Effectiveness and safety of filgotinib in rheumatoid arthritis: a real-life multicentre experience.

OBJECTIVES: We investigated the effectiveness and safety of filgotinib in a real-life multicentre cohort of rheumatoid arthritis (RA) patients. METHODS: RA patients were evaluated at baseline and after 12 and 24 weeks and were stratified based on previous treatments as biologic disease-modifying anti-rheumatic drug (bDMARD)-naive and bDMARD-insufficient responders (IR). Concomitant usage of methotrexate (MTX) and oral glucocorticoids (GC) was recorded. At each timepoint we recorded disease activity, laboratory parameters and adverse events. RESULTS: 126 patients were enrolled. 15.8% were bDMARD-naive (G0), while 84% were bDMARD-IR (G1). In G0, 45% of patients were in monotherapy (G2) and 55% were taken MTX (G3). In G1, 50% of patients were in monotherapy (G4) and 50% used MTX (G5).A significant reduction in all parameters at 12 weeks was observed; in the extension to 24 weeks the significant reduction was maintained for patient global assessment (PGA), examiner global assessment (EGA), visual analogue scale (VAS) pain, VAS fatigue, disease activity score (DAS)28- C-reactive protein (CRP) and CRP values. Filgotinib in monotherapy showed better outcomes in bDMARD-naive patients, with significant differences for patient reported outcomes (PROs) and DAS28-CRP. At 12 weeks, low disease activity (LDA) and remission were achieved in a percentage of 37.2 % and 10.7 % by simplified disease activity index (SDAI), 42.6 % and 5.7 % by clinical disease activity index (CDAI), 26.8 % and 25.2 % by DAS28-CRP, respectively. A significant decrease in steroid dose was evidenced in all patients. We observed a major adverse cardiovascular event in one patient and an increase in transaminase in another. No infections from Herpes Zoster were reported. CONCLUSIONS: Our real-world data confirm the effectiveness and safety of filgotinib in the management of RA, especially in bDMARD-naive patients.

Polybutylene Succinate Processing and Evaluation as a Micro Fibrous Graft for Tissue Engineering Applications.

A microfibrous tubular scaffold has been designed and fabricated by electrospinning using poly (1,4-butylene succinate) as biocompatible and biodegradable material. The scaffold morphology was optimized as a small diameter and micro-porous conduit, able to foster cell integration, adhesion, and growth while avoiding cell infiltration through the graft's wall. Scaffold morphology and mechanical properties were explored and compared to those of native conduits. Scaffolds were then seeded with adult normal human dermal fibroblasts to evaluate cytocompatibility in vitro. Haemolytic effect was evaluated upon incubation with diluted whole blood. The scaffold showed no delamination, and mechanical properties were in the physiological range for tubular conduits: elastic modulus (17.5 ± 1.6 MPa), ultimate tensile stress (3.95 ± 0.17 MPa), strain to failure (57 ± 4.5%) and suture retention force (2.65 ± 0.32 N). The shown degradation profile allows the graft to provide initial mechanical support and functionality while being colonized and then replaced by the host cells. This combination of features might represent a step toward future research on PBS as a biomaterial to produce scaffolds that provide structure and function over time and support host cell remodelling.

Antibody Response against Circulating Omicron Variants 8 Months after the Third Dose of mRNA Vaccine.

The COVID-19 wave is being recently propelled by BA.2 and, particularly, BA.5 lineages, showing clear transmission advantages over the previously circulating strains. In this study, neutralizing antibody responses against SARS-CoV-2 Wild-Type, BA.2 and BA.5 Omicron sublineages were evaluated among vaccinees, uninfected or infected with Omicron BA.1 strain, 8 months after the third dose of SARS-CoV-2 vaccine. The aim of this study was to compare the cross-protective humoral response to the currently circulating variant strains induced by vaccination, followed by Omicron infection in some subjects. Results showed a low antibody titer against all three variants in uninfected vaccinated subjects. On the other hand, vaccinated subjects, infected with BA.1 variant after receiving the third dose (about 40 days later), showed a strong response against both BA.2 and BA.5 strains, albeit with lower titers. This reinforces the concept that vaccination is fundamental to induce an adequate and protective immune response against SARS-CoV-2, but needs to be updated, in order to also widen the range of action towards emerging variants, phylogenetically distant from the Wuhan strain, against which the current formulation is targeted.

Omicron Infection Evokes Cross-Protection against SARS-CoV-2 Variants in Vaccinees.

Due to the rapid global spread of the Omicron (B.1.1.529) variant, efforts to scale up COVID-19 booster vaccination have been improved, especially in light of the increasing evidence of reduced neutralizing antibody (NT Ab) over time in vaccinated subjects. In this study, neutralizing antibody responses against the Wild-Type, Delta, and Omicron strains were evaluated among vaccinees, both infected with Omicron or uninfected, and non-vaccinated subjects infected with Omicron. The aim of the study was to compare the cross-protective humoral response to the variant strains induced by vaccination and/or Omicron infection. The results showed a significant difference in the neutralizing antibody response between the vaccinees and the Omicron-infected vaccinated subjects against the three tested strains (p < 0.001), confirming the booster effect of the Omicron infection in the vaccinees. By contrast, Omicron infection only did not enhance the antibody response to the other variants, indicating a lack of cross-protection. These results suggest the importance of updating the current formulation of the SARS-CoV-2 vaccine to protect people against the Omicron subvariants. A specific Omicron vaccine, administered as a booster for the previously adopted mRNA vaccines, may protect against a wider range of SARS-CoV-2 variants. However, it is unlikely that the Omicron vaccine alone would be able to protect non-vaccinated subjects against other circulating variants.

Improved Bone Regeneration Using Biodegradable Polybutylene Succinate Artificial Scaffold in a Rabbit Model.

The treatment of extensive bone loss represents a great challenge for orthopaedic and reconstructive surgery. Most of the time, those treatments consist of multiple-stage surgeries over a prolonged period, pose significant infectious risks and carry the possibility of rejection. In this study, we investigated if the use of a polybutylene succinate (PBS) micro-fibrillar scaffold may improve bone regeneration in these procedures. In an in vivo rabbit model, the healing of two calvarial bone defects was studied. One defect was left to heal spontaneously while the other was treated with a PBS scaffold. Computed tomography (CT) scans, histological and immunohistochemical analyses were performed at 4, 12 and 24 weeks. CT examination showed a significantly larger area of mineralised tissue in the treated defect. Histological examination confirmed a greater presence of active osteoblasts and mineralised tissue in the scaffold-treated defect, with no evidence of inflammatory infiltrates around it. Immunohistochemical analysis was positive for CD56 at the transition point between healthy bone and the fracture zone. This study demonstrates that the use of a PBS microfibrillar scaffold in critical bone defects on a rabbit model is a potentially effective technique to improve bone regeneration.

Antibody response to SARS-CoV-2 in infected patients with different clinical outcome.

Data regarding antibody responses to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in patients infected with COVID-19 are not yet available. In this study, we aimed to evaluate serum antibody responses in patients regardless of the outcome. We measured the circulating immunoglobulin G (IgG) antibody levels in 60 subjects with a certified history of SARS-CoV-2 infection by using immunoenzymatic, chemiluminescent, and Neutralization assays. Half patients had a severe infection, the other half were pauci-symptomatic. We analyzed their antibody response to see the trend of the humoral response. Our results showed a significant difference in circulating IgG level among the two groups. The neutralizing antibody response against SARS-CoV-2 was significantly higher among those who had severe disease. Furthermore, ten subjects from each group were screened twice, and a declining antibody trend was observed in pauci-symptomatic individuals. These findings provide evidence that humoral immunity against SARS-CoV-2 in pauci-symptomatic people is weak and may not be long-lasting. This may have implications for immunity strategy and prevention, since it is still not clear whether a time-dependent decrease of both circulating and neutralizing antibodies to nonprotective levels could occur in a longer time span and whether potential vaccines are able to induce a herd immunity and a durable response.

Association between cortisol levels and pain threshold in systemic sclerosis and major depression.

Pain perception and threshold show complex interactions with the inflammatory, psychiatric and neuroendocrine stimuli. This study aims to test whether lower serum cortisol levels are associated with lower pain thresholds and higher degree of depression in systemic sclerosis (SSc) and major depression with atypical features (MD-AF) patients compared to controls. 180 female subjects (SSc = 60, MD-AF = 60, healthy controls = 60) participated in this observational, cross-sectional, parallel group study. Pressure pain threshold (PPT) was assessed in three anatomical sites: nail bed (NB), metacarpophalangeal joint (MCP) and quadriceps muscle (QDR). Depressive symptoms were evaluated using the Beck Depression Inventory (BDI) scale and morning serum cortisol levels were collected. In SSc patients, quality of life was measured through the Health Assessment Questionnaire (HAQ-DI) and the scleroderma-specific visual analogue scales (scleroderma-VAS). Lower PPT scores (NB 4.42 ± 1.6; MCP 4.66 ± 1.4; QDR 4.79 ± 1.5) were observed in SSc patients compared to both MD-AF (NB 7.33 ± 2.2; MCP 6.01 ± 1.9; QDR 6.31 ± 1.6; p < 0.005) and controls (NB 9.57 ± 2; MCP 7.9 ± 2.1 and QDR 8.43 ± 2.1; p < 0.0001), while MD-AF patients had lower PPT scores compared to controls (p < 0.0001). SSc patients had also lower serum cortisol levels compared to MD-AF patients (8.78 vs 13.6 µg/dl; p < 0.05). A direct correlation was observed between serum cortisol and PPT scores both in SSc (r 2 for NB 0.29; for MCP 0.25; for QDR 0.27) and in MD-AF (r 2 for NB 0.34; for MCP 0.25; for QDR 0.47; p < 0.05), while depressive symptoms negatively correlated with serum cortisol (r 2 for NB 0.34; for MCP 0.17; for QDR 0.15) and in MD-AF (r 2 for NB 0.19; for MCP 0.31; for QDR 0.30; p < 0.05). Among SSc patients, those with serum cortisol levels below the normal range (n = 16) had higher BDI scores (15, 6-21 vs 9, 2-15; p < 0.005), lower PPTs (NB 4 ± 1.4 vs 4.9 ± 0.9; MCP 4.1 ± 0.8 vs 4.8 ± 0.9; QDR 4.1 ± 1.2 vs 5 ± 0.9; p < 0.005) and higher HAQ-DI (1.25, 0.25-2 vs 0.75, 0-1.25; p < 0.05) and scleroderma-VAS scores (VAS overall severity 7, 5.5-9.5 vs 4.5, 2.5-6; p < 0.05). The effect of cortisol serum levels upon pain mechanism, in chronic inflammatory conditions warrants longitudinal studies to detect treatable variations in pain thresholds, depressive symptoms and to improve quality of life.

Pulsed electromagnetic fields in knee osteoarthritis: a double blind, placebo-controlled, randomized clinical trial.

OBJECTIVES: This trial aimed to test the effectiveness of a wearable pulsed electromagnetic fields (PEMF) device in the management of pain in knee OA patients. METHODS: In this randomized [with equal randomization (1:1)], double-blind, placebo-controlled clinical trial, patients with radiographic evidence of knee OA and persistent pain higher than 40 mm on the visual analog scale (VAS) were recruited. The trial consisted of 12 h daily treatment for 1 month in 60 knee OA patients. The primary outcome measure was the reduction in pain intensity, assessed through VAS and WOMAC scores. Secondary outcomes included quality of life assessment through the 36-item Medical Outcomes Study Short-Form version 2 (SF-36 v2), pressure pain threshold (PPT) and changes in intake of NSAIDs/analgesics. RESULTS: Sixty-six patients were included, and 60 completed the study. After 1 month, PEMF induced a significant reduction in VAS pain and WOMAC scores compared with placebo. Additionally, pain tolerance, as expressed by PPT changes, and physical health improved in PEMF-treated patients. A mean treatment effect of -0.73 (95% CI - 1.24 to - 0.19) was seen in VAS score, while the effect size was -0.34 (95% CI - 0.85 to 0.17) for WOMAC score. Twenty-six per cent of patients in the PEMF group stopped NSAID/analgesic therapy. No adverse events were detected. CONCLUSION: These results suggest that PEMF therapy is effective for pain management in knee OA patients and also affects pain threshold and physical functioning. Future larger studies, including head-to-head studies comparing PEMF therapy with standard pharmacological approaches in OA, are warranted. TRIAL REGISTRATION: ClinicalTrials.gov, http://www.clinicaltrials.gov, NCT01877278.

Bone mineral density, bone turnover markers and fractures in patients with systemic sclerosis: a case control study.

OBJECTIVE: The aim of our study was to elucidate the pathophysiology of systemic sclerosis-related osteoporosis and the prevalence of vertebral fragility fracture in postmenopausal women with systemic sclerosis (SSc). METHODOLOGY: Fifty-four postmenopausal women with scleroderma and 54 postmenopausal controls matched for age, BMI, and smoking habits were studied. BMD was measured by dual energy-x-ray absorptiometry at spine and femur, and by ultrasonography at calcaneus The markers of bone turnover included serum osteocalcin and urinary deoxypyridinoline. All subjects had a spine X-ray to ascertain the presence of vertebral fractures. RESULTS: bone mineral density at lumbar spine (BMD 0.78±0.08 vs 0.88±0.07; p<0,001), femoral neck (BMD: 0.56±0.04 vs 0.72±0.07; p<0,001) and total femur (BMD: 0.57±0.04 vs 0.71±0.06; p<0,001) and ultrasound parameter at calcaneus (SI: 80.10±5.10 vs 94.80±6.10 p<0,001) were significantly lower in scleroderma compared with controls; bone turnover markers and parathyroid hormone level were significantly higher in scleroderma compared with controls, while serum of 25(OH)D3 was significantly lower. In scleroderma group the serum levels of 25(OH)D3 significantly correlated with PTH levels, BMD, stiffness index and bone turnover markers. One or more moderate or severe vertebral fractures were found in 13 patients with scleroderma, wherease in control group only one patient had a mild vertebral fracture. CONCLUSION: Our data shows, for the first time, that vertebral fractures are frequent in subjects with scleroderma, and suggest that lower levels of 25(OH)D3 may play a role in the risk of osteoporosis and vertebral fractures.

[A series of cases of sinonasal cancer among shoemakers and tannery workers]. / Analisi di una serie di casi di neoplasie maligne delle fosse nasali e dei seni accessori nel settore conciario e delle calzature.

A series of cases of sinunasal cancer has been observed among shoe-makers (11 cases) and tannery workers (8 cases) in the leather production area in Tuscany in the period 1990-2002. We stress the possible etiologic role of tannins both in leather and in wood industry.