Ultrasound sensitive and specific for initial diagnosis of acute appendicitis in ED

1st April 2022

The use of ultrasound has been found to have a high sensitivity and specificity for the initial diagnosis of acute appendicitis within an ED

Using ultrasound within an emergency department is both a sensitive and specific imaging modality for the diagnosis of patients with acute appendicitis. This was the conclusion of a retrospective study by researchers from the Department of Emergency Medicine, Inselspital University Hospital Bern, Bern, Switzerland.

Acute abdominal pain accounts for between 7 and 10% of all Emergency Department (ED) visits. Furthermore, in a retrospective review of 2222 patients with acute abdominal pain who underwent contrast enhanced CT scanning within 24 hours after admission, acute appendicitis accounted for 15.9% of all cases.

The diagnosis of acute appendicitis (AA) is crucial, particularly in older patients, with one study finding that among those older than 55 years of age, 29% had perforated appendicitis after 36 hours of symptoms and 67% between 36 and 48 hours of symptoms. 

Moreover, another study identified a perforation rate among those with appendicitis of 16 % and revealed how the cause of perforation was mostly physician-related in children and adults. It is also important to reduce the incidence of negative appendectomy (NA), i.e., the non-incidental removal of a normal appendix as there are significant clinical and financial costs incurred by patients undergoing NA during the treatment of presumed appendicitis.

The gold standard imaging modality for AA is computed tomography (CT), which has been shown to have a pooled sensitivity and specificity for diagnosis in adults of 83% and 93% respectively. Though CT is the preferred diagnostic imaging technique, there are concerns over both irradiation (especially in children), access and the costs of the technique.

At the researcher’s hospital, the current practice is to initially use an ultrasound scan for a patient with suspected AA and where this is positive, the patient proceeds to surgery. In contrast, negative or uncertain scans are followed up with a CT scan.

For the present study, the team undertook a retrospective analysis to evaluate their current strategy. They collected all suspected cases of AA over a 2-year period and classified the outcome of the sonographic examination as either AA; normal appendix or inconclusive. The sonography results were compared to a gold standard of either the CT result or intra-operative or histopathological findings where CT scans were not used.

These results were then classed as a true positive and true negative where the ultrasound findings matched the gold standard and either a false positive or negative where the ultrasound diagnosis differed from the gold standard or finally, as inconclusive.

An additional factor analysed since it might relevant, was the type of sonographer and which was categorised as either a radiologist or an experienced or inexperienced emergency care physician.

Ultrasound and diagnosis of AA

A total of 508 patients with mean ages ranging from 31.3 to 44.9 years who were scanned were included in the analysis. The prevalence of AA in the whole cohort was 34% and among the 508 patients, 308 (60.4%) had a conclusive ultrasound examination.

The sonography was positive in 115 patients, of whom 103 (89.6%) had appendicitis based on the reference standard. The sonogram was read as negative for AA in 193 patients and 12 of these (6.2%) had AA based on the reference standard, i.e., were false negatives.

Overall, the results suggested that ultrasound had a sensitivity for AA of 89.6% (95% CI 82.1 – 94.3%) and a specificity of 93.8% (95% CI 89.1 – 96.6%).

For the remaining 200 patients who had an inconclusive ultrasound, 29% were ultimately diagnosed with AA.

Comparison of radiographers, experienced physicians and inexperienced physicians showed that the sensitivities were 90.3%, 90.9% and 87.5% respectively. For instance, inexperienced physicians reached a definitive conclusion in 48.1% of exams compared to 76% for their experienced colleagues.

Commenting on their findings, the authors suggested that while ultrasound was able to identify AA in a large number of cases, where it was inconclusive, 29% of patients were eventually diagnosed with the condition.

They concluded that while an initial ultrasound might be negative, further investigation was warranted given that 6% of cases were likely to be false negatives.

Citation
Lehmann B et al. Diagnostic accuracy of a pragmatic, ultrasound-based approach to adult patients with suspected acute appendicitis in the ED Emerg Med J 2022

Hand-held and high-end vascular ultrasound devices show good agreement for carotid disease detection

25th February 2022

Hand-held carotid ultrasound has been demonstrated to have good agreement with conventional duplex ultrasound in ruling out carotid disease

A hand-held carotid ultrasound device shows an acceptable level of agreement with conventional duplex ultrasound for the examination of patients with suspected transitory ischaemic attack (TIA) or ischaemic stroke. This was the conclusion by a team of researchers from the Department of Internal Medicine, Levanger Hospital, Norway.

According to the World Stroke Organisation, 1 in 4 adults over the age of 25 will have a stroke in their lifetime and in 2019, there were 12·2 million incident cases of strokes, accounting for 11.6% of all global deaths.

Moreover, the presence of narrowing of the carotid artery or carotid stenosis, has been found to be associated with increased risk of ischaemic stroke. Carotid endarterectomy as a treatment, has been found to be of some benefit for patients with 50% to 69% symptomatic stenosis, in reducing the risk of stroke.

However, carotid stenosis cannot be adequately assessed through a physical examination and carotid ultrasonography has become a reproducible imaging method used to detect carotid atherosclerosis.

But could a hand-held carotid and hence much more portable, ultrasound device be just as reliable for the examination of patients with suspected TIA or an ischaemic stroke compared to a conventional high-end vascular ultrasound (HIGH)? This was the essential question addressed in the current study by the Norwegian team.

They included patients admitted to a community hospital with a suspected stroke or transient ischaemic attack. The patients were examined using a hand-held carotid ultrasound and the severity of carotid stenosis graded on a 7-point ordinal scale from 1 (normal) to 7 (occluded). Following this initial assessment, a HIGH was performed by a second cardiologist who remained unaware of the findings from the hand-held device and graded the degree of stenosis using the same scale.

The results of the two scans were then compared by weighted Cohen’s Kappa and which is designed to assess the level of agreement between the two techniques. Scores range from 0 to 1 with 0.41 – 0.60 rated as moderate agreement, 0.61 – 0.80 as substantial and over 0.81 as almost perfect agreement.

Hand-held carotid ultrasound agreement with HIGH

A total of 80 patients with a mean age of 71.5 years (47.5% women) were included in the study, 27.5% of whom, had a previous history of cardiovascular ischaemic events (i.e., ischaemic stroke, TIA, or myocardial infarction). From the total cohort, 11% were found to have a greater than 50% internal carotid stenosis (ICS) on examination. Overall, 77.5% of patients were discharged with a diagnosis of ischaemic stroke or TIA.

The overall agreement between the hand-held device and HIGH for the classification of the degree of internal carotid stenosis was 69%. In addition, the weighted Kappa agreement between the hand-held device and HIGH was 0.76 (95% CI 0.66 – 0.85). Nevertheless, there was evidence that the hand-held device overestimated ICS compared to HIGH when there was >50% occlusion (odds ratio for agreement = 0.15, 95% CI 0.06 – 0.42) using < 50% stenosis as the reference.

In discussing their results, the authors stated that there was a strong correlation between ICS grading between the hand-held carotid device and HIGH. They concluded that examining the level of carotid stenosis with a hand-held device was a reliable method for ruling out significant carotid artery disease.

But given the potential for overestimation when the carotid stenosis was greater than 50%, the authors suggested that the hand-device device should not be used for detailed classification of carotid disease.

Citation
Saxhaug LM et al. Reliability and agreement of point-of-care carotid artery examinations by experts using hand-held ultrasound devices in patients with ischaemic stroke or transitory ischaemic attack Open Heart 2022

Ultrasound imaging of value for diagnosis of Achilles tendon rupture in ED

3rd December 2021

Ultrasound imaging has been found to be highly sensitive modality for the diagnosis of both partial and complete Achilles tendon rupture in ED

The use of ultrasound imaging for the detection of both a partial and complete rupture of the Achilles tendon has been found to be a highly sensitive modality according to a systematic review and meta-analysis by a team from Department of Emergency Medicine, University of California, US.

The Achilles tendon is the strongest tendon in the body and rupture of the tendon has become a common problem among athletes involved in activities such as running, jumping and ball sports. An acute rupture of the tendon will often result in a sudden onset of pain and in some cases an audible “snapping” sound can be heard at the site of injury, leading to significant pain and disability. However, the diagnosis tendon rupture is not always clinically clear and any delay or misdiagnosis can result in a significant patient morbidity and in fact, it has been suggested that sush injuries are often misdiagnosed as an ankle sprain in 20% to 25% of patients. 

The use of ultrasound imaging for the diagnosis of Achilles tendon rupture has been described in the literature although there have been no meta-analytic studies assessing the overall performance of this imaging modality as a diagnostic tool in emergency departments. For the present study, the US team sought to systematically evaluate the sensitivity and specificity of ultrasound imaging for detecting complete and partial Achilles tendon ruptures in patients who were treated surgically.

The researchers performed a literature search in all the major databases for studies that included at least 5 patients and which reported on the sonographic diagnosis of Achilles tendon rupture compared with surgery as the reference standard. The set the primary outcome measure as complete tear of the Achilles tendon and they calculated the sensitivity, specificity and positive/negative likelihood ratios.

Findings

The literature search identified 15 eligible studies with 808 patients, all of whom were suspected of having an acute Achilles tendon injury. In addition, the ultrasound imaging procedure used was similar across all studies. The overall sensitivity of ultrasound for detecting a complete rupture was 94.8% (95% CI 91.3% – 97.2%) and the specificity 98.7% (95% CI 97.03% – 99.6%). The positive likelihood ratio was 74 and the negative likelihood ratio 0.05. Based on these results, it was therefore 74 times more likely that there would be a positive ultrasound in a patient with a complete Achilles tendon rupture compared to a patient without such a rupture. Similarly, there is a 20-fold decrease in the odds that a negative ultrasound will occur in a patient with a complete rupture.

There were 13 of the 15 studies which enabled assessment of a partial Achilles tendon rupture. The corresponding sensitivity was 93.7% (95% CI 95.3% – 98.7%) and the specificity was 97.4% (95% CI 95.3% – 98.7%). The positive likelihood ratio was 35.6% and the negative likelihood ratio 0.07.

Discussing their results, the authors suggested in the presence of a normal Achilles tendon on ultrasound, there is a very low likelihood that the patient had suffered a complete tendon rupture. For a partial rupture, the low negative likelihood ratio (0.07) indicated that it was 14-fold less likely that a negative ultrasound would occur in a patient with a partial tendon rupture.

They concluded that ultrasound imaging is a useful and valuable modality to minimise the misdiagnosis of a partial or complete Achilles tendon rupture with an emergency department.

Citation

Aminlari A et al. Diagnosing Achilles Tendon Rupture with Ultrasound in Patients Treated Surgically: A Systematic Review and Meta-Analysis. J Emerg Med 2021

Focused ultrasound controls CAR-T cells and suppresses tumour growth

18th August 2021

Using CAR-T cell therapy controlled with focused ultrasound improved solid tumour suppression and mitigated off-target activity in mice.

The treatment of cancer has traditionally involved surgery, chemotherapy or radiotherapy although in recent years, there has been increased interest in immunotherapy which makes use of the patient’s immune system to fight cancer. One form of immunotherapy is Chimeric Antigen Receptor (CAR) T-cell therapy which involves genetic modification of a patient’s T cells to express a specific tumour antigen. After modification, these modified T cells are infused back into a patient, attacking and destroying chemotherapy-resistant cancer. However, a major limitation to the use of CAR-T cells is that the tumour antigen can also be expressed by normal, healthy tissue and the modified T cells are unable to differentiate between malignant and benign cells. It is therefore not always easy to identify a specific antigen that is preferentially expressed on tumour cells. This led a team from the Department of Bioengineering, University of California, US, to create inducible cells that were engineered to express the surface protein but only in response to short-pulsed, focused ultrasound stimulation.

Findings
The team subcutaneously injected the specific CAR-T cells at the site of a tumour in mice, followed by three 5-minute pulses of focused ultrasound at 43 degrees centigrade. This resulted in a significant reduction in tumour size. To ensure that it was specifically the combination of the CAR-T cells and focused ultrasound that were shrinking the tumour, the team used two control groups of mice with tumours. In one group, the pulsed ultrasound was used in the absence of the specific CAR-T cells injected and this had no impact on tumour growth. The second group of mice also received the ultrasound but this time, but this time in the presence of naïve T cells, as opposed to the CAR-T cells and again, there was no effect on tumour growth. Finally, the researchers examined whether localised, pulsed ultrasound was effective using mice with both a local and distal tumour. Injection of standard CAR-T cells reduced the size of both the local and distal tumour. However, after injection of the CAR-T cells and directing the ultrasound only at the local tumour, there was a dramatic reduction in size of the local, but not distal tumour.

Discussing their findings, the authors noted the use of the targeted pulsed ultrasound was a potentially effective approach to the treatment of localised tumours. They added the local administration of the CAR-T cells has already been tested in animals and patients and a further advantage of their technique was the potential for a reduction in off-target activity, i.e., where the CAR-T cells affected healthy tissue.

While this novel approach appeared to be effective, further work is required to ensure that the method represents a much safer form of cell therapy.

Citation
Wu Y et al. Control of the activity of CAR-T cells within tumours via focused ultrasound. Nat Biomed Eng 2021