Interleukin-17A (IL-17A): A silent amplifier of COVID-19

One of the hallmarks of COVID-19 is the cytokine storm that provokes primarily pneumonia followed by systemic inflammation. Emerging evidence has identified a potential link between elevated interleukin-17A (IL-17A) levels and disease severity and progression. Considering that per se, IL-17A can activate several inflammatory pathways, it is plausible to hypothesize an involvement of this cytokine in COVID-19 clinical outcomes. Thus, IL-17A could represent a marker of disease progression and/or a target to develop therapeutic strategies. This hypothesis paper aims to propose this "unique" cytokine as a silent amplifier of the COVID-19 immune response and (potentially) related therapy

IL-17A neutralizing antibody regulates monosodium urate crystal-induced gouty inflammation

Gout is a paradigm of acute, self-limiting inflammation caused by the deposition of monosodium urate (MSU) crystals within intra-and/or peri-articular areas, leading to excruciating pain, joint swelling and stiffness. The infiltration of leukocytes drives the inflammatory response and remains an attractive target for therapeutic intervention. In this context, emerging evidence supports the view that systemic differentiation of Th17 cells and their in situ infiltration as one of the potential mechanisms by which these cells, and their main product IL-17, causes damage to target tissues. To test if IL-17 was having a detrimental role in gouty onset and progression we targeted this cytokine, using a neutralizing antibody strategy, in an experimental model of gout. Joint inflammation was induced in CD-1 mice by the intra-articular (i.a.) administration of MSU crystals (200 μg/20 μl). Animals from IL-17Ab-treated groups received 1, 3 and 10 μg (i.a.) in 20 μl of neutralizing antibody after MSU crystals administration. Thereafter, joints were scored macroscopically, and knee joint oedema determined with a caliper. Histological analysis, myeloperoxidase assay and western blots analysis for COX-2/mPGEs-1/IL-17R pathway were conducted at 18 h (peak of inflammation) to evaluate leukocytes infiltration and activation, followed by the analysis, in situ, of pro/anti-inflammatory cytokines and chemokines. Flow cytometry was also used to evaluate the modulation of infiltrated inflammatory monocytes and systemic Th17 and Treg profile. Treatment with IL-17Ab revealed a dose-dependent reduction of joint inflammation scores with maximal inhibition at 10 μg. The neutralizing antibody was also able to significantly reduce leukocytes infiltration and MPO activity as well the expression of JE, IL-1α, IL-1β, IL-16, IL-17, C5a, BLC and, with a less extent IP-10, Rantes, KC, TIMP-1, SDF-1 and metalloproteinases in inflamed tissues. Biochemical analysis also revealed that IL-17Ab treatment modulated COX-2/mPGEs-1 pathway (and related PGE2 production) without interfering with IL-17R expression. Furthermore, flow cytometry analysis highlighted a selective modulation of infiltrating inflammatory monocytes (B220-/GR1hi-F480hi/CD115+) and circulating Th17, but not Treg, cells after IL-17Ab treatment. Collectively the results of this study report for the first time, that i.a. injection of MSU crystals stimulates in vivo production of Th17 cells and Th17-related inflammatory cyto-chemokines. In addition, we have demonstrated that the administration of a neutralizing antibody against IL-17 attenuates joint symptoms, swelling and leukocytes infiltration to the inflamed tissue, possibly providing a new strategy for the treatment of gouty inflammation and/or arthritis

One shoot seldinger central venous catheterization in dialyzed patients

Introduction: Central Venous Catheterization is necessary in uremic patient (before dialysis) and many other conditions. In this study we demonstrated the advantages of ultrasonography to perform the procedure. Materials and methods: 48 uremic patient were submitted to ultrasound-guided central venous catheterization. The procedure was performed following the Seldinger “one shot” technique. Results: The mean operative time was 4 minutes, with a high rate of success (100%) and a low percentage of complications (2%). Conclusion: The ultrasound-guided central venous catheterization is a safe procedure, rapid and easy to perform. The procedure has a low rate of failures and complications and a high rate of success. It is suitable in all patients with vascular anatomical variations, “difficult neck”, or coagulation disorders

Colorectal Cancer Stage at Diagnosis Before vs During the COVID-19 Pandemic in Italy

IMPORTANCE Delays in screening programs and the reluctance of patients to seek medical attention because of the outbreak of SARS-CoV-2 could be associated with the risk of more advanced colorectal cancers at diagnosis. OBJECTIVE To evaluate whether the SARS-CoV-2 pandemic was associated with more advanced oncologic stage and change in clinical presentation for patients with colorectal cancer. DESIGN, SETTING, AND PARTICIPANTS This retrospective, multicenter cohort study included all 17 938 adult patients who underwent surgery for colorectal cancer from March 1, 2020, to December 31, 2021 (pandemic period), and from January 1, 2018, to February 29, 2020 (prepandemic period), in 81 participating centers in Italy, including tertiary centers and community hospitals. Follow-up was 30 days from surgery. EXPOSURES Any type of surgical procedure for colorectal cancer, including explorative surgery, palliative procedures, and atypical or segmental resections. MAIN OUTCOMES AND MEASURES The primary outcome was advanced stage of colorectal cancer at diagnosis. Secondary outcomes were distant metastasis, T4 stage, aggressive biology (defined as cancer with at least 1 of the following characteristics: signet ring cells, mucinous tumor, budding, lymphovascular invasion, perineural invasion, and lymphangitis), stenotic lesion, emergency surgery, and palliative surgery. The independent association between the pandemic period and the outcomes was assessed using multivariate random-effects logistic regression, with hospital as the cluster variable. RESULTS A total of 17 938 patients (10 007 men [55.8%]; mean [SD] age, 70.6 [12.2] years) underwent surgery for colorectal cancer: 7796 (43.5%) during the pandemic period and 10 142 (56.5%) during the prepandemic period. Logistic regression indicated that the pandemic period was significantly associated with an increased rate of advanced-stage colorectal cancer (odds ratio [OR], 1.07; 95%CI, 1.01-1.13; P = .03), aggressive biology (OR, 1.32; 95%CI, 1.15-1.53; P < .001), and stenotic lesions (OR, 1.15; 95%CI, 1.01-1.31; P = .03). CONCLUSIONS AND RELEVANCE This cohort study suggests a significant association between the SARS-CoV-2 pandemic and the risk of a more advanced oncologic stage at diagnosis among patients undergoing surgery for colorectal cancer and might indicate a potential reduction of survival for these patients

Riflessioni sulla religione civile tra laicità e diritti

Riflessioni sulla religione civile tra laicità e diritt

La bioetica tra laicità e diritto

1. Per una definizione di bioetica e sue articolazioni 1. La bioetica è definita «come un sapere (teorico-applicativo), che riflette sui limiti di liceità e di illiceità degli interventi dell’uomo sulla vita, […], interventi resi possibili, […], dal progressivo sviluppo della scienza e della tecnologia in biologia e in medicina». È una disciplina che fa riferimento alla biologia e alla medicina ma che non può non tenere in considerazione la persona umana e i suoi diritti. Tra le diverse prosp..

Il declino della legge dinanzi all’ascesa del diritto giurisprudenziale: dalla verità legislativa a quella giurisprudenziale

The article makes a synthetic reconstruction of the current role of jurisprudence, becoming a creative source of law. We are faced with a state based on dynamic values, proper to an open society: the regulatory provisions are structured in such a way as to entrust the judge with the task of determining the actual regulatory meaning of the same.L’articolo opera una sintetica ricostruzione del ruolo attuale della giurisprudenza, divenendone fonte creativa del diritto. Siamo dinanzi ad uno Stato fondato su valori dinamici, propri di una società aperta: le disposizioni normative vengono strutturate in modo da affidare al giudice il compito di determinare l’effettivo significato normativo delle stesse

SECULARISM AND CIVIL RELIGION IN EUROPE

The place to be attributed to the phenomenon of religion in relation to secularism, has returned to the limelight in the debate on the preamble of the future European Constitution, involving the ‘person’, with his rights and his dignity. The reference to God is not present in any constitution of democratic countries because it can not and should not legitimize any State. This return of religion in the public sense, has been determined by three factors such as migration influx, globalization and terrorism