What Is the Malignant Potential of Small (<2 cm), Nonpalpable Testicular Incidentalomas in Adults? A Systematic Review.

CONTEXT: Unlike palpable lumps, a large number of nonpalpable testicular lesions found incidentally at ultrasound in asymptomatic postpuberal males are either benign tumours or non-neoplastic lesions. The prevalence of malignancy, however, is appraised based on small case series. Dedicated studies report a large number of patients, and systematic review articles are lacking. OBJECTIVE: This systematic review is aimed to assess, from the analysis of the pooled data of the available literature, the incidence of benign tumours, malignant tumours, and non-neoplastic lesions, and to identify predictive characteristics for malignancy. EVIDENCE ACQUISITION: A systematic review of PubMed, Scopus, Google Scholar, Turning Research Into Practice (TRIP) database, and the Cochrane Library was conducted on January 6, 2022, according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. Studies were retrieved reporting on adult asymptomatic men, with single, incidentally identified small testicular lesions, either fertile or infertile, with negative tumour markers and without specific risk factors for malignancy. Lesions ≤20 mm were considered small. Seventy-four studies were selected for inclusion in this analysis. Twenty-six additional publications have been retrieved by the bibliography quoted in the selected articles. EVIDENCE SYNTHESIS: Pooled data of 1348 lesions in 1348 patients were collected. Of these lesions, 408 could be retrieved individually, 44.6% were benign, 27.2% were malignant, and 20.8% were non-neoplastic. Virtually all lesions <3 mm and 86.6% of lesions <5 mm were benign. Lesions >10 mm have a 38.14% probability of being benign. Hyperechoic lesions are likely benign. Fertility status does not affect the risk of malignancy. CONCLUSIONS: Very small (<3 mm) and small (<5 mm) incidentally detected testicular lesions in asymptomatic postpuberal men with normal tumour markers could be frequently benign. More prospective studies are needed to better support this finding. Management strategies should be developed for these patients to reduce overtreatment. PATIENT SUMMARY: Small testicular lesions are incidentally founded at ultrasound. It is not easy to distinguish a benign lesion from a malignant one. Results of this study are reporting a higher incidence of benign lesions with a diameter of <5 mm. More studies are needed to better understand the biology and the management strategy for small testicular lesions.

Diagnostic Performance of Contrast-Enhanced Ultrasound in the Evaluation of Small Renal Masses: A Systematic Review and Meta-Analysis.

Ultrasound (US) is a highly sensitive imaging tool in the detection of renal masses. However, the detection rate of small renal masses (SRMs) (<4 cm) is still limited. In this scenario, contrast-enhanced ultrasound (CEUS) is a relatively novel, but increasingly utilized, diagnostic modality which aims to increase the overall diagnostic ability in the identification of SRMs. In consequence, we performed a systematic review (SR) and pooled meta-analysis to investigate the diagnostic performance of CEUS in the evaluation of SRMs confirmed by pathology. A SR up to April 2022 was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The diagnostic performance of CEUS was evaluated basing on malignant vs. benign SMRs. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) from eligible studies were pooled, and summary receiver operating characteristic (SROC) curves were constructed for each endpoint. Overall, five qualified studies were deemed suitable for this meta-analysis. Finally, diagnostic performance of CEUS showed an accuracy of 0.93 in detecting malignant masses (sensitivity of 0.94, PPV of 0.95, specificity of 0.78, and NPV of 0.73). Taken together, CEUS may represent a promising minimally invasive diagnostic tool for characterization of SMRs, since it allows clinicians to identify malignant lesions.

Contrast Enhanced Ultrasound Compared with MRI and CT in the Evaluation of Post-Renal Transplant Complications.

Renal transplantation (RT) is the treatment of choice for end-stage renal disease, significantly improving patients' survival and quality of life. However, approximately 3-23% of patients encounter post-operative complications, and radiology plays a major role for their early detection and treatment or follow-up planning. CT and MRI are excellent imaging modalities to evaluate renal transplant post-operative course; nevertheless, they are both associated with a high cost and low accessibility, as well as some contraindications, making them not feasible for all patients. In particular, gadolinium-based contrast can lead to the rare condition of nephrogenic systemic fibrosis, and iodine-based contrast can lead to contrast-induced nephropathy (CIN). CT also exposes the patients who may require multiple examinations to ionizing radiation. Therefore, considering the overall advantages and disadvantages, contrast-enhanced ultrasound (CEUS) is presently considered an effective first-line imaging modality for post-operative early and long-term follow-up in RT, reducing the need for biopsies and providing adequate guidance for drainage procedures. Hence, this paper aims to review the updated knowledge on CEUS compared with CT and MRI for the evaluation of RT renal transplant complications; advantages, limitations, and possible recommendations are provided.

Contrast-Enhanced Ultrasound (CEUS) in the Evaluation of Renal Masses with Histopathological Validation-Results from a Prospective Single-Center Study.

BACKGROUND: To evaluate the diagnostic accuracy of contrast-enhanced ultrasound (CEUS) in characterizing between malignant and benign renal lesions confirmed by histological examination. METHODS: Overall, 110 patients, for a total of 118 renal masses previously identified at CT and MRI underwent CEUS. An expert radiologist evaluated morphological, qualitative and quantitative parameters. Acquired data were analyzed to assess the value of each parameter to differentiate between malignant and benign lesions. RESULTS: Histological results of 118 renal masses showed 88 (75%) malignant lesions and 30 (25%) benign lesions. Among morphological features, inhomogeneous echogenicity was the best predictor of malignancy depicting a sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 76%, 76%, 88% and 57%, respectively. Among qualitative parameters, the most reliable parameter was the presence of pseudo-capsule. Here, sensitivity, specificity, positive PPV and NPV were 85%, 86%, 94% and 71%, respectively. Among quantitative parameters, the most reliable parameters were peak intensity (PI) and the area under the (AUC) with sensitivity, specificity, PPV and NPV values of 94%, 92%, 96% and 87% and 99%, 92%, 97% and 97%, respectively. Finally, the most reliable parameters were combined to distinguish between benign and malignant lesions. The best combination obtained was restricted to CEUS parameters (PI and AUC). Here, sensitivity, specificity, PPV, NPV and accuracy rate were 93%, 100%, 100%, 83% and 93%, respectively. CONCLUSIONS: CEUS increases the US accuracy to discriminate between benign and malignant renal lesions.

Role of Contrast-Enhanced Voiding Urosonography in the Evaluation of Renal Transplant Reflux - Comparison with Voiding Cystourethrography and a New Classification.

Vesicoureteral reflux (VUR) is a common urological complication in renal transplant patients. THE AIM: of this study is to evaluate the performance of contrast-enhanced voiding urosonography (CEvUS) in the diagnosis and classification of reflux into the renal allograft, to evaluate and classify VUR into the allograft using voiding cystourethrography (VCUG) and CEvUS, to compare the two methods, and to propose a new classification of reflux into the allograft based on CEvUS and VCUG assessment, in line with the international reflux grading system. MATERIALS AND METHODS: From January 2017 to July 2019, 84 kidney transplant patients were enrolled. All patients underwent VCUG and CEvUS. RESULTS: In 76 cases there was agreement between VCUG and CEvUS (90 %) (Kappa = 0.7). The sensitivity of CEvUS using VCUG as the gold standard was 90 %, and the specificity was 92 %. Of the 7 cases diagnosed by VCUG and not by CEvUS, 6 were grade 1 and 1 was grade 2. CONCLUSION: Transplant patients with reflux symptoms should undergo CEvUS. If the outcome is negative, VCUG should be performed. The classification that we propose is better suited to describe VUR in transplant patients, because it is simpler and takes into account whether reflux occurs not only during urination but also when the bladder is relaxed.

An unusual location of hand, foot and mouth disease.

Hand, foot, and mouth disease (HFMD) is a childhood febrile disease. Oral lesions and papulovesicular lesions on the hands and feet are the clinical signs of the disease. In our case, a 17-year-old boy presented to the emergency department, where he was diagnosed with HFMD. After 6 days, he felt intense pain in his right testicle, and therefore an ultrasound (US) examination was performed. US detected a hypoechoic mass-like area in the right testis. Viral etiology was suspected, and no therapy was prescribed. After a little more than 3 months, US examination showed a reduced lesion size. Viral epididymo-orchitis should be suspected in young men with a recent history of HFMD and testicular pain.

Role of multiparametric ultrasound in testicular focal lesions and diffuse pathology evaluation, with particular regard to elastography: Review of literature.

BACKGROUND: Ultrasound is the main requested technique for the assessment of traumatic, vascular, neoplastic, and inflammatory testicular pathology. Moreover, the role of ultrasound has broadened over the years along with the introduction of new techniques, such as contrast enhanced ultrasound and ultrasound elastography. OBJECTIVE: An updated representation of the pre-existing Literature evidence for multiparametric ultrasound imaging with particular regard to elastography, in the evaluation of focal and diffuse testicular pathologies, has been presented. METHODS: The search was performed in PubMed, Cochrane, EMBASE, Web of Science and Scopus databases from the earliest available article (1977) until January 2021. Based on the evidence of the Literature, the current role of US imaging for focal and diffuse testicular pathologies has been reported and illustrated, with emphasis on examination technique, classification, and pitfalls. RESULTS: Multiparametric Ultrasound has a recognized role for testicle focal and diffuse disease. Elastography is nowadays recognized as an essential part of the multiparametric ultrasound examination. However, in the setting of testicular pathology this method showed some promising results in the setting of varicocoele and for focal lesions characterization. In the remaining field its role is still under debate. DISCUSSION: B-mode ultrasound and color Doppler ultrasound have been for a long time the diagnostic gold standard for testicular pathologies. The introduction of both contrast enhanced ultrasound and elastography in the last two decades has brought to the emergence of the multiparametric ultrasound concept. These methods are currently able to increase diagnostic confidence especially for testicular lesions characterization, with different relevance depending on the pathology under consideration. CONCLUSION: Multiparametric ultrasound testis assessment, with specific regard to elastography is nowadays recommended for focal and diffuse disease evaluation. Further and larger studies are however needed to validate these results and to understand if the role of elastography in testicular pathology may be broadened.

Varicocoele. Classification and pitfalls.

BACKGROUND: Varicocoeles have been considered for a long time potentially correctable causes for male infertility, even though the correlation of this condition with infertility and sperm damage is still debated. OBJECTIVE: To present a summary of the evidence evaluation for imaging varicocoeles, to underline the need for a standardized examination technique and for a unique classification, and to focus on pitfalls in image interpretation. METHODS: Based on the evidence of the literature, the current role of ultrasound (US) imaging for varicocoeles has been reported and illustrated, with emphasis on examination technique, classification, and pitfalls. RESULTS: US is the imaging modality of choice. It is widely used in Europe, while in other countries clinical classification of varicocoeles is considered sufficient to manage the patient. A number of US classifications exist for varicocoeles, in which the examinnation is performed in different ways. DISCUSSION: An effort toward standardization is mandatory, since lack of standardization contributes to the confusion of the available literature, and has a negative impact on the understanding of the role itself of imaging in patients with varicocoeles. CONCLUSION: Use of the Sarteschi/Liguori classification for varicocoeles is recommended, since it is the most complete and widely used US scoring system available today. Tubular extratesticular structures resembling varicocoeles, either at palpation or at US, should be identified and correctly characterized.

Diagnostic imaging in COVID-19 pneumonia: a literature review.

In December 2019 in Wuhan (China), a bat-origin coronavirus (2019-nCoV), also known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was identified, and the World Health Organization named the related disease COVID-19. Its most severe manifestations are pneumonia, systemic and pulmonary thromboembolism, acute respiratory distress syndrome (ARDS), and respiratory failure. A swab test is considered the gold standard for the diagnosis of COVID-19 despite the high number of false negatives. Radiologists play a crucial role in the rapid identification and early diagnosis of pulmonary involvement. Lung ultrasound (LUS) and computed tomography (CT) have a high sensitivity in detecting pulmonary interstitial involvement. LUS is a low-cost and radiation-free method, which allows a bedside approach and needs disinfection of only a small contact area, so it could be particularly useful during triage and in intensive care units (ICUs). High-resolution computed tomography (HRCT) is particularly useful in evaluating disease progression or resolution, being able to identify even the smallest changes.

Contrast-enhanced ultrasound after successful cryoablation of benign and malignant renal tumours: how long does tumour enhancement persist?

INTRODUCTION: To investigate how long successfully ablated tumours take to become completely avascular at CEUS after cryoablation. METHODS: Ninety-five patients had percutaneous cryoablation of 103 renal tumours investigated at CEUS on post-operative day one. If the lesion was avascular, a contrast-CT/MR was scheduled six months after the procedure, while CEUS was repeated if the lesion still displayed enhancement, until the disappearance of intralesional vascularity. Technical success was defined when the tumour was covered completely by the ablation zone. Technique efficacy was assessed at six months of follow-up. RESULTS: Technical efficacy was obtained for 101/103 cryoablations, 56% of which (57/101) were avascular on post-operative day one. After one week, two weeks, one month 83%, 91% and 100% of these 101 lesions, respectively, were avascular. Two tumours were unsuccessfully treated. They displayed persistent intralesional vascularity at CEUS one month after the procedure. CONCLUSIONS: After cryoablation, obtaining CEUS before one month may be misleading. When technical efficacy is obtained, disappearance of intralesional enhancement is observed within two weeks in the majority of cases (91%), but can persist until one month. Identification of tumour enhancement after one month may be concerning for residual viable tumour.

EFSUMB 2020 Proposal for a Contrast-Enhanced Ultrasound-Adapted Bosniak Cyst Categorization - Position Statement.

The well-established Bosniak renal cyst classification is based on contrast-enhanced computed tomography determining the malignant potential of cystic renal lesions. Ultrasound has not been incorporated into this pathway. However, the development of ultrasound contrast agents coupled with the superior resolution of ultrasound makes it possible to redefine the imaging of cystic renal lesions. In this position statement, an EFSUMB Expert Task Force reviews, analyzes, and describes the accumulated knowledge and limitations and presents the current position on the use of ultrasound contrast agents in the evaluation of cystic renal lesions.

Duplex ultrasound versus CT angiography for the treatment planning of lower-limb arterial disease.

PURPOSE: This study aimed to assess the diagnostic accuracy of duplex sonography (DUS) compared with that of computed tomography angiography (CTA) in detecting occlusion and stenosis in peripheral arterial disease (PAD) in candidate patients for endovascular revascularization with intraprocedural digital subtraction angiography (DSA). METHODS: The study involved 94 patients suffering from PAD who were candidates for endovascular procedures requiring DSA. They were all submitted preoperatively to DUS and CTA. Based on image analysis, five segments of the arterial tree were assessed: iliac, common femoral, superficial femoral, popliteal, and infrageniculate. According to the stenosis or occlusion degree, the arteries were rated as nonstenotic, stenotic, and occluded. RESULTS: The agreement between DUS and CTA findings using DSA as a reference modality was expressed as a Cohen's kappa (κ) statistic agreement. Our results show that DUS has been less accurate than CTA in evaluating iliac arterial diseases (Cohen's κ agreement of 0.91 and 1.0, respectively) when measured against DSA. We found good diagnostic concordance between DUS and DSA in detecting hemodynamic stenosis and occlusion of the femoro-popliteal axis (Cohen's κ agreement between 0.96 and 0.93). Below the knee, CTA showed even less concordance with DSA (Cohen's κ 0.75). CONCLUSIONS: Because of its accuracy, high-quality DUS performed by well-trained operators may therefore represent a good alternative to CTA in patients undergoing endovascular revascularization to minimize the use of contrast-enhanced radiological imaging. Nevertheless, preoperative CTA imaging is required in cases of nondiagnostic DUS or when a more complete overview of the vascular tree is needed for complex invasive interventions.

Multiparametric ultrasound in the evaluation of kidney disease in elderly.

After the age of 30 years, GFR progressively declines at an average rate of 8 mL/min/1.73 m/decade. A problem of advanced age is that the evaluation of renal function on the basis of indicators valid in young adults, such as creatininemia, is unreliable. In fact, many patients with chronic renal failure may have serum creatinine levels within the normal range even if they have a significant reduction in renal function. Ultrasound has become a routine method of investigation in renal disease: kidney size and parenchymal echogenicity are considered markers of renal function, so US is useful in assessing the presence and degree of renal failure. CEUS is useful in the evaluation of kidney disease in the elderly: the increased hemodynamic resistance of renal microvessels reduces perfusion in the renal cortex, so fewer microbubbles enter the renal cortex. EcoColor and EcoDoppler are also useful in the evaluation of senile alterations: here, the distribution of color-signals, as compared to that in the young adult population, appears more attenuated, limited to intersegmental and interlobar districts. Among the ecoDoppler parameters, the resistance index can be considered a marker of renal damage progression, with attention needing to paid to possible concomitant confounding factors. Ultrasonography, color-Doppler and CEUS are a non-invasive and convenient modality for managing kidney disease; their integration with anamnestic, objective and laboratory data permits fast and reliable clinical, diagnostic, and therapeutic classification. It also allows early therapeutic intervention and, ultimately, improvements in patient management.

MRI ultrasound fusion biopsy in prostate cancer detection: Are randomized clinical trials reproducible in everyday clinical practice?

INTRODUCTION:: The aim of this study was to evaluate the performance of multiparametric magnetic resonance imaging (mpMRI)-ultrasound (US) fusion-targeted biopsies (TB) in men with primary and repeated biopsies comparing the cancer detection rate (CDR) of random biopsies (RB) + TB versus only TB. METHODS:: The present study is a real-life study on patients with primary and prior negative prostate biopsies with suspicious PCa. A total of 130 men with prostate-specific antigen (PSA) value >2.5 ng/dL and/or abnormal digital rectal examination (DRE) were included in the study and subjected to mpMRI. Patients with >2 previous biopsies and/or with ⩾3 suspected lesions on MRI and/or prostate imaging-reporting and data system (PIRADS) value ⩾4 (n:30 pts) were subjected only to TB on the areas indicated by mpMRI. All the other patients (n:70 pts) were subjected to standard random laterally directed 10-core plus TB on the areas indicated by mpMRI. RESULTS:: The overall CDR was 53% (53/100). In relation to PIRADS score, the overall CDR was 0, 40% (12/30), 56.83% (29/51), and 84% (11/13) for PIRADS 2, 3, 4, and 5, respectively. According to biopsy modality, CDR for RB + TB was 50% (35/70) and CDR for TB was 60% (18/30) with a p-value of 0.3632. DISCUSSION:: MRI-US fusion biopsy is associated with a high CDR of clinically significant PCa (csPCa). MRI-US fusion biopsy could be a reasonable approach in patients with previous negative biopsy and high PIRADS score on MRI, to ensure a high CDR of csPCa and to reduce the diagnosis of clinically insignificant tumors.

Diagnostic imaging and CEUS findings in a rare case of Desmoid-type fibromatosis. A case report.

Desmoid-type fibromatosis (DF), also known as aggressive fibromatosis, is a locally aggressive benign fibroblastic neoplasm that can infiltrate or recur but cannot metastasize. It is rare, with an estimated annual incidence of two to four new cases per million people. Most DFs occur sporadically, but it may also be associated with the hereditary syndrome familial adenomatous polyposis. Treatment is necessary when the disease is symptomatic, especially in case of compression of critical structures. When possible, surgical resection is the treatment of choice; however, recurrence is common. Due to the high rate of recurrence, imaging plays an important role not only in diagnosis, but also in the management of DF. Although there are a number of studies describing CT and MRI findings of DF, there is no description of contrast-enhanced ultrasound findings.

The EFSUMB Guidelines and Recommendations for the Clinical Practice of Contrast-Enhanced Ultrasound (CEUS) in Non-Hepatic Applications: Update 2017 (Long Version).

The updated version of the EFSUMB guidelines on the application of non-hepatic contrast-enhanced ultrasound (CEUS) deals with the use of microbubble ultrasound contrast outside the liver in the many established and emerging applications.

The EFSUMB Guidelines and Recommendations for the Clinical Practice of Contrast-Enhanced Ultrasound (CEUS) in Non-Hepatic Applications: Update 2017 (Short Version).

The updated version of the EFSUMB guidelines on the application of non-hepatic contrast-enhanced ultrasound (CEUS) deals with the use of microbubble ultrasound contrast outside the liver in the many established and emerging applications.

99mTc-labeled White Blood Cell Scan as a Guide to Open Biopsy in the Management of Hip and Knee Prosthesis Infection: Preliminary Results.

OBJECTIVE: The aim of the present prospective study was to evaluate the usefulness of labeled leukocyte scan as a guide to open biopsy for the management of hip and knee prosthesis infection in patients without loosening of orthopedic device. METHODS: Twenty-six patients with suspected hip (24) and knee (2) prosthesis infection underwent routine analysis of blood, plain radiography and 99mTc-HMPAO labelled leukocyte scan (WBCS). On these basis, patients were subdivided in the following groups: bone infection without loosening (n°=14), septic loosening (n°=8), superficial infection (n°=2), no infection (n°=2). Patients with septic loosening underwent empirical antibiotic therapy in order to avoid two-stage reimplantation. When the medical treatment was effective patients were submitted to one-stage operation. Patients without loosening of prosthesis but positive WBCS results underwent open biopsy: bone samples and periprosthetic tissues were taken from the regions showing pathological leukocyte uptake at the scan. Samples were submitted to microbiological examination and antibiotic treatments were undertaken in cases of bacterial growth. A 24-months clinical and instrumental follow-up was carried out in all patients. RESULTS: WBCS showed 22 patients affected by bone infection, 2 by superficial infection and 2 not infected. Height out of the 22 patients affected by deep infection had a septic loosening. In these cases, the medical treatment was inadequate in 6 patients and effective in 2. Fourteen patients with bone infection without loosening were submitted to open biopsy: in 9 cases a complete remission of the disease was found. Two patients, without infection, underwent single-stage surgery for mechanical problems. Superficial infection was assessed and successfully treated in 2 patients. CONCLUSION: The obtained results indicate that a multidisciplinary approach to infection of orthopedic prostheses, characterized by the combined use of open biopsy, WBC, and microbiological examination, produced positive outcome in 9 out of 14 patients.

Toxicity assessment of (99m)technetium-labeled human beta-defensin-3 in CD1 mice.

OBJECTIVE: Human beta-defensin-3 (HBD-3) is an antimicrobial peptide which is up-regulated during inflammation. Based on the previously demonstrated capacity of technetium-99m ((99m)Tc) labelled HBD-3 of distinguishing infection from inflammation in rats, we have decided to collect information on the potential toxicity of the tracer in view of its possible use for imaging in humans. MATERIALS AND METHODS: Recombinant HBD-3 underwent labeling with (99m)Tc. The CD1 mice were selected as standard rodent species. Ten mice, 5 male and 5 female, were subjected to physical examination and housed in a dedicated room in 5 per cage. After 9 days pre-test period, all mice were weighted for dose adjustment and received intravenously 6mcg/mouse of (99m)Tc-HBD-3. Mortality was recorded daily, while body weight was registered once a week. Clinical observation of animals was performed daily for sickness symptoms due to the drug treatment. At day 19 a second dose of 6mcg/mouse (99m)Tc-HBD-3, was administered. Twenty-four hours after the second dose (day 20) the animals were euthanized. A piece of liver, kidneys, heart and lungs was collected for histopathological analysis. RESULTS: Our results showed that the labelled-HBD-3 dose did not induce significant toxicity in mice. Of course these parameters were not sufficient to authorize use in humans. This non-toxic dose of HBD-3 when translated from animals to humans resulted in an equivalent dose of approximately 25 times higher than that needed for imaging. CONCLUSION: Our non toxicity data of using (99m)Tc-beta-defensin-3 in mice offer a further indication in favour of the clinical use of this radiopharmaceutical in all cases where discrimination between infection and inflammation is needed.

Ultrasound-guided aspiration and steroid injection of a posterior cruciate ligament ganglion cyst: report of a case.

Ganglion cysts are benign masses that originate from mucinous degeneration of the connective tissues and are quite rare when arising from the knee joint. Symptoms are often represented by pain, joint tenderness, effusion and occasional swelling with a palpable mass in the popliteal region of the knee. Percutaneous aspiration followed by a corticosteroid injection of a ganglion cyst has either a diagnostic or therapeutic meaning and its guidance through ultrasound allows the operator to make more accurate the procedure, ensuring the correct placement of the needle inside the lesion. We report our experience in the treatment of a voluminous ganglion cyst of the posterior cruciate ligament performed through the ultrasound guidance in a symptomatic young patient.