Sanjeev Madan

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.

Outcomes of hip arthroscopy. A prospective analysis and comparison between patients under 25 and over 25 years of age

Objective To compare the results of hip arthroscopy in patients under the age of 25 with those over 25 years. Design From March 2006 until May 2010, data were collected on all patients who underwent hip arthroscopy for symptomatic intra-articular hip pathology. The patients were divided into two groups based on age (less than 25 years and over 25 years). Patients completed the modified Harris hip score (MHHS), non-arthritic hip score (NAHS) and hip dysfunction and osteoarthritis outcome score (HOOS) questionnaires at baseline then at 6 weeks, 6 months, 12 months and at latest follow-up. Participants 88 patients who underwent 94 hip arthroscopies by the senior author. Mean age was 24.3 (range 11–57 years). Results The mean NAHS and HOOS subscales for pain and activities of daily living were worse at baseline in over 25 groups. Follow-up ranged from 9 to 68 months. 45 hips had greater than 3 year follow-up. The MHHS improved in both groups with a mean difference in the under-25 group of 16.22, and 20.88 in the over 25s. Improvements in the NAHS and HOOS subscales were also of a similar magnitude. There was no statistically significant difference between outcome scores of the two groups at the latest follow-up visit. Conclusions We found a comparable improvement in outcome between those patients under 25 years and those over 25 years. We propose that hip arthroscopy is of potential benefit to patients with symptoms of femoroacetabular impingement regardless of age.

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

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

Arthroscopic treatment of femoroacetabular impingement following slipped capital femoral epiphysis

UNLABELLED Slipped capital femoral epiphysis (SCFE) may lead to symptomatic femoroacetabular impingement (FAI). We report our experience of arthroscopic treatment, including osteochondroplasty, for the sequelae of SCFE. Data were prospectively collected on patients undergoing arthroscopy of the hip for the sequelae of SCFE between March 2007 and February 2013, including demographic data, radiological assessment of the deformity and other factors that may influence outcome, such as the presence of established avascular necrosis. Patients completed the modified Harris hip score (mHHS) and the non-arthritic hip score (NAHS) before and after surgery. In total, 18 patients with a mean age of 19 years (13 to 42), were included in the study. All patients presented with pain in the hip and mechanical symptoms, and had evidence of FAI (cam or mixed impingement) on plain radiographs. The patients underwent arthroscopic osteoplasty of the femoral neck. The mean follow-up was 29 months (23 to 56). The mean mHHS and NAHS scores improved from 56.2 (27.5 to 100.1) and 52.1 (12.5 to 97.5) pre-operatively to 75.1 (33.8 to 96.8, p = 0.01) and 73.6 (18.8 to 100, p = 0.02) at final follow-up, respectively. Linear regression analysis demonstrated a significant association between poorer outcome scores and increased time to surgery following SCFE (p < 0.05 for all parameters except baseline MHHS). Symptomatic FAI following (SCFE) may be addressed using arthroscopic techniques, and should be treated promptly to minimise progressive functional impairment and chondrolabral degeneration. TAKE HOME MESSAGE Arthroscopy of the hip can be used to treat femoroacetabular impingement successfully following SCFE. However, this should be performed promptly after presentation in order to prevent irreversible progression and poorer clinical outcomes.

Pelvic Osteotomy Techniques and Comparative Effects on Biomechanics of the Hip: A Kinematic Study

Dysplasia of the hip is characterized by malpositioning of the proximal femur in a shallow acetabulum, providing deficient femoral head coverage. This abnormal relationship leads to altered biomechanics of the hip joint, as predicted by measurement of kinematic parameters such as increased load over reduced acetabular weight-bearing area, leading to increased joint contact stresses, which subsequently results in secondary osteoarthrosis, pain, and disability. To prevent these sequelae, particularly in children and younger adults, various osteotomies have been performed with varying degrees of success. The goal of this study was to devise a simple and reproducible laboratory method to perform a kinematic analysis of the individual and comparative effects of 5 commonly performed pelvic osteotomy techniques: Chiari pelvic osteotomy, Salter innominate bone wedge osteotomy, Steel triple pelvic osteotomy, Tönnis triple pelvic osteotomy, and Ganz periacetabular pelvic osteotomy. The aim was to determine which of the osteotomy techniques caused greater correction in most of the kinematic parameters used to estimate changes in the biomechanics of the hip joint. Our hypothesis was that pelvic osteotomies such as Chiari and Salter produced favorable changes and were relatively easily reproducible, but that more biomechanical correction in all planes would be achieved by the relatively more complex triple innominate bone and Ganz osteotomy.

Inherited Skeletal Dysplasias and Collagen Diseases

Inherited skeletal dysplasias are a heterogeneous group of genetic disorders associated with abnormalities in the skeletal system frequently presenting with limb abnormalities and disproportionate short stature. There are over 100 distinct skeletal dysplasias, which have been classified primarily on the basis of the clinical or radiographic characteristics (International Working Group, 1998). The management of these conditions require a combined effort involving various specialists including radiologists, orthopaedic surgeons, clinical geneticists, physiotherapists, rehabilitation clinicians and clinical psychologists.

Minimally invasive (MIS) Tönnis osteotomy– A technical annotation and review of short term results

Aims We detail a modified single incision approach to perform the Tonnis triple pelvic osteotomy by a minimally invasive approach. Patients and Methods 12 children underwent minimally invasive Tonnis Osteotomy. There were five boys and seven girls in this study group. Average age was 11 years (9-15 years) at the time of surgery. Mean follow-up was 20.5 months (13-39 months). Results The average preoperative Antero-Posterior (AP) Centre Edge (CE) angle was -8.8° (-38.6°-18°), the average post-operative AP CE angle was 29.7° (25.1°-43.7°). The average preoperative lateral CE angle was -4.7° (-16°-0°), the average postoperative Lateral CE angle was 28.5° (21.3°-37.4°). The Sharps angle before and after surgery were 55.7° (51.3°-66°) and 32.4° (16.1°-40.1°) respectively. The mean Tönnis angle before and after the osteotomy were 28.86° (19.7°-43.4°) and 6.3° (0.5°-9.4°) respectively. There was one major complication with sciatic nerve palsy which is in the recovery phase on followup and six minor complications including two cases of transient lateral femoral cutaneous nerve injury, two cases of ischial non-union, over granulation of the wound in one case, and metalwork irritation in one case. Conclusion We have described a minimally invasive Tonnis osteotomy as a viable option based on our results. This technique is recommended for those who are conversant with the traditional pelvicosteotomies.

Brief concept of hip preservation

Restoration of the anatomy of the hip joint and biomechanics across it, carry the immense importance to prevent future osteoarthritis of the joint. The aim of this review is to provide the brief concept of the methods to preserve the hip, especially in young adults. Attempts to preserve the hips start with the intense preoperative planning of the corrective procedure. Different parameters regarding the femur and acetabulum in all 3 dimensions need to be assessed. Especially, measurement of the anteversion of the femur and acetabulum is a significant step to avoid osteoarthritis. In addition, the suprapelvic and infrapelvic (spine and lower limb lengths) alignment needs to be considered in the planning. Correction of the femoral side of the hip needs the understanding of the blood supply of the proximal femur which carries the risk of avascular necrosis more so with intracapsular osteotomies. Acetabular reorientation, to re-distribute the forces over the weight bearing part, can be carried out with re-directional osteotomy such as periacetabular osteotomy. It needs the understanding of the acetabular anatomy and the force distribution in it. To conclude, correction of both femoral and acetabular side parameters need to be considered in decision making depending on the alterations due to various etiologies causing the hip disorders.