James A. Fernandes

The treatment of severe slipped capital femoral epiphysis via the Ganz surgical dislocation and anatomical reduction

We present our experience of the modified Dunn procedure in combination with a Ganz surgical dislocation of the hip to treat patients with severe slipped capital femoral epiphysis (SCFE). The aim was to prospectively investigate whether this technique is safe and reproducible. We assessed the degree of reduction, functional outcome, rate of complications, radiological changes and range of movement in the hip. There were 28 patients with a mean follow-up of 38.6 months (24 to 84). The lateral slip angle was corrected by a mean of 50.9° (95% confidence interval 44.3 to 57.5). The mean modified Harris hip score at the final follow-up was 89.1 (sd 9.0) and the mean Non-Arthritic Hip score was 91.3 (sd 9.0). Two patients had proven pre-existing avascular necrosis and two developed the condition post-operatively. There were no cases of nonunion, implant failure, infection, deep-vein thrombosis or heterotopic ossification. The range of movement at final follow-up was nearly normal. This study adds to the evidence that the technique of surgical dislocation and anatomical reduction is safe and reliable in patients with SCFE.

Changing pattern of femoral fractures in osteogenesis imperfecta with prolonged use of bisphosphonates

PurposeOsteogenesis imperfecta (OI) has been treated with bisphosphonates for many years, with some clear clinical benefits. In adults, there are reports of a new pattern of atraumatic subtrochanteric fractures with bisphosphonate treatment. This study assesses if bisphosphonate treatment leads to an altered pattern of femoral fractures.MethodsRetrospective review of imaging for a cohort of 176 bisphosphonate-treated OI patients to identify the locations of femoral fractures over a two-year period, as compared to a historical control group managed pre-bisphosphonates.ResultsSixteen femoral fractures were identified in this time period in the bisphosphonate-treated group. All but two were within the subtrochanteric region. In comparison, the historical group—composed of 26 femoral fractures—had a more widespread fracture pattern, with the most frequent location being the mid-diaphysis. Many of the subtrochanteric fractures in the treatment group occurred with minimal trauma.ConclusionsIt appears that concerns over the treatment of the adult osteoporotic population with bisphosphonates are amplified and mirrored in OI. It is possible that the high bending moments in the proximal femur together with altered mechanical properties of cortical bone secondary to the use of this group of drugs increase the risk of this type of injury, which warrants further modification of surgical management of the femur.

Triplane fractures of the distal tibia requiring open reduction and internal fixation: Pre-operative planning using computed tomography

Computed tomography (CT) of triplane fractures provides useful information not available on conventional radiographs. Knowledge of the size and position of displaced fragments, the location of the intra-articular fracture and any associated articular incongruency is useful when undertaking pre-operative planning.A postal survey of surgeons revealed only 38% always requested CT scans before undertaking open reduction and internal fixation of displaced triplane fractures. Examples of the usefulness of CT scans in pre-operative planning is presented in two cases.

A small molecule modulator of prion protein increases human mesenchymal stem cell lifespan, ex vivo expansion, and engraftment to bone marrow in NOD/SCID mice.

Human mesenchymal stem cells (hMSCs) have been shown to have potential in regenerative approaches in bone and blood. Most protocols rely on their in vitro expansion prior to clinical use. However, several groups including our own have shown that hMSCs lose proliferation and differentiation ability with serial passage in culture, limiting their clinical applications. Cellular prion protein (PrP) has been shown to enhance proliferation and promote self‐renewal of hematopoietic, mammary gland, and neural stem cells. Here we show, for the first time, that expression of PrP decreased in hMSC following ex vivo expansion. When PrP expression was knocked down, hMSC showed significant reduction in proliferation and differentiation. In contrast, hMSC expanded in the presence of small molecule 3/689, a modulator of PrP expression, showed retention of PrP expression with ex vivo expansion and extended lifespan up to 10 population doublings. Moreover, cultures produced a 300‐fold increase in the number of cells generated. These cells showed a 10‐fold increase in engraftment levels in bone marrow 5 weeks post‐transplant. hMSC treated with 3/689 showed enhanced protection from DNA damage and enhanced cell cycle progression, in line with data obtained by gene expression profiling. Moreover, upregulation of superoxide dismutase‐2 (SOD2) was also observed in hMSC expanded in the presence of 3/689. The increase in SOD2 was dependent on PrP expression and suggests increased scavenging of reactive oxygen species as mechanism of action. These data point to PrP as a good target for chemical intervention in stem cell regenerative medicine. STEM CELLS2012;30:1134–1143

Limb lengthening and correction of deformity in the lower limbs of children with osteogenesis imperfecta

We performed limb lengthening and correction of deformity of nine long bones of the lower limb in six children (mean age, 14.7 years) with osteogenesis imperfecta (OI). All had femoral lengthening and three also had ipsilateral tibial lengthening. Angular deformities were corrected simultaneously. Five limb segments were treated using a monolateral external fixator and four with the Ilizarov frame. In three children, lengthening was done over previously inserted femoral intramedullary rods. The mean lengthening achieved was 6.26 cm (mean healing index, 33.25 days/cm). Significant complications included one deep infection, one fracture of the femur and one anterior angulation deformity of the tibia. The abnormal bone of OI tolerated the external fixators throughout the period of lengthening without any episodes of migration of wires or pins through the soft bone. The regenerate bone formed within the time which is normally expected in limb-lengthening procedures performed for other conditions. We conclude that despite the abnormal bone characteristics, distraction osteogenesis to correct limb-length discrepancy and angular deformity can be performed safely in children with OI.

Use of the Sheffield telescopic intramedullary rod system for the management of osteogenesis imperfecta: clinical outcomes at an average follow-up of nineteen years.

BACKGROUND Elongating intramedullary rods have been used in the management of osteogenesis imperfecta for the past fifty years. The complication rates reported in many reviews of the available techniques have been high. This study reviews the long-term functional outcomes and complications following the use of the Sheffield system of telescopic intramedullary rods. METHODS We conducted a retrospective analysis of patients with osteogenesis imperfecta who were at least eighteen years of age and who had at least thirteen years of follow-up. Complications, reoperations, and data from a disease-specific questionnaire and the Short Form-36 questionnaire were recorded. RESULTS Data for twenty-two patients with osteogenesis imperfecta who had been treated with Sheffield telescopic intramedullary rods were available at an average of nineteen years after the initial surgery. Reoperations involving thirty-three (50%) of the sixty-six rods were performed: ten rods (15%) were exchanged because of rod disengagement due to growth, thirteen rods (20%) were exchanged because of complications, and ten rods (15%) required further surgery other than exchange because of complications. Mobility was significantly improved at the initial postoperative visit (p = 0.0015), and this improvement was maintained into adulthood (p = 0.0077). Back pain was the most frequent symptom. Symptoms related to rod insertion across the knee and ankle were rare, but symptoms related to proximal femoral trochanteric entry were common. Physeal damage was not seen following surgery, and all rods elongated with growth. All patients were satisfied with the outcome of the surgical procedures. Short Form-36 scores for all physical domains and for social function and vitality were significantly worse than those in a normal population. CONCLUSIONS The outcomes of this technique are satisfactory in adulthood; reoperation rates are high but are most commonly related to the patient outgrowing the rods. Concerns regarding insertion of this fixed device at the knee and ankle were unfounded, although proximal femoral fixation remains a problem.

Closed reduction and stabilization of supracondylar fractures of the humerus in children: the crucial factor of surgical experience.

We reviewed the outcome following operative management of displaced (Gartland II and III) supracondylar fractures of the humerus in children over a 2-year period and tried to correlate the outcome with various factors including experience of the treating surgeon. Of the 71 children who formed the study group, 62 (87.3%) had a good outcome irrespective of the treatment modality. Closed reduction followed by plaster immobilization or percutaneous pinning resulted in a better outcome than open reduction. There was a direct involvement of the consultant in the primary management of these injuries in 17 cases (24%), none of which had a poor outcome. Of the 54 cases in whom the primary management was carried out independently by trainees without any consultant supervision, nine patients (17%) developed complications or needed reoperations. The proportion of unsatisfactory outcomes increased to 20.3% when failure to achieve a satisfactory reduction by closed means was also considered as a perioperative complication. There is a learning curve associated with percutaneous pinning after closed reduction and experience of the surgeon seems to be one of the factors that have an influence on the outcome.

Zoledronate Attenuates Accumulation of DNA Damage in Mesenchymal Stem Cells and Protects Their Function

Mesenchymal stem cells (MSCs) undergo a decline in function following ex vivo expansion and exposure to irradiation. This has been associated with accumulation of DNA damage and has important implications for tissue engineering approaches or in patients receiving radiotherapy. Therefore, interventions, which limit accumulation of DNA damage in MSC, are of clinical significance. We were intrigued by findings showing that zoledronate (ZOL), an anti‐resorptive nitrogen containing bisphosphonate, significantly extended survival in patients affected by osteoporosis. The effect was too large to be simply due to the prevention of fractures. Moreover, in combination with statins, it extended the lifespan in a mouse model of Hutchinson Gilford Progeria Syndrome. Therefore, we asked whether ZOL was able to extend the lifespan of human MSC and whether this was due to reduced accumulation of DNA damage, one of the important mechanisms of aging. Here, we show that this was the case both following expansion and irradiation, preserving their ability to proliferate and differentiate in vitro. In addition, administration of ZOL before irradiation protected the survival of mesenchymal progenitors in mice. Through mechanistic studies, we were able to show that inhibition of mTOR signaling, a pathway involved in longevity and cancer, was responsible for these effects. Our data open up new opportunities to protect MSC from the side effects of radiotherapy in cancer patients and during ex vivo expansion for regenerative medicine approaches. Given that ZOL is already in clinical use with a good safety profile, these opportunities can be readily translated for patient benefit. Stem Cells 2016;34:756–767

Joint distraction and reconstruction in complex knee contractures.

We retrospectively reviewed the results of joint distraction and reconstruction in complex knee contractures in 6 patients with 9 knees. The circular Ilizarov fixator was used in all cases. Extensor mechanism alignment with frame in situ was performed in 4 cases and alignment of mechanical axis of the lower limb was done in 2. All patients had a mean total arc of movement of 79 degrees before operation; however, this was nonfunctional because of the degree of flexion contracture. Three of the 6 patients were nonambulant before surgery. After joint distraction and reconstruction, mean total arc of movement remained unchanged, but this was more functional with improvement in the mobility status. At an average follow-up of 53 months, the mean flexion contracture was 100 degrees (range, 0-70 degrees), with further flexion possible up to 90 degrees (range, 60-120 degrees). Four patients had no recurrence. All 6 patients were ambulant with or without orthosis. Rebound phenomenon with loss of achieved correction was observed in 2 patients. Four patients were quite satisfied with results of surgery. Realignment of the extensor mechanism and mechanical axis is an important part that needs to be addressed in flexion contractures of the knee. Proper preoperative planning and staged procedures reduce the risk of recurrence. A treatment protocol is proposed to help in planning and further management.

Overcorrection and generalized joint laxity in surgically treated congenital talipes equino-varus.

Fifty patients with 70 previously operated clubfeet were assessed for overcorrection (using Tachdjians flat foot grade) and generalized joint laxity. Twenty-eight patients (40 feet) had signs of generalized joint laxity using the Biro score and of these 25 feet were overcorrected. Of the 22 patients (30 feet) who did not have signs of joint laxity, only three overcorrected. This difference was statistically significant (P<0.001). A significant correlation exists between flat foot grade and laxity score (P<0.01). Overcorrection is a complication largely ignored in the published literature but we believe it is a serious complication of open release often resulting in poor long-term function. For those patients requiring surgery, the authors urge caution and recommend a limited surgical release, particularly if joint laxity is suspected, or the Ponseti method of treatment, which will probably avoid this complication.