Analisi di impatto di budget di pasireotide in pazienti con Acromegalia nella prospettiva del Servizio Sanitario Nazionale

Background: L’obiettivo dell’analisi è stato quello di valutare l’impatto economico dell’introduzione di pasireotide nella prospettiva del Servizio Sanitario Nazionale (SSN). Metodi: I dati epidemiologici e di costo che hanno implementato il modello di budget impact (BI) sono stati ottenuti tramite una revisione sistematica della letteratura. Il BI è stato stimato confrontando uno scenario senza l’introduzione di pasireotide rispetto ad uno scenario con nella prospettiva del SSN. Inoltre, è stata sviluppate una analisi di sensibilità deterministica (DSA) e l’applicazione del metodo payoff. Risultati: Il modello ha stimato un totale di circa 2.314 pazienti acromegalici ad oggi trattati con una seconda linea farmacologica. L’introduzione di pasireotide consente una riduzione complessiva di spesa pari a € 662.095 nei 5 anni di analisi. La DSA ed il valore atteso di pay-off confermano la robustezza dei risultati. Conclusioni: L’introduzione sul mercato di pasireotide non comporta un aggravio di spesa per il SSN, ma genera una reale riduzione dei cost

HCV cirrhotic patients treated with direct acting antivirals: detection of tubular dysfunction and resolution after viral clearance

Background/aims: Hepatitis C virus (HCV) has been identified in tubular epithelial cells of infected patients, however the presence of tubular dysfunction, which is a risk factor for chronic kidney disease, has never been examined in vivo. The present prospective longitudinal study aimed to estimate the prevalence of tubular dysfunction alone or with glomerular damage and its evolution after HCV clearance in cirrhotic patients. Methods: One-hundred-thirty-five consecutive Child-Pugh-A cirrhotic patients were evaluated before antiviral treatment and six months after the end of therapy. Tubular dysfunction was evaluated by urinary-alpha1-microglobulin-to-creatinine-ratio (α1-MCR), glomerular damage was assessed by urinary-albumin-to-creatinine-ratio (ACR). Results: Almost all the patients (93.3%) showed a normal or mildly decreased e-GFR (KDIGO-G1/G2-categories). Tubular dysfunction was found in 23.7% (32/135) of patients, co-occurring with glomerular damage in 37.5% (12/32) of cases, while glomerular damage was found in 16.3% (22/135) of patients. In multiple logistic regression, glomerular damage and the concomitant presence of diabetes and hypertension were the only predictors significantly associated with tubular dysfunction. After HCV-clearance, patients experienced a significant reduction of α1-MCR levels (21.0 vs 10.5 μg/mg, p=0.009) and tubular dysfunction resolved in 57.1% of subjects. Conclusions: Tubular dysfunction is an unrecognized feature of HCV-related kidney disease in cirrhotic patients and its presence should be primarily investigated in subjects with glomerular damage, diabetes and hypertension, despite normal e-GFR. Tubular dysfunction resolves in the majority of cases after HCV clearance, however, it may persist after antiviral treatment and further studies should evaluate its long term impact on kidney function

Safety of COVID-19 Vaccines in Patients with Autoimmune Diseases, in Patients with Cardiac Issues, and in the Healthy Population

The coronavirus disease 2019 (COVID-19) has been a challenge for the whole world since the beginning of 2020, and COVID-19 vaccines were considered crucial for disease eradication. Instead of producing classic vaccines, some companies pointed to develop products that mainly function by inducing, into the host, the production of the antigenic protein of SARS-CoV-2 called Spike, injecting an instruction based on RNA or a DNA sequence. Here, we aim to give an overview of the safety profile and the actual known adverse effects of these products in relationship with their mechanism of action. We discuss the use and safety of these products in at-risk people, especially those with autoimmune diseases or with previously reported myocarditis, but also in the general population. We debate the real necessity of administering these products with unclear long-term effects to at-risk people with autoimmune conditions, as well as to healthy people, at the time of omicron variants. This, considering the existence of therapeutic interventions, much more clearly assessed at present compared to the past, and the relatively lower aggressive nature of the new viral variants

RB137 and RB138 antibodies recognize human cathelicidin LL37 by ELISA

LL37 is a cationic antimicrobial peptide (AMP), which can undergo post-translational modifications (PTM), such as citrullination and carbamylation. We demonstrate here that recombinant antibodies RB137 and RB138 are specific for native LL37 and do not recognize modified LL37 (citrullinated and carbamylated). They thus represent tools to assess the presence of native, unmodified LL37 in body fluids by ELISA

The pro-healing effects of heparan sulfate and growth factors are enhanced by the heparinase enzyme: New association for skin wound healing treatment

: Effective treatment strategies for skin wound repair are the focus of numerous studies. New pharmacological approaches appear necessary to guarantee a correct and healthy tissue regeneration. For these reasons, we purposed to investigate the effects of the combination between heparan sulfate and growth factors further adding the heparinase enzyme. Interestingly, for the first time, we have found that this whole association retains a marked pro-healing activity when topically administered to the wound. In detail, this combination significantly enhances the motility and activation of the main cell populations involved in tissue regeneration (keratinocytes, fibroblasts and endothelial cells), compared with single agents administered without heparinase. Notably, using an experimental C57BL/6 mouse model of skin wounding, we observed that the topical treatment of skin lesions with heparan sulfate + growth factors + heparinase promotes the highest closure of wounds compared to each substance mixed with the other ones in all the possible combinations. Eosin/hematoxylin staining of skin biopsies revealed that treatment with the whole combination allows the formation of a well-structured matrix with numerous new vessels. Confocal analyses for vimentin, FAP1α, CK10 and CD31 have highlighted the presence of activated fibroblasts, differentiated keratinocytes and endothelial cells at the closed region of wounds. Our results encourage defining this combined treatment as a new and appealing therapy expedient in skin wound healing, as it is able to activate cell components and promote a dynamic lesions closure

RB139, RB140, RB141 and RB142 antibodies recognize human citrullinated LL37 by ELISA

LL37 is a natural antibiotic, active against bacteria and fungi and some viruses. Here we show that three monoclonal antibodies (RB139, RB141, and RB142) are exclusively specific for citrullinated LL37, whereas RB140 recognizes both native LL37 and cit-LL37. None recognizes LL37 modified by carbamylation. These antibodies can represent previously unavailable tools to detect the presence of citrullinated LL37 in body fluids by ELISA in the course of autoimmune and infectious diseases

Antigen-specific responses assessment for the evaluation of Bordetella pertussis T cell immunity in humans

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Heparin-Independent and Heparin-Dependent Anti-CXCL4 Antibodies Have a Reciprocal Expression in a Systemic Sclerosis Patients’ Cohort

Systemic sclerosis (SSc) is a chronic disease characterized by skin/internal organ fibrosis, vasculopathy and autoimmunity. Chemokine (C-X-C motif) ligand 4 (CXCL4) is an early SSc biomarker that predicts worse disease outcome. We previously reported that CXCL4 is an autoantigen in SSc, and anti-CXCL4 antibodies correlated with IFN-I and were more abundant in patients with lung fibrosis. However, it is unclear whether antibodies to CXCL4 in SSc are only directed to CXCL4 or recognize complexes formed by CXCL4 and heparin. Here, by analyzing an SSc cohort, we addressed the occurrence of circulating heparin-dependent VS heparin-independent anti-CXCL4 antibodies and their relationship with a few disease parameters. We found that heparin-dependent, like the heparin-independent antibodies, are higher in SSc as compared to healthy donors; they are detectable in 24% and 30% of the SSc patients, respectively, and appear inversely correlated and mutually exclusive. Like the heparin-independent antibodies, heparin-dependent antibodies correlated with digital ulcers. However, in contrast to heparin-independent antibodies, heparin-dependent antibodies did not correlate with IFN-I, but were largely expressed in patients with pulmonary arterial hypertension. This pilot study indicates that heparin-dependent antibodies are worth studying in larger SSc cohorts to address whether they discriminate SSc sub-groups with different pathological characteristics and outcomes

Generation of Monoclonal Antibodies Specific for Native LL37 and Citrullinated LL37 That Discriminate the Two LL37 Forms in the Skin and Circulation of Cutaneous/Systemic Lupus Erythematosus and Rheumatoid Arthritis Patients

Human cathelicidin LL37 is a cationic antimicrobial peptide active against bacteria and viruses and exerting immune modulatory functions. LL37 can be also a target of autoreactive B- and T-lymphocytes in autoimmune settings. Irreversible post-translational modifications, such as citrullination and carbamylation, mainly occurring at the level of cationic amino acids arginine and lysine, can affect the inflammatory properties and reduce antibacterial effects. Moreover, these modifications could be implicated in the rupture of immune tolerance to LL37 in chronic conditions such as psoriatic disease and cutaneous lupus (LE)/systemic lupus erythematosus (SLE). Here, we describe the generation and fine specificity of six recombinant antibodies (MRB137–MRB142), produced as a monovalent mouse antibody with the antigen-binding scFv portion fused to a mouse IgG2a Fc, and their ability to recognize either native or citrullinated LL37 (cit-LL37) and not cross-react to carbamylated LL37. By using these antibodies, we detected native LL37 or cit-LL37 in SLE and rheumatoid arthritis (RA) sera, and in LE skin, by ELISA and immunohistochemistry, respectively. Such antibodies represent previously unavailable and useful tools to address relationships between the presence of post-translational modified LL37 and the immune system status (in terms of innate/adaptive responses activation) and the clinical characteristics of patients affected by chronic immune-mediated diseases or infectious diseases