Efficacy of cardiometabolic drugs in reduction of epicardial adipose tissue: a systematic review and meta-analysis.

BACKGROUND: Epicardial adipose tissue (EAT) plays an important role in cardiometabolic risk. EAT is a modifiable risk factor and could be a potential therapeutic target for drugs that already show cardiovascular benefits. The aim of this study is to evaluate the effect of cardiometabolic drugs on EAT reduction. METHODS: A detailed search related to the effect on EAT reduction due to cardiometabolic drugs, such as glucagon-like peptide-1 receptor agonist (GLP-1 RA), sodium-glucose cotransporter-2 inhibitors (SGLT2-i), and statins was conducted according to PRISMA guidelines. Eighteen studies enrolling 1064 patients were included in the qualitative and quantitative analyses. RESULTS: All three analyzed drug classes, in particular GLP-1 RA, show a significant effect on EAT reduction (GLP-1 RA standardize mean difference (SMD) = - 1.005; p < 0.001; SGLT2-i SMD = - 0.552; p < 0.001, and statin SMD = - 0.195; p < 0.001). The sensitivity analysis showed that cardiometabolic drugs strongly benefit EAT thickness reduction, measured by ultrasound (overall SMD of - 0.663; 95%CI - 0.79, - 0.52; p < 0.001). Meta-regression analysis revealed younger age and higher BMI as significant effect modifiers of the association between cardiometabolic drugs and EAT reduction for both composite effect and effect on EAT thickness, (age Z: 3.99; p < 0.001 and Z: 1.97; p = 0.001, respectively; BMI Z: - 4.40; p < 0.001 and Z: - 2.85; p = 0.004, respectively). CONCLUSIONS: Cardiometabolic drugs show a significant beneficial effect on EAT reduction. GLP-1 RA was more effective than SGLT2-i, while statins had a rather mild effect. We believe that the most effective treatment with these drugs should target younger patients with high BMI.

Non-stenotic fibro-calcific aortic valve as a predictor of myocardial infarction recurrence.

BACKGROUND: Patients with acute myocardial infarction (AMI) are at increased risk of recurrent cardiovascular events. Non-stenotic aortic valve fibro-calcific remodeling (AVSc), reflecting systemic damage, may serve as a new marker of risk. OBJECTIVES: To stratify subgroups of AMI patients with specific probabilities of recurrent AMI and to evaluate the importance of AVSc in this setting. METHODS: Consecutive AMI patients (n = 2530) were admitted at Centro Cardiologico Monzino (2010-2019) and followed up for 5 years. Patients were divided into study (n = 1070) and test (n = 966) cohorts. Topological data analysis (TDA) was used to stratify patient subgroups, while Kaplan-Meier and Cox regressions analyses were used to evaluate the significance of baseline characteristics. RESULTS: TDA identified 11 subgroups of AMI patients with specific baseline characteristics. Two subgroups showed the highest rate of reinfarction after 5 years from the indexed AMI with a combined hazard ratio (HR) of 3.8 (95%CI: 2.7-5.4) compared to the other subgroups. This was confirmed in the test cohort (HR = 3.1; 95%CI: 2.2-4.3). These two subgroups were mostly men, with hypertension and dyslipidemia, who exhibit higher prevalence of AVSc, higher levels of high-sensitive c-reactive protein and creatinine. In the year-by-year analysis, AVSc, adjusted for all confounders, showed an independent association with the increased risk of reinfarction (odds ratio of ∼2 at all time-points), in both the study and the test cohorts (all p < 0.01). CONCLUSIONS: AVSc is a crucial variable for identifying AMI patients at high risk of recurrent AMI and its presence should be considered when assessing the management of AMI patients. The inclusion of AVSc in risk stratification models may improve the accuracy of predicting the likelihood of recurrent AMI, leading to more personalized treatment decisions.

We wanted to understand the factors that make some acute myocardial infarction (AMI) patients more likely to experience recurrent infarction after leaving the hospital. Specifically, we asked whether a heart valve condition called non-stenotic aortic valve fibro-calcific remodeling (AVSc) could be a crucial factor. Our study used advanced data analysis techniques, including topological data analysis (TDA), to explore this question. We unveil that AVSc is indeed a significant predictor of recurrent infarction in AMI patients. Our findings suggest that the presence of aortic valve remodeling should be taken into account when assessing the risk of recurrent AMI and managing these patients.

Anti-Inflammation and Anti-Oxidation: The Key to Unlocking the Cardiovascular Potential of SGLT2 Inhibitors and GLP1 Receptor Agonists.

Type 2 diabetes mellitus (T2DM) is a prevalent and complex metabolic disorder associated with various complications, including cardiovascular diseases. Sodium-glucose co-transporter 2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP1-RA) have emerged as novel therapeutic agents for T2DM, primarily aiming to reduce blood glucose levels. However, recent investigations have unveiled their multifaceted effects, extending beyond their glucose-lowering effect. SGLT2i operate by inhibiting the SGLT2 receptor in the kidneys, facilitating the excretion of glucose through urine, leading to reduced blood glucose levels, while GLP1-RA mimic the action of the GLP1 hormone, stimulating glucose-dependent insulin secretion from pancreatic islets. Both SGLT2i and GLP1-RA have shown remarkable benefits in reducing major cardiovascular events in patients with and without T2DM. This comprehensive review explores the expanding horizons of SGLT2i and GLP1-RA in improving cardiovascular health. It delves into the latest research, highlighting the effects of these drugs on heart physiology and metabolism. By elucidating their diverse mechanisms of action and emerging evidence, this review aims to recapitulate the potential of SGLT2i and GLP1-RA as therapeutic options for cardiovascular health beyond their traditional role in managing T2DM.

[Guiding the patient with end-stage renal disease in the choice of replacement therapy: role of the predialysis outpatient department]. / L'orientamento del paziente uremico nella scelta del trattamento sostitutivo: ruolo dell'ambulatorio di predialisi.

The predialysis outpatient department has three main objectives: ensuring patients' conscious and informed choice of dialysis treatment; clinical followup of patients with stage IV-V kidney disease; supporting patients and their families in their treatment choice. The aim of this work is to evaluate a) the effectiveness of the predialysis outpatient department in informing patients about the problems inherent in their disease; b) the differences in the choice of dialysis treatment between patients who benefited from the predialysis program and those who did not have that opportunity. Ninety-six patients were included in the study: 77 started renal replacement therapy after following a program at the predialysis outpatient department, while the remaining 19 patients started dialysis in an unplanned way. The patients monitored during predialysis were given a questionnaire to evaluate the usefulness of the followed program. The 77 patients who attended the predialysis outpatient department proved to be equally divided between hemodialysis and peritoneal dialysis: 43% vs 57%; the other 19 patients were directed mainly towards hemodialysis: 86% vs 14%, respectively. Analysis of the questionnaires showed that patients expressed a good degree of satisfaction. The results pointed to the usefulness of creating a predialysis outpatient department that should be able to a) optimize the predialytic treatments; b) plan the preparation of vascular or peritoneal access; c) guarantee patients a conscious choice of their replacement therapy.

Macrophages in the heart: Active players or simple bystanders?

Today, more and more studies focus on the processes in which macrophages are involved. These discoveries provide new perspectives on the cellular mechanisms that regulate the physiological functions of the healthy heart. Moreover, they offer a deeper knowledge of the pathologic processes underlying the onset and the evolution of specific cardiac impairment. The heterogeneous population of macrophages within the heart can be divided by origin, expression profile, and function. The pool of cardiac macrophages includes at least two distinct subsets with different ontogeny. The first one has an embryonic origin, deriving from the yolk sac and the fetal liver, while the other macrophage subset results from the postnatal recruitment of monocytes produced in the bone marrow. This review will focus on new phenotypes and functions of cardiac macrophages that have been identified in the last years and that need to be deeply studied to unveil new potential therapies aimed at treating cardiac diseases.

Purinergic Receptor P2Y2 Stimulation Averts Aortic Valve Interstitial Cell Calcification and Myofibroblastic Activation.

Rationale-Calcific aortic valve stenosis (CAVS) is a pathological condition of the aortic valve with a prevalence of 3% in the general population. It is characterized by massive rearrangement of the extracellular matrix, mostly due to the accumulation of fibro-calcific deposits driven by valve interstitial cells (VIC), and no pharmacological treatment is currently available. The aim of this study was to evaluate the effects of P2Y2 receptor (P2RY2) activation on fibro-calcific remodeling of CAVS. Methods-We employed human primary VICs isolated from CAVS leaflets treated with 2-thiouridine-5'-triphosphate (2ThioUTP, 10 µM), an agonist of P2RY2. The calcification was induced by inorganic phosphate (2 mM) and ascorbic acid (50 µg/mL) for 7 or 14 days, while the 2ThioUTP was administered starting from the seventh day. 2ThioUTP was chronically administered for 5 days to evaluate myofibroblastic activation. Results-P2RY2 activation, under continuous or interrupted pro-calcific stimuli, led to a significant inhibition of VIC calcification potential (p < 0.01). Moreover, 2ThioUTP treatment was able to significantly reduce pro-fibrotic gene expression (p < 0.05), as well as that of protein α-smooth muscle actin (p = 0.004). Conclusions-Our data suggest that P2RY2 activation should be further investigated as a pharmacological target for the prevention of CAVS progression, acting on both calcification and myofibroblastic activation.

Extraction-Free Absolute Quantification of Circulating miRNAs by Chip-Based Digital PCR.

Circulating microRNAs (miRNA) have been proposed as specific biomarkers for several diseases. Quantitative Real-Time PCR (RT-qPCR) is the gold standard technique currently used to evaluate miRNAs expression from different sources. In the last few years, digital PCR (dPCR) emerged as a complementary and accurate detection method. When dealing with gene expression, the first and most delicate step is nucleic-acid isolation. However, all currently available protocols for RNA extraction suffer from the variable loss of RNA species due to the chemicals and number of steps involved, from sample lysis to nucleic acid elution. Here, we evaluated a new process for the detection of circulating miRNAs, consisting of sample lysis followed by direct evaluation by dPCR in plasma from healthy donors and in the cardiovascular setting. Our results showed that dPCR is able to detect, with high accuracy, low-copy-number as well as highly expressed miRNAs in human plasma samples without the need for RNA extraction. Moreover, we assessed a known myocardial infarction-related miR-133a in acute myocardial infarct patients vs. healthy subjects. In conclusion, our results show the suitability of the extraction-free quantification of circulating miRNAs as disease markers by direct dPCR.

[Brachial artery pseudoaneurysm: a rare but serious complication in hemodialysis patients with arteriovenous fistula].

A pseudoaneurysm or false aneurysm of the brachial artery is an uncommon occurrence in patients receiving hemodialysis with arteriovenous fistula (AVF). We describe the case of a 76-year-old woman presenting with a large, tender, pulsatile mass in the right antecubital region 10 cm from the AVF. B-mode ultrasound examination revealed a saccular hematoma. Color doppler showed a recirculation movement of blood, creating a two colors image called "Korean flag". The patient was transferred to the surgical unit where she first underwent ultrasound-guided compression and then surgical repair of the pseudoaneurysm. Two weeks after surgery the AVF was used again as an access for hemodialysis. Differentiating between a false and a true aneurysm based on ultrasound is not always straightforward. Doppler ultrasound findings can be decisive for the early diagnosis of a pseudoaneurysm to ensure proper treatment planning given the dangerous complications of ruptures. Treatment options include: compression, percutaneous thrombin injection, endovascular exclusion with covered stents, aneurysmectomy and surgical repair.

[Analysis of clinical Risk and adoption of shared procedures: experience of nephrology and dialysis unit of ASL BA]. / Dall'analisi del rischio clinico all'adozione di procedure condivise: esperienza della s.c. di nefrologia e dialisi della ASL BA.

Currently, English scientific literature is lacking in studies showing that medical assistance may be delivered without errors. Since two years ago, the department of nephrology and urology of ASL BA has been establishing a process of clinical risk management.Starting with the reporting of a single error, a related database was subsequently developed, in order to validate technical and organizational procedures that would be of common use in the daily clinical practice.With regard to error reporting, the system of incident reporting was adopted: that is a structured collection of significant events for the safety of patients with a specific form for reporting to be filled out by health professionals. Reports have been collected, coded and analysed. Finally measures were adopted to reduce the recurrence of the error.This first phase consisted on writing the procedures in order to create structured diagnostic-therapeutic protocols. In 18 months of observation adopting the incident reporting form, 48 errors have been reported: 52% due to adverse events; 12.5% to adverse reactions; 31.2% near misses and 2% to sentinel events. In 35.4 % of cases the error occurred in the administration or prescription of drug therapies, in 18.7% of cases it occurred in the organizational stage, in 12.5% it was a surgical error, in 18.7% of cases the error was due to incorrect asepsis, in 8.3% of cases it occurred during the medical examination and finally in 8.3% during dialysis. An analysis of the error database resulted in the choice of more urgent procedures. It is our view that only the observation of procedures can ensure the achievement of a high quality with improved clinical outcomes, reduction of complications, elimination of inappropriate interventions and increased patient satisfaction.

[A rare case of acute renal failure related to amanita proxima ingestion]. / Nefropatia tubulo-interstiziale acuta da amanita proxima.

OBJECTIVE: The first cases of acute renal tubulopathy related to Amanita proxima poisoning were described in 1994; the mushroom contains a toxin responsible for the allenic-norleucine syndrome, characterised by a kidney damage that occur earlier than in Cortinarius orellanus poisoning and generally improve with complete resolution within ten days. CASE REPORT: A 45 years old woman was admitted to the hospital because of nausea, vomiting, and heartburn started the day before. Symptoms occurred eight hours after eating a single big wild mushroom; three friends who had the same meal were all asymptomatic. Twelve hours after the admission the woman became anuric and blood tests showed an impaired renal function: creatinine 13 mg/dL urea 240 mg/dL, AST 240 U / L, ALT 350 U / l. The patient was transferred to the nephrology unit of the Hospital Di Venere of Bari and the PCC of Milan was consulted. The toxicologist supposed a nephrotoxic syndrome caused by the consumption of Amanita proxima and sent a picture of the mushroom ingested to a mycologist who identified the specie as Amanita proxima Dumé, Bull (typical volva reddish-orange, ivory white hat, scaly stalk) sometimes mistaken for Amanita ovoidea. Haemodialysis was performed for five days followed by supportive care. Urine output gradually increased, serum creatinine decreased and Ast - Alt normalized. CONCLUSIONS: Amanita proxima contains an allenic-norleucine toxin (different from orellanine for the absence of inhibition of alkaline phosphatase), responsible for the reversible kidney damage, characterised by tubulointerstitial nephritis with acute tubular necrosis and renal failure. Occurrence and seriousness of symptoms seem to be variable and dependent on the amount ingested.

[It's not always a cyst]. / Non sempre cisti: fistola arterovenosa intrarenale.

Congenital arteriovenous renal fistulas are rare malformations due to abnormal communications between arterial and the venous systems. There are two types of congenital arteriovenous malformations: crisoid or, as in the present study, aneurysmal. Hematuria is the major and most common symptom, along with other clinical manifestations, such as hypertension, left ventricular hypertrophy, cardiac failure, and abdominal pain, but the congenital aneurysmatic arteriovenous renal fistulas can be also asymptomatic. Diagnosis can arise from a focused survey, suggested by a medical case or to be occasional, as in the present case of study. Ultrasonography with color duplex studies is the first line of imaging studies used in the diagnosis of renal arteriovenous malformations, The differential diagnosis must be made with other anechoic lesion: abscesses, tumors, hydronephrosis or, as in this case, a renal cyst. Angiography is the gold standard in the diagnosis of arteriovenous malformations, especially in those cases where the diagnostic -therapeutic treatment requires the endovascular treatment of the vessel, as in the case of a 46 years old man submitted in our clinic to the ultrasonography follow-up for a renal cyst.