Investigating the role connective tissue fibroblasts play in the altered muscle anatomy associated with the limb abnormality, Radial Dysplasia.

Radial dysplasia (RD) is a congenital upper limb birth defect that presents with changes to the upper limb anatomy, including a shortened or absent radius, bowed ulna, thumb malformations, a radially deviated hand and a range of muscle and tendon malformations, including absent or abnormally shaped muscle bundles. Current treatments to address wrist instability caused by a shortened or absent radius frequently require an initial soft tissue distraction intervention followed by a wrist stabilisation procedure. Following these surgical interventions, however, recurrence of the wrist deviation remains a common, long-term problem following treatment. The impact of the abnormal soft connective tissue (muscle and tendon) anatomy on the clinical presentation of RD and the complications following surgery are not understood. To address this, we have examined the muscle, fascia and the fascial irregular connective tissue (ICT) fibroblasts found within soft connective tissues, from RD patients. We show that ICT fibroblasts isolated from RD patients are functionally abnormal when compared to the same cells isolated from control patients and secrete a relatively disordered extracellular matrix (ECM). Furthermore, we show that ICT fibroblast dysfunction is a unifying feature found in RD patients, even when the RD clinical presentation is caused by distinct genetic syndromes.

RADIATE - Radial Dysplasia Assessment, Treatment and Aetiology: protocol for the development of a core outcome set using a Delphi survey.

BACKGROUND: Radial dysplasia (RD) is a disfiguring, potentially disabling congenital upper limb anomaly. Multiple surgical techniques are in current use, with little agreement on the optimal treatment approach. At present, no core outcome set exists specifically for RD, and the literature is dominated by retrospective case series. A recent systematic review by this group demonstrated significant heterogeneity on which outcomes are measured and how they are measured. METHODS/DESIGN: The RADIATE study will conduct a three-round online Delphi process, involving adult RD patients, the parents of children with RD, hand surgeons and hand therapists. The initial list of outcomes was drawn from our recent systematic review and will be supplemented by suggestions from the stakeholder groups. Following the Delphi process, outcomes that meet the consensus in definition will be ratified at a final consensus meeting. We will then follow the COSMIN guidelines to select outcome measurement instruments. Where appropriate, these will overlap with the outcome measures specified in the forthcoming standard set for congenital upper limb anomalies published by the International Consortium for Health Outcomes Measurement. DISCUSSION: The Radial Dysplasia Assessment, Treatment and Aetiology (RADIATE) study aims to address the uncertainty in the treatment of RD, and to begin to answer the question 'What is the most appropriate treatment of the forearm and hand for children with RD?' by establishing a core outcome set. TRIAL REGISTRATION: COMET initiative study, 902 . Registered in May 2016.

Correction of "Wrist" Deformity in Radial Dysplasia: A Systematic Review and Meta-Analysis.

BACKGROUND: Radial dysplasia affects 1 in 6,000 to 8,000 births, classically presenting with a shortened, bowed ulna and radially deviated hand. The optimal treatment remains unclear, with several opposing approaches advocated. This review aims to clarify the long-term outcomes of nonsurgical and surgical treatment of the "wrist" deformity. METHODS: The Embase, MEDLINE, PubMed, Cochrane Central, ClinicalTrials.gov, and World Health Organization International Clinical Trials Registry Platform (ICTRP) databases were searched for published and unpublished studies reporting long-term outcomes of surgical or nonsurgical treatment of children with radial dysplasia. Results were not restricted by date or language. Primary outcomes were hand-forearm angle, ulnar length, and "wrist" active range of motion (ROM). Studies were assessed using the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) criteria. Data for the change in hand-forearm angle were pooled using random-effects meta-analysis, and mean differences and 95% confidence intervals were obtained. Primary outcome data at last follow-up were pooled, and means and standard deviations were obtained. The PROSPERO registration of this study was CRD42016036665. RESULTS: Of 104 studies identified, 12 were included in this review. Five were retrospective cohort studies and 7 were case series. No randomized studies were found. Study quality was low or very low according to the GRADE criteria. The hand-forearm angle of nonsurgically treated patients worsened during childhood, from 66° to 84°, whereas "wrist" active ROM, at 61°, was better than that for most surgically treated patients. Ulnar length with nonsurgical treatment was predicted to be 64% of normal, but was not directly reported. Isolated soft-tissue release provided a modest reduction in hand-forearm angle compared with nonsurgical treatment. Soft-tissue distraction with centralization or radialization achieved the best hand-forearm angle correction (16° radial deviation). Radialization maintained better "wrist" active ROM (46°) and ulnar length than centralization. Microvascular second metatarsophalangeal joint transfer yielded better reported "wrist" active ROM (83°) and good ulnar length compared with other surgical techniques, but a slightly worse hand-forearm angle (28°). CONCLUSIONS: There was low-quality evidence that soft-tissue distraction plus centralization or radialization achieved the best correction of the hand-forearm angle for children with radial dysplasia. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Does negative-pressure wound therapy influence subjacent bacterial growth? A systematic review.

BACKGROUND: Negative-pressure wound therapy is a ubiquitous wound management resource. The influence of NPWT on the bacterial bioburden of the subjacent wound remains unclear. We sought to examine the evidence. DATASOURCES: MEDLINE, Embase, PubMed, the Cochrane Database of Systematic Reviews and the Cochrane Controlled Trials Register were searched for articles quantitatively evaluating bacterial load under NPWT. RESULTS: Twenty-four studies met the inclusion criteria including 4 randomised controlled trials, 8 clinical series and 12 experimental studies. Twenty studies evaluated conventional NPWT, while 4 evaluated infiltration-based NPWT. While 8 studies using conventional NPWT failed to demonstrate an observable effect on bacterial load, 7 studies reported that NPWT was inherently bacteriostatic and 5 others reported species selectivity with suppression of non-fermentative gram-negative bacilli (NFGNB), including Pseudomonas spp. Simultaneously, there was some evidence of enhanced proliferation of gram-positive cocci where the niche was cleared of NFGNB. Two of the 4 studies using infiltration-based NPWT also reported selectively impaired proliferation of Pseudomonas spp. CONCLUSION: The assumption that NPWT suppresses bacterial proliferation is oversimplified. There is evidence that NPWT exhibits species selectivity, suppressing the proliferation of NFGNB. However, this may depopulate the niche for exploitation by gram-positive cocci. This, in turn, has implications for the use of NPWT where highly virulent strains of gram-positive cocci have been isolated and the duration of NPWT therapy and frequency of dressing changes.

Tbx5 Buffers Inherent Left/Right Asymmetry Ensuring Symmetric Forelimb Formation.

The forelimbs and hindlimbs of vertebrates are bilaterally symmetric. The mechanisms that ensure symmetric limb formation are unknown but they can be disrupted in disease. In Holt-Oram Syndrome (HOS), caused by mutations in TBX5, affected individuals have left-biased upper/forelimb defects. We demonstrate a role for the transcription factor Tbx5 in ensuring the symmetric formation of the left and right forelimb. In our mouse model, bilateral hypomorphic levels of Tbx5 produces asymmetric forelimb defects that are consistently more severe in the left limb than the right, phenocopying the left-biased limb defects seen in HOS patients. In Tbx hypomorphic mutants maintained on an INV mutant background, with situs inversus, the laterality of defects is reversed. Our data demonstrate an early, inherent asymmetry in the left and right limb-forming regions and that threshold levels of Tbx5 are required to overcome this asymmetry to ensure symmetric forelimb formation.

Oxygen reduces tourniquet-associated pain: a double-blind, randomized, controlled trial for application in hand surgery.

BACKGROUND: Why do limb tourniquets cause pain? If ischemia is the mechanism, can supplemental oxygen reduce pain? The Reducing Tourniquet Associated Pain study investigated whether this simple treatment could extend tourniquet tolerance time to facilitate hand surgery under local or regional anesthesia. METHODS: The Reducing Tourniquet Associated Pain study was a double-blind, randomized, controlled trial of healthy volunteers. Participants received either 50% inhaled oxygen or air placebo via a face mask for 3 minutes before and up to 30 minutes after upper arm tourniquet inflation to 250 mmHg. Pain scores were recorded at 2-minute intervals using a validated 100-mm visual analogue scale. The primary outcomes were (1) difference in visual analogue scale score and (2) difference in time taken to reach visual analogue score of 40 mm or more in oxygen and air groups. RESULTS: Fifty participants enrolled and, after exclusion criteria were applied, 46 were analyzed (oxygen, n = 23; air, n = 23). Oxygen supplementation was associated with a 29 percent mean reduction in pain on visual analogue scoring compared with air placebo over the entire period of inhalation (p = 0.027). Oxygen also extended the time to visual analogue scale score of 40 mm or more by a mean of 6½ minutes compared with air placebo (p = 0.008). CONCLUSIONS: Oxygen is a readily available, low-risk, low-cost treatment that significantly reduced tourniquet-associated pain in this study and significantly increased the time taken to reach visual analogue scale score of 40 or more. The authors recommend oxygen to facilitate hand surgery under a tourniquet and when a regional block fails to control tourniquet pain.

Pulmonary perfusion and ventricular ejection imaging by frequency domain filtering of EIT (electrical impedance tomography) images.

While EIT images can produce clinically useful qualitative information, the extraction of quantitative data is essential in clinical monitoring. In the case of imaging of the thorax the parameters available relate to cardiac activity and pulmonary perfusion. Imaging the relatively small changes in the resistivity of the lungs due to pulmonary perfusion in the presence of noise and the larger ventilation component is difficult. Suggested solutions involve multiple time averaging of cardiac gated data or reconstructed images. The required number of data frames for this type of processing is large (at least 100 cardiac cycles). Because the ventilation and perfusion components of the resistivity signals are well separated in the frequency domain, they can be differentiated by filtering. We report the results of this analysis which requires a data collection period of typically 15 s.

The spectral expansion of a head model in electrical impedance tomography.

This paper examines whether electrical impedance tomography (EIT) can provide information of use to magneto-encephalographic modelling (MEG). The EIT image domain is expanded in a complete set of orthogonal basis images, the number of which is given by the number of independent measurements (104 for 16 electrodes). They are ordered according to their sensitivity to data noise, with more centrally located features and higher spatial frequency components appearing towards the higher terms in the series, in the case of uniform resistivity distribution. This indicates that the resolution can be improved at the expense of degrading signal-to-noise in the reconstructed image. Applied to an approximate model of the head, the technique generates a set of basis images that emphasises central features of the head.

A transputer implemented algorithm for electrical impedance tomography.

Electrical impedance tomography (EIT) offers a non-invasive technique of great scope for producing clinically important information in a number of medical applications. Initial work by Brown used an isopotential approach to solving the complex backprojection problem. In this study a less restrictive algorithm for EIT has been developed based on the work of Yorkey and of Kaczmarz. Since considerably more processing is required this has been implemented on a transputer in Occam 2 with the aim of achieving real-time imaging. Data were collected, using a Sheffield prototype EIT system, from a test object and a human thorax. Image processing used both the 'Sheffield' and the Yorkey/Kaczmarz algorithms. Our initial results indicate that the images generated using the latter approach were more representative of the source impedance distributions.