Shared genetic susceptibility between trigger finger and carpal tunnel syndrome: a genome-wide association study.

Background: Trigger finger and carpal tunnel syndrome are the two most common non-traumatic connective tissue disorders of the hand. Both of these conditions frequently co-occur, often in patients with rheumatoid arthritis. However, this phenotypic association is poorly understood. Hypothesising that the co-occurrence of trigger finger and carpal tunnel syndrome might be explained by shared germline predisposition, we aimed to identify a specific genetic locus associated with both diseases. Methods: In this genome-wide association study (GWAS), we identified 2908 patients with trigger finger and 436579 controls from the UK Biobank prospective cohort. We conducted a case-control GWAS for trigger finger, followed by co-localisation analyses with carpal tunnel syndrome summary statistics. To identify putative causal variants and establish their biological relevance, we did fine-mapping analyses and expression quantitative trait loci (eQTL) analyses, using fibroblasts from healthy donors (n=79) and tenosynovium samples from patients with carpal tunnel syndrome (n=77). We conducted a Cox regression for time to trigger finger and carpal tunnel syndrome diagnosis against plasma IGF-1 concentrations in the UK Biobank cohort. Findings: Phenome-wide analyses confirmed a marked association between carpal tunnel syndrome and trigger finger in the participants from UK Biobank (odds ratio [OR] 11·97, 95% CI 11·1-13·0; p<1 × 10-300). GWAS for trigger finger identified five independent loci, including one locus, DIRC3, that was co-localised with carpal tunnel syndrome and could be fine-mapped to rs62175241 (0·76, 0·68-0·84; p=5·03 × 10-13). eQTL analyses found a fibroblast-specific association between the protective T allele of rs62175241 and increased DIRC3 and IGFBP5 expression. Increased plasma IGF-1 concentrations were associated with both carpal tunnel syndrome and trigger finger in participants from UK Biobank (hazard ratio >1·04, p<0·02). Interpretation: In this GWAS, the DIRC3 locus on chromosome 2 was significantly associated with both carpal tunnel syndrome and trigger finger, possibly explaining their co-occurrence. The disease-protective allele of rs62175241 was associated with increased expression of long non-coding RNA DIRC3 and its transcriptional target, IGBP5, an antagonist of IGF-1 signalling. These findings suggest a model in which IGF-1 is a driver of both carpal tunnel syndrome and trigger finger, and in which the DIRC3-IGFBP5 axis directly antagonises fibroblastic IGF-1 signalling. Funding: Wellcome Trust, National Institute for Health Research, Medical Research Council.

Is the Quality of Mobile Health Applications for Burns Being Adequately Assessed?

High-quality mobile health applications (mHealth apps) have the potential to enhance the prevention, diagnosis, and treatment of burns. The primary aim of this study was to evaluate whether the quality of mHealth apps for burns care is being adequately assessed. The secondary aim was to determine whether these apps meet regulatory standards in the United Kingdom. We searched AMED, BNI, CINAHL, Cochrane Library, Embase, Emcare, Medline, and PsychInfo to identify studies assessing mHealth app quality for burns. The PRISMA reporting guideline was adhered to. Two independent reviewers screened abstracts to identify relevant studies. The quality of identified studies was assessed according to the framework proposed by Nouri et al, including design, information/content, usability, functionality, ethical issues, security/privacy, and user-perceived value. Of the 28 included studies, none assessed all seven domains of quality. Design was assessed in 4 of 28 studies; information/content in 26 of 28 studies; usability in 12 of 28 studies; functionality in 10 of 28 studies; ethical issues were never assessed in any studies; security/privacy was not assessed; subjective assessment was made in 9 of 28 studies. About 17 of 28 studies included apps that met the definition of "medical device" according to Medicines and Healthcare products Regulatory Agency guidance, yet only one app was appropriately certified with the UK Conformity Assessed mark. The quality of mHealth apps for burns is not being adequately assessed. The majority of apps should be considered medical devices according to UK standards, yet only one was appropriately certified. Regulatory bodies should support mHealth app developers, so as to improve quality control while simultaneously fostering innovation.

Safeguarding Skin Grafts: An Evidence-Based Summary of Fixation Techniques.

BACKGROUND: Effective skin graft fixation is vital in preventing sheering forces, seroma, and hematoma from compromising graft take. Yet, selecting the ideal technique for securing skin grafts remains a contentious subject, with significant variation in practice existing between surgeons. There is, therefore, benefit to be derived from assessing the literature for evidence-based recommendations to guide the decision-making process. METHODS: A search of Medline and Embase was performed using appropriate key terms, yielding 419 articles. Reference lists were analyzed. Inclusion and exclusion criteria were composed. Level I to III studies, as defined by the Centre for Evidence-Based Medicine, that compared skin graft fixation methods were analyzed. Rayyan QCRI was used for abstract and title screening. After full text screening, 41 studies were included for qualitative analysis. All included randomized control trials (RCTs) were assessed for risk of bias using the Cochrane Risk-of-Bias 2 (ROB2) tool. RESULTS: We identified 4 groups of fixation technique: "tie-over bolster" (TOB), "no TOB," "adhesive glues," and "negative pressure wound therapy" (NPWT). Twelve studies compared TOB with no TOB, with no difference in graft take demonstrated. Sixteen studies compared adhesive glues with traditional methods, with no difference in graft take demonstrated. Thirteen studies compared NPWT with traditional methods, with enhanced graft take demonstrated. Risk of bias was deemed low in 1 of 13 RCTs. CONCLUSIONS: Based on the current evidence, only NPWT is associated with enhanced graft take. However, there is a scarcity of robust level I evidence comparing different fixation techniques, meaning that strong recommendations cannot be made. We propose examples of hypothesis-driven RCTs, in predetermined clinical settings, based on the theoretical benefits of the techniques that would add value to clinical practice.

Patient-Reported Outcome Measures for Soft-Tissue Facial Reconstruction: A Systematic Review and Evaluation of the Quality of Their Measurement Properties.

BACKGROUND: A patient's health-related quality of life can be significantly impacted by facial scarring and disfigurement. Facial soft-tissue reconstruction should aim to improve this, with outcomes measured from the patient's perspective using patient-reported outcome measures. This systematic review identifies patient-reported outcome measures for soft-tissue facial reconstruction and appraises their methodologic and psychometric properties using up-to-date methods. METHODS: A systematic search of the MEDLINE, Embase, PsychINFO, and Cochrane databases was performed. Identified patient-reported outcome measures were assessed using the updated Consensus-Based Standards for the Selection of Health Measurement Instruments checklist. Psychometric properties were also assessed and a modified Grading of Recommendation Assessment, Development and Evaluation analysis was performed to aid in recommendations for future questionnaire use. RESULTS: Thirty-four studies covering nine patient-reported outcome measures were included. Methodologic quality and psychometric evidence were variable. FACE-Q, Skin Cancer Index, Patient Outcome of Surgery-Head/Neck, and the Derriford Appearance Scale 59/24 all demonstrated high enough evidence to be recommended as having potential for inclusion in future studies. CONCLUSIONS: This is the first systematic review to identify and critically appraise patient-reported outcome measures for soft-tissue facial reconstruction using internationally accepted criteria. Four questionnaires were deemed to have adequate levels of methodologic and psychometric evidence, although further studies should be conducted before they are used routinely in patients undergoing facial reconstruction. Through the use of psychometrically well-validated questionnaires, it is hoped that patients' concerns can be truly appreciated, the level of care improved, and the quality of reconstructive options offered advanced.

Regulation of Dense-Core Granule Replenishment by Autocrine BMP Signalling in Drosophila Secondary Cells.

Regulated secretion by glands and neurons involves release of signalling molecules and enzymes selectively concentrated in dense-core granules (DCGs). Although we understand how many secretagogues stimulate DCG release, how DCG biogenesis is then accelerated to replenish the DCG pool remains poorly characterised. Here we demonstrate that each prostate-like secondary cell (SC) in the paired adult Drosophila melanogaster male accessory glands contains approximately ten large DCGs, which are loaded with the Bone Morphogenetic Protein (BMP) ligand Decapentaplegic (Dpp). These DCGs can be marked in living tissue by a glycophosphatidylinositol (GPI) lipid-anchored form of GFP. In virgin males, BMP signalling is sporadically activated by constitutive DCG secretion. Upon mating, approximately four DCGs are typically released immediately, increasing BMP signalling, primarily via an autocrine mechanism. Using inducible knockdown specifically in adult SCs, we show that secretion requires the Soluble NSF Attachment Protein, SNAP24. Furthermore, mating-dependent BMP signalling not only promotes cell growth, but is also necessary to accelerate biogenesis of new DCGs, restoring DCG number within 24 h. Our analysis therefore reveals an autocrine BMP-mediated feedback mechanism for matching DCG release to replenishment as secretion rates fluctuate, and might explain why in other disease-relevant systems, like pancreatic ß-cells, BMP signalling is also implicated in the control of secretion.