School of medicine, Alma mater studiorum, university of Bologna, 1999-2005
Orthopaedics and traumatology residency, Rizzoli orthopedic Institute, 2005-2011
Consultant Orthopaedic Surgeon, Rizzoli Orthopaedic Institute, Rizzoli Sicilia Department, 2011 to present
RESEARCH INTERESTS
Hip biomechanics, biomaterials, outcomes of total hip and total knee replacement, periprosthetic joint infections
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Scopus Publications
Scopus Publications
Timing Expression of miR203a-3p during OA Disease: Preliminary In Vitro Evidence Viviana Costa, Marcello De Fine, Lavinia Raimondi, Daniele Bellavia, Aurora Cordaro, et al. International Journal of Molecular Sciences, 2023 Osteoarthritis (OA) is a degenerative bone disease that involves the microenvironment and macroenvironment of joints. Progressive joint tissue degradation and loss of extracellular matrix elements, together with different grades of inflammation, are important hallmarks of OA disease. Therefore, the identification of specific biomarkers to distinguish the stages of disease becomes a primary necessity in clinical practice. To this aim, we investigated the role of miR203a-3p in OA progression starting from the evidence obtained by osteoblasts isolated from joint tissues of OA patients classified according to different Kellgren and Lawrence (KL) grading (KL ≤ 3 and KL > 3) and hMSCs treated with IL-1β. Through qRT-PCR analysis, it was found that osteoblasts (OBs) derived from the KL ≤ 3 group expressed high levels of miR203a-3p and low levels of ILs compared with those of OBs derived from the KL > 3 group. The stimulation with IL-1β improved the expression of miR203a-3p and the methylation of the IL-6 promoter gene, favoring an increase in relative protein expression. The gain and loss of function studies showed that the transfection with miR203a-3p inhibitor alone or in co-treatments with IL-1β was able to induce the expression of CX-43 and SP-1 and to modulate the expression of TAZ, in OBs derived from OA patients with KL ≤ 3 compared with KL > 3. These events, confirmed also by qRT-PCR analysis, Western blot, and ELISA assay performed on hMSCs stimulated with IL-1β, supported our hypothesis about the role of miR203a-3p in OA progression. The results suggested that during the early stage, miR203a-3p displayed a protective role reducing the inflammatory effects on CX-43, SP-1, and TAZ. During the OA progression the downregulation of miR203a-3p and consequently the upregulation of CX-43/SP-1 and TAZ expression improved the inflammatory response and the reorganization of the cytoskeleton. This role led to the subsequent stage of the disease, where the aberrant inflammatory and fibrotic responses determined the destruction of the joint.
The role of subscapularis repair following reverse shoulder arthroplasty: systematic review and meta-analysis M. De Fine, M. Sartori, G. Giavaresi, R. De Filippis, G. Agrò, et al. Archives of Orthopaedic and Trauma Surgery, 2022 Inadequate subscapularis repair has been advocated as one of the contributing factors for dislocation in reverse total shoulder arthroplasty; nonetheless the need to restore the subscapularis tendon integrity is under debate. The aim of this systematic review was to answer the question: does subscapularis reattachment following reverse total shoulder arthroplasty improve joint stability, range of motion and functional scores? The literature was systematically screened in accordance with PRISMA guidelines looking for papers evaluating clinical outcomes of reverse total shoulder arthroplasty in relation to the management of subscapularis tendon. Studies comparing clinical outcomes, complications and dislocation rate with or without subscapularis repair were included. Studies in which reverse total shoulder arthroplasty was performed for trauma or tumors were excluded. The methodology of included articles was scored with MINORS scale and the Risk of Bias was assessed adopting the ROBINS-I (Risk Of Bias In Non-randomized Studies of Interventions) developed by the Cochrane Group. A meta-analysis was also performed combining the studies to increase the sample size and hence the power to obtain meaningful data. The database search identified 1062 records, and 6 full-text articles were finally included. A total number of 1085 reverse total shoulder arthroplasty were assessed on. Except for one study, lateralized prosthetic designs have been used. Dislocation occurred in 0.8% (5/599 patients) of the patient with repaired subscapularis and in 1.6% (8/486 patients) of the tenotomized patients, and subscapularis repair was not associated with a higher risk of dislocation (pooled Peto OR: 0.496, 95% CI: 0.163 to 1.510, p = 0.217). Qualitative assessment revealed no differences in the range of motion and clinical scores. Subscapularis repair after reverse total shoulder arthroplasty produces no clinically meaningful benefits, particularly using lateralized prosthetic designs. Subscapularis re-attachment does not improve implant stability, nor increases range of motion or clinical scores. Given these results, keeping in mind the antagonistic effect of the repaired subscapularis on external rotation, no evidence lead to suggest subscapularis reattachment following reverse total shoulder arthroplasty with lateralized prosthetic designs.
How mir-31-5p and mir-33a-5p regulates sp1/cx43 expression in osteoarthritis disease: Preliminary insights Viviana Costa, Marcello De Fine, Valeria Carina, Alice Conigliaro, Lavinia Raimondi, et al. International Journal of Molecular Sciences, 2021 Osteoarthritis (OA) is a degenerative bone disease that involved micro and macro-environment of joints. To date, there are no radical curative treatments for OA and novel therapies are mandatory. Recent evidence suggests the role of miRNAs in OA progression. In our previous studies, we demonstrated the role of miR-31-5p and miR-33a families in different bone regeneration signaling. Here, we investigated the role of miR-31-5p and miR-33a-5p in OA progression. A different expression of miR-31-5p and miR-33a-5p into osteoblasts and chondrocytes isolated from joint tissues of OA patients classified in based on different Kellgren and Lawrence (KL) grading was highlighted; and through a bioinformatic approach the common miRNAs target Specificity proteins (Sp1) were identified. Sp1 regulates the expression of gap junction protein Connexin43 (Cx43), which in OA drives the modification of (i) osteoblasts and chondrocytes genes expression, (ii) joint inflammation cytokines releases and (iii) cell functions. Concerning this, thanks to gain and loss of function studies, the possible role of Sp1 as a modulator of CX43 expression through miR-31-5p and miR-33a-5p action was also evaluated. Finally, we hypothesize that both miRNAs cooperate to modulate the expression of SP1 in osteoblasts and chondrocytes and interfering, consequently, with CX43 expression, and they might be further investigated as new possible biomarkers for OA.
Pushing Ceramic-on-Ceramic in the most extreme wear conditions: A hip simulator study Marcello De Fine, Silvio Terrando, Martin Hintner, Alessandro Alan Porporati, Giovanni Pignatti Orthopaedics and Traumatology Surgery and Research, 2021 BACKGROUND Hip revision surgery for fractured ceramic components may represent the worst-case wear scenario due to the high risks of recurrent dislocations, instability, and third body wear. The ideal bearing choice for the new prosthetic articulation is still subject of debate, while alumina matrix composite (AMC) articulations offer theoretical superior performances; the present work was designed to test the wear behaviour of ceramic on ceramic articulations (liner and head) in a worst-case scenario by adding ceramic third-body particles to the test lubricant with combined walking and subluxation cycles in a hip joint simulator. Therefore, we performed an in vitro study aiming to assess how does AMC articulation perform with 1) third-body particles added to the test environment and 2) under subluxation stresses. HYPOTHESIS We hypothesised that AMC articulations offer superior performances in such worst conditions. MATERIALS AND METHODS A hip simulator test was designed to analyse how AMC articulation performs with third-body particles added to the test environment and under subluxation stresses. Two different load patterns including level walking and subluxation of the ceramic liner were applied. The test fluid lubricant was contaminated by adding coarse ceramic particles during the first 2 million cycles and fine ceramic particles from 2 to 4 million cycles. Group 1 consisted of an alumina matrix composite articulation (liner and head); group 2 consisted of an alumina liner and an alumina matrix composite head. A control group consisting of an alumina ceramic liner articulated against an alumina matrix composite head was provided and only axially loaded. The liners of groups 1 and 2 were tested at an in vivo angle of 45° in the medial lateral plane (inclinationangle), which corresponds to an angle L=30° relative to the ISO standard fixated position used for in vitro testing. All mass measurements were performed using a high precision balance (Sartorius BP211D). During each examination, images on dedicated location of the bearing surfaces were taken using a digital microscope. RESULTS Mean cumulative wear of 0.09mg per million cycles between 2 and 4 million cycles was detected in group 2, and this value was significantly lower (p=0.016) in comparison with the average value in group 1 (0.21mg per million cycle). This result can be explained in light of a possible transformation phase of zirconia in AMC liners, probably due to excessive stress during subluxation cycles. However, wear levels observed are close to the gravimetric measurement detection limit of the Sartorious Balance (about 0.1-0.2mg); therefore, wear can be considered negligible in all groups. CONCLUSION Our results confirm that AMC couplings perform very well even in the worst-case wear scenario. Since AMC articulations revealed 25% lower cumulative wear respect to AMC on cross linked polyethylene in same simulator setup, AMC articulations should be considered the bearing of choice in revision surgery in light of the high risk of recurrent dislocations, instability, and third body wear. LEVEL OF EVIDENCE III, prospective case-control study, in vitro.
The role of synovial fluid analysis in the detection of periprosthetic hip and knee infections: a systematic review and meta-analysis Marcello De Fine, Gianluca Giavaresi, Milena Fini, Andrea Illuminati, Silvio Terrando, et al. International Orthopaedics, 2018 IntroductionThis study tried to ascertain (1) the accuracy of synovial fluid white blood cell count and polymorphonucleate percentage in the diagnosis of periprosthetic hip and knee infections, (2) which test yielded superior test performance, and (3) the influence on diagnostic accuracy of study characteristics such as patient number, study design, study level, anatomic site, and threshold value.MethodsA systematic search was conducted including papers assessing more effective cutoffs for synovial fluid tests, having comparative design, evaluating an exclusive cohort of hip or knee prostheses, including a clear definition of infected cases, and reporting sufficient data for the calculation of true-positive, false-positive, false-negative, and true-negative.ResultsA total of 375 articles were collected and, given the inclusion criteria, ten manuscripts were included. These studies assessed 1155 hip prostheses (276 infected cases) and 1235 knee prostheses (401 infected cases). The specificity of synovial fluid white blood cell count was significantly increased by using the threshold value ≥ 3000 cell/μL (p = 0.006); the sensitivity of polymorphonucleate percentage was significantly higher in detecting knee infections (p = 0.034).DiscussionBoth tests had a high specificity and sensitivity in detecting periprosthetic joint infections, and no clear superiority of one over the other existed. Furthermore, cutoff and anatomic site significantly influenced synovial fluid white blood cell count and polymorphonucleate percentage, respectively.ConclusionSynovial fluid analysis is adequate in differentiating patients with periprosthetic hip and knee infections. Our data confirms international guidelines suggesting the use of 3000 cell/μL as cutoff threshold for synovial fluid white blood cell count. Since an anatomic site effect has been demonstrated, the goal of future studies will be to identify different cutoffs for hip and knee prostheses.
Saphenous nerve injury during hamstring tendons harvest: Does the incision matter? A systematic review A. Ruffilli, M. De Fine, F. Traina, F. Pilla, D. Fenga, et al. Knee Surgery Sports Traumatology Arthroscopy, 2017 PurposeInfrapatellar branch of saphenous nerve injury is a common complication following hamstring graft harvest during anterior cruciate ligament reconstruction. The direction of skin incision performed at proximal tibial metaphysis may affect the rate of iatrogenic nerve damage. Aim of the present systematic review was to evaluate evidence that would substantiate the adoption of one incision over another for hamstring graft harvesting.MethodsThe available literature was systematically screened searching studies dealing with iatrogenic injury to the saphenous nerve after anterior cruciate ligament reconstruction using hamstring tendons. A search was performed using the keywords “Saphenous” and “Infrapatellar branch” in combination with “Anterior cruciate ligament”, “arthroscopy” and “hamstrings”, supplying no limits regard the publication year. Coleman methodological score was performed in all the retained articles.ResultsFive articles matched the inclusion criteria. There were two randomized controlled trials, one prospective comparative study and two retrospective comparative series. Poor methodological quality was found overall. A vertical incision was found to significantly affect the presence of hypoesthesia and the extent of the area of sensory loss in three articles; no difference was registered in one, and a trend towards a lower rate of iatrogenic nerve damage using an oblique incision was found in the remaining one, without any statistical significance.ConclusionAlthough the low methodological quality of the analysed studies does not permit to draw definitive conclusions, the anatomical course of the nerve along with the results obtained in the available studies seems to suggest lower rate of neurological impairment adopting an oblique incision. This kind of incision may therefore be preferred in the routine clinical practice.Level of evidence Systematic review, Level II.
Effect of different postoperative flexion regimes on the outcomes of total knee arthroplasty: randomized controlled trial Marcello De Fine, Francesco Traina, Gianluca Giavaresi, Eugenio Leo, Ilaria Sanzarello, et al. Knee Surgery Sports Traumatology Arthroscopy, 2017 Purpose A consistent limb position strategy could be an attractive and easier alternative to reduce blood loss and increase range of motion following total knee arthroplasty. The aim of this study was to understand the proper amount of flexion required to improve functional outcomes with limited patients’ discomfort.MethodsEighty-five patients undergoing total knee arthroplasty were randomly assigned to receive mild (30° of knee flexion) or high-flexion protocol (70° of knee flexion), 48 h after surgery. The same daily rehabilitation scheme was followed. Total blood loss, hidden blood loss, haemoglobin and haematocrit levels, fixed flexion deformity, range of motion and limb circumference at the superior patellar pole were evaluated preoperatively and 7 days after surgery.ResultsDemographics, blood parameters and preoperative range of motion did not show any significant difference between the two groups. No complications were recorded in both groups. High-flexion group had greater rate of dropout due to excessive patients’ discomfort. A significantly lower Hb at day 1 was found in the high-flexion group. No differences were recorded regarding the remaining parameters.ConclusionNo significant differences were found between the high-flexion and mild-flexion protocols; however, mild-flexion protocol was better tolerated by patients. We therefore recommend a 30° flexion protocol to be routinely used 48 h postoperatively after total knee arthroplasty. This is an easy strategy to improve functional outcomes, which is a fundamental issue considering the steady increase in knee prostheses utilization.Level of evidenceRandomized controlled trial, Level II.
Is there a role for femoral offset restoration during total hip arthroplasty? A systematic review M. De Fine, M. Romagnoli, A. Toscano, A. Bondi, M. Nanni, et al. Revue De Chirurgie Orthopedique Et Traumatologique, 2017 Benefits of femoral offset restoration during total hip arthroplasty should be the reduction of bearing surfaces wear, implant loosening and dislocation rates. Modular neck stems ensure offset customization, but fretting corrosion and catastrophic failures are well-documented complications. Since clinical evidences are needed to substantiate the effectiveness of femoral offset restoration and promote modular neck choice, we systematically reviewed the literature to ascertain whether femoral offset itself has a proven clinical influence: (1) on bearing surfaces wear, (2) implant loosening and (3) dislocation rates. A systematic literature screening was conducted to find papers dealing with the influence of femoral offset on wear, dislocation and loosening, including articles with conventional radiographic femoral offset assessment and with comparative design. Observational studies, case reports, instructional course lectures, cadaveric and animal studies as well as biomechanical studies, letters to the editor, surgical techniques or technical notes were all excluded. No limits about publication date were supplied, but only papers in English were taken into account. Data were extracted into an anonymous spreadsheet. Offset values, dislocation rates, wear rates, follow-up and surgical approaches were all detailed. Ten manuscripts were finally selected. A statistically significant correlation between femoral offset restoration and the reduction of conventional ultra-high-molecular-weight polyethylene wear was found in two out of three papers investigating this issue, but no correlations were found between femoral offset and dislocation rates or implant loosening. Femoral offset modification influences ultra-high-molecular-weight polyethylene liners wear, but no correlation was found with dislocation rates or implant loosening. Advantages on wear can be counterbalanced by the use of hard bearing surfaces or highly cross linked polyethylene liners, besides the availability of larger femoral heads improving implant stability further reduces the importance of femoral offset restoration by means of modularity. We believe that efforts in restoring femoral offset during total hip arthroplasty do not translate into tangible clinical profits and consequently we do not advise the routinely usage of modular neck stems in total hip arthroplasty. Level of evidence: level III, systematic review of case-control studies.
Is there a role for femoral offset restoration during total hip arthroplasty? A systematic review M. De Fine, M. Romagnoli, A. Toscano, A. Bondi, M. Nanni, et al. Orthopaedics and Traumatology Surgery and Research, 2017 Benefits of femoral offset restoration during total hip arthroplasty should be the reduction of bearing surfaces wear, implant loosening and dislocation rates. Modular neck stems ensure offset customization but fretting corrosion and catastrophic failures are well-documented complications. Since clinical evidences are needed to substantiate the effectiveness of femoral offset restoration and promote modular neck choice, we systematically reviewed the literature to ascertain whether femoral offset itself has a proven clinical influence: (1) on bearing surfaces wear, (2) implant loosening, (3) and dislocation rates. A systematic literature screening was conducted to find papers dealing with the influence of femoral offset on wear, dislocation and loosening, including articles with conventional radiographic femoral offset assessment and with comparative design. Observational studies, case reports, instructional course lectures, cadaveric and animal studies as well as biomechanical studies, letters to the editor, surgical techniques or technical notes were all excluded. No limits about publication date were supplied but only papers in English were taken into account. Data were extracted into an anonymous spreadsheet. Offset values, dislocation rates, wear rates, follow-up and surgical approaches were all detailed. Ten manuscripts were finally selected. A statistically significant correlation between femoral offset restoration and the reduction of conventional ultrahigh-molecular-weight polyethylene wear was found in two out of three papers investigating this issue, but no correlations were found between femoral offset and dislocation rates or implant loosening. Femoral offset modification influences ultrahigh-molecular-weight polyethylene liners wear, but no correlation was found with dislocation rates or implant loosening. Advantages on wear can be counterbalanced by the use of hard bearing surfaces or highly cross-linked polyethylene liners, besides the availability of larger femoral heads improving implant stability further reduces the importance of femoral offset restoration by means of modularity. We believe that efforts in restoring femoral offset during total hip arthroplasty do not translate into tangible clinical profits and consequently, we do not advise the routinely usage of modular neck stems in total hip arthroplasty. LEVEL OF EVIDENCE level III, systematic review of case-control studies.
