Delineation and agreement of FET PET biological volumes in glioblastoma: results of the nuclear medicine credentialing program from the prospective, multi-centre trial evaluating FET PET In Glioblastoma (FIG) study-TROG 18.06.

PURPOSE: The O-(2-[18F]-fluoroethyl)-L-tyrosine (FET) PET in Glioblastoma (FIG) trial is an Australian prospective, multi-centre study evaluating FET PET for glioblastoma patient management. FET PET imaging timepoints are pre-chemoradiotherapy (FET1), 1-month post-chemoradiotherapy (FET2), and at suspected progression (FET3). Before participant recruitment, site nuclear medicine physicians (NMPs) underwent credentialing of FET PET delineation and image interpretation. METHODS: Sites were required to complete contouring and dynamic analysis by ≥ 2 NMPs on benchmarking cases (n = 6) assessing biological tumour volume (BTV) delineation (3 × FET1) and image interpretation (3 × FET3). Data was reviewed by experts and violations noted. BTV definition includes tumour-to-background ratio (TBR) threshold of 1.6 with crescent-shaped background contour in the contralateral normal brain. Recurrence/pseudoprogression interpretation (FET3) required assessment of maximum TBR (TBRmax), dynamic analysis (time activity curve [TAC] type, time to peak), and qualitative assessment. Intraclass correlation coefficient (ICC) assessed volume agreement, coefficient of variation (CoV) compared maximum/mean TBR (TBRmax/TBRmean) across cases, and pairwise analysis assessed spatial (Dice similarity coefficient [DSC]) and boundary agreement (Hausdorff distance [HD], mean absolute surface distance [MASD]). RESULTS: Data was accrued from 21 NMPs (10 centres, n ≥ 2 each) and 20 underwent review. The initial pass rate was 93/119 (78.2%) and 27/30 requested resubmissions were completed. Violations were found in 25/72 (34.7%; 13/12 minor/major) of FET1 and 22/74 (29.7%; 14/8 minor/major) of FET3 reports. The primary reasons for resubmission were as follows: BTV over-contour (15/30, 50.0%), background placement (8/30, 26.7%), TAC classification (9/30, 30.0%), and image interpretation (7/30, 23.3%). CoV median and range for BTV, TBRmax, and TBRmean were 21.53% (12.00-30.10%), 5.89% (5.01-6.68%), and 5.01% (3.37-6.34%), respectively. BTV agreement was moderate to excellent (ICC = 0.82; 95% CI, 0.63-0.97) with good spatial (DSC = 0.84 ± 0.09) and boundary (HD = 15.78 ± 8.30 mm; MASD = 1.47 ± 1.36 mm) agreement. CONCLUSION: The FIG study credentialing program has increased expertise across study sites. TBRmax and TBRmean were robust, with considerable variability in BTV delineation and image interpretation observed.

Long-Term Outcomes Following Rapid Access Chest Pain Clinic Assessment: First Australian Data.

Australian guidelines recommend prompt evaluation of patients presenting to emergency departments with chest pain, found to be low risk for acute coronary syndromes, and cardiologist-led Rapid Access Chest Pain Clinics (RACPC) have been proposed as a model to provide such care. Initial Australian experience of RACPCs suggests excellent short-term outcomes, and that they are cost-beneficial, though little data exists examining longer-term outcomes. The present study therefore examines such longer-term outcomes to beyond 5 years following presentation to an RACPC in an Australian tertiary metropolitan centre.

Long-Term Real-Time In Vivo Drug Release Monitoring with AIE Thermogelling Polymer.

A new drug concentration meter is developed. In vivo drug release can be monitored precisely via a self-indicating drug delivery system consisting of a new aggregation-induced emission thermoresponsive hydrogel. By taking the advantage of a self-indicating system, one can easily detect the depletion of drugs, and reinject to maintain a dosage in the optimal therapeutic window.

Growth and Utilization of Radiology Instagram Accounts: Insight and Template From an Online Radiologist Educator.

Instagram is a rapidly growing platform with more than 1 billion monthly active users. It is increasingly becoming recognized as a tool for education in visually rich fields of medicine, being particularly suited to radiology. The purpose of this manuscript is to describe the key strategies employed by an online radiologist educator to optimally utilize and grow a radiology Instagram account. The authors hope that these insights serve as a reproducible template for radiologists seeking to explore this online platform.

Development and evaluation of cancer differentiation analysis technology: a novel biophysics-based cancer screening method.

BACKGROUND: Routine health checkup is an essential strategy for monitoring population health and maintaining healthy workforces. However, there was a lack of cancer screening tests among routine health checkups due to high costs and unreliable methods. METHODS: We conducted a two-stage study to evaluate the value of a blood test, Cancer Differentiation Analysis (CDATM), which is developed to differentiate the blood samples of healthy individuals from those of cancer patients through measuring and analyzing multiple biophysical properties. RESULTS: The first stage of a cross-sectional study included 75,942 healthy individuals in routine health checkup, and the second stage of a prospective population-based cohort included 1,957 healthy community members. Forty-eight and ten cancer cases were identified among cross-sectional study and prospective population-based cohort, respectively. Using a pre-determined cutoff, we found that the CDA™ test could differentiate blood samples between healthy and cancer individuals with >93% specificity and >55% sensitivity in both studies. CONCLUSIONS: With high specificity and moderate sensitivity of CDA™ test, our study indicates that we can analyze biophysical properties in the blood to rapidly and reliably screen healthy individuals from cancer patients in a health checkup setting where most individuals are healthy or with average risk of cancer.

Ontario COVID-19 assessment centre practices in patient counselling, education, and follow-up care: A provincial survey.

Background: In March 2020, COVID-19 assessment centres were launched across the province of Ontario to facilitate COVID-19 testing outside of emergency departments. We aimed to study the degree to which assessment centres provide education and follow-up care for patients with suspected COVID-19. Methods: We conducted an online survey of Ontario COVID-19 assessment centre directors between September 15 and October 15, 2020. The primary outcomes studied were the types of educational modalities employed and information conveyed, methods and frequency of test result communication, and any follow-up care that was offered. Survey respondents were also asked to provide descriptions of barriers to patient education and test communication. Results: A total of 56 directors (representing 73 assessment centres) completed the survey. The most frequent educational modalities employed were educational handouts (92%), direct in-person counselling (89%), and referral to website (72%). Seventy-one percent of respondents indicated patients with positive test results would be notified, and 61% of respondents indicated that follow-up care would be offered. The most frequently reported barriers to patient education were insufficient time and high volume of tests, while the most frequently reported barriers to communication of test results were difficulty accessing online health portals and high volume of tests. Conclusion: The ability of many assessment centres to provide patient education is limited by both individual patient and system-level factors. Assessment centres may benefit from standardization of educational materials, improved accessibility to test results for patients in marginalized groups, and virtual pathways to facilitate additional counselling and care for individuals who test positive.

Historique : En mars 2020, des centres d'évaluation de la COVID-19 ont été lancés dans la province de l'Ontario afin de favoriser le dépistage de la COVID-19 hors des services d'urgence. Les chercheurs visaient à étudier dans quelle mesure ces centres transmettent de l'information et des soins de suivi aux patients chez qui on présume une COVID-19. Méthodologie : Les chercheurs ont réalisé un sondage en ligne auprès des directeurs des centres d'évaluation de la COVID-19 de l'Ontario entre le 15 septembre et le 15 octobre 2020. Le type de modalités pédagogiques utilisé et d'information transmise, les modes et la fréquence de communication des résultats des tests et les soins de suivi offerts étaient les résultats cliniques primaires à l'étude. Les répondants au sondage ont également été invités à décrire les obstacles à la transmission d'information aux patients et à la communication des résultats. Résultats : Au total, 56 directeurs (représentant 73 centres d'évaluation) ont rempli le sondage. Les principales modalités pédagogiques étaient la remise de document d'information (92 %), des conseils individuels directs (89 %) et l'orientation vers un site Web (72 %). Ainsi, 71 % des répondants ont indiqué que les patients obtenant un résultat positif en étaient avisés, et 61 %, que des soins de suivi seraient offerts. Les principaux obstacles à la transmission d'information aux patients étaient le manque de temps et le volume élevé de tests, tandis que les principaux obstacles à la transmission des résultats étaient la difficulté d'accès aux portails santé en ligne et le volume élevé de tests. Conclusion : La capacité de nombreux centres d'évaluation à transmettre de l'information aux patients est limitée à la fois par des facteurs liés aux patients eux-mêmes et par des facteurs systémiques. Les centres d'évaluation pourraient tirer profit de la standardisation des documents pédagogiques, d'un meilleur accès aux résultats des tests pour les patients de groupes marginalisés et de trajectoires virtuelles pour favoriser la transmission de conseils et de soins supplémentaires aux personnes dont les résultats sont positifs.

The polyphenol epigallocatechin-3-gallate affects lipid rafts to block activation of the c-Met receptor in prostate cancer cells.

The HGF/c-Met pathway is an important regulator of signaling pathways responsible for invasion and metastasis of most human cancers, including prostate cancer. Exposure of DU145 prostate tumor cells to HGF stimulates the PI3-kinase and MAPK pathways, leading to increased scattering, motility, and invasion, which was prevented by the addition of EGCG. EGCG acted at the level of preventing phosphorylation of tyrosines 1234/1235 in the kinase domain of the c-Met receptor without effecting dimerization. HGF-induced changes were independent of the formation of reactive oxygen species, suggesting that EGCG functioned independent of its antioxidant ability. ECG, another tea polyphenol, was as effective as EGCG, while EGC and EC were less effective. EGCG added up to 4 h after the addition of HGF still blocked cell scattering and reduced the HGF-induced phosphorylation of c-Met, Akt, and Erk, suggesting that EGCG could act both by preventing activation of c-Met by HGF and by attenuating the activity of pathways already induced by HGF. HGF did not activate the MAPK and PI3-K pathways in cells treated with methyl-beta-cyclodextrin (mCD) to remove cholesterol. Furthermore, subcellular fractionation approaches demonstrated that only phosphorylated c-Met accumulated in Triton X-100 membrane insoluble fractions, supporting a role for lipid rafts in regulating c-Met signaling. Finally, EGCG treatment inhibited DiIC16 incorporation into membrane lipid ordered domains, and cholesterol partially inhibited the EGCG effects on signaling. Together, these results suggest that green tea polyphenols with the R1 galloyl group prevent activation of the c-Met receptor by altering the structure or function of lipid rafts.

Discrepancies between positron emission tomography/magnetic resonance imaging and positron emission tomography/computed tomography in a cohort of oncological patients.

INTRODUCTION: This study aims to evaluate discrepant findings between positron emission tomography/magnetic resonance imaging (PET/MRI) and positron emission tomography/computed tomography (PET/CT) in a cohort of oncological patients and to undertake a phantom study to assess the potential for extended PET acquisitions to lead to false-positive findings on PET/MRI. METHODS: Discrepant findings from a series of 106 patients undergoing same-day 18 F-fluorodeoxyglucose (FDG)-PET/CT and PET/MRI were reviewed. Phantom studies explored the potential for PET acquisition time to contribute to discrepancy. RESULTS: There were 14 discrepant cases, 5 (35.7%) of which related to PET/MRI acquisitions that had been extended to 10 min. Three of these five cases proved to be falsely positive. Phantom studies showed greater contrast recovery and signal to noise ratio for 10-min PET/MRI acquisitions compared to 2-min acquisitions using PET/CT. There were no discrepancies when PET/CT showed disseminated disease (P = 0.036). CONCLUSIONS: Extended PET/MRI acquisitions used to accommodate multiple MRI sequences may be associated with false-positive findings compared to PET/CT. PET/MRI is more likely to have incremental value when the prior probability for disseminated disease is low.

A photostable AIE luminogen with near infrared emission for monitoring morphological change of plasma membrane.

The morphology of plasma membrane is dynamic and keeps changing in order to maintain its homeostasis. Abnormality in cell membrane shape could be viewed as a sign of unhealthy cells. A lipophilic cyanostilbene derivative (AS2CP-TPA) composed of a hydrophilic pyridinium salt and a hydrophobic triphenylamino group was designed for staining the cell membrane and monitoring membrane morphology under different conditions. Due to strong donor-acceptor interaction and aggregation-induced emission property, AS2CP-TPA emits weak emission in aqueous solution, but it lights up the plasma membrance of HeLa cells with near infrared fluorescence under an excitation wavelength of 460 nm. With merits of high photostability and high specificity to plasma membrane, AS2CP-TPA is capable of long-term monitoring of the morphological changes of cell membrane during Hg2+ and trypsin treatments.

Mitochondrion-Anchoring Photosensitizer with Aggregation-Induced Emission Characteristics Synergistically Boosts the Radiosensitivity of Cancer Cells to Ionizing Radiation.

The first mitochondrion-anchoring photosensitizer that specifically generates singlet oxygen (1 O2 ) in mitochondria under white light irradiation that can serve as a highly effective radiosensitizer is reported here, significantly sensitizing cancer cells to ionizing radiation. An aggregation-induced emission luminogen (AIEgen), namely DPA-SCP, is rationally designed with α-cyanostilbene as a simple building block to reveal AIE, diphenylamino (DPA) group as a strong electron donating group to benefit red emission and efficient light-controlled 1 O2 generation, as well as a pyridinium salt as the targeting moiety to ensure specific mitochondrial localization. The AIE signature endows DPA-SCP with the capacity to visualize mitochondria in a fluorescence turn-on mode. It is found that under optimized experimental condition, DPA-SCP with white light does not lead to apoptosis/death of cancer cells, whereas provides an elevated 1 O2 environment in the mitochondria. More importantly, increasing intracellular level of 1 O2 originated from mitochondria is demonstrated to be a generic method to enhance the radiosensitivity of cancer cells with a supra-additive synergistic effect of "0 + 1 > 1." Noteworthy is that "DPA-SCP + white light" achieves a high SER10 value of 1.62, which is much larger than that of the most popularly used radiosensitizers, gold nanoparticles (1.19), and paclitaxel (1.32).

A red-emissive antibody-AIEgen conjugate for turn-on and wash-free imaging of specific cancer cells.

An antibody-AIEgen conjugate is designed and developed as a "turn-on" fluorescent probe for wash-free specific cancer cell imaging. The cetuximab-conjugated AIEgen shows red fluorescence only when it is internalized and accumulated in cancer cells with overexpressed epidermal growth factor receptor through endocytosis. The probe first lights up the lysosomes. After hydrolysis, its residue is accumulated in mitochondria, making them highly emissive with a long cell retention time. Compared with conventional "always-on" fluorescent probes, the antibody-AIEgen conjugate exhibits a very good image contrast during wash-free cancer cell imaging and less interference from normal cells. To the best of our knowledge, this is the first time "turn-on" antibody-AIEgen conjugates have been reported. This new strategy can be further extended to many proteins and water-soluble AIEgens, and many of their potential applications such as real-time tracking of cell dynamics and cancer theranostics will be explored. The present work is expected to inspire more marvellous research in the fields of AIE and cancer imaging.

A photostable AIEgen for nucleolus and mitochondria imaging with organelle-specific emission.

Dynamic visualization of the morphology of membrane-bound organelles offers useful insights for studying various intracellular activities. Fluorescent probes with superior specificity and photostability are desirable for long-term tracking of these processes. In this work, we present the design and synthesis of an α-cyanostilbene derivative, abbreviated as ASCP, with the aggregation-induced emission (AIE) characteristic, and its application in cell imaging. ASCP can simultaneously label mitochondria and nucleolus in live cells with distinct fluorescence, which is demonstrative of a single molecule with dual-colour organelle imaging.

Engineering of nanoparticle size via electrohydrodynamic jetting.

Engineering the physical properties of particles, especially their size, is an important parameter in the fabrication of successful carrier systems for the delivery of therapeutics. Here, various routes were explored for the fabrication of particles in the nanosize regime. It was demonstrated that the use of a charged species and/or solvent with high dielectric constant can influence the size and distribution of particles, with the charged species having a greater effect on the size of the particles and the solvent a greater effect on the distribution of the particles. In addition to the fabrication of nanoparticles, their fractionation into specific size ranges using centrifugation was also investigated. The in vitro particle uptake and intracellular transport of these nanoparticles was studied as a function of size and incubation period. The highest level of intralysosomal localization was observed for the smallest nanoparticle group (average of 174 nm), followed by the groups with increasing sizes (averages of 378 and 575 nm), most likely due to the faster endosomal uptake of smaller particles. In addition, the internalization of nanoparticle clusters and number of nanoparticles per cell increased with longer incubation periods. This work establishes a technological approach to compartmentalized nanoparticles with defined sizes. This is especially important as relatively subtle differences in size can modulate cell uptake and determine intercellular fate. Future work will need to address the role of specific targeting ligands on cellular uptake and intracellular transport of compartmentalized nanoparticles.

Prospective randomized controlled trial comparing plasmakinetic vaporesection and conventional transurethral resection of the prostate.

OBJECTIVE: Plasmakinetic vaporesection of the prostate (PKVP) using normal saline irrigation has the theoretical advantage of avoiding transurethral resection syndrome and minimizing blood loss. It may also shorten the operative time since tissue is resected instead of just vaporized. The aim of this study was to evaluate the efficiency, safety and advantages of PKVP compared with standard transurethral resection of the prostate (TURP) at a regional acute hospital. METHODS: A total of 60 consecutive men admitted from a waiting list for surgery for benign prostatic hyperplasia (BPH) were prospectively randomized to either PKVP or TURP. Peri- and postoperative outcome data at 3 months were obtained. RESULTS: The PKVP loop achieved a fast and sharp cutting action similar to that with the traditional TURP loop. Data analysis was based on 51 patients. There were no significant differences between the methods in resection time, postoperative catheterization time and hospital stay. The mean reductions in serum sodium 2 hours after PKVP and on postoperative day 1 were 0.52 mmol/L and 3.35 mmol/L, respectively, while mean reductions in haemoglobin were 0.36 g/dL and 0.24 g/dL, respectively. There was no significant difference in haemoglobin reductions between PKVP and TURP (p = 0.326 at 2 hours; p = 0.192 on day 1) and serum sodium (p = 0.757 at 2 hours; p = 0.888 on day 1). Both groups achieved comparable improvement in International Prostate Symptom Score (p = 0.862), quality-of-life score (p = 0.169) and peak flow rate (p = 0.96) at 3-month follow-up. CONCLUSION: PKVP achieved comparable results to traditional TURP and was an effective and safe procedure. However, it did not demonstrate obvious advantages over TURP in this acute regional hospital regular TURP list setting.

Real-time monitoring of the mitophagy process by a photostable fluorescent mitochondrion-specific bioprobe with AIE characteristics.

An isothiocyanate-functionalized tetraphenylethene is synthesized and used as a fluorescent bioprobe for mitochondrion imaging with high specificity and photostability. The covalent conjugation of the bioprobe to mitochondrial proteins endows it with high resistance to microenvironmental changes, enabling it for real-time monitoring of mitophagy.

Photostable AIE fluorogens for accurate and sensitive detection of S-phase DNA synthesis and cell proliferation.

Two azide-functionalized tetraphenylethene derivatives with AIE features are synthesized and used as fluorescent agents for detecting S-phase DNA synthesis and cell proliferation based on EdU assay. Compared to the Alexa-azide dye, a commercial DNA bioprobe, the AIE fluorogens show better photostability and sensitivity, making them promising alternatives.

A tetraphenylethene-based caged compound: synthesis, properties and applications.

A tetraphenylethene-based caged compound (TPE-C) is designed and synthesized. TPE-C is non-fluorescent either in solution or in aggregated state, but its emission can be induced to emit strong cyan emission in the aggregated state by UV irradiation. This property enables TPE-C to be applied in photo-patterning and anti-counterfeiting related areas.

Optimizing secondary prevention: Statin prescribing across East and West London in accordance with NICE guidelines.

OBJECTIVES: Statins are a well-known primary and secondary prevention drug for cardiovascular disease and NICE guidelines have been issued to identify key indicators for their use. An audit looking into statin prescribing for medical inpatients was carried out in two geographically distinct London hospitals. DESIGN: A prospective inpatient audit of medical prescription charts was performed. Blood results were reviewed for the inpatients during their admission to identify any contraindications for statin usage (rhabdomyolysis). The medical notes were also reviewed for patient refusal of statin therapy. SETTING: The study was carried out at two distinct hospitals in London. Whipps Cross University Hospital (WCUH) and Chelsea & Westminster Hospital (CWH) are located in East London and West London, respectively. Acute medical, surgical, obstetrics and gynaecology, paediatric and palliative wards were excluded. PARTICIPANTS: A total of 309 inpatient medical notes and prescription chart data were collected from WCUH (n = 211) and CWH (n = 98). MAIN OUTCOME MEASURES: High percentage of hospitalized patients are not prescribed statins despite clear clinical indications for their use. Regardless of geographical and socioeconomic factors between hospitals, statin prescribing remains suboptimal. RESULTS: The patient demographics in both hospitals were very similar; the mean age at WCUH was 78 ± 15 1SD while at CWH the mean age was 74 ± 15 1SD. The results showed that approximately one-third of patients (30% at WCUH and 33% at CWH) had at least one indication for statin therapy according to NICE guidelines and yet they were not prescribed a statin. Ten percent of patients at WCUH and 13% of patients at CWH had ischaemic heart disease (IHD) and yet were not prescribed statins. CONCLUSION: Statin prescription is often overlooked in secondary care with patients being discharged without the appropriate assessment (NICE guidelines), which subsequently means repeat prescriptions are not provided by the GP. This study is the first to show that this problem is not due to resources or geography, but is inherent within the NHS system. Consequently, a revised prescription chart checking system has been suggested for pharmacists and junior doctors.

False-positive MIBG uptake in pneumonia in a patient with stage IV neuroblastoma.

A 32-month-old female child with a history of stage IV favorable biology neuroblastoma with a 123-I MIBG (metaiodobenzylguanidine scan) avid adrenal mass, with retroperitoneal nodal extension and bony metastasis, was in complete remission after intense multimodal therapy. Seventeen months after diagnosis a surveillance 123-I MIBG scan showed abnormal tracer uptake in the midzone of the right thorax. Chest x-ray and CT scan confirmed right upper lobe consolidation corresponding to the tracer uptake. Chest x-ray after antibiotics showed resolution of the abnormality. 123-I MIBG scan 3 months later showed no abnormal uptake. False-positive MIBG uptake in pneumonia has not been previously reported.

The changing face of radiology: from local practice to global network.

Rapid advances in communications and computing technology have opened up new opportunities for clinical teleradiology. The quality of teleradiology reporting, when carried out properly, is on par with onsite reporting, and offers the potential for increased accuracy and improved patient outcomes. Local and international industry organisations and professional bodies are creating standards, policies and protocols for every aspect of teleradiology in response to concerns about the use of this technology. The key factor for the long-term success of teleradiology has been identified as a commitment to ensuring duty of care to patients (encompassing high-quality service and patient safety) is the first priority. Evidence indicates that increased use of teleradiology will be a step forward if managed well, but requires a commitment to excellence, patience and perseverance.