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.
The August 2012 Research Roundup360 looks at: PRP and chondrogenic differentiation; basic fibroblast growth factor; whether glucosamine works; randomised trials; ossification of the ligamentum flavum; treadmill running; inhibiting BMP antagonists; and whether NSAIDs delay union after all.
In this study we used subject-specific finite
element analysis to investigate the mechanical effects of rotational acetabular
osteotomy (RAO) on the hip joint and analysed the correlation between
various radiological measurements and mechanical stress in the hip
joint. We evaluated 13 hips in 12 patients (two men and ten women, mean
age at surgery 32.0 years; 19 to 46) with developmental dysplasia
of the hip (DDH) who were treated by RAO. Subject-specific finite element models were constructed from
CT data. The centre–edge (CE) angle, acetabular head index (AHI),
acetabular angle and acetabular roof angle (ARA) were measured on
anteroposterior pelvic radiographs taken before and after RAO. The
relationship between equivalent stress in the hip joint and radiological measurements
was analysed. The equivalent stress in the acetabulum decreased from 4.1 MPa
(2.7 to 6.5) pre-operatively to 2.8 MPa (1.8 to 3.6) post-operatively
(p <
0.01). There was a moderate correlation between equivalent
stress in the acetabulum and the radiological measurements: CE angle
(R = –0.645, p <
0.01); AHI (R = –0.603, p <
0.01); acetabular
angle (R = 0.484, p = 0.02); and ARA (R = 0.572, p <
0.01). The equivalent stress in the acetabulum of patients with DDH
decreased after RAO. Correction of the CE angle, AHI and ARA was
considered to be important in reducing the mechanical stress in
the hip joint. Cite this article:
The February 2015 Oncology Roundup360 looks at: Achieving global collaboration; A new standard for limb salvage; Inoperable chondrosarcoma and chemotherapy; Soft-tissue sarcoma and adjuvant chemotherapy; Missed diagnoses and malpractice in sarcoma; Radiofrequency and cartilage tumours
In this study we evaluated whether pre-operative
Western Ontario and McMaster Universities (WOMAC) osteoarthritis
scores can predict satisfaction following total hip arthroplasty
(THA). Prospective data for a cohort of patients undergoing THA
from two large academic centres were collected, and pre-operative
and one-year post-operative WOMAC scores and a 25-point satisfaction
questionnaire were obtained for 446 patients. Satisfaction scores
were dichotomised into either improvement or deterioration. Scatter
plots and Spearman’s rank correlation coefficient were used to describe
the association between pre-operative WOMAC and one-year post-operative WOMAC
scores and patient satisfaction. Satisfaction was compared using
receiver operating characteristic (ROC) analysis against pre-operative,
post-operative and δ WOMAC scores. We found no relationship between pre-operative WOMAC scores and
one-year post-operative WOMAC or satisfaction scores, with Spearman’s
rank correlation coefficients of 0.16 and –0.05, respectively. The
ROC analysis showed areas under the curve (AUC) of 0.54 (pre-operative
WOMAC), 0.67 (post-operative WOMAC) and 0.43 (δ WOMAC), respectively,
for an improvement in satisfaction. We conclude that the pre-operative WOMAC score does not predict
the post-operative WOMAC score or patient satisfaction after THA,
and that WOMAC scores can therefore not be used to prioritise patient
care. Cite this article:
The maintenance of quality and integrity in clinical
and basic science research depends upon peer review. This process
has stood the test of time and has evolved to meet increasing work
loads, and ways of detecting fraud in the scientific community.
However, in the 21st century, the emphasis on evidence-based medicine
and good science has placed pressure on the ways in which the peer
review system is used by most journals. This paper reviews the peer review system and the problems it
faces in the digital age, and proposes possible solutions. Cite this article:
Salubrinal is a synthetic agent that elevates phosphorylation
of eukaryotic translation initiation factor 2 alpha (eIF2α) and
alleviates stress to the endoplasmic reticulum. Previously, we reported
that in chondrocytes, Salubrinal attenuates expression and activity
of matrix metalloproteinase 13 (MMP13) through downregulating nuclear
factor kappa B (NFκB) signalling. We herein examine whether Salubrinal
prevents the degradation of articular cartilage in a mouse model
of osteoarthritis (OA). OA was surgically induced in the left knee of female mice. Animal
groups included age-matched sham control, OA placebo, and OA treated
with Salubrinal or Guanabenz. Three weeks after the induction of
OA, immunoblotting was performed for NFκB p65 and p-NFκB p65. At
three and six weeks, the femora and tibiae were isolated and the sagittal
sections were stained with Safranin O.Objectives
Methods
Whether to use total or unicompartmental knee
replacement (TKA/UKA) for end-stage knee osteoarthritis remains controversial.
Although UKA results in a faster recovery, lower rates of morbidity
and mortality and fewer complications, the long-term revision rate
is substantially higher than that for TKA. The effect of each intervention on
patient-reported outcome remains unclear. The aim of this study
was to determine whether six-month patient-reported outcome measures
(PROMs) are better in patients after TKA or UKA, using data from
a large national joint registry (NJR). We carried out a propensity score-matched cohort study which
compared six-month PROMs after TKA and UKA in patients enrolled
in the NJR for England and Wales, and the English national PROM
collection programme. A total of 3519 UKA patients were matched
to 10 557 TKAs. The mean six-month PROMs favoured UKA: the Oxford Knee Score
was 37.7 (95% confidence interval (CI) 37.4 to 38.0) for UKA and
36.1 (95% CI 35.9 to 36.3) for TKA; the mean EuroQol EQ-5D index
was 0.772 (95% CI 0.764 to 0.780) for UKA and 0.751 (95% CI 0.747
to 0.756) for TKA. UKA patients were more likely to achieve excellent
results (odds ratio (OR) 1.59, 95% CI 1.47 to 1.72, p <
0.001)
and to be highly satisfied (OR 1.27, 95% CI 1.17 to 1.39, p <
0.001), and
were less likely to report complications than those who had undergone
TKA. UKA gives better early patient-reported outcomes than TKA; these
differences are most marked for the very best outcomes. Complications
and readmission are more likely after TKA. Although the data presented
reflect the short-term outcome, they suggest that the high revision
rate for UKA may not be because of poorer clinical outcomes. These
factors should inform decision-making in patients eligible for either
procedure. Cite this article:
The February 2015 Foot &
Ankle Roundup360 looks at: Syndesmosis screw removal in randomised controlled trial; Diagnostic value of Hawkins sign; Chevron rules supreme?; Diabetes and ankle replacement; Fixed-bearing ankle replacement; Fusion for osteomyelitis of the ankle; ‘Reformed’ fallers.
The February 2015 Trauma Roundup360 looks at: Evaluating the syndesmosis in ankle fractures; Calcaneal fracture management an ongoing problem; Angular stable locking in low tibial fractures did not improve results; Open fractures: do the seconds really count?; Long-term outcomes of tibial fractures; Targeted performance improvements in pelvic fractures
The management of children’s fractures has evolved
as a result of better health education, changes in lifestyle, improved
implant technology and the changing expectations of society. This
review focuses on the changes seen in paediatric fractures, including
epidemiology, the increasing problems of obesity, the mechanisms
of injury, non-accidental injuries and litigation. We also examine
the changes in the management of fractures at three specific sites:
the supracondylar humerus, femoral shaft and forearm. There has
been an increasing trend towards surgical stabilisation of these
fractures. The reasons for this are multifactorial, including societal
expectations of a perfect result and reduced hospital stay. Reduced hospital
stay is beneficial to the social, educational and psychological
needs of the child and beneficial to society as a whole, due to
reduced costs. Cite this article:
Large-head metal-on-metal (MoM) total hip replacements
(THR) have given rise to concern. Comparative studies of small-head
MoM THRs over a longer follow-up period are lacking. Our objective
was to compare the incidence of complications such as infection,
dislocation, revision, adverse local tissue reactions, mortality
and radiological and clinical outcomes in small-head (28 mm) MoM
and ceramic-on-polyethylene (CoP) THRs up to 12 years post-operatively. A prospective cohort study included 3341 THRs in 2714 patients.
The mean age was 69.1 years (range 24 to 98) and 1848 (55.3%) were
performed in women, with a mean follow-up of 115 months (18 to 201).
There were 883 MoM and 2458 CoP bearings. Crude incidence rates
(cases/1000 person-years) were: infection 1.3 In conclusion, we found similar results for small-head MoM and
CoP bearings up to ten years post-operatively, but after ten years
MoM THRs had a higher risk of all-cause revision. Furthermore, the
presence of an adverse response to metal debris seen in the small-head
MOM group at revision is a cause for concern. Cite this article:
Clinicians are often asked by patients, “When
can I drive again?” after lower limb injury or surgery. This question
is difficult to answer in the absence of any guidelines. This review
aims to collate the currently available evidence and discuss the
factors that influence the decision to allow a patient to return
to driving. There is currently insufficient evidence for any authoritative
body to determine fitness to drive. The lack of guidance could result
in patients being withheld from driving for longer than is necessary,
or returning to driving while still unsafe. Cite this article:
This study demonstrates a significant correlation
between the American Knee Society (AKS) Clinical Rating System and
the Oxford Knee Score (OKS) and provides a validated prediction
tool to estimate score conversion. A total of 1022 patients were prospectively clinically assessed
five years after TKR and completed AKS assessments and an OKS questionnaire.
Multivariate regression analysis demonstrated significant correlations between
OKS and the AKS knee and function scores but a stronger correlation
(r = 0.68, p <
0.001) when using the sum of the AKS knee and
function scores. Addition of body mass index and age (other statistically
significant predictors of OKS) to the algorithm did not significantly
increase the predictive value. The simple regression model was used to predict the OKS in a
group of 236 patients who were clinically assessed nine to ten years
after TKR using the AKS system. The predicted OKS was compared with
actual OKS in the second group. Intra-class correlation demonstrated
excellent reliability (r = 0.81, 95% confidence intervals 0.75 to
0.85) for the combined knee and function score when used to predict
OKS. Our findings will facilitate comparison of outcome data from
studies and registries using either the OKS or the AKS scores and
may also be of value for those undertaking meta-analyses and systematic
reviews. Cite this article:
Over a 15-year prospective period, 201 infants
with a clinically unstable hip at neonatal screening were subsequently
reviewed in a ‘one stop’ clinic where they were assessed clinically
and sonographically. Their mean age was 1.62 weeks (95% confidence
interval (CI) 1.35 to 1.89). Clinical neonatal hip screening revealed
a sensitivity of 62% (mean, 62.6 95%CI 50.9 to 74.3), specificity
of 99.8% (mean, 99.8, 95% CI 99.7 to 99.8) and positive predictive value
(PPV) of 24% (mean, 26.2, 95% CI 19.3 to 33.0). Static and dynamic
sonography for Graf type IV dysplastic hips had a 15-year sensitivity
of 77% (mean, 75.8 95% CI 66.9 to 84.6), specificity of 99.8% (mean,
99.8, 95% CI 99.8 to 99.8) and a PPV of 49% (mean, 55.1, 95% CI
41.6 to 68.5). There were 36 infants with an irreducible dislocation
of the hip (0.57 per 1000 live births), including six that failed
to resolve with neonatal splintage. Most clinically unstable hips referred to a specialist clinic
are female and stabilise spontaneously. Most irreducible dislocations
are not identified from this neonatal instability group. There may
be a small subgroup of females with instability of the hip which
may be at risk of progression to irreducibility despite early treatment
in a Pavlik harness. A controlled study is required to assess the value of neonatal
clinical screening programmes. Cite this article:
Many different lengths of stem are available
for use in primary total hip replacement, and the morphology of
the proximal femur varies greatly. The more recently developed shortened
stems provide a distribution of stress which closely mimics that
of the native femur. Shortening the femoral component potentially
comes at the cost of decreased initial stability. Clinical studies
on the performance of shortened cemented and cementless stems are promising,
although long-term follow-up studies are lacking. We provide an
overview of the current literature on the anatomical features of
the proximal femur and the biomechanical aspects and clinical outcomes
associated with the length of the femoral component in primary hip
replacement, and suggest a classification system for the length
of femoral stems. Cite this article:
Reported rates of dislocation in hip hemiarthroplasty
(HA) for the treatment of intra-capsular fractures of the hip, range
between 1% and 10%. HA is frequently performed through a direct
lateral surgical approach. The aim of this study is to determine
the contribution of the anterior capsule to the stability of a cemented
HA through a direct lateral approach. A total of five whole-body cadavers were thawed at room temperature,
providing ten hip joints for investigation. A Thompson HA was cemented
in place via a direct lateral approach. The cadavers were then positioned
supine, both knee joints were disarticulated and a digital torque
wrench was attached to the femur using a circular frame with three
half pins. The wrench applied an external rotation force with the
hip in extension to allow the hip to dislocate anteriorly. Each
hip was dislocated twice; once with a capsular repair and once without
repairing the capsule. Stratified sampling ensured the order in
which this was performed was alternated for the paired hips on each
cadaver. Comparing peak torque force in hips with the capsule repaired
and peak torque force in hips without repair of the capsule, revealed
a significant difference between the ‘capsule repaired’ (mean 22.96
Nm, standard deviation ( Cite this article:
Our aim was to compare polylevolactic acid screws
with titanium screws when used for fixation of the distal tibiofibular
syndesmosis at mid-term follow-up. A total of 168 patients, with
a mean age of 38.5 years (18 to 72) who were randomly allocated
to receive either polylevolactic acid (n = 86) or metallic (n =
82) screws were included. The Baird scoring system was used to assess
the overall satisfaction and functional recovery post-operatively.
The demographic details and characteristics of the injury were similar
in the two groups. The mean follow-up was 55.8 months (48 to 66).
The Baird scores were similar in the two groups at the final follow-up.
Patients in the polylevolactic acid group had a greater mean dorsiflexion
(p = 0.011) and plantar-flexion of the injured ankles (p <
0.001).
In the same group, 18 patients had a mild and eight patients had
a moderate foreign body reaction. In the metallic groups eight had
mild and none had a moderate foreign body reaction (p <
0.001).
In total, three patients in the polylevolactic acid group and none
in the metallic group had heterotopic ossification (p = 0.246). We conclude that both screws provide adequate fixation and functional
recovery, but polylevolactic acid screws are associated with a higher
incidence of foreign body reactions. Cite this article: