Objectives
It has been suggested that a low plasma high‐density lipoprotein cholesterol (HDL‐C) level contributes to the high cardiovascular disease risk of patients with chronic kidney disease ...(CKD), especially those undergoing haemodialysis (HD). The present study was conducted to gain further understanding of the mechanism(s) responsible for the low HDL‐C levels in patients with CKD and to separate the impact of HD from that of the underlying CKD.
Methods
Plasma lipids and lipoproteins, HDL subclasses and various cholesterol esterification parameters were measured in a total of 248 patients with CKD, 198 of whom were undergoing HD treatment and 40 healthy subjects.
Results
Chronic kidney disease was found to be associated with highly significant reductions in plasma HDL‐C, unesterified cholesterol, apolipoprotein (apo)A‐I, apoA‐II and LpA‐I:A‐II levels in both CKD cohorts (with and without HD treatment). The cholesterol esterification process was markedly impaired, as indicated by reductions in plasma lecithin:cholesterol acyltransferase (LCAT) concentration and activity and cholesterol esterification rate, and by an increase in the plasma preβ‐HDL content. HD treatment was associated with a further lowering of HDL levels and impaired plasma cholesterol esterification. The plasma HDL‐C level was highly significantly correlated with LCAT concentration (R = 0.438, P < 0.001), LCAT activity (R = 0.243, P < 0.001) and cholesterol esterification rate (R = 0.149, P = 0.031). Highly significant correlations were also found between plasma LCAT concentration and levels of apoA‐I (R = 0.432, P < 0.001), apoA‐II (R = 0.275, P < 0.001), LpA‐I (R = 0.326, P < 0.001) and LpA‐I:A‐II (R = 0.346, P < 0.001).
Conclusion
Acquired LCAT deficiency is a major cause of low plasma HDL levels in patients with CKD, thus LCAT is an attractive target for therapeutic intervention to reverse dyslipidaemia, and possibly lower the cardiovascular disease risk in these patients.
On‐pump cardiac surgery may trigger inflammation and accelerate platelet cyclooxygenase‐1 renewal, thereby modifying low‐dose aspirin pharmacodynamics. Thirty‐seven patients on standard aspirin 100 ...mg once‐daily were studied before surgery and randomized within 36 hours postsurgery to 100 mg once‐daily, 100 mg twice‐daily, or 200 mg once‐daily for 90 days. On day 7 postsurgery, immature and mature platelets, platelet mass, thrombopoietin, glycocalicin, leukocytes, C‐reactive protein, and interleukin‐6 significantly increased. Interleukin‐6 significantly correlated with immature platelets. At day 7, patients randomized to 100 mg once‐daily showed a significant increase in serum thromboxane (TX)B2 within the 24‐hour dosing interval and urinary TXA2 metabolite (TXM) excretion. Aspirin 100 mg twice‐daily lowered serum TXB2 and prevented postsurgery TXM increase (P < 0.01), without affecting prostacyclin metabolite excretion. After cardiac surgery, shortening the dosing interval, but not doubling the once‐daily dose, rescues the impaired antiplatelet effect of low‐dose aspirin and prevents platelet activation associated with acute inflammation and enhanced platelet turnover.
To investigate the prevalence of erectile dysfunction (ED) in patients with CAD according to clinical presentation, acute coronary syndrome (ACS) vs. chronic coronary syndrome (CCS), and extent of ...vessel involvement (single vs. multi-vessel disease).
285 patients with CAD divided into three age-matched groups: group 1 (G1, n=95), ACS and one-vessel disease (1-VD); group 2 (G2, n=95), ACS and 2,3-VD; group 3 (G3, n=95), chronic CS. Control group (C, n=95) was composed of patients with suspected CAD who were found to have entirely normal coronary arteries by angiography. Gensini's score used to assess extent of CAD. ED as any value <26 according to the International Index of Erectile Function (IIEF). ED prevalence was lower in G1 vs. G3 (22 vs. 65%, P<.0001) as a result of less atherosclerotic burden as expressed by Gensini's score 2 (0-6) vs. 40 (19-68), P=0.0001. Controls had ED rate values similar to G1 (24%). Group 2 ED rate, IIEF, and Gensini's scores were significantly different from G1 55%, P<0.0001; 24 (17-29), P=0.0001; 21 (12.5-32), P<0.0001 and similar to G3 suggesting that despite similar clinical presentation, ED in ACS differs according to the extent of CAD. No significant difference between groups was found in the number and type of conventional risk factors. Treatment with beta-blockers was more frequent in G3 vs. G1 and G2. In G3 patients who had ED, onset of sexual dysfunction occurred before CAD onset in 93%, with a mean time interval of 24 12-36 months. In logistic regression analysis, age (OR=1.1; 95% confidence interval (CI), 1.05-1.16; P=<0.0001), multi-vessel vs. single-vessel (OR=2.53; 95% CI, 1.43-4.51; P=0.0002), and CCS vs. ACS (OR=2.32; 95% CI, 1.22-4.41; P=0.01) were independent predictors of ED.
ED prevalence differs across subsets of patients with CAD and is related to coronary clinical presentation and extent of CAD. In patients with established CAD, ED comes before CAD in the majority by an average of 2 up to 3 years.
A longitudinal psycholinguistic study was conducted with 107 students from different Italian universities that produced daily photo-diary entries for two weeks, one at the beginning and the other at ...the end of the first Italian lockdown period, imposed in view of the rapid dissemination of COVID -19. The task was to take a daily photo accompanied by a short description (text). The texts accompanying the photos were analysed using Linguistic Inquiry and Word Count (LIWC) software to analyze linguistic markers representing psychological processes related to the experience of the pandemic and the lockdown, identifying potential changes in psycholinguistic variables useful for understanding the psychological impact of such harsh and extended restricted living conditions on Italian students. LIWC categories related to negation, anger, cognitive mechanisms, tentative discourse, past, and future increased statistically significantly between the two time points, while word count, prepositions, communication, leisure, and home decreased statistically significantly. While male participants used more articles at both time points, females used more words related to anxiety, social processes, past, and present at T1 and more related to insight at T2. Participants who lived with their partner showed higher scores on negative emotions, affect, positive feelings, anger, optimism, and certainty. Participants from southern Italy tended to describe their experiences from a collective and social perspective rather than an individual perspective. By identifying, discussing, and comparing these phenomena with the broader literature, a spotlight is shed for the first time on the psycholinguistic analysis of students at the national level who faced the first COVID -19 lockdown in Italy.
Background
Ischaemic stroke and coronary heart disease are important contributors to the global disease burden and share atherosclerosis as the main underlying cause. Recent evidence from a ...genome‐wide association study (GWAS) suggested that single nucleotide polymorphisms (SNP) near the MMP12 gene at chromosome 11q22.3 were associated with large‐vessel ischaemic stroke. Here, we evaluated and extended these results by examining the relationship between MMP12 and atherosclerosis in clinical and experimental studies.
Methods and Results
Plasma concentrations of MMP12 were measured at baseline in 3394 subjects with high‐risk for cardiovascular disease (CVD) using the Olink ProSeek CVD I array. The plasma MMP12 concentration showed association with incident cardiovascular and cerebrovascular events (130 and 67 events, respectively, over 36 months) and carotid intima‐media thickness progression (P = 3.6 × 10−5). A GWAS of plasma MMP12 concentrations revealed that SNPs rs499459, rs613084 and rs1892971 at chr11q22.3 were independently associated with plasma MMP12 (P < 5 × 10−8). The lead SNPs showed associations with mRNA levels of MMP12 and adjacent MMPs in atherosclerotic plaques. MMP12 transcriptomic and proteomic levels were strongly significantly increased in carotid plaques compared with control arterial tissue and in plaques from symptomatic versus asymptomatic patients. By combining immunohistochemistry and proximity ligation assay, we demonstrated that MMP12 localizes to CD68 + macrophages and interacts with elastin in plaques. MMP12 silencing in human THP‐1‐derived macrophages resulted in reduced macrophage migration.
Conclusions
Our study supports the notion that MMP12 is implicated in large‐artery atherosclerotic stroke, functionally by enhancing elastin degradation and macrophage invasion in plaques.
Background
Ventricular tachycardia (VT) is a life-threatening condition, which usually implies the need of an implantable cardioverter defibrillator in combination with antiarrhythmic drugs and ...catheter ablation. Stereotactic body radiotherapy (SBRT) represents a common form of therapy in oncology, which has emerged as a well-tolerated and promising alternative option for the treatment of refractory VT in patients with structural heart disease.
Objective
In the STRA-MI-VT trial, we will investigate as primary endpoints safety and efficacy of SBRT for the treatment of recurrent VT in patients not eligible for catheter ablation. Secondary aim will be to evaluate SBRT effects on global mortality, changes in heart function, and in the quality of life during follow-up.
Methods
This is a spontaneous, prospective, experimental (phase Ib/II), open-label study (NCT04066517); 15 patients with structural heart disease and intractable VT will be enrolled within a 2-year period. Advanced multimodal cardiac imaging preceding chest CT-simulation will serve to elaborate the treatment plan on different linear accelerators with target and organs-at-risk definition. SBRT will consist in a single radioablation session of 25 Gy. Follow-up will last up to 12 months.
Conclusions
We test the hypothesis that SBRT reduces the VT burden in a safe and effective way, leading to an improvement in quality of life and survival. If the results will be favorable, radioablation will turn into a potential alternative option for selected patients with an indication to VT ablation, based on the opportunity to treat ventricular arrhythmogenic substrates in a convenient and less-invasive manner.
Abstract Objectives To investigate the association between environmental tobacco smoke, plasma cotinine concentration, and respiratory cancer or death. Design Nested case-control study within the ...European prospective investigation into cancer and nutrition (EPIC). Participants 303 020 people from the EPIC cohort (total 500 000) who had never smoked or who had stopped smoking for at least 10 years, 123 479 of whom provided information on exposure to environmental tobacco smoke. Cases were people who developed respiratory cancers or died from respiratory conditions. Controls were matched for sex, age (plus or minus 5 years), smoking status, country of recruitment, and time elapsed since recruitment. Main outcome measures Newly diagnosed cancer of lung, pharynx, and larynx; deaths from chronic obstructive pulmonary disease or emphysema. Plasma cotinine concentration was measured in 1574 people. Results Over seven years of follow up, 97 people had newly diagnosed lung cancer, 20 had upper respiratory cancers (pharynx, larynx), and 14 died from chronic obstructive pulmonary disease or emphysema. In the whole cohort exposure to environmental tobacco smoke was associated with increased risks (hazard ratio 1.30, 95% confidence interval 0.87 to 1.95, for all respiratory diseases; 1.34, 0.85 to 2.13, for lung cancer alone). Higher results were found in the nested case-control study (odds ratio 1.70, 1.02 to 2.82, for respiratory diseases; 1.76, 0.96 to 3.23, for lung cancer alone). Odds ratios were consistently higher in former smokers than in those who had never smoked; the association was limited to exposure related to work. Cotinine concentration was clearly associated with self reported exposure (3.30, 2.07 to 5.23, for detectable/non-detectable cotinine), but it was not associated with the risk of respiratory diseases or lung cancer. Frequent exposure to environmental tobacco smoke during childhood was associated with lung cancer in adulthood (hazard ratio 3.63, 1.19 to 11.11, for daily exposure for many hours). Conclusions This large prospective study, in which the smoking status was supported by cotinine measurements, confirms that environmental tobacco smoke is a risk factor for lung cancer and other respiratory diseases, particularly in ex-smokers.
Abstract Background and purpose To compare the effects of regular cigarettes (RCs) and light cigarettes (LCs) on brachial artery flow-mediated dilation (FMD) and sublingual glyceryl ...trinitrate-induced dilation (GTN), markers of endothelial dependant and independent function, respectively. Methods 206 subjects (age 51.5 ± 12.8 yr, 122 men) had their smoking habits recorded and FMD and GTN measured by B-mode ultrasound. Cigarettes were categorized as RCs or LCs according to their content of tar, nicotine and CO. The chronic effect was assessed in current smokers of RCs ( n = 85) or LCs ( n = 53) and in never smokers (NS; n = 68). The acute effect was assessed in current smokers by measuring FMD before and 10-min after smoking a single regular ( n = 29) or light ( n = 51) cigarette. Results FMD was significantly lower in consumers of RCs (6.26%, 95% C.I. 5.58, 6.94) or LCs (5.59%, 95% C.I. 4.74, 6.45) compared to NS (8.68%, 95% C.I. 7.92, 9.44) (both P < 0.0001), but did not differ ( P > 0.05) when compared to each other. GTN was similar in the three groups. Analyses adjusted for clinical confounders and for markers involved in oxidative stress, arginine/nitric oxide pathway, and inflammation provided identical results. Smoking a single cigarette, either regular or light, reduced FMD (−0.88% and −1.17%, respectively, both P < 0.05), without significant difference between cigarette type. RCs and LCs produced analogous chronic and acute effects when FMD was calculated with respect to the last 60 s of the low-flow phase (FMD60s ). Conclusions LCs impair endothelial-dependant vasodilation as much as RCs. Thus, smoking LCs cannot be considered an alternative to the only safe choice of a complete and permanent smoking cessation.
To determine the clinical utility and limitations of guided prostate biopsy Power Doppler in patients with elevated serum PSA levels.
Prospective study. From April 2012 to May 2013, 111 men over 45 ...years of age with serum PSA level greater than 4.0ng/dl who underwent a transrectal prostate biopsy were included. The hypoechoic nodules in the peripheral region were considered positive on the gray scale. Subsequently, the study was conducted with the Power Doppler, where the vascularization of suspicious images was analyzed for sampling. In addition, samples were taken from the suspected areas when performing the digital rectal examination. We calculated sensitivity, specificity, positive predictive value and negative predictive value of the three tests (digital rectal examination, standard gray scale ultrasound and power Doppler).
Prostate cancer was diagnosed in 48 of the 111 patients (43%). Fifty-nine cases (53%) were defined as positive with the Power Doppler. Of these, 39 (66%) corresponded to a diagnosis of prostate adenocarcinoma. The Power Doppler was positive in 39 cases of the 48 patients diagnosed with cancer and the gray scale ultrasound was positive in 31 cases. Overall sensitivity of the power Doppler was 81%, specificity 68%, PPV 66% and NPV 82%, which was higher compared to the other methods (P<.05).
Currently, prostate biopsy using Power Doppler does not seem to identify prostate cancer with sufficient accuracy to omit the guided systematic biopsy gray scale, the combined use of these methods being preferable.
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