The molecular targets of the vast majority of autoantibodies in systemic lupus erythematosus (SLE) are unknown. We set out to identify novel autoantibodies in SLE to improve diagnosis and identify ...subgroups of SLE individuals.
A baculovirus-insect cell expression system was used to create an advanced protein microarray with 1543 full-length human proteins expressed with a biotin carboxyl carrier protein (BCCP) folding tag, to enrich for correctly folded proteins. Sera from a discovery cohort of UK and US SLE individuals (n = 186) and age/ethnicity matched controls (n = 188) were assayed using the microarray to identify novel autoantibodies. Autoantibodies were validated in a second validation cohort (91 SLE, 92 controls) and a confounding rheumatic disease cohort (n = 92).
We confirmed 68 novel proteins as autoantigens in SLE and 11 previous autoantigens in both cohorts (FDR<0.05). Using hierarchical clustering and principal component analysis, we observed four subgroups of SLE individuals associated with four corresponding clusters of functionally linked autoantigens. Two clusters of novel autoantigens revealed distinctive networks of interacting proteins: SMAD2, SMAD5 and proteins linked to TGF-β signalling; and MyD88 and proteins involved in TLR signalling, apoptosis, NF-κB regulation and lymphocyte development. The autoantibody clusters were associated with different patterns of organ involvement (arthritis, pulmonary, renal and neurological). A panel of 26 autoantibodies, which accounted for four SLE clusters, showed improved diagnostic accuracy compared to conventional antinuclear antibody and anti-dsDNA antibody assays.
These data suggest that the novel SLE autoantibody clusters may be of prognostic utility for predicting organ involvement in SLE patients and for stratifying SLE patients for specific therapies.
•Protein microarray reveals molecular identity of 68 novel SLE autoantigens.•SLE autoantibodies cluster into four biologically functional groups.•SLE autoantigen clusters link to TGF-β/Wnt signalling and TLR signalling/apoptosis regulation.•Novel autoantibodies show selectivity for different SLE manifestations (arthritis, renal, thrombocytopenia).•26-autoantibody panel improves diagnostic accuracy compared to conventional serology.
Patients with Achilles tendon rupture who have non-operative treatment have traditionally been treated with immobilisation of the tendon in plaster casts for several weeks. Functional bracing is an ...alternative non-operative treatment that allows earlier mobilisation, but evidence on its effectiveness and safety is scarce. The aim of the UKSTAR trial was to compare functional and quality-of-life outcomes and resource use in patients treated non-operatively with plaster cast versus functional brace.
UKSTAR was a pragmatic, superiority, multicentre, randomised controlled trial done at 39 hospitals in the UK. Patients (aged ≥16 years) who were being treated non-operatively for a primary Achilles tendon rupture at the participating centres were potentially eligible. The exclusion criteria were presenting more than 14 days after injury, previous rupture of the same Achilles tendon, or being unable to complete the questionnaires. Eligible participants were randomly assigned (1:1) to receive a plaster cast or functional brace using a centralised web-based system. Because the interventions were clearly visible, neither patients nor clinicians could be masked. Participants wore the intervention for 8 weeks. The primary outcome was patient-reported Achilles tendon rupture score (ATRS) at 9 months, analysed in the modified intention-to-treat population (all patients in the groups to which they were allocated, excluding participants who withdrew or died before providing any outcome data). The main safety outcome was the incidence of tendon re-rupture. Resource use was recorded from a health and personal social care perspective. The trial is registered with ISRCTN, ISRCTN62639639.
Between Aug 15, 2016, and May 31, 2018, 1451 patients were screened, of whom 540 participants (mean age 48·7 years, 79% male) were randomly allocated to receive plaster cast (n=266) or functional brace (n=274). 527 (98%) of 540 were included in the modified intention-to-treat population, and 13 (2%) were excluded because they withdrew or died before providing any outcome data. There was no difference in ATRS at 9 months post injury (cast group n=244, mean ATRS 74∙4 SD 19∙8; functional brace group n=259, ATRS 72∙8 20∙4; adjusted mean difference –1∙38 95% CI –4∙9 to 2∙1, p=0·44). There was no difference in the rate of re-rupture of the tendon (17 6% of 266 in the plaster cast group vs 13 5% of 274 in the functional brace group, p=0·40). The mean total health and personal social care cost was £1181 for the plaster cast group and £1078 for the functional bract group (mean between-group difference –£103 95% CI –289 to 84).
Traditional plaster casting was not found to be superior to early weight-bearing in a functional brace, as measured by ATRS, in the management of patients treated non-surgically for Achilles tendon rupture. Clinicians may consider the use of early weight-bearing in a functional brace as a safe and cost-effective alternative to plaster casting.
UK National Institute for Health Research Health Technology Assessment Programme.
To assess wrist function, quality of life, and complications in adult patients with a dorsally displaced fracture of the distal radius, treated with either a moulded cast or surgical fixation with ...K-wires.
Multicentre randomised clinical superiority trial, SETTING: 36 hospitals in the UK National Health Service (NHS).
500 adults aged 16 or over with a dorsally displaced fracture of the distal radius, randomised after manipulation of their fracture (255 to moulded cast; 245 to surgical fixation).
Manipulation and moulded cast was compared with manipulation and surgical fixation with K-wires plus cast. Details of the application of the cast and the insertion of the K-wires were at the discretion of the treating surgeon, according to their normal clinical practice.
The primary outcome measure was the Patient Rated Wrist Evaluation (PRWE) score at 12 months (five questions about pain and 10 about function and disability; overall score out of 100 (best score=0 and worst score=100)). Secondary outcomes were PRWE score at three and six months, quality of life, and complications, including the need for surgery due to loss of fracture position in the first six weeks.
The mean age of participants was 60 years and 417 (83%) were women; 395 (79%) completed follow-up. No statistically significant difference in the PRWE score was seen at 12 months (cast group (n=200), mean 21.2 (SD 23.1); K-wire group (n=195), mean 20.7 (22.3); adjusted mean difference -0.34 (95% confidence interval -4.33 to 3.66), P=0.87). No difference was seen at earlier time points. In the cast group, 33 (13%) of participants needed surgical fixation for loss of fracture position in the first six weeks compared with one revision surgery in the K-wire group (odds ratio 0.02, 95% confidence interval 0.001 to 0.10).
Among patients with a dorsally displaced distal radius fracture that needed manipulation, surgical fixation with K-wires did not improve patients' wrist function at 12 months compared with a cast.
ISRCTN registry ISRCTN11980540.
This study explores data quality in operation type and fracture classification recorded as part of a large research study and a national audit with an independent review.
At 17 centres, an expert ...surgeon reviewed a randomly selected subset of cases from their centre with regard to fracture classification using the AO system and type of operation performed. Agreement for these variables was then compared with the data collected during conduct of the World Hip Trauma Evaluation (WHiTE) cohort study. Both types of surgery and fracture classification were collapsed to identify the level of detail of reporting that achieved meaningful agreement. In the National Hip Fracture Database (NHFD), the types of operation and fracture classification were explored to identify the proportion of "highly improbable" combinations.
The records were reviewed for 903 cases. Agreement for the subtypes of extracapsular fracture was poor; most centres achieved no better than "fair" agreement. When the classification was collapsed to a single option for "extracapsular" fracture, only four centres failed to have at least "moderate" agreement. There was only "moderate" agreement for the subtypes of intracapsular fracture, which improved to "substantial" when collapsed to "intracapsular". Subtrochanteric fracture types were well reported with "substantial" agreement. There was near "perfect" agreement for internal fixation procedures. "Perfect" or "substantial" agreement was achieved when the type of arthroplasty surgery was reported at the level of "hemiarthroplasty" and "total hip replacement". When reviewing data submitted to the NHFD, a minimum of 5.2% of cases contained "highly improbable" procedures for the stated fracture classification.
The complexity of collecting fracture classification data at a national scale compromises the accuracy with which detailed classification systems can be reported. Data around type of surgery performed show similar tendencies. Data capture, reporting, and interpretation in future studies must take this into account. Cite this article:
2019;101-B:1292-1299.
The primary aim of this study was to report the radiological outcomes of patients with a dorsally displaced distal radius fracture who were randomized to a moulded cast or surgical fixation with ...wires following manipulation and closed reduction of their fracture. The secondary aim was to correlate radiological outcomes with patient-reported outcome measures (PROMs) in the year following injury.
Participants were recruited as part of DRAFFT2, a UK multicentre clinical trial. Participants were aged 16 years or over with a dorsally displaced distal radius fracture, and were eligible for the trial if they needed a manipulation of their fracture, as recommended by their treating surgeon. Participants were randomly allocated on a 1:1 ratio to moulded cast or Kirschner wires after manipulation of the fracture in the operating theatre. Standard posteroanterior and lateral radiographs were performed in the radiology department of participating centres at the time of the patient's initial assessment in the emergency department and six weeks postoperatively. Intraoperative fluoroscopic images taken at the time of fracture reduction were also assessed.
Patients treated with surgical fixation with wires had less dorsal angulation of the radius versus those treated in a moulded cast at six weeks after manipulation of the fracture; the mean difference of -4.13° was statistically significant (95% confidence interval 5.82 to -2.45). There was no evidence of a difference in radial shortening. However, there was no correlation between these radiological measurements and PROMs at any timepoint in the 12 months post-injury.
For patients with a dorsally displaced distal radius fracture treated with a closed manipulation, surgical fixation with wires leads to less dorsal angulation on radiographs at six weeks compared with patients treated in a moulded plaster cast alone. However, the difference in dorsal angulation was small and did not correlate with patient-reported pain and function.
Tibial lengthening: does the fibula migrate? Saleh, Michael; Bashir, Hassan M; Farhan, Munther J ...
Journal of pediatric orthopaedics. B,
2002-October, Letnik:
11, Številka:
4
Journal Article
Recenzirano
A retrospective study of 32 patients who underwent tibial lengthening was performed in order to establish the need for distal tibio-fibular fixation. In 16 patients stabilization of the inferior ...tibio-fibular joint was carried out and in the other 16 no stabilization was performed. Three established and one new radiographic index of the tibio-fibular relationship at the ankle were used to assess proximal fibular migration. All patients showed proximal migration of the distal fibula, but those without stabilization demonstrated marked migration of the fibula associated with a valgus tendency. The difference between the groups was statistically significant ( <0.001), confirming the need for fibular fixation.
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