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The elastic and mechanical behaviour of isolated papillar muscle was studied in aged and in young rats. The spontaneous fall in tension (stress relaxation phenomenon) and the duration of the active state of the contractile element during the isometric and isotonic contraction were greater in aged than in young rats. The elastic properties of the elements in parallel and in series and the intensity of the active state in the contractile elements, on the contrary, did not exhibit any significant difference between aged and young rats. [ABSTRACT FROM PUBLISHER]

Reports on the effects of single and multiple doses of methimazole on serum thyroxine and heart rate in hyperthyroid patients. Advantages of using single over divided dose of an antithyroid drug; Preference of methimazole to propylthiouracil; Dependence of antithyroid effectiveness of the thionamides on their ability to inhibit the organification of iodine; Percholrate discharge test to evaluate the degree of inhibition.

Purpose: The aim of this study is to present a case of inflammatory myofibroblastic tumor (IMT) of the liver in a 4-year-old girl. We will discuss the diagnostic challenges, the role of the radiologist in differential diagnosis, treatment modalities, and clinical outcomes., Methods: A case report of a 4-year-old girl with IMT of the liver is presented. We will review the patient's clinical presentation, diagnostic imaging findings, histological features, treatment, and follow-up., Results: The patient presented with vomiting and jaundice, but no fever. Imaging studies revealed an hepatic lesion suspicious for IMT; pathology confirmed the diagnosis. The patient underwent surgical intervention with successful resolution., Conclusion: IMT of the liver is a rare but important diagnosis to consider in children with abdominal masses. Radiologists play a crucial role in differential diagnosis. Surgical resection can be an effective treatment option for IMT, leading to favorable clinical outcomes., Competing Interests: Declarations. Conflict of interest: The authors have no relevant financial or non-financial interests to disclose. Informed consent: Informed consent was obtained from all individual participants included in the study., (© 2024. Società Italiana di Ultrasonologia in Medicina e Biologia (SIUMB).)

Cat-scratch disease is a well-known infection in childhood. It usually presents as tender lymphadenopathy and should be included in the differential diagnosis of any lymphadenopathy syndrome. An history of exposure to cats supports the suspect and a positive serologic test to Bartonella henselae confirms the diagnosis. Ultrasound is the first line radiologic imaging performed in case of lymphadenopathy. The presence of hypoechoic lobular or oval mass with central hyperaemia and a possible adjacent fluid collection and surrounding oedema may differentiate the disease from other aetiologies. We describe the case of a 7-year-old girl presenting with an axillary lymphadenopathy, without a reported recent history of exposure to cats, with sonographic findings suggestive for cat-scratch disease. In this case, ultrasound was very useful in orienteering the diagnosis and insist on the medical history. Serology resulted positive for B. henselae and at the end the family remembered that 6 months before the child was scratched by a kitten., (© 2024. The Author(s).)

Genomic studies have identified frequent mutations in subunits of the SWI/SNF chromatin remodeling complex including SMARCA4 and ARID1A in non-small cell lung cancer. Previously, we and others have identified that SMARCA4 -mutant lung cancers are highly dependent on oxidative phosphorylation (OXPHOS). Despite initial excitements, therapeutics targeting metabolic pathways such as OXPHOS have largely been disappointing due to rapid adaptation of cancer cells to inhibition of single metabolic enzymes or pathways, suggesting novel combination strategies to overcome adaptive responses are urgently needed. Here, we performed a functional genomics screen using CRISPR-Cas9 library targeting genes with available FDA approved therapeutics and identified ROCK1/2 as a top hit that sensitizes cancer cells to OXPHOS inhibition. We validate these results by orthogonal genetic and pharmacologic approaches by demonstrating that KD025 (Belumosudil), an FDA approved ROCK inhibitor, has highly synergistic anti-cancer activity in vitro and in vivo in combination with OXPHOS inhibition. Mechanistically, we showed that this combination induced a rapid, profound energetic stress and cell cycle arrest that was in part due to ROCK inhibition-mediated suppression of the adaptive increase in glycolysis normally seen by OXPHOS inhibition. Furthermore, we applied global phosphoproteomics and kinase-motif enrichment analysis to uncover a dynamic regulatory kinome upon combination of OXPHOS and ROCK inhibition. Importantly, we found converging phosphorylation-dependent regulatory cross-talk by AMPK and ROCK kinases on key RHO GTPase signaling/ROCK-dependent substrates such as PPP1R12A, NUMA1 and PKMYT1 that are known regulators of cell cycle progression. Taken together, our study identified ROCK kinases as critical mediators of metabolic adaptation of cancer cells to OXPHOS inhibition and provides a strong rationale for pursuing ROCK inhibitors as novel combination partners to OXPHOS inhibitors in cancer treatment., Competing Interests: Declaration of Interests Y.L. and N.B. are in the process of filing a patent application of this work.

Biliary atresia (BA) is a congenital disease that occurs when extrahepatic bile ducts are either absent or deficient, resulting in liver fibrosis, portal hypertension, and eventually cirrhosis. It is the most common cause of persistent obstructive jaundice in newborns lasting more than two weeks is this condition. Abdominal ultrasound (US) is the primary imaging technique used to diagnose BA, while computed tomography (CT) is reserved for more complex cases. The gold standard for diagnosing BA is still intraoperative cholangiogram with liver biopsy. Treatment for BA usually involves Kasai hepatoportoenterostomy, but some patients still require liver transplantation due to diagnostic delays and advanced disease. In this study, the authors present the case of a 3-month-old infant with biliary atresia and its ultrasound characteristics, who underwent liver transplantation due to advanced disease. The primary objective of imaging is to provide a prompt diagnosis, given the crucial significance of timely surgical intervention., (© 2024. Società Italiana di Ultrasonologia in Medicina e Biologia (SIUMB).)

Cutaneous myiasis is an infestation of the skin with larvae of some dipteran species. Among humans, Dermatobia hominis is the most frequently encountered dipteran responsible for cutaneous myiasis. This insect is endemic to tropical and subtropical regions, consequently, individuals travelling from non-endemic areas are most susceptible to infection due to a lack of prior exposure. Three clinical variants of myiasis are distinguished: furuncular, migratory, and wound myiasis. Furuncular myiasis represents the most common form among travelers, yet it is a rare cause of pediatric skin manifestations in developed countries. Limited awareness of this condition in non-endemic regions contributes to diagnostic challenges. In this scenario, ultrasound is useful in the diagnostic workup, enabling the identification of the viable larva., (© 2024. Società Italiana di Ultrasonologia in Medicina e Biologia (SIUMB).)

The Testicular Juvenile Granulosa Cell Tumor (JGCT) is a rare testicular neoplasm that appears in the first months of life as a painless testicular mass. Following an accurate radiological ultrasound diagnosis, through which the cystic appearance of the lesion is observed, and histological confirmation, showing follicular growth pattern and an immunoreactivity for inhibin, the treatment process involves, when feasible, conservative surgery. We present the case of a 2-months old infant with a bilateral JGCT of the testis and we review the classical findings of the patology., (© 2024. Società Italiana di Ultrasonologia in Medicina e Biologia (SIUMB).)

Incidental findings of renal masses are increasing. However, a substantial portion of surgically treated renal masses turn out to be benign on histopathological examination. Thus, there is a clear need for improved pre-surgical assessment to minimize unnecessary invasive procedures. The challenge intensifies when distinguishing between renal cell carcinoma (RCC) and angiomyolipoma (AML) in renal lesions smaller than 4 cm with minimal adipose tissue. In such cases, contrast-enhanced ultrasound (CEUS) has emerged as a valuable diagnostic tool, by utilizing both qualitative and quantitative parameters. Quantitative measures offer objectivity, reliability, and reproducibility compared to qualitative parameters, enabling the characterization of RCC subtypes and differentiation from AML. Qualitative features as enhancement pattern, degree, and peak were less helpful in distinguishing triphasic minimal fat AML (TAML) from epithelioid AML (EAML), with the pseudocapsule sign potentially being the only distinguishing qualitative feature. The pseudocapsule sign was more frequently observed in ccRCCs (38.0%) than in AMLs (15.6%). Moreover, it was detected in 40.0% of EAMLs and 34.5% of ccRCCs but not in TAMLs due to similar growth patterns between EAMLs and low-grade ccRCCs. Quantitative measures such as the time-to-peak (TTP) ratio can further enhance diagnostic accuracy and also TOC ratio should be considered, as it was higher in clear cell RCCs (ccRCCs) and in EAMLs compared to TAMLs, indicating behavior similar to ccRCCs. However, CEUS remains an operator-dependent exam., (© 2024. The Author(s).)

Molecular routes to metastatic dissemination are critical determinants of aggressive cancers. Through in vivo CRISPR-Cas9 genome editing, we generated somatic mosaic genetically engineered models that faithfully recapitulate metastatic renal tumors. Disruption of 9p21 locus is an evolutionary driver to systemic disease through the rapid acquisition of complex karyotypes in cancer cells. Cross-species analysis revealed that recurrent patterns of copy number variations, including 21q loss and dysregulation of the interferon pathway, are major drivers of metastatic potential. In vitro and in vivo genomic engineering, leveraging loss-of-function studies, along with a model of partial trisomy of chromosome 21q, demonstrated a dosage-dependent effect of the interferon receptor genes cluster as an adaptive mechanism to deleterious chromosomal instability in metastatic progression. This work provides critical knowledge on drivers of renal cell carcinoma progression and defines the primary role of interferon signaling in constraining the propagation of aneuploid clones in cancer evolution., (© 2023. The Author(s).)

Renal medullary carcinoma (RMC) is an aggressive kidney cancer that almost exclusively develops in individuals with sickle cell trait (SCT) and is always characterized by loss of the tumor suppressor SMARCB1 . Because renal ischemia induced by red blood cell sickling exacerbates chronic renal medullary hypoxia in vivo, we investigated whether the loss of SMARCB1 confers a survival advantage under the setting of SCT. Hypoxic stress, which naturally occurs within the renal medulla, is elevated under the setting of SCT. Our findings showed that hypoxia-induced SMARCB1 degradation protected renal cells from hypoxic stress. SMARCB1 wild-type renal tumors exhibited lower levels of SMARCB1 and more aggressive growth in mice harboring the SCT mutation in human hemoglobin A (HbA) than in control mice harboring wild-type human HbA. Consistent with established clinical observations, SMARCB1-null renal tumors were refractory to hypoxia-inducing therapeutic inhibition of angiogenesis. Further, reconstitution of SMARCB1 restored renal tumor sensitivity to hypoxic stress in vitro and in vivo. Together, our results demonstrate a physiological role for SMARCB1 degradation in response to hypoxic stress, connect the renal medullary hypoxia induced by SCT with an increased risk of SMARCB1-negative RMC, and shed light into the mechanisms mediating the resistance of SMARCB1-null renal tumors against angiogenesis inhibition therapies.

Testicular metastasis are rare findings and bilateral metastasis of testes are extremely rare. Here we are describing for the first time a case of bilateral testicular metastasis in a patient with a known ileocecal valve NET using an in-depth ultra-sound studying including microvascular flow imaging (MV-flow), ultra-sound new technique, able to detect small vessel slow-signal., (© 2022. Società Italiana di Ultrasonologia in Medicina e Biologia (SIUMB).)

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.

Meigs syndrome is a rare disease defined by the coexistence of benign ovarian neoplasm, ascites and hydrothorax, which mainly affects women over the age of 30. This clinical condition refers only to cases in which the ovarian neoformation is a fibroid, a thecoma, a granulosa cell tumor or a Brenner tumor with disappearance of symptoms and effusions after removal of the neoplasm. Meigs syndrome is most frequently characterized by the presence of an ovarian fibroid, which in childhood is very rare and not commonly associated with the disease. In this article we report the case of an 11- year-old girl who came to our observation for a high fever for five days accompanied by cough and abdominal pain; imaging methods revealed bilateral hydrothorax, ascites, and a voluminous expansive right ovarian formation. On histological examination, the mass showed a cellular fibroid and the diagnosis of Meigs syndrome was made. Furthermore, we present a review of the literature aimed at detecting the state of knowledge on this disease in pediatric age, giving particular emphasis to the condition for which, in the presence of pleural effusion and ascites, an ovarian neoformation is not necessarily malignant. KEY WORDS: CT, Meigs syndrome, Pediatric, Pelvic mass, Ultrasounds.