Diabetes mellitus comprises a group of carbohydrate metabolism disorders that share a common main feature of chronic hyperglycemia that results from defects of insulin secretion, insulin action, or ...both. Insulin is an important anabolic hormone, and its deficiency leads to various metabolic abnormalities in proteins, lipids, and carbohydrates. Atherosclerosis develops as a result of a multistep process ultimately leading to cardiovascular disease associated with high morbidity and mortality. Alteration of lipid metabolism is a risk factor and characteristic feature of atherosclerosis. Possible links between the two chronic disorders depending on altered metabolic pathways have been investigated in numerous studies. It was shown that both types of diabetes mellitus can actually induce atherosclerosis development or further accelerate its progression. Elevated glucose level, dyslipidemia, and other metabolic alterations that accompany the disease development are tightly involved in the pathogenesis of atherosclerosis at almost every step of the atherogenic process. Chronic inflammation is currently considered as one of the key factors in atherosclerosis development and is present starting from the earliest stages of the pathology initiation. It may also be regarded as one of the possible links between atherosclerosis and diabetes mellitus. However, the data available so far do not allow for developing effective anti-inflammatory therapeutic strategies that would stop atherosclerotic lesion progression or induce lesion reduction. In this review, we summarize the main aspects of diabetes mellitus that possibly affect the atherogenic process and its relationship with chronic inflammation. We also discuss the established pathophysiological features that link atherosclerosis and diabetes mellitus, such as oxidative stress, altered protein kinase signaling, and the role of certain miRNA and epigenetic modifications.
Coronavirus disease 2019 (COVID-19) poses a major health threat to healthy individuals and those with comorbidities, but its impact on patients with cirrhosis is currently unknown. Herein, we aimed ...to evaluate the impact of COVID-19 on the clinical outcome of patients with cirrhosis.
In this multicentre retrospective study, patients with cirrhosis and a confirmed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection were enrolled between 1st and 31th March 2020. Clinical and biochemical data at diagnosis of COVID-19 and at the last outpatient visit were obtained through review of medical records.
Fifty patients with cirrhosis and confirmed SARS-CoV-2 infection were enrolled (age 67 years, 70% men, 38% virus-related, 52% previously compensated cirrhosis). At diagnosis, 64% of patients presented fever, 42% shortness of breath/polypnea, 22% encephalopathy, 96% needed hospitalization or a prolonged stay if already in hospital. Respiratory support was necessary in 71%, 52% received antivirals, 80% heparin. Serum albumin significantly decreased, while bilirubin, creatinine and prothrombin time significantly increased at COVID-19 diagnosis compared to last available data. The proportion of patients with a model for end-stage liver disease (MELD) score ≥15 increased from 13% to 26% (p = 0.037), acute-on-chronic liver failure and de novo acute liver injury occurred in 14 (28%) and 10 patients, respectively. Seventeen patients died after a median of 10 (4–13) days from COVID-19 diagnosis, with a 30-day-mortality rate of 34%. The severity of lung and liver (according to CLIF-C, CLIF-OF and MELD scores) diseases independently predicted mortality. In patients with cirrhosis, mortality was significantly higher in those with COVID-19 than in those hospitalized for bacterial infections.
COVID-19 is associated with liver function deterioration and elevated mortality in patients with cirrhosis.
Coronavirus disease 2019 (COVID-19) poses a major health threat to healthy individuals and those with comorbidities. Herein, we assessed its impact on patients with cirrhosis. Infection with COVID-19 was associated with liver function deterioration and elevated mortality in patients with cirrhosis.
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•50 patients with cirrhosis and SARS-CoV-2 infection were studied, with an overall 30-day mortality rate of 34%.•Mortality was higher in patients with respiratory failure and in those with worsening liver function at COVID-19 diagnosis.•30-day mortality rates were higher in patients with cirrhosis and COVID-19 than in those with bacterial infections.•No major adverse events were related to the thromboprophylaxis with heparin (given to 80% of patients) or antiviral treatments.
Background
Real-time tissue elastography (RTE), acoustic radiation force impulse (ARFI) imaging, and transient elastography (TE) are new technologies that are used for liver stiffness evaluation. The ...aim of this study was to compare these methods in the same population and to determine their diagnostic accuracy in the prediction of liver fibrosis.
Methods
Forty-five consecutive, previously biopsied, patients with chronic liver disease and 27 normal subjects underwent TE, RTE, and ARFI on the right liver lobe. Correlation coefficients between measurements, Metavir fibrosis stage, and histological necro-inflammatory activity (adjusted for fibrosis stage) were evaluated via Spearman’s rank order correlation coefficients. Areas under the receiver operating characteristic curve (AUROCs) were calculated to predict each fibrosis stage.
Results
Failure or inconsistent results occurred in 12.5% of the attempts at TE, but in none of the attempts at RTE and ARFI. The three methods showed high correlation with fibrosis and poor correlation with necro-inflammatory activity. TE and ARFI exhibited high diagnostic accuracy (AUROCs ≥0.9) in diagnosing cirrhosis (F4 Metavir). All three methods presented fair (AUROCs >0.7) to good (AUROCs >0.8) diagnostic accuracy in diagnosing fibrosis (F1–4 Metavir) and significant fibrosis (F2–4 Metavir), with TE showing the best performance (AUROCs were 0.878 for fibrosis and 0.897 for significant fibrosis).
Conclusions
TE and ARFI provide high diagnostic accuracy in the diagnosis of cirrhosis. When feasible, TE may perform better than RTE and ARFI in predicting fibrosis and significant fibrosis, but larger studies are needed.
Biliary cyst tumors （cystadenoma and cystadenocarcinoma） are an indication for liver resection. They account for only 5% of all solitary cystic lesions of the liver, but differential diagnosis with ...multiloculated or complicated biliary cysts, atypical hemangiomas, hamartomas and lymphangiomas may be difficult. The most frequent challenge is to differentiate biliary cyst tumors from hemorrhagic cysts. Computerized tomography （CT） and magnetic resonance imaging （MRI） are often not diagnostic and in these cases fine needle aspiration （FNA） is used to confirm the presence of atypical biliary cells. FNA, however, lacks adequate sensitivity and specificity and should always be used in conjunction with imaging. Pre-operative differentiation of cystadenoma from cystadenocarcinoma is impossible and surgery must be performed if a biliary cyst tumor is suspected. When multiple cystic lesions are observed throughout the liver parenchyma, it is important to exclude liver metastasis, of which colonic cancer is the most common primary site. Multiple biliary hamartomas （von Meyenburg complex） can appear as a mixture of solid and cystic lesions and can be confused with cystic metastasis. Strong and uniform T2 hyperintensity on MRI is usually diagnostic, but occasionally a percutaneous biopsy may be required.
Calcific aortic valve disease (CAVD) is the most common valvular heart disease in developed countries predominantly affecting the elderly population therefore posing a large economic burden. It is a ...gradually progressive condition ranging from mild valve calcification and thickening, without the hemodynamic obstruction, to severe calcification impairing leaflet motion, known as aortic stenosis (AS). The progression of CAVD occurs over many years, and it is extremely variable among individuals. It is also associated with an increased risk of coronary events and mortality. The recent insights into the CAVD pathophysiology included an important role of sex. Accumulating evidence suggests that, in patients with CAVD, sex can determine important differences in the relationship between valvular calcification process, fibrosis, and aortic stenosis hemodynamic severity between men and women. Consequently, it has implications on the development of different valvular phenotypes, left ventricular hypertrophy, and cardiovascular outcomes in men and women. Along these lines, taking into account the sex-related differences in diagnosis, prognosis, and treatment outcomes is of profound importance. In this review, the sex-related differences in patients with CAVD, in terms of pathobiology, clinical phenotypes, and outcomes were discussed.
Inflammation is a physiological process by which the body responds to external insults and stress conditions, and it is characterized by the production of pro-inflammatory mediators such as ...cytokines. The acute inflammatory response is solved by removing the threat. Conversely, a chronic inflammatory state is established due to a prolonged inflammatory response and may lead to tissue damage. Based on the evidence of a reciprocal regulation between inflammation process and calcium unbalance, here we described the involvement of a calcium sensor in cardiac diseases with inflammatory drift. Indeed, the Ca
/calmodulin-dependent protein kinase II (CaMKII) is activated in several diseases with an inflammatory component, such as myocardial infarction, ischemia/reperfusion injury, pressure overload/hypertrophy, and arrhythmic syndromes, in which it actively regulates pro-inflammatory signaling, among which includes nuclear factor kappa-B (NF-κB), thus contributing to pathological cardiac remodeling. Thus, CaMKII may represent a key target to modulate the severity of the inflammatory-driven degeneration.
Background and Aims
Metabolic dysfunction (MD)‐associated fatty liver disease has been proposed to identify individuals at risk of liver events irrespectively of the contemporary presence of other ...liver diseases. The aim of this study was to examine the impact of MD in patients cured of chronic hepatis C (CHC).
Patients and Methods
We analysed data from a real‐life cohort of 2611 Italian patients cured of CHC with direct antiviral agents and advanced liver fibrosis, without HBV/HIV, transplantation and negative for hepatocellular carcinoma (HCC) history (age 61.4 ± 11.8 years, 63.9% males, median follow‐up 34, 24–40 months). Information about ultrasonographic steatosis (US) after sustained virological response was available in 1978.
Results
MD affected 58% of patients, diagnosed due to the presence of diabetes (MD‐diabetes, 19%), overweight without diabetes (MD‐overweight, 37%) or multiple metabolic abnormalities without overweight and diabetes (MD‐metabolic, 2%). MD was more frequent than and not coincident with US (32% MD‐only, 23% MD‐US and 13% US‐only). MD was associated with higher liver stiffness (p < 0.05), particularly in patients with MD‐diabetes and MD‐only subgroups, comprising older individuals with more advanced metabolic and liver disease (p < 0.05). At Cox proportional hazard multivariable analysis, MD was associated with increased risk of HCC (HR 1.97, 95% CI 1.27–3.04; p = 0.0023). Further classification according to diagnostic criteria improved risk stratification (p < 0.0001), with the highest risk observed in patients with MD‐diabetes. Patients with MD‐only appeared at highest risk since the sustained virological response achievement (p = 0.008), with a later catch‐up of those with combined MD‐US, whereas US‐only was not associated with HCC.
Conclusions
MD is more prevalent than US in patients cured of CHC with advanced fibrosis and identifies more accurately individuals at risk of developing HCC.
Background & Aims The current guidelines recommend the surveillance of cirrhotic patients for early diagnosis of hepatocellular carcinoma (HCC), based on liver ultrasonography repetition at either 6 ...or 12 month intervals, since there is no compelling evidence of superiority of the more stringent program. This study aimed at comparing cancer stage, treatment applicability, and survival between patients on semiannual or annual surveillance. Methods We analyzed the clinical records of 649 HCC patients in Child-Pugh class A or B, observed in ITA.LI.CA centers. HCC was detected in 510 patients submitted to semiannual surveillance (Group 1) and in 139 submitted to annual surveillance (Group 2). In Group 1 the survival was presented as observed and corrected for the lead time. Results The cancer stage was less severe in Group 1 than in Group 2 ( p < 0.001), with more single tiny (⩽2 cm) and less advanced tumors. Treatment applicability was improved by the semiannual program ( p = 0.020). The median observed survival was 45 months (95% CI 40.0–50.0) in Group 1 and 30 months (95% CI 24.0–36.0) in Group 2 ( p = 0.001). The median corrected survival of Group 1 was 40.3 months (95% CI 34.9–45.7) ( p = 0.028 with respect to the observed survival of Group 2). Age, platelet count, α-fetoprotein, Child-Pugh class, cancer stage, and hepatocellular carcinoma treatment were independent prognostic factors. Conclusions Semiannual surveillance increases the detection rate of very early hepatocellular carcinomas and reduces the number of advanced tumors as compared to the annual program. This translates into a greater applicability of effective treatments and into a better prognosis.
Atherosclerosis is a common cause of cardiovascular disease, which, in turn, is often fatal. Today, we know a lot about the pathogenesis of atherosclerosis. However, the main knowledge is that the ...disease is extremely complicated. The development of atherosclerosis is associated with more than one molecular mechanism, each making a significant contribution. These mechanisms include endothelial dysfunction, inflammation, mitochondrial dysfunction, oxidative stress, and lipid metabolism disorders. This complexity inevitably leads to difficulties in treatment and prevention. One of the possible therapeutic options for atherosclerosis and its consequences may be metformin, which has already proven itself in the treatment of diabetes. Both diabetes and atherosclerosis are complex metabolic diseases, the pathogenesis of which involves many different mechanisms, including those common to both diseases. This makes metformin a suitable candidate for investigating its efficacy in cardiovascular disease. In this review, we highlight aspects such as the mechanisms of action and targets of metformin, in addition to summarizing the available data from clinical trials on the effective reduction of cardiovascular risks.
Diabetes mellitus (DM) is one of the most common and costly disorders that affect humans around the world. Recently, clinicians and scientists have focused their studies on the effects of glycemic ...variability (GV), which is especially associated with cardiovascular diseases. In healthy subjects, glycemia is a very stable parameter, while in poorly controlled DM patients, it oscillates greatly throughout the day and between days. Clinically, GV could be measured by different parameters, but there are no guidelines on standardized assessment. Nonetheless, DM patients with high GV experience worse cardiovascular disease outcomes. In vitro and in vivo studies showed that high GV causes several detrimental effects, such as increased oxidative stress, inflammation, and apoptosis linked to endothelial dysfunction. However, the evidence that treating GV is beneficial is still scanty. Clinical trials aiming to improve the diagnostic and prognostic accuracy of GV measurements correlated with cardiovascular outcomes are needed. The present review aims to evaluate the clinical link between high GV and cardiovascular diseases, taking into account the underlined biological mechanisms. A clear view of this challenge may be useful to standardize the clinical evaluation and to better identify treatments and strategies to counteract this DM aspect.
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