Lessons Learnt from Managing Orthopaedic Trauma During the First Wave of the COVID-19 Pandemic at a UK District General Hospital.

Background: The Coronavirus disease (COVID-19) pandemic has contributed to over 1,000,000 deaths worldwide. Hospitals responded by expanding services to accommodate the forecasted rise in COVID-19-related admissions. We describe the effects these changes had on management of orthopaedic trauma and patient outcomes at a district general hospital in Southern England. Methods: Data were extrapolated retrospectively from two separate 6-week periods in 2019 and 2020 (1st April-13th May) using electronic records of patients referred to the orthopaedic team. Soft tissue injuries were included where a confirmed diagnosis was made with radiological evidence. Patients were excluded if no orthopaedic intervention was required. Data were compared between the two time periods. Results: There were fewer attendances to hospital in 2020 compared with 2019 (178 vs. 328), but time from presentation to surgery significantly increased in 2020 (2.94 days vs. 4.91 days, p = 0.009). There were fewer operative complications in 2020 (36/145 vs. 11/88, p < 0.001). However, ordinal logistic regression analysis found a significantly greater complication severity in 2020 including death (p = 0.039). Complication severity was unrelated to COVID-19 status. Conclusions: Restructuring of orthopaedic services in response to the COVID-19 pandemic has been associated with significant delays to surgery and higher post-operative complication severity. Our results demonstrate the need for fast-track emergency operative orthopaedic services in UK district general hospitals whilst the COVID-19 pandemic continues.

Inadequate pelvic radiographs: implications of not getting it right the first time.

Introduction Pelvic radiography is a frequent investigation. European guidelines aim to ensure appropriate use and adequate quality. When initial images are inadequate, repeat radiographs are often required, which may have significant patient safety and economic implications. Objectives The study aimed to assess the adequacy of pelvic imaging across three orthopaedic centres, to identify causes for inadequate imaging and to establish the cost of inadequate imaging from financial and patient safety perspectives. Methods Pelvic radiographs were identified on Picture Archiving and Communication System software at three UK hospitals. Radiographs were assessed against European guidelines and indications for repeat imaging were analysed. Results A total of 1,531 sequential pelvic radiographs were reviewed. The mean age of patients was 60 years (range 5 months to 101 years). Of this total, 51.9% of images were suboptimal, with no significant difference across the three hospitals (P > 0.05). Hospital 3 repeated radiographs in 6.3% of cases, compare with 18.1% and 19.7% at hospitals 1 and 2, respectively (P > 0.05). Hospital 3 identified pathology missed on the initial radiograph in 1% of cases, compared with 5.4% and 5.5% at hospitals 1 and 2, respectively (P > 0.05). Out-of-hours imaging is associated with a higher rate of suboptimal quality (69.1%) compared with normal working hours (51.3%; P = 0.006). Adequacy rates vary with age (χ 2 = 43.62, P < 0.001). Risk of having a suboptimal radiograph increases above the age of 60-years (χ 2 = 4.45, P < 0.05). The annual cost of repeat radiographs was £56,200 per hospital. Discussion and conclusion High rates of pelvic radiograph inadequacy can lead to missed pathology and the requirement for repeat imaging, which has significant patient safety and financial implications. Risk factors for inadequate radiographs include older patients and those having out-of-hours imaging.

Isolated proximal rupture of flexor digitorum longus tendon in a traumatic open subtalar dislocation.

Tendon ruptures associated with ankle fractures and dislocations or subtalar dislocations are very rare entities with only a few reports of these in the literature. We report a case of an open subtalar dislocation and associated isolated proximal rupture of the flexor digitorum longus tendon at the musculotendinous junction, following a relatively low energy trauma. The finding of the avulsed flexor digitorum longus tendon was intraoperative, and management involved thorough washout of the joint and a primary side-to-side tenodesis with the flexor hallucis longus tendon. The patient has made a good functional recovery from his injuries. This case is reported because of the rarity of this combination of injuries and the associated management dilemma with which it presented us.

WT1-targeted immunotherapy of leukaemia.

Since malignant cells are derived from normal cells, many tumour-associated antigens are also expressed in normal tissues. For examples, WT1 is expressed at elevated levels in most leukaemias, but it is also expressed at reduced levels in normal CD34+ haematopoietic stem cells and in progenitor cells of other tissues. Antigen expression in normal tissues is likely to trigger immunological tolerance and thus blunt T cell responses. This could explain the observation that WT1 vaccination in mice frequently fails to stimulate high avidity cytotoxic T cell responses. In order to circumvent tolerance, we have isolated from HLA-A2-negative donors high avidity CTL specific for HLA-A2-presented peptide epitopes of WT1. These allorestricted CTL efficiently kill HLA-A2-positive leukaemia cells but not normal CD34+ haematopoietic stem cells. However, adoptive cellular therapy with allorestricted CTL could only be performed in leukaemia patients rendered tolerant to the infused CTL by prior allogeneic stem cell transplantation. In order to circumvent this limitation, we propose to exploit the TCR of allorestricted CTL as therapeutic tool. TCR gene transfer can be used to take advantage of the specificity of allorestricted CTL and transfer it to patient CTL, while avoiding the transfer of immunogenic alloantigens from the donor CTL to the patient.

Use of the allogeneic TCR repertoire to enhance anti-tumor immunity.

It is well established that antigen-specific T lymphocytes can inhibit tumor growth in humans and in mice, leading to complete tumor elimination in some cases. However, in many cases T cell immunity is unable to successfully control tumor progression. Since tumors are derived from normal tissues, most antigens are shared with normal tissues, although expression levels are usually elevated in malignant cells. Nevertheless, low-level expression in normal cells can be sufficient to render autologous T cells tolerant and thus unable to mount effective immune responses against tumors. Here, we review how allogeneic T cells can be used to isolate T cells that effectively recognise and kill tumor cells, but not normal cells with low level of antigen expression. The TCR of allogeneic T cells can be introduced into patient T cells to equip them with anti-tumor specificity that may not be present in the autologous T cell repertoire.