To determine the risk of total knee replacement (TKR) for primary osteoarthritis (OA) associated with overweight/obesity in the Australian population. This population-based study analyzed 191,723 cases of TKR collected by the Australian Orthopaedic Association National Joint Registry and population data from the Australian Bureau of Statistics. The time-trend change in incidence of TKR relating to BMI was assessed between 2015-2018. The influence of obesity on the incidence of TKR in different age and gender groups was determined. The population attributable fraction (PAF) was then calculated to estimate the effect of obesity reduction on TKR incidence. The greatest increase in incidence of TKR was seen in patients from obese class III. The incidence rate ratio for having a TKR for obesity class III was 28.683 at those aged 18-54 years but was 2.029 at those aged >75 years. Females in obesity class III were 1.7 times more likely to undergo TKR compared to similarly classified males. The PAFs of TKR associated with overweight or obesity was 35%, estimating 12,156 cases of TKR attributable to obesity in 2018. The proportion of TKRs could be reduced by 20% if overweight and obese population move down one category. Obesity has resulted in a significant increase in the incidence of TKR in the youngest population in Australia. The impact of obesity is greatest in the young and the female population. Effective strategies to reduce the national obese population could potentially reduce 35% of the TKR, with over 10,000 cases being avoided.
The 2020 London International Hamstring Consensus meeting was convened to improve our understanding and treatment of hamstring injuries. The multidisciplinary consensus panel included 14 International specialists on the management of hamstring injuries. The Delphi consensus process consisted of two rounds of surveys which were completed by 19 surgeons from a total of 106 participants. Consensus on individual statements was regarded as over 70% agreement between panel members. The consensus group agreed that the indications for operative intervention included the following: gapping at the zone of injury (86.9%); high functional demands of the patient (86.7%); symptomatic displaced bony avulsions (74.7%); and proximal free tendon injuries with functional compromise refractory to non-operative treatment (71.4%). Panel members agreed that surgical intervention had the capacity to restore anatomy and function, while reducing the risk of injury recurrence (86.7%). The consensus group did not support the use of corticosteroids or endoscopic surgery without further evidence. These guidelines will help to further standardise the treatment of hamstring injuries and facilitate decision-making in the surgical treatment of these injuries.
Despite the increase in the surgical repair of proximal hamstring tears, there exists a lack of consensus in the optimal timing for surgery. There is also disagreement on how partial tears managed surgically compare with complete tears repaired surgically. This study aims to compare the mid-term functional outcomes in, and operating time required for, complete and partial proximal hamstring avulsions, that are repaired both acutely and chronically. This is a prospective series of 156 proximal hamstring surgical repairs, with a mean age of 48.9 years (21.5 to 78). Functional outcomes were assessed preinjury, preoperatively, and postoperatively (six months and minimum three years) using the Sydney Hamstring Origin Rupture Evaluation (SHORE) score. Operating time was recorded for every patient.Aims
Methods
Osteoarthritis (OA) is traditionally believed to affect the osteochondral unit by wear-and-tear from the superficial zone to the deep zone of cartilage and extended to subchondral plate. Obesity is commonly considered as a risk of OA development and hence total knee replacement (TKR), but the mechanism remains unclear. We hypothesized that obesity accelerated OA development by deteriorating tidemarks and increasing bone remodelling. 616,495 cases of TKR for OA from Australia and British joint replacement registries were collected, and data indicated that patients with higher BMI had TKR at earlier age. Specifically, patients with BMI ≤25kg/m2 showed 8 years younger than patients with BMI ≥40kg/m2 (P<0.0001) when they received TKR. We next examined tibia plateaus of 88 knee OA patients by micro-CT and histomorphometry. Linear regression showed that less cartilage degradation was associated with increased BMI in the load-bear compartment (p<0.05), while 58.3% of patients with BMI≥40kg/m2 demonstrated a clear anatomical separation close to tidemarks filled with fibrosis, erythrocytes and bone fragments (compared to BMI ≤25kg/m2 group: 7.7%, p<0.01). In subchondral bone, elevated bone formation was associated with increased BMI, as higher thickness of osteoid (p<0.01), percent osteoid volume (p<0.01), percent osteoid surface (p<0.01) were found in obese patients. However, no alteration of bone resorption and microstructural parameters was found to be associated with BMI. We suspected that the abnormal loading in knee joint due to high BMI led to the direct deterioration of binding site of osteochondral unit, which might be the mechanism of the rapid progression in obesity-related OA.
Training the next generation of surgeon's forms part of routine Consultant practice. Stress causes activation of the Autonomic Nervous System and this can be directly measured using heart rate (HR). Training time is limited with pressures from EWTD and management and efficiency targets. The aim of this study was to assess whether being an orthopaedic trainer is more stressful than performing the surgery. This was a prospective multicentre study. Consultant orthopaedic surgeon HR was monitored intra-operatively using a ‘Wahoo Fitness’ chest strap and the data recorded by the proprietary Android app. Data was collected prior to surgery to obtain a resting heart rate, and at set points during total hip arthroplasty (THA) and total knee arthroplasty (TKA). The peak and mean HR for each stage of the operation were recorded and compared to cases where the consultant surgeon was performing the case or assisting a trainee. Data was compared with a 2-way ANOVA with repeated measures.Introduction
Methodology
Obesity is a global epidemic of 2.1 billion people and a well known cause of osteoarthritis. Joint replacement in the obese attracts more complications, poorer outcomes and higher revision rates. It is a reversible condition and the fundamental principles of dealing with reversible medical conditions prior to elective total joint replacement should apply to obesity. The dilemma for orthopaedic surgeons is when to offer surgery in the face of a reversible condition, which if treated may obviate joint replacement and reduce the risk and severity of obesity related disease in both the medical arena and the field of orthopaedics.
The most concerning infection of allografts and operative procedures
is methicillin resistant An iontophoresis cell was set up with varying concentrations
of Vancomycin within the medulla of a section of sheep tibia, sealed
from an external saline solution. The cell was run for varying times,
Vancomycin concentrations and voltages, to gain information on optimisation
of conditions for impregnating the graft. Each graft was then sectioned
and dust ground from the exposed surface. The dust was serially
washed to extract the Vancomycin and concentrations measured and
plotted for all variables tested.Objectives
Methods
This article provides an overview of the role of genomics in sarcomas and describes how new methods of analysis and comparative screening have provided the potential to progress understanding and treatment of sarcoma. This article reviews genomic techniques, the evolution of the use of genomics in cancer, the current state of genomic analysis, and also provides an overview of the medical, social and economic implications of recent genomic advances.
To determine the outcome after the Semi-tendinosis tendon was used in reconstruction of the Medial Patella-femoral ligament using a fixed dynamic stabilising structure. The Adductor Magnus tendon insertion at the Adductor tubercle of the medial femoral condyle was used as a dynamic and fixed stabilising point preventing patella subluxation. This is a constant landmark in most patients and eliminates the need to find the isometric stabilisation point of the Medial Patella-femoral ligament. The Semi-tendinosus tendon was routed from its distal tibia attachment through a drill hole in the patella from distal to proximal. It was then transferred sub-vastus around the Adductor Magnus femoral attachment and sutured back onto itself at the inferior patella pole. It was tensioned at 30 degrees of knee flexion. Between 2004 and 2011 forty knees were reconstructed using the Semi-tendinosus tendon combined with an extra-synovial lateral release. All had failed conservative therapy for repeated patella instability. Post-operatively the patients followed a strict rehabilitation protocol. At follow-up the patients were questioned for any symptoms of patella instability or dislocation. Any complications of the surgery were documented. Patients were examined for any signs of patella apprehension or abnormal patella tracking.Purpose of the study
Method
There is ongoing debate on the benefits of fixed versus mobile bearing Unicompartmental Knee Replacement (UKR). We report the results from a randomised controlled trial comparing fixed and mobile bearing of the same UKR prosthesis. Forty patients were randomized to receive identical femoral components and either a fixed or mobile bearing tibial component. At 6.5 years follow-up 37% of the mobile bearing design had been revised and 14% for the fixed bearing design. The main reasons for revision were pain and loosening. These results were compared with data from The Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR) that show a cumulative percent revision of 24.2% for the mobile bearing Preservation UKR at 6.5 years. All locally explanted mobile bearings were examined microscopically, and 83% demonstrated significant backside wear. Constraint on the undersurface of the bearing coupled with a congruent upper surface may have contributed to the excessive revision rate. This is the first randomised controlled trial examining mobile and fixed variations of the same UKR prosthesis and shows this design of UKR with the mobile bearing has an unacceptably high revision rate and patients with this knee design should be closely monitored.
Richard Carey Smith is an orthopaedic oncology surgeon with fellowship training in the UK, USA, Australia and Canada, and has worked in Zambia, Zimbabwe and Papa New Guinea. David Wood is head of the University Department of Orthopaedics in Perth, Western Australia. He did his masters in Africa, and first experienced Papa New Guinea on his medical elective, starting a lifelong commitment to medical aid work there.
The aim of this study was to compare a single-incision minimally invasive (MI) posterior approach with a standard posterior approach in a double-blind prospective randomised controlled trial. A pilot study was carried out to assess the efficacy of the MI approach. Primary total hip replacements meeting the inclusion criteria were randomised to either the MI approach or the standard posterior approach. Patients were blinded to allocation. Patients were scored by a blinded physiotherapist pre-operatively, at Day 2, 2 weeks and 6 weeks. The primary outcome measure was function, assessed using the Oxford hip score, SF-12 questionnaire, Iowa score, 6-minute walk test and the number of walking aids required after 2 and 6 weeks post-operatively. Secondary outcomes were complication rates, patient satisfaction, soft tissue trauma and radiographic analysis.Aim
Method
We have conducted a prospective, observational clinical trial of 34 patients with dual compartment osteoarthritis of the knee treated with a 2/3 Knee.
Exclusion criteria included obesity, inflammatory arthritis and a fixed flexion deformity >
10 degrees. Subjective outcome measures included Oxford Knee Scores (OKS) and EQ-5D Scores. RSA beads were implanted at surgery to detect loosening, micro-motion and prosthesis wear. Gait analysis was conducted at 1 year post op in a subgroup of patients.
The patients have recorded Significant improvement in their Oxford Knee Scores at 6 months (mean reduction all patients: 17.3, resurfaced 20). Early RSA results have not detected Significant migration to indicate early loosening. Gait analysis has shown that patients return to approximate normal rather than pre-operative gait.
It is essential that patients undergo primary patella resurfacing to prevent crepitus and associated anterior knee pain. A study comparing clinical outcomes of 2/3 Knee vs TKA is underway at our institution.
Articular cartilage has limited regenerative potential. Regeneration via autografts or cell therapy is clinically efficacious but the extent of regenerative success depends upon use of an appropriate cell source. The aim of this study was to compare the proliferative and chondrogenic potentials of three human cell types (human bone marrow stromal cells - HBMSCs, neonatal and adult chondrocytes) commonly used in cartilage tissue engineering. HBMSCs, neonatal and adult chondrocytes (passage 2) were cultured in basal and chondrogenic media. At 2, 4 and 6 days, the cells were analysed for morphology and doubling time. Alkaline phosphatase specific activity (ALPSA) was quantified for each group at 2, 4 and 6 weeks. Chondrogenic potential of each cell type was assessed via a pellet culture model. Cryosections were stained with Alcian blue/Sirius Red. HBMSCs showed either elongated or polymorphic phenotypes, with a doubling time of 40 h. Neonatal chondrocytes showed a uniform spindle shape and had the shortest doubling time (16 h). Adult chondrocytes, were also spindle shaped, though slightly larger than the neonatal cells, with a longer doubling time of 22 h. Expression of ALPSA in basal media was of the order HBMSCs >
adult chondrocytes >
, neonatal chondrocytes. In chondrogenic culture, this order changed to adult chondrocytes >
HBMSCs >
neonatal chondrocytes. In 3D pellet cultures, all three cell types stained positive for Alcian Blue and showed the presence of chondrocyte-like cells enclosed in lacunae. This comparative study suggests that neonatal chondrocytes are the most proliferative with lowest ALP expression. However, in terms of clinical applications, HBMSCs may be better for cartilage regeneration given their lower ALP expression under chondrogenic conditions when compared with adult chondrocytes under the same conditions. The study has provided information to inform clinical cell therapy for cartilage regeneration.
Calcitonin has been recently shown to have a direct protective effect on articular cartilage against joint degenerative disease. It has been proposed that calcitonin might act through the calcitonin receptor (CTR) to activate the cyclic AMP pathway and protect type II collagen degradation. In this study, we examined the presence of the CTR in human articular cartilage and chondrocytes and investigated the potential pharmacological effects and transduction pathway of salmon calcitonin in human chondrocytes. Five human articular cartilage samples were examined for the expression of the CTR by polymerase chain reaction (PCR), immunostaining and Western blotting. Cyclic AMP levels in human chondrocyte stimulated with salmon calcitonin were measured by ELISA. The effect of salmon calcitonin on the gene expression profiles, including aggrecan, type II collagen, matrix metalloproteinase (MMP)-1, MMP-3 and MMP-13, of human chondrocytes was also examined by Real-time PCR. It was shown that CTR was not detectable in human cartilage and chondrocytes. The cAMP level in human chondrocytes in vitro was significantly increased by forskolin (100μM) by >
10 fold (P<
0.001), but was not induced by salmon calcitonin (10^-7M, 10^-8M, 10^-9M). Real-time PCR demonstrated that salmon calcitonin tended to reduce the gene expression of MMPs, yet without statistical significance. In contrast to previous reports, our data showed that human cartilage and chondrocytes do not express calcitonin receptors. There was no direct effect of salmon calcitonin on human chondrocytes. The result suggests that the chondroprotective effect of calcitonin observed in vivo may be indirect via its effect on subchondral bone resorptive activity.
Patella instability can be a disabling condition predominately affecting younger patients, restricting activity and potentially leading to premature osteoarthritis. We describe and evaluate a new technique of stabilising the joint. Between November 2000 and January 2002 we operated on 24 unstable knees (belonging to 23 patients). All patients had failed a course of conservative treatment and the average number of dislocations pre-operatively was 7. All patients had an extra-synovial lateral release and stabilisation by harvesting the semitendinosus tendon which was then tunnelled through a vertical hole in the patella, under the vastus medialis, wrapped around the adductor magnus and tied to itself at the lower border of the patella. The patients were assessed clinically and radiologically at an average of 19 months, following the procedure. There were 19 knees assessed: 13 female /6 male, 10 left /9 right, average age 22 years. 13 patients had retro-patella chondral damage none had meniscal or cruciate pathology. The visual analogue score increased from 4 pre-op to 7.5 after operation. The Kujala patello-femoral score was 74 post procedure. 53% of patients described their knee as excellent, 47% as good. Only one patient has re-dislocated to date (single event). There were no specific risk factors.
We treated 34 patients with recurrent dislocation of the hip with a constrained acetabular component. Roentgen stereophotogrammetric analysis was performed to assess migration of the prosthesis. The mean clinical follow-up was 3.0 years (2.2 to 4.8) and the radiological follow-up was 2.7 years (2.0 to 4.8). At the latest review six patients had died and none was lost to follow-up. There were four acetabular revisions, three for aseptic loosening and one for deep infection. Another acetabular component was radiologically loose with progressive radiolucent lines in all Gruen zones and was awaiting revision. The overall rate of aseptic loosening was 11.8% (4 of 34). Roentgen stereophotogrammetric analysis in the non-revised components confirmed migration of up to 1.06 mm of translation and 2.32° of rotation at 24 months. There was one case of dislocation and dissociation of the component in the same patient. Of the 34 patients, 33 (97.1%) had no further episodes of dislocation. The constrained acetabular component reported in our study was effective in all but one patient with instability of the hip, but the rate of aseptic loosening was higher than has been reported previously and requires further investigation.
Compartment syndrome is a rare complication of total knee arthroplasty that requires early recognition and prompt decompression in order to prevent long-term disability. We have found only one previous case report in the literature. We present a series of seven cases from four hospitals and five surgeons. Six of the cases resulted in the loss of at least one compartment, and one resulted in amputation. Four of the cases resulted in legal action. We suggest that important risk factors contributing to the development of this condition include complex surgery, soft-tissue compromise, previous surgery, and possibly vascular disease. Delay in the diagnosis and hence delay in decompression was common in our series, and in five cases appeared to be related to the use of a postoperative epidural infusion for pain relief. The presence of associated neurological compromise may have also been a significant factor in the delay to diagnosis in two cases.
Eleven patients had a lateral closing wedge osteotomy; the medial opening wedge was performed in a case of leg shortening. Mean operation duration was 72 minutes (60–90). The graft was fixed with fibrin glue in all cases, and augmented with stitches or vicryl pins in five cases. Mean defect size was 6.2cm2 (2–12). There were three complications: one DVT, a haemarthrosis and a graft detachment. Average follow-up was 16 months. MRI scans at three months show oedematous tissue at the defect sites, contrasting with the fluid filled defects seen preoperatively. Scans at one-year show hyaline-like cartilage infill with similar signal characteristics to native hyaline cartilage. Six minute walk test and knee injury and osteoarthritis outcome score indicate significantly improved functional capacity at six months and one year.
Minimum follow-up was 3 years in group 1 and 1.5 years in group 2. There were 3 dislocations in group 1, and none in group 2. There were 2 re-operations in both groups. The relative improvement in WOMAC scores was significantly greater in group 2 at 3 months and 1 year (P<
0.05).
We carried out a blinded prospective randomised controlled trial comparing 2-octylcyanoacrylate (OCA), subcuticular suture (monocryl) and skin staples for skin closure following total hip and total knee arthroplasty. We included 102 hip replacements and 85 of the knee. OCA was associated with less wound discharge in the first 24 hours for both the hip and the knee. However, with total knee replacement there was a trend for a more prolonged wound discharge with OCA. With total hip replacement there was no significant difference between the groups for either early or late complications. Closure of the wound with skin staples was significantly faster than with OCA or suture. There was no significant difference in the length of stay in hospital, Hollander wound evaluation score (cosmesis) or patient satisfaction between the groups at six weeks for either hips or knees. We consider that skin staples are the skin closure of choice for both hip and knee replacements.
Allograft bone is widely used in orthopaedic surgery, but peri-operative infection of the graft remains a common and disastrous complication. The efficacy of systemic prophylactic antibiotics is unproven, and since the graft is avascular it is likely that levels of antibiotic in the graft are low. Using an electrical potential to accelerate diffusion of antibiotics into allograft bone, high levels were achieved in specimens of both sheep and human allograft. In human bone these ranged from 187.1 mg/kg in endosteal ( Structural allograft can be supplemented directly with antibiotics using iontophoresis. The technique is simple and inexpensive and offers a potential means of reducing the rate of peri-operative infection in allograft surgery. Iontophoresis into allograft bone may also be applicable to other therapeutic compounds.
periostial-covered autologous chondrocyte implantation (PACI); collagen-covered autologous chondrocyte implantation (CACI); matrix-induced autologous chondrocyte implantation (MACI). The team at the University of Western Australia has concentrated on CACI and MACI techniques because of concerns over fibroblast formation and hypertrophy with PACI. Definitive evidence regarding the role of the membrane in enhancing chondrocyte-mediated cartilage regeneration is lacking.
Patients were scored pre-operatively and followed up prospectively. The only special instruments required are two large curved Hohmann retractors and an angled cup introducer.
Forty-two percent of patients were male. Mean age was 68.9 years (42–90) and BMI 26 (14–39). Average operation time was 64.1 minutes and anaesthetic time 92.5 minutes. Mean fall in haemoglobin in the first 24 hours was 2.3g/dl. Mean incision length was 7.4cm. Follow-up was a minimum of one year (range 12–29 months). There was a highly statistically significant improvement in WOMAC and SF-36 scores at three and 12 months post-operatively (p<
0.0001). Early medical complications occurred in 12 patients, including two superficial infections, all of which resolved. There were no peri-prosthetic fractures and importantly, no dislocations. There were two re-operations: one revision for cup displacement and one washout for deep infection.
In our clinical series, over 30% of patients experienced paraesthesia and some experienced a burning dysaesthesia in the distribution of the LFCN.
In relation to the conduct of this study, one or more of the authors is in receipt of a research grant from a non-commercial source.
Successful reconstructive surgery with allografts is severely limited by a failure rate of 30 – 40%. Allograft failure is due to nonunion of the graft-host junction. The molecular mechanism by which this occurs is not yet fully elucidated. Using a sheep femoral allograft model, we have investigated the cellular and molecular mechanisms associated with nonunion of bone allografts. Five, from a total of twelve operations, resulted in the development of graft-host nonunion, reflecting a failure rate of 42%. Histological assessment revealed that allograft failure was due to the excessive accumulation of and resorption by, osteoclasts (Ocs) on the surface of the bone allograft. Three distinct layers, lying adjacent to the allograft bone surface, in the nonunion groups, were identified. The outer fibroblastic layer contained abundant fibroblasts and connective tissue. Underlying this layer were synovial-like cells and some multinuclear giant cells. The third layer, opposing the bone surface, consisted of Ocs and round mononuclear cells. Histomorphometric analysis showed that allograft unions, featured a large amount of newly formed bone on the surface, (OS/BS = 47.81%) with a small proportion of eroded surface (ES/BS = 20.59%). The number of osteoclasts associated with the allograft bone surface were few (Oc/B.Pm = 1.7190/mm) and activity (ES/BS = 46.68%) of Ocs with a reduced amount of new bone formation (OS = 6.35%). Both calcitonin receptor and H+ATPase mRNA, characteristically expressed by Ocs, were localised to the multinuclear giant cells, indicating that they were Ocs. Synovial-like cells in the histological layer above the Ocs, expressed gene transcript for the Osteoprotegrin Ligand (OPGL), a membrane bound factor that is critical for the induction of Oc activity and osteoclastogenesis. In conclusion, these findings suggest that failure of bone allografts is partially due to excessive resorption by host Ocs, accompanied by reduced bone formation. The production of OPGL by synovial-like cells, may be responsible for the recruitment and generation of Ocs.
A paper was presented two years ago reviewing evidence of absorption of the Bio Interference screw and tunnel widening at three, six and 12 months following anterior cruciate ligament reconstruction using double-stranded hamstrings. The femoral fixation was with an Endobutton with a double loop of Mercylene tape with a Bio Interference screw and an extra small staple for the distal fixation. This paper presents further magnet resonance imaging (MRI) studies at least two years after surgery on 10 of those patients to assess if there was any MRI evidence of absorption of the Bio Interference screw or tunnel widening (in particular ganglion formation) in the femoral or tibial tunnels. The results showed that at least two years after surgery there was little evidence of Bio Interference screw absorption. There was no evidence of tunnel widening.
Articular cartilage defects of the knee occur commonly in sports injuries and trauma. Increasing evidence suggests that the only technique that enables the regeneration of articular hyaline cartilage in chondral defects is autologous chondrocyte implantation (ACI). Here we have reported our clinical experience of autologous chondrocyte implantation using biodegradable type I/III collagen membrane (CACI). A total of 26 patients (age range from 19 to 60 years, average 37 years) was conducted with CACI. Pre-operative magnetic resonance imaging (MRI) scans were performed on all patients. Post-operative MRI scans were planned for approximately three and 12 months after the surgery to determine the success of integration of implanted chondrocytes. The results demonstrated that the initial post-operative MRI scans at three months showed the presence of oedematous tissue at the defect sites in 23 patients, contrasting with the fluid filled defects seen preoperatively and with and MRI signal differing from that of the surrounding normal hyaline articular cartilage. MRI scans in nine patients at 12 months after their operations showed maturation of cartilage graft in all patients. Apopototic testing of the chondrocytes using Annexin IV before implantation showed that the viability of the chondrocytes was over 85% where the apopototic rate of chondrocytes was less than 2%. One patient with an apopototic rate of over 10% has a delayed repair in cartilage defects as shown by MRI. In conclusion, early phase clinical studies showed that autologous chondrocyte implantation remains promising for the treatment of chondral defects with restoration of hyaline cartilage. Longer clinical follow-up of the patients and better assessment of cellular phenotype of chondrocytes before implantation are required.
We report a prospective study of the influence of various factors on the six-month mortality of 531 patients with subcapital hip fractures. We performed univariate and multivariate analyses on the 403 patients treated surgically. The most significant predictors of the six-month mortality were dementia, postoperative chest infection, malignant neoplasia, old age and deep-wound infection, in that order. A simple test of mental ability was the most significant prognostic indicator and this test should be included in future studies of the management of hip fractures in the elderly.
The early results of revision osteoarticular allografts in weight-bearing joints are reported. Sixteen consecutive patients underwent surgery over a six-year period between 1982 and 1988. At the time of review eight patients (50%) had surviving second allografts with an average follow-up time of 48 months (range 12 to 87). Five patients were graded excellent according to the Mankin scale, one good and two fair. Eight patients (50%) required further surgery, but only two patients came to amputation.