Pre-transplant management and sensitisation in vascularised composite allotransplantation: A systematic review.

INTRODUCTION: Vascularised composite allotransplantation (VCA) permits like-for-like reconstruction following extensive soft tissue injuries. The initial management of extensive soft tissue injury can lead to the development of anti-HLA antibodies through injury-related factors, transfusion and cadaveric grafting. The role of antibody-mediated rejection, donor-specific antibody formation and graft rejection in the context of VCA remains unclear. This systematic review aimed to determine whether pre-transplant management strategies influence immunological outcome following VCA. METHODS: A systematic review of MEDLINE, EMBASE and CINAHL using a PRISMA-compliant methodology up to February 2019 was conducted. Pre-transplant, procedural and long-term outcome data were collected and recorded for all VCA recipients on an individual patient basis. RESULTS: The search revealed 3,847 records of which 114 met inclusion criteria and reported clinical data related to 100 patients who underwent 129 VCA transplants. Trauma (50%) and burns (15%) were the most frequent indications for VCA. Of all 114 studies, only one reported acute resuscitative management. Fifteen patients were sensitised prior to reconstructive transplantation with an 80%%incidence of acute rejection in the first post-operative year. Seven patients demonstrated graft vasculopathy, only one of whom had demonstrated panel reactive antibodies. CONCLUSIONS: Currently employed acute management strategies may predispose to the development of anti-HLA antibodies, adding to the already complex immunological challenge of VCA. To determine whether association between pre-transplant management and outcomes exists, further refinement of international registries is required.

A 5-year single-centre retrospective study of potential drug interactions in burns inpatients with psychiatric comorbidities.

INTRODUCTION: Burns patients with psychiatric comorbidities may be at increased risk of harm from drug interactions. We aimed to identify the most common classes of drug involved, the potential clinical effects and any clinical evidence for their occurrence. METHODS: The International Burn Injury Database was used to identify all admission episodes for patients with a psychiatric comorbidity over a 5-year period at an adult regional burns unit. For this group, all drugs administered were categorised as either a new or continuing medication. Following this, an established online tool was used to screen for potential interactions between drugs. Where one was identified, a retrospective notes review was used to investigate whether it had occurred clinically. RESULTS: Ninety-one admission episodes were identified and records were available for 60 of these. In total, 145 incidences of severe potential interactions were identified (89 between a new drug and a continuing drug and 56 between two new drugs). The most frequently involved continuing drugs with the potential for interaction were neurotransmitter reuptake-inhibiting antidepressants and mirtazapine, while the most common new drugs identified were ondansetron, fentanyl and tramadol. The most frequently identified potential consequence of interactions were serotonin syndrome, arrhythmias and hypokalaemia. Clinically, there was minimal evidence for any interaction. CONCLUSION: We have found many potential severe interactions in this patient group and psychotropic drugs were more commonly implicated than other drug classes. However, there was little evidence of the clinical manifestations of interaction. Serious drug interactions in burns patients are likely rare, but clinicians should be aware of the most likely drugs involved and the possible sequelae.

Surgical Skills Workshops Should Be a Part of the United Kingdom Undergraduate Medical Curriculum.

INTRODUCTION:  Medical students across the United Kingdom (UK) report poor satisfaction with surgical teaching. The Surgical Skills Day (SSD) begins to address this by exposing medical students to surgery through an easily accessible one-day practical workshop. This study shows how the SSD encourages undergraduate engagement in surgery. METHOD:  Feedback forms were emailed to attendees of the SSD and their anonymised responses were used to evaluate the SSD. RESULTS:  A total of 144 students attended the SSD across three years and the feedback response rate was 74% (n = 107). Key findings were that 100% of respondents (n = 107) would like the SSD to be an annual event, 79% (n = 83) were more inclined to pursue a surgical career following the event, and 97% (n = 103) would like to see practical surgical skills incorporated into the curriculum. The SSD was able to engage undergraduates with surgery through mentorship, practical skills, specialty exposure, and teaching of the General Medical Council (GMC) mandated skills. CONCLUSIONS:  Undergraduate surgical teaching in the UK is insufficient. The student-led annual SSD showed improved engagement in practical surgical skills and increased enthusiasm for a surgical career. In light of this, the authors feel the SSD or similar event should be integrated into the UK medical school curriculum.

Assessment of Myocardial Microstructural Dynamics by In Vivo Diffusion Tensor Cardiac Magnetic Resonance.

BACKGROUND: Cardiomyocytes are organized in microstructures termed sheetlets that reorientate during left ventricular thickening. Diffusion tensor cardiac magnetic resonance (DT-CMR) may enable noninvasive interrogation of in vivo cardiac microstructural dynamics. Dilated cardiomyopathy (DCM) is a condition of abnormal myocardium with unknown sheetlet function. OBJECTIVES: This study sought to validate in vivo DT-CMR measures of cardiac microstructure against histology, characterize microstructural dynamics during left ventricular wall thickening, and apply the technique in hypertrophic cardiomyopathy (HCM) and DCM. METHODS: In vivo DT-CMR was acquired throughout the cardiac cycle in healthy swine, followed by in situ and ex vivo DT-CMR, then validated against histology. In vivo DT-CMR was performed in 19 control subjects, 19 DCM, and 13 HCM patients. RESULTS: In swine, a DT-CMR index of sheetlet reorientation (E2A) changed substantially (E2A mobility ∼46°). E2A changes correlated with wall thickness changes (in vivo r2 = 0.75; in situ r2 = 0.89), were consistently observed under all experimental conditions, and accorded closely with histological analyses in both relaxed and contracted states. The potential contribution of cyclical strain effects to in vivo E2A was ∼17%. In healthy human control subjects, E2A increased from diastole (18°) to systole (65°; p < 0.001; E2A mobility = 45°). HCM patients showed significantly greater E2A in diastole than control subjects did (48°; p < 0.001) with impaired E2A mobility (23°; p < 0.001). In DCM, E2A was similar to control subjects in diastole, but systolic values were markedly lower (40°; p < 0.001) with impaired E2A mobility (20°; p < 0.001). CONCLUSIONS: Myocardial microstructure dynamics can be characterized by in vivo DT-CMR. Sheetlet function was abnormal in DCM with altered systolic conformation and reduced mobility, contrasting with HCM, which showed reduced mobility with altered diastolic conformation. These novel insights significantly improve understanding of contractile dysfunction at a level of noninvasive interrogation not previously available in humans.