Guido Garavaglia

Non-hematopoietic human bone marrow contains long-lasting, pluripotential mesenchymal stem cells.

Mesenchymal stem cells (MSC) are considered as potential agents for reconstructive and gene‐targeting therapies since they differentiate into various cell‐lineages, exhibit an extended survival once injected into a host, and can easily be transfected with engineered DNA. MSC are essentially isolated from hematopoietic bone marrow (BM), a process that is rather invasive and may raise ethical concerns. In an attempt to find an alternative source, we evaluated whether non‐hematopoietic (nh)BM recovered from femoral heads of patients undergoing hip arthroplasty contained MSC. Ex vivo, 99% of nhBM cells were CD45+ leukocytes. After culture, leukocytes were replaced by a homogenous layer of adherent CD45− CD14− CD34− CD11b− CD90+ HLA‐ABC+ cells. Culture doubling time (mean = 4 days, range 1.6–6.7 days) was not correlated with patient age (27–81 years, n = 16). Amplified cultures supported long‐term hematopoiesis, and could be differentiated in vitro into adipocytes and chondrocytes. Moreover, a small fraction of nhBM cells spontaneously expressed MyoD1 and formed myotubes, suggesting that myogenic differentiation also occurred. nhBM contained clonogenic cells whose frequency (1/13,000), doubling time (2.1 days), and maximal amplification (up to 106‐fold) were not age‐related. All 14 clones analyzed (from five patients, ages 27–78 years) differentiated into at least one mesenchymal lineage, and 66% were bipotential (n = 8/12), or tripotential (n = 2/3). In conclusion, nhBM contains pluripotential mesenchymal progenitors which are similar to hematopoietic BM‐derived MSC, and whose biological functions are not altered by aging. Furthermore, if MSC‐based therapies hold their promises, nhBM may become the source of choice for responding to the increasing demand for MSC. J. Cell. Physiol. 198: 110–118, 2004.

Outcomes of obese and nonobese patients undergoing revision total hip arthroplasty.

OBJECTIVE To evaluate the effect of obesity on the incidence of adverse events (surgical site infection, dislocation, re-revision, or > or =1 adverse event), functional outcome, residual pain, and patient satisfaction after revision total hip arthroplasty (THA). METHODS We conducted a university hospital-based prospective cohort study including 52 obese and 152 nonobese patients with revision THA performed between 1996 and 2006. We used incidence rates, rate ratios, and hazard ratios (HRs) to compare the incidence of events in obese and nonobese patients and in 4 body mass index (BMI) categories (<25, 25-29.9, 30-34.9, > or =35). Functional outcome and pain were measured 5 years postoperative using the Harris Hip Score. RESULTS The incidence rate for > or =1 complication increased with rising BMI (1.8, 3.4, 10.3, and 17.9 cases/100 person-years). The increase was small between normal and overweight patients (adjusted HR 1.5, 95% confidence interval [95% CI] 0.5, 4.7), significantly greater with BMI 30-34.9 (adjusted HR 4.5, 95% CI 1.4, 14.0), and most evident with BMI > or =35 (adjusted HR 10.9, 95% CI 2.9, 41.1). The adjusted HR for surgical site infection (obese versus nonobese) was 4.1 (95% CI 1.1, 15.0) and for dislocation 3.5 (95% CI 1.3, 9.3). Eighty patients had a followup visit at 5 years. Obese patients had moderately lower functional results and higher levels of residual pain, but patient satisfaction was almost similar. CONCLUSION Revision THA is technically challenging, particularly in obese patients, probably due to more difficult anatomic conditions. We found an increased risk of adverse events, notably surgical site infection and dislocation in these patients.

Accuracy of Stress Radiography Techniques in Grading Isolated and Combined Posterior Knee Injuries: A Cadaveric Study

Background Stress radiography techniques have been shown to be superior to the arthrometer and clinical examination in evaluating the posterior cruciate ligament—deficient knee, but no precise relationship has been established between the extent of the lesion and the laxity measured by stress radiography. Hypothesis It is possible to establish a precise relation between posterior laxity and the anatomical lesions of the posterior cruciate ligament and posterior structures using stress radiography. Study Design Controlled laboratory study. Methods Measurements were performed on 15 fresh-frozen cadaveric knee specimens. A partial posterior cruciate ligament lesion was created by sectioning the anterolateral bundle, followed by a complete section. Then the lateral collateral ligament and the posterolateral corner were transected, and finally the medial collateral ligament and the posteromedial corner were sectioned. Stress radiography was performed first on the intact knee and again after each lesion was created using 4 techniques: Gravity Sag View, PCL-Press, Telos at 80°, and Telos at 30° of flexion. Results Telos 30 and Telos 80 revealed the best overall performance as a diagnostic test in terms of accuracy in discriminating between the different types of lesions. Using the Telos device, we determined the following cut-off points: for a partial lesion, less than 3 mm at 30° and less than 6 mm at 80°; for a complete lesion, between 4 mm and 9 mm at 30° and between 7 mm and 12 mm at 80°; for associated peripheral lesions, more than 9 mm at 30° and more than 12 mm at 80°. Conclusion The Telos 30° and 80° allow us to accurately distinguish between the different types of lesion and permit grading of posterior knee laxity. Clinical Relevance Stress radiography allows characterization of posterior knee injuries and helps to determine treatment strategy.

Autologous transplantation of porcine myogenic precursor cells in skeletal muscle

Myoblast transplantation is a potential therapy for severe muscle trauma, myopathies and heart infarct. Success with this therapy relies on the ability to obtain cell preparations enriched in myogenic precursor cells and on their survival after transplantation. To define myoblast transplantation strategies applicable to patients, we used a large animal model, the pig. Muscle dissociation procedures adapted to porcine tissue gave high yields of cells containing at least 80% myogenic precursor cells. Autologous transplantation of 3[H]-thymidine labeled porcine myogenic precursor cells indicated 60% survival at day 1 followed by a decay to 10% at day 5 post-injection. Nuclei of myogenic precursor cells transduced with a lentivirus encoding the nls-lacZ reporter gene were present in host myotubes 8 days post-transplantation, indicating that injected myogenic precursor cells contribute to muscle regeneration. This work suggests that pig is an adequate large animal model for exploring myogenic precursor cells transplantation strategies applicable in patients.

BMI and severity of clinical and radiographic signs of hip osteoarthritis.

Obesity might be involved in the pathogenesis of osteoarthritis (OA) not only via increased mechanical loading, but also via an inflammatory component possibly causing increased pain and functional disability. The study aim was to examine the relationship between BMI and clinical symptoms as well as radiographic severity of OA in patients scheduled for primary total hip arthroplasty (THA). We conducted a cross‐sectional study of 855 patients scheduled for a first THA for primary OA at a single centre between November 2001 and December 2006. The primary outcome was clinical and radiographic severity of OA, which was evaluated in four BMI categories (18.5–24.9, 25–29.9, 30–34.9 and ≥35 kg/m2). We used the Harris Hip Score (HHS) and the Western Ontario McMaster Universities Osteoarthritis Index (WOMAC) to assess pain and function. The severity of radiographic hip joint damage was evaluated using the Kellgren–Lawrence classification. Multivariate analyses were performed to adjust for potential confounders. In patients scheduled for THA, increasing BMI was associated with significantly higher levels of pain and functional disability on both HHS (P for trend <0.001) and WOMAC (P for trend <0.001). However, the degree of radiographic joint damage remained similar across BMI categories. These findings emphasize the need to further investigate the potential pathogenic role of obesity and low‐grade inflammation in OA and underscore the importance of obesity prevention to avoid early prosthetic replacement of the hip.

α-Smooth muscle actin and TGF-β receptor I expression in the healing rabbit medial collateral and anterior cruciate ligaments

The aim of our study was to advance the knowledge about the biological differences in the healing of the anterior cruciate ligament (ACL) versus the medial collateral ligament (MCL). We quantified α-smooth muscle actin (α-SMA) expression and TGF-β receptor I (TGF-βRI) expression in experimentally injured rabbit ligaments (from day 3 to 12 weeks post-injury). Myofibroblasts (α-SMA positive cells) were identified as early as the third day post-injury in MCL and their density increased steadily up to day 21. Myofibroblasts were also detected in injured ACL but their density remained very low at all time points. The percentage of positive TGF-βRI area significantly increased in both injured ligaments compared to controls, with a peak expression at day 21; however, it remained constantly lower in ACL compared to MCL. A significant correlation was found between the percentage of TGF-βRI positive cells and the percentage of α-SMA expression only in injured MCL. These results provide evidence that myofibroblasts are important players in MCL remodelling after injury. The combined presence of myofibroblasts and TGF-βRI in the first 3 weeks post-MCL injury may partially explain the difference in the MCL and ACL healing process.

Trans-trapezium carpo-metacarpal dislocation of the thumb

We report a case of carpo-metacarpal dislocation associated with an isolated horizontal fracture of the trapezium. It is a rare lesion which is difficult to diagnose by standard radiography, and CT may be necessary for the diagnosis and correct treatment. In our case, stable osteosynthesis was achieved by internal screw fixation, and at follow-up there was an unrestricted, painless range of motion of the thumb.

Strong association between smoking and the risk of revision in a cohort study of patients with metal-on-metal total hip arthroplasty

Thus far the ability to predict who will develop early failure following the insertion of a metal‐on‐metal (MoM) bearing has been very limited. Our objective was to assess the effect of smoking on failure rates in patients with MoM bearing, compared with patients with ceramic‐on‐polyethylene (CoP) bearing. From a prospective hospital‐based registry we included all primary THAs operated upon between 1/2001 and 12/2011 with MoM or CoP bearings of the same cup design and head size (28 mm). We compared revision rates through 10/2013 classified by smoking status and type of bearing. We included 1,964 patients (median age 71, 57% women), 663 with MoM and 1,301 with CoP bearing. Mean follow‐up was 6.9 years (range 1.8–12.8). Revisions were required for 56 THAs. In patients with MoM bearing the adjusted incidence rate of revision among ever‐smokers was four times greater than among never‐smokers (95% CI 1.4–10.9). Among those with CoP bearing, the rate ratio was only 1.3 (95% CI 0.6–2.5). We found a strong association between smoking and increased failure of MoM THAs. In contrast, the association was weak for patients with CoP bearing. Smoking might be a trigger or an effect amplifier for adverse reactions to metal debris from MoM bearings.

Analysis of the Inter- and Intra-Observer Agreement in Radiographic Evaluation of Wrist Fractures Using the Multimedia Messaging Service

BackgroundOrthopaedic surgeons are often asked to evaluate X-rays of patients admitted to the Accident and Emergency Department with the suspicion of a wrist fracture or, in the case of an evident fracture, to decide the correct treatment. The aim of this study was to evaluate the feasibility of a correct interpretation of the images of injured wrists on the screen of a last generation mobile phone, in order to evaluate if the specialist could make the right diagnosis and choose the correct treatment.MethodsFive orthopaedic and one hand surgeons have evaluate the X-rays of 67 patients who sustained an injury to their wrist. In the case of fracture, they were asked to classify it according to the AO and Mayo classification systems. The evaluation of the images was accomplished through the PACS and using a mobile phone, at a different time. In order to check the inter- and intra-observer reliability, the same pattern was followed after a few months.ResultsThe mobile phone showed basically the same agreement between the observers highlighting the worsening of the inter- and intra-observer reliability with the increment of the variables considered by a classification system.ConclusionsThe present paper confirms that a last generation mobile phone can already be used in the clinical practise of orthopaedic surgeons on call who could use it as a useful device in remote or poorly served areas for a rapid and economic consultationLevel of EvidenceThe level of evidence of this case is economic and decision analysis, level 2

A comparative assessment of small-head metal-on-metal and ceramic-on-polyethylene total hip replacement

Large-head metal-on-metal (MoM) total hip replacements (THR) have given rise to concern. Comparative studies of small-head MoM THRs over a longer follow-up period are lacking. Our objective was to compare the incidence of complications such as infection, dislocation, revision, adverse local tissue reactions, mortality and radiological and clinical outcomes in small-head (28 mm) MoM and ceramic-on-polyethylene (CoP) THRs up to 12 years post-operatively. A prospective cohort study included 3341 THRs in 2714 patients. The mean age was 69.1 years (range 24 to 98) and 1848 (55.3%) were performed in women, with a mean follow-up of 115 months (18 to 201). There were 883 MoM and 2458 CoP bearings. Crude incidence rates (cases/1000 person-years) were: infection 1.3 vs 0.8; dislocation 3.3 vs 3.1 and all-cause revision 4.3 vs 2.2, respectively. There was a significantly higher revision rate after ten years (adjusted hazard ratio 9.4; 95% CI 2.6 to 33.6) in the MoM group, and ten of 26 patients presented with an adverse local tissue reaction at revision. No differences in mortality, osteolysis or clinical outcome were seen. In conclusion, we found similar results for small-head MoM and CoP bearings up to ten years post-operatively, but after ten years MoM THRs had a higher risk of all-cause revision. Furthermore, the presence of an adverse response to metal debris seen in the small-head MOM group at revision is a cause for concern.