P11.01: Fetal hemodynamic adaptations to maternal chronic low level carbon monoxide exposure

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Economic evaluation of a bioinductive implant for the repair of rotator cuff tears compared with standard surgery in Italy

Introduction: Rotator cuff tear (RCT) is a painful, progressive condition resulting from damage to the rotator cuff tendons and is the leading cause of shoulder-related disability. Surgical repair of rotator cuff is an established standard of care (SOC); however, failure of the procedure can occur. In this context, the use of collagen-based bioinductive implant REGENETEN showed long-term improvements in clinical scores. The aim of the study was to assess the cost-effectiveness of REGENETEN combined with SOC (SOC + REGENETEN) compared to SOC alone from both National Healthcare Service (NHS) and societal perspectives in Italy. Methods: A decision analytic model was developed to estimate the number of tears healed and costs for the two considered treatment strategies over 1 year. Clinical data were retrieved from the literature, and the clinical pathways for the management of patients with RCTs were retrieved from four key opinion leaders in Italy. Results: Over a 1-year time horizon, healed lesions were 90.70% and 72.90% for surgical repair of RCTs with and without REGENETEN, respectively. Considering the NHS perspective, mean costs per patient were €7828 and €4650 for the two strategies, respectively, leading to an incremental cost-effectiveness ratio (ICER) of €17,857 per healed tear. From the societal perspective, the mean costs per patient were €12,659 for SOC and €11,784 for REGENETEN, thus showing savings of €4918 per healed tear when the bioinductive implant is used. The sensitivity analyses confirmed the robustness of the model results. Conclusion: In the context of paucity of cost-effectiveness studies, our findings provide additional evidence for clinicians and payers regarding the value of a new treatment option that supports a tailored approach for the management of patients with RCTs

Socioeconomic impact of migraine in Italy: Results of a national survey

Background: Literature data indicate that migraine has a stronger impact on both healthcare consumption and quality of life (QoL) in women. Objectives: The objective of this article is to evaluate out-of-pocket (OoP) costs, productivity losses and cost of informal care of migraine in Italy, with a special focus on the detection of potential differences between male and female subjects. Methods: A cross-sectional study was conducted. Data were collected via a web-based survey platform, which included a socioeconomic questionnaire (five sections: clinical history; occupational status; informal assistance; visits, exams and treatments; and loss of productivity) and two questionnaires on QoL (EuroQol 5D 5L and Migraine-Specific Questionnaire, MSQ). Results: Six hundred and seven participants took part in the survey (average age of 42 years; female 70%). The duration of the attack (4-72 hours) was significantly much longer in women than in men (71% vs. 49%; p < 0.001). Seventy per cent of the sample reported to be employed. Lower income was associated with women (p < 0.001). Men received more informal assistance days than women (5.2 vs. 3.9 days; p = 0.007). The quarterly cost including OoP costs, informal assistance and lost productivity averaged €1,088 and was higher for men compared to women (€1,515 vs. €908; p < 0.001). The MSQ reported a significantly worse QoL for women. Conclusion: The results seemed to prove that migraine is a gender disease. Moreover, a potentially unequal access to informal assistance and healthcare resources not covered by the Italian National Health Service is highlighted for women because of their lower average income and purchasing power compared to men

Inhibition of β-catenin signalling in dermal fibroblasts enhances hair follicle regeneration during wound healing.

New hair follicles (HFs) do not form in adult mammalian skin unless epidermal Wnt signalling is activated genetically or within large wounds. To understand the postnatal loss of hair forming ability we monitored HF formation at small circular (2 mm) wound sites. At P2, new HFs formed in back skin, but HF formation was markedly decreased by P21. Neonatal tail also formed wound-associated HFs, albeit in smaller numbers. Postnatal loss of HF neogenesis did not correlate with wound closure rate but with a reduction in Lrig1-positive papillary fibroblasts in wounds. Comparative gene expression profiling of back and tail dermis at P1 and dorsal fibroblasts at P2 and P50 showed a correlation between loss of HF formation and decreased expression of genes associated with proliferation and Wnt/β-catenin activity. Between P2 and P50, fibroblast density declined throughout the dermis and clones of fibroblasts became more dispersed. This correlated with a decline in fibroblasts expressing a TOPGFP reporter of Wnt activation. Surprisingly, between P2 and P50 there was no difference in fibroblast proliferation at the wound site but Wnt signalling was highly upregulated in healing dermis of P21 compared with P2 mice. Postnatal β-catenin ablation in fibroblasts promoted HF regeneration in neonatal and adult mouse wounds, whereas β-catenin activation reduced HF regeneration in neonatal wounds. Our data support a model whereby postnatal loss of hair forming ability in wounds reflects elevated dermal Wnt/β-catenin activation in the wound bed, increasing the abundance of fibroblasts that are unable to induce HF formation

Mutant Lef1 controls Gata6 in sebaceous gland development and cancer

Mutations in Lef1 occur in human and mouse sebaceous gland (SG) tumors, but their contribution to carcinogenesis remains unclear. Since Gata6 controls lineage identity in SG, we investigated the link between these two transcription factors. Here, we show that Gata6 is a β-catenin-independent transcriptional target of mutant Lef1. During epidermal development, Gata6 is expressed in a subset of Sox9-positive Lef1-negative hair follicle progenitors that give rise to the upper SG Overexpression of Gata6 by in utero lentiviral injection is sufficient to induce ectopic sebaceous gland elements. In mice overexpressing mutant Lef1, Gata6 ablation increases the total number of skin tumors yet decreases the proportion of SG tumors. The increased tumor burden correlates with impaired DNA mismatch repair and decreased expression of Mlh1 and Msh2 genes, defects frequently observed in human sebaceous neoplasia. Gata6 specifically marks human SG tumors and also defines tumors with elements of sebaceous differentiation, including a subset of basal cell carcinomas. Our findings reveal that Gata6 controls sebaceous gland development and cancer

Predictors of Mortality and Cardiovascular Outcome at 6 Months after Hospitalization for COVID-19

Clinical outcome data of patients discharged after Coronavirus disease 2019 (COVID-19) are limited and no study has evaluated predictors of cardiovascular prognosis in this setting. Our aim was to assess short-term mortality and cardiovascular outcome after hospitalization for COVID-19. A prospective cohort of 296 consecutive patients discharged after COVID-19 from two Italian institutions during the first wave of the pandemic and followed up to 6 months was included. The primary endpoint was all-cause mortality. The co-primary endpoint was the incidence of the composite outcome of major adverse cardiac and cerebrovascular events (MACCE: cardiovascular death, myocardial infarction, stroke, pulmonary embolism, acute heart failure, or hospitalization for cardiovascular causes). The mean follow-up duration was 6 ± 2 months. The incidence of all-cause death was 4.7%. At multivariate analysis, age was the only independent predictor of mortality (aHR 1.08, 95% CI 1.01–1.16). MACCE occurred in 7.2% of patients. After adjustment, female sex (aHR 2.6, 95% CI 1.05–6.52), in-hospital acute heart failure during index hospitalization (aHR 3.45, 95% CI 1.19–10), and prevalent atrial fibrillation (aHR 3.05, 95% CI 1.13–8.24) significantly predicted the incident risk of MACCE. These findings may help to identify patients for whom a closer and more accurate surveillance after discharge for COVID-19 should be considered