P=0.037) and non-HDL-C (r=0.17, P=0.038) variations, but not LDL-C. In contrast to what was observed for glucose parameters (FPG, HOMA-IR), correlation between PCSK9 and non-HDL-C changes after RYGB was independent of total weight loss. CONCLUSION: RYGB, but not SG, promotes a significant reduction in plasma PCSK9 levels, and such changes in circulating PCSK9 levels after RYGB appear to be more associated with glucose improvement than with lipid homoeostasis parameters.

High flow nasal cannula: Influence of gas type and flow rate on airway pressure and CO2 clearance in adult nasal airway replicas.

BACKGROUND: High flow nasal cannula therapy is a form of respiratory support which delivers high flow rates of heated, humidified gas to the nares via specialized cannula. Two primary mechanisms of action attributed to the therapy are the provision of positive airway pressure as well as clearance of CO2-rich exhaled gas from the upper airways. METHODS: Physiologically accurate nose-throat airway replicas were connected at the trachea to a lung simulator, where CO2 was supplied to mimic the CO2 content in exhaled gas. Cannula delivered either air, oxygen or heliox (80/20%volume helium/oxygen) to the replicas at flow rates ranging from 0 to 60 l/min. Five replicas and three cannulas were compared. Tracheal pressure and CO2 concentration were continuously measured. The lung simulator provided breaths with tidal volume of 500 ml and frequency of 18 breaths/min. Additional clearance measurements were conducted for tidal volume and breathing frequency of 750 ml and 27 breaths/min, respectively. FINDINGS: Cannula flow rate was the dominant factor governing CO2 concentration. Average CO2 concentration decreased with increasing cannula flow rate, but above 30 L/min this effect was less pronounced. Tracheal positive end-expiratory pressure increased with flow rate and was lower for heliox than for air or oxygen. A predictive correlation was developed and used to predict positive end-expiratory pressure for a given cannula size as a function of supplied flow rate and occlusion of the nares. INTERPRETATION: Compared with administration of air or oxygen, administration of heliox is expected to result in similar CO2 clearance from the upper airway, but markedly lower airway pressure.

Predicted airway obstruction distribution based on dynamical lung ventilation data: A coupled modeling-machine learning methodology.

In asthma and chronic obstructive pulmonary disease, some airways of the tracheobronchial tree can be constricted, from moderate narrowing up to closure. Those pathological patterns of obstructions affect the lung ventilation distribution. While some imaging techniques enable visualization and quantification of constrictions in proximal generations, no noninvasive technique exists to provide the airway morphology and obstruction distribution in distal areas. In this work, we propose a method that exploits lung ventilation measures to access positions of airway obstructions (restrictions and closures) in the tree. This identification approach combines a lung ventilation model, in which a 0D tree is strongly coupled to a 3D parenchyma description, along with a machine learning approach. On the basis of synthetic data generated with typical temporal and spatial resolutions as well as reconstruction errors, we obtain very encouraging results of the obstruction distribution, with a detection rate higher than 85%.

Circulating PCSK9 levels in acute coronary syndrome: Results from the PC-SCA-9 prospective study.

BACKGROUND: Serum proprotein convertase subtilisin/kexin type 9 (PCSK9) concentrations have been shown to be positively associated with LDL cholesterol (LDL-C), but the relationship between PCSK9 and coronary atherosclerosis lesions remains unclear. OBJECTIVE: This study aims to investigate the correlation between serum PCSK9 levels and coronary damage severity in patients hospitalized for acute coronary syndrome (ACS). METHODS: In this prospective proof-of-concept study, coronary lesions were assessed using SYNTAX scores. Serum PCSK9 concentrations were measured on admission (Day 0) for ACS by Elisa, and on every day of hospitalization. Spearman's correlations were used to determine the association between PCSK9 levels, SYNTAX score and metabolic parameters. RESULTS: A total of 174 patients (mean age: 59±14 years, 79% male) with ACS (on Day 0, 119 patients were not taking statins, but 55 were) were included. After initiation of high-intensity statin therapy, serum PCSK9 concentrations increased significantly, reaching maximum levels on Day 2 (+31% vs. Day 0), and remained stable up to Day 4 (P<0.001, by mixed model). Serum PCSK9 on Day 0 was associated with LDL-C (rho=0.226, P=0.017) and apolipoprotein B (rho=0.282, P=0.005) in the statin-naïve group only, and with triglycerides and non-HDL-C in all groups. More important, PCSK9 levels on Day 0 were positively associated with SYNTAX scores in the statin-naïve group (rho=0.239, P=0.009), but not in the statin-treated group (P=NS). This association was maintained after adjusting for LDL-C (P=0.014) and major CV risk factors (P=0.008). CONCLUSION: Serum PCSK9 levels are positively associated with severity of coronary artery lesions independently of LDL-C concentrations in patients hospitalized for ACS. This reinforces the potential importance of PCSK9 inhibition in the management of ACS.

Calculated ventilation and effort distribution as a measure of respiratory disease and Heliox effectiveness.

In spite of numerous clinical studies, there is no consensus on the benefit Heliox mixtures can bring to asthmatic patients in terms of work of breathing and ventilation distribution. In this article we use a 3D finite element mathematical model of the lung to study the impact of asthma on effort and ventilation distribution along with the effect of Heliox compared to air. Lung surface displacement fields extracted from computed tomography medical images are used to prescribe realistic boundary conditions to the model. Asthma is simulated by imposing bronchoconstrictions to some airways of the tracheo-bronchial tree based on statistical laws deduced from the literature. This study illuminates potential mechanisms for patient responsiveness to Heliox when affected by obstructive pulmonary diseases. Responsiveness appears to be function of the pathology severity, as well as its distal position in the tracheo-bronchial tree and geometrical position within the lung.

Using helium-oxygen to improve regional deposition of inhaled particles: mechanical principles.

BACKGROUND: Helium-oxygen has been used for decades as a respiratory therapy conjointly with aerosols. It has also been shown under some conditions to be a means to provide more peripheral, deeper, particle deposition for inhalation therapies. Furthermore, we can also consider deposition along parallel paths that are quite different, especially in a heterogeneous pathological lung. It is in this context that it is hypothesized that helium-oxygen can improve regional deposition, leading to more homogeneous deposition by increasing deposition in ventilation-deficient lung regions. METHODS: Analytical models of inertial impaction, sedimentation, and diffusion are examined to illustrate the importance of gas property values on deposition distribution through both fluid mechanics- and particle mechanics-based mechanisms. Also considered are in vitro results from a bench model for a heterogeneously obstructed lung. In vivo results from three-dimensional (3D) imaging techniques provide visual examples of changes in particle deposition patterns in asthmatics that are further analyzed using computational fluid dynamics (CFD). RESULTS AND CONCLUSIONS: Based on analytical modeling, it is shown that deeper particle deposition is expected when breathing helium-oxygen, as compared with breathing air. A bench model has shown that more homogeneous ventilation distribution is possible breathing helium-oxygen in the presence of heterogeneous obstructions representative of central airway obstructions. 3D imaging of asthmatics has confirmed that aerosol delivery with a helium-oxygen carrier gas results in deeper and more homogeneous deposition distributions. CFD results are consistent with the in vivo imaging and suggest that the mechanics of gas particle interaction are the source of the differences seen in deposition patterns. However, intersubject variability in response to breathing helium-oxygen is expected, and an example of a nonresponder is shown where regional deposition is not significantly changed.

Atomic oxygen recombination on quartz at high temperature: experiments and molecular dynamics simulation.

A joint experimental and theoretical approach has been developed to study oxygen atom recombination on a beta-quartz surface. The experimental MESOX setup has been applied for the direct measurement of the atomic oxygen recombination coefficient gamma at T(S) = 1000 K. The time evolution of the relative atomic oxygen concentration in the cell is described by the diffusion equation because the mean free path of the atoms is less than the characteristic dimension of the reactor. The recombination coefficient gamma is then calculated from the concentration profile obtained by visible spectroscopy. We get an experimental value of gamma = 0.008, which is a factor of about 3 less than the gamma value reported for O recombination over beta-cristobalite. The experimental results are discussed and compared with the semiclassical collision dynamics calculations performed on the same catalytic system aimed at determining the basic features of the surface catalytic activity. Agreement, both qualitative and quantitative, between the experimental and the theoretical recombination coefficients has been found that supports the Eley-Rideal recombination mechanism and gives more evidence of the impact that surface crystallographic variation has on catalytic activity. Also, several interesting aspects concerning the energetics and the mechanism of the surface processes involving the oxygen atoms are pointed out and discussed.