Partial Fanconi syndrome induced by ifosfamide.

Ifosfamide-induced proximal tubular nephropathy can present as a spectrum of disease, from isolated hyperaminoaciduria to a partial or complete Fanconi syndrome. We report a case of ifosfamide-induced partial Fanconi syndrome in a man with metastatic progressive Ewing sarcoma and put forth a hypothesis on the mechanism.

Patellectomy for osteoarthritis: a new tension preserving surgical technique to reconstruct the extensor mechanism with retrospective review of long-term follow-up.

BACKGROUND: The management of severe patellofemoral arthritis in young patients remains a significant problem. For many, patellofemoral replacement is not a desirable option. Current surgical techniques for patellectomy disrupt the extensor lever arm causing weakness. We describe a new technique that maintains the extensor mechanism tension and a case series showing good results for patella-only arthritis at a mean follow-up of 11 years. METHODS: Eight patellectomies were performed using a new surgical technique in patients with a mean age of 38 years, and an average follow-up of 11 years (range 8-16 years). Patients were followed up using a pain visual analogue scale, Lysholm knee score and patient-reported outcome measures. RESULTS: All patients experienced pain relief following surgery. Those with patella-only arthritis had better outcomes than patients who had patella and trochlea disease. All patients had either full or near full extension. Lysholm scores were better in patients who had disease confined to the patella. CONCLUSION: We believe patellectomy with this tension-preserving technique has a role for the management of anterior knee pain secondary to severe patella-only arthritis in young patients where arthroplasty is not desirable.

Patients' preferred mode of travel to the orthopaedic theatre.

AIM: To determine the preferred mode of travel to the operating theatre for elective orthopaedic patients. METHODS: Data was collected prospectively over a 2-wk period at an elective Orthopaedic Treatment Centre. Patients were asked to complete a patient satisfaction questionnaire following their surgery on their experience and subsequent preferred mode of transport to theatre. The data was then recorded in a tabulated format and analysed with percentages. Fisher's exact test was used to determine if there was any statistical association between patients' preference to walk and various groups; in-patient or day case procedures, and whether patients were < 60 years or > 60 years of age. RESULTS: Seventy patients (40 females and 30 males) fully completed the questionnaire. In total there were 33 d-cases and 37 in-patients. The spectrum of orthopaedic sub-specialties included was knee (41%), hip (17%), foot and ankle (24%), spine (13%) and upper limb (4%). Patient satisfaction for overall experience of travelling to theatre was either excellent (77%) or good (23%). Following their experience of travelling to theatre, 87% (95%CI: 79%-95%) of the total cohort would have preferred to walk to the operating theatre. There was a statistically significant association (P = 0.003) between patients' preference to walk and whether they were day-case or in-patients. Similarly, there was a statistically significance association (P = 0.028) between patients' preference to walk and whether they were < 60 years or > 60 years of age. CONCLUSION: This study confirms the majority of Orthopaedic elective patients would prefer to walk to theatre, when given the choice and if practically possible.

Anterior cruciate ligament reconstruction best practice: A review of graft choice.

There is much literature about differing grafts used in anterior cruciate ligament (ACL) reconstruction. Much of this is of poor quality and of a low evidence base. We review and summarise the literature looking at the four main classes of grafts used in ACL reconstruction; bone-patella tendon-bone, hamstrings, allograft and synthetic grafts. Each graft has the evidence for its use reviewed and then compared, where possible, to the others. We conclude that although there is no clear "best" graft, there are clear differences between the differing graft choices. Surgeon's need to be aware of the evidence behind these differences, in order to have appropriate discussions with their patients, so as to come to an informed choice of graft type to best suit each individual patient and their requirements.

Trunnionosis: A pain in the neck.

Metal-on-metal (MoM) hip replacements have proven to be a modern day orthopaedic failure. The early enthusiasm and promise of a hard, durable bearing was quickly quashed following the unanticipated wear rates. The release of metal ions into the blood stream has been shown to lead to surrounding soft tissue complications and early failure. The devastating destruction caused has led to a large number of revision procedures and implant extractions. The resulting research into this field has led to a new area of interest; that of the wear at the trunnion of the prosthesis. It had been previously thought that the metal debris was generated solely from the weight bearing articulation, however with the evolution of modularity to aid surgical options, wear at the trunnion is becoming more apparent. The phenomenon of "trunnionosis" is a rapidly developing area of interest that may contribute to the overall effect of metallosis in MoM replacements but may also lead to the release of metal ions in non MoM hip designs. The aim of this paper is to introduce, explain and summarise the evidence so far in the field of trunnionosis. The evidence for this phenomenon, the type of debris particles generated and a contrast between MoM, non MoM and resurfacing procedures are also presented.

Anterior cruciate ligament reconstruction with the ligament augmentation and reconstruction system: a systematic review.

PURPOSE: The Ligament Augmentation and Reconstruction System (LARS) is a third generation of synthetic ligament, designed to overcome the issues of graft failure and synovitis which led previous generations of synthetic ligaments to fall out of favour. The theoretical benefits of LARS are appealing but this has not led to widespread uptake of the system in preference to autograft. The aim of this systematic review is to assess whether the evidence exists to support the use of LARS with respect to outcomes and complications. METHODS: A systematic search process was undertaken from January 1990 to June 2012 to identify primary evidence relating to the use of LARS in anterior cruciate ligament (ACL) single ligament reconstruction. RESULTS: Nine studies were found meeting the search criteria including a single randomised controlled trial, two comparative series and six further observational case series. Overall the methodological quality of the studies was poor with follow-up to a maximum of five years. Reported outcome scores were good for LARS and comparable to autograft techniques. Complication rates were low and comparable to those published for autograft techniques within the wider literature. Two reported incidences of synovitis were identified in case reports. CONCLUSIONS: The current literature supports the use of LARS in the short to medium term. However, high-quality studies with long-term follow-up are required to determine whether the use of LARS is preferable to autograft for ACL reconstruction over the longer term. Synovitis appears to be a rare complication closely related to imperfect graft positioning.

Functional redundancy of class I phosphoinositide 3-kinase (PI3K) isoforms in signaling growth factor-mediated human neutrophil survival.

We have investigated the contribution of individual phosphoinositide 3-kinase (PI3K) Class I isoforms to the regulation of neutrophil survival using (i) a panel of commercially available small molecule isoform-selective PI3K Class I inhibitors, (ii) novel inhibitors, which target single or multiple Class I isoforms (PI3Kα, PI3Kß, PI3Kδ, and PI3Kγ), and (iii) transgenic mice lacking functional PI3K isoforms (p110δ(KO)γ(KO) or p110γ(KO)). Our data suggest that there is considerable functional redundancy amongst Class I PI3Ks (both Class IA and Class IB) with regard to GM-CSF-mediated suppression of neutrophil apoptosis. Hence pharmacological inhibition of any 3 or more PI3K isoforms was required to block the GM-CSF survival response in human neutrophils, with inhibition of individual or any two isoforms having little or no effect. Likewise, isolated blood neutrophils derived from double knockout PI3K p110δ(KO)γ(KO) mice underwent normal time-dependent constitutive apoptosis and displayed identical GM-CSF mediated survival to wild type cells, but were sensitized to pharmacological inhibition of the remaining PI3K isoforms. Surprisingly, the pro-survival neutrophil phenotype observed in patients with an acute exacerbation of chronic obstructive pulmonary disease (COPD) was resilient to inactivation of the PI3K pathway.

Development of isoform selective PI3-kinase inhibitors as pharmacological tools for elucidating the PI3K pathway.

Using a parallel synthesis approach to target a non-conserved region of the PI3K catalytic domain a pan-PI3K inhibitor 1 was elaborated to provide alpha, delta and gamma isoform selective Class I PI3K inhibitors 21, 24, 26 and 27. The compounds had good cellular activity and were selective against protein kinases and other members of the PI3K superfamily including mTOR and DNA-PK.

Automated detection of toxigenic Clostridium difficile in clinical samples: isothermal tcdB amplification coupled to array-based detection.

Clostridium difficile can carry a genetically variable pathogenicity locus (PaLoc), which encodes clostridial toxins A and B. In hospitals and in the community at large, this organism is increasingly identified as a pathogen. To develop a diagnostic test that combines the strengths of immunoassays (cost) and DNA amplification assays (sensitivity/specificity), we targeted a genetically stable PaLoc region, amplifying tcdB sequences and detecting them by hybridization capture. The assay employs a hot-start isothermal method coupled to a multiplexed chip-based readout, creating a manual assay that detects toxigenic C. difficile with high sensitivity and specificity within 1 h. Assay automation on an electromechanical instrument produced an analytical sensitivity of 10 CFU (95% probability of detection) of C. difficile in fecal samples, along with discrimination against other enteric bacteria. To verify automated assay function, 130 patient samples were tested: 31/32 positive samples (97% sensitive; 95% confidence interval [CI], 82 to 99%) and 98/98 negative samples (100% specific; 95% CI, 95 to 100%) were scored correctly. Large-scale clinical studies are now planned to determine clinical sensitivity and specificity.

A cheap and readily available assistant in hand surgery.

Controlling the digits during hand surgery can be challenging. During elective and emergency surgery, a "lead hand" can be used; however, during fracture surgery where an image intensifier is required, the lead hand prevents imaging. Sterile surgical gloves provide a cheap and readily available radiolucent alternative. The surgeon can use bands cut from the cuff of the glove. Performing procedures such as Kirschner wiring or plating of phalangeal fractures without an assistant become much easier with the use of this technique.

Design and synthesis of a library of chemokine antagonists.

A library of chemokine antagonists has been synthesized using a combination of solid and solution-phase chemistry. Structures of known chemokine antagonists were used to produce a pharmacophore which served to guide monomer selection. Several combinations of monomers have resulted in providing novel chemokine antagonists which in some cases display dual chemokine receptor antagonism.

Sciatic palsy after total hip arthroplasty associated with vascular graft occlusion.

Sciatic nerve palsy is a well-recognised complication of total hip arthroplasty, and causes include direct injury during surgery (crushing or electrocautery), compression or stretching of the nerve, thermal damage caused by leaked bone cement, trauma during dislocation or reduction of the hip, haematoma, traction caused by leg lengthening or inadvertent intraneural injection from nerve blocks. We describe what we believe to be a case of sciatic nerve ischemia due to intra-operative arterial occlusion, and we discuss the vascular anatomy which may have contributed.

Bone mineral density in the femoral neck increases after hip resurfacing: a cohort with five-year follow-up.

Hip resurfacing is an effective treatment modality for arthritis of the hip in carefully selected patients; however, its use remains controversial due to its higher revision rates compared with conventional total hip replacement surgery. The most frequent reason for revision is femoral neck fracture, and preoperative bone mineral density is an important factor when considering the option of hip resurfacing. Whilst reduction in bone mineral density following total hip replacement is well documented, little is known about the long-term changes in femoral neck bone mineral density after hip resurfacing. We followed 15 patients (ten male and five female) who underwent unilateral hip resurfacing for osteoarthritis with standardised dual energy X-ray absorbiometry scans at two weeks, three months, one year, two years and five years postoperatively to determine changes in the femoral neck bone mineral density. Both males and females initially had decreases in bone mineral density at three months postoperatively, but had gradual mean increases to 119% of their initial measurements by five years. This study demonstrates that femoral neck bone mineral density increases after hip resurfacing and that this increase continues for at least five years.

Bilateral hip arthroplasty: is 1-week staging the optimum strategy?

Seventy-nine patients underwent bilateral hip arthroplasty staged either at 1 week (Group 1) or after greater intervals (as suggested by the patients, mean 44 weeks, range 16-88 weeks) (Group 2), over a five year period at one Institution. Sixty-eight patients (29 bilateral hip resurfacings and 39 total hip replacements) completed questionnaires regarding their post-operative recovery, complications and overall satisfaction with the staging of their surgery.There was no significant age or ASA grade difference between the patient groups. Complication rates in the two groups were similar and overall satisfaction rates were 84% in Group 1 (n = 32) and 89% in Group 2 (n = 36). Cumulative hospital lengths of stay were significantly longer in Group 1 patients (11.9 days vs 9.1 days)(p < 0.01); this was true for both hip resurfacing and total hip arthroplasty patients, however resurfacing patients stays were significantly shorter in both groups (p < 0.01). Postoperative pain resolved earlier in Group 1 patients at a mean of 20.9 weeks compared with a cumulative 28.9 weeks (15.8 and 13.1 weeks) for Group 2 patients (p = 0.03).The mean time to return to part-time work was 16.4 weeks for Group 1, and a cumulative 17.2 weeks (8.8 and 8.4 weeks) for Group 2. The time to return to full-time work was significantly shorter for Group 1 patients (21.0 weeks, compared with a cumulative 29.7 weeks for Group 2)(p < 0.05). The time to return to both full and part-time work was significantly shorter in total hip replacement patients with 1-week staging compared with delayed staging (22.0 vs 35.8 weeks (p = 0.02), and 13.8 vs 19.3 weeks (p = 0.03) respectively).Hip resurfacing patients in Group 2 had significantly shorter durations of postoperative pain and were able to return to part-time and full time work sooner than total hip arthroplasty patients. There was a general trend towards a faster recovery and resumption of normal activities following the second operation in Group 2 patients, compared with the first operation.Bilateral hip arthroplasty staged at a 1-week interval resulted in an earlier resolution of hip pain, and an earlier return to full-time work (particularly following total hip replacement surgery), with high levels of patient satisfaction and no increased risk in complications; however the hospital length of stay was significantly longer. The decision for the timing of staged bilateral surgery should be made in conjunction with the patient, making adjustments to accommodate their occupational needs and functional demands.

Differences in hip morphology between the sexes in patients undergoing hip resurfacing.

There is limited morphological data on the sex differences between the commonly used pelvic parameters. This study analysed the CT scans of 100 consecutive Caucasian patients, 61 males and 39 females, undergoing hip resurfacing arthroplasty surgery for hip osteoarthritis in one institution.There were no sex differences in femoral torsion/anteversion, femoral neck angle and acetabular inclination. Males had a mean femoral torsion/anteversion of 8 degrees (range -5 to 26 degrees), a mean femoral neck angle of 129 degrees (range 119 to 138 degrees) and a mean acetabular inclination of 55 degrees (range 40 to 86 degrees). Females had a mean femoral torsion/anteversion of 9 degrees (range -2 to 31 degrees), a mean femoral neck angle of 128 degrees (range 121 to 138) and a mean acetabular inclination of 57 degrees (range 44 to 80 degrees). Females had a significantly greater acetabular version of 23 degrees (range 10 to 53) compared with 18 degrees in males (range 7 to 46 degrees (p = 0.02) and males had a significantly greater femoral offset of 55 mm (range 42 to 68 mm) compared with 48 mm (range 37 to 57 mm) in females (p = 0.00). There were no significant differences between measurements taken from each patient's right and left hips.These findings may be useful for the future design and the implantation of hip arthroplasty components.

Bilateral ganglion cysts of the cruciate ligaments: a case report.

Symptomatic ganglion cysts of the cruciate ligaments are rare, and bilateral cases are extremely rare, with only one reported case in the literature. We report a case of bilateral cruciate ligament ganglion cysts successfully treated with arthroscopic resection, and review the literature regarding aetiology, diagnosis and management.

Biomechanical testing of implant free wedge shaped bone block fixation for bone patellar tendon bone anterior cruciate ligament reconstruction in a bovine model.

BACKGROUND: The use of an interference fit wedged bone plug to provide fixation in the tibial tunnel when using bone-patellar tendon-bone autograft for anterior cruciate ligament reconstruction offers many theoretic advantages including the potential to offer a more economical and biological alternative to screw fixation. This technique has not been subjected to biomechanical testing. We hypothesised that a wedged bone plug fixation technique provides equivalent tensile load to failure as titanium interference screw fixation. METHODS: In a controlled laboratory setting, anterior cruciate ligament reconstruction was performed in 36 bovine knees using bone-patella-bone autograft. In 20 knees tibial fixation relied upon a standard cuboid bone block and interference screw. In eight knees a wedge shaped bone block with an 11 mm by 10 mm base without a screw was used. In a further eight knees a similar wedge with a 13 mm by 10 mm base was used. Each specimen used a standard 10 mm tibial tunnel. The reconstructions were tested biomechanically in a physiological environment using an Instron machine to compare ultimate failure loads and modes of failure. RESULTS: Statistical analysis revealed no significant difference between wedge fixation and screw fixation (p = 0.16), or between individual groups (interference screw versus 11 mm versus 13 mm wedge fixation) (P = 0.35). CONCLUSIONS: Tibial tunnel fixation using an impacted wedge shaped bone block in anterior cruciate ligament reconstruction has comparable ultimate tensile strength to titanium interference screw fixation.

The long-term benefit of computer-assisted surgical navigation in unicompartmental knee arthroplasty.

We reviewed the outcomes of 30 consecutive primary unicompartmental knee arthroplasties (UKA) performed by a single surgeon for medial compartmental osteoarthritis. Fifteen Allegretto knees were implanted without computer navigation and 15 EIUS knees were implanted with navigation. We compared the survivorship, radiological and clinical outcomes of the two groups at an average of 8.9 years and 6.9 years respectively. The patients were assessed clinically using the Oxford Knee Score (OKS) and radiologically using long-leg weightbearing films and non-weightbearing computed tomography alignment measurements. The overall survivorship was 86.7% at 9 years. A higher proportion of navigated knees were well aligned with a more reproducible position and malaligned knees tended to have a less favourable OKS. However, we found no statistically significant difference in survivorship, clinical outcome and radiological alignment between the two groups.

Rare case of bilateral posterior fracture dislocation of the shoulders secondary to a syncopal episode.

Bilateral posterior fracture-dislocations of the shoulders are a rare injury that usually occurs secondary to a tonic-clonic seizure, electrocution or a high energy trauma. In this unique case, we present the first case of this injury resulting from a simple syncope in a 49 year old man with no history of epilepsy. He was fully investigated and no cause was found for his syncope. His shoulder fracture dislocations were reduced acutely and treated conservatively with full functional recovery.