Tumor associated macrophages as key contributors and targets in current and future therapies for melanoma.

INTRODUCTION: Despite the success of immunotherapies for melanoma in recent years, there remains a significant proportion of patients who do not yet derive benefit from available treatments. Immunotherapies currently licensed for clinical use target the adaptive immune system, focussing on Tcell interactions and functions. However, the most prevalent immune cells within the tumor microenvironment (TME) of melanoma are macrophages, a diverse immune cell subset displaying high plasticity, to which no current therapies are yet directly targeted. Macrophages have been shown not only to activate the adaptive immune response, and enhance cancer cell killing, but, when influenced by factors within the TME of melanoma, these cells also promote melanoma tumorigenesis and metastasis. AREAS COVERED: We present a review of the most up-to-date literatureavailable on PubMed, focussing on studies from within the last 10 years. We also include data from ongoing and recent clinical trials targeting macrophages in melanoma listed on clinicaltrials.gov. EXPERT OPINION: Understanding the multifaceted role of macrophages in melanoma, including their interactions with immune and cancer cells, the influence of current therapies on macrophage phenotype and functions and how macrophages could be targeted with novel treatment approaches, are all critical for improving outcomes for patients with melanoma.

The Wire Study-a protocol for a multi-stage feasibility study evaluating K-wire fixation of hand fractures in the UK.

BACKGROUND: Hand fractures are common and sometimes require surgery to restore function. Placement of Kirschner wires (K-wires) is the most common form of surgical fixation. After placement, a key decision is whether to bury the end of a K-wire or leave it protruding from the skin (exposed). A recent systematic review found no evidence to support either approach and a national clinician and surgeon survey demonstrated further uncertainty. We aim to determine the design of a definitive randomised controlled trial assessing the cost and clinical effectiveness of buried versus exposed Kirschner wires for adults with metacarpal or phalangeal fractures. METHODS: We will employ three methodologies: a national service evaluation of current clinical practice, patient and surgeon focus groups and a consensus meeting to finalise the protocol for a randomised controlled trial. For the service evaluation, all outcomes will be summarised using descriptive statistics overall and split by group (buried versus exposed K-wires). Information collected in the patient focus groups will be analysed thematically. The surgeon consensus meeting will address each part of the design in turn and through discussion agree a final protocol. DISCUSSION: The study may be monitored, or audited in accordance with the current approved protocol, Good Clinical Practice (GCP), relevant regulations and standard operating procedures. The Chief Investigator will submit and, where necessary, obtain approval from the above parties for all substantial amendments to the original approved documents. A feasibility study report will be published by the Wire Study Steering committee. Additional members of the steering group and citable collaborators will be listed within the manuscript and their roles identified.

Systematic Review of the Use of Patient Reported Outcome Measures in Studies of Electively-Managed Hand Conditions.

Background: Electively-managed conditions account for over 100 000 inpatient surgeries a year in the English National Health Service alone, with further procedures in other regions of the UK, or performed on an outpatient basis. To quality assure this care and to conduct research, effective outcome measurement is critical. Traditional surgeon-centric outcome measures correlate poorly with hand function and are seldom important to patients. There has been an advent in the use of patient reported outcome measures (PROMs) in hand surgery although consensus of PROM choice appears to be lacking. This systematic review aimed to describe the use of relevant PROMs in clinical research of electively-managed hand conditions. Methods: A PRISMA-compliant methodology was used. A bespoke search strategy was developed in conjunction with a search strategist, and applied to Medline, EMBASE, CINAHL and PSYCHINFO from 1992 to June 2017. Pre-specified stepwise inclusion criteria were used to identify studies describing adult patients undergoing treatment for electively-managed hand conditions distal to the distal radius, with clinical outcomes measured using one or more PROMs. Results: Of 4554 results, 834 met inclusion criteria. PROMs identified included 9 disease-specific, 8 site-specific and 4 generic quality of life measures. Across all, the Disabilities of the Arm, Shoulder and Hand (DASH) was the most commonly used (overall frequency 41.0%). The most commonly reported disease-specific measure was the Boston Carpal Tunnel Questionnaire (overall frequency 23.0%). The most commonly reported generic quality of life of measure was the SF-36 (overall frequency 4%). Time-analysis demonstrated predominance of site-specific PROMs since the year 2000. Conclusions: Various PROMs have been used to study electively-managed hand conditions, with site-specific PROMs most popular. However, there appears to be limited consensus on choices. A future systematic evaluation of the published psychometric properties of identified PROMs may inform standardisation of measurement.

Compartment syndrome resulting from undetected ulnar artery injury in the absence of a forearm fracture.

A 6-year-old boy presented following a transient crush injury to his forearm. He displayed mild abrasions but no laceration or associated fractures. The injury resulted in traumatic rupture of the ulnar artery, which caused a large forearm haematoma and an acute forearm compartment syndrome. Prompt clinical diagnosis and operative intervention were required to prevent disastrous consequences.

Nerve conduits for peripheral nerve surgery.

Autologous nerve grafts are the current criterion standard for repair of peripheral nerve injuries when the transected nerve ends are not amenable to primary end-to-end tensionless neurorrhaphy. However, donor-site morbidities such as neuroma formation and permanent loss of function have led to tremendous interest in developing an alternative to this technique. Artificial nerve conduits have therefore emerged as an alternative to autologous nerve grafting for the repair of short peripheral nerve defects of less than 30 mm; however, they do not yet surpass autologous nerve grafts clinically. A thorough understanding of the complex biological reactions that take place during peripheral nerve regeneration will allow researchers to develop a nerve conduit with physical and biological properties similar to those of an autologous nerve graft that supports regeneration over long nerve gaps and in large-diameter nerves. In this article, the authors assess the currently available nerve conduits, summarize research in the field of developing these conduits, and establish areas within this field in which further research would prove most beneficial.

Complex regional pain syndrome (Type 1) following steroid injection for stenosing tenosynovitis.

Complex regional pain syndrome (CRPS) is a chronic progressive disease characterised by severe pain, swelling and changes in the skin. Precipitating factors include injury and surgery, and a variety of causes have been described. We present the case of a 68-year-old lady who presented with features indicative of a CRPS following steroid injection for a 'trigger' thumb.