Aim

This study aimed to evaluate the impact on length of hospital stay from dedicated infectious diseases input for orthopaedic infection patients compared to sporadic infection specialist input.

Introduction: Fibroblast growth factor receptor 3 (FGFR3) is a tyrosine kinase membrane-spanning protein whose function is to regulate chondrocyte proliferation, differentiation and matrix production during cartilage development. Several mutations in FGFR3 have now been documented to link to human diseases. A number of these mutations result in constitutive activation of the FGFR3, leading to proliferation and premature differentiation of chondrocytes. Depending on the mutation and the resultant level of FGFR3 activation, mild to severe skeletal dysplasias such as achondroplasia (ACH), hypochondroplasia (HCH), thanatophoric dysplasia type I (TDI) and type II (TDII), and severe achondroplasia with developmental delay and acanthosis nigrans (SADDAN) may result. It has been postulated that the signalling pathways downstream of FGFR3 may be responsible for activating transcription factors, leading to up-regulation of cell cycle inhibitors and causing abnormal suppression of chondrocyte cell proliferation. However, the precise signalling pathways involved in FGFR3 mutation have as yet to be elucidated. The aim of this study was to investigate and compare the differences in the downstream signalling pathways between FGFR3 mutants.

Methods and Results: Wild type FGFR3 has been cloned into expression vector pcDNA3 and the construct has been used to generate four different FGFR3 mutants using site-directed mutagenesis. The mutations which have been introduced and the types of dysplasia they correspond to were as follows: K380R (ACH), N540K (HCH) and K650E (TDII). A kinase dead form of the receptor, K504R has also been generated. Wild type and each of the four mutant FGFR3 proteins in pcDNA3 vector have been successfully transfected into 293T cells using the calcium phosphate method. Immunoprecipitation and Western Blot analysis of cell lysates revealed expression of wild type protein in three isoforms of size 135kDa (mature), 120kDa (intermediate) and 98kDa (immature). The mutant proteins all followed a similar pattern of expression with the exception of the TDII mutant that did not express the mature form of the FGFR3. Changes in MAPK, PLCã and STAT 1 signalling pathways in response to FGFs-1, 2, 9 and 18 in the 293-cells of wild type and mutant forms of FGFR3 are now under investigation, in an attempt to define which pathways are mostly responsible for the resultant abnormal phenotypes.

Discussion: Genomics studies have demonstrated that FGFR3 expression is significantly upregulated during the osteoblastic differentiation of mesenchymal stem cells (MSCs) under BMP-2 stimulation in vitro. Subsequent functional studies have demonstrated that a selective ligand for FGFR3, FGF9, is able to induce tyrosine kinase signalling, and the osteoblastic differentiation of MSCs in vitro. Further understanding the signalling mechanisms of FGFR3 activation in normal and mutant forms may lead to discover potential anabolic agents that are based on FGFR3-FGFs pathways.

Introduction: Patient specific cementless femoral components for THR were developed as a means of addressing the anatomic variations of the proximal femur and hip joint in an effort to achieve long term implant survival and optimum patient function. Design rules were developed with goals of achieving rigid initial stability, maximal endosteal contact for bone integration, and the precise restoration of hip kinematics.

Methods: Beginning in 1989, this series of cementless titanium implants included proximal circumferential HA coating over a macrotextured surface for biologic fixation. All patients who were candidates for cementless arthroplasty (age < 65, active, or overweight) received a custom femoral component. Forty-nine consecutive primary THR in 39 patients were performed during the study period. No patients died and one patient was lost prior to 10 years; all had well fixed stems at latest follow up. The remaining 38 patients (48 hips), 16 females and 22 males, with average age 54 (28-70) and weight 181 (98-270) at surgery, were evaluated at minimum 10 years (range 10-11).

Results: Average modified Harris Hip Scores were 49 (27-87) pre- and 89 (24-100) postoperatively, with pain scores of 17 (0-40) and 42 (10-44) respectively. All femoral components remain well-fixed (Engh Class 1) at final follow-up. No areas of osteolysis were seen distal to the proximal HA-bone interface. Small, focal areas of probable osteolysis were seen at the implant shoulder (4 cases), at the calcar corner (2 cases), and at both sites (1 case). Complications included four proximal margin femoral fissures recognised at surgery, two patients with dislocation, and one non-fatal PE. Reoperations included six head and liner exchanges; two for recurrent dislocation, and four for excessive wear with associated osteolysis (3 pelvic, 1 femoral); and one for fixation and grafting of a trochanteric nonunion.

Discussion: The use of cementless femoral implants based on individual patient characteristics and a set of strict design rules has resulted in excellent clinical and radiographic results at 10-year follow-up. Recent data with some OTS systems have shown comparable excellent results and have diminished the need for the routine use of custom implants in uncomplicated primary situations. However, this series validates the design concepts of this system, supports its use in more complex situations, and suggests applicability on a routine basis where other available implants may be less than optimal.

Introduction: Conventional approaches to cementless revision THR include cemented and cementless stems, which are graft dependent for initial stability (Type 3 reconstructions), distally fixed extensively porous coated implants and modular implants. CT and radiographic visualization, preoperative planning, and patient specific implant fabrication enable the surgeon to achieve the following objectives simultaneously and without compromise: bypass or fill specific bony defects, implement precisely the surgeon’s individual implant design goals, optimise proximal, distal, or regional fit objectives, achieve supplemental fixation via collars, fluted stems, and targeted ingrowth zones/ treatments, and establish head center, neck length, lateral offset, anteversion angle, and leg length.

Methods: This series of cementless titanium implants achieved initial press-fit fixation on host bone with bony attachment via proximally HA coated macrotextured surface. The extramedullary portion of the implant is designed to restore leg length and normal joint mechanics. The initial 44 consecutive revision hips using this rationale were reviewed for inclusion. At surgery, all femoral reconstructions were completed without resorting to Type 3 structural grafts. Six patients died prior to 10 years f/u, and three (4 hips) were lost. Two stems were removed prior to minimum follow up: one at five weeks post-op for deep sepsis, and one for aseptic loosening presumed secondary to metabolic derangements from poorly controlled end-stage renal disease. The remaining 31 patients (34 hips), 18 females and 13 males with a mean age of 61 (range 31-75) and average weight of 168 (85-240) pounds, were evaluated at minimum 10 years (range 10 to 11 years).

Results: All 34 components remain well-fixed (Engh Class 1) at last follow up (97% implant survival). Stress shielding was uncommon outside the calcar region. Average modified Harris Hip Scores were 49 (10-88) pre-operative and 81 (48-100) at final follow-up, with pain scores of 18 (0-44) and 41 (30-44) respectively. Complications included fracture (intraop: 4 fissures, 2 stable type II, 1 unstable type III, and 1 late periprosthetic fractures distally), and three dislocations.

Discussion: The concept of a metaphysical loading, proximally ingrown, collared patient specific revision implant gave results comparable to Engh’s series of extensively coated revision stems, while avoiding the high failure rate associated with structural allograft, the worrisome proximal bone loss associated with fully porous coated stems, the high cost of modular implants.