A multicentre, open-label, single-arm phase II trial of the efficacy and safety of sclerotherapy using 3% polidocanol foam to treat second-degree haemorrhoids (SCLEROFOAM)

Background: The aim of the present study was to evaluate the efficacy and safety of 3% polidocanol foam for treating 2nd-degree haemorrhoids. Methods: A multicentre, open-label, single-arm, phase 2 trial involving 10 tertiary referral centres for haemorrhodal disease (HD) was performed. Between January and June 2019, patients with 2nd-degree haemorrhoids were prospectively included in this study. The primary outcome was to establish the success rate after one sclerotherapy session in terms of complete resolution of bleeding episodes one week after the injection. The Hemorrhoidal Disease Symptom Score (HDSS), the Short Health Scale for HD (SHS-HD) score and the Vaizey incontinence score were used to assess symptoms and their impact on quality of life and continence. Pain after the procedure, subjective symptoms and the amount and type of painkillers used were recorded. Patients were followed up for 1 year. Results: There were 183 patients [111 males; 60.7%, mean age 51.3 ± 13.5 (18–75) years]. Complete resolution of bleeding was reached in 125/183 patients (68.3%) at 1 week and the recurrence rate was 12% (15/125). Thirteen patients (7.4%) underwent a second sclerotherapy session, while only 1 patient (1.8%) had to undergo a third session. The overall 1-year success rate was 95.6% (175/183). The HDSS and the SHS score significantly improved from a median preoperative value of 11 and 18 to 0 and 0, respectively (p < 0.001). There were 3 episodes of external thrombosis. No serious adverse events occurred. Conclusions: Sclerotherapy with 3% polidocanol foam is a safe, effective, painless, repeatable and low-cost procedure in patients with bleeding haemorrhoids

A multicentre, open-label, single-arm phase II trial of the efficacy and safety of sclerotherapy using 3% polidocanol foam to treat second-degree haemorrhoids (SCLEROFOAM)

Background The aim of the present study was to evaluate the efficacy and safety of 3% polidocanol foam for treating 2nd-degree haemorrhoids. Methods A multicentre, open-label, single-arm, phase 2 trial involving 10 tertiary referral centres for haemorrhodal disease (HD) was performed. Between January and June 2019, patients with 2nd-degree haemorrhoids were prospectively included in this study. The primary outcome was to establish the success rate after one sclerotherapy session in terms of complete resolution of bleeding episodes one week after the injection. The Hemorrhoidal Disease Symptom Score (HDSS), the Short Health Scale for HD (SHS-HD) score and the Vaizey incontinence score were used to assess symptoms and their impact on quality of life and continence. Pain after the procedure, subjective symptoms and the amount and type of painkillers used were recorded. Patients were followed up for 1 year. Results There were 183 patients [111 males; 60.7%, mean age 51.3 +/- 13.5 (18-75) years]. Complete resolution of bleeding was reached in 125/183 patients (68.3%) at 1 week and the recurrence rate was 12% (15/125). Thirteen patients (7.4%) underwent a second sclerotherapy session, while only 1 patient (1.8%) had to undergo a third session. The overall 1-year success rate was 95.6% (175/183). The HDSS and the SHS score significantly improved from a median preoperative value of 11 and 18 to 0 and 0, respectively (p < 0.001). There were 3 episodes of external thrombosis. No serious adverse events occurred. Conclusions Sclerotherapy with 3% polidocanol foam is a safe, effective, painless, repeatable and low-cost procedure in patients with bleeding haemorrhoids. © 2022, The Author(s)

A 12-month follow-up of the immune response to SARS-CoV-2 primary vaccination: evidence from a real-world study

A real-world population-based longitudinal study, aimed at determining the magnitude and duration of immunity induced by different types of vaccines against COVID-19, started in 2021 by enrolling a cohort of 2,497 individuals at time of their first vaccination. The study cohort included both healthy adults aged ≤65 years and elderly subjects aged >65 years with two or more co-morbidities. Here, patterns of anti-SARS-CoV-2 humoral and cell-mediated specific immune response, assessed on 1,182 remaining subjects, at 6 (T6) and 12 months (T12) after the first vaccine dose, are described. At T12 median anti-Spike IgG antibody levels were increased compared to T6. The determinants of increased anti-Spike IgG were the receipt of a third vaccine dose between T6 and T12 and being positive for anti-Nucleocapside IgG at T12, a marker of recent infection, while age had no significant effect. The capacity of T12 sera to neutralize in vitro the ancestral B strain and the Omicron BA.5 variant was assessed in a subgroup of vaccinated subjects. A correlation between anti-S IgG levels and sera neutralizing capacity was identified and higher neutralizing capacity was evident in healthy adults compared to frail elderly subjects and in those who were positive for anti-Nucleocapside IgG at T12. Remarkably, one third of T12 sera from anti-Nucleocapside IgG negative older individuals were unable to neutralize the BA.5 variant strain. Finally, the evaluation of T-cell mediated immunity showed that most analysed subjects, independently from age and comorbidity, displayed Spike-specific responses with a high degree of polyfunctionality, especially in the CD8 compartment. In conclusion, vaccinated subjects had high levels of circulating antibodies against SARS-CoV-2 Spike protein 12 months after the primary vaccination, which increased as compared to T6. The enhancing effect could be attributable to the administration of a third vaccine dose but also to the occurrence of breakthrough infection. Older individuals, especially those who were anti-Nucleocapside IgG negative, displayed an impaired capacity to neutralize the BA.5 variant strain. Spike specific T-cell responses, able to sustain immunity and maintain the ability to fight the infection, were present in most of older and younger subjects assayed at T1

Measurement of Epstein-Barr virus DNA load using a novel quantification standard containing two EBV DNA targets and SYBR Green I dye

<p>Abstract</p> <p>Background</p> <p>Reactivation of Epstein-Barr virus (EBV) infection may cause serious, life-threatening complications in immunocompromised individuals. EBV DNA is often detected in EBV-associated disease states, with viral load believed to be a reflection of virus activity. Two separate real-time quantitative polymerase chain reaction (QPCR) assays using SYBR Green I dye and a single quantification standard containing two EBV genes, Epstein-Barr nuclear antigen-1 (EBNA-1) and BamHI fragment H rightward open reading frame-1 (BHRF-1), were developed to detect and measure absolute EBV DNA load in patients with various EBV-associated diseases. EBV DNA loads and viral capsid antigen (VCA) IgG antibody titres were also quantified on a population sample.</p> <p>Results</p> <p>EBV DNA was measurable in ethylenediaminetetraacetic acid (EDTA) whole blood, peripheral blood mononuclear cells (PBMCs), plasma and cerebrospinal fluid (CSF) samples. EBV DNA loads were detectable from 8.0 × 10²to 1.3 × 10⁸copies/ml in post-transplant lymphoproliferative disease (n = 5), 1.5 × 10³to 2.0 × 10⁵copies/ml in infectious mononucleosis (n = 7), 7.5 × 10⁴to 1.1 × 10⁵copies/ml in EBV-associated haemophagocytic syndrome (n = 1), 2.0 × 10²to 5.6 × 10³copies/ml in HIV-infected patients (n = 12), and 2.0 × 10²to 9.1 × 10⁴copies/ml in the population sample (n = 218). EBNA-1 and BHRF-1 DNA were detected in 11.0% and 21.6% of the population sample respectively. There was a modest correlation between VCA IgG antibody titre and BHRF-1 DNA load (rho = 0.13, p = 0.05) but not EBNA-1 DNA load (rho = 0.11, p = 0.11).</p> <p>Conclusion</p> <p>Two sensitive and specific real-time PCR assays using SYBR Green I dye and a single quantification standard containing two EBV DNA targets, were developed for the detection and measurement of EBV DNA load in a variety of clinical samples. These assays have application in the investigation of EBV-related illnesses in immunocompromised individuals.</p

The geometry of nonlinear elasticity

Elasticity is the prototype of constitutive models in Continuum Mechanics. In the nonlinear range, the elastic model claims for a geometrically consistent physico-mathematical formulation providing also the logical premise for linearized approximations. A theoretic framework is envisaged here with the aim of contributing a conceptually clear, physically consistent, and computationally convenient formulation. A reasoning about the physics of the model, from a geometric point of view, leads to conceive constitutive relations as instantaneous incremental responses to a finite set of tensorial state variables and to their time rates along the space-time motion. Integrability of the tangent elastic compliance, existence of an elastic stress potential, and conservativeness of the elastic response, under the conservation of mass, are given a brand new treatment. Finite elastic strains have no physical interpretation in the new rate theory, and referential local placements are appealed to, just as loci for operations of linear calculus. Frame invariance is assessed with a consistent geometric treatment, and the clear distinction between the new notion and the property of isotropy is pointed out, thus overcoming the improper statement of material frame indifference. Extension of the theory to elasto-visco-plastic constitutive models is briefly addressed. Basic computational steps are described to illustrate feasibility and convenience of calculations according to the new theory of elasticity

Genesis and progress of virtual power principle

The virtual power principle (VPP) of continuum mechanics states a celebrated variational equality between external and internal virtual powers for any virtual velocity field conforming with linear kinematic constraints. The topic is here addressed to investigate how the original ideas born in the early XIX century are modelled by modern formulations based on Functional Analysis and Differential Geometry. These notions are able to provide an effective mathematical context for proving existence of Lagrange multipliers associated with the constraint of rigidity on velocity fields. The VPP stands as privileged tool for giving to stress fields a consistent definition based on duality with conforming virtual stretching fields. By complementarity, the VPP generates a variational condition for integrability of stretching fields, with self-equilibrated stresses as test fields. Progress is got by the formulation of the rate virtual power principle (RVPP) by time derivation of the VPP along the motion, with internal virtual power integrated per unit mass. The basic distinction between spatial and material fields according to the geometric paradigm is prompted to replace the one previously adopted in the literature. The need for a non-redundant implicit formulation of the rigidity constraint is emphasised to contrast degeneracy. This logical demand avoids proliferation of multipliers, in the spirit of Ockham’s Razor, a celebrated philosophical motto with multiform applications. The shining mathematical theory set out by Leonhard Euler, Jean-Baptiste Le Rond d’Alembert, Joseph Louis Lagrange, and Augustin Cauchy is in this respect a point of optimality. A geometric rate theory of elasticity meets the call for no-dissipation in push-closed elastic cycles, with non need of any finite strain elastic energy functional, thus leading to a proper statement of rate equilibrium problems, basilar for computational formulations and for investigations about instability phenomena and post-critical behaviours