Retroperitoneal fibrosis: a case of a patient (63y/o) treated with low-dose methotrexate (MTX) and 6-methylprednisolone (6-MP)

Retroperitoneal fibrosis (RPF), is a rare fibroinflammatory disease. The pathogenesis of RPF is still unclear and numerous theories have been reported such as environmental factors, immunologic process, genetic component, local inflammation and advanced atherosclerosis. RPF is characterized by the presence of a particular retroperitoneal fibrotic tissue which is white, woody and involving retroperitoneal structures such as the great vessels, ureters and psoas muscle. The main complication of RPF is the obstruction of local structures such as the ureters due to the fibrosis and the treatment of this aspect represents the main challenge for this pathology. RPF medical treatment consists of corticosteroids or/and immunosuppressive therapy. We report a case of a patient (63y/o) affected by idiopathic RPF treated with low-dose methotrexate (MTX) and 6-methylprednisolone (6-MP) for two years, describing and confirming the effectiveness and safety of a long-term low-dose MTX and 6-MP treatment

Echocardiography combined with cardiopulmonary exercise testing for the prediction of outcome in idiopathic pulmonary arterial hypertension

BACKGROUND: Right ventricular (RV) function is a major determinant of exercise intolerance and outcome in idiopathic pulmonary arterial hypertension (IPAH). The aim of the study was to evaluate the incremental prognostic value of echocardiography of the RV and cardiopulmonary exercise testing (CPET) on long-term prognosis in these patients. METHODS: One hundred-thirty treatment-naïve IPAH patients were enrolled and prospectively followed. Clinical worsening (CW) was defined by a reduction in 6-minute walk distance plus an increase in functional class, or non elective hospitalization for PAH, or death. Baseline evaluation included clinical, hemodynamic, echocardiographic and CPET variables. Cox regression modeling with c-statistic and bootstrapping validation methods were done. RESULTS: During a mean period of 528 ± 304 days, 54 patients experienced CW (53%). Among demographic, clinical and hemodynamic variables at catheterization, functional class and cardiac index were independent predictors of CW (Model-1). With addition of echocardiographic and CPET variables (Model-2), peak O2 pulse (peak VO2/heart rate) and RV fractional area change (RVFAC) independently improved the power of the prognostic model (AUC: 0.81 vs 0.66, respectively; p=0.005). Patients with low RVFAC and low O2 pulse (low RVFAC + low O2 pulse) and high RVFAC+low O2 pulse showed 99.8 and 29.4 increase in the hazard ratio, respectively (relative risk -RR- of 41.1 and 25.3, respectively), compared with high RVFAC+high O2 pulse (p=0.0001). CONCLUSIONS: Echocardiography combined with CPET provides relevant clinical and prognostic information. A combination of low RVFAC and low O2 pulse identifies patients at a particularly high risk of clinical deterioration

Italian immunization calendar implementation: Time to optimize number of vaccination appointments?

In the Italian vaccination schedule, at least six vaccination appointments are scheduled in the first year of life. This implies more discomfort for both the patient and the parents. This was particularly evident during the COVID-19 pandemic, during which several appointments were missed. A UK experience with three injectable vaccines and an oral one co-administered at the same appointment (4-in-1) at 2 and 4 months of age showed interesting results. The vaccination coverage was high, consistent with previous practice, and no relevant increase in adverse events was reported. Translating the UK experience into the Italian context would not be immediate, due to several organizational and social issues. Nevertheless, this option warrants some further considerations, which are discussed in this manuscript

New insight of human-IgH 3′regulatory regions in immunoglobulins switch

Background: Several studies in animal models have demonstrated the role of the 3′ Regulatory Region (3′RR) in the B cell maturation in mammals. In healthy humans, the concentration of each class of circulating immunoglobulins (Igs) has stable but different levels, due to several control mechanisms that also involve a duplicated version of the 3′RR on the chromosome 14 (chr14). The classes’ equilibrium can be altered during infections and in other pathological conditions. Material and methods: We studied the concentrations of IgA, IgM, IgG classes and IgG subclasses in a cohort of 1235 people having immunoglobulin concentrations within normal range to determine the presence of any correlation between the Igs serum concentrations, age and ratio among Ig classes and IgG subclasses in healthy humans. Furthermore, we assessed the concentrations of IgE and the allelic frequency of 3′RR1 hs1.2 enhancer in a group of 115 subjects with high levels of circulating IgE due to acute exacerbation of allergic asthma and in a control group of 118 healthy subjects. Results: In both children and adult subjects, the concentrations of the four IgG subclasses decreased from IgG1 to IgG4. Furthermore, the 3′RR1 enhancer hs1.2 alleles contribute to the control of the IgG subclasses levels, but it does not affect the IgE levels. Conclusion: The 3′RR1 controls IgG and IgE through different mechanisms, only in the IgG case involving the hs1.2 alleles. Thus, considering the IgH constant genes loci on the chromosome 14 and the multiple steps of switch that rearrange the whole region, we found that in humans the classes of Igs are modulated by mechanisms involving a complex interaction and transition between 3′RR1 and 3′RR2, also in physiological conditions

Ozone as adjuvant support in the treatment of covid-19: a preliminary report of probiozovid trial

This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1002/jmv.26636.Rationale: The evaluation of new therapeutic resources against COVID-19 represents a priority in clinical research considering the minimal options currently available. Objectives: To evaluate the adjuvant use of systemic oxygen-ozone administration in the early control of disease progression in patients with COVID-19 pneumonia. Methods: PROBIOZOVID is an ongoing, interventional, randomized, prospective, double-arm trial enrolling patient with COVID-19 pneumonia. From a total of 85 patients screened, 28 were recruited. Patients were randomly divided into ozone- autohemotherapy group (14) and control group (14). The procedure consisted in a daily double-treatment with systemic Oxygen-Ozone administration for 7 days. All patients were treated with ad interim best available therapy. Measurements and Main Results: The primary outcome was delta in the number of patients requiring orotracheal-intubation despite treatment. Secondary outcome was the difference of mortality between the two groups. Moreover, haematological parameters were compared before and after treatment. No differences in the characteristics between groups were observed at baseline. As a preliminary report we have observed that one patient for each group needed intubation and was transferred to ITU. No deaths were observed at 7-14 days of follow up. Thirty-day mortality was 8,3% for ozone group and 10% for controls. Ozone therapy didn’t significantly influence inflammation markers, haematology profile and lymphocyte subpopulations of patients treated. Ozone therapy had an impact on the need for the ventilatory support, although didn’t reach statistical significance. Finally, no adverse events related to the use of ozone-autohemotherapy were reported. Conclusions: Preliminary results, although not showing statistically significant benefits of ozone on COVID-19, did not report any toxicity

Vaccinazioni: stato dell\u2019arte, falsi miti e prospettive. Il ruolo chiave della prevenzione.

La pratica vaccinale in Italia \ue8 organizzativamente incardinata all\u2019interno del Servizio Sanitario Nazionale (SSN) e nei Servizi Sanitari Regionali (SSR). I luoghi \u201cclassici\u201d in cui viene effettuata la procedura/prestazione vaccinale sono i servizi di vaccinazione della Aziende Sanitarie Locali (ASL) o Provinciali (ASP) delle varie Regioni

Riociguat treatment in patients with chronic thromboembolic pulmonary hypertension: Final safety data from the EXPERT registry

Objective: The soluble guanylate cyclase stimulator riociguat is approved for the treatment of adult patients with pulmonary arterial hypertension (PAH) and inoperable or persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH) following Phase

Direct electrochemistry of membrane-entrapped horseradish peroxidase. Part II: Amperometric detection of hydrogen peroxide

Direct (unmediated) electrochemistry of horseradish peroxidase (HRP) immobilized within a polymeric film is investigated at a pyrolytic graphite electrode by de cyclic voltammetry, in the absence and in the presence of hydrogen peroxide. Under the latter condition. a reduction wave centered at approx. -280 mV (vs. SCE) is observed, the intensity of which is strictly dependent on the hydrogen peroxide concentration. This permits a voltammetric investigation of the electrocatalytic reduction of hydrogen peroxide. Flow and flow-injection measurements carried out at constant potential under the same conditions, support voltammetric data. The suitability of the immobilized HRP-based electrodic system to monitor the presence of important analytes, such as glucose or choline, in solution, is also discussed. To this issue, suitable amounts of HRP and glucose oxidase (or, in turn, choline oxidase) were simultaneously entrapped in the polymer. The results obtained are of potential value for basic and applied biochemistry and represent a first step for construction of a mediator-free (third-generation) biosensor which may find application in the biosensoristic area. (C) 1998 Elsevier Science S.A. All rights reserved

Direct electrochemistry of membrane-entrapped horseradish peroxidase. Part I. A voltammetric and spectroscopic study

This paper reports the electrochemical behaviour, relative to the Fe(III)-Fe(II) conversion, of horseradish peroxidase (HRP) entrapped within a solid matrix, at a pyrolytic graphite electrode. The results indicate that (i) immobilization enhances the electron exchange between the protein and the electrode surface; (ii) reversible electron transfer (eT) is achieved within a wide pH range (pH 3.0-12.0) even in the absence of mediators, (ii) the embedded protein shows native-like structural properties and increased stability. The results obtained may be of potential value, since they represent a first step for engineering a novel 'solid-state' electrode system, of importance for basic and applied biochemistry.This paper reports the electrochemical behaviour, relative to the Fe(III)-Fe(II) conversion, of horseradish peroxidase (HRP) entrapped within a solid matrix, at a pyrolytic graphite electrode. The results indicate that (i) immobilization enhances the electron exchange between the protein and the electrode surface; (ii) reversible electron transfer (eT) is achieved within a wide pH range (pH 3.0-12.0) even in the absence of mediators, (ii) the embedded protein shows native-like structural properties and increased stability. The results obtained may be of potential value, since they represent a first step for engineering a novel `solid-state' electrode system, of importance for basic and applied biochemistry

Direct electrochemical evidence for an equilibrium intermediate in the guanidine-induced unfolding of cytochrome c

This paper reports a voltammetric and spectroscopic investigation of the guanidine-induced unfolding of cytochrome c at neutral pH and 25 degrees C. Electrochemical data provide direct evidence for the presence of an equilibrium intermediate (form I) strictly dependent on the denaturant concentration. The midpoint potential of farm I has been determined (E(1/2) = +0.010 V vs. NHE) and its structural features defined rom analysis of the circular dichroism and absorbance spectroscopy data obtained under the same experimental conditions. From the correlation of electrochemical and spectroscopic data, we propose that the features detected by the intermediate conform to the molten globule state