Giulio Guido

Use of Autologous Human mesenchymal Stromal Cell/Fibrin Clot Constructs in Upper Limb Non-Unions: Long-Term Assessment

Background Tissue engineering appears to be an attractive alternative to the traditional approach in the treatment of fracture non-unions. Mesenchymal stromal cells (MSCs) are considered an appealing cell source for clinical intervention. However, ex vivo cell expansion and differentiation towards the osteogenic lineage, together with the design of a suitable scaffold have yet to be optimized. Major concerns exist about the safety of MSC-based therapies, including possible abnormal overgrowth and potential cancer evolution. Aims We examined the long-term efficacy and safety of ex vivo expanded bone marrow MSCs, embedded in autologous fibrin clots, for the healing of atrophic pseudarthrosis of the upper limb. Our research work relied on three main issues: use of an entirely autologous context (cells, serum for ex vivo cell culture, scaffold components), reduced ex vivo cell expansion, and short-term MSC osteoinduction before implantation. Methods and Findings Bone marrow MSCs isolated from 8 patients were expanded ex vivo until passage 1 and short-term osteo-differentiated in autologous-based culture conditions. Tissue-engineered constructs designed to embed MSCs in autologous fibrin clots were locally implanted with bone grafts, calibrating their number on the extension of bone damage. Radiographic healing was evaluated with short- and long-term follow-ups (range averages: 6.7 and 76.0 months, respectively). All patients recovered limb function, with no evidence of tissue overgrowth or tumor formation. Conclusions Our study indicates that highly autologous treatment can be effective and safe in the long-term healing of bone non-unions. This tissue engineering approach resulted in successful clinical and functional outcomes for all patients.

External fixation in pelvic fractures.

Pelvic fractures account for 4–5% of all fracturated patients, and they occur in 4–5% of politraumatized patients. In the most of the cases, they are consequent to high-energy trauma with a high percentage of lesions of other organs (cerebral, thoracic, and abdominal lesions. The most of the patients (80%) who die are dying within the first hours after trauma for a massive hemorrhagic shock. When the pelvic fracture and the patient’s hemodynamic conditions are both unstable, osteosynthesis of the fracture is mandatory. Fracture stabilization should be performed within the first hour after trauma (as soon as possible), and it should be considered as part of the resuscitation procedure. We usually make an urgent stabilization of pelvic fracture with an anterior external fixator technique. We have revised all unstable pelvic fractures treated in our department (Orthopaedic Clinic Pisa University) from 2000 up to the 2005 to determine a correct treatment protocol for these lesions. Pelvic stabilization, reducing the pelvic volume and bleeding from the stumps of fracture, determines the arrest of the hemorrhage, as evidenced by the sharp decline in the number of transfusions in postoperative period. In these cases, there is an absolute indication for an urgent pelvic stabilization. Pelvic stabilization, whether temporary or permanent, allows to control the bleeding because it (1) leads to a reduction in the volume pelvis with a containment on the retro-peritoneal hematoma (2) reduces bleeding from the fracture fragments (3) reduces motility fracture promoting the blood clotting. The stabilization of the pelvis also makes it easier to manage the patient and his mobilization for the implementation of subsequent investigations. In our experience, external fixator accounts for its characteristics the gold standard approach for the urgent stabilization of these lesions, and, for most of them, it can be used as the definitive treatment. External fixation is a quick and easy procedure for pelvic fractures stabilization for surgeons with experience with this technique.

The role of external fixation in the treatment of humeral shaft fractures: A retrospective case study review on 85 humeral fractures

There is no consensus among surgeons on the treatment for humeral fractures: the best it is still a matter of some debate. The aim of our work was to demonstrate that external fixation may be considered a valid method not only in emergencies but also for the definitive treatment of such fractures. We perform a retrospective case study review on 85 humeral fractures, 62 shaft fractures, and 23 extrarticular distal third fractures treated with external fixation. Clinical (Disabilities of the Arm, Shoulder and Hand (DASH) score and SF-36) and radiographic follow-up lasted on average 30 months (minimum 12 to maximum 36). Complete healing of fractures was achieved in 97.6% of cases (83 patients), with an average consolidation time of about 12 weeks (83.2 days). One case of delayed union and one case of refracture were encountered. Eighty-one patients demonstrated SF-36 scores at or above the national average and an average DASH score of 8.9. External fixation of humeral shaft fractures is considered a valid treatment method as it provides good results in terms of stability of reduction, tolerability, healing times, and functional recovery.

Pseudoarthrosis in atypical femoral fracture: case report.

Atypical femoral fractures can be subsequent to a long-term biphosphonates treatment; they have a high frequency of delayed healing. The authors describe a femoral pseudoarthrosis of an atypical fracture treated with intramedullary nailing in a female after prolonged alendronate therapy. Atypical femoral fractures can be subsequent to a long-term biphosphonates treatment even if, in the literature, there is no clarity on the exact pathogenetic mechanism. The Task Force of the American Society for Bone and Mineral Research described the major and minor features to define atypical fractures and recommends that all the five major features must be present while minor features are not necessary. Another controversial aspect regarding the atypical femoral fractures is the higher frequency of the delayed healing that can be probably related to a suppressed bone turnover caused by a prolonged period of bisphosphonates treatment. This concept could be corroborated by the Spet Tc exam. In the case of a pseudoarthrosis, there is not a standardization of the treatment. In this report, the authors describe a femoral pseudoarthrosis of an atypical fracture treated with intramedullary nailing in a female after prolonged alendronate therapy; the patient was studied with clinical, bioumoral end SPECT-Tc exam of both femurs. Many studies show the relationship between bisphosphonates and the presence of atypical fractures. These fractures should be monitored more closely due to the risk of nonunion and they require considering an initial treatment with pharmacological augmentation to reduce the complications for the patient and the health care costs.

Total hip replacement in osteoarthritis: the role of bone metabolism and its complications.

Osteoarthritis is one of the most common joint disorder. For treatment of hip symptomatic osteoarthritis, when conservative medical therapy has failed, total hip arthroplasty (THA) is a successful orthopaedic procedures that reduces pain and improves function and quality of life. Incidence of osteoarthritis is constantly increasing with raising life expectancy. This aging process also has led to an increasing number of patients with osteoporosis who need hip replacement for osteoarthritis. Osteoporosis have 3 major potential complications in total hip arthroplasty: perioperative fracture, an increased risk of periprosthetic fracture, and late aseptic loosening. The purpose of the present study was to examine the effects of osteoporosis on total hip replacement procedure outcome and highlight the importance of adequate study of calcium-phosphorus metabolism in patient candidate for hip surgery, and the need to start a suitable therapy to recover the bone mass before surgery. Bone quality of the hip joint has become an important risk factor limiting the durability of THA.

Hip replacement in femoral head osteonecrosis: current concepts.

Osteonecrosis of the femoral head is a destructive disease that usually affects young adults with high functional demands and can have devastating effects on hip joint. The treatment depends on extent and location of the necrosis lesion and on patients factors, that suggest disease progression, collapse probability and also implants survival. Non-idiopathic osteonecrosis patients had the worst outcome. There is not a gold standard treatment and frequently it is necessary a multidisciplinary approach. Preservation procedures of the femoral head are the first choice and can be attempted in younger patients without head collapse. Replacement procedure remains the main treatment after failure of preserving procedures and in the late-stage ONFH, involving collapse of the femoral head and degenerative changes to the acetabulum. Resurfacing procedure still has good results but the patient selection is a critical factor. Total hip arthroplasties had historically poor results in patients with osteonecrosis. More recently, reports have shown excellent results, but implant longevity and following revisions are still outstanding problems.

Stemless humeral component in reverse shoulder prosthesis in patient with Parkinson's disease: a case report.

INTRODUCTION In patients with Parkinsons disease falling is very common and for this reason, the prosthetic surgical indication in shoulder is reserved for special cases. PD has been linked to several interrelated factors that may contribute to failure of shoulder arthroplasty. CASE PRESENTATION A 65-year-old woman with PD, severe pain, recurrent bursitis, swelling and functional limitation to all movements in left shoulder presented to our attention. Radiographic and CT exams show cuff-tear arthropathy. The patient was submitted to implantation of a Reverse Shoulder Comprehensive Nano cementless modular system (Biomet(®), Warsaw, IN, USA) with anterosuperior surgical approach. We chose this kind of solution of stemless humeral component after bone mineral consideration. DISCUSSION Reverse shoulder arthroplasty represents an option in the management of glenohumeral arthritis. Poor functional results of RTSA in patients with PD have been attributed to increased muscle tone, severity of tremor and an increased mortality rate. In general, post operative complications related to the humeral component are dominated by fractures (between 1 and 3%): in patients with PD this percentage is higher because of falls often occur. With a stemless implant revisions can be performed easily. Overall, the anterosuperior surgical exposure gives a low risk of postoperative instability. CONCLUSION In selected cases of patients with PD, after carefully analysis of bone quality, the use of a stemless component is of benefit in the possible revision cases for periprosthetic fractures and the use of an anterosuperior exposure reduces the percentage of instability. The results obtained about the pain relief are excellent in contrast with functional outcomes that remain poor.

Histological study of atraumatic periprosthetic fractures: does atypical periprosthetic fracture exist?

Purpose Is it possible a correlation between some periprosthetic femoral fractures and atypical fractures? Case We present a case of a 77-year-old woman with atypical periprosthetic femoral fracture. The patient had a history of long-term bisphosphonate use. We performed an open reduction, a synthesis of the fracture and a histological exam. The patient stopped the bisphosphonate (BF) therapy. Three months later, before starting the teriparatide treatment, the patient had a re-fracture so we did a second osteosynthesis and began a teriparatide therapy. After six months, the radiography showed a bone healing at the fracture site. Result The histological examination confirmed the diagnosis of atypical femoral fracture. Conclusion At first, the fracture showed a delayed union which led to a new surgery, as often happens in BF-related atypical fractures. Appropriate treatment (BF suspension and teriparatide beginning) permitted fracture healing. The atypical characteristic of the fracture was confirmed by histological exam.Some periprosthetic femoral fractures in patients treated with BF, especially in long time therapies, should be suspected as atypical fractures and a specific medical treatment should be performed, as well as a correct surgical treatment.

Algodystrophy: complex regional pain syndrome and incomplete forms.

The algodystrophy, also known as complex regional pain syndrome (CRPS), is a painful disease characterized by erythema, edema, functional impairment, sensory and vasomotor disturbance. The diagnosis of CRPS is based solely on clinical signs and symptoms, and for exclusion compared to other forms of chronic pain. There is not a specific diagnostic procedure; careful clinical evaluation and additional test should lead to an accurate diagnosis. There are similar forms of chronic pain known as bone marrow edema syndrome, in which is absent the history of trauma or triggering events and the skin dystrophic changes and vasomotor alterations. These incomplete forms are self-limited, and surgical treatment is generally not needed. It is still controversial, if these forms represent a distinct self-limiting entity or an incomplete variant of CRPS. In painful unexplained conditions such as frozen shoulder, post-operative stiff shoulder or painful knee prosthesis, the algodystrophy, especially in its incomplete forms, could represent the cause.