A comparison of myopia control in European children and adolescents with defocus incorporated multiple segments (DIMS) spectacles, atropine, and combined DIMS/atropine

PURPOSE: To evaluate the efficacy of a myopia control spectacle lens (DIMS) at slowing the progression of myopia in a population of European children in comparison with 0.01% atropine and combined DIMS and atropine. METHODS: The study was a non-randomised experimenter-masked prospective controlled observational study of individuals aged 6-18 years with progressing myopia but no ocular pathology. Participants were allocated, according to patient/parent choice, to receive 0.01% atropine eyedrops, DIMS (Hoya® MiyoSmart®) spectacles, combined atropine+DIMS or single vision spectacle lenses (control group). The key outcome variables, cycloplegic autorefraction spherical equivalent refraction (SER) and axial length (AL), were measured at baseline and after three, six, and 12 months. RESULTS: Of the 146 participants (mean age 10.3y ±3.2), 53 received atropine, 30 DIMS spectacles, 31 atropine+DIMS, and 32 single vision control spectacles. Generalized linear mixed model analysis revealed for SER, whilst controlling for age and SER at baseline, at each stage all treatment groups had significantly reduced progression compared with the control group (p<0.016). For AL, whilst controlling for baseline age and AL, at 6 and 12 months all treatment groups had significantly less progression than the control group (p<0.005). For SER only, in pairwise comparisons at 12 months the atropine+DIMS group had significantly reduced progression compared with the DIMS only and Atropine only groups (p<0.001). CONCLUSION: In a European population, DIMS and atropine are effective at reducing myopia progression and axial elongation in progressing myopia and are most successful at reducing myopia progression when used in combination

Co-firing of biomass and other wastes in fluidised bed systems

A project on co-firing in large-scale power plants burning coal is currently funded by the European Commission. It is called COPOWER. The project involves 10 organisations from 6 countries. The project involves combustion studies over the full spectrum of equipment size, ranging from small laboratory-scale reactors and pilot plants, to investigate fundamentals and operating parameters, to proving trials on a commercial power plant in Duisburg. The power plant uses a circulating fluidized bed boiler. The results to be obtained are to be compared as function of scale-up. There are two different coals, 3 types of biomass and 2 kinds of waste materials are to be used for blending with coal for co-firing tests. The baseline values are obtained during a campaign of one month at the power station and the results are used for comparison with those to be obtained in other units of various sizes. Future tests will be implemented with the objective to achieve improvement on baseline values. The fuels to be used are already characterized. There are ongoing studies to determine reactivities of fuels and chars produced from the fuels. Reactivities are determined not only for individual fuels but also for blends to be used. Presently pilot-scale combustion tests are also undertaken to study the effect of blending coal with different types of biomass and waste materials. The potential for synergy to improve combustion is investigated. Early results will be reported in the Conference. Simultaneously, studies to verify the availability of biomass and waste materials in Portugal, Turkey and Italy have been undertaken. Techno-economic barriers for the future use of biomass and other waste materials are identified. The potential of using these materials in coal fired power stations has been assessed. The conclusions will also be reported

Disease-Modifying Therapies and Coronavirus Disease 2019 Severity in Multiple Sclerosis

Objective: This study was undertaken to assess the impact of immunosuppressive and immunomodulatory therapies on the severity of coronavirus disease 2019 (COVID-19) in people with multiple sclerosis (PwMS). Methods: We retrospectively collected data of PwMS with suspected or confirmed COVID-19. All the patients had complete follow-up to death or recovery. Severe COVID-19 was defined by a 3-level variable: mild disease not requiring hospitalization versus pneumonia or hospitalization versus intensive care unit (ICU) admission or death. We evaluated baseline characteristics and MS therapies associated with severe COVID-19 by multivariate and propensity score (PS)-weighted ordinal logistic models. Sensitivity analyses were run to confirm the results. Results: Of 844 PwMS with suspected (n = 565) or confirmed (n = 279) COVID-19, 13 (1.54%) died; 11 of them were in a progressive MS phase, and 8 were without any therapy. Thirty-eight (4.5%) were admitted to an ICU; 99 (11.7%) had radiologically documented pneumonia; 96 (11.4%) were hospitalized. After adjusting for region, age, sex, progressive MS course, Expanded Disability Status Scale, disease duration, body mass index, comorbidities, and recent methylprednisolone use, therapy with an anti-CD20 agent (ocrelizumab or rituximab) was significantly associated (odds ratio [OR] = 2.37, 95% confidence interval [CI] = 1.18–4.74, p = 0.015) with increased risk of severe COVID-19. Recent use (&lt;1 month) of methylprednisolone was also associated with a worse outcome (OR = 5.24, 95% CI = 2.20–12.53, p = 0.001). Results were confirmed by the PS-weighted analysis and by all the sensitivity analyses. Interpretation: This study showed an acceptable level of safety of therapies with a broad array of mechanisms of action. However, some specific elements of risk emerged. These will need to be considered while the COVID-19 pandemic persists. ANN NEUROL 2021

Clinically relevant radioresistant rhabdomyosarcoma cell lines: Functional, molecular and immune-related characterization

Background: The probability of local tumor control after radiotherapy (RT) remains still miserably poor in pediatric rhabdomyosarcoma (RMS). Thus, understanding the molecular mechanisms responsible of tumor relapse is essential to identify personalized RT-based strategies. Contrary to what has been done so far, a correct characterization of cellular radioresistance should be performed comparing radioresistant and radiosensitive cells with the same isogenic background. Methods: Clinically relevant radioresistant (RR) embryonal (RD) and alveolar (RH30) RMS cell lines have been developed by irradiating them with clinical-like hypo-fractionated schedule. RMS-RR cells were compared to parental isogenic counterpart (RMS-PR) and studied following the radiobiological concept of the "6Rs", which stand for repair, redistribution, repopulation, reoxygenation, intrinsic radioresistance and radio-immuno-biology. Results: RMS-RR cell lines, characterized by a more aggressive and in vitro pro-metastatic phenotype, showed a higher ability to i) detoxify from reactive oxygen species; ii) repair DNA damage by differently activating non-homologous end joining and homologous recombination pathways; iii) counteract RT-induced G2/M cell cycle arrest by re-starting growth and repopulating after irradiation; iv) express cancer stem-like profile. Bioinformatic analyses, performed to assess the role of 41 cytokines after RT exposure and their network interactions, suggested TGF-β, MIF, CCL2, CXCL5, CXCL8 and CXCL12 as master regulators of cancer immune escape in RMS tumors. Conclusions: These results suggest that RMS could sustain intrinsic and acquire radioresistance by different mechanisms and indicate potential targets for future combined radiosensitizing strategies

COVID-19 Severity in Multiple Sclerosis: Putting Data Into Context

BACKGROUND AND OBJECTIVES: It is unclear how multiple sclerosis (MS) affects the severity of COVID-19. The aim of this study is to compare COVID-19-related outcomes collected in an Italian cohort of patients with MS with the outcomes expected in the age- and sex-matched Italian population. METHODS: Hospitalization, intensive care unit (ICU) admission, and death after COVID-19 diagnosis of 1,362 patients with MS were compared with the age- and sex-matched Italian population in a retrospective observational case-cohort study with population-based control. The observed vs the expected events were compared in the whole MS cohort and in different subgroups (higher risk: Expanded Disability Status Scale [EDSS] score &gt; 3 or at least 1 comorbidity, lower risk: EDSS score 64 3 and no comorbidities) by the \u3c72 test, and the risk excess was quantified by risk ratios (RRs). RESULTS: The risk of severe events was about twice the risk in the age- and sex-matched Italian population: RR = 2.12 for hospitalization (p &lt; 0.001), RR = 2.19 for ICU admission (p &lt; 0.001), and RR = 2.43 for death (p &lt; 0.001). The excess of risk was confined to the higher-risk group (n = 553). In lower-risk patients (n = 809), the rate of events was close to that of the Italian age- and sex-matched population (RR = 1.12 for hospitalization, RR = 1.52 for ICU admission, and RR = 1.19 for death). In the lower-risk group, an increased hospitalization risk was detected in patients on anti-CD20 (RR = 3.03, p = 0.005), whereas a decrease was detected in patients on interferon (0 observed vs 4 expected events, p = 0.04). DISCUSSION: Overall, the MS cohort had a risk of severe events that is twice the risk than the age- and sex-matched Italian population. This excess of risk is mainly explained by the EDSS score and comorbidities, whereas a residual increase of hospitalization risk was observed in patients on anti-CD20 therapies and a decrease in people on interferon

IRIS: methodological assessment of psychopathological disease in a cohort of hirsute women.

Hirsutism in females can be a source of considerable psychological distress and a threat to female identity. The aim of our study was to evaluate a possible relationship between facial, total body hair involvement and physical, mental and social well--being during 12 months of follow--up and treatment. Both objective and subjective methods of evaluating hirsutism were used: the Ferriman-Gallwey scoring method and the questionnaires GHQ--12, PCOSQ and SF--12. The total of 469 female patients (mean age 27.61±7.63 years) was enrolled in 27 Italian centres participating in this study. Higher total body score was correlated to significant emotional discomfort. The correlation between the FG total body score, the facial score and physical/mental health was found to be significant in all the patients assessed by SF--12 questionnaire. The ongoing reduction of GHQ--12 score was found for the facial FG score at the first follow--up (T0--T1 period) and at the second one (T0--T2). No relationship was found between T1 and T2. At both six (T1) and twelve months (T2) follow--up an increase of PCOSQ score (psychological improvement) was accompanied by a concomitant reduction of the FG score (reduction of hirsutism). Physical health assessed by SF--12 questionnaire does not change at both six and twelve months' follow--up, but mental health decreased at both T1 and T2. The clinical improvement was achieved at six months regardless on treatment used and it was maintained for the next six--month's follow--up. The clinical outcome could be assessed both by Ferriman--Gallwey score both through questionnaires administrated to each patient with hirsutism. For the evaluation of psychopathological discomfort the most appropriate questionnaire was GHQ--12, because of it major sensitivity to identify the psychological discomfort in the hirsutism

Breakthrough SARS-CoV-2 infections after COVID-19 mRNA vaccination in MS patients on disease modifying therapies during the Delta and the Omicron waves in Italy

Background In this study we aimed to monitor the risk of breakthrough SARS-CoV-2 infection in patients with MS (pwMS) under different DMTs and to identify correlates of reduced protection.Methods This is a prospective Italian multicenter cohort study, long-term clinical follow-up of the CovaXiMS (Covid-19 vaccine in Multiple Sclerosis) study. 1855 pwMS scheduled for SARS-CoV-2 mRNA vaccination were enrolled and followed up to a mean time of 10 months. The cumulative incidence of breakthrough Covid-19 cases in pwMS was calculated before and after December 2021, to separate the Delta from the Omicron waves and to account for the advent of the third vaccine dose.Findings 1705 pwMS received 2 m-RNA vaccine doses, 21/28 days apart. Of them, 1508 (88.5%) had blood assessment 4 weeks after the second vaccine dose and 1154/1266 (92%) received the third dose after a mean interval of 210 days (range 90-342 days) after the second dose. During follow-up, 131 breakthrough Covid-19 infections (33 during the Delta and 98 during the Omicron wave) were observed. The probability to be infected during the Delta wave was associated with SARS-CoV-2 antibody levels measured after 4 weeks from the second vaccine dose (HR=0.57, p &lt; 0.001); the protective role of antibodies was preserved over the whole follow up (HR=0.57, 95%CI=0.43-0.75, p &lt; 0.001), with a significant reduction (HR=1.40, 95%CI=1.01-1.94, p=0.04) for the Omicron cases. The third dose significantly reduced the risk of infection (HR=0.44, 95%CI=0.21-0.90,p=0.025) during the Omicron wave.Interpretation The risk of breakthrough SARS-CoV-2 infections is mainly associated with reduced levels of the virus-specific humoral immune response. Copyright (c) 2022 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/

Breakthrough SARS-CoV-2 infections in MS patients on disease-modifying therapies

Background: Patients with multiple sclerosis (pwMS) treated with anti-CD20 or fingolimod showed a reduced humoral response to SARS-CoV-2 vaccines. Objective: In this study we aimed to monitor the risk of breakthrough SARS-CoV-2 infection in pwMS on different disease-modifying therapies (DMTs). Methods: Data on the number of vaccinated patients and the number of patients with a breakthrough infection were retrospectively collected in 27 Italian MS centers. We estimated the rate of breakthrough infections and of infection requiring hospitalization per DMT. Results: 19,641 vaccinated pwMS were included in the database. After a median follow-up of 8 months, we observed 137 breakthrough infections. Compared with other DMTs, the rate of breakthrough infections was significantly higher on ocrelizumab (0.57% vs 2.00%, risk ratio (RR) = 3.55, 95% CI = 2.74-4.58, p &lt; 0.001) and fingolimod (0.58% vs 1.62%, RR = 2.65, 95% CI = 1.75-4.00, p &lt; 0.001), while there were no significant differences in any other DMT group. In the ocrelizumab group the hospitalization rate was 16.7% versus 19.4% in the pre-vaccination era (RR = 0.86, p = 0.74) and it was 3.9% in all the other DMT groups versus 11.9% in the pre-vaccination period (RR = 0.33, p = 0.02). Conclusions: The risk of breakthrough SARS-CoV-2 infections is higher in patients treated with ocrelizumab and fingolimod, and the rate of severe infections was significantly reduced in all the DMTs excluding ocrelizumab

Antibody response elicited by the SARS-CoV-2 vaccine booster in patients with multiple sclerosis: Who gains from it?

Background and purpose: Although two doses of COVID-19 vaccine elicited a protective humoral response in most persons with multiple sclerosis (pwMS), a significant group of them treated with immunosuppressive disease-modifying therapies (DMTs) showed less efficient responses. Methods: This prospective multicenter observational study evaluates differences in immune response after a third vaccine dose in pwMS. Results: Four hundred seventy-three pwMS were analyzed. Compared to untreated patients, there was a 50-fold decrease (95% confidence interval [CI] = 14.3–100.0, p &lt; 0.001) in serum SARS-CoV-2 antibody levels in those on rituximab, a 20-fold decrease (95% CI = 8.3–50.0, p &lt; 0.001) in those on ocrelizumab, and a 2.3-fold decrease (95% CI = 1.2–4.6, p = 0.015) in those on fingolimod. As compared to the antibody levels after the second vaccine dose, patients on the anti-CD20 drugs rituximab and ocrelizumab showed a 2.3-fold lower gain (95% CI = 1.4–3.8, p = 0.001), whereas those on fingolimod showed a 1.7-fold higher gain (95% CI = 1.1–2.7, p = 0.012), compared to patients treated with other DMTs. Conclusions: All pwMS increased their serum SARS-CoV-2 antibody levels after the third vaccine dose. The mean antibody values of patients treated with ocrelizumab/rituximab remained well below the empirical "protective threshold" for risk of infection identified in the CovaXiMS study (&gt;659 binding antibody units/mL), whereas for patients treated with fingolimod this value was significantly closer to the cutoff