The SToICAL trial: study protocol for the soft tissue injection of corticosteroid and local anaesthetic trial-a single site, non-inferiority randomised control trial evaluating pain after soft tissue corticosteroid injections with and without local anaesthetic.

BACKGROUND: Corticosteroid injections are used in the treatment of hand and wrist conditions. The co-administration of a local anaesthetic and corticosteroid aims to reduce pain after the injection, although no studies have directly compared this with using corticosteroid alone. The aim is to determine whether pain experienced during the 24 h after a corticosteroid injection to the hand and wrist is no worse than (not inferior to) the pain experienced after a corticosteroid and local anaesthetic injection. METHODS: A single-site, patient- and assessor-blinded, non-inferiority randomised control trial recording pain visual analogue scale (VAS) scores in patients with a clinical diagnosis of trigger finger, de Quervains tenosynovitis or carpal tunnel syndrome, treated with a 1-ml triamcinolone (40 mg/1 ml) injection co-administered with or without 1 ml of 1% lidocaine. The primary aim is to investigate a difference in pain VAS scores at 1 h after the injection using a mean change score. A 95% power calculation was made using a minimally clinical important difference of 20 mm as the clinically admissible margin of non-inferiority and an assumed standard deviation of 25 mm, from previous studies. Including a 20% fall out rate, 100 patients are required. DISCUSSION: Patients with a clinical diagnosis of trigger finger, de Quervains and carpal tunnel syndrome, are over the age 18 years old and who are able to give written informed consent will be included. Patients will be excluded if they have had previous surgery or corticosteroid injection for the condition being treated at the site considered for injection. Patients will be electronically randomised and injections delivered during their clinic appointment. Pain is assessed using a 100-mm VAS score taken, before and at the time of injection and at 5 min, 1 h, 2 h, 3 h and 24 h after the injection. The secondary outcomes are to determine a difference in pain VAS score at the time of injection and during the 24 h after. TRIAL REGISTRATION: This study is registered on the IRAS (259336) on November 11, 2019, and EudraCT database on October 31, 2019 (2019-003742-32). REC/HRA approval was given in January 2020, and Clinical Trial Authorisation from the MHRA was given in December 2019. The study is registered on ClinicalTrials.gov ( NCT04253457 ) on February 5, 2020.

Functional outcome and complications following surgery for Dupuytren's disease: a multi-centre cross-sectional study.

Variables associated with recurrent Dupuytren's disease, or a 'diathesis', have been investigated, but those associated with functional outcome and complications are less well studied. Outcomes 1 or 5 years after an aponeurotomy, fasciectomy or dermofasciectomy were assessed by patient interview and examination at five UK centres. A total of 432 procedures were studied. The reoperation rate did not differ at 1 year ( p = 0.396, Chi-square test with Monte Carlo simulation), but was higher after aponeurotomy in the 5-year group (30%, versus 6% after fasciectomy and 0% after dermofasciectomy, p = 0.003, Chi square test with Monte Carlo simulation). Loss of function (DASH>15) did not differ between procedures at 5 years, even when reoperation and other variables were controlled. Diabetes, female gender and previous ipsilateral surgery were associated with poorer function in logistic regression analysis. The variables associated with poor function after treatments differ from diathesis variables. Aponeurotomy had lower complication rates than fasciectomy and dermofasciectomy. This may counterbalance the former's higher recurrence rate and explain why aponeurotomy demonstrated similar long-term functional outcome compared with excisional surgery in this study. LEVEL OF EVIDENCE: III.

Recovery, responsiveness and interpretability of patient-reported outcome measures after surgery for Dupuytren's disease.

This prospective cohort study investigated the responsiveness and interpretability of the Disabilities of the Arm, Shoulder and Hand (DASH) and Unité Rhumatologique des Affections de la Main (URAM) outcome measures for assessing recovery after fasciectomy and dermofasciectomy for Dupuytren's disease. DASH outcome scores at 1 year were significantly better than at 6 weeks, suggesting that recovery is not complete by 6 weeks. Of the 101 patients recruited to the DASH cohort, 71 completed preoperative, 6 week and 1 year postoperative DASH scores; 68 of them completed preoperative and 1 year postoperative DASH scores and an external anchor question. In the URAM cohort, 30/44 completed the preoperative and the 1 year postoperative URAM scores and the anchor question. The DASH score exhibited moderate responsiveness but poor interpretability on receiver operating characteristic curve analysis, such that a minimal important change could not be estimated. The URAM score showed acceptable responsiveness, and an MIC of 10.5 on receiver operating characteristic analysis. LEVEL OF EVIDENCE: II.

Dorsally displaced fractures of the distal radius: a critical appraisal of the DRAFFT (distal radius acute fracture fixation trial) study.

The results of the DRAFFT (distal radius acute fracture fixation trial) study, which compared volar plating with Kirschner (K-) wire fixation for dorsally displaced fractures of the distal radius, were published in August 2014. The use of K-wires to treat these fractures is now increasing, with a concomitant decline in the use of volar locking plates. We provide a critical appraisal of the DRAFFT study and question whether surgeons have been unduly influenced by its headline conclusions.

Validity of the Disabilities of the Arm, Shoulder and Hand patient-reported outcome measure (DASH) and the Quickdash when used in Dupuytren's disease.

UNLABELLED: This study investigated aspects of the validity and reliability of the 30-item Disabilities of the Arm, Shoulder and Hand patient-reported outcome measure (DASH) and its relationship with the shorter 11-item QuickDASH in patients with Dupuytren's disease.Seven hundred and fifty-nine DASH questionnaires were studied, covering pre- and postoperative patients undergoing different treatments for Dupuytren's disease. Items related to pain rose early after treatment before returning to baseline, suggesting that studying pain is relevant during postoperative recovery. Across all 759 sets of responses, the QuickDASH agreed closely with the DASH. In exploratory factor analysis, the DASH was not unidimensional, questioning the validity of the DASH summary score in Dupuytren's disease.Further validation of existing PROMs for use in Dupuytren's disease is needed. These data suggest that pain is a relevant symptom to study during postoperative recovery following treatment for Dupuytren's disease. LEVEL OF EVIDENCE: III.

The supination deformity and associated deformities of the upper limb in severe birth lesions of the brachial plexus.

We reviewed 42 consecutive children with a supination deformity of the forearm complicating severe birth lesions of the brachial plexus. The overall incidence over the study period was 6.9% (48 of 696). It was absent in those in Narakas group I (27.6) and occurred in 5.7% of group II (13 of 229), 9.6% of group III (11 of 114) and 23.4% of group IV (18 of 77). Concurrent deformities at the shoulder, elbow, wrist and hand were always present because of muscular imbalance from poor recovery of C5 and C7, inconsistent recovery of C8 and T1 and good recovery of C6. Early surgical correction improved the function of the upper limb and hand, but there was a tendency to recurrence. Pronation osteotomy placed the hand in a functional position, and increased the arc of rotation of the forearm. The supination deformity recurred in 40% (17 of 42) of those treated by pronation osteotomy alone, probably because of remodelling of the growing bone. Children should be followed up until skeletal maturity, and the parents counselled on the likelihood of multiple operations.

Delayed post-traumatic midcarpal dislocation.

We report a case of delayed post-traumatic volar midcarpal dislocation in a 39 year-old woman. The dislocation was a gradual process starting from the time of injury. Initial X-rays showed a normal midcarpal joint. By 6 weeks, lunocapitate subluxation was apparent radiologically and by the 18 week X-ray, midcarpal dislocation had occurred. This type of wrist injury has not been previously reported. Because of advanced degenerative changes in the lunocapitate joint, a partial wrist fusion was performed with a successful outcome.

Local and systemic concentrations of tumour necrosis factor-alpha, interleukin-6 and interleukin-8 in bacterial osteomyelitis.

Osteomyelitis is a major cause of morbidity worldwide but there are few data investigating pathogenesis of infection and no investigations into local secretion of proinflammatory cytokines in patients. Tumour necrosis factor-alpha (TNF), interleukin (IL)-6 and IL-8 concentrations were measured in pus of infected bone from 30 Zambian patients with chronic osteomyelitis (principally caused by Staphylococcus aureus), in plasma, and after lipopolysaccharide stimulation of whole-blood leucocytes. Patients had reduced body mass index compared to controls (P = 0.025) and an acute-phase response. Elevated concentrations of proinflammatory cytokines were detected in bone compared to plasma (all P < 0.0002). Bone IL-8 concentrations were greater than IL-8 levels after lipopolysaccharide stimulation of whole blood (P < 0.01). In contrast, systemic and ex-vivo-stimulated concentrations of proinflammatory cytokine were similar in patients and controls, despite differences in body mass index and an acute-phase response. In summary, we observed marked local TNF, IL-6 and IL-8 secretion in established bacterial osteomyelitis without systemic cytokine release.

Major limb deformities as complications of vascular access in neonates.

Four case histories are used to illustrate orthopaedic complications of vascular access in neonates. The two main pathologies, extravasation and thrombosis, are discussed and the management of each outlined. Mechanisms of avoidance of such complications are described and advocated.

Identification of spectrin-related peptides associated with the reticulocyte heme-controlled alpha subunit of eukaryotic translational initiation factor 2 kinase and of Mr 95,000 peptide that appears to be the catalytic subunit.

An isolation procedure for the reticulocyte heme-controlled alpha subunit of eukaryotic translational initiation factor 2 (eIF-2 alpha) kinase is described which yields different fractions with kinase activity. Each is associated with a different spectrin-related peptide as identified by anti-spectrin monoclonal antibodies. The most abundant of these peptides is the Mr 90,000 species characterized previously (Kudlicki, W., Fullilove, S., Kramer, G., and Hardesty, B. (1985) Proc. Natl. Acad. Sci. U.S.A. 82, 5332-5336). Association with the spectrin-related peptides appears to account for the heterogeneity of the enzyme during its isolation and for its highly asymmetric structure. Isolated alpha or beta spectrin subunits as well as the separated homogeneous Mr 90,000 peptide cause an increase in the initial rate of eIF-2 alpha phosphorylation that is related to a decrease in Km with little or no effect on Vmax for the phosphorylation reaction. Fractionation of highly purified eIF-2 alpha kinase preparations using affinity chromatography on monoclonal anti-spectrin antibodies has separated eIF-2 alpha kinase activity from the Mr 100,000 phosphopeptide which copurifies with the kinase during all other purification steps. A Mr 95,000 peptide, detectable only by photoaffinity labeling with 8-azido-[alpha 32P]ATP, is shown to be distinct from the Mr 100,000 phosphopeptide and appears to be the catalytic subunit of the eIF-2 alpha kinase.

Interaction of the 56,000-dalton phosphoprotein phosphatase from reticulocytes with regulin and inhibitor 2.

The interaction of divalent metal ions with a homogeneous 56,000-dalton phosphoprotein phosphatase isolated from rabbit reticulocytes was studied. The effects of the ions on enzymatic activity and on fluorescence from a 3-(4-maleimidylphenyl)-4-methyl-7-(diethylamino)coumarin derivative of the protein were compared. Enzymatic activity is dependent on Mn2+. The apparent association constant for Mn2+ is about 0.5 mM-1 as judged from enzymatic activity and from changes in fluorescence caused by binding of the metal ion; Ca2+ and Mg2+ do not affect enzymatic activity and appear not to bind tightly to the enzyme; however, Co2+, Fe2+, and Zn2+ bind to the protein and inhibit the Mn2+-activated enzyme. The 56,000-dalton phosphoprotein phosphatase was found to interact with regulin, a spectrin-associated protein also isolated from reticulocytes, and with skeletal muscle phosphatase inhibitor 2. The interaction was followed by changes in the enzymatic activity and by quenching of fluorescence from the coumarin derivative of the phosphatase. Homogeneous regulin (Mr approximately 230,000) increases the activity of the enzyme severalfold; this stimulation is Mn2+-dependent. Inhibitor 2 decreases enzyme activity but only if the two proteins are preincubated in the absence of Mn2+. Comparable differences in the effect of Mn2+ were also observed in parallel experiments in which changes in fluorescence from the coumarin-labeled 56,000-dalton phosphatase were measured. In these experiments, it was shown that Mn2+ enhances the interaction between regulin and the 56,000-dalton phosphatase, but inhibits the interaction between the phosphatase and inhibitor 2.

The 90-kDa component of reticulocyte heme-regulated eIF-2 alpha (initiation factor 2 alpha-subunit) kinase is derived from the beta subunit of spectrin.

Antibodies from three different lines of monoclonal hybridomas crossreact with both the beta subunit of spectrin and the 90-kDa peptide present in highly purified preparations of the heme-controlled eIF-2 alpha (initiation factor 2 alpha-subunit) kinase from rabbit reticulocytes. Antibodies from two of the three lines enhance the enzymatic activity of the kinase preparation for phosphorylation of the alpha subunit of eukaryotic translational initiation factor 2 (eIF-2) and for phosphorylation of the 100-kDa peptide thought to be a peptide of the kinase that is phosphorylated during its activation. Also, it is shown that both the beta subunit of spectrin and the 90-kDa peptide can be phosphorylated by two protein kinases from reticulocytes, the catalytic subunit of cAMP-dependent protein kinase and a cAMP-independent protein kinase similar to casein kinase II. Furthermore, a phosphorylated 90-kDa peptide can be derived from phosphorylated beta subunit of spectrin by tryptic proteolysis. We conclude that the 90-kDa peptide is derived by proteolysis from the beta subunit of spectrin, probably from its carboxyl terminus, and suggest that the heme-sensitive eIF-2 alpha kinase, like the 56-kDa phosphatase [Wollny, E., Watkins, K., Kramer, G. & Hardesty, B. (1984) J. Biol. Chem. 259, 2484-2492], is associated with an element of the membrane skeleton in intact reticulocytes.

Partial characterization of a 230,000-dalton reticulocyte protein and peptides derived from it that affect the activity of a protein phosphatase.

Monoclonal antibodies were raised that recognize a series of highly antigenic, protease-sensitive peptides that modulate protein phosphatase activity in reticulocyte extracts. Purified antigen peptides cause a 3-fold increase in the enzymatic activity of a homogeneous Mr congruent to 56,000 protein phosphatase. The monoclonal antibodies inhibit protein phosphatase activity in crude extracts but do not recognize the protein phosphatase itself. The antigen peptides are associated with the phosphatase throughout its purification from the postribosomal supernatant of rabbit reticulocytes but are separated from it during size exclusion high performance liquid chromatography (see accompanying article: Wollny, E., Watkins, K., Kramer, G., and Hardesty, B. (1984) J. Biol. Chem. 259, 2484-2492). The series of antigenic peptides appears to be derived by proteolysis from a 230,000-Da precursor, which is relatively abundant in undegraded form in the membrane fraction of rabbit reticulocytes and is present in erythrocyte ghosts. Antigen peptides are extracted with spectrin from both sources. The Mr congruent to 230,000 peptide is not the alpha or beta subunit of spectrin or ankyrin and appears not to have been recognized previously. The name "regulin" is proposed.