2,227 research outputs found

    Updates on radiotherapy-immunotherapy combinations: Proceedings of 6th annual ImmunoRad conference.

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    Focal radiation therapy (RT) has attracted considerable attention as a combinatorial partner for immunotherapy (IT), largely reflecting a well-defined, predictable safety profile and at least some potential for immunostimulation. However, only a few RT-IT combinations have been tested successfully in patients with cancer, highlighting the urgent need for an improved understanding of the interaction between RT and IT in both preclinical and clinical scenarios. Every year since 2016, ImmunoRad gathers experts working at the interface between RT and IT to provide a forum for education and discussion, with the ultimate goal of fostering progress in the field at both preclinical and clinical levels. Here, we summarize the key concepts and findings presented at the Sixth Annual ImmunoRad conference

    The Italian Consensus Conference on FAI Syndrome in Athletes (Cotignola Agreement)

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    Background. Femoro-acetabular impingement (FAI) is an important topic in literature because of its strong relationship with sport populations. Methods. Sixty-five experts participated in “this Consensus Conference (CC)”. They discussed, voted and approved a consensus document on the FAI syndrome in athletes. Results. The CC experts approved document provided suggestions concerning: 1) Epidemiology of FAI; 2) Clinical evaluation; 3) Radiological evaluation; 4) Conservative treatment; 5) Surgical criteria; 6) Surgical techniques; 7) Post-surgical rehabilita-tion; 8) Outcome evaluation; 9) FAI-associated clinical frameworks. Conclusions. The CC offers a multidisciplinary approach to the diagnosis and treatment of FAI syndrome in athletes taking into account all the different steps needed to approach this pathology in sport populations

    A growth curve model to assess the effectiveness of a community-based intervention for the empowerment of Malian females in the decision to disclose (or not) their HIV status (ANRS-12373 Gundo-So)

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    International audienceBACKGROUND: In Mali, women living with HIV (WLHIV) who disclose their positive status are often confronted with stigma, violence, economic pressure, and social exclusion, including from family. We aimed to evaluate the effectiveness of an intervention for the empowerment of WLHIV on the decision to disclose or not their HIV-positive status, and associated factors.METHODS: ANRS-12373/Gundo-So (Chamber of Secrets in Bambara) was implemented in 6 community-based clinics in Mali in 2019/2020. The intervention consisted of 9 weekly sessions of peer-support for strengthening the capacity of WLHIV to manage the consequences concerning (non)disclosure of their HIV-positive status. Individual and psychosocial characteristics were collected at enrolment, pre- /post-intervention, then quarterly over 9 months. Effectiveness was evaluated using a scale measuring the psychological burden related to the sero-status secret from 0 (none) to 5 (very high). A growth curve model using Poisson distribution was estimated to investigate changes before(=0) and after the intervention(=1). Random-effects allowed controlling for unobserved/unobservable characteristics. This technique accounts for missing data and unequally spaced time points.RESULTS: Among 240 WLHIV enrolled, 222 (92.5%) and 146 (60.8%) responded to the pre-/post-intervention questionnaires respectively. Then, 139 (58.0%) continued follow-up at M3, and 136 (56.6%) at both M6 and M9. Analyses were carried out over the 1019 observations. At baseline, median age[IQR] was 33[28-39] years, 76.7% of participants did not have any education level/low-level. The psychological burden of sero-status secret was self-evaluated =1 by 50% of participants, whereas it was =4 for 23%. Estimations without confounders showed that the psychological burden decreased on average by 42% after the intervention (IRR:0.58, 95%CI[0.46-0.61]). Including covariates showed that the psychological burden decreases with age (IRR:0.98, 95%CI[0.97-0.99]), easy ARV uptake (IRR:0.81, 95%CI[0.68-0.97]), and absence of loneliness (IRR:0.83, 95%CI[0.71-0.96]). The intervention effectiveness persisted after including covariates. The psychological burden decreased of 44% after the intervention (IRR:0.56, 95%CI[0.48-0.65]).CONCLUSIONS: Our results have demonstrated that the Gundo-So intervention was effective for the empowerment of Malian WLHIV to reduce the psychological burden of HIV disclosure-related issues. Social and behavioral interventions adopting a community-based approach can effectively promote health outcomes among people confronted to sociocultural hostile environments such as Mali

    Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19

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    BackgroundWe previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15-20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in similar to 80% of cases.MethodsWe report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded.ResultsNo gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5-528.7, P=1.1x10(-4)) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR=3.70[95%CI 1.3-8.2], P=2.1x10(-4)). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR=19.65[95%CI 2.1-2635.4], P=3.4x10(-3)), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR=4.40[9%CI 2.3-8.4], P=7.7x10(-8)). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD]=43.3 [20.3] years) than the other patients (56.0 [17.3] years; P=1.68x10(-5)).ConclusionsRare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old

    Antibody responses to Influenza vaccination are diminished in patients with inflammatory bowel disease on infliximab or tofacitinib

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    BACKGROUND AND AIMS: We sought to determine whether six commonly used immunosuppressive regimens were associated with lower antibody responses after seasonal influenza vaccination in patients with IBD. METHODS: We conducted a prospective study including 213 IBD patients and 53 healthy controls; 165 who had received seasonal influenza vaccine and 101 who had not. IBD medications included infliximab, thiopurines, infliximab and thiopurine combination therapy, ustekinumab, vedolizumab or tofacitinib. The primary outcome was antibody responses against influenza/A H3N2 and A/H1N1, compared to controls, adjusting for age, prior vaccination and interval between vaccination and sampling. RESULTS: Lower antibody responses against influenza A/H3N2 were observed in patients on infliximab (Geometric Mean Ratio 0.35 [95% CI 0.20-0.60], p=0.0002), combination of infliximab and thiopurine therapy (0.46 [0.27-0.79], p=0.0050) and tofacitinib (0.28 [0.14-0.57], p=0.0005) compared to controls. Lower antibody responses against A/H1N1 were observed in patients on infliximab (0.29 [0.15-0.56], p=0.0003), combination of infliximab and thiopurine therapy (0.34 [0.17-0.66], p=0.0016), thiopurine monotherapy (0.46 [0.24-0.87], p=0.017) and tofacitinib (0.23 [0.10-0.56], p=0.0013). Ustekinumab and vedolizumab were not associated with reduced antibody responses against A/H3N2 or A/H1N1. Vaccination in the previous year was associated with higher antibody responses to A/H3N2. Vaccine-induced anti-SARS-CoV-2 antibody concentration weakly correlated with antibodies against H3N2 (r=0.27; p=0.0004) and H1N1 (r=0.33; p<0.0001). CONCLUSIONS: Vaccination in both the 2020-2021 and 2021-2022 seasons was associated with significantly higher antibody responses to influenza/A than no vaccination or vaccination in 2021-2022 alone. Infliximab and tofacitinib are associated with lower binding antibody responses to Influenza/A, similar to COVID-19 vaccine-induced antibody responses.Published version, accepted version (12 month embargo), submitted versionThe article is available via Open Access. Click on the 'Additional link' above to access the full-text

    Changes in preterm birth and stillbirth during COVID-19 lockdowns in 26 countries.

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    Preterm birth (PTB) is the leading cause of infant mortality worldwide. Changes in PTB rates, ranging from -90% to +30%, were reported in many countries following early COVID-19 pandemic response measures ('lockdowns'). It is unclear whether this variation reflects real differences in lockdown impacts, or perhaps differences in stillbirth rates and/or study designs. Here we present interrupted time series and meta-analyses using harmonized data from 52 million births in 26 countries, 18 of which had representative population-based data, with overall PTB rates ranging from 6% to 12% and stillbirth ranging from 2.5 to 10.5 per 1,000 births. We show small reductions in PTB in the first (odds ratio 0.96, 95% confidence interval 0.95-0.98, P value <0.0001), second (0.96, 0.92-0.99, 0.03) and third (0.97, 0.94-1.00, 0.09) months of lockdown, but not in the fourth month of lockdown (0.99, 0.96-1.01, 0.34), although there were some between-country differences after the first month. For high-income countries in this study, we did not observe an association between lockdown and stillbirths in the second (1.00, 0.88-1.14, 0.98), third (0.99, 0.88-1.12, 0.89) and fourth (1.01, 0.87-1.18, 0.86) months of lockdown, although we have imprecise estimates due to stillbirths being a relatively rare event. We did, however, find evidence of increased risk of stillbirth in the first month of lockdown in high-income countries (1.14, 1.02-1.29, 0.02) and, in Brazil, we found evidence for an association between lockdown and stillbirth in the second (1.09, 1.03-1.15, 0.002), third (1.10, 1.03-1.17, 0.003) and fourth (1.12, 1.05-1.19, <0.001) months of lockdown. With an estimated 14.8 million PTB annually worldwide, the modest reductions observed during early pandemic lockdowns translate into large numbers of PTB averted globally and warrant further research into causal pathways

    A growth curve model to assess the effectiveness of a community-based intervention for the empowerment of Malian females in the decision to disclose (or not) their HIV status (ANRS-12373 Gundo-So)

    No full text
    International audienceBACKGROUND: In Mali, women living with HIV (WLHIV) who disclose their positive status are often confronted with stigma, violence, economic pressure, and social exclusion, including from family. We aimed to evaluate the effectiveness of an intervention for the empowerment of WLHIV on the decision to disclose or not their HIV-positive status, and associated factors.METHODS: ANRS-12373/Gundo-So (Chamber of Secrets in Bambara) was implemented in 6 community-based clinics in Mali in 2019/2020. The intervention consisted of 9 weekly sessions of peer-support for strengthening the capacity of WLHIV to manage the consequences concerning (non)disclosure of their HIV-positive status. Individual and psychosocial characteristics were collected at enrolment, pre- /post-intervention, then quarterly over 9 months. Effectiveness was evaluated using a scale measuring the psychological burden related to the sero-status secret from 0 (none) to 5 (very high). A growth curve model using Poisson distribution was estimated to investigate changes before(=0) and after the intervention(=1). Random-effects allowed controlling for unobserved/unobservable characteristics. This technique accounts for missing data and unequally spaced time points.RESULTS: Among 240 WLHIV enrolled, 222 (92.5%) and 146 (60.8%) responded to the pre-/post-intervention questionnaires respectively. Then, 139 (58.0%) continued follow-up at M3, and 136 (56.6%) at both M6 and M9. Analyses were carried out over the 1019 observations. At baseline, median age[IQR] was 33[28-39] years, 76.7% of participants did not have any education level/low-level. The psychological burden of sero-status secret was self-evaluated =1 by 50% of participants, whereas it was =4 for 23%. Estimations without confounders showed that the psychological burden decreased on average by 42% after the intervention (IRR:0.58, 95%CI[0.46-0.61]). Including covariates showed that the psychological burden decreases with age (IRR:0.98, 95%CI[0.97-0.99]), easy ARV uptake (IRR:0.81, 95%CI[0.68-0.97]), and absence of loneliness (IRR:0.83, 95%CI[0.71-0.96]). The intervention effectiveness persisted after including covariates. The psychological burden decreased of 44% after the intervention (IRR:0.56, 95%CI[0.48-0.65]).CONCLUSIONS: Our results have demonstrated that the Gundo-So intervention was effective for the empowerment of Malian WLHIV to reduce the psychological burden of HIV disclosure-related issues. Social and behavioral interventions adopting a community-based approach can effectively promote health outcomes among people confronted to sociocultural hostile environments such as Mali

    Changes in preterm birth and stillbirth during COVID-19 lockdowns in 26 countries

    No full text
    Preterm birth (PTB) is the leading cause of infant mortality worldwide. Changes in PTB rates, ranging from -90% to +30%, were reported in many countries following early COVID-19 pandemic response measures ('lockdowns'). It is unclear whether this variation reflects real differences in lockdown impacts, or perhaps differences in stillbirth rates and/or study designs. Here we present interrupted time series and meta-analyses using harmonized data from 52 million births in 26 countries, 18 of which had representative population-based data, with overall PTB rates ranging from 6% to 12% and stillbirth ranging from 2.5 to 10.5 per 1,000 births. We show small reductions in PTB in the first (odds ratio 0.96, 95% confidence interval 0.95-0.98, P value <0.0001), second (0.96, 0.92-0.99, 0.03) and third (0.97, 0.94-1.00, 0.09) months of lockdown, but not in the fourth month of lockdown (0.99, 0.96-1.01, 0.34), although there were some between-country differences after the first month. For high-income countries in this study, we did not observe an association between lockdown and stillbirths in the second (1.00, 0.88-1.14, 0.98), third (0.99, 0.88-1.12, 0.89) and fourth (1.01, 0.87-1.18, 0.86) months of lockdown, although we have imprecise estimates due to stillbirths being a relatively rare event. We did, however, find evidence of increased risk of stillbirth in the first month of lockdown in high-income countries (1.14, 1.02-1.29, 0.02) and, in Brazil, we found evidence for an association between lockdown and stillbirth in the second (1.09, 1.03-1.15, 0.002), third (1.10, 1.03-1.17, 0.003) and fourth (1.12, 1.05-1.19, <0.001) months of lockdown. With an estimated 14.8 million PTB annually worldwide, the modest reductions observed during early pandemic lockdowns translate into large numbers of PTB averted globally and warrant further research into causal pathways
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