The EFSUMB Guidelines and Recommendations for Musculoskeletal Ultrasound - Part II: Joint Pathologies, Pediatric Applications, and Guided Procedures.

The second part of the Guidelines and Recommendations for Musculoskeletal Ultrasound (MSUS), produced under the auspices of EFSUMB, following the same methodology as for Part 1, provides information and recommendations on the use of this imaging modality for joint pathology, pediatric applications, and musculoskeletal ultrasound-guided procedures. Clinical application, practical points, limitations, and artifacts are described and discussed for every joint or procedure. The document is intended to guide clinical users in their daily practice.

The EFSUMB Guidelines and Recommendations for Musculoskeletal Ultrasound - Part I: Extraarticular Pathologies.

The first part of the guidelines and recommendations for musculoskeletal ultrasound, produced under the auspices of the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB), provides information about the use of musculoskeletal ultrasound for assessing extraarticular structures (muscles, tendons, entheses, ligaments, bones, bursae, fasciae, nerves, skin, subcutaneous tissues, and nails) and their pathologies. Clinical applications, practical points, limitations, and artifacts are described and discussed for every structure. After an extensive literature review, the recommendations have been developed according to the Oxford Centre for Evidence-based Medicine and GRADE criteria and the consensus level was established through a Delphi process. The document is intended to guide clinical users in their daily practice.

B cell-activating factor (BAFF) in children with inflammatory bowel disease.

BACKGROUND: Assessing the inflammation is important in the follow-up of paediatric patients with inflammatory bowel disease (IBD). We aim to evaluate the value of B cell-activating factor (BAFF) in paediatric IBD as a potential biomarker for follow-up. METHOD: We determined BAFF in serum and faeces and faecal calprotectin (CP) in 32 IBD children-16 Crohn's disease (CD) and 16 ulcerative colitis (UC). Twenty-six healthy children and 10 children with irritable bowel syndrome (IBS) were included as controls. RESULTS: No differences were found in serum BAFF between IBD, IBS, and healthy group: 1037.35, 990.9 and 979.8 pg/ml, respectively, all p > 0.05, but faecal BAFF was higher in the IBD group: 15.1, 8.5 and 8.2 pg/ml, respectively, p < 0.05, and higher in the UC group (55.975 pg/ml) compared to the CD group (10.95 pg/ml), p = 0.015. Splitting the IBD group in relation to the CP level, the serum BAFF had no significantly different values between the subgroups, but the faecal BAFF was significantly higher in the >250 µg/g subgroup. Cut-off values of BAFF were calculated. CONCLUSION: Faecal BAFF is a promising marker for monitoring the children with IBD, higher levels of BAFF being correlated with high CP. IMPACT: Faecal BAFF is a promising marker in monitoring the children with IBD, higher levels of BAFF being correlated with high faecal calprotectin. To our knowledge, this is the first paediatric study concerning BAFF evaluation in IBD. Faecal BAFF levels could be considered a potential non-invasive marker in monitoring IBD activity in paediatric population with clinically mild or inactive disease.

Shear wave elastography as a new method to identify parotid lymphoma in primary Sjögren Syndrome patients: an observational study.

Parotid non-Hodgkin lymphoma (NHL) in primary Sjögren syndrome (pSS) has no specific biomarker for diagnosis. Salivary glands ultrasound (US) is largely used, but its contribution in detecting parotid NHL has not been established. The aim of our study was to determine the added value of bidimensional shear wave elastography (2D-SWE) in pSS diagnosis and to determine its accuracy in identifying parotid NHL. Grey-scale US (GSUS) and 2D-SWE of salivary glands were performed in 35 patients with pSS and 35 healthy controls. The GSUS scores were calculated and the mean of three SWE consecutive measurements was used to appreciate the gland stiffness. SWE increase the diagnostic rate at a cut-off of 6.45 kPa (from 88.6 to 94.2%, p < 0.001) only if applied in patients with insufficient GSUS criteria for pSS diagnosis. The parotid glands with NHL (8 patients, all mucosa-associated lymphoid tissue type) had hyperechoic bands in more than half of the glandular parenchyma (in 68.75% of the glands), large hypoechoic area > 20 mm (all glands), traced gland area over 5 cm2 (all glands), parotid US score greater than 13 (in 68.75% of the glands), and high stiffness (elasticity modulus 13.9 ± 4.08 vs 6.32 ± 2.24) (all p < 0.001). These findings give high sensitivity (92.3%), specificity (100%), and positive (100%) and negative predictive values (98.3%) for NHL identification. The rest of GSUS findings did not correlate with the classic risk factors for lymphoma development (all p > 0.05). 2D-SWE had added value for pSS diagnosis in cases where GSUS aspect is normal or nonspecific. The higher stiffness of parotid NHL can be used for early diagnosis, biopsy guidance, and, possible, for treatment monitoring.

SERS-based liquid biopsy of saliva and serum from patients with Sjögren's syndrome.

In this preliminary study, we employed surface-enhanced Raman scattering (SERS) of saliva and serum samples for diagnosing Sjogren's syndrome (SjS), a systemic autoimmune disease characterized by dryness of the mouth and eyes. The saliva and serum samples from n = 29 patients with SjS and n = 21 controls were deproteinized with methanol and then the SERS spectra were acquired using silver nanoparticles synthesized by reduction with hydroxylamine hydrochloride. In the case of both saliva and serum, the SERS spectra were dominated by similar bands attributed to purine metabolites such as uric acid, xanthine, and hypoxanthine. Principal component analysis-linear discriminant analysis (PCA-LDA) models built from SERS spectra of saliva and serum yielded an overall classification accuracy of 94% and 98%, respectively. These results suggest that the SERS analysis of saliva and serum is able to capture the complex biochemical perturbations that accompany the onset of SjS, a strategy which could be translated in the future into a novel point-of-care diagnosis method. Graphical abstract.

Knee tuberculosis in the context of MALT lymphoma: the diagnostic role of ultrasound and CEUS. A case report.

Tuberculosis (TB) arthritis remains a diagnostic challenge. In addition to clinical presentation, the use of imaging techniques and confirmation of Mycobacterium tuberculosis are essential. We present the case of a 69-year-old female in whom the diagnosis of knee TB arthritis was simultaneously established with the diagnosis of MALT lymphoma. This case report aims to highlight the role of multimodal ultrasound (US) in both diagnosis and its utility in interventional procedures, such as aspiration and synovial biopsy.

Shear-Wave Elastography of the Achilles tendon: reliability analysis and impact of parameters modulating elasticity values.

PURPOSE: Shear wave elastography (SWE) has seen many advancements in Achilles tendon evaluation in recent years, yet standardization of this technique is still problematic due to the lack of knowledge regarding the optimal way to perform the examination. The purpose of this study was to evaluate the effects of ankle position, probe frequency and physical effort on the shear modulus of the Achilles tendon, but also to determine the intra and inter-observer reliability of the technique. METHODS: 37 healthy volunteers were included; SWE protocol was performed by two examiners. We analyzed the shear modulus of the tendon with the ankle in neutral, maximum dorsiflexion and maximum plantar flexion using two different high frequency probes. Afterwards, the subjects performed a brief physical exercise and SWE measurements were repeated. RESULTS: The L18-5 probe showed the highest ICC values (ICC = 0.798, 95% CI 0.660-0.880, p < 0.001) when positioned at 2 cm from the calcaneal insertion with the ankle in a neutral state. Conversely, utilizing the same L18-5 probe at 1 cm from the insertion during maximum plantar flexion of the ankle resulted in the lowest ICC (ICC = 0.422, 95% CI 0.032-0.655, p = 0.019). Significant variations in elasticity values were noted among different ankle positions and probe types, while no significant changes in elasticity were observed post-physical exercise. CONCLUSION: Ankle position and probe frequency are factors that influence elasticity values of the Achilles tendon. An ankle position between 10 and 20 degrees of plantar flexion is the most suitable for SWE evaluation. However, more research focusing on Achilles tendon SWE is essential due to the challenges encountered in standardizing this region.

A new form of severe acute localized reactions following intra-articular hyaluronic acid injections in knee osteoarthritis. A case report.

Intra-articular hyaluronic acid (HA) injections are widely used for the treatment of symptomatic knee osteoarthritis. Adverse reactions were described in a limited number of patients and consist in local inflammatory reactions and severe acute inflammatory reactions (pseudosepsis). We present the case of a 71-year-old woman who experienced a severe acute adverse effect immediately (within minutes) following intraarticular HA administration, attributed to HA precipitation. The severe very early local manifestations were accompanied by important systemic reactions, necessitating treatment with systemic corticosteroids besides joint lavage.

Ultrasound in bone fracture diagnosis - a comparative meta-analysis and systematic review.

AIM: This meta-analysis evaluates the diagnostic accuracy of ultrasound (US) for bone fractures over the past 47 years, comparing it to established imaging standards. MATERIAL AND METHODS: We adhered to PRISMA 2020 guidelines to search Medline, EMBASE, and the Cochrane Library using tailored search strategies. The primary outcome, US diagnostic performance, was analyzed across various subgroups including clinical relevance, patient age, and anatomical considerations. The QUADAS-2 tool was employed to assess study quality and minimize bias. RESULTS: From 5,107 initially identified studies, 75 met the inclusion criteria, encompassing 7,769 participants and 3,575 diagnosed fractures. The majority of studies were prospective (79%) and compared US primarily with plain radiography (76%) and CT scans (19%). Of these, 61 studies were amenable to systematic analysis, revealing US to have a sensitivity and specificity of 91% (95% CI: 90%-92%) and 91.3% (95% CI: 90.5%-92.1%), respectively. Likelihood ratios were favorable, with a positive value of 9.955 and a negative value of 0.087, and an odds ratio of 132.67. The area under the curve stood at 0.9715, indicating high diagnostic accuracy despite significant heterogeneity (I²=81.3% for sensitivity, 89.3% for specificity). CONCLUSION: The evidence supports US as a highly accurate diagnostic tool for bone fractures, rivalling standard imaging methods like CT and radiography. Its notable diagnostic efficacy, combined with advantages in reducing pain, wait times, and radiation exposure, advocates for its broader application. Further validation in large-scale, randomized trials is essential to integrate US more fully into clinical guidelines for fracture management.

Macrophages as Potential Therapeutic Targets in Acute Myeloid Leukemia.

Acute myeloid leukemia (AML) is a heterogenous malignant hemopathy, and although new drugs have emerged recently, current treatment options still show limited efficacy. Therapy resistance remains a major concern due to its contribution to treatment failure, disease relapse, and increased mortality among patients. The underlying mechanisms of resistance to therapy are not fully understood, and it is crucial to address this challenge to improve therapy. Macrophages are immune cells found within the bone marrow microenvironment (BMME), of critical importance for leukemia development and progression. One defining feature of macrophages is their plasticity, which allows them to adapt to the variations in the microenvironment. While this adaptability is advantageous during wound healing, it can also be exploited in cancer scenarios. Thus, clinical and preclinical investigations that target macrophages as a therapeutic strategy appear promising. Existing research indicates that targeting macrophages could enhance the effectiveness of current AML treatments. This review addresses the importance of macrophages as therapeutic targets including relevant drugs investigated in clinical trials such as pexidartinib, magrolimab or bexmarilimab, but also provides new insights into lesser-known therapies, like macrophage receptor with a collagenous structure (MACRO) inhibitors and Toll-like receptor (TLR) agonists.

Factors influencing the Shear Wave Elastography evaluation of the patellar tendon.

AIM: There is no clear standardization for tendon Shear Wave Elastography (SWE), and data regarding the factors that influence the correctness of evaluation are scarce. We aimed to determine the intra- and interobserver agreement in patellar tendon SWE, and to establish the influence of various factors on elasticity values. MATERIALS AND METHODS: We recruited 37 healthy volunteers; SWE of the patellar tendon was performed by two examiners. The following factors were analyzed: probe frequency, degree of joint flexion, size of region of interest (ROI), distance of the color box from the probe footprint, utilization of coupling gel as standoff, and the effect of physical exercise on elastic modulus values. RESULTS: Highest overall interobserver [k=0.767, 95%CI (0.717-0.799), p<0.001] and intraobserver agreement [k=0.920 (0.909-0.929) for examiner 1, k=0.891 (0.875-0.905) for examiner 2] was obtained with the knee in the neutral position, using the L18-5 probe. With the knee flexed at 30º and 45º, the elasticity values were higher compared to the neutral position (p<0.001). With the probe immersed in 0.25 and 0.50 cm coupling gel, the median values were lower compared to the probe placed on the skin (p=0.001, p=0.018). The ROI dimensions and the placement of the SWE box at the level of the skin or at 0.5 cm below skin did not significantly influence the elastic modulus. After physical exercise, the elasticity values decreased in the proximal and middle portion of the tendon (p=0.002, p<0.001). CONCLUSION: The best results obtained in patellar tendon SWE were with the knee in neutral position, in the proximal or middle tendon, after 10 minutes of relaxation and with the probe placed directly on the skin with minimal pressure. The size and position of ROI do not significantly influence the examination.

The "starry night" (diffuse microcalcific myopathy) - thousands of muscle microcalcifications after 30 years of Trichinella infection detected by ultrasound.

Trichinellosis, a parasitosis transmitted through consumption of raw or undercooked meat from pigs and game animals, is responsible for a specific myositis. The calcifications of infected myocytes and larva can be detected during many years postin-fection. We present the case of a male patient with a history of severe trichinellosis with disease onset 30 years ago, presenting with generalized muscle microcalcifications detected during musculoskeletal ultrasound evaluation. The ultrasound aspect of the muscles was indeed spectacular; hence, the comparison with a "starry night".

Diagnostic role of CXCL13 biomarker in primary Sjogren's syndrome patients with parotid non-Hodgkin's lymphoma complication.

INTRODUCTION: Serum biomarkers are important predictive factors for development of parotid non-Hodgkin's lymphoma (NHL) complication in primary Sjogren's syndrome (pSS) patients. The aim was to evaluate the diagnostic accuracy of serum CXCL13 chemokine in pSS patients with parotid NHL complication. MATERIAL AND METHODS: Serum CXCL13 chemokine was assessed in 33 patients with pSS [7 with parotid NHL complication (pSS+NHL subgroup) and 26 without NHL (pSS-NHL subgroup)] and 30 healthy subjects. RESULTS: The serum CXCL13 levels in pSS+NHL subgroup [175.2 (107.9-220.4) pg/ml] were significantly higher comparing to the healthy subjects group (p=0.018) and the pSS-NHL subgroup (p=0.048). A cut-off value of 123.45pg/ml (Se=71.4%, Sp=80.8%, AUROC=0.747) was established for parotid lymphoma diagnosis. CONCLUSION: The serum CXCL13 biomarker could be considered a valuable tool for the diagnosis of parotid NHL complication in pSS patients.

The value of abdominal ultrasonography compared to colonoscopy and faecal calprotectin in following up paediatric patients with ulcerative colitis.

AIM: To evaluate the value of abdominal ultrasonography (US) in the follow-up of paediatric patients with ulcerative colitis (UC) compared to faecal calprotectin (FC) and colonoscopy. MATERIAL AND METHOD: In this retrospective study we enrolled 30 paediatric patients previously diagnosed with UC, examined by abdominal US and colonoscopy within the same week. FC was also determined during the same week. Disease activity was established using the paediatric ulcerative colitis activity index (PUCAI). The global endoscopic activity was evaluated using the Mayo endoscopic subscore. RESULTS: Endos-copy revealed pathological findings of active disease in 27 out of 30 patients; 3 patients were in endoscopic remission. Only 18 of them had clinical active disease (PUCAI >10), [sensitivity (Se) 66.7% and specificity (Sp) 33% of PUCAI in detecting endoscopic active disease). Twenty-three (76.7%) patients had FC >250 mcg/g, but in 2 of these cases the colonoscopy was normal (Se 77.8% and Sp 33.3% in detecting active disease). At US examination, pathological findings (increased bowel wall thickness, hypervascularity, lymphadenopathies, and/or mesenteric inflammatory fat) were found in 27 patients (90%), all with endoscopic active disease (agreement US - colonoscopy, at patient level, k=1.0, p<0.001, Se 100% and Sp 100%). At seg-ment level (totally 180 bowel segments examined by US), the overall agreement between US and colonoscopy was k=0.767, p<0.001, Se 86.5%, Sp 90.1%. Of the 27 patients with US pathological findings in any of colonic segments, 23 had FC >250 mcg/g (85.1%). The inter-observer agreement for the US measurements had an overall ICC of 0.926 with p<0.001. CONCLUSION: Abdominal US findings demonstrate a good to excellent concordance with endoscopic examination and are correlated with elevated FC levels. Therefore, US appears as an accurate technique in assessing activity in patients with UC and might replace colonoscopic evaluation for the follow-up.

The evaluation of oxidative stress in osteoarthritis.

Osteoarthritis (OA) is a whole joint disease driven by abnormal biomechanics and attendant cell-derived and tissue-derived factors. The disease is multifactorial and polygenic, and its progression is significantly related to oxidative stress and reactive oxygen species (ROS). Augmented ROS generation can cause the damage of structural biomolecules of the joint and, by acting as intracellular signaling component, ROS are associated with various inflammatory responses. By activating several signaling pathways, ROS have a vital importance in the patho-physiology of OA. This review is focused on the mechanism of ROS which regulate intracellular signaling processes, chondrocyte senescence and apoptosis, extracellular matrix synthesis and degradation, along with synovial inflammation and dysfunction of the subcondral bone, targeting the complex oxidative stress signaling pathways.

Combining surface-enhanced Raman scattering (SERS) of saliva and two-dimensional shear wave elastography (2D-SWE) of the parotid glands in the diagnosis of Sjögren's syndrome.

In this study, we combine the molecular structural information gained by SERS of saliva samples with the morphological data given by two-dimensional shear wave elastography (2D-SWE) (SuperSonic Imagine, Aixplorer) of parotid glands in the case of n = 31 patients with Sjögren's syndrome (SjS) and n = 22 controls, with the aim to discriminate between the two groups. The overall classification accuracy yielded by a hybrid principal component analysis-linear discriminant analysis (PCA-LDA) model based on both SERS and elastography (81%) was superior to that yielded by SERS spectra alone (75%) and elastography data alone (71%). This preliminary study is the first report on the use of 2D-SWE of parotid glands for the diagnosis of SjS as well as the first to describe the diagnosis of SjS based on the SERS spectra of dried saliva samples, the results suggesting that the strategy of combining the two methods could improve the diagnosis of SjS.

Multimodal ultrasound investigation (grey scale, Doppler and 2D-SWE) of salivary and lacrimal glands in healthy people and patients with diabetes mellitus and/or obesity, with or without sialosis.

AIM: To evaluate the ultrasound (US) modifications [grey scale, Doppler, 2D-share wave elastography (2D-SWE)] ofsalivary (parotid and submandibular) and lacrimal glands in healthy people and patients with diabetes mellitus and/or obesity, with or without sialosis. MATERIAL AND METHODS: We evaluated 170 patients (1020 glands, 1700 grey scale and Doppler images), split in two groups (group 1- healthy people, group 2- obese and/or diabetes patients, with or without sialosis). For each patient we assessed the parotid, submandibular and lacrimal glands in grey scale US (echogenicity, homogeneity, glandular contour, posterior border, lymph nodes), color Doppler US and 2D-SWE. All images were analyzed by two examiners blinded to each other or to patients. RESULTS: The interobserver agreement was strong or moderate for all parameters. In group 2, the salivary glands had increased echogenicity, homogeneous aspect and invisible posterior border (all p<0.001). There was no significant variation of elasticity modulus in the groups analyzed (5.46±1.57 vs 5.67±1.81 in parotid, 8.63±1.84 vs 8.55±1.94 in submandibular and 9.47±2.1 vs 9.53±2.23 in lacrimal glands, all p>0.05) or according to the body mass index (BMI), sex, patient age, the aspect in grey scale/Doppler US or the presence of sialosis (all p>0.05). CONCLUSION: The main US differences between healthy people and patients with diabetes mellitus and/or obesity are suggested by the echogenicity, homogeneity, posterior border and the size of glandular area. No significant differences of elasticity modulus were found between the analyzed groups or related to BMI, sex, patient age or other grey scale/Doppler US items analyzed.

Multimodal ultrasonographic evaluation in a case with unossified primary synovial osteochondromatosis.

Primary synovial osteochondromatosis is a rare disorder and its diagnosis remains a challenge to the physician. We present the case of 36 year old patient with right knee monoarthritis in which ultrasound findings, corroborated with clinical and histopathological evidence confirmed the diagnosis of unossified primary synovial osteochondromatosis. The arthroscopy with synovectomy found multiple intra-articular loose bodies occupying the entire joint. The ultrasonographic findings were extensively evaluated.

Pain in bilateral knee osteoarthritis - correlations between clinical examination, radiological, and ultrasonographical findings.

AIMS: The aim of the study was to evaluate the correlations between clinical symptoms (pain), physical examination, ultrasound (US), and radiological findings in patients with bilateral knee osteoarthritis (OA). MATERIAL AND METHODS: Knee pain was appreciated during medial and lateral palpation of each knee joint and using visual analogue scale (VAS) and The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). US evaluation (osteophytes, meniscal protrusion, synovial fluid, femoral hyaline cartilage thickness) and radiological assessment (osteophytes, femoral-tibial space, Kellgren-Lawrence [K-L] score, enthesopathies) were performed by two examiners blinded to the clinical results and to each other. All these findings were scored with a five-point scale. RESULTS: A total of 52 consecutive patients aged 63.44+/-9.49 were examined, 33 (80.5%) being females. In patients with bilateral knee OA the pain, evaluated by WOMAC score and VAS, was correlated with the presence of osteophytes and cartilage thickness but no association with medial meniscal protrusion and effusion was demonstrated. Pain produced by palpation of the knee was strongly associated with the presence of medial osteophytes. VAS and WOMAC scores increased with the severity of radiological and US findings. The presence of osteophytes and articular cartilage damage at US examination were strongly and positively correlated with radiological K-L score. US examiners agreement was good for osteophytes and moderate for meniscal protrusion, cartilage damage, and synovial fluid. The cartilage damage score was the only independent predictor for VAS scale; for WOMAC score the sex, cartilage damage, the presence of medial osteophytes and lateral meniscal protrusion were the independent predictors. CONCLUSION: Pain intensity was correlated with the severity of US findings, cartilage damage score being an independent predictor for both VAS and WOMAC scores. Medial osteophytes and lateral meniscal protrusion and are independent predictors for WOMAC score.