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3rd December 2021
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.
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.
Aminlari A et al. Diagnosing Achilles Tendon Rupture with Ultrasound in Patients Treated Surgically: A Systematic Review and Meta-Analysis. J Emerg Med 2021
18th August 2021
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.
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.
Wu Y et al. Control of the activity of CAR-T cells within tumours via focused ultrasound. Nat Biomed Eng 2021