Phase Angle and Handgrip Strength Are Sensitive Early Markers of Energy Intake in Hypophagic,Non-Surgical Patients at Nutritional Risk,with Contraindications to Enteral Nutrition

The assessment of nutritional intakes during hospitalization is crucial, as it is known that nutritional status tends to worsen during the hospital stay, and this can lead to the negative consequences of malnutrition. International guidelines recommend the use of parenteral nutrition (PN) in hypophagic, non-surgical patients at nutritional risk, with contraindications to enteral nutrition. However, to date, there are no published data regarding either energy intake or objective measurements associated with it in this patient population. The aim of the present exploratory methodological study was to evaluate whether phase angle (PhA) and handgrip strength normalized for skeletal muscle mass (HG/SMM) are sensitive early markers of energy intake in hypophagic, non-surgical patients at nutritional risk, with contraindications to enteral nutrition. We evaluated 30 eligible patients, who were treated with personalized dietary modifications and supplemental PN for at least one week during hospitalization. In a liner regression model adjusted for age, gender, basal protein intake and the basal value of each variable, a trend toward improvement of PhA and preservation of HG/SMM was observed in patients satisfying the estimated calorie requirements (N = 20), while a significant deterioration of these parameters occurred in those who were not able to reach the target (N = 10). The mean adjusted difference and 95% CI were +1.4° (0.5–2.3) (p = 0.005) for PhA and +0.23 (0.20–0.43) (p = 0.033) for HG/SMM. A significant correlation between PhA and HG/SMM variations was also observed (r = 0.56 (95% CI, 0.23–0.77); p = 0.0023). PhA and HG/SMM were able to distinguish between hypophagic, non-surgical patients at nutritional risk who satisfied their estimated caloric requirements and those who did not after a one-week personalized nutritional support. Clinical studies are warranted, in order to verify these preliminary observations and to validate the role of PhA variations as early markers of anabolic/catabolic fluctuations.     

Mast cell recruitment after subcutaneous injection of RANTES in the sole of the rat paw

Granulocyte colony-stimulating factor (G-CSF)-induced alteration of phosphoprotein during differentiation of HL-60 cells was studied. From the two-dimensional gel electrophoresis analysis of phosphoproteins, a 45 kD phosphoprotein in the cytosolic fraction of DMSO-pretreated HL-60 cells was rapidly dephosphorylated by the addition of G-CSF. This 45 kD phosphoprotein migrated into four or five spots between 4.5 and 5.5 pI. The dephosphorylation of 45 kD protein was observed within at least 10 min and reached a maximum at 60 min. Phosphoamino acid analysis showed that only serine residue of 45 kD phosphoprotein was phosphorylated, suggesting that G-CSF induced an activation of serine phosphatase. Furthermore, Staurosporine and calphostin C inhibited the phosphorylation of 45 kD protein, suggesting that protein kinase C or its downstream kinase(s) is involved in the phosphorylation of 45 kD protein. These results indicate that G-CSF causes dephosphorylation of a 45 kD cytosolic phosphoprotein which may play a role in signal transduction of G-CSF.     

Arrhythmia recurrence in patients with an old myocardial infarct treated by implantable defibrillator: an analysis according to the initial clinical presentation

INTRODUCTION AND OBJECTIVES: The importance of the clinical presentation in the frequency and type of recurrences of ventricular arrhythmias in patients that received an automatic implantable defibrillator is not well known. The purpose of this study was to analyze the frequency and type of recurrences in patients with an old myocardial infarction that received an automatic implantable defibrillator with electrogram recording. METHODS AND RESULTS: We analyzed 100 patients classified in 3 groups according to their clinical presentation: Sustained Monomorphic Ventricular Tachycardia (VT Group n = 65), Cardiac Arrest (CA Group = 19), and Syncope (Syncope Group n = 16). There were no significant differences in the clinical variables among the different groups, nor in the inducibility of arrhythmia at the electrophysiologic study. In a follow-up 27 +/- 14 months, 54% of patients presented at last one episode of sustained ventricular arrhythmia. All recurrences except one were as sustained monomorphic ventricular tachycardia (776 episodes). 81% of episodes of sustained monomorphic ventricular tachycardia (630) were treated with antitachycardia pacing with an effectiveness of 89%. There were no differences in the probability of arrhythmic recurrence among groups but death probability was higher in the ventricular fibrillation group at 36 follow-up months (38% vs 7% and 12% in the sustained monomorphic ventricular tachycardia and syncope groups respectively, p = 0.0113). CONCLUSIONS: In the patients with an old myocardial infarction and malignant ventricular arrhythmias, most of recurrences are due to sustained monomorphic ventricular tachycardia independently of the clinical presentation. The antitachycardia pacing is not only effective in patients with documented sustained monomorphic ventricular tachycardia but also in those that are presented as cardiac arrest or syncope.     

Association of high-risk coronary atherosclerosis at CCTA with clinical and circulating biomarkers: Insight from CAPIRE study

BackgroundHigh-risk coronary atherosclerosis features evaluated coronary CT angiography (CCTA) were suggested to have a prognostic role. The present study aimed to evaluate the association of circulating biomarkers with high-risk plaque features assessed by CCTA.MethodsA consecutive cohort of subjects who underwent CCTA because of suspected CAD was screened for inclusion in the CAPIRE study. Based on risk factors (RF) burden patients were defined as having a low clinical risk (0–1 RF with the exclusion of patients with diabetes mellitus as single RF) or an high clinical risk (≥3 RFs). In all patients, measurement of inflammatory biomarkers and CCTA analysis focused on high-risk plaque features were performed. Univariate and multivariate logistic regression analysis were used to evaluate the relationship between clinical and biological variables with CCTA advanced plaque features.Results528 patients were enrolled in CAPIRE study. Older age and male sex appeared to be predictors of qualitative high-risk plaque features and associated with the presence of elevated total, non-calcified and low-attenuation plaque volume. Among circulating biomarkers only hs-CRP was found to be associated with qualitative high-risk plaque features (OR 2.02, p = 0.004 and 2.02, p = 0.012 for LAP and RI > 1.1, respectively) with borderline association with LAP-Vol (OR 1.52, p = 0.076); HbA1c and PTX-3 resulted to be significantly associated with quantitative high-risk plaque features (OR 1.71, p = 0.003 and 1.04, p = 0.002 for LAP-Vol, respectively).ConclusionsOur results support the association between inflammatory biomarkers (hs-CRP, PTX- 3), HbA1c and high-risk atherosclerotic features detected by CCTA. Male sex and older age are significant predictors of high-risk atherosclerosis.     

Family climate in children living with parents who harmfully consume alcohol

The family climate has notable impact on cognitive, emotional, behavioural, social and physical development of children and adolescents and can be influenced by parents' health status. The present study aimed at evaluating whether living with a parent with alcohol use disorder negatively influences the perceived emotional family climate, parental attitudes and internal representations of family relationships. Forty-five children living with a parent with alcohol use disorder and 45 controls, matched for sex and age, completed the Level of Expressed Emotion Scale and the Family Attitudes Questionnaire. Their significant parent completed the Parental Attitudes Scale. The results suggested that living with a parent with an alcohol use disorder increased the risk of having perceived higher levels of emotional response, attitude towards illness and expectations from their parents; it also increased the probability of being exposed to lower parental pleasure and of having represented worse family relationships. Emotion regulation interventions might be useful to protect children living with a parent with alcohol use disorder from a potential chaotic and unpredictable family environment.     

Early predictors of mortality in refractory cardiogenic shock following acute coronary syndrome treated with extracorporeal membrane oxygenator

We aimed to analyze the outcome and identify predictors of hospital mortality in patients with refractory cardiac arrest (CA) complicating acute coronary syndromes (ACS) and requiring veno-arterial extracorporeal membrane oxygenation (VA-ECMO) treatment. Between Jan-2005 and Dec-2019, 51 patients underwent urgent VA-ECMO implantation for CA in ACS. Patients were divided in two groups: “in-hospital” cardiac arrest (IHCA) and “out-of-hospital” cardiac arrest (OHCA). Prospectively collected data were retrospectively analyzed and compared between groups. Predictors for hospital mortality were investigated. IHCA and OHCA patients were 32 (62.7%) and 19 (37.3%), respectively. The groups differed for: male gender (72% vs 95%; p?=?0.070), lactate peak level (8.5?±?4.3vs10.7?±?2.9; p?=?0.023), total elapsed time from CA to VA-ECMO implantation in both groups (p?<?0.001) and elapsed time from CA (IHCA group) or hospital arrival (OHCA group) to VA-ECMO implantation (38 min vs 80 min; p?=?0.001). At logistic regression analysis, concomitant lactate level greater than 8.0 mmol/L and elapsed time from CA to VA-ECMO?≥?30 min were predictors of increased mortality (OR 3.9; 95% CI 1.19–12.79; p?=?0.025) for the entire population. In-hospital mortality was 60.8% (31/51 patients): 68.4% in OHCA group and 56.2% in IHCA group. No risk factors related to 30-day mortality resulted significant at univariable analysis. When rapidly instituted, VA-ECMO improves survival in patients with refractory cardiac arrest allowing coronary syndrome treatment. The association of an elapsed time from CA to VA-ECMO implantation longer than 30 min and a preoperative lactate peak level over 8.0 mmol/L predict a poor outcome, independently from being IHCA or OHCA.

     

Diffusion Tensor Imaging Mapping of Brain White Matter Pathology in Mitochondrial Optic Neuropathies

BACKGROUND AND PURPOSE:Brain white matter is frequently affected in mitochondrial diseases; optic atrophy gene 1-autosomal dominant optic atrophy and Leber hereditary optic neuropathy are the most frequent mitochondrial monosymptomatic optic neuropathies. In this observational study, brain white matter microstructure was characterized by DTI in patients with optic atrophy gene 1-autosomal dominant optic atrophy and Leber hereditary optic neuropathy, in relation to clinical and genetic features.MATERIALS AND METHODS:Nineteen patients with optic atrophy gene 1-autosomal dominant optic atrophy and 17 with Leber hereditary optic neuropathy older than 18 years of age, all genetically diagnosed, and 19 healthy volunteers underwent DTI by using a 1.5T MR imaging scanner and neurologic and ophthalmologic assessments. Brain white matter DTI metrics were calculated for all participants, and, in patients, their correlations with genetics and clinical findings were calculated.RESULTS:Compared with controls, patients with optic atrophy gene 1-autosomal dominant optic atrophy had an increased mean diffusivity in 29.2% of voxels analyzed within major white matter tracts distributed throughout the brain, while fractional anisotropy was reduced in 30.3% of voxels. For patients with Leber hereditary optic neuropathy, the proportion of altered voxels was only 0.5% and 5.5%, respectively, of which half was found within the optic radiation and 3.5%, in the smaller acoustic radiation. In almost all regions, fractional anisotropy diminished with age in patients with optic atrophy gene 1-autosomal dominant optic atrophy and correlated with average retinal nerve fiber layer thickness in several areas. Mean diffusivity increased in those with a missense mutation. Patients with Leber hereditary optic neuropathy taking idebenone had slightly milder changes.CONCLUSIONS:Patients with Leber hereditary optic neuropathy had preferential involvement of the optic and acoustic radiations, consistent with trans-synaptic degeneration, whereas patients with optic atrophy gene 1-autosomal dominant optic atrophy presented with widespread involvement suggestive of a multisystemic, possibly a congenital/developmental, disorder. White matter changes in Leber hereditary optic neuropathy and optic atrophy gene 1-autosomal dominant optic atrophy may be exploitable as biomarkers.

Mutations in optic atrophy gene 1 are the main cause of autosomal dominant optic atrophy (DOA) (Online Mendelian Inheritance in Man 605290).^1,2 DOA is characterized clinically by insidiously progressive visual loss in childhood, centrocecal scotoma, dyschromatopsia, and temporal or diffuse pallor of the optic discs, due to selective loss of retinal ganglion cells leading to atrophy of the optic nerve.^1,2 Similarly, Leber hereditary optic neuropathy (LHON) (Online Mendelian Inheritance in Man 535000) is characterized by subacute loss of central vision, dyschromatopsia, and optic atrophy due to maternally inherited point mutations in mitochondrial DNA that affect respiratory complex I.^1,2DOA and LHON represent the so-called nonsyndromic mitochondrial optic neuropathies, characterized by optic nerve atrophy as the only or at least prevalent pathologic feature with an early and preferential involvement of the small fibers in the papillomacular bundle.^3,4 Recent MR imaging studies by using voxel-based morphometry,⁵ DWI,⁶ and DTI⁷ have also indicated abnormalities of the optic radiation in patients with LHON, confirmed by postmortem investigation,⁶ suggesting a trans-synaptic degeneration. A similar secondary involvement of the retrogeniculate visual pathway could also be hypothesized in patients with DOA. Furthermore, given that the optic atrophy gene 1 (OPA1) is highly expressed in the retina but also in the brain^1,2,8 and that a subgroup of patients with specific OPA1 mutations have a multisystem neurologic disorder,⁹ it is reasonable to also hypothesize a subclinical extravisual brain involvement in patients with OPA1-DOA.The aim of the present study was to investigate the brain white matter of patients with OPA1-DOA compared with those with LHON and healthy controls, by using a voxelwise analysis of DTI, which can disclose abnormal water diffusivity in brain areas where atrophy and/or gliosis occur,¹⁰ to look for subtle structural alterations.