Addressing adolescent social and emotional concerns: Insights from loneliness, burnout, and preferred conversation topics in Asian and UK contexts post-pandemic.

This study investigated relationships between social and emotional concerns, loneliness, and school burnout, as these factors are associated with adaptive functioning during adolescence residence in Asia (i.e., China, Hong Kong) and the UK. Analysis of data from 2849 participants illuminated compelling insights. The participants reported a high level of loneliness, notably among girls in the UK. The research generated 11 preferred conversation topics (i.e., future and aspirations, anything, learning, nothing, mental health, personal interests, health, relationships, psychosocial issues, social issues, feelings). Among them, future and aspirations lead the way, aligning with developmental needs. A desire for mental health discussions coexisted with heightened loneliness and burnout among participants who pursued such conversations. The low achievers tended to talk about mental health issues or have nothing to say. High achievers were drawn to social issues, emphasizing their distinct socio-emotional needs. Forging a connection between personal interests and mitigated school burnout underscores the potential for individual passions to harmonize with educational experience. These findings underscore the exigency for bespoke interventions addressing the evolving emotional terrain of adolescents, especially in the pandemic's aftermath. The study's implications underscore the importance of empathetic listening and proactive engagement between adolescents and supportive adults. This research enriches the comprehension of pandemic-induced adolescent experiences and suggests avenues for future investigations into long-term emotional well-being. CLASSIFICATION CODE: 2800 (Developmental Psychology).

Shigella sonnei utilises colicins during inter-bacterial competition.

The mammalian colon is one of the most densely populated habitats currently recognised, with 1011-1013 commensal bacteria per gram of colonic contents. Enteric pathogens must compete with the resident intestinal microbiota to cause infection. Among these enteric pathogens are Shigella species which cause approximately 125 million infections annually, of which over 90 % are caused by Shigella flexneri and Shigella sonnei. Shigella sonnei was previously reported to use a Type VI Secretion System (T6SS) to outcompete E. coli and S. flexneri in in vitro and in vivo experiments. S. sonnei strains have also been reported to harbour colicinogenic plasmids, which are an alternative anti-bacterial mechanism that could provide a competitive advantage against the intestinal microbiota. We sought to determine the contribution of both T6SS and colicins to the anti-bacterial killing activity of S. sonnei. We reveal that whilst the T6SS operon is present in S. sonnei, there is evidence of functional degradation of the system through SNPs, indels and IS within key components of the system. We created strains with synthetically inducible T6SS operons but were still unable to demonstrate anti-bacterial activity of the T6SS. We demonstrate that the anti-bacterial activity observed in our in vitro assays was due to colicin activity. We show that S. sonnei no longer displayed anti-bacterial activity against bacteria that were resistant to colicins, and removal of the colicin plasmid from S. sonnei abrogated anti-bacterial activity of S. sonnei. We propose that the anti-bacterial activity demonstrated by colicins may be sufficient for niche competition by S. sonnei within the gastrointestinal environment.

Long-range air dispersion of Candida auris in a cardiothoracic unit outbreak in Hong Kong.

BACKGROUND: Nosocomial outbreaks of Candida auris, a multidrug-resistant fungus, are increasingly reported worldwide; the mode of transmission has usually been reported to be via direct contact. Some studies previously suggested potential short-distance air dispersal during high-turbulence activities, but evidence on long-range air dispersal remains scarce. AIM: To describe a C. auris nosocomial outbreak involving two wards (H7, 5E) in two local hospitals. METHODS: Samples were taken from patients, ward surfaces (frequently touched items and non-reachable surfaces) while settle plates were used for passive air sampling to investigate possible contributions by direct contact and air dispersal. Epidemiological and phylogenetic analyses were also performed on the C. auris isolates from this outbreak. FINDINGS: Eighteen patients were confirmed to have asymptomatic C. auris skin colonization. C. auris was expectedly identified in samplings from frequently touched ward items but was also isolated in two samples from ceiling supply air grilles which were 2.4 m high and inaccessible by patients. Moreover, one sample from a corridor return air grille as far as 9.8 m away from the C. auris cohort area was also positive. Two passive air samplings were positive, including one from a cubicle with no confirmed cases for four days, suggesting possible air dispersal of C. auris. Whole-genome sequencing confirmed clonality of air, environment, and patients' isolates. CONCLUSION: This is the first study to demonstrate potential long-range air dispersal of C. auris in an open-cubicle ward setting. Ventilation precautions and decontamination of out-of-reach high-level surfaces should be considered in C. auris outbreak management.

Associations between diet composition, dietary pattern, and weight outcomes after bariatric surgery: a systematic review.

INTRODUCTION: Literature describing the impact of dietary intake on weight outcomes after bariatric surgery has not been synthesized. This study aimed to synthesize the evidence regarding any association between diet composition and weight outcomes post-bariatric surgery. METHODS: CINAHL, Cochrane, Embase, MEDLINE and Scopus were searched for adult studies up to June 2021 that assessed any association between dietary intakes (≥1-macronutrient, food group, or dietary pattern) and weight outcomes at 12-months or longer after bariatric surgery. Risk of bias and quality assessments were conducted using the Scottish Intercollegiate Guidelines Network checklists and the NHMRC's Level of Evidence and Grades for Recommendations. Study findings were presented according to the time of post-surgery dietary intake assessment (≤12months, between 12 and 24 months, ≥24months). RESULTS: 5923 articles were identified, 260 were retrieved for full text screening, and 36 were eligible for inclusion (9 interventional including five randomized-controlled trials, and 27 observational cohort studies; sample sizes: 20-1610; total sample: 5065; follow-up periods: 1 year-12 years; level of evidence: II to IV, risk of bias: low to high). Findings on the association between long-term weight outcomes and dietary composition up to 24-months were mixed. After 24-months, studies consistently suggested no significant associations between weight loss and macronutrient composition or core food group patterns, or between carbohydrate, protein or food group patterns and weight recurrence. A single cohort study reported a weak association between diet quality score and weight-recurrence after 24-months. CONCLUSION: There was no strong evidence to support significant associations between diet composition and weight outcomes post-bariatric surgery. The heterogeneity in study design and quality may reduce generalizability to external populations. Individualized dietary recommendations may be useful to support long-term post-surgery weight outcomes. More studies are needed to define and measure diet quality in this patient cohort. REGISTRATION: PROSPERO (CRD42021264120).

An 80-million-year sulphur isotope record of pyrite burial over the Permian-Triassic.

Despite the extensive use of sulphur isotope ratios (δ34S) for understanding ancient biogeochemical cycles, many studies focus on specific time-points of interest, such as the end-Permian mass extinction (EPME). We have generated an 80 million-year Permian-Triassic δ34Sevap curve from the Staithes S-20 borehole, Yorkshire, England. The Staithes δ34Sevap record replicates the major features of the global curve, while confirming a new excursion at the Olenekian/Anisian boundary at ~ 247 million years ago. We incorporate the resultant δ34Sevap curve into a sulphur isotope box model. Our modelling approach reveals three significant pyrite burial events (i.e. PBEs) in the Triassic. In particular, it predicts a significant biogeochemical response across the EPME, resulting in a substantial increase in pyrite burial, possibly driven by Siberian Traps volcanism. Our model suggests that after ~ 10 million years pyrite burial achieves relative long-term stability until the latest Triassic.

The dynamics of indigenous epiphytic bacterial and fungal communities of barley grains through the commercial malting process in Western Canada.

Microbial activity is present at every step of the malting process. It is, therefore, critical to manage the grain-associated microbial communities for the production of high-quality malts. This study characterized barley and malt epiphytic microbiota by metabarcoding the internal transcribed spacer (ITS) 2 region and the 16S rRNA gene V1-V4 metabarcodes, respectively. We elucidated the changes in the diversity and the compositional and functional changes of the grain-associated microbiota and inferred the impact of such changes on malting efficiency and premature yeast flocculation (PYF) of the commercial malt end product. Through the malting process, the fungal diversity decreased while bacterial community diversity increased. Lactic acid bacteria (LAB) and some mycotoxin-producing fungi (e.g. Fusarium spp.) were found to be significantly enriched in malts. Most potential fungal pathogens, however, did not change in abundance through the malting process. Fungi (e.g. Aureobasidium, Candida) and bacteria (e.g. LAB, Arthrobacter, Brachybacterium) with the potential to generate organic acids or exhibit high hydrolytic enzymatic activity for degrading the endosperm cell walls and storage proteins were detected in greater abundance in kilned malt, suggesting their contribution to malting efficiency. Bacterial and fungal operational taxonomic units (OTUs) associated with PYF-positive malt were mainly identified as Aureobasidium, Candida, and Leuconostoc, while Pleosporaceae, Steptococcus, and Leucobacter were associated with PYF-negative malt. The ecological networks of the field and steeped barley samples were found to be larger and denser, while that of the malt microbiome was smaller and less connected. A decrease in the proportion of negative interactions through the malting process suggested that malting destabilized the microbial networks. In summary, this study profiled the microbiota of commercial malting barley and malt samples in western Canada; the findings expanded our knowledge in the microbiology of malting while providing potential insights regarding the management of microbial-associated problems, such as PYF, in commercial malting.

Corrigendum to "Validation of the 5-D Itch Scale in Three Ethnic Groups and Exploring Optimal Cutoff Values Using the Itch Numerical Rating Scale".

[This corrects the article DOI: 10.1155/2021/7640314.].

Measurement invariance of the Multidimensional Depression Assessment Scale (MDAS) across gender and ethnic groups of Asian, Caucasian, Black, and Hispanic.

BACKGROUND: Major Depressive Disorder is a severe and highly disabling mental illness. Almost all self-reported questionnaires have overlooked the interpersonal symptoms of depression which are important across gender and culture. The Multidimensional Depression Assessment Scale (MDAS) developed by Cheung and Power (2012) entails comprehensive emotional, cognitive, somatic, and interpersonal subscales. It addresses the criticism that existing self-report depression scales might not cover sufficient phenomenological heterogeneity of depression. The current study aimed to evaluate the psychometric properties of the MDAS across gender and four major ethnic groups of Caucasian, Black, Asian and Hispanic, including reliability and concurrent validity against the Centre for Epidemiological Studies Depression Scale (CESD) and Patients Health Questionnaire (PHQ-9). It also aimed to establish a stable factor structure across gender and ethnic groups and test the measurement invariance to enhance its potential for clinical use. METHODS: A community sample of 3499 participants from four ethnic groups were recruited via online crowdsourcing sites of Qualtrics and Amazon M Turk. Each individual completed a demographic questionnaire, the MDAS, CESD and PHQ-9. RESULTS: There was good internal consistency (Cronbach's alpha >0.90) and concurrent reliability across gender and ethnic groups. Strict measurement invariance was established for MDAS over a four-factor factor structure corresponding to the four subscales. CONCLUSIONS: The MDAS showed good psychometric properties and measurement invariance of a four-factor structure, suggesting its potential to be used in clinical settings across gender and ethnic groups. LIMITATIONS: Participants all answered the questionnaires in English, which could hinder cultural variations in their expression of symptoms.

Validation of the 5-D Itch Scale in Three Ethnic Groups and Exploring Optimal Cutoff Values Using the Itch Numerical Rating Scale.

BACKGROUND: Chronic pruritus is a common and distressing condition that has serious emotional and psychosocial consequences. Due to its subjective nature, self-report questionnaires are widely implemented as cost-effective measures to gauge the severity of chronic pruritus. The current study is aimed at validating the 5-D itch scale in three ethnic groups-Black, Asian, and Hispanic-with the well-validated Itch Numerical Rating Scale (NRS) and Worst Itch NRS (WI-NRS) and developing its cutoff value using receiver operating characteristics (ROC) and inspection of the area under the curve (AUC) across ethnic groups. At the same time, it is aimed at comparing the concurrent prevalence of itch and depression in these populations, who often form ethnic minorities in many countries. The current study addresses the knowledge gap of cultural adaptation of the 5-D pruritus scale for greater usage. METHODS: Community samples of three ethnic groups were recruited from an online platform of Qualtrics and administered the self-report questionnaires of Itch-NRS, 5-D itch scale, and Patient Health Questionnaire-9 (PHQ-9) to measure their pruritus domains, itch intensity, depression screening, and its severity. Informed consent was obtained from all participants. Subgroup analysis was conducted, including concurrent validity and cutoff values compared between each ethnic group. Concurrent prevalence of itch and depression was evaluated using the cutoff value of Itch-NRS and PHQ-9. RESULT: A total of 2323 participants were included in the study. A significant positive correlation (p < 0.001) was found between the Itch-NRS, WI-NRS, and 5-D itch scale. The cutoff value of the 5-D itch scale was established for the three ethnic groups using ROC, with a cutoff value of Itch-NRS as a reference. CONCLUSIONS: The 5-D itch scale has demonstrated sound psychometric properties in three ethnic groups and is closely related to Itch-NRS. The analysis of the cutoff value of the 5-D itch scale suggests that different cutoff values should be considered to reduce the inflation of pruritus severity.

Challenges and opportunities for artificial intelligence in oncological imaging.

Imaging plays a key role in oncology, including the diagnosis and detection of cancer, determining clinical management, assessing treatment response, and complications of treatment or disease. The current use of clinical oncology is predominantly qualitative in nature with some relatively crude size-based measurements of tumours for assessment of disease progression or treatment response; however, it is increasingly understood that there may be significantly more information about oncological disease that can be obtained from imaging that is not currently utilized. Artificial intelligence (AI) has the potential to harness quantitative techniques to improve oncological imaging. These may include improving the efficiency or accuracy of traditional roles of imaging such as diagnosis or detection. These may also include new roles for imaging such as risk-stratifying patients for different types of therapy or determining biological tumour subtypes. This review article outlines several major areas in oncological imaging where there may be opportunities for AI technology. These include (1) screening and detection of cancer, (2) diagnosis and risk stratification, (3) tumour segmentation, (4) precision oncology, and (5) predicting prognosis and assessing treatment response. This review will also address some of the potential barriers to AI research in oncological imaging.

Porcine dermal collagen mesh (Permacol™) as a bioprosthesis in the ligation of intersphincteric tract (BioLIFT) procedure.

BACKGROUND: Ligation of intersphincteric tract (LIFT) is a sphincter-saving technique used to treat anal fistulas. Incorporation of a bioprosthesis in LIFT (BioLIFT) aims to improve healing. The use of cross-linked porcine dermal collagen mesh Permacol™ in BioLIFT has never been investigated. The aim of this study was to compare the healing rates and outcome of LIFT and BioLIFT for complex anal fistulas using the Permacol™ biological mesh. METHODS: A retrospective analysis of all patients having LIFT or BioLIFT for complex fistulas from January 2010 to November 2019 was performed in a tertiary referral centre. Patient data from a prospectively collected database of all patients having LIFT or BioLIFT were analyzed. RESULTS: LIFT and BioLIFT were performed in 48 (82.8%) and 10 (17.2%) patients, respectively. All BioLIFT patients had previous interventions for their fistulas compared to 30 (62.5%) of patients who had LIFT, p = 0.023. The primary healing rate for LIFT was 87.5% (42/48) compared to 80% (8/10) in BioLIFT, (p = 0.42). Eight (13.8%) patients developed complications, 6 (12.5%) in the LIFT group vs 2 (20%) in the BioLIFT group (p = 0.62). On univariate analysis, the number of previous operations was predictive of complications (p = 0.03). BioLIFT was not associated with complication (OR = 1.75, 95% CI: 0.30-10.3, p = 0.54) or primary healing (OR = 0.57, 95% CI: 0.97-3.36, p = 0.54). There was no significant difference in recurrence (LIFT 12.5% vs BioLIFT 0%, p = 0.58). Kaplan-Meier analysis found no difference in time to recurrence between the two groups (p = 0.65). CONCLUSION: Permacol™ mesh in BioLIFT is feasible and achieves a high primary healing rate of 80%. Prospective evidence is needed to establish the benefits of BioLIFT and determine whether Permacol™ is superior to the non-cross-linked porcine submucosal mesh.

Naturally Occurring Cardenolides Affecting Schistosoma mansoni.

Schistosomiasis is a neglected tropical disease of considerable public health burden. We recently discovered a micromolar activity of several cardenolides against newly transformed schistosomula (NTS) of the parasitic flatworm Schistosoma mansoni in a small compound screen including different substance classes of both natural products as well as synthetic molecules. In further experiments, a focused library of naturally occurring and synthetic steroids was explored against NTS and adult S. mansoni, revealing seven cardenolides with comparable activities as known anthelminthics such as praziquantel. Of these, gomphoside monoacetate and uscharin showed suitable therapeutic indices. In a first in vivo study, at a dose of 10 mg/kg, only minor activity in mice harboring a chronic S. mansoni infection could be shown, which will be further investigated by structure-activity relationship studies as well as pharmacodynamic and pharmacokinetic approaches.

Brain death in children: a retrospective review of patients at a paediatric intensive care unit.

PURPOSE: Among patients in paediatric intensive care units (PICUs), death is sometimes inevitable despite advances in treatment. Some PICU patients may have irreversible cessation of all brain function, which is considered as brain death (BD). This study investigated demographic and clinical differences between PICU patients with BD and those with cardiopulmonary death. METHODS: All children who died in the PICU at a university-affiliated trauma centre between October 2002 and October 2018 were included in this retrospective study. Demographics and clinical characteristics were compared between patients with BD and patients with cardiopulmonary death. RESULTS: Of the 2784 patients admitted to the PICU during the study period, 127 died (4.6%). Of these 127 deaths, 22 (17.3%) were BD and 105 were cardiopulmonary death. Length of PICU stay was shorter for patients with cardiopulmonary death than for patients with BD (2 vs 8.5 days, P=0.0042). The most common mechanisms of injury in patients with BD were hypoxic-ischaemic injury (40.9%), central nervous system infection (18.2%), and traumatic brain injury (13.6%). The combined proportion of accident and trauma-related injury was greater in patients with BD than in patients with cardiopulmonary death (27.3% vs 3.8%, P<0.001). Organ donation was approved by the families of four of the 22 patients with BD (18.2%) and was performed successfully in three of these four patients. CONCLUSIONS: These findings emphasise the importance of injury prevention in childhood, as well as the need for education of the public regarding acceptance of BD and support for organ donation.

Association between biochemical control and comorbidities in patients with acromegaly: an Italian longitudinal retrospective chart review study.

PURPOSE: Achieving biochemical control (normalization of insulin-like growth factor-1 [IGF-1] and growth hormone [GH]) is a key goal in acromegaly management. However, IGF-1 and GH fluctuate over time. The true potential impact of time-varying biochemical control status on comorbidities is unclear and relies on multiple, longitudinal IGF-1 and GH measurements. This study assessed the association between time-varying biochemical control status and onset of selected comorbidities in patients with acromegaly. METHODS: Medical charts of adults with confirmed acromegaly and ≥ 6 months of follow-up at an Italian endocrinology center were reviewed. Patients were followed from the first diagnosis of acromegaly at the center until loss to follow-up, chart abstraction, or death. Biochemical control status was assessed annually and defined as IGF-1 ≤ the upper limit of normal, or GH ≤ 2.5 µg/L in the few cases where IGF-1 was unavailable. Time-varying Cox models were used to assess the association between biochemical control status and comorbidities. RESULTS: Among 150 patients, 47% were female, average age at diagnosis was 43.1, and mean length of follow-up was 10.4 years. Biochemical control was significantly associated with a lower hazard of diabetes (HR = 0.36, 95% CI 0.15; 0.83) and cardiovascular system disorders (HR = 0.54, 95% CI 0.31; 0.93), and a higher hazard of certain types of arthropathy (HR = 1.68, 95% CI 1.04; 2.71); associations for other comorbidities did not reach statistical significance. CONCLUSION: Results further support the importance of achieving biochemical control, as this may reduce the risk of high-burden conditions, including diabetes and cardiovascular system disorders. The association for arthropathy suggests irreversibility of this impairment. Due to limitations, caution is required when interpreting these results.

Survey on common reference intervals for general chemistry analytes in Hong Kong.

INTRODUCTION: Reference intervals (RIs) are essential tool for proper interpretation of results. There is a global trend towards implementing common RIs to avoid confusion and enhance patient management across different laboratories. However, local practices with respect to RIs lack harmonisation. METHODS: We have conducted the first local survey regarding RIs for 14 general chemistry analytes in 10 chemical pathology laboratories that employ four different analytical platforms (Abbott Architect, Beckman Coulter AU, Roche Cobas, and Siemens Dimension EXL). Analytical bias was assessed by an inter-laboratory results comparison of external quality assurance programmes. RESULTS: Sufficient inter-laboratory and inter-platform agreement regarding the 10 analytes (albumin, alanine aminotransferase, aspartate aminotransferase, chloride, gamma-glutamyl transferase, phosphate, potassium, sodium, total protein, and urea) were demonstrated. However, the RIs were heterogeneous across all laboratories, with percentage differences of the upper RI value of up to 47% for aspartate aminotransferase (absolute difference of 16 U/L), 29% for urea (1.8 mmol/L), and 18% for potassium (0.8 mmol/L). The percentage difference between lower RI values was up to 24% for urea (0.6 mmol/L), 22% for phosphate (0.16 mmol/L), and 8% for total protein (5 g/L). The coefficients of variation of the upper RI values of potassium and sodium were 1.2 times and 1.0 times of their corresponding between-subject biological variation, respectively, representing unnecessary variations that are overlooked and unchecked in current practice. CONCLUSIONS: We recommend the use of common RIs for general chemistry analytes in Hong Kong to prevent interpreter confusion, improve electronic data transfer, and unite laboratory practice. This is the first local study on this topic, and our data can lay the groundwork for increasing harmonisation of RIs across more laboratory tests.

Seasonal variation of chemical characteristics of fine particulate matter at a high-elevation subtropical forest in East Asia.

The aim of this study was to chemically characterize the fine particulate matter (PM2.5) at a subtropical forest in East Asia under the influences of anthropogenic and biogenic sources and a complex topographic setting. Four seasonal campaigns were conducted at the Xitou Experimental Forest in central Taiwan from the winter of 2013 to the autumn of 2014. The results indicated that the ambient levels and chemical features of PM2.5 exhibited pronounced seasonal variations. Non-sea-salt sulfate (nss-SO42-) constituted the major component of PM2.5, followed by ammonium (NH4+) and nitrate (NO3-) during winter, summer and autumn. However, it was revealed that the mass fraction of NO3- increased to be comparable with that of nss-SO42- in springtime. The mass contribution of secondary organic carbon (SOC) to PM2.5 peaked in summer (13.2%), inferring the importance of enhanced photo-oxidation reactions in SOC formation. Diurnal variations of O3 and SO2 coincided with each other, suggesting the transport of aged pollutants from distant sources, whereas CO and NOx were shown to be under the influences of both local and regional sources. Notably high sulfur oxidation ratio (SOR) and nitrogen oxidation ratio (NOR) were observed, which were 0.93 ±â€¯0.05 and 0.39 ±â€¯0.20, respectively. Precursor gases (i.e. SO2 and NOx) could be converted to sulfate and nitrate during the transport by the uphill winds. Furthermore, due to the high relative humidity at Xitou, enhanced aqueous-phase and/or heterogeneous reactions could further contribute to the formation of sulfate and nitrate at the site. This study demonstrated the significant transport of urban pollutants to a subtropical forest by the mountain-valley circulations as well as the long-range transport from regional sources, whereas the implications of which for regional climate change necessitated further investigation.

Validation and modification of the Ottawa subarachnoid haemorrhage rule in risk stratification of Asian Chinese patients with acute headache.

OBJECTIVE: To validate the Ottawa subarachnoid haemorrhage (SAH) rule in an Asian Chinese cohort and to explore the roles of blood pressure and vomiting in prediction of SAH in patients with nontraumatic acute headache. METHODS: A retrospective cohort study was conducted in two regional hospitals. All patients aged ≥16 years who presented with non-traumatic acute headache to the study centres from July 2013 to June 2016 were included. A logistic regression model was created for the variables of the Ottawa SAH rule and other potential predictors, including vomiting and systolic blood pressure (SBP) >160 mm Hg. Model discrimination was evaluated using the area under the receiver operating characteristic curve. Net reclassification improvement and integrated discrimination improvement indices were evaluated. The model's diagnostic characteristics, including sensitivities and specificities, were evaluated. RESULTS: A total of 500 eligible headache cases were included, in 50 of which SAH was confirmed (10%). In addition to the predictors of the Ottawa SAH rule, vomiting and SBP >160 mm Hg were found to be significant independent predictors of SAH. Net reclassification improvement and integrated discrimination improvement indices indicated that including vomiting and SBP >160 mm Hg would improve the model prediction. The Ottawa SAH rule had 94% sensitivity and 32.9% specificity. The modified Ottawa SAH rule that included both vomiting and SBP >160 mm Hg as criteria improved sensitivity to 100%, specificity to 13.1%, positive predictive value to 11.3%, and negative predictive value to 100%. CONCLUSIONS: The Ottawa SAH rule demonstrated high sensitivity. Addition of vomiting and SBP >160 mm Hg to the Ottawa SAH rule may increase its sensitivity.

Molecular Imaging of Radiolabeled Bispecific T-Cell Engager 89Zr-AMG211 Targeting CEA-Positive Tumors.

Purpose: AMG 211, a bispecific T-cell engager (BiTE) antibody construct, targets carcinoembryonic antigen (CEA) and the CD3 epsilon subunit of the human T-cell receptor. AMG 211 was labeled with zirconium-89 (89Zr) or fluorescent dye to evaluate the tumor-targeting properties.Experimental Design: 89Zr-AMG211 was administered to mice bearing CEA-positive xenograft tumors of LS174T colorectal adenocarcinoma or BT474 breast cancer cells, as well as CEA-negative HL-60 promyelocytic leukemia xenografts. Biodistribution studies with 2- to 10-µg 89Zr-AMG211 supplemented with unlabeled AMG 211 up to 500-µg protein dose were performed. A BiTE that does not bind CEA, 89Zr-Mec14, served as a negative control. 89Zr-AMG211 integrity was determined in tumor lysates ex vivo Intratumoral distribution was studied with IRDye800CW-AMG211. Moreover, 89Zr-AMG211 was manufactured according to Good Manufacturing Practice (GMP) guidelines for clinical trial NCT02760199Results: 89Zr-AMG211 demonstrated dose-dependent tumor uptake at 6 hours. The highest tumor uptake was observed with a 2-µg dose, and the lowest tumor uptake was observed with a 500-µg dose. After 24 hours, higher uptake of 10-µg 89Zr-AMG211 occurred in CEA-positive xenografts, compared with CEA-negative xenografts. Although the blood half-life of 89Zr-AMG211 was approximately 1 hour, tumor retention persisted for at least 24 hours. 89Zr-Mec14 showed no tumor accumulation beyond background level. Ex vivo autoradiography revealed time-dependent disintegration of 89Zr-AMG211. 800CW-AMG211 was specifically localized in CEA-expressing viable tumor tissue. GMP-manufactured 89Zr-AMG211 fulfilled release specifications.Conclusions: 89Zr-AMG211 showed dose-dependent CEA-specific tumor targeting and localization in viable tumor tissue. Our data enabled its use to clinically evaluate AMG 211 in vivo behavior. Clin Cancer Res; 24(20); 4988-96. ©2018 AACR.