Radiologist-patient consultation of imaging findings after neck ultrasonography:An opportunity to practice value-based radiology

Objective: To investigate how patients experience a radiologist-patient consultation of imaging findings directly after neck ultrasonography (US), and how much time this consumes. Materials and methods: This prospective randomized study included 109 consecutive patients who underwent neck US, of whom 44 had a radiologist-patient consultation of US results directly after the examination, and 65 who had not. Results: The median ratings of all healthcare quality metrics (friendliness of the radiologist, explanation of the radiologist, skill of the radiologist, radiologist's concern for comfort during the examination, radiologist's concern for patient questions/worries, overall rating of the examination, and likelihood of recommending the examination) were either good/high or very good/very high, without any significant differences between both patient groups. Patients who did not discuss the US results with the radiologist, were significantly more worried during the examination (P = 0.040) and had significantly higher anxiety levels after completion of the US examination (P = 0.027) than patients who discussed the US results with the radiologist. Fifty-one out of 55 responding patients (92.7%) indicated a radiologist-patient consultation of US results to be important. The median duration of US examinations that included a radiologist-patient consultation of US results was 7.57 min (range: 5.15-12.10 min), while the median duration of US examinations without a radiologist-patient consultation of US results was 7.34 min (range: 3.45-14.32 min), without any significant difference (P = 0.637). Conclusion: A radiologist-patient consultation of imaging findings after neck US decreases patient anxiety, is desired by most patients, and does not significantly prolong total examination time

Can FDG-PET/CT replace blind bone marrow biopsy of the posterior iliac crest in Ewing sarcoma?

OBJECTIVE: To determine and compare the value of (18)F-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (FDG-PET/CT) to blind bone marrow biopsy (BMB) of the posterior iliac crest in detecting metastatic bone marrow involvement in newly diagnosed Ewing sarcoma. MATERIALS AND METHODS: This retrospective study included 20 patients with newly diagnosed Ewing sarcoma who underwent pretreatment FDG-PET/CT and a total of 38 blind BMBs (two unilateral and 18 bilateral) of the posterior iliac crest. FDG-PET/CT scans were evaluated for bone marrow involvement, both in the posterior iliac crest and other sites, and compared to blind BMB results. RESULTS: FDG-PET/CT was positive for bone marrow involvement in 7/38 posterior iliac crests, whereas BMB was positive in 5/38 posterior iliac crests. FDG-PET/CT and BMB results in the posterior iliac crest agreed in 36/38 cases (94.7%, 95% confidence interval [CI]: 82.7-98.5%). On a patient level, FDG-PET/CT was positive for bone marrow involvement in 4/20 patients, whereas BMB of the posterior iliac crest was positive in 3/20 patients. On a patient level, FDG-PET/CT and BMB results agreed in 19/20 patients (95.0%, 95% CI: 76.4-99.1%). The only discrepancies between FDG-PET/CT and BMB were observed in two BMBs of one patient. Both BMBs in this patient were negative, whereas FDG-PET/CT indicated bilateral posterior iliac crest involvement and also extensive bone marrow involvement elsewhere. CONCLUSIONS: FDG-PET/CT appears to be a valuable method for metastatic bone marrow assessment in newly diagnosed Ewing sarcoma. The routine use of blind BMB of the posterior iliac crest should be reconsidered when FDG-PET/CT is available

MRI after Whoops procedure:diagnostic value for residual sarcoma and predictive value for an incomplete second resection

OBJECTIVE: To determine the value of MRI for the detection and assessment of the anatomic extent of residual sarcoma after a Whoops procedure (unplanned sarcoma resection) and its utility for the prediction of an incomplete second resection. MATERIALS AND METHODS: This study included consecutive patients who underwent a Whoops procedure, successively followed by gadolinium chelate-enhanced MRI and second surgery at a tertiary care sarcoma center. RESULTS: Twenty-six patients were included, of whom 19 with residual tumor at the second surgery and 8 with an incomplete second resection (R1: n = 6 and R2: n = 2). Interobserver agreement for residual tumor at MRI after a Whoops procedure was perfect (κ value: 1.000). MRI achieved a sensitivity of 47.4% (9/19), a specificity of 100% (7/7), a positive predictive value of 100% (9/9), and a negative predictive value of 70.0% (7/17) for the detection of residual tumor. MRI correctly classified 2 of 19 residual sarcomas as deep-seated (i.e., extending beyond the superficial muscle fascia) but failed to correctly classify 3 of 19 residual sarcomas as deep-seated. There were no significant associations between MRI findings (presence of residual tumor, maximum tumor diameter, anatomic tumor extent, tumor margins, tumor spiculae, and tumor tail on the superficial fascia) with an incomplete (R1 or R2) second resection. CONCLUSION: Gadolinium chelate-enhanced MRI is a reproducible method to rule in residual sarcoma, but it is insufficiently accurate to rule out and assess the anatomic extent or residual sarcoma after a Whoops procedure. Furthermore, MRI has no utility in predicting an incomplete second resection

Culture yield of repeat percutaneous image-guided biopsy after a negative initial biopsy in suspected spondylodiscitis:a systematic review

Objective: To systematically review the published data on the culture yield of a repeat (second) percutaneous image-guided biopsy after negative initial biopsy in suspected spondylodiscitis. Materials and methods: A systematic search was performed of the PubMed/Medline and Embase databases. The methodological quality of the studies included was assessed. The proportions of positive cultures among all initial biopsies and second biopsies (after a negative initial biopsy) were calculated for each study and assessed for heterogeneity (defined as I2 > 50%). Results: Eight studies, comprising a total of 107 patients who underwent a second percutaneous image-guided biopsy after a culture-negative initial biopsy in suspected spondylodiscitis, were included. All eight studies were at risk of bias and were concerning with regard to applicability, particularly patient selection, flow of patients through the study, and timing of the biopsy. The proportions of positive cultures among all initial biopsies ranged from 10.3 to 52.5%, and were subject to heterogeneity (I2 = 73.7%). The proportions of positive cultures among all second biopsies after negative initial biopsy ranged from 0 to 60.0%, and were not subject to heterogeneity (I2 = 38.7%). Conclusion: Although a second percutaneous image-guided biopsy may have some value in patients with suspected spondylodiscitis, its exact value remains unclear, given the available poor-quality evidence. Future well-designed studies are needed to determine the role of a second percutaneous image-guided biopsy in this setting. Such studies should clearly describe the spectrum of patients that was selected for a second percutaneous image-guided biopsy, the method of biopsy, and differences compared with the first biopsy, if any

Impact of plastic-related compounds on the gene expression signature of HepG2 cells transfected with CYP3A4

The presence of plastic and microplastic within the oceans as well as in marine flora and fauna have caused a multitude of problems that have been the topic of numerous investigations for many years. However, their impact on human health remains largely unknown. Such plastic and microplastic particles have been detected in blood and placenta, underlining their ability to enter the human body. Plastics also contain other compounds, such as plasticizers, antioxidants, or dyes, whose impact on human health is currently being studied. Critical enzymes within the metabolism of endogenous molecules, especially of xenobiotics, are the cytochrome P450 monooxygenases (CYPs). Although their importance in maintaining cellular balance has been confirmed, their interactions with plastics and related products are poorly understood. In this study, the possible relationship between different plastic-related compounds and CYP3A4 as one of the most important CYPs was analyzed using hepatic cells overexpressing this enzyme. Beginning with virtual compound screening and molecular docking of more than 1000 plastic-related compounds, several candidates were identified to interact with CYP3A4. In a second step, RNA-sequencing was used to study in detail the transcriptome-wide gene expression levels affected by the selected compounds. Three candidate molecules ((2,2′-methylenebis(6-tert-butyl-4-methylphenol), 1,1-bis(3,5-di-tert-butyl-2-hydroxyphenyl)ethane, and 2,2′-methylenebis(6-cyclohexyl-4-methylphenol)) had an excellent binding affinity to CYP3A4 in-silico as well as cytotoxic effects and interactions with several metabolic pathways in-vitro. We identified common pathways influenced by all three selected plastic-related compounds. In particular, the suppression of pathways related to mitosis and ‘DNA-templated DNA replication’ which were confirmed by cell cycle analysis and single-cell gel electrophoresis. Furthermore, several mis-regulated metabolic and inflammation-related pathways were identified, suggesting the induction of hepatotoxicity at different levels. These findings imply that these compounds may cause liver problems subsequently affecting the entire organism

Cynaropicrin disrupts tubulin and c-Myc-related signaling and induces parthanatos-type cell death in multiple myeloma

The majority of blood malignancies is incurable and has unforeseeable remitting-relapsing paths in response to different treatments. Cynaropicrin, a natural sesquiterpene lactone from the edible parts of the artichoke plant, has gained increased attention as a chemotherapeutic agent. In this study, we investigated the effects of cynaropicrin against multiple myeloma (MM) cells in vitro and assessed its in vivo effectiveness in a xenograft tumor zebrafish model. We showed that cynaropicrin exerted potent cytotoxicity against a panel of nine MM cell lines and two leukemia cell lines with AMO1 being the most sensitive cell line (IC50 = 1.8 ± 0.3 µM). Cynaropicrin (0.8, 1.9, 3.6 µM) dose-dependently reduced c-Myc expression and transcriptional activity in AMO1 cells that was associated with significant downregulation of STAT3, AKT, and ERK1/2. Cell cycle analysis showed that cynaropicrin treatment arrested AMO1 cells in the G2M phase along with an increase in the sub-G0G1 phase after 24 h. With prolonged treatment times, cells accumulated more in the sub-G0G1 phase, implying cell death. Using confocal microscopy, we revealed that cynaropicrin disrupted the microtubule network in U2OS cells stably expressing α-tubulin-GFP. Furthermore, we revealed that cynaropicrin promoted DNA damage in AMO1 cells leading to PAR polymer production by PARP1 hyperactivation, resulting in AIF translocation from the mitochondria to the nucleus and subsequently to a novel form of cell death, parthanatos. Finally, we demonstrated that cynaropicrin (5, 10 µM) significantly reduced tumor growth in a T-cell acute lymphoblastic leukemia (T-ALL) xenograft zebrafish model. Taken together, these results demonstrate that cynaropicrin causes potent inhibition of hematopoietic tumor cells in vitro and in vivo

Diagnostic value of MRI signs in differentiating Ewing sarcoma from osteomyelitis

Background: The value of magnetic resonance imaging (MRI) signs in differentiating Ewing sarcoma from osteomyelitis has not be thoroughly investigated. Purpose: To investigate the value of various MRI signs in differentiating Ewing sarcoma from osteomyelitis. Material and Methods: Forty-one patients who underwent MRI because of a bone lesion of unknown nature with a differential diagnosis that included both Ewing sarcoma and osteomyelitis were included. Two observers assessed several MRI signs, including the transition zone of the bone lesion, the presence of a soft-tissue mass, intramedullary and extramedullary fat globules, and the penumbra sign. Results: Diagnostic accuracies for discriminating Ewing sarcoma from osteomyelitis were 82.4% and 79.4% for the presence of a soft-tissue mass, and 64.7% and 58.8% for a sharp transition zone of the bone lesion, for readers 1 and 2 respectively. Inter-observer agreement with regard to the presence of a soft-tissue mass and the transition zone of the bone lesion were moderate (κ = 0.470) and fair (κ = 0.307), respectively. Areas under the receiver operating characteristic curve of the diameter of the soft-tissue mass (if present) were 0.829 and 0.833, for readers 1 and 2 respectively. Mean inter-observer difference in soft-tissue mass diameter measurement ± limits of agreement was 35.0 ± 75.0 mm. Diagnostic accuracies of all other MRI signs were all < 50%. Conclusion: Presence and size of a soft-tissue mass, and sharpness of the transition zone, are useful MRI signs to differentiate Ewing sarcoma from osteomyelitis, but inter-observer agreement is relatively low. Other MRI signs are of no value in this setting

CT-guided biopsy in suspected spondylodiscitis:microbiological yield, impact on antimicrobial treatment, and relationship with outcome

Purpose: To investigate the clinical impact of CT-guided biopsy, as performed in routine clinical practice, in patients with suspected spondylodiscitis on MRI in terms of culture yield, impact on antimicrobial treatment, and outcome. Methods: This study included 64 patients with MRI findings compatible with spondylodiscitis who underwent CT-guided biopsy. Results: Initial CT-guided biopsies were culture-positive in 20/64 (31.3%, 95% confidence interval [CI] 21.2–43.3%). Repeat CT-guided biopsies (after initial negative biopsy) were culture-positive in an additional 5/15 (33.3%, 95% CI 15.2–58.3%). Serum leukocytes, C-reactive protein, pre-biopsy use of antibiotics, neurological symptoms, MRI findings, vertebral height loss, and hyperkyphosis were not significantly different between culture-positive and culture-negative cases (P = 0.214–1.000); 75% (15/20) of initial CT-guided biopsies that were culture-positive provided additional information to clinicians for guiding antibiotic treatment. Sixty-two of 64 patients (96.9%, 95% CI 89.3–99.1%) would have been adequately treated if a strategy was followed that would subject all patients without clinical findings suspicious for “atypical” microorganisms and negative blood cultures to empirical antibiotics (i.e., clindamycin for coverage of Gram-positive bacteria) without using biopsy results to determine the optimal antibiotic regimen. Outcome within 6 months (development of neurologic or orthopedic complications, surgery, and death) was not significantly different (P = 0.751) between culture-positive and culture-negative patients. Conclusions: Although CT-guided biopsies are culture-positive in a minority of cases, the majority of positive cultures are useful to tailor antibiotic treatment. Empirical treatment with clindamycin may cover almost all micro-organisms in positive biopsy specimens, provided patients are not immunocompromised. Outcome appears similar between culture-positive and culture-negative patients

Serum Amyloid A Impairs the Antiinflammatory Properties of HDL

HDL from healthy humans and lean mice inhibits palmitate-induced adipocyte inflammation; however, the effect of the inflammatory state on the functional properties of HDL on adipocytes is unknown. Here, we found that HDL from mice injected with AgNO3 fails to inhibit palmitate-induced inflammation and reduces cholesterol efflux from 3T3-L1 adipocytes. Moreover, HDL isolated from obese mice with moderate inflammation and humans with systemic lupus erythematosus had similar effects. Since serum amyloid A (SAA) concentrations in HDL increase with inflammation, we investigated whether elevated SAA is a causal factor in HDL dysfunction. HDL from AgNO3-injected mice lacking Saa1.1 and Saa2.1 exhibited a partial restoration of antiinflammatory and cholesterol efflux properties in adipocytes. Conversely, incorporation of SAA into HDL preparations reduced antiinflammatory properties but not to the same extent as HDL from AgNO3-injected mice. SAA-enriched HDL colocalized with cell surface–associated extracellular matrix (ECM) of adipocytes, suggesting impaired access to the plasma membrane. Enzymatic digestion of proteoglycans in the ECM restored the ability of SAA-containing HDL to inhibit palmitate-induced inflammation and cholesterol efflux. Collectively, these findings indicate that inflammation results in a loss of the antiinflammatory properties of HDL on adipocytes, which appears to partially result from the SAA component of HDL binding to cell-surface proteoglycans, thereby preventing access of HDL to the plasma membrane

\u27Links2HealthierBubs\u27 cohort study: Protocol for a record linkage study on the safety, uptake and effectiveness of influenza and pertussis vaccines among pregnant Australian women

Introduction: Pregnant women and infants are at risk of severe influenza and pertussis infection. Inactivated influenza vaccine (IIV) and diphtheria-tetanus-acellular pertussis vaccine (dTpa) are recommended during pregnancy to protect both mothers and infants. In Australia, uptake is not routinely monitored but coverage appears sub-optimal. Evidence on the safety of combined antenatal IIV and dTpa is fragmented or deficient, and there remain knowledge gaps of population-level vaccine effectiveness. We aim to establish a large, population-based, multi-jurisdictional cohort of mother-infant pairs to measure the uptake, safety and effectiveness of antenatal IIV and dTpa vaccines in three Australian jurisdictions. This is a first step toward assessing the impact of antenatal vaccination programmes in Australia, which can then inform government policy with respect to future strategies in national vaccination programmes. Methods and analysis: ‘Links2HealthierBubs’ is an observational, population-based, retrospective cohort study established through probabilistic record linkage of administrative health data. The cohort includes births between 2012 and 2017 (~607 605 mother-infant pairs) in jurisdictions with population-level antenatal vaccination and health outcome data (Western Australia, Queensland and the Northern Territory). Perinatal data will be the reference frame to identify the cohort. Jurisdictional vaccination registers will identify antenatal vaccination status and the gestational timing of vaccination. Information on maternal, fetal and child health outcomes will be obtained from hospitalisation and emergency department records, notifiable diseases databases, developmental anomalies databases, birth and mortality registers. Ethics and dissemination: Ethical approval was obtained from the Western Australian Department of Health, Curtin University, the Menzies School of Health Research, the Royal Brisbane and Women’s Hospital, and the West Australian Aboriginal Health Ethics Committees. Research findings will be disseminated in peer-reviewed journals, at scientific meetings, and may be incorporated into communication materials for public health agencies and the public