Predictors of long-term survival in 5,680 patients admitted to a UK major trauma centre with thoracic injuries.

INTRODUCTION: The long-term outcomes of chest trauma are largely unknown. We sought to determine the predictors of in-hospital and long-term survival in patients admitted to a major trauma centre (MTC) with chest injuries and to evaluate spatial patterns of injury in our network area. METHODS: Retrospective analysis of data collected on the National Trauma Audit Research Network (TARN) database using multivariate analysis and Cox regression analysis. Spatial analysis was performed using ArcGis 10.7.1. RESULTS: Some 5,680 patients were admitted with chest trauma between December 1999 and December 2019. Median patient age was 45 years and the median Injury Severity Score (ISS) was 20. The proportion of patients who had an operation was 39.8%. Age, blood transfusion, head injury, shock, emergency thoracotomy and heart disease were predictors of hospital mortality (p < 0.05). However, having an operation on concomitant injuries was protective. ISS and Glasgow Coma Score were discriminators of in-hospital mortality (C-indices 0.76 and 0.80, respectively). The 10-year survival values for patients who survived to discharge from hospital and who were aged <40, 50, 60, 70, 80 and >80 years were 99%, 93%, 95%, 87%, 75% and 43%, respectively. Preadmission lung disease and alcohol/drug misuse were poor predictors of long-term survival (p < 0.05). Hotspot analysis revealed the areas with the highest incidents were all close to the MTC. CONCLUSIONS: The MTC is geographically central to areas with high numbers of trauma incidents. Although emergency thoracotomy was a predictor of poor in-hospital outcomes, having surgery for concomitant injuries improved outcomes. Patients surviving to discharge have good long-term survivals.

Management of thoracic trauma.

Managing major thoracic trauma begins with identifying and anticipating injuries associated with the mechanism of injury. The key aims are to reduce early mortality and the impact of associated complications to expedite recovery and restore the patient to their pre-injury state. While imaging is imperative to identify the extent of thoracic trauma, some pathology may require immediate treatment. The majority can be managed with adequate pleural drainage, but respiratory failure and poor gas exchange may require either non-invasive or invasive ventilation. Ventilation strategies to protect from complications such as barotrauma, volutrauma and ventilator-induced lung injury are important to consider. The management of pain is vital in reducing respiratory complications. A multimodal strategy using local, regional and systemic analgesia may mitigate respiratory side effects of opioid use. With optimal pain management, physiotherapy can be fully utilised to reduce respiratory complications and enhance early recovery. Thoracic surgeons should be consulted early for consideration of surgical management of specific injuries. With a greater understanding of the mechanisms of injury and the appropriate use of available resources, favourable outcomes can be reached in this cohort of patients. Overall, a multidisciplinary and holistic approach results in the best patient outcomes.

The surgical application of point-of-care haemostasis and platelet function testing.

BACKGROUND: Disordered coagulation complicates many diseases and their treatments, often predisposing to haemorrhage. Conversely, patients with cardiovascular disease who demonstrate antiplatelet resistance may be at increased thromboembolic risk. Prompt identification of these patients facilitates optimization of haemostatic dysfunction. Point-of-care (POC) tests are performed 'near patient' to provide a rapid assessment of haemostasis and platelet function. METHODS: This article reviews situations in which POC tests may guide surgical practice. Their limitations and potential developments are discussed. The paper is based on a Medline and PubMed search for English language articles on POC haemostasis and platelet function testing in surgical practice. RESULTS: POC tests identifying perioperative bleeding tendency are already widely used in cardiovascular and hepatic surgery. They are associated with reduced blood loss and transfusion requirements. POC tests to identify thrombotic predisposition are able to determine antiplatelet resistance, predicting thromboembolic risk. So far, however, these tests remain research tools. CONCLUSION: POC haemostasis testing is a growing field in surgical practice. Such testing can be correlated with improved clinical outcome.

Platelet function and antiplatelet therapy.

BACKGROUND: Platelets have roles other than haemostasis and many are relevant to surgical practice. This review examines both the pathophysiology of platelets in haemostasis and thrombosis, and other roles of clinical importance. METHODS: A literature review of the various functional roles of platelets was performed (Medline search, English language) including their action in inflammation (in particular in atherothrombosis), antimicrobial defence and tumour growth. Current clinical evidence for antiplatelet therapy is also reviewed. RESULTS AND CONCLUSION: Platelet functions are multiple, complex and not limited to haemostasis. Understanding of platelet pathophysiology continues to grow and this is relevant to many aspects of surgical practice, particularly the clinical use of antiplatelet therapy.

Ischaemic skeletal muscle increases serum ischaemia modified albumin.

OBJECTIVES: Ischaemia modified albumin (IMA) has been used as a marker of myocardial ischaemia but little is known about its production during ischaemia of other tissues. The clinical models of patients with intermittent claudication and major arterial surgery were used to investigate IMA production from ischaemic skeletal muscle. DESIGN: Prospective clinical study. MATERIALS AND METHODS: IMA was measured pre-operatively, at end ischaemia, and 5 min, 4, 24, 48, 72 and 144 h post-surgery in patients undergoing (a) revascularisation for intermittent claudication (IC, n=15), (b) abdominal aortic aneurysm repair (AAA, n=12) and controls (n=16). RESULTS: The median pre-operative IMA concentration in IC patients was significantly higher than the AAA group (88.3 versus 83.5 U/ml, p=0.036) and controls (88.3 versus 80.3 U/ml, p=0.031). IMA concentrations increased significantly during arterial clamping in both IC and AAA groups (88.3 versus 120.0 U/ml, p=0.001; 83.5 versus 118.8 U/ml, p=0.002, respectively) consistent with increased skeletal muscle ischaemia. In contrast, there was only a mild perioperative increase in the controls (80.3 versus 91.6 U/ml, p=0.012). CONCLUSIONS: Patients with intermittent claudication have significantly elevated IMA and skeletal muscle ischaemia during arterial surgery results in significantly increased circulating IMA. When IMA is used to detect myocardial ischaemia, ischaemic skeletal muscle must be excluded.

Increased nitrotyrosine production in patients undergoing abdominal aortic aneurysm repair.

BACKGROUND: Vascular inflammation is implicated in the pathogenesis of atherosclerosis and abdominal aortic aneurysm (AAA), and is thought to involve reactive species such as the nitric oxide-derived oxidant peroxynitrite. In the present study nitrotyrosine was measured as a stable marker of peroxynitrite production in vivo. METHODS: Perioperative blood samples were obtained from patients undergoing elective open or endovascular repair of an AAA and from patients with intermittent claudication, smoking aged-matched controls, non-smoking aged-matched controls and non-smoking young healthy controls. Plasma nitrotyrosine was measured by an enzyme-linked immunosorbent assay. RESULTS: The median plasma nitrotyrosine concentration in patients with an AAA (0.46 nmol nitrated bovine serum albumin equivalents per mg protein) was significantly higher than that in patients with intermittent claudication (0.35 nmol; P = 0.002), smoking controls (0.36 nmol; P = 0.001), non-smoking controls (0.35 nmol; P = 0.002) and young healthy controls (0.27 nmol; P < 0.001). Nitrotyrosine concentrations increased during early reperfusion in open AAA repair, but not during endovascular repair. AAA exclusion from the circulation reduced levels to control values (P = 0.001). CONCLUSION: Patients with an AAA had raised levels of circulating nitrated proteins compared with patients with claudication and controls, suggesting a greater degree of ongoing inflammation that was not related to smoking.

Penetrating atherosclerotic ulcers of the aorta.

BACKGROUND: Penetrating aortic ulcers burrow into the aortic wall and can have fatal consequences. Although they were first described as long ago as 1934 they have only recently been recognized as a distinct pathological entity. METHOD: A review of the current literature was undertaken, based primarily on an English language Medline search with secondary references obtained from key articles. RESULTS: Penetrating aortic ulcer is principally a disease of elderly hypertensive men. It may run a benign course or may produce complications such as aortic rupture, embolization and aneurysm formation. Presentation may be identical to that of classical aortic dissection, but the distinction is important because an ulcer may be more likely to cause rupture. CONCLUSION: Open surgical repair has been the 'gold standard' of treatment but endovascular stenting is an attractive option in this group of frail patients.

Light and electron microscopic in situ hybridization: non-radioactive labeling and detection, double hybridization, and combined hybridization-immunocytochemistry.

We performed light and electron microscopic in situ hybridization, according to the same protocol and without pretreatment of sections, on Lowicryl- and LR Gold-embedded cells. Digoxigenin (DIG)- or biotin-labeled riboprobes were visualized by direct or indirect immunodetection using commercially available gold-antibody conjugates with 0.8-10-nm gold grains. At the ultrastructural level, the main findings were that DIG-labeled probes gave a slightly higher labeling intensity (grains per signal) than biotin. The direct detection method produced a more compact signal, which led to better resolution at medium and high magnifications. Labeling intensities of all gold grain sizes were essentially equal. Grain sizes of 5 nm and larger were highly preferable because available enhancement methods are unsatisfactory for ultrasmall grains. The optimized immunodetection protocols are suitable for double hybridization with two different probes and for combined hybridization and immunocytochemistry.

Functional heterogeneity of CD4-positive T-cell subsets: the correlation between effector functions and lymphokine secretion is limited.

Several effector functions and the lymphokine secretion pattern of 30 antigen-specific CD4+ T-cell clones have been investigated. The clones were generated directly by limiting dilution cloning of nylon wool-purified T-cells obtained from KLH immunized BALB/c mice and avoiding an initial bulk culture phase. Using this approach the CD4+ T-cell clones were grouped into helper and nonhelper subsets. Among the helper subset, clones which helped B-cells for specific antibody production by either cognate or noncognate recognition were identified. Some but not all of these helper clones fitted into the Th1 and Th2 scheme, if the lymphokine secretion pattern was evaluated. Among the nonhelper subset CD4+ clones which killed activated APC in a MHC class II-restricted and antigen-specific manner were identified. In addition, one clone which suppressed B-cell antibody production mediated by helper clones was found. However, neither the suppression of antibody responses nor the inability of the nonhelper clones to help B-cells is due to the killing of B-cells. Various attempts were made to convert nonhelper into helper clones and helper into killer clones, without success. Thus, the functional properties of these clones are stable traits and not convertible by varying the experimental conditions.

CD4+ T cell-mediated killing of MHC class II-positive antigen-presenting cells. I. Characterization of target cell recognition by in vivo or in vitro activated CD4+ killer T cells.

Ag-specific as well as Ia-restricted killing of certain APC by CD4+ T cells was investigated. The CD4-mediated killing is not only a characteristic of in vitro long term cultured T cell lines or clones, but is also manifest after in vivo priming. Thus, CD4+ killer T cells are generated in vivo as well. CD4+ killer T cells are detected in the Th1, but not in the Th2 subset, and they do not appear to lyse Ia+ APC or bystander cells by a pathway mediated by secreted T cell factors. The latter observation is demonstrated by cold target inhibition experiments as well as by the failure of puromycin to inhibit killing, if applied in doses which completely block lymphokine secretion. Ia+ APC differ in their susceptibility to lysis. Transformed APC are usually better lysed than nontransformed APC. Unstimulated B cells are not killed, while LPS-stimulated B cell blasts are killed. The results of cold target inhibition and bystander killing experiments suggest that CD4+ killer T cells are activated by the common pathway, i.e., by Ag presented in the context of Ia, but killing requires the recognition of additional determinant(s) on APC. It is proposed that these killing-inducing determinants are continuously expressed on most transformed Ia+ cells and on nontransformed but stimulated APC.