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People with chronic low back pain (LBP) exhibit changes in postural control. Stereotypical muscle activations resulting from external perturbations include anticipatory (APAs) and compensatory (CPAs) postural adjustments. The aim and objective of this study was to determine differences in postural control strategies (peak amplitude, APAs and CPAs) between symptomatic and asymptomatic adults with and without Lumbar Disc Degeneration (LDD) using surface electromyography during forward postural perturbation. Ninety-seven subjects participated in the study (mean age 50 years (SD 12)). 3T MRI was used to acquire T2 weighted images (L1-S1). LDD was determined using Pfirrmann grading. A bespoke translational platform was designed to deliver horizontal perturbations in sagittal and frontal planes. Electromyographic activity was analysed bilaterally from 8 trunk and lower limb muscles during four established APA and CPA epochs. A Kruskal-Wallis H test with Bonferroni correction for multiple comparisons was conducted. Four groups were identified: no LDD no pain (n = 19), LDD no pain (n = 38), LDD pain (n = 35) and no LDD pain (n = 5). There were no significant differences in age or gender between groups. The most significant difference between groups was observed during forward perturbation. In the APA and CPA phases of predictable forward perturbation there were significant differences ankle strategy between groups (p = 0.007–0.008); lateral gastrocnemius and tibialis anterior activity was higher in the LDD pain than the LDD no pain group. There were no significant differences in the unpredictable condition (p>0.05). These findings were different from the remaining groups, where significant differences in hip strategy were observed during both perturbation conditions (p = 0.004–0.006). Symptomatic LDD patients exhibit different electromyographic strategies to asymptomatic LDD controls. Future LBP electromyographic research should benefit from considering assessment of both lower limbs in addition to the spine. This approach could prevent underestimation of postural control deficits and guide targeted rehabilitation.

Ultrasound practice is a longstanding tradition for radiology departments, being part of the family of imaging techniques. Ultrasound is widely practiced by non-radiologists but becoming less popular within radiology. The position of ultrasound in radiology is reviewed, and a possible long-term solution to manage radiologist expectations is proposed. An international group of experts in the practice of ultrasound was invited to describe the current organisation of ultrasound within the radiology departments in their own countries and comment on the interaction with non-radiologists and training arrangements. Issues related to regulation, non-medical practitioners, and training principles are detailed. A consensus view was sought from the experts regarding the position of ultrasound within radiology, with the vision of the best scenario for the continuing dominance of radiologists practising ultrasound. Comments were collated from nine different countries. Variable levels of training, practice, and interaction with non-radiologist were reported, with some countries relying on non-physician input to manage the service. All experts recognised there was a diminished desire to practice ultrasound by radiologists. Models varied from practising solely ultrasound and no other imaging techniques to radiology departments being central to the practice of ultrasound by radiologists and non-radiologist, housed within radiology. The consensus view was that the model favoured in select hospitals in Germany would be the most likely setup for ultrasound radiologist to develop and maintain practice. The vision for 20 years hence is for a central ultrasound section within radiology, headed by a trained expert radiologist, with non-radiologist using the facilities.Critical relevance statement The future of ultrasound within the radiology department should encompass all ultrasound users, with radiologists expert in ultrasound, managing the ultrasound section within the radiology department. The current radiology trainees must learn of the importance of ultrasound as a component of the ‘holistic’ imaging of the patient.Key points: 1. Ultrasound imaging within radiology departments precedes the introduction of CT and MR imaging and was first used over 50 years ago.2. Non-radiology practitioners deploy ultrasound examinations to either ‘problem solve’ or perform a comprehensive ultrasound examination; radiologists provide comprehensive examinations or use ultrasound to direct interventional procedures.3. Radiology does not ‘own’ ultrasound, but radiologists are best placed to offer a comprehensive patient-focused imaging assessment.4. A vision of the future of ultrasound within the radiology department is encompassing all ultrasound users under radiologists who are experts in ultrasound, positioned within the radiology department.5. The current radiology trainee must be aware of the importance of ultrasound as a component of the ‘holistic’ imaging of the patient.

Background Lumbar disc degeneration (LDD) is a condition associated with recurrent low back pain (LBP). Knowledge regarding effective management is limited. As a step towards the identification of risk, prognostic or potentially modifiable factors in LDD patients, the aim of this study was to explore the hypothesis that intrinsic lumbar spine shape is associated with LDD and clinical outcomes in symptomatic adults. Methods 3 T MRI was used to acquire T2-weighted sagittal images (L1-S1) from 70 healthy controls and LDD patients (mean age 49 years, SD 11, range 31–71 years). Statistical Shape Modelling (SSM) was used to describe lumbar spine shape. SSM identified variations in lumbar shape as ‘modes’ of variation and quantified deviation from the mean. Intrinsic shape differences were determined between LDD groups using analysis of variance with post-hoc comparisons. The relationship between intrinsic shape and self-reported function, mental health and quality of life were also examined. Results The first 7 modes of variation explained 91% of variance in lumbar shape. Higher LDD sum scores correlated with a larger lumbar lordosis (Mode 1 (55% variance), P  = 0.02), even lumbar curve distribution (Mode 2 (12% variance), P  = 0.05), larger anterior-posterior (A-P) vertebral diameter (Mode 3 (10% variance), P  = 0.007) and smaller L4-S1 disc spaces (Mode 7 (2% variance), P  ≤ 0.001). In the presence of recurrent LBP, LDD was associated with a larger A-P vertebral diameter (Mode 3) and a more even lumbar curvature with smaller L5/S1 disc spaces (Mode 4), which was significantly associated with patient quality of life ( P  = 0.002–0.04, r p  = 0.43–0.61)). Conclusions This exploratory study provides new evidence that intrinsic shape phenotypes are associated with LDD and quality of life in patients. Longitudinal studies are required to establish the potential role of these risk or prognostic shape phenotypes.

Background Breast cancer (BC) is the most common cancer in women, and despite the introduction of new screening programmes, therapies and monitoring technologies, there is still a need to develop more useful tests for monitoring treatment response and to inform clinical decision making. The purpose of this study was to compare circulating cell-free DNA (cfDNA) and circulating tumour cells (CTCs) with conventional breast cancer blood biomarkers (CA15-3 and alkaline phosphatase (AP)) as predictors of response to treatment and prognosis in patients with metastatic breast cancer (MBC). Methods One hundred ninety-four female patients with radiologically confirmed MBC were recruited to the study. Total cfDNA levels were determined by qPCR and compared with CELLSEARCH® CTC counts and CA15-3 and alkaline phosphatase (AP) values. Blood biomarker data were compared with conventional tumour markers, treatment(s) and response as assessed by RECIST and survival. Non-parametric statistical hypothesis tests were used to examine differences, correlation analysis and linear regression to determine correlation and to describe its effects, logistic regression and receiver operating characteristic curve (ROC curve) to estimate the strength of the relationship between biomarkers and clinical outcomes and value normalization against standard deviation to make biomarker values comparable. Kaplan–Meier estimator and Cox regression models were used to assess survival. Univariate and multivariate models were performed where appropriate. Results Multivariate analysis showed that both the amount of total cfDNA ( p value = 0.024, HR = 1.199, CI = 1.024–1.405) and the number of CTCs ( p value = 0.001, HR = 1.243, CI = 1.088–1.421) are predictors of overall survival (OS), whereas total cfDNA levels is the sole predictor for progression-free survival (PFS) ( p value = 0.042, HR = 1.193, CI = 1.007–1.415) and disease response when comparing response to non-response to treatment (HR = 15.917, HR = 12.481 for univariate and multivariate analysis, respectively). Lastly, combined analysis of CTCs and cfDNA is more informative than the combination of two conventional biomarkers (CA15-3 and AP) for prediction of OS. Conclusion Measurement of total cfDNA levels, which is a simpler and less expensive biomarker than CTC counts, is associated with PFS, OS and response in MBC, suggesting potential clinical application of a cheap and simple blood-based test.

The Controlled Attenuation Parameter (CAP score) is based on ultrasonic properties of retropropagated radiofrequency signals acquired by Fibroscan (Echosens, Paris, France). Since ultrasound propagation is influenced by the presence of fat, CAP score was developed to quantify steatosis. The aim of this study was to delineate the accuracy of CAP in diagnosing hepatic steatosis, compared to the gold standard of liver biopsy. A total of 150 patients underwent same-day liver biopsy and measurement of hepatic steatosis with Fibroscan. Only examinations with 10 satisfactory measurements, and an inter-quartile range of less than 30% of the median liver stiffness values were included for data analysis. Histological staging was then correlated with median values and Spearman correlation calculated. P values of <0.05 were considered statistically significant. For diagnosis of hepatic steatosis (HS), CAP could predict the steatosis S2 with AUROC 0.815 (95% CI 0.741-0.889), sensitivity (0.81) and specificity (0.73) when the optimal cut-off value was set at 288 dB/m. CAP detected histological grade S3 with AUROC 0.735 (95% CI 0.618-0.851), sensitivity (0.71) and specificity (0.74), with a cut-off value of 330 dB/m. The AUROC for steatosis grade S1 was 0.741 (95% CI 0.650-0.824), with a cut-off value of 263 dB/m with sensitivity 0.75 and specificity 0.70. Univariate analysis showed a correlation between CAP and diabetes (p 0.048). The performance of CAP to diagnose steatosis severity decreases as steatosis progresses. CAP is associated with diabetes but not other clinical factors and parameters of the metabolic syndrome.

Objectives To compare liver stiffness measurement (LSM) provided by Canon 2D-shear wave elastography (2D-SWE) and transient elastography (TE), the latter being the reference method. Methods Prospective study conducted in four European centres from 2015 to 2016 including patients with various chronic liver diseases who had LSMs with both 2D-SWE and TE on the same day. Median of 10 valid measurements (in kPa) was used for comparison using paired t test, Pearson correlation, intraclass correlation coefficient (ICC) and Bland-Altman plot. The ability of 2D-SWE to stratify patient according to recognised LSM-TE thresholds was assessed by ROC curve analysis. Results Six hundred forty patients were scanned, where 593 (92.7%), 572 (89.4%) and 537 (83.9%) had reliable LSMs by TE, 2D-SWE and both combined, respectively. In the latter ( n = 537, 310 [57.7%] male, mean 55.3 ± 14.8 years), median LSM-TE and LSM-2D-SWE had a mean of 10.1 ± 9.4 kPa (range 2.4–75) and 9.1 ± 6.1 kPa (range 3.6–55.7) (paired t test: p < 0.001), respectively. These were significantly correlated (Pearson r = 0.932, p < 0.001, ICC 0.850 (0.825–0.872), bias 0.99 ± 4.33 kPa [95% limits of agreement − 9.48 to + 7.49] with proportional error towards higher LSM values). LSM-2D-SWE values significantly increased with TE categories (ANOVA: p < 0.001). AUROCs ranged from 0.935 ± 0.010 (95% CI 0.910–0.954) to 0.973 ± 0.009 (95% CI 0.955–0.985), resulting in correct classification of 390/537 (73%) patients. Three 2D-SWE measurements were sufficient for reliable LSMs. Conclusion LSM using 2D-SWE correlates well with TE. It tends to underestimate higher stages of liver fibrosis but correctly classifies the majority of patients. It may be used in TE-derived algorithms to manage patients. Key Points • Liver stiffness measurement (LSM) by 2D-shear wave elastography (2D-SWE) and transient elastography (TE) are strongly correlated. • 2D-SWE shows proportionately lower LSM values compared to TE, particularly with the higher LSM range. • Three individual measurements by 2D-SWE are sufficient to assess LSM reliably.

Approximately 30% of ERα breast cancer patients relapse with metastatic disease following adjuvant endocrine therapies. The connection between acquisition of drug resistance and invasive potential is poorly understood. In this study, we demonstrate that the type II keratin topological associating domain undergoes epigenetic reprogramming in aromatase inhibitors (AI)-resistant cells, leading to Keratin-80 (KRT80) upregulation. KRT80 expression is driven by de novo enhancer activation by sterol regulatory element-binding protein 1 (SREBP1). KRT80 upregulation directly promotes cytoskeletal rearrangements at the leading edge, increased focal adhesion and cellular stiffening, collectively promoting cancer cell invasion. Shearwave elasticity imaging performed on prospectively recruited patients confirms KRT80 levels correlate with stiffer tumors. Immunohistochemistry showed increased KRT80-positive cells at relapse and, using several clinical endpoints, KRT80 expression associates with poor survival. Collectively, our data uncover an unpredicted and potentially targetable direct link between epigenetic and cytoskeletal reprogramming promoting cell invasion in response to chronic AI treatment. ERα breast cancer can relapse to metastatic disease following endocrine therapy. Here, the authors find that when aromatase inhibitor treatment resistance develops, epigenomic reprogramming drives Keratin-80 upregulation via SREBP1, and promotes cytoskeletal rearrangements that drive cancer cell invasion.

Vascular liver diseases (VLDs) include different pathological conditions that affect the liver vasculature at the level of the portal venous system, hepatic artery, or venous outflow system. Although serological investigations and sometimes histology might be required to clarify the underlying diagnosis, imaging has a crucial role in highlighting liver inflow or outflow obstructions and their potential causes. Cross-sectional imaging provides a panoramic view of liver vascular anatomy and parenchymal patterns of enhancement, making it extremely useful for the diagnosis and follow-up of VLDs. Nevertheless, multiparametric ultrasound analysis provides information useful for differentiating acute from chronic portal vein thrombosis, distinguishing neoplastic invasion of the portal vein from bland thrombus, and clarifying the causes of venous outflow obstruction. Color Doppler analysis measures blood flow velocity and direction, which are very important in the assessment of VLDs. Finally, liver and spleen elastography complete the assessment by providing intrahepatic and intrasplenic stiffness measurements, offering further diagnostic information.

The 50th year of the European Federation of Societies in Ultrasound in Medicine and Biology (EFSUMB) has been celebrated 2022 publishing articles on the history of US. Contrast enhanced ultrasound (CEUS) allows to visualize blood flow and tissue perfusion. CEUS has proven to be safe without risk of nephrotoxicity. The availability of a contrast agent (tracer) for ultrasound imaging allows for the first time a dynamic assessment of tissue perfusion (blood flow and wash-in/wash-out pattern) which is an essential part for the detection and characterisation of pathological tissue and abnormal organ function. It was an outstanding achievement of academic centers in close cooperation with EFSUMB to investigate and validate the clinical potential of this new technology for the diagnosis and monitoring of various diseases and to develop clinical guidelines based on an in-depth assessment of the existing scientific publications. An important part of the implementation of CEUS in clinical practice was the development of contrast-specific imaging modes on the ultrasound scanners (in close cooperation with the machine manufacturers), the optimization of the machine setups for contrast imaging and the education provided to clinical users in form of workshops, webinars, textbooks and scientific congresses.

Purpose Irosustat is a first-generation, orally active, irreversible steroid sulfatase inhibitor. We performed a multicentre, open label phase II trial of the addition of Irosustat to a first-line aromatase inhibitor (AI) in patients with advanced BC to evaluate the safety of the combination and to test the hypothesis that the addition of Irosustat to AI may further suppress estradiol levels and result in clinical benefit. Experimental design Postmenopausal women with ER-positive locally advanced or metastatic breast cancer who had derived clinical benefit from a first-line AI and who subsequently progressed were enrolled. The first-line AI was continued and Irosustat (40 mg orally daily) added. The primary endpoint was clinical benefit rate (CBR). Secondary endpoints included safety, tolerability, and pharmacodynamic end points. Results Twenty-seven women were recruited, four discontinued treatment without response assessment. Based on local reporting, the CBR was 18.5% (95% CI 6.3–38.1%) on an intent to treat basis, increasing to 21.7% (95% CI 7.4–43.7%) by per-protocol analysis. In those patients that achieved clinical benefit ( n  = 5), the median (interquartile range) duration was 9.4 months (8.1–11.3) months. The median progression-free survival time was 2.7 months (95% CI 2.5–4.6) in both the ITT and per-protocol analyses. The most frequently reported grade 3/4 toxicities were dry skin (28%), nausea (13%), fatigue (13%), diarrhoea (8%), headache (7%), anorexia (7%) and lethargy (7%). Conclusions The addition of Irosustat to aromatase inhibitor therapy resulted in clinical benefit with an acceptable safety profile. The study met its pre-defined success criterion by both local and central radiological assessments.