Adipokines in obesity and metabolic diseases

Adipose tissue secretes many adipokines that regulate important physiological functions. Growing studies have highlighted that these bioactive molecules may contribute to the development of metabolic and cardiovascular diseases. Adipokines exert systemic metabolic effects and independent activity on numerous cells of the cardiovascular system, including cardiomyocytes and vascular cell walls. Adiponectin shows anti-inflammatory and anti-atherosclerotic activity on blood vessels. Conversely, resistin is endowed with pro-inflammatory effects and stimulates the proliferation of smooth muscle cells, thus promoting the development of atherosclerotic plaque. Leptin plays an important role in cardiac remodeling and blood pressure regulation through the activation of the sympathetic system. Obesity is a pathological condition associated with hypertrophy of white adipose tissue, which stimulates the production of pro-inflammatory adipokines while, it reduces the production of anti-inflammatory adipokines. The delicate balance among the production of pro-and anti-inflammatory molecules generated by adipose tissue affects, not only the development of metabolic complications associated with obesity, but also the onset and progression of atherosclerosis. Therefore, adipokines may be regarded as potential agents of clinical interest in the treatment of a wide range of metabolic disorders and as potential biomarkers useful for early detection of metabolic, cardiovascular and inflammatory diseases

Effects of 3,5-diiodo-L-thyronine on the liver of high fat diet fed rats

Experimental studies have highlighted that the administration of 3,5-diiodo-L-thyronine (T2) to rats fed diets rich in lipids induces a decrease of cholesterol and triglycerides plasma levels and body weight (BW) without inducing liver steatosis. On the basis of these observations we carried out some experimental in vivo studies to assess the effects of multiple high doses of T2 on the pituitary thyroid axis of rats fed diet rich in lipids. Fifteen male Wistar rats were divided into three groups of five animals each. The first group (N group) received standard diet, the second group was fed with a high fat diet (HFD group), while the third group (HFDT2 group) was additionally given T2 intraperitoneally at a dose level of 70 µg/100 g of BW three times a week up to four weeks. At the end of the treatment, blood sample from each animal was collected, centrifuged and the serum was stored at -20°C. The serum concentrations of thyroidstimulating hormone (TSH), triiodothyronine, thyroxine, adrenocorticotropic hormone, triglycerides, cholesterol, glucose, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase were then determined. In addition, liver of rats was examined by histology in order to assess the presence and degree of steatosis. The administration of T2 to rats fed with a high fat diet suppressed TSH secretion (P=0.013) while no steatosis was observed in the liver of these animals. Our data show that multiple administrations of high doses of T2 to rats fed diets rich in lipid inhibit TSH secretion and prevent the onset of liver steatosis in these animals

A Difficult Case of Ventriculitis in a 40-Year-Old Woman with Acute Myeloid Leukemia

Ventriculitis and nosocomial meningitis caused by carbapenem-resistant Gram-negative and vancomycin-resistant Gram-positive bacteria represent a growing treatment challenge. A case of ventriculitis and bacteremia caused by carbapenem-resistant, KPC-producing Klebsiella pneumoniae and vancomycin-resistant Enterococcus faecium in a young woman with acute leukemia who was successfully treated with meropenem/vaborbactam (MVB), rifampicin, and linezolid is described in this paper. This case report emphasizes the importance of a multidisciplinary strategy, including infectious focus control, for the treatment of device-associated central nervous system (CNS) infections from multidrug-resistant bacteria. Considering the novel resistance patterns, more research on drug penetration into the central nervous system, as well as on the necessity of association therapies, is needed

Antibodies Responses to SARS-CoV-2 in a Large Cohort of Vaccinated Subjects and Seropositive Patients

COVID-19 is a current global threat, and the characterization of antibody response is vitally important to update vaccine development and strategies. In this study we assessed SARS-CoV-2 antibody concentrations in SARS-CoV-2 positive patients (N = 272) and subjects vaccinated with the BNT162b2 m-RNA COVID-19 vaccine (N = 1256). For each participant, socio-demographic data, COVID-19 vaccination records, serological analyses, and SARS-CoV-2 infection status were collected. IgG antibodies against S1/S2 antigens of SARS-CoV-2 were detected. Almost all vaccinated subjects (99.8%) showed a seropositivity to anti-SARS-COV-2 IgG and more than 80% of vaccinated subjects had IgG concentrations > 200 AU/mL. In a Tobit multivariable regression analysis, SARS-CoV-2 vaccination was statistically significantly associated with increased IgG concentrations (β coef = 266.4; p < 0.001). A statistically significant reduction in SARS-CoV-2 IgG concentrations was found with older age (β coef = -1.96 per year increase; p < 0.001), male sex (β coef = -22.3; p < 0.001), and days after immunization (β coef = -1.67 per day increase; p < 0.001). Our findings could support the vaccination campaigns confirming the high immunogenicity of the SARS-CoV-2 vaccine under investigation with respect to the natural infection. Further studies will be required for evaluating the role of age and days after immunization in the persistence of vaccine antibodies and protection from the disease

Evaluation of T2 Magnetic Resonance (T2MR®) Technology for the Early Detection of ESKAPEc Pathogens in Septic Patients

Bloodstream infections (BSIs) and sepsis are a major cause of morbidity and mortality. Appropriate early antibiotic therapy is crucial for improving the survival of patients with sepsis and septic shock. T2 magnetic resonance (T2MR®) technology may enable fast and sensitive detection of ESKAPEc pathogens directly from whole-blood samples. We aimed to evaluate concordance between the T2Bacteria® Panel and standard blood culture and its impact on antibiotic therapy decisions. We conducted a single-centre retrospective study on patients with sepsis-induced hypotension or septic shock admitted to general, post-operative/neurosurgical, and cardiothoracic Intensive Care Units who were tested with the T2Bacteria® Panel from January 2021 to December 2022. Eighty-five consecutively admitted patients were included, for a total of 85 paired tests. A total of 48 ESKAPEc pathogens were identified by the T2Bacteria® Panel. The concordance rate between the T2Bacteria® Panel and blood cultures was 81% (69/85), with 20 concordant-positive and 49 concordant-negative cases. For the 25 microorganisms grown from accompanying blood cultures, blood pathogen coverage by the T2Bacteria® Panel was 88%. In this cohort of severely ill septic patients, the T2Bacteria® Panel was highly concordant and was able to detect more ESKAPEc pathogens, with a significantly shorter turn-around time compared to conventional blood cultures. The T2Bacteria® Panel also significantly impacted decisions on antibiotic therapy

Increase of multidrug-resistant bacteria after the COVID-19 pandemic in a major teaching Hospital in Sicily (2018-2021)

Introduction: The COVID-19 pandemic has further highlighted the continuing threat of antimicrobial resistance (AMR) to global health and economic development. In the last two decades, AMR has raised increasing concern, with an estimated 4.95 million deaths globally due to bacterial AMR in 2019 alone. The aim of this study was to analyse the impact of the pandemic on the spread of multidrug-resistant organisms (MDROs) using data from the Hospital "P. Giaccone" in Palermo, comparing pre-pandemic and pandemic periods. Methods: This observational study involved adult patients who were discharged from the hospital between 01 January 2018 and 31 December 2021. Hospital Discharge Cards were linked with microbiological laboratory reports to assess MDRO isolations. SARS-CoV-2 positivity during hospitalisation was evaluated using the National Institute of Health surveillance system. Results: A total of 58 427 hospitalisations were evaluated in this study. Half the patients were aged over 65 years (N=26 984) and most admissions were in the medical area (N=31 716). During the hospitalisation period, there were 2681 patients (5%) with MDROs isolations, and 946 patients (2%) were positive for SARS-CoV-2. Multivariable analyses showed that during 2020 and 2021, there was a significantly increased risk of isolation of Staphylococcus aureus, Acinetobacter baumannii, and Klebsiella pneumoniae. Age, weight of the Diagnosis-Related Group (DRG), wards with higher intensity of care, and length-of-stay were associated with a higher risk of MDRO isolation. Conclusion: This study provides new insights into the impact of the COVID-19 pandemic on MDRO isolation and has important implications for infection control and prevention efforts in healthcare facilities. Age, DRG-weight, and longer hospital stays further increased the risk of MDRO isolation. Thus, it is imperative to improve and follow hospital protocols to prevent healthcare-associated infections

Serum Albumin Is Inversely Associated With Portal Vein Thrombosis in Cirrhosis

We analyzed whether serum albumin is independently associated with portal vein thrombosis (PVT) in liver cirrhosis (LC) and if a biologic plausibility exists. This study was divided into three parts. In part 1 (retrospective analysis), 753 consecutive patients with LC with ultrasound-detected PVT were retrospectively analyzed. In part 2, 112 patients with LC and 56 matched controls were entered in the cross-sectional study. In part 3, 5 patients with cirrhosis were entered in the in vivo study and 4 healthy subjects (HSs) were entered in the in vitro study to explore if albumin may affect platelet activation by modulating oxidative stress. In the 753 patients with LC, the prevalence of PVT was 16.7%; logistic analysis showed that only age (odds ratio [OR], 1.024; P = 0.012) and serum albumin (OR, -0.422; P = 0.0001) significantly predicted patients with PVT. Analyzing the 112 patients with LC and controls, soluble clusters of differentiation (CD)40-ligand (P = 0.0238), soluble Nox2-derived peptide (sNox2-dp; P < 0.0001), and urinary excretion of isoprostanes (P = 0.0078) were higher in patients with LC. In LC, albumin was correlated with sCD4OL (Spearman's rank correlation coefficient [r(s)], -0.33; P < 0.001), sNox2-dp (r(s), -0.57; P < 0.0001), and urinary excretion of isoprostanes (r(s), -0.48; P < 0.0001) levels. The in vivo study showed a progressive decrease in platelet aggregation, sNox2-dp, and urinary 8-iso prostaglandin F2 alpha-III formation 2 hours and 3 days after albumin infusion. Finally, platelet aggregation, sNox2-dp, and isoprostane formation significantly decreased in platelets from HSs incubated with scalar concentrations of albumin. Conclusion: Low serum albumin in LC is associated with PVT, suggesting that albumin could be a modulator of the hemostatic system through interference with mechanisms regulating platelet activation

Contemporary lipid-lowering management and risk of cardiovascular events in homozygous familial hypercholesterolaemia: insights from the Italian LIPIGEN Registry

Aims: The availability of novel lipid-lowering therapies (LLTs) has remarkably changed the clinical management of homozygous familial hypercholesterolaemia (HoFH). The impact of these advances was evaluated in a cohort of 139 HoFH patients followed in a real-world clinical setting. Methods and results: The clinical characteristics of 139 HoFH patients, along with information about LLTs and low-density lipoprotein cholesterol (LDL-C) levels at baseline and after a median follow-up of 5 years, were retrospectively retrieved from the records of patients enrolled in the LIPid transport disorders Italian GEnetic Network-Familial Hypercholesterolaemia (LIPIGEN-FH) Registry. The annual rates of major atherosclerotic cardiovascular events (MACE-plus) during follow-up were compared before and after baseline. Additionally, the lifelong survival free from MACE-plus was compared with that of the historical LIPIGEN HoFH cohort. At baseline, LDL-C level was 332 ± 138 mg/dL. During follow-up, the potency of LLTs was enhanced and, at the last visit, 15.8% of patients were taking quadruple therapy. Consistently, LDL-C decreased to an average value of 124 mg/dL corresponding to a 58.3% reduction (Pt < 0.001), with the lowest value (∼90 mg/dL) reached in patients receiving proprotein convertase subtilisin/kexin type 9 inhibitors and lomitapide and/or evinacumab as add-on therapies. The average annual MACE-plus rate in the 5-year follow-up was significantly lower than that observed during the 5 years before baseline visit (21.7 vs. 56.5 per 1000 patients/year; P = 0.0016). Conclusion: Our findings indicate that the combination of novel and conventional LLTs significantly improved LDL-C control with a signal of better cardiovascular prognosis in HoFH patients. Overall, these results advocate the use of intensive, multidrug LLTs to effectively manage HoFH