Controversies in endobronchial ultrasound.

Endobronchial ultrasound (EBUS) is a minimally invasive highly accurate and safe endoscopic technique for the evaluation of mediastinal lymphadenopathy and mediastinal masses including centrally located lung tumors. The combination of transbronchial and transoesophageal tissue sampling has improved lung cancer staging, reducing the need for more invasive and surgical diagnostic procedures. Despite the high level of evidence regarding EBUS use in the aforementioned situations, there are still challenges and controversial issues such as follows: Should informed consent for EBUS and flexible bronchoscopy be different? Is EBUS able to replace standard bronchoscopy in patients with suspected lung cancer? Which is the best position, screen orientation, route of intubation, and sedation/anesthesia to perform EBUS? Is it advisable to use a balloon in all procedures? How should the operator acquire skills and how should competence be ensured? This Pro-Con article aims to address these open questions.

Comments and illustrations of the European Federation of Societies for Ultrasound in Medicine guidelines: Rare pancreatic tumors, ultrasound and contrast-enhanced ultrasound features-Malignant mesenchymal tumors.

Rare malignant mesenchymal pancreatic tumors are systematized and reported in this review. The focus is on the appearance on imaging. The present overview summarizes the data and shows that not every pancreatic tumor corresponds to the most common entities of ductal adenocarcinoma or neuroendocrine tumor.

Enhancement of keratinocyte survival and migration elicited by interleukin 24 upregulation in dermal microvascular endothelium upon welding-fume exposure.

Occupational exposure to welding fumes constitutes a serious health concern. Although the effects of fumes on the respiratory tract have been investigated, few apparent reports were published on their effects on the skin. The purpose of this study was to investigate the effects of exposure to welding fumes on skin cells, focusing on interleukin-24 (IL-24), a cytokine involved in the pathophysiology of skin conditions, such as atopic dermatitis and psoriasis. Treatment with welding fumes increased IL-24 expression and production levels in human dermal microvascular endothelial cells (HDMEC) which were higher than that in normal human epidermal keratinocytes. IL-24 levels in Trolox and deferoxamine markedly suppressed welding fume-induced IL-24 expression in HDMEC, indicating that oxidative stress may be involved in this cytokine expression. IL-24 released from HDMEC protected keratinocytes from welding fume-induced damage and enhanced keratinocyte migration. Serum IL-24 was higher in welding workers than in general subjects and was positively correlated with elevated serum levels of 8-hydroxy-2'-deoxyguanosine, an oxidative stress marker. In summary, welding fumes enhanced IL-24 expression in HDMEC, stimulating keratinocyte survival and migration. IL-24 expression in endothelial cells may act as an adaptive response to welding-fume exposure in the skin.

Liver Imaging Reporting and Data System Contrast-Enhanced US Nonradiation Treatment Response Assessment Version 2024.

The American College of Radiology Liver Imaging Reporting and Data System (LI-RADS) standardizes the imaging technique, reporting lexicon, disease categorization, and management for patients with or at risk for hepatocellular carcinoma (HCC). LI-RADS encompasses HCC surveillance with US; HCC diagnosis with CT, MRI, or contrast-enhanced US (CEUS); and treatment response assessment (TRA) with CT or MRI. LI-RADS was recently expanded to include CEUS TRA after nonradiation locoregional therapy or surgical resection. This report provides an overview of LI-RADS CEUS Nonradiation TRA v2024, including a lexicon of imaging findings, techniques, and imaging criteria for posttreatment tumor viability assessment. LI-RADS CEUS Nonradiation TRA v2024 takes into consideration differences in the CEUS appearance of viable tumor and posttreatment changes within and in close proximity to a treated lesion. Due to the high sensitivity of CEUS to vascular flow, posttreatment reactive changes commonly manifest as areas of abnormal perilesional enhancement without washout, especially in the first 3 months after treatment. To improve the accuracy of CEUS for nonradiation TRA, different diagnostic criteria are used to evaluate tumor viability within and outside of the treated lesion margin. Broader criteria for intralesional enhancement increase sensitivity for tumor viability detection. Stricter criteria for perilesional enhancement limit miscategorization of posttreatment reactive changes as viable tumor. Finally, the TRA algorithm reconciles intralesional and perilesional tumor viability assessment and assigns a single LI-RADS treatment response (LR-TR) category: LR-TR nonviable, LR-TR equivocal, or LR-TR viable.

Comparing Sonazoid contrast-enhanced ultrasound to contrast-enhanced CT and MRI for differentially diagnosing renal lesions: a prospective multicenter study.

PURPOSE: To evaluate the diagnostic performance of contrast-enhanced (CE) ultrasound using Sonazoid (SNZ-CEUS) by comparing with contrast-enhanced computed tomography (CE-CT) and contrast-enhanced magnetic resonance imaging (CE-MRI) for differentiating benign and malignant renal masses. MATERIALS AND METHODS: 306 consecutive patients (from 7 centers) with renal masses (40 benign tumors, 266 malignant tumors) diagnosed by both SNZ-CEUS, CE-CT or CE-MRI were enrolled between September 2020 and February 2021. The examinations were performed within 7 days, but the sequence was not fixed. Histologic results were available for 301 of 306 (98.37%) lesions and 5 lesions were considered benign after at least 2 year follow-up without change in size and image characteristics. The diagnostic performances were evaluated by sensitivity, specificity, positive predictive value, negative predictive value, and compared by McNemar's test. RESULTS: In the head-to-head comparison, SNZ-CEUS and CE-MRI had comparable sensitivity (95.60 vs. 94.51%, P = 0.997), specificity (65.22 vs. 73.91%, P = 0.752), positive predictive value (91.58 vs. 93.48%) and negative predictive value (78.95 vs. 77.27%); SNZ-CEUS and CE-CT showed similar sensitivity (97.31 vs. 96.24%, P = 0.724); however, SNZ-CEUS had relatively lower than specificity than CE-CT (59.09 vs. 68.18%, P = 0.683). For nodules > 4 cm, CE-MRI demonstrated higher specificity than SNZ-CEUS (90.91 vs. 72.73%, P = 0.617) without compromise the sensitivity. CONCLUSIONS: SNZ-CEUS, CE-CT, and CE-MRI demonstrate desirable and comparable sensitivity for the differentiation of renal mass. However, the specificity of all three imaging modalities is not satisfactory. SNZ-CEUS may be a suitable alternative modality for patients with renal dysfunction and those allergic to gadolinium or iodine-based agents.

Octyl itaconate enhances VSVΔ51 oncolytic virotherapy by multitarget inhibition of antiviral and inflammatory pathways.

The presence of heterogeneity in responses to oncolytic virotherapy poses a barrier to clinical effectiveness, as resistance to this treatment can occur through the inhibition of viral spread within the tumor, potentially leading to treatment failures. Here we show that 4-octyl itaconate (4-OI), a chemical derivative of the Krebs cycle-derived metabolite itaconate, enhances oncolytic virotherapy with VSVΔ51 in various models including human and murine resistant cancer cell lines, three-dimensional (3D) patient-derived colon tumoroids and organotypic brain tumor slices. Furthermore, 4-OI in combination with VSVΔ51 improves therapeutic outcomes in a resistant murine colon tumor model. Mechanistically, we find that 4-OI suppresses antiviral immunity in cancer cells through the modification of cysteine residues in MAVS and IKKß independently of the NRF2/KEAP1 axis. We propose that the combination of a metabolite-derived drug with an oncolytic virus agent can greatly improve anticancer therapeutic outcomes by direct interference with the type I IFN and NF-κB-mediated antiviral responses.

An [illustrative] update on pediatric emergency medicine ultrasound: part 1 - trauma and thoracic applications.

Point-of-care ultrasound (POCUS) plays an essential role in emergency medicine, providing a range of diagnostic and procedural modalities. It does not involve any ionizing radiation and can improve procedural accuracy and safety. The role of POCUS in the care of pediatric patients differs somewhat from that of adult patients, as there are a range of conditions specific to infants and children. The technical background of pediatric POCUS and its current applications for trauma and thoracic scanning are reviewed and illustrated in this first article of this series.

History of contrast enhanced ultrasound (CEUS).

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

Mechanisms underlying aryl hydrocarbon receptor-driven divergent macrophage function.

Macrophages play an essential role in the innate immune system by differentiating into functionally diverse subsets in order to fight infection, repair damaged tissues, and regulate inappropriate immune responses. This functional diversity stems from their ability to adapt and respond to signals in the environment, which is in part mediated through aryl hydrocarbon receptor (AHR)-signaling. AHR, an environmental sensor, can be activated by various ligands, ranging from environmental contaminants to microbially derived tryptophan metabolites. This review discusses what is currently known about how AHR-signaling influences macrophage differentiation, polarization, and function. By discussing studies that are both consistent and divergent, our goal is to highlight the need for future research on the mechanisms by which AHR acts as an immunological switch in macrophages. Ultimately, understanding the contexts in which AHR-signaling promotes and/or inhibits differentiation, proinflammatory functions, and immunoregulatory functions, will help uncover functional predictions of immunotoxicity following exposure to environmental chemicals as well as better design AHR-targeted immunotherapies.

The value of contrast-enhanced ultrasound in percutaneous biopsy of retroperitoneal masses.

PURPOSE: To evaluate the diagnostic yield of contrast-enhanced ultrasound (CEUS)-guided biopsy of retroperitoneal masses (RMs). MATERIALS AND METHODS: Between 2006 and 2023, 87 patients presented at our US center for biopsy of an RM. In all biopsies, CEUS was performed prior to the intervention. The technical success rate of biopsy, the presence of diagnostic tissue in solid tumor biopsy samples, the accuracy of the biopsy and the occurrence of post-interventional complications were evaluated. RESULTS: A US-guided biopsy could be conducted in 84/87 cases (96.6%). In 3/87 cases (3.4%), US-guided biopsy was impossible because the planned needle path was obstructed by vital structures. Of 84 lesions, 80 (95.2%) were solid lesions, and 4 (4.8%) were lesions containing fluid. In all solid tumors, 80/80 (100%), diagnostic vital tissue was successfully obtained. CEUS-guided biopsy showed a sensitivity of 93.2%, a specificity of 100%, a positive predictive value of 100%, a negative predictive value of 72.2%, and a diagnostic accuracy of 94.2% for the differentiation between malignant and benign RMs. In one of the 84 cases (1.2%), there was a complication of postinterventional abdominal pain. CONCLUSION: Percutaneous CEUS-guided biopsy is a safe procedure with a high diagnostic yield and a low complication rate.

Comments and Illustrations of Ultrasound Findings in Extrapulmonary Tuberculosis Manifestations.

This review describes the appearance of extrapulmonary tuberculosis manifestations in comprehensive and multiparametric ultrasound imaging. The aim is to increase awareness of typical ultrasound findings regarding extrapulmonary tuberculosis, correlate those with pathological features, and facilitate differential diagnosis. Point of care ultrasound protocols can be used as a screening method in high-risk populations, although the negative findings do not exclude tuberculosis. Conversely, the diagnosis of extrapulmonary tuberculosis can never be made using ultrasound alone, as many ultrasound findings in extrapulmonary tuberculosis are non-specific. However, ultrasound-based sampling techniques can significantly facilitate the collection of samples for microbiological or molecular proof of tuberculosis, as well as facilitating the establishment of alternative diagnoses.

Simulation-based education in ultrasound - diagnostic and interventional abdominal focus. / Simulationsbasierte Ausbildung im Ultraschall ­ Fokus auf der diagnostischen und interventionellen Abdomen-Sonografie.

Simulation-based training (SBT) is increasingly acknowledged worldwide and has become a popular tool for ultrasound education. Ultrasound simulation involves the use of technology and software to create a virtual training setting. Simulation-based training allows healthcare professionals to learn, practice, and improve their ultrasound imaging skills in a safe learning-based environment. SBT can provide a realistic and focused learning experience that creates a deep and immersive understanding of the complexity of ultrasound, including enhancing knowledge and confidence in specific areas of interest. Abdominal ultrasound simulation is a tool to increase patient safety and can be a cost-efficient training method. In this paper, we provide an overview of various types of abdominal ultrasound simulators, and the benefits, and challenges of SBT. We also provide examples of how to develop SBT programs and learning strategies including mastery learning. In conclusion, the growing demand for medical imaging increases the need for healthcare professionals to start using ultrasound simulators in order to keep up with the rising standards.

SAM68 directs STING signaling to apoptosis in macrophages.

DNA is a danger signal sensed by cGAS to engage signaling through STING to activate innate immune functions. The best-studied downstream responses to STING activation include expression of type I interferon and inflammatory genes, but STING also activates other pathways, including apoptosis. Here, we report that STING-dependent induction of apoptosis in macrophages occurs through the intrinsic mitochondrial pathway and is mediated via IRF3 but acts independently of gene transcription. By intersecting four mass spectrometry datasets, we identify SAM68 as crucial for the induction of apoptosis downstream of STING activation. SAM68 is essential for the full activation of apoptosis. Still, it is not required for STING-mediated activation of IFN expression or activation of NF-κB. Mechanistic studies reveal that protein trafficking is required and involves SAM68 recruitment to STING upon activation, with the two proteins associating at the Golgi or a post-Golgi compartment. Collectively, our work identifies SAM68 as a STING-interacting protein enabling induction of apoptosis through this DNA-activated innate immune pathway.

Student ultrasound education - current views and controversies.

As an extension of the clinical examination and as a diagnostic and problem-solving tool, ultrasound has become an established technique for clinicians. A prerequisite for high-quality clinical ultrasound practice is adequate student ultrasound training. In light of the considerable heterogeneity of ultrasound curricula in medical studies worldwide, this review presents basic principles of modern medical student ultrasound education and advocates for the establishment of an ultrasound core curriculum embedded both horizontally and vertically in medical studies.

The budding yeast Fkh1 Forkhead associated (FHA) domain promoted a G1-chromatin state and the activity of chromosomal DNA replication origins.

In Saccharomyces cerevisiae, the forkhead (Fkh) transcription factor Fkh1 (forkhead homolog) enhances the activity of many DNA replication origins that act in early S-phase (early origins). Current models posit that Fkh1 acts directly to promote these origins' activity by binding to origin-adjacent Fkh1 binding sites (FKH sites). However, the post-DNA binding functions that Fkh1 uses to promote early origin activity are poorly understood. Fkh1 contains a conserved FHA (forkhead associated) domain, a protein-binding module with specificity for phosphothreonine (pT)-containing partner proteins. At a small subset of yeast origins, the Fkh1-FHA domain enhances the ORC (origin recognition complex)-origin binding step, the G1-phase event that initiates the origin cycle. However, the importance of the Fkh1-FHA domain to either chromosomal replication or ORC-origin interactions at genome scale is unclear. Here, S-phase SortSeq experiments were used to compare genome replication in proliferating FKH1 and fkh1-R80A mutant cells. The Fkh1-FHA domain promoted the activity of 100 origins that act in early to mid- S-phase, including the majority of centromere-associated origins, while simultaneously inhibiting 100 late origins. Thus, in the absence of a functional Fkh1-FHA domain, the temporal landscape of the yeast genome was flattened. Origins are associated with a positioned nucleosome array that frames a nucleosome depleted region (NDR) over the origin, and ORC-origin binding is necessary but not sufficient for this chromatin organization. To ask whether the Fkh1-FHA domain had an impact on this chromatin architecture at origins, ORC ChIPSeq data generated from proliferating cells and MNaseSeq data generated from G1-arrested and proliferating cell populations were assessed. Origin groups that were differentially regulated by the Fkh1-FHA domain were characterized by distinct effects of this domain on ORC-origin binding and G1-phase chromatin. Thus, the Fkh1-FHA domain controlled the distinct chromatin architecture at early origins in G1-phase and regulated origin activity in S-phase.

[State of the art: Simulation in US]. / State of the art: Simulation in der Ultraschallausbildung.

Technical simulation of diagnostic and therapeutic procedures is of growing relevance for student education and advanced medical training and has already been introduced in the field of ultrasound. This review gives a broad overview on different levels of simulation for ultrasound diagnostics and highlights the technical background of the methodology. A critical review of the literature reveals recommendations for implementing simulation techniques in medical studies and professional ultrasound training. An analysis of strengths and weaknesses shows the advantages of simulation especially in the context of individual learning situations and COVID-19-related restrictions for personal interaction. However, simulation techniques cannot replace the experiences of complex clinical examinations with direct interaction to real patients. Therefore, future applications may focus on repetition and assessment of achieved competencies by using standardized feedback mechanisms in order to preserve the limited resources for practical medical training.

Dynamics of torque teno virus load in kidney transplant recipients with indication biopsy and therapeutic modifications of immunosuppression.

Following kidney transplantation, lifelong immunosuppressive therapy is essential to prevent graft rejection. On the downside, immunosuppression increases the risk of severe infections, a major cause of death among kidney transplant recipients (KTRs). To improve post-transplant outcomes, adequate immunosuppressive therapy is therefore a challenging but vital aspect of clinical practice. Torque teno virus load (TTVL) was shown to reflect immune competence in KTRs, with low TTVL linked to an elevated risk for rejections and high TTVL associated with infections in the first year post-transplantation. Yet, little is known about the dynamics of TTVL after the first year following transplantation and how TTVL changes with respect to short-term modifications in immunosuppressive therapy. Therefore, we quantified TTVL in 106 KTRs with 108 clinically indicated biopsies, including 65 biopsies performed >12 months post-transplantation, and correlated TTVL to histopathology. In addition, TTVL was quantified at 7, 30, and 90 days post-biopsy to evaluate how TTVL was affected by changes in immunosuppression resulting from interventions based on histopathological reporting. TTVL was highest in patients biopsied between 1 and 12 months post-transplantation (N = 23, median 2.98 × 107 c/mL) compared with those biopsied within 30 days (N = 20, median 7.35 × 103 c/mL) and > 1 year post-transplantation (N = 65, median 1.41 × 104 c/mL; p < 0.001 for both). Patients with BK virus-associated nephropathy (BKVAN) had significantly higher TTVL than patients with rejection (p < 0.01) or other pathologies (p < 0.001). When converted from mycophenolic acid to a mTOR inhibitor following the diagnosis of BKVAN, TTVL decreased significantly between biopsy and 30 and 90 days post-biopsy (p < 0.01 for both). In KTR with high-dose corticosteroid pulse therapy for rejection, TTVL increased significantly between biopsy and 30 and 90 days post-biopsy (p < 0.05 and p < 0.01, respectively). Of note, no significant changes were seen in TTVL within 7 days of changes in immunosuppressive therapy. Additionally, TTVL varied considerably with time since transplantation and among individuals, with a significant influence of age and BMI on TTVL (p < 0.05 for all). In conclusion, our findings indicate that TTVL reflects changes in immunosuppressive therapy, even in the later stages of post-transplantation. To guide immunosuppressive therapy based on TTVL, one should consider inter- and intraindividual variations, as well as potential confounding factors.

Normal value of virtual touch imaging quantification elastography in measurements of pancreas.

OBJECTIVE: To evaluate pancreatic tissue stiffness and provide a normal reference shear wave velocity (SWV) value of pancreas from healthy adults by Virtual Touch Imaging Quantification (VTIQ) measurements. METHODS: Healthy adult volunteers without known history of hepatobiliary or pancreatic diseases were included. VTIQ elastography (Siemens ACUSON Sequoia, 5C-1 transducer) was used. SWV values were measured at the cephalic, corpus and tail of pancreas and replicated different operators' obtained data. Subgroups were classified according to the volunteers' gender, age, body mass index (BMI), depth of measurements and the echogenicity of the pancreas. RESULTS: From February 2023 to July 2023, 33 healthy adult volunteers were included. The success rate of VTIQ measurements in cephalic, corpus and tail regions was 90.90 % (30/33), 96.97 % (32/33) and 90.90 % (30/33) respectively. The color elastograms of healthy adult pancreas showed uniform blue or simultaneously blue and green. The average SWV values were 0.97±0.26 m/s for cephalic, 0.91±0.24 m/s for corpus and 0.97±0.25 m/s for pancreatic tail respectively (P = 0.198). The mean SWV values of pancreas did not show significant difference with age, gender or depth (P >  0.05). BMI was an influence factor in the measurements of SWV values of cephalic and tail of pancreas (P <  0.05). Pancreas with hyperechoic parenchyma showed higher mean SWV values (P <  0.05). The intra-observer (ICC = 0.938 [95% CI: 0.869-0.971]) and the inter-observer (ICC = 0.887 [95% CI: 0.760-0.947]) agreements of VTIQ measurements were excellent. CONCLUSIONS: The mean SWV value of the pancreas in healthy adults was 0.96±0.20 m/s (range: 0.52-1.74 m/s). VTIQ technique can be used in pancreatic stiffness measurements with good reliability.