Post-acute cardiac complications following SARS-CoV-2 infection in partial lipodystrophy due to LMNA gene p.R349W mutation.

PURPOSE: SARS-CoV-2 infection may cause varying degrees of cardiac injury and the presence of underlying cardiovascular morbidities contributes to the frequency and severity of occurrence of this complication. Lipodystrophy syndromes are frequently characterized by severe metabolic derangements that represent relevant cardiovascular risk factors. Besides causing lipodystrophy, mutations in the lamin A/C (LMNA) gene can lead to a wide spectrum of tissue-specific disorders including cardiac involvement. METHODS AND RESULTS: We herein examine the case of two patients affected by atypical progeroid syndrome and partial lipodystrophy due to a heterozygous missense LMNA mutation c.1045 C > T (p.R349W) who presented initially with mild COVID-19 and developed severe cardiovascular complications within few weeks of SARS-CoV-2 infection. Before being infected with SARS-CoV-2, our patients had cardiovascular morbidities (mild mitral regurgitation in one patient, ischemic heart disease with bifascicular block in the other patient) in adjunct to cardiovascular risk factors, but the SARS-CoV-2 infection contributed to quickly and significantly decompensate their balance. CONCLUSION: These findings warn that patients affected by LMNA p.R349W mutation and likely other LMNA mutations associated with cardiovascular morbidity should be considered at extremely elevated risk of post-acute cardiological manifestations and should therefore undergo a vigilant follow-up after SARS-CoV-2 infection. Both patients developed COVID-19 before the specific vaccination was available to them and this unfortunate situation should remark the importance of vaccination coverage against SARS-CoV-2 infection for all patients affected by lipodystrophy, especially those with underlying comorbidities.

T2-weighted, apparent diffusion coefficient and 18F-FDG PET histogram analysis of rectal cancer after preoperative chemoradiotherapy.

BACKGROUND: The aim of our study was to investigate the correlation among T2-weighted (T2w) images, apparent diffusion coefficient (ADC) maps, 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) images, histogram analysis and the pathological response in locally advanced rectal cancer (LARC) after preoperative chemoradiotherapy (pCRT). METHODS: Patients with LARC were prospectively enrolled between February 2015 and August 2018 and underwent PET/magnetic resonance imaging (MRI). MRI included T2w and diffusion-weighted imaging (DWI)-sequences. ADC maps and PET images were matched to the T2w images. Voxel-based standardized uptake values (SUVs,) ADC and T2w-signal-intensity values were collected from the volumes of interest (VOIs) and mean, skewness and kurtosis were calculated. Spearman's correlation coefficient was applied to evaluate the correlation among the variables and tumor regression grade (TRG), T stage, N stage and fibrosis. RESULTS: Twenty-two patients with biopsy-proven LARC in the low or mid rectum were enrolled [17 males, mean age was 69 years (range 49-85 years)]. Seven patients experienced complete regression (TRG1). A significant positive correlation was found between SUV mean values (ρ = 0.480; p = 0.037) and TRG. No other significant correlations were found. CONCLUSIONS: Histogram analysis of SUV values is a predictor of TRG in LARC.

Measurement of myocardial amyloid deposition in systemic amyloidosis: insights from cardiovascular magnetic resonance imaging.

BACKGROUND: Cardiac involvement in systemic amyloidosis is caused by the extracellular deposition of misfolded proteins, mainly immunoglobulin light chains (AL) or transthyretin (ATTR), and may be detected by cardiovascular magnetic resonance (CMR). The aim of this study was to measure myocardial extracellular volume (ECV) in amyloid patients with a novel T1 mapping CMR technique and to determine the correlation between ECV and disease severity. METHODS: Thirty-six patients with biopsy-proven systemic amyloidosis (mean age 70 ± 9 years, 31 men, 30 with AL and six with ATTR amyloidosis) and seven patients with possible amyloidosis (mean age 64 ± 10 years, six men) underwent comprehensive clinical and CMR assessment, with ECV estimation from pre- and postcontrast T1 mapping. Thirty healthy subjects (mean age 39 ± 17 years, 21 men) served as the control group. RESULTS: Amyloid patients presented with left ventricular (LV) concentric hypertrophy with impaired biventricular systolic function. Cardiac ECV was higher in amyloid patients (definite amyloidosis, 0.43 ± 0.12; possible amyloidosis, 0.34 ± 0.11) than in control subjects (0.26 ± 0.04, P < 0.05); even in amyloid patients without late gadolinium enhancement (0.35 ± 0.10), ECV was significantly higher than in the control group (P < 0.01). A cut-off value of myocardial ECV >0.316, corresponding to the 95th percentile in normal subjects, showed a sensitivity of 79% and specificity of 97% for discriminating amyloid patients from control subjects (area under the curve of 0.884). Myocardial ECV was significantly correlated with LV ejection fraction (R(2)  = 0.16), LV mean wall thickness (R(2)  = 0.41), LV diastolic function (R(2)  = 0.21), right ventricular ejection fraction (R(2)  = 0.13), N-terminal fragment of the pro-brain natriuretic peptides (R(2)  = 0.23) and cardiac troponin (R(2)  = 0.33). CONCLUSION: Myocardial ECV was increased in amyloid patients and correlated with disease severity. Thus, measurement of myocardial ECV represents a potential noninvasive index of amyloid burden for use in early diagnosis and disease monitoring.

Aldosterone receptor antagonism and heart failure: insights from an outpatient clinic.

OBJECTIVE: In randomized clinical trials, aldosterone antagonists have been shown to reduce mortality and morbidity in heart failure (HF). The aim of the present study was to examine the risk-benefit profile of aldosterone antagonists in routine clinical practice. METHODS: A retrospective analysis, extending over a 1-year period, of the clinical, instrumental and laboratory data of 264 HF outpatients was performed. All patients were on a beta-blocker and an ACE-inhibitor (or angiotensin-II receptor-blocker) and 151 were taking an aldosterone antagonist. RESULTS: At baseline, subjects treated with aldosterone antagonists had a higher NYHA class, a larger left-ventricular end-diastolic volume, a worse ejection fraction and a higher systolic pulmonary arterial pressure (sPAP). During follow-up, a greater reduction in sPAP and a tendency towards improved systolic and diastolic function were observed in subjects treated with aldosterone antagonists. Moreover, clinical and laboratory parameters did not deteriorate in patients taking aldosterone antagonists. Mortality rates were similar in the two groups (8.6% vs. 8.8%, P = NS). CONCLUSIONS: The use of aldosterone antagonists in HF is associated with an improvement in cardiac function and is well tolerated. In the present study, patients administered these agents had a comparable clinical outcome to that of the control group, despite important differences in baseline risk.

Prognostic value of pulmonary blood volume by first-pass contrast-enhanced CMR in heart failure outpatients: the PROVE-HF study.

Aims: Pulmonary blood volume (PBV) is a novel clinical application of cardiovascular magnetic resonance (CMR) imaging for the quantitative grading of haemodynamic congestion. In this study, we aimed to assess the prognostic value of PBV in a cohort of outpatients with chronic heart failure (HF). Methods and results: One hundred and twelve consecutive patients (91 men, 67 ± 12 years) and 53 age- and sex-matched healthy controls underwent echocardiography and contrast-enhanced CMR. PBV was calculated as the product of stroke volume and the number of cardiac cycles for an intravenous bolus of gadolinium contrast to pass through the pulmonary circulation determined by first-pass perfusion imaging. Compared with healthy controls, HF outpatients showed significantly higher PBV index (PBVI, 308 ± 92 vs. 373 ± 175, mL/m2, P = 0.012) and pulmonary transit time (6.8 ± 1.8 vs. 9.5 ± 4 s, P ≤0.001). During a median follow-up of 26 ± 17 months, 27 patients (24%) reached the composite end point of cardiovascular death, HF hospitalization, or sustained ventricular arrhythmias/appropriate implantable cardioverter-defibrillator intervention. Using a cut-off point of PBVI >492 mL/m2, corresponding to two standard deviations above the mean of healthy controls, event-free survival was significantly lower in patients with higher PBVI (P < 0.001). At multivariable-adjusted Cox regression analysis, PBVI was an independent predictor of the composite cardiovascular end point (per 10% increase hazard ratio 1.31, 95% confidence interval: 1.02-1.69, P = 0.03). Conclusions: PBVI is a novel application of perfusion CMR potentially useful to quantitatively determine haemodynamic congestion as a surrogate marker of left ventricular diastolic dysfunction. PBVI might prove to be helpful in stratifying the prognosis of asymptomatic or mildly symptomatic patients with left ventricular dysfunction.

Plasma phospholipid fatty acid composition and desaturase activity in women with gestational diabetes mellitus before and after delivery.

AIMS: Analyze plasma phospholipid fatty acids (PPFA) composition and desaturase activity in women with gestational diabetes (GDM) and in women with a normal glucose tolerance (NGT) before and after delivery, and to evaluate the possible relationship between desaturase activity and inflammatory parameters. METHODS: PPFA composition was analyzed by gas chromatography in 21 women with GDM and from 21 with NGT, during the third trimester of pregnancy and 6 months after delivery. We used fatty acid product-to-precursor ratios to estimate desaturase activity, and we also measured in all women interleukins six and ten, tumor necrosis factor alpha and C-reactive protein. RESULTS: No significant differences were observed between NGT and GDM women in terms of PPFA composition, both in pregnancy and after pregnancy. Estimated desaturase Δ9-18 activity was significantly higher, and estimated desaturase Δ5 activity was significantly lower during pregnancy in all women. We observed no correlations between inflammatory markers and desaturases activity, during or after pregnancy, in both groups. CONCLUSIONS: Our data suggest that GDM does not influence PPFA composition and desaturase activity during pregnancy. In addition, late pregnancy characterized by hyperinsulinemia appears to upregulate desaturase Δ9-18 activity in NGT and GDM women.

Quantitative criteria for the diagnosis of the congenital absence of pericardium by cardiac magnetic resonance.

BACKGROUND: Congenital absence of the left ventricular pericardium (LCAP) is a rare and poorly known cardiac malformation. Cardiac Magnetic Resonance (CMR) is generally used for the diagnosis of LCAP because of its high soft tissue contrast, multiplanarity and cine capability, but the diagnosis is usually made by only qualitative criteria. The aim of the present study was to establish quantitative criteria for the accurate diagnosis of LCAP on CMR. METHODS: We enrolled nine consecutive patients affected by LCAP (mean age 26±8years, 7 males), 13 healthy controls, 13 patients with dilated cardiomyopathy (DCM), 12 patients with hypertrophic cardiomyopathy (HCM) and 13 patients with right ventricular overload (RVO). All patients underwent CMR. The whole-heart volume was measured in end-systole and end-diastole. Whole-heart volume change (WHVC), was the systo-diastolic change of volume, expressed percentage of the end-diastolic volume. The angle of clockwise-rotation of the heart was also measured in the end-diastolic phase of the axial cine stack. RESULTS: The WHVC was significantly higher in LCAP (21.9±5.4), compared to healthy subjects (8.6±2.4, p<0.001), DCM (7.1±1.8, p<0.001), HCM (9.3±2.4, p<0.001) and RVO (8±2.4, p<0.001). The clockwise-rotation was significantly higher in LCAP (76±14°) than healthy controls (40±11°, p<0.001), DCM (41±5°, p<0.001), HCM (30±6°, p<0.001) and RVO (49±8°, p<0.001). WHVC had the highest sensitivity (100%) and specificity (100%) for diagnosing LCAP, using a threshold of >13%. CONCLUSIONS: In LCAP the systo-diastolic WHVC was significantly higher than controls, DCM, HCM and RVO patients and resulted an optimal quantitative criteria for the diagnosis of LCAP.

Fructosamine assay: an index of medium-term metabolic control parameters in diabetic disease.

The fructosamine levels and some metabolic control parameters were evaluated in 120 diabetics and in 60 controls. Higher levels of fructosamine were found in diabetics compared to normals (3.22 +/- 0.06 vs. 1.82 +/- 0.05 mmol/l; P less than 0.001). Positive correlations were found between fructosamine and metabolic control parameters in diabetic subjects. Moreover, non-insulin-dependent diabetic subjects had better correlations. The study of fructosamine variation in relation to plasma glucose change showed that fructosamine levels were modified after at least 2 weeks of good metabolic control. In conclusion, the fructosamine assay could be a useful method for medium-term metabolic control evaluation.

Synthesis of metal-oxide matrix with embedded nickel nanoparticles by a bottom-up chemical process.

Here we describe a new chemical route for obtaining highly dispersed nanometric Ni particles embedded in different matrices based on Al2O3, MgO, and TiO2 and in the heterogeneous matrices CeO2-doped Al2O3 and MgO-doped Al2O3. The synthesis method is based on a modification of the polymeric precursor method. The Ni nanoparticles (particles in the range of 1-40 nm) were obtained in a single process, without the use of an external reducing agent (hydrogen atmosphere).

Antinociceptive, anti-inflammatory and antioxidant activities of aqueous extract from Remirea maritima (Cyperaceae).

ETHNOPHARMACOLOGICAL RELEVANCE: Remirea maritima Aubl., popularly known as "capim-da-praia", is popularly employed in the treatment of diarrhea, kidney disease, fever, and for analgesic and anti-inflammatory purposes through the preparation of teas. Few studies have focused on the chemical composition and its biological properties. AIM OF THE STUDY: This work evaluated the antinocipetive, anti-inflammatory and antioxidant activities of the aqueous extract from Remirea maritima Aubl. as well as the isolation and identification of the chemical compounds. MATERIALS AND METHODS: Compounds were isolated from aqueous extract of Remirea maritima through preparative HPLC and the structures were identified by means of NMR and MS analysis. The tests for antinociceptive, anti-inflammatory, and antioxidant activities, along with motor coordination test (Rota rod), were performed over the aqueous extract. RESULTS: The phytochemical investigation of aqueous extract of Remirea maritima resulted in the isolation of three flavone glycosides. The structures of these compounds were determined by means of MS and 1D and 2D NMR data as vitexin-2″-O-ß-D-glucopyranoside, isovitexin-2″-O-ß-D-glucopyranoside, and luteolin-7-O-glucuronide. Acute pretreatment with aqueous extract (100, 200 or 400mg/kg, i.p.) caused a significant decrease (p<0.001) in the number of abdominal writhes. In the formalin test, higher doses significantly inhibited the late (inflammatory pain) phase of formalin-induced licking (p<0.05 or 0.001). In the hot plate test, there was no significant difference in nociceptive behavior, discarding the possible central effect of the aqueous extract. In the rota rod test, it was verified that the aqueous extract in all concentration evaluated does not alter the motor coordination of mice, such antinociceptive results were unlikely to be caused by motor abnormality. In the peritonitis test, induced by carrageenan, the treatment with aqueous extract produced a significant reduction in leukocyte migration in all concentration evaluated. Additionally, a significant reduction of lipoperoxidation (TBARS test) and in nitric oxide formation (.NO Scavenging assay) was observed in antioxidant activity assay. CONCLUSION: The biological and phytochemical investigations of the aqueous extract of Remirea maritima resulted in the identification of three flavone glycosides that have been described here for the first time in Remirea and effective analgesic activity in various pain models, probably mediated via the inhibition of peripheral mediators which could be related to its strong antioxidant effect observed in vitro.

The effects of psyllium on lipoproteins in type II diabetic patients.

We examined the effects of 2 months of psyllium treatment in optimizing metabolic control and lipoprotein profile, and its postprandial effects on lipids in type II diabetes. We recruited 40 type II diabetic patients who were on sulfonylureas and a controlled diet, sequentially assigning them to psyllium treatment (G1) or to a control group (G2) treated with dietary measures alone. After 2 months of treatment, body mass index, waist circumference, HbA1c (hemoglobin A1c) and fasting plasma glucose levels had significantly decreased in both groups. There were no postprandial differences in the lipoprotein profile between the two groups. Triglycerides were significantly lower in G1, but not in G2. Our study contributes toward elucidating the effects of psyllium on serum lipids, and suggests that psyllium treatment may help in reducing triglycerides (a known risk factor for cardiovascular disease) in type II diabetic patients.

Glycated serum proteins and glucose tolerance.

Glycated serum proteins (GSP), stable glycated hemoglobin (HbA1c) together with some metabolic parameters were evaluated in 120 subjects, 30 with normal glucose tolerance (NGT), 30 with impaired glucose tolerance (IGT), 30 with non-insulin-dependent diabetes mellitus (NIDD), and 30 with insulin-dependent diabetes mellitus (IDD). GSP levels were significantly higher in IGT, NIDD and IDD than in NGT. HbA1c levels were not significantly higher in IGT in comparison with NGT, but were significantly higher in NIDD and in IDD than in NGT and IGT. GSP correlated better than HbA1c with all metabolic parameters considered. Taking into account the distribution of the values, GSP showed a smaller overlap than HbA1c in all four groups studied. Moreover, only 9 subjects (30%) with IGT showed GSP levels above the normal range. Therefore, GSP assay is able to distinguish between normal and diabetic subjects but is unable by itself to discriminate subjects with normal from those with reduced glucose tolerance.