Publications by authors named "Andrea Giorgini"

19 Publications

  • Page 1 of 1

Pediatric elbow arthroscopy: clinical outcomes and complications after long-term follow-up.

J Orthop Traumatol 2021 Dec 20;22(1):55. Epub 2021 Dec 20.

Department of Orthopaedic Surgery, Azienda Ospedaliero Universitaria Di Modena, University of Modena and Reggio Emilia, Modena, Italy.

Background: Elbow arthroscopy is becoming increasingly important for the treatment of a wide range of acute and chronic elbow pathologies. Even if elbow arthroscopy is technically demanding, in the pediatric population this minimally invasive technique is preferred by many surgeons for the treatment of pathologies such as osteochondritis dissecans (OCD), posttraumatic stiffness (PTS), or elbow posterior impingement (PI). The aim of this study is to evaluate outcomes and safety of elbow arthroscopy in the pediatric and adolescent population after long-term follow-up.

Materials And Methods: In this retrospective study, 26 patients younger than 18 years old undergoing elbow arthroscopy were evaluated. All surgeries were performed by a single senior surgeon. Patients were divided into three subgroups based on preoperative diagnosis: OCD, PTS, and PI. After at least 60 months follow-up, several outcome measures, including range of motion (ROM), Mayo Elbow Performance Score (MEPS), and visual analog scale (VAS) were evaluated in relation to preoperative values. The level of patient satisfaction on a five-level Likert scale, any limitation or change in sport activity, and the onset of any possible complications were also evaluated.

Results: In the study population, we found an improvement in ROM (flexion of 14.4 ± 13.6°, extension of 19.5 ± 13.9°, pronation of 5.8 ± 5.7°, and supination of 8.5 ± 11.6°) and in validated outcome measures (MEPS of 21.0 ± 13.5 points and VAS of 3.8 ± 2.2 points). The satisfaction rate was 4.5, with no dissatisfaction. Eighty-seven percent of patients fully recovered their performance levels, 9% changed sport, and 4% were unable to return to sport. We identified one major and one minor complication, with an overall complication rate of 7.7%. No neurovascular injuries were detected.

Conclusions: Elbow arthroscopy in a pediatric population can be considered an effective and safe procedure for selected pathologies when performed by an experienced surgeon. At long-term follow-up, we reported excellent clinical outcomes (both objective and subjective), with a relatively low complication rate without permanent injuries.

Level Of Evidence: Level IV-case series.
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http://dx.doi.org/10.1186/s10195-021-00619-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8688672PMC
December 2021

A Long-Term Follow-Up of Post-Operative Periprosthetic Humeral Fracture in Shoulder Arthroplasty.

Geriatr Orthop Surg Rehabil 2021 26;12:21514593211039908. Epub 2021 Sep 26.

Orthopaedic and Traumatology Department, University of Modena and Reggio Emilia, Modena, Italy.

Background: During the last decades, the growing number of shoulder replacement has increased the associated complications. Periprosthetic fractures have a low incidence but can be a severe clinical condition, especially in elderly population. There are still no guidelines to define the best treatment protocol for post-operative periprosthetic humeral fractures. Factors associated to these fractures and consequently the decision-making for the best treatment seem to be patient-related but also correlated with the type of implant. The aim of this study is to analyze the patient's risk factors, fracture pattern, implant type and treatment, evaluating the outcome with a long-term follow-up.

Methods: A retrospective study was performed on more than 2700 shoulder prostheses implanted over 10 years in two specialized centers, identifying 19 patients who underwent surgery for post-operative periprosthetic fracture. Gender, age, comorbidities, type of prosthetic implant, type of fracture, and cortical index of each patient were evaluated. All patients underwent surgery and were evaluated with a mean follow-up of 5 years with radiographic controls and functional assessment with the Constant-Murley score.

Results: Complete healing was achieved in 18 of 19 patients. All patients presented a lower Constant-Murley score than the pre-fracture score, there were no significant differences between prosthetic implants, and the cortical index was lower than the threshold level in more than 60% of cases.

Conclusion: The results of this study showed that a correct preoperative planning is essential to evaluate the type of implant and possible signs of stem mobilization. With a stable stem, it is preferable to maintain it and proceed to a synthesis. The decision process is more complex in periprosthetic fractures with a reduced cortical index, when some radiolucency lines are present in stems with high primary stability, because it is not always indicative of an unstable stem.

Level Of Evidence: Therapeutic III.
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http://dx.doi.org/10.1177/21514593211039908DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8477678PMC
September 2021

Microfragmented adipose tissue is associated with improved ex vivo performance linked to HOXB7 and b-FGF expression.

Stem Cell Res Ther 2021 08 28;12(1):481. Epub 2021 Aug 28.

Department of Medical and Surgical Sciences for Children and Adults, University-Hospital of Modena and Reggio Emilia, Modena, Italy.

Introduction: Adipose tissue (AT) has become a source of mesenchymal stromal/stem cells (MSC) for regenerative medicine applications, in particular skeletal disorders. Several enzymatic or mechanical procedures have been proposed to process AT with the aim to isolate cells that can be locally implanted. How AT is processed may impact its properties. Thus, we compared AT processed by centrifugation (C-AT) to microfragmentation (MF-AT). Focusing on MF-AT, we subsequently assessed the impact of synovial fluid (SF) alone on both MF-AT and isolated AT-MSC to better understand their cartilage repair mechanisms.

Materials And Methods: MF-AT and C-AT from the same donors were compared by histology and qRT-PCR immediately after isolation or as ex vivo cultures using a micro-tissue pellet system. The in vitro impact of SF on MF-AT and AT-MSC was assessed by histological staining and molecular analysis.

Results: The main AT histological features (i.e., increased extracellular matrix and cellularity) of the freshly isolated or ex vivo-cultured MF-AT persisted compared to C-AT, which rapidly deteriorated during culture. Based on our previous studies of HOX genes in MSC, we investigated the involvement of Homeobox Protein HOX-B7 (HOXB7) and its target basic Fibroblast Growth Factor (bFGF) in the molecular mechanism underlying the improved performance of MF-AT. Indeed, both these biomarkers were more prominent in freshly isolated MF-AT compared to C-AT. SF alone preserved the AT histological features of MF-AT, together with HOXB7 and bFGF expression. Increased cell performance was also observed in isolated AT-MSC after SF treatment concomitant with enhanced HOXB7 expression, although there was no apparent association with bFGF.

Conclusions: Our findings show that MF has a positive effect on the maintenance of AT histology and may trigger the expression of trophic factors that improve tissue repair by processed AT.
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http://dx.doi.org/10.1186/s13287-021-02540-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8399787PMC
August 2021

Supracondylar fractures in children: management and treatment.

Acta Biomed 2021 07 26;92(S3):e2021015. Epub 2021 Jul 26.

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Supracondylar humeral fractures are widely considered the most common elbow fracture in children. Gartland classification plays a fundamental role in decision-making regarding management and prognosis. Recent literature recommends conservative management for non or minimally displaced fractures, whereas there seems to be a trend towards surgical treatment for all displaced fractures. The preferred treatment for displaced Gartland II and Gartland III fractures is closed reduction and percutaneous fixation with lateral pins. In particular patterns medial pin is recommended for obtain a stable construct. Neurovascular complications are mostly associated with Type III fractures and sometimes surgical exploration with fracture reduction is needed. Correct diagnosis and proper management protocol is mandatory for avoid early and late complications such as neurovascular impairment and malunion.
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http://dx.doi.org/10.23750/abm.v92iS3.11725DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8420822PMC
July 2021

Computer-Assisted Surgery in Reverse Shoulder Arthroplasty: Early Experience.

Indian J Orthop 2021 Aug 27;55(4):1003-1008. Epub 2021 Jan 27.

Azienda Ospedaliero Universitaria Policlinico di Modena, via del Pozzo 71, Modena, Italy.

Background: In the last decade, new technologies have been applied to shoulder arthroplasty. The aim of this work was to show that navigated RSA allows the surgeon to reach the planned version/inclination in all cases. In this article are shown preliminary data, advantages, disadvantages and limits of the technique.

Methods: Eighteen computer-assisted reverse shoulder arthroplasty were performed. Preoperative glenoid version and inclination were evaluated with preoperative CT scan using Orthoblue (Exactech, Gainesville, FL,USA) software, as well as baseplate type, planned glenoid component seating, planned postoperative version, planned postoperative inclination, intraoperative glenoid version/inclination, screw length and surgical time. A senior shoulder surgeon has analyzed the advantages, disadvantages and limitation of this kind of surgery.

Results: Mean surgical time of the primary implants was 92 ± 12 min (min 75-max 110). Mean preoperative inclination was + 2.6° ± 6.4, mean preoperative version was - 7.6° ± 8.4. Mean planned postoperative inclination was - 2.7° ± 2.3, mean planned postoperative version was - 1.6° ± 2.9 and mean planned glenoid seating was 89% ± 8%. Planned settings were reached in all cases during surgery. Baseplate implanted were in nine cases 8° posterior augmented, in six cases standard and in three cases 10° superior augmented. Mean screw length was 33.5 mm ± 4.2 mm. No GPS system failure has been recorded. One coracoid fracture occurred during the first case.

Discussion: Intraoperative navigation system is a reliable and user-friendly technology that allows the surgeon to reach planned glenoid positioning during surgery. Furthermore, this technology will allow the surgeon to compare clinical outcomes to component positioning data. The lack of humeral implant navigation is the main limit of this technique.
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http://dx.doi.org/10.1007/s43465-020-00344-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8192603PMC
August 2021

The GLAD Lesion: are the definition, diagnosis and treatment up to date? A Systematic Review.

Acta Biomed 2020 12 30;91(14-S):e2020020. Epub 2020 Dec 30.

Orthopaedic Department, University of Modena and Reggio Emilia, 41124 Modena, Italy.

Introduction: Although GLAD lesions are quite common, only sporadic case reports describe surgical techniques and clinical outcomes. Even if cartilage defects can result from various pathogenic mechanisms, the resulting defect has some similarities with GLAD, and its management can be a starting point to treat both types of lesion. Aim of the present study is to find a commonly accepted definition for GLAD lesions in order to understand its pathogenesis, diagnosis and possible treatments.

Methods: A search of PubMed (MEDLINE) database has been performed in June 2020 to identify relevant articles including a combination of the following search terms: "GlenoLabral Articular Disruption" OR "GLAD" AND "shoulder" AND "cartilage, articular".

Results: Abstract evaluation included 31 articles in the full-text review. Various studies showed that the performance of MR arthrography in the detection of glenohumeral cartilage lesions, including GLAD lesions, was moderate. Different therapeutic solutions have been described. Arthroscopic debridement of the lesion and reattachment of the labrum have been often used. In case of large articular defects, the labrum could be advanced in the cartilage defect to cover it. In case of cartilage flap with reparable margins, this could be reattached with different suture constructs. Neglected GLAD lesions following a chronic trauma or shoulder instability have not been described in literature.

Conclusions: The definition of GLAD injury has changed over the time. Many authors associate this lesion with shoulder instability, with trauma in abduction and extra rotation, while Neviaser's original definition described stable shoulders following a trauma in adduction.
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http://dx.doi.org/10.23750/abm.v91i14-S.10987DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7944697PMC
December 2020

Surgical tips and tricks for coronal shear fractures of the elbow.

Arch Orthop Trauma Surg 2021 Feb 3;141(2):261-270. Epub 2020 Jun 3.

Orthopaedic and Traumatology Department, University of Modena and Reggio Emilia, Via del Pozzo 71, 41124, Modena, Italy.

Introduction: Coronal shear fractures of the distal humerus represent an uncommon lesion and could be burdened by high complications. This complex lesion requires an accurate reduction and surgical fixation for a better outcome. Different techniques have been described, however no standard protocol have been proposed. Purpose of this retrospective study, is to evaluate the clinical and radiological outcome with posterior cannulated self-tapping headless screws followed by an early-active-motion protocol and to outline the surgical tips and tricks for different fracture patterns.

Materials And Methods: From 2013 to 2019, a consecutive series of 24 patients with coronal shear fracture undergoing ORIF were included in the study. Fractures were classified according to Dubberley's classification. Cannulated self-tapping headless screws were used to fix the fragments. When necessary, additional cannulated half-threaded screws on the lateral edge of the humerus were used, as well as bone chips and fibrin sealant on severe comminution. All patients underwent an assisted early-active-motion rehabilitation protocol. Mean follow-up was 30 months; patients underwent standard X-rays and clinical outcome assessment with range of motion, Broberg and Morrey score and MEPI score.

Results: Surgical fixation with headless screw guaranteed complete healing of all shear fractures examined, no loss of reduction were reported. ROM assessment showed good results with an average arc of 113.1°. Excellent to good Broberg-Morrey and MEPI score were reported. No cases of avascular necrosis nor post-traumatic osteoarthritis resulted in our series. Complications occurred in 16.6% of the patients.

Conclusion: Coronal shear fracture represents a challenging injury to treat. Anatomical reduction and the use of cannulated self-tapping headless screws from posterior provide a stable fixation, high union rates and good elbow function, with a low cartilage damage and risks of necrosis over 2 years of follow-up.

Level Of Evidence: Therapeutic III.
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http://dx.doi.org/10.1007/s00402-020-03500-9DOI Listing
February 2021

Volar PEEK plate for distal radius fracture: analysis of adverse events.

Eur J Orthop Surg Traumatol 2020 Oct 20;30(7):1293-1298. Epub 2020 May 20.

Orthopaedic and Traumatology Department, Policlinic of Modena, University of Modena and Reggio Emilia, Via del Pozzo 71, 41124, Modena, Italy.

Background: The aim of the present retrospective study was to evaluate complications following carbon-fiber-reinforced polyetheretherketon (CFR-PEEK) volar plating in distal radius fracture in a large cohort of patients. As an alternative to conventional metallic devices, CFR-PEEK plates have been introduced over the last few years.

Methods: We performed a retrospective study including all patients who were treated for distal radius fracture using a volar fixed-angle plate DiPHOS-RM (Lima Corporate, Udine, Italy). All CFR-PEEK plates implanted were reviewed between May 2012 and December 2017. Plate removal, second surgery and adverse events were collected by reviewing medical records. A total of 110 patients were included with a mean follow-up of 4 years.

Results: Adverse side effects were observed in 9 cases (8%), developed during or after treatment. The most frequent complication was represented by intraoperative plate rupture (4%). Infection was reported in one case.

Discussion: The rate of complications of PEEK volar plates seems to be similar to those occurring with plates of different materials. Advantages of PEEK plates are the absence of the cold-welding phenomenon and the absence of exuberant bone callus on the plate, ensuring an easy hardware removal. Intraoperative rupture remains the main complication correlated with PEEK material. These complications can be reduced with an accurate surgical technique, especially at the beginning of the learning curve.

Level Of Evidence: Therapeutic IV.
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http://dx.doi.org/10.1007/s00590-020-02701-7DOI Listing
October 2020

Navigated, soft tissue-guided total knee arthroplasty restores the distal femoral joint line orientation in a modified mechanically aligned technique.

Knee Surg Sports Traumatol Arthrosc 2021 Mar 15;29(3):966-974. Epub 2020 May 15.

Department of Orthopaedic Surgery, Azienda Ospedaliero Universitaria Di Modena, University of Modena and Reggio-Emilia, Via del Pozzo, 71, 41124, Modena, Italy.

Purpose: To investigate the femoral component alignment in patients undergoing soft tissue-guided, navigated total knee arthroplasty (TKA). It was hypothesized that with a mechanically aligned tibial component, the soft tissues tensioned and symmetric medial and lateral gaps in flexion/extension, the femoral component would be aligned to the preoperative distal femoral joint line, as measured on knee radiographs.

Methods: Between 2015 and 2017, 77 patients (78 knees) underwent navigated soft tissue-guided TKA at a single centre. Pre and postoperative radiographs were collected and varus knees were taken into account. The tibial cut was performed with navigation in neutral alignment. The femoral cuts were adjusted based on tensioned soft tissues, aiming for equal medial and lateral gaps in flexion and extension. The Knee Injury and Osteoarthritis Outcome Score (KOOS) and Knee Society Score (KSS) were collected pre and postoperatively as a secondary outcome measure.

Results: A total of 58 TKAs on varus knees were assessed. On average, the femoral component was placed at 1.7° (SD 1.7) varus in the coronal plane. The comparison between the radiographic native distal femoral alignment and the orientation of the femoral component coronal cut demonstrated a statistically significant (p < 0.0001), linear inverse relationship (r = 0.5). Satisfactory knee function and excellent pain remission were demonstrated by KOOS and KSS scores at a mean of 2.8 years (SD 0.5) follow-up. One TKA was revised, resulting in a 98.3% survivorship at three years.

Conclusion: The proposed soft tissue-guided, navigated technique, aiming to preserve the integrity of the ligaments and a neutrally aligned tibial cut, provided a joint line respecting femoral coronal cut and encouraging short-term clinical results.

Level Of Evidence: III.
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http://dx.doi.org/10.1007/s00167-020-06056-8DOI Listing
March 2021

Mechanical alignment changes during flexion in total knee arthroplasty without affecting clinical outcomes.

Clin Biomech (Bristol, Avon) 2020 02 29;72:63-68. Epub 2019 Nov 29.

Policlinico di Modena, Department of Orthopaedic and Traumatology, Via del Pozzo 71, Modena, Italy. Electronic address:

Background: Primary aim of this study is to investigate if Hip-Knee-Ankle angle, measured in the coronal plane, changes with knee flexion after total knee arthroplasty. The secondary aim is to assess the relationship between Hip-Knee-Ankle during knee flexion and clinical outcome at mid-term follow up.

Methods: 334 computer assisted total knee arthroplasties were retrospectively evaluated. A total of 233 patients were available for assessment of clinical outcomes at last follow up (mean 35 months). Hip-Knee-Ankle angle at different degrees of knee flexion and components' alignment were recorded intraoperatively.

Findings: Patients were stratified based on the preoperative alignment: 202 varus knees, 99 neutral knees, and 33 valgus knees. In the varus knee group, 146 patients (89%) maintained a neutral overall limb alignment when flexed to 20°, 118 (72%) remained neutrally aligned at 45° and 92 (54%) at 90°. In valgus knee group, 26 (90%) remained neutrally aligned at 20°, 22 (75%) at 45° and 16 (55%) at 90°. In neutrally-aligned knee group, 88 (96%) remained neutrally aligned at 20°, 73 (79%) at 45° and 61 (66%) at 90°. Femoral component external rotation was correlated with varus alignment in flexion. Good outcomes were reported in 181 (78%) cases, fair results in 28 (12%) cases, poor results in 24 (10%) of cases. Poor results were not correlated to Hip-Knee-Ankle angle at different knee flexion angles.

Interpretation: This study demonstrates that intraoperative Hip-Knee-Ankle angle changes as the knee moves into deeper flexion. However, neutral Hip-Knee-Ankle through the range of motion does not correlate with superior outcomes.
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http://dx.doi.org/10.1016/j.clinbiomech.2019.11.026DOI Listing
February 2020

Isolated displaced type II partial articular radial head fracture: correlation of preoperative imaging with intraoperative findings of lateral ulnar collateral ligament tear.

J Shoulder Elbow Surg 2020 Jan 11;29(1):132-138. Epub 2019 Sep 11.

Orthopaedic and Trauma Unit, University of Modena and Reggio Emilia, Modena, Italy.

Background: The aim of this study was to determine the lateral ulnar collateral ligament (LUCL) injury associated with isolated radial head fracture (RHF) and the relationship of the ligament injury with the displacement of the fragment-loss of contact-in unstable displaced partial articular RHF in individuals without any history of ulnohumeral dislocation.

Methods: We retrospectively identified 131 consecutive patients who underwent open reduction and internal fixation of isolated closed Mason type II RHF performed at our institution. We identified 3 subsets by the pattern of RHF and the position of the unstable fragment (anterior or posterior) relative to the capitulum humeri: displaced stable (group I), displaced anterior unstable (group II), and displaced posterior unstable (group III). Standard radiographs were obtained preoperatively and postoperatively. The pattern of lateral collateral ligament avulsion and its distribution were inferred from intraoperative records.

Results: Preoperative radiographs of the 131 patients showed 101 nonseparated fractures (77%, group I) and 30 unstable fractures (23%). Anterior displacement of the fragment was found in 18 elbows (14%, group II) and posterior displacement in 12 (9%, group III). LUCL avulsion was found in 18 of 30 unstable RHFs (60%) and in 1 of 60 stable RHFs (1.6%).

Conclusion: RHF is a complex fracture often associated with soft tissue lesions. It is important to determine which structures need to be repaired to avoid complications that could lead to elbow instability. The RHF pattern and classification as stable or unstable can help the surgeon in the identification and treatment of LUCL lesions.
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http://dx.doi.org/10.1016/j.jse.2019.07.006DOI Listing
January 2020

Volar PEEK plate for distal radial fracture: analysis of plate ruptures in a group of 120 patients.

J Hand Surg Eur Vol 2019 11 31;44(9):983-984. Epub 2019 Jul 31.

Orthopaedic and Traumatology Department, University of Modena and Reggio Emilia, Modena, Italy.

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http://dx.doi.org/10.1177/1753193419865124DOI Listing
November 2019

Changes in total knee arthroplasty design affect in-vivo kinematics in a redesigned total knee system: A fluoroscopy study.

Clin Biomech (Bristol, Avon) 2018 05 20;54:92-102. Epub 2018 Mar 20.

Department of Orthopaedic Surgery, Azienda Ospedaliero Universitaria di Modena, University of Modena and Reggio Emilia, Via del Pozzo, 71, 41124 Modena, Italy.

Background: Journey II Bi-Cruciate-Stabilized knee system was designed to overcome the complications of Journey Bi-Cruciate-Stabilized, including ilio-tibial band inflammation and episodes of dislocation. The purpose of this study was to assess differences in knee kinematics between the first and second-generation design by means of video-fluoroscopy. Re-designed prosthesis in-vivo kinematics was analyzed during activities of daily living and results were eventually compared with those of the previous system, as reported in a previously published study. It was hypothesized that changes in components' design influences replaced knee's kinematic patterns.

Methods: Sixteen patients (3 males, 13 females) implanted with the redesigned prosthesis were assessed by video-fluoroscopy during stair-climbing, chair-rising and leg-extension at 8 months of follow-up. Patterns of axial rotation and antero-posterior motion of the medial and lateral femoral condyles were obtained. Range of Motion and International Knee Society Score were recorded pre- and post-operatively. Student t-tests were applied to compare the mean of each interesting variables.

Findings: The comparison of the kinematics of the two designs revealed similar patterns of axial rotation, with progressive femoral external rotation in flexion and reduced absolute values of displacement for the new system. Reduced posterior displacements of the medial and lateral condyles were observed in Journey II patients. In terms of absolute location, the lateral condyle in the redesigned prosthesis showed a more anterior position on the tibial-baseplate embedded coordinate system at maximal flexion.

Interpretation: Design changes in the recently-introduced total knee system contributed to modify its in-vivo knee kinematics as demonstrated by video-fluoroscopy.
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http://dx.doi.org/10.1016/j.clinbiomech.2018.03.014DOI Listing
May 2018

Potency Biomarker Signature Genes from Multiparametric Osteogenesis Assays: Will cGMP Human Bone Marrow Mesenchymal Stromal Cells Make Bone?

PLoS One 2016 6;11(10):e0163629. Epub 2016 Oct 6.

Department of Medical and Surgical Sciences for Children & Adults, University Hospital of Modena and Reggio Emilia, Modena, Italia.

In skeletal regeneration approaches using human bone marrow derived mesenchymal stromal cells (hBM-MSC), functional evaluation before implantation has traditionally used biomarkers identified using fetal bovine serum-based osteogenic induction media and time courses of at least two weeks. However, emerging pre-clinical evidence indicates donor-dependent discrepancies between these ex vivo measurements and the ability to form bone, calling for improved tests. Therefore, we adopted a multiparametric approach aiming to generate an osteogenic potency assay with improved correlation. hBM-MSC populations from six donors, each expanded under clinical-grade (cGMP) conditions, showed heterogeneity for ex vivo growth response, mineralization and bone-forming ability in a murine xenograft assay. A subset of literature-based biomarker genes was reproducibly upregulated to a significant extent across all populations as cells responded to two different osteogenic induction media. These 12 biomarkers were also measurable in a one-week assay, befitting clinical cell expansion time frames and cGMP growth conditions. They were selected for further challenge using a combinatorial approach aimed at determining ex vivo and in vivo consistency. We identified five globally relevant osteogenic signature genes, notably TGF-ß1 pathway interactors; ALPL, COL1A2, DCN, ELN and RUNX2. Used in agglomerative cluster analysis, they correctly grouped the bone-forming cell populations as distinct. Although donor #6 cells were correlation slope outliers, they contrastingly formed bone without showing ex vivo mineralization. Mathematical expression level normalization of the most discrepantly upregulated signature gene COL1A2, sufficed to cluster donor #6 with the bone-forming classification. Moreover, attenuating factors causing genuine COL1A2 gene down-regulation, restored ex vivo mineralization. This suggested that the signature gene had an osteogenically influential role; nonetheless no single biomarker was fully deterministic whereas all five signature genes together led to accurate cluster analysis. We show proof of principle for an osteogenic potency assay providing early characterization of primary cGMP-hBM-MSC cultures according to their donor-specific bone-forming potential.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0163629PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5053614PMC
June 2017

Development of a Patient-Derived Xenograft (PDX) of Breast Cancer Bone Metastasis in a Zebrafish Model.

Int J Mol Sci 2016 Aug 22;17(8). Epub 2016 Aug 22.

Department of Molecular Cell Biology, Institute of Biology, Leiden University, Sylviusweg 72, 2333BE Leiden, The Netherlands.

Bone metastasis is a complex process that needs to be better understood in order to help clinicians prevent and treat it. Xenografts using patient-derived material (PDX) rather than cancer cell lines are a novel approach that guarantees more clinically realistic results. A primary culture of bone metastasis derived from a 67-year-old patient with breast cancer was cultured and then injected into zebrafish (ZF) embryos to study its metastatic potential. In vivo behavior and results of gene expression analyses of the primary culture were compared with those of cancer cell lines with different metastatic potential (MCF7 and MDA-MB-231). The MCF7 cell line, which has the same hormonal receptor status as the bone metastasis primary culture, did not survive in the in vivo model. Conversely, MDA-MB-231 disseminated and colonized different parts of the ZF, including caudal hematopoietic tissues (CHT), revealing a migratory phenotype. Primary culture cells disseminated and in later stages extravasated from the vessels, engrafting into ZF tissues and reaching the CHT. Primary cell behavior reflected the clinical course of the patient's medical history. Our results underline the potential for using PDX models in bone metastasis research and outline new methods for the clinical application of this in vivo model.
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http://dx.doi.org/10.3390/ijms17081375DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5000770PMC
August 2016

The Impact of Bone Deformity on Osteoarthritic Varus Knee Correctability.

J Arthroplasty 2016 12 15;31(12):2677-2684. Epub 2016 Jul 15.

Department of Orthopaedic Surgery, Azienda Ospedaliero-Universitaria Policlinico di Modena, University of Modena and Reggio-Emilia, Modena, Italy.

Background: Bone deformities in the varus osteoarthritic knee may influence soft-tissue balancing and therefore knee correctability. The hypothesis of the present study was that the grade of coronal plane knee deformity may influence directly knee correctability along the entire range of motion from 0° to 90°. Tibial and femoral epiphyseal bone deformities were also analyzed to determine which kind had the greater impact on knee correctability.

Methods: A coronal plane deformity radiographic assessment and an intraoperative correctability assessment using computer-assisted surgery were performed on 118 varus osteoarthritic knees undergoing total knee arthroplasty. Knees were divided into groups taking into account the kind of bone deformity (tibial, femoral, and combined).

Results: A significant inverse correlation was found between coronal plane deformity and knee correctability at every 10 degrees of flexion. Correlation was strong at 0° and progressively got weaker at further flexion angles. According to literature, knees with a varus deformity >10° were rarely correctable in full extension, but often correctable in flexion, whereas knees with varus deformity >15° showed to be almost never correctable. Combined deformity group had a significantly lower rate of correctability along the entire range of motion.

Conclusion: The severity of varus knee malalignment always influenced knee correctability with the knee in full extension, in further flexion (20°-60°), correctability was mildly affected. Isolated tibial epiphyseal deformity and combined epiphyseal deformity have the greatest impact on knee correctability.
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http://dx.doi.org/10.1016/j.arth.2016.07.007DOI Listing
December 2016

Kif1Bbeta isoform is enriched in motor neurons but does not change in a mouse model of amyotrophic lateral sclerosis.

J Neurosci Res 2003 Mar;71(5):732-9

Mario Negri Research Institute for Pharmacological Research, Milan, Italy.

The kinesin superfamily motor protein Kif1B is expressed in two isoforms, Kif1Balpha and Kif1Bbeta, with distinct cargo-binding domains. We examined the mRNA distribution of the two isoforms in adjacent sections of brain and spinal cord of adult mice using in situ hybridization analysis. Kif1Bbeta mRNA is enriched in several regions of brain and spinal cord. Its levels are four to five times higher than that of the alpha isoform, which was barely detectable. The highest mRNA levels of Kif1Bbeta were found in the cortex, hippocampus, cerebellum and the grey matter of the spinal cord. At the cellular level the highest signal was found in motor neurons in the motor nuclei of medulla oblongata and the ventral horn of spinal cord. Because expression of other Kif genes is altered in amyotrophic lateral sclerosis (ALS) models, we examined the expression level of Kif1Bbeta mRNA in the spinal cord of transgenic mice carrying the SOD1G93A mutation, a model of familial ALS, at presymptomatic and early stages of the disease. No changes were observed in Kif1Bbeta mRNA in motor neurons or in other regions of the spinal cord. These findings indicate that Kif1Balpha, which modulates the transport of mitochondria, may play a major role in tissues other than the central nervous system. Instead Kif1Bbeta, responsible for the transport of synaptic vesicle precursors, seems to play an important role in the nervous system, particularly in the lower motor neurons. The absence of changes of Kif1Bbeta mRNA in transgenic SOD1G93A mice suggests that other molecular mechanisms may play a role in the disruption of axonal transport occurring in the motor neurons of these mice.
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http://dx.doi.org/10.1002/jnr.10517DOI Listing
March 2003
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