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Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_3 | Pages 42 - 42
1 Mar 2021
Moldovan F Parent S Barchi S Hassan A Patten K
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The etiology of adolescent idiopathic scoliosis (AIS) is largely unknown, but clinical observations revealed the role of hereditary and rapid growth in the development of this condition. More recently, several genes were suspected to cause or contribute to AIS. Our group identified gene variants of POC5 centriolar protein in a French and French-Canadian families with multiple members affected with AIS. We sought to expand on this study and to investigate for the role of POC5 gene and mutated protein. In this work, the potential pathogenic effect of mutated POC5 was investigated in vitro (human osteoblats cell culture) and in vivo in a zebrafish animal model.

To investigate the role of POC5 in AIS, we investigated subcellular localization of POC5 with respect to cilia in cells overexpressing wt or POC5 variants (C1286T, A429V) and in human osteoblasts from scoliotic patients carrying these POC5 variants and normal control cells (in vitro study). We also created a loss-of-function model in zebrafish (in vivo study). The role of POC5 was investigated by: 1) mass spectroscopy analysis and co-immunoprecipitation to identify differences in binding partners between the wild-type (wt POC5 and mut POC5 protein; 2) immunolocalization of POC5 wt and mut proteins at the cellular level; 3) histology and immunohistochemistry performed on tissues from wt (control) and scoliotic (poc5 mut) zebrafish.

Our work identified several interacting partners with POC5, and documented functional connections with respect to cilia and centrosome dysfunction. A number of ciliary proteins were identified to be interacting with wt POC5 but not mut POC5. At the cellular level, localization and co-localisation of wt POC5 and mut POC5 protein with alpha acetylated tubulin (cilia marker), confirmed the consequence of the mutation on subcellular location with respect to cilium structure, length and staining intensity of cilia. In vivo, several defects in the retina were identified in mut poc5 zebrafish compared wt zebrafish. Finally, using different markers for retinal layers and acetylated tubulin, the defects were localized in ganglion cell layer and cones of the retina.

Our findings confirm the involvement of POC5 in scoliosis. A role of POC5 with respect to the primary cilia was attributed. These findings open new avenues for the understanding the primary causes of AIS at the molecular and physiological levels.


Orthopaedic Proceedings
Vol. 102-B, Issue SUPP_6 | Pages 64 - 64
1 Jul 2020
Lin K Wong F Wang M Teo KY Chuah SJ Ren X Wu Y Hassan A Lai RC Lim S Hui JHP Toh W Lee E Zhang S
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Osteochondral (OC) defects of the knee are associated with pain and significant limitation of activity. Studies have demonstrated the therapeutic efficacy of mesenchymal stem cell (MSC) therapies in treating osteochondral defects. There is increasing evidence that the efficacy of MSC therapies may be a result of the paracrine secretion, particularly exosomes. Here, we examine the effects of MSC exosomes in combination with Hyaluronic Acid (HA) as an injectable therapy on functional osteochondral regeneration in a rabbit osteochondral defect model.

Exosomes were purified from human MSC conditioned medium by size fractionation. A circular osteochondral defect of 4.5 mm diameter and 2.5 mm depth was surgically created in the trochlear grooves of 16 rabbit knees. Thereafter, eight knees received three weekly injections of 200 µg of exosomes in one ml of 3% HA, and the remaining eight knees received three weekly injections of one ml of 3% HA only. The rabbits were sacrificed at six weeks. Analyses were performed by macroscopic and histological assessments, and functional competence was analysed via Young Modulus calculation at five different points (central, superior, inferior, medial and lateral) of the repaired osteochondral defect site.

MSC exosomes displayed a modal size of 100 nm and expressed exosome markers (CD81, TSG101 and ALIX). When compared to HA alone, MSC exosomes in combination with HA showed significantly better repair histologically and biomechanically. The Young Modulus was higher in 4 out of the 5 points. In the central region, the Young Modulus of MSC exosome and HA combination therapy was significantly higher: 5.42 MPa [SD=1.19, 95% CI: 3.93–6.90] when compared to HA alone: 2.87 MPa [SD=2.10, 95% CI: 0.26–5.49], p < 0 .05. The overall mean peripheral region was also significantly higher in the MSC exosome and HA combination therapy group: 5.87 MPa [SD=1.19, 95% CI: 4.40–7.35] when compared to HA alone: 2.70 MPa [SD=1.62, 95% CI: 0.79–4.71], p < 0 .05. The inferior region showed a significantly higher Young Modulus in the combination therapy: 7.34 MPa [SD=2.14, 95% CI: 4.68–10] compared to HA alone: 2.92 MPa [SD=0.98, 95% CI: 0.21–5.63], p < 0.05. The superior region showed a significantly higher Young Modulus in the combination therapy: 7.31 MPa [SD=3.29, 95% CI: 3.22–11.39] compared to HA alone: 3.59 MPa [SD=2.55, 95% CI: 0.42–6.76], p < 0.05. The lateral region showed a significantly higher Young Modulus in the combination therapy: 8.05 MPa [SD=2.06, 95% CI: 5.49–10.61] compared to HA alone: 3.56 MPa [SD=2.01, 95% CI: 1.06–6.06], p < 0.05. The medial region showed a higher Young Modulus in the combination therapy: 6.68 MPa [SD=1.48, 95% CI: 4.85–8.51] compared to HA alone: 3.45 MPa [SD=3.01, 95% CI: −0.29–7.19], but was not statistically significant. No adverse tissue reaction was observed in all the immunocompetent animals treated with MSC exosomes.

Three weekly injections of MSC exosomes in combination with HA therapy results in a more functional osteochondral regeneration as compared to HA alone.


Orthopaedic Proceedings
Vol. 93-B, Issue SUPP_IV | Pages 583 - 584
1 Nov 2011
Letts RM Hassan A
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Purpose: To assess the efficacy of the Taylor Spatial Frame in the correction of rigid long standing foot deformities in older children.

Method: Children presenting with rigid longstanding foot deformities were fitted with a Taylor Spatial Frame (TSF) utilizing specialized small foot rings. Prior to surgery an operative plan was devised including soft tissue release and osteotomies usually consisting of a curved midfoot osteotomy and a dome shaped hind foot osteotomy. About 30% correction was obtained at surgery and held with the TSF. Postoperatively a computerized program of correction over a period of 8 weeks was calculated for each foot beginning 5 days after surgery and including an initial lengthening at each osteotomy site of 1 cm.

Results: A total of eight feet have been corrected utilizing this technique with the TSF. All feet have been successfully returned to a plantigrade position enabling the child to don normal footwear. Ankle-foot orthosis are utilized for one year following surgery. Although the feet are stiff none are painful and all children arev fully ambulatory and weight bearing. All have at least 10 degrees of ankle motion which is improving with time. Families have been very pleased with the improved anatomical appearance of the feet as well as the child’s ability to use normal footwear.

Conclusion: The Taylor Spatial Frame is an efficient and safe method to effect excellent correction of a rigid club foot deformity in combination with osteotomies and soft tissue releases of the foot.


The Journal of Bone & Joint Surgery British Volume
Vol. 92-B, Issue 6 | Pages 880 - 884
1 Jun 2010
Hassan A Whately C Letts M

Stüve-Wiedemann syndrome is an autosomal-recessive disorder characterised by bowing of the long bones, progressive scoliosis, episodic hyperthermia and respiratory distress, usually resulting in death in infancy. We reviewed five children with the condition who had been followed since birth and who survived into childhood with a mean age at operation of 7.8 years (5 to 14). There was marked functional impairment with dysplasia of the long bones and scoliosis. Treatment of the triplanar deformities of the femora involved the use of the Ilizarov technique with the Taylor Spatial Frame.

Walking was preserved and improved in three children along with considerable enhancement of the appearance. Early insertion of a growing rod to control the progressive juvenile scoliosis was beneficial. The use of the Taylor Spatial Frame is strongly recommended to address the major complex deformities of the lower limbs which are encountered in this condition and to prevent their progression.


Orthopaedic Proceedings
Vol. 87-B, Issue SUPP_III | Pages 332 - 332
1 Sep 2005
Ball C Hassan A
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Introduction and Aims: Isolated rupture of the subscapularis tendon is an uncommon condition that has generally been treated by early surgical repair. However, very little information is available regarding functional outcome following surgery. The purpose of this study was to evaluate patient reported outcome following surgical repair with a minimum follow-up of 12 months.

Method: Thirteen consecutive patients underwent arthroscopy followed by open surgical repair of an isolated traumatic rupture of the subscapularis tendon. A deltopectoral approach was used in all cases with repair of the tendon using suture anchors. Tenodesis of the long head of the biceps tendon was carried out in all patients because of instability or rupture. Standardised pre- and post-operative examinations were performed which included goniometric measurements of range of motion and an assessment of subscapularis function and strength. The ASES Shoulder Assessment Form was completed both pre-operatively and at final review.

Results: All patients reported significant pain and functional limitations pre-operatively, with an average pain score of 7/10 and ASES score of 41.2. Limitation of active arm elevation and clinical evidence of sub-scapularis rupture was present in all but one patient. At an average follow-up of 18 months all patients were satisfied and would undergo the procedure again. The average ASES score improved to 91.9, with all patients reporting minimal or no pain. All patients regained overhead elevation and external rotation to within 10 degrees of the other side. Internal rotation and subscapularis function improved in all patients. There were no complications.

Conclusion: Early surgical repair of isolated tears of the subscapularis tendon provides excellent pain relief and reliable restoration of shoulder function and strength. Patient satisfaction is high and the average ASES score can be significantly improved. Associated abnormalities of the long head of biceps tendon are common and should be addressed at the time of surgery.


Orthopaedic Proceedings
Vol. 87-B, Issue SUPP_I | Pages 31 - 31
1 Mar 2005
Hassan A Brown C
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Elbow contracture is a recognized sequel of elbow trauma. We aim at reviewing the clinical outcome of surgical capsulectomy and elbow debridement.

The operative notes as well as pre and post-operative clinical records were reviewed for 15 patients who sustained an elbow trauma which resulted in elbow contracture and were managed with open capsulectomy and debridement. In addition two patients had anterior transfer of the ulnar nerve, twohad removal of loose bodies, two had excision of heterotopic bone, one patient had reconstruction of the medial collateral ligament and one patient had repair of the lateral collateral ligament .

These patients were followed up for a mean of 21 months (6 to 37).

Elbow flexion contracture improved from a mean of 37° (10° to 55°), to a mean of 10° (0° to 25°). Elbow flex-ion improved from a mean of 125° (95° to 140°) to a mean of 129° (90° to 140°). There were no major complications. Two patients underwent repeat debridement due to recurrence of contracture. One patient developed serious collection that settled gradually.

We conclude that open capsulectomy and debridement is a satisfactory way of management of post-traumatic elbow contracture in the short and intermediate term.


Orthopaedic Proceedings
Vol. 85-B, Issue SUPP_I | Pages 9 - 9
1 Jan 2003
Gupte C Hassan A McDermott I Thomas R
Full Access

The objective of this study was to examine patients’ use of the Internet to obtain medical information, their opinions on the quality of medical Web sites and their attitudes towards Internet-based consultations.

The study made use of a questionnaire given to 398 patients, aged 10 to 95 years (mean 55 years), visiting the orthopaedic outpatient clinics of a London district general hospital over a 2 week period. The major outcome measures were; 1) the rate of Internet use by patients, 2) the perception of the quality of medical websites, 3) future intentions and attitudes towards internet-based consultations, and 4) concurrence between information obtained from Web sites and advice given by the orthopaedic surgeon in the clinic. Results were considered significant at p< 0.05. The Chi2 test was used to compare proportions. Spearman’s correlation coefficients were used to quantify correlation.

From 369 respondents (response rate 91%), 55.3% of patients had accessed the Internet. Of these 52.0% had obtained medical information from this source. Access was linearly correlated with age (r2 =0.975, p< 0.01) and was also related to social status. Of the 12.3% of patients who had researched their particular orthopaedic condition, 20% reported that the advice received from the surgeon in the clinical contradicted that obtained from the Internet. A total of 37.5% of patients would undergo an Internet-based consultation, whilst a further 25.5% would consider this, depending on the medical condition in question.

This is the first detailed UK study examining patient attitude towards Web-based medical learning. Over half of the patients were willing to access the Internet for medical information, with younger patients more likely to undertake this activity. As the commercial advantages of a captive patient population become apparent, there is the potential for inaccurate or misleading information, that has not undergone peer review, to be disseminated over the Internet The increased use of medical Websites by patients raised important issues regarding the need for quality control, which orthopaedic surgeons and their institutions both need to address. This also impacts significantly upon the changing nature of the surgeon-patient relationship.


The Journal of Bone & Joint Surgery British Volume
Vol. 80-B, Issue 2 | Pages 372 - 372
1 Mar 1998
BARWELL J ANDERSON G HASSAN A RAWLINGS I


The Journal of Bone & Joint Surgery British Volume
Vol. 79-B, Issue 2 | Pages 265 - 268
1 Mar 1997
Barwell J Anderson G Hassan A Rawlings I

We studied the effects of the timing of tourniquet release in 88 patients randomly allocated for release after wound closure and bandaging (group A), or before the quadriceps layer had been closed allowing control of bleeding before suture (group B). The groups were similar in mean age, weight, gender, preoperative knee score, radiographic grading, and prosthesis implanted.

Patients in group B had less postoperative pain, achieved earlier straight-leg raising, and had fewer wound complications. Five patients in group A had to return to theatre, three for manipulation under anaesthesia, one for secondary closure of wound dehiscence, and one for drainage of a haematoma. The last patient later developed a deep infection, which was treated by a two-stage revision. There were no significant differences between the two groups in operating time, or the decrease in haemoglobin concentration at 48 hours postoperatively.

Some of the adverse effects of the use of a tourniquet for knee surgery can be significantly reduced by early tourniquet release, with haemostasis before the quadriceps mechanism and the wound are closed.