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This report describes the restoration of the healed single implant in the posterior region by using a lithium disilicate crown supported by an Acuris abutment. The restored implants were placed in the premolar and molar region of both the mandible and the maxilla by using a 1-stage approach. The definitive Acuris abutment was placed after an implant healing period of at least 3 months. Definitive impressions were made at least 3 months after surgery. The precrystallized lithium disilicate crown was adapted to a laboratory abutment and evaluated. The crown was then crystallized, finished, colored, and cemented to the definitive abutment by using an adhesive resin cement. The definitive restoration engaged the abutment without the use of screws or cement. A single healed implant can be successfully restored by using a lithium disilicate restoration supported by an Acuris abutment.

Systemic sclerosis (SSc) is a connective tissue disease secondary to three cardinal pathological features: immune-system alterations, diffuse microangiopathy, and fibrosis involving the skin and internal organs. The etiology of SSc remains quite obscure; it may encompass multiple host genetic and environmental -infectious/chemical-factors. The present review focused on the potential role of environmental agents in the etiopathogenesis of SSc based on epidemiological, clinical, and laboratory investigations previously published in the world literature. Among infectious agents, some viruses that may persist and reactivate in infected individuals, namely human cytomegalovirus (HCMV), human herpesvirus-6 (HHV-6), and parvovirus B19 (B19V), and retroviruses have been proposed as potential causative agents of SSc. These viruses share a number of biological activities and consequent pathological alterations, such as endothelial dysfunction and/or fibroblast activation. Moreover, the acute worsening of pre-existing interstitial lung involvement observed in SSc patients with symptomatic SARS-CoV-2 infection might suggest a potential role of this virus in the overall disease outcome. A variety of chemical/occupational agents might be regarded as putative etiological factors of SSc. In this setting, the SSc complicating silica dust exposure represents one of the most promising models of study. Considering the complexity of SSc pathogenesis, none of suggested causative factors may explain the appearance of the whole SSc; it is likely that the disease is the result of a multifactorial and multistep pathogenetic process. A variable combination of potential etiological factors may modulate the appearance of different clinical phenotypes detectable in individual scleroderma patients. The in-deep investigations on the SSc etiopathogenesis may provide useful insights in the broad field of human diseases characterized by diffuse microangiopathy or altered fibrogenesis.

Purpose To evaluate the 2-year performance of definitive implant- or tooth-supported three-unit fixed dental prostheses made of zirconia-reinforced lithium silicate placed to restore premolars and molars in clinical cases of partial edentulism. Materials and methods All patients received a three-unit fixed restoration made of monolithic, hot-pressed, zirconia-reinforced lithium silicate glass-ceramic. The restoration was cemented to two natural teeth or attached to two 3.5- or 4.5-mm-diameter square threaded, grit-blasted, acid-etched integrated implants with a Morse taper connection. Peri-implant pocket depth and bone and soft tissue remodeling were recorded for 2 years at each follow-up visit. Esthetic, functional, and biologic United States Public Health Services (USPHS) parameters modified by the World Dental Federation study design were assessed yearly until the final follow-up appointment. At the time of placement of the definitive restorations and at the 2-year follow-up visit, the opposing dentitions were identified by type of restoration and supporting structures. Results A total of 100 patients were consecutively enrolled in the period between June 2016 and July 2017, and 50 patients each received an implant-supported restoration (Group A) or a tooth-supported restoration (Group B). One (2%) of the 50 implant-supported prostheses fractured after 21 months of function. None of the other prostheses failed or became loose or detached. No significant differences involving probing levels or bone and soft tissue remodeling were found between the follow-up times. No cases of inflammation or infection of the mucosal cuff around the neck of the implants were recorded. The most common issue occurred immediately after placement of the prosthesis, when 3 patients (6%) from Group A and 4 patients (8%) from Group B asked for a modification of tooth shade. Conclusion Implant-supported or tooth-supported three-unit fixed dental prostheses made of zirconia-reinforced lithium silicate can be used to successfully restore cases of posterior partial edentulism. The 2-year results of this report will be studied more in depth in ongoing long-term research.

Purpose To evaluate the performance of definitive, implant-supported, lithium disilicate fixed dental prostheses (LS2 FDPs) manufactured with a computer-assisted design/computer-assisted manufacturing (CAD/CAM) system. All patients received two-unit restorations placed in posterior regions, supported by osseointegrated implants with cone-in-cone connection abutments. Materials and methods Two implants (Ankylos) were placed into healed sites or fresh extraction sockets in the maxillary/mandibular posterior regions of partially edentulous patients. Definitive digital impressions were made 3 months after surgery. Twenty-four patients received fixed monolithic LS2 restorations manufactured with the CEREC system. All restorations were connected to the implants using cone-in-cone connection abutments. Peri-implant pocket depths were recorded for 2 years at each follow-up visit. Esthetic, functional, and biologic United States Public Health Services (USPHS) parameters modified by the FDI World Dental Federation study design were assessed yearly until the last follow-up appointment. The opposing dentitions were identified by type of restoration and supporting structures at the time of placement of the definitive restorations and at the 2-year follow-up visits. Results One patient (4.16%) moved to an unknown location during the study. A total of 23 FDPs (95.8%) supported by 46 implants reached the 2-year follow-up. None of the prostheses failed, or became loose or detached. No significant difference involving probing levels between the experimental times were found. Conclusions The results of this research indicated that the abutment-prostheses connection using a cone-in-cone approach was successful within the 2-year period of this study. None of the studied monolithic LS2 glass-ceramic prostheses milled using the CEREC CAD/CAM system fractured or became detached.

Systemic sclerosis (SSc) is an autoimmune disease characterized by vasculopathy, excessive extracellular matrix deposition, and fibrosis of the skin and internal organs. Several infectious agents, including human herpesvirus-6 (HHV-6), have been suggested as possible triggering factors, but a direct association is still missing. We characterized 26 SSc patients for the presence of HHV-6 in tissues and blood, the anti-HHV-6 response, HLA-G plasma levels, and KIR typing. Given the prominent role of endothelial cells (EC) in SSc pathogenesis, along with HHV-6 tropism for EC, we also investigated the expression of pro-fibrosis factors in HHV-6 infected EC. Results showed the presence of HHV-6A in skin biopsies, and an increased virus load was associated with disease severity and poor natural killer (NK) response against the virus, particularly in subjects exhibiting a KIR2 phenotype. HLA-G plasma levels were significantly higher in HHV-6A/B-KIR2 positive SSc patients and in vitro HHV-6A infection-induced pro-fibrosis factors expression in EC, supporting its role in the development of the fibrosing process. Our data suggest an association between virus infection/reactivation and disease, opening the way to future studies to understand the mechanisms by which HHV-6A might contribute to the multifactorial pathogenesis of SSc.

Background: Systemic Sclerosis (SSc) is a connective tissue disease, characterized by endothelial dysfunction and fibrosis, potentially affecting internal organs and reducing life expectancy. Digital ulcers (DUs), as well as hand and face skin thickening, are the hallmarks of the disease. These alterations lead to pain, functional impairment, aesthetic damages, and psychological distress. Autologous fat grafting (AFG) is a surgical technique used also to promote tissue regeneration. In the last decade, AFG has been successfully developed to treat clinical conditions characterized by skin atrophy or fibrosis. AFG composition of multipotent cells, carrying angiogenic, and immunogenic properties, may be able to restore the damaged tissues. Objectives: Evaluate our experience with AFG to treat and prevent damage and disability due to DUs and SSc skin complications. Methods: We analyzed 25 SSc patients, extrapolated from a larger series of 45 subjects, complaining about mouth and/or hand impairment, due to skin involvement, and, in some cases, long-lasting DUs (M/F 6/19, mean age 55.69±9.25-SD-years, mean disease duration 184.68±121.09-SD-months, L/D cutaneous subsets 21/4). Surgical procedures consisted in the injection of centrifuged and purified autologous fat, harvested from hips or abdomen. 2ml of fat were grafted in each of the 8 sites around the mouth, while 0.5 or 1 ml around the neurovascular bundle at the base of each finger. The study included: preoperative data collection; 2 or 3 surgical sessions at a distance of 6 months one from the other; data collection at 3 months after each surgical session; data collection at 3 and 6 months of follow up-FU after the last surgical procedure. Data collection consisted of clinic-serological SSc features and clinimetric measures about hand and mouth, if present DUs were assessed as well. Furthermore, patients were asked to fill in questionnaires in order to express their level of satisfaction with hand and mouth functionality. Results: Overall 63 surgical procedures were performed. After 1 to 3 procedures, patients reported an improvement of perioral skin tension (p=0.0238) and a reduced dry mouth feeling (p=0.0269). Similarly, patients stated an improvement of hands tension (p=0.0037). Furthermore, we observed a complete healing of DUs in 8/9 patients (p=0.0297). These positive clinical changes were mirrored by a subjective amelioration. In particular, pain decreased, evaluated by short-form McGill Pain Questionnaire (SF-MPQ), scrutinizing sensory (p=0.3340) and affective (p=0.2234) descriptors. The perception of disability improved too, showing an amelioration trend in Health Assessment Questionnaire-HAQ (p=0.4301) and Mouth Handicap in Systemic Sclerosis scale-MHISS- (p=0.9775). Conclusion: Our results confirm the potential efficacy of AFG to treat SSc skin complications and DUs. We reported an almost complete healing of DUs and a promising improvement of skin thickness and hardness both at hands and mouth, with good safety profiles. These clinical results were reflected by the subjective improvement of patients’ well-being. Population enlargement and extended FU is ongoing to identify more responsive SSc subsets. Long term results with soft tissue biopsies will give us further data to finally evaluate the efficacy of this approach that aims to improve the care and quality of life of our SSc patients. Disclosure of Interests: None declared

Objective This study evaluated Neem oil and Hypericum perforatum (Holoil®) for treatment of scleroderma skin ulcers related to calcinosis (SU-calc). Procedure: We retrospectively analyzed 21 consecutive systemic sclerosis (SSc) patients with a total of 33 SU-calcs treated daily with Holoil® cream compared with a control group of 20 patients with 26 SU-calcs. Holoil® was directly applied to skin lesions, while the control group received only standard medication. Results Application of Holoil® either resulted in crushing and complete resolution of calcium deposits or facilitated sharp excision of calcinosis during wound care sessions in 27/33 cases (81.8%). Complete healing of SU-calc occurred in 15/33 (45%) of cases within a time period of 40.1 ± 16.3 (mean ± SD) days, while 18/33 (55%) of lesions improved in terms of size, erythema, fibrin and calcium deposits. Patients reported a reduction of pain (mean numeric rating scale 7.3 ± 1.9 at baseline versus 2.9 ± 1.4 at follow-up) The control group had longer healing times and a higher percentage of infections. Conclusions The efficacy of local treatment with neem oil and Hypericum perforatum suggest that Holoil® could be a promising tool in the management of SSc SU-calc.

Parvovirus B19 (B19V) has been proposed as a triggering agent for some autoimmune diseases including systemic sclerosis (SSc). In this study, we investigated whether B19V infection in vitro differently activates inflammatory pathways, including those dependent on caspase-1 activation, in monocytes from patients with SSc and healthy controls. We showed that B19V can infect both THP-1 cells and primary monocytes but is not able to replicate in these cells. B19V infection increases the production of tumor necrosis factor-α and induces NLRP3-mediated caspase-1 activation in both THP-1 cells differentiated with phorbol 12-myristate 13-acetate and in monocytes from patients with SSc but not from healthy controls. B19V infection was sufficient for THP-1 to produce mature IL-1β. Monocytes from patients with SSc required an additional stimulus, here represented by lipopolysaccharides, to activate cytokine genes. Following B19V infection, however, lipopolysaccharide-activated monocytes from patients with SSc strongly increased the production of IL-1β and tumor necrosis factor-α. Altogether, these data suggest that viral components might potentiate the response to endogenous and/or exogenous toll-like receptor 4 ligands in monocytes from patients with SSc. The B19V-mediated activation of inflammatory pathways in monocytes might contribute to the disease progression and/or development of specific clinical phenotypes.

Human cytomegalovirus (HCMV) is a highly prevalent opportunistic agent in the world population, which persists as a latent virus after a primary infection. Besides the well-established role of this agent causing severe diseases in immunocompromised individuals, more recently, HCMV has been evoked as a possible factor contributing to the pathogenesis of autoimmune diseases such as systemic sclerosis (SSc). The interplay between HCMV and immune surveillance is supposed to become unbalanced in SSc patients with expanded anti-HCMV immune responses, which are likely involved in the exacerbation of inflammatory processes. In this study, blood samples from a cohort of SSc patients vs. healthy subjects were tested for anti-HCMV immune responses (IgM, IgG antibodies, and T cells to peptide pools spanning the most immunogenic HCMV proteins). Statistically significant increase of HCMV-specific CD8+ T cell responses in SSc patients vs. healthy subjects was observed. Moreover, significantly greater HCMV-specific CD8+ T cell responses were found in SSc patients with a longer disease duration and those with higher modified Rodnan skin scores. Given the known importance of T cells in the development of SSc and that this virus may contribute to chronic inflammatory diseases, these data support a relevant role of HCMV-specific CD8+ T cell responses in SSc pathogenesis.

Background Systemic sclerosis (SSc) is a chronic, multisystem connective tissue disease characterised by by immune dys-regulation, obliterative microvasculopathy and fibrosis. Endothelial dysfunction, immune system imbalance and fibroblast activation constitute the three major factors of the pathogenetic process. In this context, oxidative stress could play a significant role through direct damage of endothelial cells and the persistent activation of the immune system. 1,2 Objectives This study investigated the presence of advanced protein oxidation products (AOPP) in serum of patients with SSc and its correlation with disease’s features. Methods 50 patients with SSc (M:F 1:7, mean age 57.3±11.2 SD, mean duration of disease 10±9.1 SD years), were screened for AOPP in the serum, using the AOPP OxiSelect Kit of CELL BIOLABS (San Diego, Ca, USA). Among 50 SSc patients, 39 had limited cutaneous subset, while 11 had the diffuse one. Anamnestic and clinical data were collected for all SSc patients. As a control group 50 consecutive healthy subjects, sex and age matched, were recruited. Results We found serum levels of AOPP increased in the SSc group compared with the controls (p Conclusions Serum AOPP levels are significantly higher in patients with SSc than in controls. In addition, the correlations of AOPP with SSc diffuse cutaneous subset, digital ulcers, and pulmonary involvement (indicative of progressive disease and worse prognosis) suggest a possible role of this marker in the identification of the cases with worse clinical evolution. The data of this preliminary study should be confirmed on larger case series and analysed in prospective studies, in order to understand its eventual usefulness during the follow-up of SSc patients. References [1] Ferri C, Valentini G, Cozzi F, Sebastiani M, Michelassi C, La Montagna G, et al. Systemic Sclerosis: Demographic, Clinical, and Serologic Features and Survival in 1,012 Italian Patients. Medicine (Baltimore). 2002; 81:139–153 [2] Steen VD. The many faces of scleroderma. Rheum Dis Clin North Am. 2008; 34:1–15 Disclosure of Interest None declared

Background: Systemic sclerosis (SSc) is an autoimmune systemic disease characterized by diffuse fibrosis of skin and visceral organs due to different genetic, infectious, and/or environmental/occupational causative factors, including the inhalation of silica dust. Objectives: To investigate serum trace elements including silicon (s-Si) levels in SSc patients living in a restricted geographical area with high density of worksites with silica exposure hazard. Methods: This case-control study included 80 SSc patients (M:F 10:70; aged 58.4 ± 11.9SD years, mean disease duration 10.1 ± 7.8SD) and 50 age-/sex-matched healthy control subjects consecutively investigated at our University-based Rheumatology Unit. Patients and controls were evaluated for environmental/occupational exposure categories (structured questionnaire), morphological characterization of serum micro-/nanoparticles (Environmental Scanning Electron Microscopy and Energy Dispersive X-ray Spectroscopy microanalysis), and quantitative assessment of trace elements (inductively coupled plasma atomic emission spectroscopy). Results: Among various categories, only occupational exposure to silica dust was recorded in a significant proportion of SSc patients compared to controls (55% vs. 11%; p

BACKGROUND Mixed cryoglobulinemia (MC) is a rare multisystem disease whose aetiopathogenesis is not completely understood. Hepatitis C virus (HCV) infection may have a causative role, and genetic and/or environmental factors may also contribute. AIMS To investigate the presence and possible role of environmental agents in MC. METHODS We recruited 30 HCV-infected MC patients with different clinical manifestations and a control group of 30 healthy, sex-/age-matched volunteers. We collected serum samples from each patient and incubated at 4°C for 7 days to obtain cryoprecipitate samples. We used environmental scanning electron microscopy (ESEM) and energy dispersive X-ray spectroscopy microanalysis to verify the presence of microparticles (MPs) and nanoparticles (NPs) in serum and cryoprecipitate samples. We evaluated environmental exposure using a medical and occupational history questionnaire for each subject. RESULTS MC patients had a significantly higher risk of occupational exposure (OR 5.6; 95% CI 1.84-17.50) than controls. ESEM evaluation revealed a significantly higher concentration, expressed as number of positive spots (NS), of serum inorganic particles in MC patients compared with controls (mean NS 18, SD = 16 versus NS 5.4, SD = 5.1; P < 0.05). Cryoprecipitate samples of MC patients showed high concentrations of inorganic particles (mean NS 49, SD = 19). We found a strong correlation between NS and cryocrit (i.e. percentage of cryoprecipitate/total serum after centrifugation at 4°C) levels (P < 0.001). CONCLUSIONS In addition to HCV infection, MPs and NPs might play an important role in the aetiopathogenesis of MC.