Effect of empagliflozin on brachial artery shear stress and endothelial function in subjects with type 2 diabetes: Results from an exploratory study:

Empagliflozin reduces the risk of cardiovascular mortality in subjects with type 2 diabetes. We demonstrated that empagliflozin increases blood viscosity and carotid shear stress and decreases carotid wall thickness. Shear stress is the force acting on the endothelial surface and modulates arterial function. The current study evaluates the influence of empagliflozin on brachial artery shear stress and endothelial function compared to incretin-based therapy. The study is a nonrandomized, open, prospective cohort study including 35 subjects with type 2 diabetes administered empagliflozin or incretin-based therapy. Shear stress was calculated with a validated formula, and endothelial function was evaluated using the flow-mediated dilation technique. Both treatments resulted in comparable reductions in blood glucose and glycated haemoglobin. Brachial artery shear stress significantly increased exclusively in the empagliflozin group (61 ± 20 vs 68 ± 25 dynes/cm2, p = 0.04), whereas no significant difference was detected in the incretin-based therapy group (60 ± 20 vs 55 ± 12 dynes/cm2, p = not significant). Flow-mediated dilation significantly increased in the empagliflozin group (4.8 ± 4.5% vs 8.5 ± 5.6%, p = 0.03). Again, no change was detected in the incretin-based therapy group (5.1 ± 4.5% vs 4.7 ± 4.7%, p = not significant). The present findings demonstrate the beneficial effect of empagliflozin on shear stress and endothelial function in subjects with type 2 diabetes independent of the hypoglycaemic effect

Asymptomatic and symptomatic deep venous thrombosis in hospitalized acutely ill medical patients: risk factors and therapeutic implications

Background Acutely ill medical patients experience deep venous thrombosis (DVT) during the hospitalization, however the time course of DVT is still unclear. Objectives To evaluate risk factors in acutely ill hospitalized medical patients for proximal asymptomatic DVT (ADVT) and symptomatic DVT (SDVT) at admission and discharge. Patients/Methods In this prospective observational study, consecutive acutely ill medical patients (hospitalized mainly for acute medical disease as infections, neoplasm, anemia, heart failure) underwent compression ultrasonography (CUS) of proximal lower limb veins within 48 h from admission and at discharge to diagnose ADVT and SDVT. Covid-19 patients, anticoagulant therapy, surgical procedures, acute SDVT, and acute pulmonary embolism, were exclusion criteria. Biographical characteristics at hospitalization, D-Dimer (assessed by ELISA)) and DD-improve score. Results Of 2,100 patients (1002 females, 998 males, age 71 +/- 16 years) 58 (2.7%) had proximal ADVT at admission. Logistic regression analysis showed that age, and active cancer were independently associated with ADVT at admission. The median length of hospitalization was 10 days [interquartile range: 6-15]. During the hospital stay, 6 patients (0.3%) with a negative CUS at admission experienced DVT (2 SDVT and 4 ADVT). In the subgroup of patients (n = 1118), in whom D-dimer was measured at admission, D-Dimer and IMPROVE-DD score were associated with ADVT at admission (n = 37) and with all DVT (n = 42) at discharge. ROC curve defined an IMPROVE-DD score of 2.5 as the optimal cut-off for discriminating patients with and without thrombotic events. Conclusions We provide evidence of early development of ADVT in unselected acutely ill medical patients suggesting the need of investigating patients by CUS immediately after hospital admission (within 48 h). Advanced age, active cancer, known thrombophilia and increased IMPROVE-DD score may identify patients at risk. The benefit of anticoagulation needs to be investigated in patients with these specific risk factors and negative CUS at admission

Fatality rate and predictors of mortality in an Italian cohort of hospitalized COVID-19 patients

Clinical features and natural history of coronavirus disease 2019 (COVID-19) differ widely among different countries and during different phases of the pandemia. Here, we aimed to evaluate the case fatality rate (CFR) and to identify predictors of mortality in a cohort of COVID-19 patients admitted to three hospitals of Northern Italy between March 1 and April 28, 2020. All these patients had a confirmed diagnosis of SARS-CoV-2 infection by molecular methods. During the study period 504/1697 patients died; thus, overall CFR was 29.7%. We looked for predictors of mortality in a subgroup of 486 patients (239 males, 59%; median age 71 years) for whom sufficient clinical data were available at data cut-off. Among the demographic and clinical variables considered, age, a diagnosis of cancer, obesity and current smoking independently predicted mortality. When laboratory data were added to the model in a further subgroup of patients, age, the diagnosis of cancer, and the baseline PaO2/FiO2 ratio were identified as independent predictors of mortality. In conclusion, the CFR of hospitalized patients in Northern Italy during the ascending phase of the COVID-19 pandemic approached 30%. The identification of mortality predictors might contribute to better stratification of individual patient risk

Hepatitis C flare due to superinfection by genotype 4 in an HCV genotype 1b chronic carrier

We report here on a patient affected by chronic hepatitis C who developed acute hepatitis C virus (HCV) superinfection with replacement of genotype 1 b by genotype 4. The history revealed no risk factors for a new exposure to HCV, with the exception of colonoscopy with mucosal biopsy performed about 3 months before. This report underlines the absence of an effective immune-mediated cross-protection against different HCV genotypes. Moreover, the possible relationship between HCV infection and colonoscopy points out the importance of strict adherence to international guidelines for disinfection and cleaning of invasive diagnostic tools for all subjects examined, including HCV chronic carriers. (C) 2002 Lippincott Williams Wilkins

Interleukin-33 Involvement in Nonsmall Cell Lung Carcinomas: An Update

Lung carcinogenesis is a multistep process involving genetic mutations and epigenetic changes, with the acquisition of a malignant phenotype characterized by apoptosis resistance, unregulated proliferation and differentiation, invasion, and metastatic abilities. However, neoplastic development and progression seem to be aided by non-neoplastic cells; the molecules they produced can either promote the immune response or, alternatively, support tumor pathogenesis. Consequently, the relative contribution of tumor-associated inflammatory pathways to cancer development has become crucial information. Interleukin-33 (IL-33) is an IL-1-like alarmin, and it is a ligand for the suppressor of tumorigenicity 2 (ST2) receptor. IL-33 functions as a dual role cytokine with the ability to induce T-helper-type 2 (Th2) immune cells and translocate into the nucleus, suppressing gene transcription. Although its function in immunity- and immune-related disorders is well known, its role in tumorigenesis is still debated. The IL-33/ST2 axis is emerging as a powerful modulator of the tumor microenvironment (TME) by recruiting immune cells, able to modify the TME, supporting malignant proliferation or improving antitumor immunity. In the present review, we discuss IL-33′s potential role in lung carcinogenesis and its possible application as a therapeutic target

Association between urticaria and virus infections: A systematic review

Background: The association between urticaria and virus infections has rarely been reported in the literature. The lack of reported cases is probably due to the difficulty in establishing a cause-And-effect relationship. It is not possible to challenge the patient with an etiologic agent. Objective: The purpose of this work was to perform a systematic review on the association between urticaria and virus infections. Methods: This systematic review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We searched for articles from January 1, 2008, through May 2015, by using two key terms related to urticaria and virus diseases, "urticaria" and one key term related to virus infections, "virus disease," then "urticaria" and the name of each virus family, and of the most representative virus serotypes. Results: We reported cases of patients affected either by acute or chronic urticaria with a concurrent virus infection. Previous other causes of urticaria had to be excluded. Herpesviridae infections and urticaria were the most frequently reported associations in children. However, hepatitis virus infections would appear to be the most-frequent cause of urticaria in adults. Conclusions: Data obtained indicated viral infection as a potential trigger and sometimes as the main etiologic agent in causing acute or chronic urticaria. In every case, urticarial manifestation cleared up after either healing or controlling of the viral infection. However, prospective studies and well-structured research is needed to better clarify the role of viruses in the pathogenesis of urticaria and their relative prevalence

Effects of aib residues insertion on the structural–functional properties of the frog skin-derived peptide esculentin-1a(1–21)NH2

Antimicrobial peptides (AMPs) play a key role in the defence mechanism of living organisms against microbial pathogens, displaying both bactericidal and immunomodulatory properties. They are considered as a promising alternative to the conventional antibiotics towards which bacteria are becoming highly resistant. Recently, a derivative of the frog skin AMP esculentin-1a, esculentin-1a(1-21)NH2 [Esc(1-21)], showed a strong and fast membranolytic activity against Gram-negative bacteria but with a lower efficacy against Gram-positive ones. Here, with the aim to increase the α-helicity of Esc(1-21) and the expected potency against Gram-positive bacteria, we designed an analog bearing three α-aminoisobutyric acid (Aib) residues at positions 1, 10, and 18 of its primary structure. We demonstrated that the incorporation of Aib residues: (1) promoted the α-helix conformation of Esc(1-21), as confirmed by circular dichroism and two-dimensional nuclear magnetic resonance spectroscopies; (2) was sufficient to make this analog more active than the parent peptide against several Gram-positive bacterial strains without affecting its activity against Gram-negative bacteria; and (3) resulted to be devoid of toxic effect toward epithelial cells at the active antimicrobial concentrations. These results suggest that replacement of L-amino acids with Aib residues has beneficial effects on the structure and properties of the membrane-active peptide Esc(1-21), making it a better candidate for the design and development of selective drugs against Gram-positive bacteria

Role of IL-33/ST2 Pathway in Inflammatory Bowel Disease: An Overview and Future Perspectives

Inflammatory bowel disease (IBD) represents a heterogenous and complex group of idiopathic chronic inflammatory conditions affecting the gastrointestinal tract and other extraintestinal systems with rising global incidences. The interplay of genetic predisposition and environmental factors contributes to its pathogenesis. Among the key cytokines implicated in IBD molecular alterations, IL-33 stands out for its multifaceted roles in both pathogenesis and repair mechanisms. IL-33, known for its action in initiating immune responses, is closely associated with Th2 immunity and is considered a potent inflammatory factor with dual functions, acting both as a pro-inflammatory cytokine and a transcriptional regulator. Primarily expressed by non-hematopoietic cells in the gastrointestinal tract, IL-33 interacts with its receptor, ST2, to modulate immune responses. In IBD, dysregulated IL-33 expression exacerbates mucosal inflammation, compromising barrier integrity and promoting tissue damage and fibrosis. Additionally, IL-33 plays a complex role in IBD-related colorectal cancer (CRC), affecting tumor progression and angiogenesis. This review summarizes the multifaceted roles of IL-33 in gastrointestinal health and disease, emphasizing its significance in the pathogenesis of IBD and CRC. Moreover, we thought it of interest to provide new insights into potential therapeutic avenues targeting IL-33 signaling for the management of these debilitating conditions

Presence of effector CD8 � T cells in hepatitis C virusexposed healthy seronegative donors

CTL responses against multiple hepatitis C virus (HCV) epitopes were detected in 7 of 29 (24.1%) healthy family members (HFM) persistently exposed to chronically HCV-infected patients (HCV-HFM). These precursor CTL were at very low or undetectable frequencies, as determined by limiting dilution analysis. However, when HCV-specific effector CD8 � T cells, freshly isolated from PBMC of HCV-HFM, were assessed by a sensitive enzyme-linked immunospot assay, their frequencies were severalfold higher than those of precursor CTL. These results indicate that the two assays detect two functionally distinct T cell populations and that the effector cells are not assayed by the 51 Cr-release assay. Furthermore, the combination of cell depletion and enzyme-linked immunospot analyses showed that the effector cells were confined into a CD8 � CD45RO � CD28 � population. The persistence of effector CD8 � T cells specific for both the structural and nonstructural viral proteins in uninfected HCV-HFM, suggest that: 1) an immunological memory is established upon a subclinical infection without any evidence of hepatitis, in a large cohort of HCV-exposed individuals; 2) because these cells required neither restimulation nor the addition of particular cytokines in vitro for differentiating in effectors, they should be capable of prompt HCV-specific effector function in vivo, possibly providing antiviral protection; and 3) the maintenance of effector T cell responses may be sustained by persisting low-level stimulation induced by inapparent infections. The Journal of Immunology, 1999, 162: 6681–6689