Left atrial remodeling in heart failure: the role of sphericity index (the SPHERICAT-HF study)

The International Journal of Cardiovascular Imaging - Left atrial sphericity index (LASI) is an echocardiographic index easily obtained; its use in patients with heart failure (HF) has never been...     

Hepatic resection for hepatocellular carcinoma in patients with Child–Pugh's A cirrhosis: is clinical evidence of portal hypertension a contraindication?

Background

According to international guidelines [European Association for the Study of the Liver (EASL) and the American Association for the Study of Liver Diseases (AASLD)], portal hypertension (PHTN) is considered a contraindication for liver resection for hepatocellular carcinoma (HCC), and patients should be referred for other treatments. However, this statement remains controversial. The aim of this study was to elucidate surgical outcomes of minor hepatectomies in patients with PHTN (defined by the presence of esophageal varices or a platelet count of <100 000 in association with splenomegaly) and well-compensated liver disease.

Methods

Between 1997 and 2012, a total of 223 cirrhotic patients [stage A according to the Barcelona Clinic Liver Cancer (BCLC) classification] were eligible for this analysis and were divided into two groups according to the presence (n = 63) or absence (n = 160) of PHTN. The demographic data were comparable in the two patient groups.

Results

Operative mortality was not different (only one patient died in the PHTN group). However, patients with PHTN had higher liver-related morbidity (29% versus 14%; P = 0.009), without differences in hospital stay (8.8 versus 9.8 days, respectively). The PHTN group showed a worse survival rate only if biochemical signs of liver decompensation existed. Multivariate analysis identified albumin levels as an independent predictive factor for survival.

Conclusions

PHTN should not be considered an absolute contraindication to a hepatectomy in cirrhotic patients. Patients with PHTN have short- and long-term results similar to patients with normal portal pressure. A limited hepatic resection for early-stage tumours is an option for Child–Pugh class A5 patients with PHTN.     

Is nonalcoholic steatohepatitis associated with a high-though-normal thyroid stimulating hormone level and lower cholesterol levels?

Hypothyroidism is associated with the risk of development of the metabolic syndrome (MS) and hypercholesterolemia. Direct evidence that hypothyroidism might be associated with advanced chronic liver disease via nonalcoholic steatohepatitis (NASH) is limited. We studied the relationship between thyroid hormones, thyroid stimulating hormone (TSH), cholesterol, and NASH. In consecutive euthyroid patients with biopsy-proven nonalcoholic fatty liver disease, TSH and thyroid hormone (FT3 and FT4) concentrations were compared in 25 patients with steatosis and 44 non-cirrhotic NASH patients featuring concurrent ballooning, lobular inflammation and steatosis. The MS was diagnosed according to ATP III criteria. A meta-analysis of previously published studies was performed to evaluate whether NASH, compared to simple steatosis, is associated with lower cholesterol levels. At univariate analysis, compared to those with steatosis, patients with NASH have a wider waist, elevated levels of BMI, ALT, AST, fasting insulin, HOMA-IR, ferritin, TSH and a lower serum cholesterol. At stepwise multivariable logistic regression analysis, the independent predictors of NASH are high HOMA and TSH and lower total cholesterol (Model 1); MS and high TSH (Model 2). At meta-analysis, serum total cholesterol levels are significantly lower in predominantly non-cirrhotic NASH than in simple steatosis. This study provides cross-sectional and meta-analytic evidence that, in euthyroid patients, high-though-normal TSH values are independently associated with NASH. Further work is needed to ascertain the role, if any, of lower cholesterol serum levels in assisting in the diagnosis of NASH.     

COPD and the metabolic syndrome: an intriguing association

Chronic Obstructive Pulmonary Disease (COPD) has been recently recognized as a condition involving more than the lungs. The presence of common factors in COPD and in other chronic extra-pulmonary diseases, as well as the co-existence of these conditions in the same adult individual, supports the hypothesis of a shared pathogenetic pathway. We will here review the interplay between coexisting COPD and the metabolic syndrome (MS), based on the most updated knowledge. We will discuss this clinical condition from the definition, to the pathophysiology and to the clinical implications. Basically, MS is more likely to be present in a COPD patients, and increased levels of circulatory pro-inflammatory proteins from both the lung and adipose tissue coincide in these patients. The relative impact of the coexisting COPD and MS may depend on several factors: the presence of physical inactivity and of systemic inflammation related to a smoking habit, sedentary lifestyle, airway inflammation and obstruction, adipose tissue and inflammatory marker activation. More studies will be required to elucidate the association between COPD and MS and to formulate individualized management approaches for this specific disease phenotype.     

Incidence of food anaphylaxis in Piemonte region (Italy): data from registry of Center for Severe Allergic Reactions

There are wide differences in estimated incidence and prevalence of anaphylaxis because of the absence, until recently, of a universal consensus on the definition of anaphylaxis and the different source of collected data. We aimed to estimate the incidence of food anaphylaxis based on the database of Piemonte Region (Italy) Reference Center for Severe Allergic Reactions. All cases of severe food allergic reactions reported in 2010 were studied. Clinical data associated to the reports were evaluated according to National Institute of Allergy and Infectious Disease and Food Allergy and Anaphylaxis Network diagnostic criteria of anaphylaxis. 75 % of the 778 cases were classified as food anaphylaxis (incidence of 13/100,000 person-years, ranging from 9.9 in adults to 29/100,000 person-years in children). Nuts were the most frequent foods causing anaphylaxis. Milk and eggs were responsible for anaphylaxis more often in children, while peach, vegetables and crustaceans were in adults. Cardiovascular symptoms were more frequent in adults. Gastrointestinal involvement was more frequent in children. A high prevalence of respiratory allergic comorbidities was observed. Food is an important cause of anaphylaxis, particularly in subjects with respiratory allergic comorbidities. Children and adults differ in triggers and clinical presentation of anaphylaxis.     

Transcriptional Network Analysis for the Regulation of Left Ventricular Hypertrophy and Microvascular Remodeling

Hypertension and cardiomyopathies share maladaptive changes of cardiac morphology, eventually leading to heart failure. These include left ventricular hypertrophy (LVH), myocardial fibrosis, and structural remodeling of coronary microcirculation, which is the morphologic hallmark of coronary microvascular dysfunction. To pinpoint the complex molecular mechanisms and pathways underlying LVH-associated cardiac remodeling independent of blood pressure effects, we employed gene network approaches to the rat heart. We used the Spontaneously Hypertensive Rat model showing many features of human hypertensive cardiomyopathy, for which we collected histological and histomorphometric data of the heart and coronary vasculature, and genome-wide cardiac gene expression. Here, we provide a large catalogue of gene co-expression networks in the heart that are significantly associated with quantitative variation in LVH, microvascular remodeling, and fibrosis-related traits. Many of these networks were significantly conserved to human idiopathic and/or ischemic cardiomyopathy patients, suggesting a potential role for these co-expressed genes in human heart disease.     

Preserving spontaneous breathing during mechanical ventilatory support: an old yet fascinating story

Facilitation of early spontaneous breathing activity is the most important measure to shorten weaning and avoid ventilator-induced lung injury and diaphragmatic injury in mechanically ventilated patients. However, the optimal degree of spontaneous muscle activity and ventilator support remains to be determined. Furthermore, effectiveness in relation to the pathophysiology of respiratory failure is unclear. In this regard the experimental study by Saddy and colleagues reveals interesting insights into the pathophysiology of ventilator-induced injury. More important, their results raise important questions that should be evaluated in further studies.In a recent issue of Critical Care, Saddy and colleagues [1] present an important article on the impact of partial ventilatory support on lung tissue inflammation and diaphragm dysfunction in mechanically ventilated rats. Their data reveal surprising results, in particular showing that the degree of diaphragmatic injury may depend not only on the amount of spontaneous respiratory activity preserved by applying specific settings of mechanical support, but also on the etiology of acute lung injury; that is, pulmonary versus extrapulmonary acute respiratory distress syndrome (ARDS). The present article reminds us that the question posed by Milic-Emili in a commentary published nearly 30 years ago as to whether weaning is an art or a science [2] is still valid, albeit a substantial body of available evidence now clearly explains several pathophysiological details of respiratory muscle failure in ICU patients [3,4].Of course, the relevance of animal models in translational research may always be questioned. This is particularly the case for rodent models, as the validity of the inflammatory response in these species as a model for human diseases has been challenged very recently [5]. Furthermore, respiratory mechanics widely differs between humans and rodents, as suggested, for example, by the different physiological respiratory rates that are relatively higher in the latter species and may, therefore, influence gas transport and exchange [6]. Nevertheless, the present study has the major merits of, firstly, having included diaphragm function and morphology (a relevant topic that still deserves fundamental research), and, secondly, having quantified diaphragmatic activity under different experimental conditions by means of the pressure–time product. This variable is calculated by tracing the esophageal pressure and is therefore particularly challenging to measure in small animals, but it is close to clinical reality as it is fairly well accessible in humans and may therefore support translating experimental results into clinical conditions [7].Taken together, the present data confirm, in principle, the well accepted notions that passive mechanical ventilation quickly damages the diaphragm [8] and promotes lung injury by atelectasis formation [9]. However, they also reveal that the impact of mechanical ventilation may be more difficult to explain, especially in extrapulmonary ARDS. In fact, under partial spontaneous breathing combined with low degree of ventilator support the authors observed an unexpected increase in diaphragmatic injury whereas atelectasis formation decreased comparable to pulmonary ARDS.These fairly surprising results may remind us that the impact of mechanical ventilation on lung tissue and the diaphragm is still far from being completely understood and merit intensive study in the future. In particular, some effort should be spent reproducing in the experimental conditions factors that potentially influence the response to mechanical ventilation in clinical settings. For example, most ICU patients are affected by co-existing diseases, especially cardiovascular diseases, diabetes, and chronic obstructive pulmonary disease, which, independent of the acute condition, also influence the muscular and diaphragmatic function and may even accentuate the impact of mechanical ventilation.Animal models mimicking conditions of co-existing chronic diseases should therefore be recommended to improve translation of experimental data into clinical situations and may be considered as the next step in studying the impact of mechanical ventilation and partial spontaneous breathing on diaphragm and lung tissue. Furthermore, most patients requiring mechanical ventilator support are affected by septic conditions leading to organ dysfunction and metabolic disorders. The utility of partial spontaneous breathing for maintaining diaphragmatic function has been well demonstrated in several experiments and nicely confirmed in the present study, but the effects of spontaneous breathing under septic conditions still need to be investigated. Finally, it is well known that not only restriction of passive movement but also muscular overload due to increased work of breathing may cause structural diaphragmatic damage that is characteristic for weaning failure. Thus, another important task of further studies is to find the perfect balance between diaphragmatic loading and unloading with regard to diaphragmatic and pulmonary function. In this context it will be interesting to see if modern spontaneous breathing modes may find their role in future concepts of lung and diaphragmatic protective ventilation strategies.In summary, the present article improves our knowledge in a fundamental topic of critical care and should encourage us to further study the influence of mechanical ventilatory support on lung tissue and diaphragm function, which is likely to be an important key to improving patient outcome in the ICU.     

Rule out of acute aortic dissection with plasma matrix metalloproteinase 8 in the emergency department

Introduction

Matrix metalloproteinases (MMPs) are involved in aortic pathophysiology. Preliminary studies have detected increased plasma levels of MMP8 and MMP9 in patients with acute aortic dissection (AAD). However, the performance of plasma MMP8 and MMP9 for the diagnosis of AAD in the emergency department is at present unknown.

Methods

The levels of MMP8 and MMP9 were measured by ELISA on plasma samples obtained from 126 consecutive patients evaluated in the emergency department for suspected AAD. All patients were subjected to urgent computed tomography (CT) scan for final diagnosis.

Results

In the study cohort (N = 126), AAD was diagnosed in 52 patients and ruled out in 74 patients. Median plasma MMP8 levels were 36.4 (interquartile range 24.8 to 69.3) ng/ml in patients with AAD and 13.2 (8.1 to 31.8) ng/ml in patients receiving an alternative final diagnosis (P <0.0001). Median plasma MMP9 levels were 169.2 (93.0 to 261.8) ng/ml in patients with AAD and 80.5 (41.8 to 140.6) ng/ml in patients receiving an alternative final diagnosis (P = 0.001). The area under the curve (AUC) on receiver-operating characteristic (ROC) analysis of MMP8 and MMP9 for the diagnosis of AAD was respectively 0.75 and 0.70, as compared to 0.87 of D-dimer. At the cutoff of 3.6 ng/ml, plasma MMP8 had a sensitivity of 100.0% (95% CI, 93.2% to 100.0%) and a specificity of 9.5% (95% CI, 3.9% to 18.5%) and ruled out AAD in 5.6% of patients. Combination of plasma MMP8 with D-dimer increased the AUC on ROC analysis to 0.89. Presence of MMP8 <11.0 ng/ml and D-dimer <1.0 or <2.0 µg/ml provided a negative predictive value of 100% and ruled out AAD in 13.6% and 21.4% of patients respectively.

Conclusions

Low levels of plasma MMP8 can rule out AAD in a minority of patients. Combination of plasma MMP8 and D-dimer at individually suboptimal cutoffs could safely rule out AAD in a substantial proportion of patients evaluated in the emergency department.     

Millisecond spatiotemporal dynamics of FRET biosensors by the pair correlation function and the phasor approach to FLIM

Here we present a fluctuation-based approach to biosensor Förster resonance energy transfer (FRET) detection that can measure the molecular flow and signaling activity of proteins in live cells. By simultaneous use of the phasor approach to fluorescence lifetime imaging microscopy (FLIM) and cross–pair correlation function (pCF) analysis along a line scanned in milliseconds, we detect the spatial localization of Rho GTPase activity (biosensor FRET signal) as well as the diffusive route adopted by this active population. In particular we find, for Rac1 and RhoA, distinct gradients of activation (FLIM-FRET) and a molecular flow pattern (pCF analysis) that explains the observed polarized GTPase activity. This multiplexed approach to biosensor FRET detection serves as a unique tool for dissection of the mechanism(s) by which key signaling proteins are spatially and temporally coordinated.