Search Results (66)

Background: The management of ovarian cysts in postmenopausal women is still a diagnostic dilemma. Although ultrasound is the diagnostic cornerstone of the initial assessment, it is limited by its interpretation in cases without clear morphological features of malignancy. Objectives: The aim of this study was to assess whether the addition of grayscale ultrasound features with inflammatory markers including the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) can improve diagnostic accuracy in the identification of malignant ovarian lesions as compared to benign cysts in postmenopausal women. Methods: A total of 103 surgically removed adnexal masses were examined retrospectively. Ultrasound morphology was categorized to either simple or complex while NLR and PLR were calculated from preoperative full blood counts. The reference standard was histopathology. Results: Of the 103 cysts taken out, 74 cysts (71.8%) were benign while 29 cysts (28.2%) were malignant. Complex morphology was shown by all malignant lesions. NLR values in malignancy vs. benignancy showed a mean NLR of 4.96 ± 2.3 in the malignant cases, while it was 2.56 ± 1.2 in the benign cases (p < 0.001). In a similar fashion, the PLR was 198.4 ± 45.1 in malignant compared to 134.2 ± 32.7 in benign cases (p < 0.001). In the group of complex cysts (n = 52), NLR and PLR were compared to differentiate between malignant and benign lesions. In logistic regression, complex morphology was an independent predictor of malignancy, while NLR showed a positive, non-significant trend; PLR was not independently associated. Conclusions: Use of NLR and PLR in combination with grayscale ultrasonographic morphology improves the diagnostic characterization of postmenopausal women with adnexal masses. This easy, cost-effective method might aid in better triage and surgery planning. Full article

Ultrasonic wave attenuation in biological tissues arises from complex interactions between mechanical, structural, and fluidic properties, making it essential to identify dominant mechanisms for accurate simulation and device design. This work introduces a novel integration of experimentally measured tissue parameters into time-explicit nonlinear acoustic wave simulations, in which the equations are directly solved in the time domain using an explicit solver. This approach captures the full transient waveform without relying on frequency-domain simplifications, offering a more realistic representation of ultrasound propagation in heterogeneous media. The study estimates both sound diffusivity and viscous damping parameters (dynamic and bulk viscosity) for a broad range of ex vivo tissues (skin, adipose tissue, skeletal muscle, trabecular/cortical bone, liver, myocardium, kidney, tendon, ligament, cartilage, and gray/white brain matter). Four regression models (power law, linear, exponential, logarithmic) were applied to characterize their frequency dependence between 0.5 and 5 MHz. Results show that attenuation is more strongly driven by bulk viscosity than dynamic viscosity, particularly in fluid-rich tissues such as liver and myocardium, where compressional damping dominates. The power-law model consistently provided the best fit for all attenuation metrics, revealing a scale-invariant frequency relationship. Tissues such as cartilage and brain showed weaker viscous responses, suggesting the need for alternative modeling approaches. These findings not only advance fundamental understanding of attenuation mechanisms but also provide validated parameters and modeling strategies to improve predictive accuracy in therapeutic ultrasound planning and the design of non-invasive, tissue-specific acoustic devices. Full article

Background/Objectives: Elastography is a non-invasive imaging technique that assesses tissue stiffness and elasticity. This study aimed to evaluate the diagnostic performance and clinical utility of elastography and S-detect in distinguishing benign from malignant thyroid nodules. S-detect (RS85) is a deep learning-based computer-aided diagnosis (DL-CAD) software that analyzes grayscale ultrasound 2D images to evaluate the morphological characteristics of thyroid nodules, providing a visual guide to the likelihood of malignancy. Method: This retrospective study included 159 patients (61 male and 98 female) aged 30–83 years (56.14 ± 11.35) who underwent thyroid ultrasonography between January 2023 and June 2024. All the patients underwent elastography, S-detect analysis, and fine needle aspiration cytology (FNAC). Malignancy status was determined based on the FNAC findings, and the diagnostic performance of the elasticity contrast index (ECI), S-detect, and evaluations by a radiologist were assessed. Based on the FNAC results, 101 patients (63.5%) had benign nodules and 58 patients (36.5%) had malignant nodules. Results: Radiologist interpretation demonstrated the highest diagnostic accuracy (area under the curve 89%), with a sensitivity of 98.28%, specificity of 79.21%, positive predictive value (PPV) of 73.1%, and negative predictive value (NPV) of 98.8%. The elasticity contrast index showed an accuracy of 85%, sensitivity of 87.93%, specificity of 81.19%, PPV of 72.9%, and NPV of 92.1%. S-detect yielded the lowest accuracy at 78%, with a sensitivity of 87.93%, specificity of 68.32%, PPV of 61.4%, and NPV of 90.8%. Conclusions: These findings offer valuable insights into the comparative diagnostic utility of elastography and AI-based S-detect for thyroid nodules in clinical practice. Although limited by its single-center design and sample size, which potentially limits the generalization of the results, the controlled environment ensured consistency and minimized confounding variables. Full article

Background: Differentiating acute kidney injury (AKI) from chronic kidney disease (CKD) in children remains a critical unmet need due to the limitations of current clinical and biochemical markers. Conventional ultrasound lacks the sensitivity to discern subtle parenchymal alterations. This study explores the application of ultrasound radiomics—a novel, non-invasive, and quantitative image analysis method—for distinguishing AKI from CKD in pediatric patients. Methods: In this retrospective cross-sectional pilot study, kidney ultrasound images were obtained from 31 pediatric subjects: 8 with oliguric AKI, 14 with CKD, and 9 healthy controls. Renal parenchyma was manually segmented, and 124 advanced texture features were extracted using the open-source ©PyFeats. Features encompassed multiple categories (e.g., GLCM, GLSZM, WP). Statistical comparisons evaluated intergroup differences. Principal Component Analysis identified the top 10 most informative features, which were used to train supervised machine learning models. Model performance used five-fold cross-validation. Results: Radiomic analysis revealed significant intergroup differences (p < 0.05). CKD cases exhibited increased echogenicity and heterogeneity, particularly in GLCM and GLSZM features, consistent with chronic fibrosis. AKI cases displayed more homogeneous texture, likely reflecting edema or acute inflammation. While echogenicity separated diseased from healthy kidneys, it lacked specificity between AKI and CKD. Among ML models, XGBoost achieved the highest macro-averaged F1 score (0.90), followed closely by SVM and Random Forest, demonstrating strong classification performance. Conclusions: Radiomics-based texture analysis of grayscale ultrasound images effectively differentiated AKI from CKD in this pilot study, offering a promising, non-invasive imaging biomarker for pediatric kidney disease. These preliminary findings justify prospective validation in larger, multicenter cohorts. Full article

Retained products of conception (RPOC) represent a significant cause of morbidity in the post-abortive and postpartum periods, potentially leading to abnormal uterine bleeding, pelvic pain, infections, and intrauterine adhesions. Accurate diagnosis is crucial to avoid unnecessary surgical interventions and to preserve future fertility. Transvaginal ultrasound constitutes the primary imaging modality for identifying RPOC, but the lack of standardized diagnostic criteria complicates clinical decision-making. This narrative review explores the current literature on sonographic findings associated with RPOC, focusing on the diagnostic value of endometrial thickness (ET), the presence of intrauterine echogenic masses, and the use of Color Doppler imaging. Although an ET ≥15 mm is frequently used to suspect RPOC, the variability in cut-off thresholds and limited specificity reduce its diagnostic reliability. The detection of an echogenic intrauterine mass appears to be the most sensitive and specific sonographic feature. Color Doppler assessment, particularly the presence of enhanced myometrial vascularity (EMV) and classification systems like the Gutenberg score, offers further insight by stratifying hemorrhagic risk and guiding therapeutic choices. However, vascular parameters such as peak systolic velocity (PSV) and resistive index (RI) demonstrate a substantial overlap between benign and pathological conditions, limiting their stand-alone utility. The review also addresses the differential diagnosis of RPOC, including blood clots, arteriovenous malformations, placental polyps, gestational trophoblastic disease, and endometrial osseous metaplasia. The role of three-dimensional ultrasound remains limited in clinical practice, offering no significant advantage over two-dimensional imaging. Finally, the timing of follow-up ultrasound after medical treatment with misoprostol is critical: delayed assessment reduces overtreatment by allowing time for spontaneous resolution. In conclusion, despite advances in ultrasound technology, the diagnosis of RPOC remains challenging due to heterogeneity in imaging findings and inter-observer variability. A multimodal approach integrating grayscale and Doppler ultrasound with clinical evaluation is essential for optimal management. Full article

Background: Plantar fasciitis (PF) is a common enthesopathy in patients with ankylosing spondylitis (AS). Shear wave elastography (SWE) and the Belgrade ultrasound enthesitis score (BUSES) may detect PF, but their comparative diagnostic performance is unclear. Objective: To compare SWE with the BUSES for identifying PF in individuals with and without AS. Methods: In this cross-sectional study, 96 participants were stratified into AS and non-AS populations, each further divided based on the presence or absence of clinical PF. Demographic data, the American Orthopedic Foot and Ankle Society Score (AOFAS), and the BASDAI score were recorded. All subjects underwent grayscale ultrasonography, the BUSES scoring, and SWE assessment of the plantar fascia. Logistic regression models were constructed for each population, controlling for age, body mass index (BMI), and fascia–skin distance. ROC curve analyses were performed to evaluate diagnostic accuracy. Results: In both AS and non-AS groups, SWE and the BUSES were significant predictors of PF (p < 0.05). SWE demonstrated slightly higher diagnostic accuracy, with area under the curve (AUC) values of 0.845 (AS) and 0.837 (non-AS), compared to the BUSES with AUCs of 0.785 and 0.831, respectively. SWE also showed stronger adjusted odds ratios in regression models. The interobserver agreement was good to excellent for both modalities. Conclusions: Both SWE and the BUSES are effective for PF detection, with SWE offering marginally superior diagnostic performance, particularly in AS patients. SWE may enhance the early identification of biomechanical changes in the plantar fascia. Full article

Background: Pigmented superficial skin lesions pose a persistent diagnostic challenge due to overlapping clinical and dermoscopic appearances between benign and malignant entities. While histopathology remains the gold standard, there is growing interest in non-invasive imaging models that can preoperatively stratify malignancy risk. This methodological pilot study was designed to explore the feasibility and initial diagnostic performance of a novel radiology-adapted logistic regression approach. To develop and preliminarily evaluate a new logistic model integrating both structural (lesion size, depth) and vascular (Doppler patterns) ultrasonographic features for non-invasive risk stratification of pigmented superficial skin lesions. Material and Methods: In this prospective single-center pilot investigation, 44 patients underwent standardized high-frequency grayscale and Doppler ultrasound prior to excisional biopsy. Lesion size, depth, and vascularity patterns were systematically recorded. Three logistic regression models were constructed: (1) based on lesion size and depth, (2) based on vascularity patterns alone, and (3) combining all parameters. Model performance was assessed via ROC curve analysis. Intra-observer reliability was determined by repeated measurements on a random subset. Results: The lesion size and depth model yielded an AUC of 0.79, underscoring the role of structural features. The vascularity-only model showed an AUC of 0.76. The combined model demonstrated superior discriminative ability, with an AUC of approximately 0.85. Intra-observer analysis confirmed excellent repeatability (κ > 0.80; ICC > 0.85). Conclusions: This pilot study introduces a novel logistic framework that combines grayscale and Doppler ultrasound parameters to enhance non-invasive malignancy risk assessment in pigmented superficial skin lesions. These encouraging initial results warrant larger multicenter studies to validate and refine this promising approach. Full article

Background: Immune checkpoint inhibitors (ICIs) transformed cancer treatment, producing significant survival benefits. However, ICIs can trigger toxicities called immune-related adverse events (irAEs), including inflammatory arthritis (IA) and polymyalgia rheumatica (PMR)-like syndromes. Our study aimed to systematically further characterize musculoskeletal ultrasound (MSKUS) findings in patients with ICI-IA and ICI-PMR, collectively referred to as “MSK-irAEs”, and explore the role of US in guiding treatment. Methods: The authors conducted a comprehensive chart review for patients receiving ICIs undergoing MSKUS at our center’s rheumatology clinics. US examinations were performed and reviewed by two MSKUS-certified rheumatologists. Descriptive statistics were performed to summarize demographic, clinical, and treatment-related variables. US findings were categorized with a novel scoring system: 0—no signs of inflammatory arthropathy or tendinopathy, 1—potential signs of inflammation (grayscale ≥ 2, effusion without power Doppler, synovial hypertrophy in the joint), and 2—active inflammation in joints and/or tendons (characterized by power Doppler) and signs of inflammation. Results: Twenty-three patients were included. The median age was 63 years, 52% were male, and 87% were White. Melanoma was the most common cancer (48%). MSK-irAEs were diagnosed in nineteen (83%), with MSKUS showing inflammation in seventeen (74%). Sixteen (70%) received escalation in MSK-irAE treatment after MSKUS. Four (17%) had erosive disease due to MSK-irAEs, while one had erosive osteoarthritis. Individuals with inflammatory erosive changes experienced prolonged intervals between symptom onset and MSKUS, ranging from 17 to 82 months, suggesting that erosions may reflect chronic, under-recognized inflammation. On MSK-irAE therapy, nine (47%) experienced symptomatic improvement, five (26%) achieved resolution, and in four (21%) cases, it was too early to assess the response. MSKUS detected other causes of MSK symptoms besides MSK-irAEs in several patients, allowing ICI resumption in one. Conclusions: Our study highlights the clinical utility of MSKUS not only as a diagnostic tool but also to guide therapeutic decision-making. Full article

Objectives: To assess the role of musculoskeletal ultrasound (MSUS) in selecting patients with rheumatoid arthritis (RA) in sustained clinical remission, suitable for tapering of biologic therapy (BT), and monitoring for a subclinical relapse. Methods: In this prospective study, seventy-eight patients with RA in sustained Disease Activity for twenty-eight joints (DAS28) clinical remission underwent ultrasound (US) examination of twenty-two joints (bilaterally wrists and metacarpophalangeal and proximal interphalangeal joints). US assessment was performed on gray scale ultrasound (GSUS) and power Doppler US (PDUS) to select patients in imaging remission, defined as a total PD score of synovitis = 0. Group 1 consisted of patients in clinical and imaging remission, in which tapering of BT was done through spacing of the Tumour Necrosis Factor Alpha (TNF-$\alpha$) blocker. Group 2 consisted of patients only in clinical remission (PDUS > 0), who continued standard therapy. Clinical and US assessment was done at months 6 and 12, and the rate of a clinical (defined as DAS28 ≥ 2.6) and an US relapse (PDUS score ≥ 1) was recorded. Results: Thirty-eight patients were in clinical and US remission (group 1) and forty patients only in clinical remission (group 2). At month 6, 26% of patients in group 1 and 10% in group 2 experienced a clinical and an US relapse, whereas 20% and 15% of them, respectively, only an US relapse. At month 12, 26% of patients in group 1 and 20% of patients in group 2 experienced a clinical and an US relapse, whereas 35% and 22% of them, respectively, only an US relapse. Conclusions: Real-world data show that MSUS is a useful tool to identify RA patients in sustained clinical remission appropriate for BT tapering. US monitoring could predict a clinical relapse and the need to re-escalate treatment in patients with subclinical US relapse during BT tapering. Full article

The aim of this prospective study was to evaluate contrast-enhanced urosonography (CE-VUS) as an alternative to radiographic retrograde cystourethrography (RCUG) in the detection of vesicoureteral reflux (VUR) in young dogs. A total of 62 dogs, ranging in age from 6 weeks to 12 months, and 124 ureterorenal units (UUs) were investigated for VUR using RCUG and CE-VUS. After a baseline gray-scale ultrasound (US) of the urinary tract, a second-generation ultrasound contrast agent (UCA), diluted in a bottle of normal saline, was instilled into the urinary bladder via a catheter and CE-VUS was performed. VUR was detected when microbubbles were observed in the ureter and/or in the renal pelvis. In addition, RCUG was performed on the same day. The findings obtained by CE-VUS and RCUG were concordant in 117/124 UUs (94.35%). No reflux was detected in 101/124 UUs (81.45%) using both methods. With RCUG as the standard of reference, the sensitivity of CE-VUS was 94.12%, and the specificity was 94.39%. The positive predictive value was 72.73%, and the negative predictive value was 99.02%. CE-VUS is highly sensitive for the detection of VUR in young dogs. Full article

Background/Objectives Recent advancements in large language models, such as ChatGPT-4o, have created new opportunities for analyzing complex multi-modal data, including medical images. This study aims to assess the potential of ChatGPT-4o in distinguishing between benign and malignant thyroid nodules via multi-modality ultrasound imaging: grayscale ultrasound, color Doppler ultrasound (CDUS), and shear wave elastography (SWE). Materials and Methods Patients who underwent thyroid nodule ultrasound examinations and had confirmed pathological diagnoses were included. ChatGPT-4o analyzed the multi-modality ultrasound data using two approaches: (1.) a dual-modality strategy which employed grayscale ultrasound and CDUS, and (2.) a triple-modality strategy which incorporated grayscale ultrasound, CDUS, and SWE. The diagnostic performance was compared against pathological findings utilizing receiver operating characteristic (ROC) curve analysis, while consistency was evaluated through Cohen’s Kappa analysis. Results A total of 106 thyroid nodules were evaluated; 65.1% were benign and 34.9% malignant. In the dual-modality approach, ChatGPT-4o achieved an area under the ROC curve (AUC) of 66.3%, moderate agreement with pathology results (Kappa = 0.298), a sensitivity of 70.3%, a specificity of 62.3%, and an accuracy of 65.1%. Conversely, the triple-modality approach exhibited higher specificity at 97.1% but lower sensitivity at 18.9%, with an accuracy of 69.8% and a reduced overall agreement (Kappa = 0.194), resulting in an AUC of 58.0%. Conclusions ChatGPT-4o exhibits potential, to some extent, in classifying thyroid nodules using multi-modality ultrasound imaging. However, the dual-modality approach unexpectedly outperforms the triple-modality approach. This indicates that ChatGPT-4o might encounter challenges in integrating and prioritizing different data modalities, particularly when conflicting information is present, which could impact diagnostic effectiveness. Full article

In recent years, defect detection based on ultrasound B-scan images has been widely utilized in industry to detect the quality and presence of defects in products. However, there are still some difficulties in the process of processing B-scan images, such as sampling noise, the large amount of data, and so on. In this paper, we analyze the acoustic characteristics of an ultrasound B-scan image time series, design an image preprocessing method to make the image information gray-scale lossless, and propose a screening method for ultrasound B-scan image segments containing defects based on the theory of image entropy and a recurrence diagram. Comparison experiments between this method and the traditional image entropy screening algorithm show that this method can solve the above difficulties to a certain extent and has its own superiority. The method proposed in this paper provides a new idea for processing ultrasound B-scan image sequences and presents a new choice when the traditional method is limited. Full article

Background: In recent years, musculoskeletal ultrasonography (MSUS) has established itself as a reliable method for evaluating disease activity in combination with clinical examination and laboratory tests. Objectives: In this pilot study, we aimed to evaluate the ultrasound response to treatment with tofacitinib and upadacitinib on tendons and joints in comparison to clinical and laboratory results in patients with RA who have shown inadequate response to conventional synthetic and/or biologic disease-modifying antirheumatic drugs (cs/b DMARDs). Methods: This study presents the MSUS assessment of therapeutic response in RA patients treated with tofacitinib or upadacitinib over a 24-week period. In a prospective, single-center study, patients were treated with upadacitinib 15 mg/daily or tofacitinib 2 × 5 mg/daily or 11 mg/daily, in combination with or without methotrexate or another conventional DMARDs. Disease activity was assessed by DAS28-CRP, CDAI, and SDAI, as well as MSUS. Patients were evaluated at baseline for ultrasound measures and at weeks 2, 4, 8, 12, and 24 for the rest of the indicators. For each patient, we used two ultrasound (US) scores (gray-scale, GS, and power Doppler, PD scores) and the system of European Alliance of Associations for Rheumatology outcome measures in rheumatology (EULAR-OMERACT) US scoring (combined GS and PD). We also calculated the tenosynovitis score (GS and PD) according to OMERACT recommendations. Results: A total of 53 patients were recruited. A total of 25 patients with a mean age of 56 ± 11.6 SD were followed in the upadacitinib group, and 22 patients with a mean age of 56.9 ± 11.3 were followed in the tofacitinib group. At baseline, DAS28-CRP for the upadacitinib group was 5.57 ± 1.24, and for tofacitinib, it was 4.77 ± 1.47. The baseline visit (GS, PD, and combined—US) and tendon US scores (GS and PD) were, respectively, 23 ± 2.96, 15 ± 2.56, 24.08 ± 3.36, 11.04 ± 2.21, and 8.44 ± 1.65 for the upadacitinib group. USGS-J—23 ± 3.55, USPD-J—13.36 ± 2.44, OMERACT composite—23.4 ± 3.84, USGS-T—12.18 ± 2.23, and USPD-T—9.5 ± 1.92 were found in the patients treated with tofacitinib. In both groups of patients, a significant reduction was found in both DAS28-CRP and the described MSUS scores at weeks 8, 12, and 24 (p < 0.05). Conclusions: Upadacitinib managed to produce lower echography scores much faster than tofacitinib; however, the differences in effectiveness evened out at weeks 12 and 24, with all patients being adequately controlled. Full article

Left ventricle (LV) segmentation is crucial for cardiac diagnosis but remains challenging in echocardiography. We present ShapeNet, a fully automatic method combining a convolutional neural network (CNN) ensemble with an improved active shape model (ASM). ShapeNet predicts optimal pose (rotation, translation, and scale) and shape parameters, which are refined using the improved ASM. The ASM optimizes an objective function constructed from gray-level profiles concatenated into a single contour appearance vector. The model was trained on 4800 augmented CAMUS images and tested on both CAMUS and EchoNet databases. It achieved a Dice coefficient of 0.87 and a Hausdorff Distance (HD) of 4.08 pixels on CAMUS, and a Dice coefficient of 0.81 with an HD of 10.21 pixels on EchoNet, demonstrating robust performance across datasets. These results highlight the improved accuracy in HD compared to previous semantic and shape-based segmentation methods by generating statistically valid LV contours from ultrasound images. Full article

Aim: To identify ultrasound (US) predictors of persistence or change in the diagnosis of rheumatoid arthritis (RA) after five years in a cohort of patients with early RA. Patients and Methods: One hundred and twenty patients with early arthritis who met the 2010 ACR/EULAR classification criteria for RA were followed for a period of five years. The US assessment at baseline included a bilateral evaluation of the wrists, second to fifth metacarpophalangeal (MCP) joints, second to fifth proximal interphalangeal (PIP) joints, the IV and VI extensor compartments of the wrists, and the flexor tendons of the second to fifth fingers. This evaluation was conducted using both grayscale ultrasound (GSUS) and power Doppler ultrasound (PDUS). The following scores were recorded for each patient: synovitis score, mini-enthesitis score (including paratenonitis of the finger extensor tendon at the MCP joint, central slip enthesitis at the PIP joint, pseudotenosynovitis, and the A1 pulley of the second finger), finger flexor tenosynovitis score, and tenosynovitis score for the IV and VI wrist extensor compartments. The receiver operating characteristic (ROC) curve was utilized to identify the ultrasound predictors for either maintaining or revising an initial diagnosis of RA. Results: At month 6, 82 (68%) patients were classified as having RA according to 1987 ACR RA criteria, 23 (19.2%) were diagnosed with psoriatic arthritis (PsA), 10 (8.3%) with systemic connective tissue disease (SCTD)–8 (6.7%) patients with Sjogren Syndrome and 2 (1.7%) patients with systemic lupus erythematosus (SLE)–and 5 (4.2%) patients with calcium pyrophosphate deposition disease (CPPD). The most significant predictor of RA in the fifth year was the VI extensor compartment tenosynovitis score, with an AUC of 0.915 and a criterion value > 0, associated with a sensitivity of 82.93% and a specificity of 100% (p < 0.001). The PDUS synovitis score demonstrated the second-best prognostic ability with an AUC of 0.823, a criterion value > 2, a sensitivity of 82.93%, and a specificity of 73.68% (p < 0.001). The mini-enthesitis score showed the best prognostic ability of a PsA diagnosis with an AUC of 0.998, a criterion value > 1, a sensitivity of 95.65%, and a specificity of 100% (p < 0.001). The paratenonitis score, pseudotenosynovitis score, and thickened A1 pulley were also predictive of PsA diagnosis with AUCs of 0.977, 0.955, and 0.919, respectively (p < 0.001 for all). Conclusions: Nearly one-third of the patients who were initially classified as having RA had their diagnosis revised at the end of the fifth year. Ultrasound of joints, tendons, and mini-entheses at baseline may serve as potential imaging predictive biomarkers for persistence or change in diagnosis after 5 years. Full article