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Biomedical subjects

Peter V Giannoudis

Publications and source records attributed to Peter V Giannoudis.

At least 19 recordsLinked to original sources
PubMed2006

Impact of timing of pelvic fixation on functional outcome.

Pelvic fractures are the third most common cause of death in motor vehicle accidents. Recent improvements in mortality can be attributed to the progress made in modern critical care medicine, multidetector CT, ATLS principles, multidisciplinary protocols and early fracture stabilisation. Currently, the timing of pelvic fixation is often based on the haemodynamic status and response of the patient to resuscitation, the fracture pattern, the presence of associated injuries and the immuno-inflammatory status of the patient. The purpose of this review is to focus on the impact of timing of reconstruction of pelvic fractures on the functional outcome of the patients. Thirty seven scientific studies on the outcome of pelvic and acetabular injuries were reviewed. Four on pelvic ring fractures, and one study on pelvic and acetabular fractures met our second inclusion criterion of prospective or retrospective studies investigating the outcome after early or late pelvic and acetabular fixation. These five studies suggested early pelvic and acetabular fixation for optimal outcome but their main difference was the definition of the length in time of that early period. In polytrauma patients, the "damage control orthopaedics" principle should be applied for haemodynamic and skeletal stabilisation (and faecal diversion, if indicated in cases of open fractures of the pelvis). The definitive fixation should be performed after the fourth post-injury day, when the physiological state of the patient is conducive to surgery.

Acetabulum↗
PubMed2006

Safety and efficacy of vena cava filters in trauma patients.

Pulmonary embolism (PE), due to its sudden onset, notoriously difficult diagnosis, unpredictable nature and often fatal outcome, remains one of the most feared complications in surgical practice. Trauma patients with multisystem injuries, extremity or pelvic fractures and head or spinal cord injuries often pose a significant dilemma for the surgeon because of the inability to use conventional measures such as anticoagulation therapy and compression devices. On the other hand, the incidence of deep vein thrombosis (DVT) is high among trauma patients and the attendant risk of PE is an important cause of morbidity and mortality. Inferior vena cava (IVC) interruption by placement of diverse filtering devices has evolved over the past three decades. With the use of these devices, the risk of PE has been reduced dramatically. However, variable rates of complications are reported from their use. In this study, we review all the available data on IVC filter placement in trauma patients and we discuss the potential complications of IVC filters in order to understand better the risk/benefit ratio of their use.

Contraindications↗
PubMed2006

Health economics: a cost analysis of treatment of persistent fracture non-unions using bone morphogenetic protein-7.

OBJECTIVE: To compare the cost implications of treatment of persistent fracture non-unions before and after application of recombinant human bone morphogenetic protein-7 (BMP-7). METHOD: Of 25 fracture non-unions, 9 were treated using BMP-7 alone and 16 using BMP-7 and bone grafting. These patients were prospectively followed up, and the costs incurred were analysed. RESULTS: The mean number of procedures per fracture performed before application of BMP-7 was 4.16, versus 1.2 thereafter. Mean hospital stay and cost of treatment per fracture before receiving BMP-7 were 26.84 days and pound 13,844.68, versus 7.8 days and pound 7338.4 thereafter. The overall cost of treatment of persistent fracture non-unions with BMP-7 was 47.0% less than that of the numerous previous unsuccessful treatments (p=0.001). CONCLUSIONS: Treating fracture non-unions is costly, but this could be reduced by early BMP-7 administration when a complex or persistent fracture non-union is present or anticipated.

Adolescent↗
PubMed2006

Intramedullary nailing for non-union of the humeral diaphysis: a review.

PubMed and Ovid Medline were searched to investigate the role of intramedullary nailing in the treatment of diaphyseal humeral non-union. Of 474 abstracts, 9 retrieved articles fulfilled our inclusion criteria and described management in 166 cases of humeral shaft non-union using several types of intramedullary nails. Union ranged from 40 to 100%; part of the variation could be explained by the quality index of the selected articles. Exchange nailing alone was not effective. Exposure of the fracture site and use of bone grafting were key to successful treatment. The total incidence of severe complications, including radial nerve damage, was very low. Thus, intramedullary nailing in the treatment of humeral shaft non-unions can lead to successful outcomes when associated with autologous bone grafting.

Adolescent↗
PubMed2006

Transcriptomics and proteomics: advancing the understanding of genetic basis of fracture healing.

Fracture healing is a complex physiological post-natal process, which involves the coordination of several different cell types. Exploring the orchestration of events and the simultaneous activation of osteogenesis and chondrogenesis that recapitulates mammalian embryological skeletal development seems to be not only sophisticated but also challenging. A large number of genes involved in the above process are known, but many more remain to be discovered. The functional characterisation of these genes promises to elucidate the repair process as well as skeletal abnormalities and aging. We here review the current knowledge on early and late gene expression during fracture healing, the genes so far associated with osteoblast and osteoclast differentiation, the BMP antagonists, and the Wnts signalling pathway.

Bone Morphogenetic Proteins↗
PubMed2006

The role of inhibitory molecules in fracture healing.

The balance between all the signalling molecules involved in bone formation with their inhibitors and most importantly between BMPs and their antagonists is critical determinant of osteogenesis, and therefore of skeletal development, fracture repair, and bone remodelling. The main identified inhibitory molecules of the osteogenic lineage, either from studies during embryonic development or from in vitro and in vivo studies are presented in the herein study. Potential treatments using these molecules either alone or in combination with BMPs to control the bone growth and overgrowth are already under investigation aiming in treatments that mimic as much as possible the natural process of bone generation in various situations including fracture healing, osteoporosis, and osteoarthritis and other metabolic disorders, in order to more closely resemble the original tissue.

Animals↗
PubMed2006

Gene therapy in orthopaedics.

Impressive advances in our knowledge of the molecular genetic basis of skeletal disorders and fracture healing have led to the development of novel therapeutics based on ectopic expression of one or more genes in patient cells that can influence repair or regenerative processes in bone. Gene therapy is an attractive new approach to the treatment of bone disorders. Orthopaedics has become one of the most promising areas of research into gene therapy. This is because many potential orthopaedic targets for gene therapy, unlike traditional targets such as cancer and severe genetic disorders, neither present difficult delivery problems nor require prolonged periods of gene expression. Gene therapy offers new possibilities for the clinical management of orthopaedic conditions that are difficult to treat by traditional surgical or medical means. Impaired bone healing, need for extensive bone formation, cartilage repair and metabolic bone diseases are all conditions where alterations of the signalling peptides involved may provide cure or improvement. In orthopaedic oncology, gene therapy may achieve induction of tumour necrosis and increased tumour sensitivity to chemotherapy. An increasing amount of evidence indicates that gene transfer can aid the repair of articular cartilage, menisci, intervertebral disks, ligaments and tendons. These developments have the potential to transform many areas of musculoskeletal care, leading to treatments that are less invasive, more effective and less expensive than existing modalities.

Animals↗
PubMed2006

Evidence-based medicine: what it is and what it is not.

The evidence-based medicine (EBM) related concepts of hierarchy of evidence, meta-analyses, confidence intervals, study design, etc. are nowadays so widespread, that clinicians willing to use today's medical literature with understanding have no choice but to become familiar with EBM principles and methodologies. Although surgeons may perceive that evidence-based medicine mandates a strict adherence to randomised trials, it more accurately involves informed and effective use of all types of evidence (from meta-analysis of randomised trials to individual case series and case reports. With the ever-increasing amount of available information, surgeons must consider a shift in paradigm from traditional practice to one that involves question formulation, validity assessment of available studies and appropriate application of research evidence to individual patients.

Data Collection↗
PubMed2006

Issues in the planning and conduct of randomised trials.

Randomised trials top the hierarchy of evidence. To provide the best evidence to guide surgical practice, randomised trials must answer clinically important questions, have important and objective outcome measurement and be sufficiently powered to detect important differences between interventions. Investigators who adhere to these principles are more likely to succeed during the conduct of their trials.

Bias↗
PubMed2006

Staged management and outcome of combined pelvic and liver trauma. An international experience of the deadly duo.

Pelvic fracture associated with liver trauma is not an uncommon injury combination in multiple trauma and is associated with high morbidity and mortality. The aim of this study was to examine the characteristics of this specific patient group, to describe the diagnostic and treatment protocols and finally to analyse risk factors associated with mortality. Data were collected over a 6-year period, ending in 2001. The pelvic injury was graded according to the Tile classification system and the hepatic injury was scored using the organ injury scale (OIS). Treatment protocol, associated injuries, complications, length of ICU/Hospital stay and mortality were recorded and analysed. A total of 140 patients (40% female) with a mean age of 35.1+/-15.9 years and a median ISS of 41 were included in this study. The overall mortality rate was 40.7%. Binomial logistic regression analysis revealed age, initial blood pressure, transfusion requirement as well as the severity of head, chest, spleen and liver injury as independent parameters predicting reduced survival rates. This deadly duo of injuries presents a challenge to the trauma surgeon. Rapid assessment and treatment is required to prevent death by haemorrhage. The presence of concomitant injuries renders the patient very sensitive to ongoing or additional physiological disturbance. The principles of 'damage control surgery' must be applied to avoid complications such as acute respiratory distress syndrome (ARDS) and multiple organ dysfunction syndrome (MODS).

Adolescent↗
PubMed2006

In vitro evaluation of the direct effect of estradiol on human osteoblasts (HOB) and human mesenchymal stem cells (h-MSCs).

Estrogen may increase the proliferation of osteoblasts depending upon their differentiation stage. Our objective was to test the hypothesis that estradiol could stimulate the proliferation of primary human osteoblast (HOB) cells or human mesenchymal stem cells (h-MSCs). To test this hypothesis, we investigated two synthetic estradiol preparations: (a) a commercially available one (in clinical use) whose effect was evaluated using MTT assay, trypan blue cell counts and total protein assays; (b) a novel synthetic preparation (not in clinical use) using Alamar Blue assays and scanning electron microscopy (SEM). Commercial estradiol increased HOB proliferation in a concentration-dependant manner between 1 nM and 8 nM reaching significance at a concentration of 8 nM (p<0.001). Small doses of 1 nM and 2 nM increased h-MSC proliferation (p<0.001) but higher doses had no effect. All novel synthetic estradiol preparations decreased HOB proliferation (p<0.001) whereas no direct effect was observed on h-MSCs. Commercial estradiol appears to induce proliferation of HOBs, although its effects on h-MSCs appears to be highly dose-dependent and requires further investigation.

Adult↗
PubMed2006

Fat embolism: special situations bilateral femoral fractures and pathologic femoral fractures.

Few data are available in the literature regarding fat embolism in cases of bilateral femoral and pathological femoral fractures. The incidence of bilateral femoral fractures ranges from 2-9.5% of the total number of patients with femoral fractures, and they usually occur in high energy trauma and multi-trauma patients. Although injury severity scores tend to underestimate the severity of these injuries, fat embolism seems to occur in increased frequency ranging from 4.8-7.5%. Intramedullary nailing, which is the preferred surgical treatment, triggers a systemic inflammatory response that poses an additional burden to pulmonary function. In addition, the femur is a common site of metastatic bone disease. The treatment of impending and actual pathological fractures is complicated by increased rates of lung damage due to various factors. Fat embolism during treatment--mainly with intramedullary nails--generally seems to range from 0-10%.

Embolism, Fat↗
PubMed2006

Experimental background--review of animal studies.

UNLABELLED: Most of the research on the physiological effects of intramedullary nailing is technically difficult or ethically impossible to perform in humans. A substantial range of factors apply in clinical cases, which means that the data obtained from this source may lack the control needed to reveal the basic mechanisms of pathophysiology associated with this surgical procedure. Consequently, animal studies have been relied upon to provide answers that would otherwise be unavailable. This review manuscript summarizes the available literature on animal studies dealing with the local and systemic effects of intramedullary nailing. It focuses on whether these studies have contributed to our clinical knowledge of the procedure's impact on perfusion and fracture healing, as well as the medical relevance of coincident systemic effects. DATA SOURCES: Medline, personal library of the first author and of the Department of Trauma Surgery, University of Pittsburgh Medical Center. STUDY SELECTION: All animal studies on intramedullary stabilization published in English, German, and French. CONCLUSIONS: The relevance of animal studies investigating the impact of a surgical procedure and its influence on concomitant injuries depends on the design and the type of the animal model. If this fact is considered, and if a model is selected that simulates a systemic impact comparable with the clinical situation, then animal studies may provide a valuable source of otherwise unobtainable information. Such an example is the study of fat embolization associated with intramedullary nailing. Animal subjects enable assessment of the intervention's additive surgical impact, measurement of side effects that may have adverse results, and influence of cofactors (eg, thoracic trauma, severe shock, polytrauma) that predispose the individual to postoperative complications.

Animals↗
PubMed2006

Fat embolism: the reaming controversy.

Intramedullary nailing is the preferred treatment method for stabilizing femoral diaphyseal fractures. Despite its superior biomechanical advantages over other implants, its use, particularly in selected groups of patients, has been questioned because of the possible harmful systemic effects of intramedullary reaming. The increase in intramedullary canal pressure during intramedullary nailing can result in intravasation of bone marrow and fat into the venous blood system. The subsequent consequences can be fat embolism syndrome (FES), adult respiratory distress syndrome (ARDS), and multiple organ failure. The lung seems to be the primary target for fat embolization and for the mediated effects primed by inflammatory reactions. In laboratory studies, both reamed and unreamed intramedullary nailing has been shown to alter selected pulmonary variables. Although transient, this effect appears to be more prominent with reamed than unreamed techniques. Additional studies are required to determine whether a subgroup of trauma patients is adversely affected by intramedullary reaming, thus necessitating other fixation techniques.

Bone and Bones↗
PubMed2006

The risk of local infective complications after damage control procedures for femoral shaft fracture.

OBJECTIVES: To determine infection rates after damage control orthopaedics (DCO) and primary intramedullary nailing (1' IMN) in multiply injured patients with femoral shaft fracture. DESIGN: Retrospective case analysis. SETTING: Level I trauma center. PATIENTS: All patients with New Injury Severity Score (NISS) >20 and femoral shaft fracture (AO 32-) treated in our unit between 1996 and 2002. INTERVENTION: Damage control orthopaedics, defined as primary external fixation of the femoral shaft fracture and subsequent conversion to an intramedullary nail, or primary IMN. MAIN OUTCOME MEASUREMENTS: Rates of infection classified as contamination (positive swabs with no clinical change), superficial, deep (requiring surgery), and removal of hardware (those requiring removal of femoral instrumentation or amputation). RESULTS: A total of 173 patients with 192 fractures were included; 111 fractures were treated by DCO and 81 by primary IMN. Mean follow-up was 19.1 months [median, 16.7, range, 1 (patient died)-67 months]. DCO patients had a significantly higher NISS and more grade III open fractures (P<0.001). IMN procedures took a median of 150 minutes compared with 85 minutes for DCO (P<0.0001). Although wound contamination (including contaminated pin sites) was more common in the DCO group (P<0.05), the risk of infectious complications was equivalent (P=0.86). Contamination was significantly more likely when conversion to IMN occurred after more than 14 days (P<0.05); however, this did not lead to more clinically relevant infections. Logistic regression analysis showed that although a DCO approach was not associated with infection, delay before conversion in the DCO group might be [P=0.002 for contamination and removal of hardware, P=0.065 for serious infection (deep or worse), not significant for other infection outcomes]. Grade III open injury also was significantly associated with serious infection in all patients (P<0.05). CONCLUSIONS: Infection rates after DCO for femoral fractures are comparable to those after primary IMN. We see no contraindication to the implementation of a damage control approach for severely injured patients with femoral shaft fracture where appropriate. Pin-site contamination was more common where the fixator was in place for more than 2 weeks. For patients treated by using a DCO approach, conversion to definitive fixation should be performed in a timely fashion.

Adult↗