Patterns of myocardial injury in recovered troponin-positive COVID-19 patients assessed by cardiovascular magnetic resonance.

BACKGROUND: Troponin elevation is common in hospitalized COVID-19 patients, but underlying aetiologies are ill-defined. We used multi-parametric cardiovascular magnetic resonance (CMR) to assess myocardial injury in recovered COVID-19 patients. METHODS AND RESULTS: One hundred and forty-eight patients (64 ± 12 years, 70% male) with severe COVID-19 infection [all requiring hospital admission, 48 (32%) requiring ventilatory support] and troponin elevation discharged from six hospitals underwent convalescent CMR (including adenosine stress perfusion if indicated) at median 68 days. Left ventricular (LV) function was normal in 89% (ejection fraction 67% ± 11%). Late gadolinium enhancement and/or ischaemia was found in 54% (80/148). This comprised myocarditis-like scar in 26% (39/148), infarction and/or ischaemia in 22% (32/148) and dual pathology in 6% (9/148). Myocarditis-like injury was limited to three or less myocardial segments in 88% (35/40) of cases with no associated LV dysfunction; of these, 30% had active myocarditis. Myocardial infarction was found in 19% (28/148) and inducible ischaemia in 26% (20/76) of those undergoing stress perfusion (including 7 with both infarction and ischaemia). Of patients with ischaemic injury pattern, 66% (27/41) had no past history of coronary disease. There was no evidence of diffuse fibrosis or oedema in the remote myocardium (T1: COVID-19 patients 1033 ± 41 ms vs. matched controls 1028 ± 35 ms; T2: COVID-19 46 ± 3 ms vs. matched controls 47 ± 3 ms). CONCLUSIONS: During convalescence after severe COVID-19 infection with troponin elevation, myocarditis-like injury can be encountered, with limited extent and minimal functional consequence. In a proportion of patients, there is evidence of possible ongoing localized inflammation. A quarter of patients had ischaemic heart disease, of which two-thirds had no previous history. Whether these observed findings represent pre-existing clinically silent disease or de novo COVID-19-related changes remain undetermined. Diffuse oedema or fibrosis was not detected.

Chemokine expression is associated with the accumulation of tumour associated macrophages (TAMs) and progression in human colorectal cancer.

Chemokines promote tumour progression by enhancing proliferation and modifying the immune response. The purpose of this study was to test the hypothesis that CCL2 monocyte chemotactic protein-1 (MCP-1) contributes to the progression of colorectal cancer by influencing the number and distribution of tumour associated macrophages (TAMs). Chemokine expression was assessed in human colorectal adenocarcinomas by ribonuclease protection assay (RPA). Colonic adenocarcinoma cell lines were used to assess chemokine production by enzyme linked immunosorbant assay (ELISA), and Boyden microchemotaxis assays were performed to determine cell line supernatant monocyte chemotactic activity. CCL2 production was assessed in paraffin embedded tumour samples by immunohistochemistry. Finally, the number of macrophages and their distribution was determined in the same colorectal adenocarcinomas and compared with CCL2 expression and tumour stage. Results showed that CCL2 produced by cell lines induced monocyte chemoattraction, the expression of this chemokine in solid cancers increased with tumour stage (P < 0.05) and immunohistochemistry localized production to tumour cells. Analysis of the macrophage infiltrate showed that the accumulation was significantly greater in tumours than controls (P < 0.005) and within tumours it was greatest in necrotic regions (median 44,600 per mm(3)). Macrophage accumulation increased with tumour stage and correlated with CCL2 expression (r(s) = 0.8). CXCL8 interleukin 8 (IL-8), a potent angiogenic factor and growth factor, was expressed in all tumours and cell lines. It is concluded that CCL2 induces the accumulation of tumour promoting TAMs in human colorectal cancer and represents a therapeutic target to modify the macrophage response and direct immune mediated therapy.

Case 36: a difficult diagnosis in a patient with fever and progressive multi-organ failure.

A man in late middle age presented with fever, systemic symptoms, raised inflammatory markers and anaemia of chronic disease. Despite two months of investigation, the diagnosis of a haematological malignancy was made only at autopsy.

Validation of a diagnostic reminder system in emergency medicine: a multi-centre study.

BACKGROUND: Diagnostic error is a significant problem in emergency medicine, where initial clinical assessment and decision making is often based on incomplete clinical information. Traditional computerised diagnostic systems have been of limited use in the acute setting, mainly due to the need for lengthy system consultation. We evaluated a novel web-based reminder system, which provides rapid diagnostic advice to users based on free text search terms. METHODS: Clinical data collected from patients presenting to three emergency departments with acute medical problems were entered into the diagnostic system. The displayed results were assessed against the final discharge diagnoses for patients who were admitted to hospital (diagnostic accuracy) and against a set of "appropriate" diagnoses for each case provided by an expert panel (potential utility). RESULTS: Data were collected from 594 patients (53.4% of screened attendances). Mean age was 49.4 years (95% CI 47.7 to 51.1) and the majority had significant past illnesses. Most were assessed first by junior doctors (70%) and 266/594 (44.6%) were admitted to hospital. Overall, the diagnostic system displayed the final discharge diagnosis in 95% of inpatients and 90% of "must-not-miss" diagnoses suggested by the expert panel. The discharge diagnosis appeared within the first 10 suggestions in 78% of cases. CONCLUSIONS: The Isabel diagnostic aid has been shown to be of potential use in reminding junior doctors of key diagnoses in the emergency department. The effects of its widespread use on decision making and diagnostic error can be clarified by evaluating its impact on routine clinical decision making.

'Ebb and flow by the moon': can we do better in hospital?

Hospitals are required to manage acutely ill patients. Optimising patient experience with regard to clinical outcomes and patient experience relies on the interaction with healthcare professionals and the manner in which patient cohorts are managed. The key to success is to keep variability to a minimum, both in terms of clinical practice and in terms of how patients are moved through the system; variability in flow increases the likelihood of queues developing, and the development of queues results in delays and has a negative impact on care. This article attempts to illuminate some of the principles which should be considered when designing whole systems. The application of relatively few principles should enable optimal flow of patient cohorts; this in turn will support optimal individual clinical management. As each site is necessarily slightly different, the figures provided are designed to simply illustrate the generic points made in the text.

Using an 'action set' for the management of acute upper gastrointestinal bleeding.

BACKGROUND: We studied the management of patients with acute upper gastrointestinal (GI) bleeding (AUGIB) at the Royal Free Hospital. The aim was to compare our performance with the national standard and determine ways of improving the delivery of care in accordance with the recently published 'Scope for improvement' report. METHODS: We randomly selected patients who presented with haematemesis, melaena, or both, and had an oesophageogastroduodenoscopy (OGD) between April and October 2009. We developed local guidelines and presented our findings in various forums. We collaborated with the British Medical Journal's Evidence Centre and Cerner Millennium electronic patient record system to create an electronic 'Action Set' for the management of patients presenting with AUGIB. We re-audited using the same standard and target. RESULTS: With the action set, documentation of pre-OGD Rockall scores increased significantly (p ≤ 0.0001). The differences in the calculation and documentation of post-OGD full Rockall scores were also significant between the two audit loops (p = 0.007). Patients who inappropriately received proton-pump inhibitors (PPIs) before endoscopy were reduced from 73.8% to 33% (p = 0.02). Patients receiving PPIs after OGD were also reduced from 66% to 50% (p = 0.01). Discharges of patients whose full Rockall score was less than or equal to two increased from 40% to 100% (p = 0.43). CONCLUSION: The use of the Action Set improved calculation and documentation of risk scores and facilitated earlier hospital discharge for low-risk patients. Significant improvements were also seen in inappropriate use of PPIs. Actions sets can improve guideline adherence and can potentially promote cost-cutting and improve health economics.

The patient with haematemesis and melaena.

Bleeding from the upper gastrointestinal (GI) tract is a common medical emergency, with an incidence of between 50-150 cases per 100,000 per year.1 A recent audit by the British Society of Gastroenterology showed the mortality rate from upper GI bleeds has fallen from 14%2 in 1993 to 10% in 2007.3 However, despite the use of proton pump inhibitors (PPIs), admission rates for peptic ulcer haemorrhage have increased in older age groups,4 probably related to increased use of antiplatelet agents such as aspirin and clopidogrel and anticoagulants in acute coronary syndromes, stroke and atrial fibrillation. The rising age of the population may also have offset further reductions in mortality and morbidity that may have otherwise come about through improved supportive and endoscopic care.

A case of fatal felodipine overdose.

A 54 year gentleman was admitted to hospital within four hours of taking an overdose of modified release felodipine tablets, with a total dose of approximately 250 mg. The initial management comprised fluid resuscitation, calcium chloride and glucagon. He remained hypotensive and was commenced on hyperinsulinaemia-euglycaemic therapy. Hypotension persisted with the development of progressive metabolic acidosis despite increasing inotropic support, haemofiltration and high dose insulin-dextrose infusions. The patient died 60 hours post overdose. The case highlights the profound, refractory circulatory collapse and lethal consequences of significant calcium channel blocker overdose and also reviews potential management strategies to attempt to reverse these changes. Despite the lack of evidence of whole bowel irrigation in overdose per se, its role in the removal of modified release compounds has not been studied. We would strongly urge emergency departments to consider this therapeutic modality, especially in overdoses involving delayed release preparations of calcium channel blockers, which are extremely toxic in overdose and are associated with very high mortality.