A bispecific antibody targeting HLA-DQ2.5-gluten peptides potently blocks gluten-specific T cells induced by gluten ingestion in patients with celiac disease.

The gluten-free diet for celiac disease (CeD) is restrictive and often fails to induce complete symptom and/or mucosal disease remission. Central to CeD pathogenesis is the gluten-specific CD4+ T cell that is restricted by HLA-DQ2.5 in over 85% of CeD patients, making HLA-DQ2.5 an attractive target for suppressing gluten-dependent immunity. Recently, a novel anti-HLA-DQ2.5 antibody that specifically recognizes the complexes of HLA-DQ2.5 and multiple gluten epitopes was developed (DONQ52). OBJECTIVE: To assess the ability of DONQ52 to inhibit CeD patient-derived T-cell responses to the most immunogenic gluten peptides that encompass immunodominant T cell epitopes. METHODS: We employed an in vivo gluten challenge model in patients with CeD that affords a quantitative readout of disease-relevant gluten-specific T-cell responses. HLA-DQ2.5+ CeD patients consumed food containing wheat, barley, or rye for 3 days with collection of blood before (D1) and 6 days after (D6) commencing the challenge. Peripheral blood mononuclear cells were isolated and assessed in an interferon (IFN)-γ enzyme-linked immunosorbent spot assay (ELISpot) testing responses to gluten peptides encompassing a series of immunodominant T cell epitopes. The inhibitory effect of DONQ52 (4 or 40 µg/mL) was assessed and compared to pan-HLA-DQ blockade (SPVL3 antibody). RESULTS: In HLA-DQ2.5+ CeD patients, DONQ52 reduced T cell responses to all wheat gluten peptides to an equivalent or more effective degree than pan-HLA-DQ antibody blockade. It reduced T cell responses to a cocktail of the most immunodominant wheat epitopes by a median of 87% (IQR 72-92). Notably, DONQ52 also substantially reduced T-cell responses to dominant barley hordein and rye secalin derived peptides. DONQ52 had no effect on T-cell responses to non-gluten antigens. CONCLUSION: DONQ52 can significantly block HLA-DQ2.5-restricted T cell responses to the most highly immunogenic gluten peptides in CeD. Our findings support in vitro data that DONQ52 displays selectivity and broad cross-reactivity against multiple gluten peptide:HLA-DQ2.5 complexes. This work provides proof-of-concept multi-specific antibody blockade has the potential to meaningfully inhibit pathogenic gluten-specific T-cell responses in CeD and supports ongoing therapeutic development.

Whole blood interleukin-2 release test to detect and characterize rare circulating gluten-specific T cell responses in coeliac disease.

Whole blood cytokine release assays (CRA) assessing cellular immunity to gluten could simplify the diagnosis and monitoring of coeliac disease (CD). We aimed to determine the effectiveness of electrochemiluminescence CRA to detect responses to immunodominant gliadin peptides. HLA-DQ2·5+ CD adults (cohort 1, n = 6; cohort 2, n = 12) and unaffected controls (cohort 3, n = 9) were enrolled. Cohort 1 had 3-day gluten challenge (GC). Blood was collected at baseline, and for cohort 1 also at 3 h, 6 h and 6 days after commencing 3-day GC. Gliadin peptide-stimulated proliferation, interferon (IFN)-γ enzyme-linked immunospot (ELISPOT) and 14- and 3-plex electrochemiluminescence CRA were performed. Poisson distribution analysis was used to estimate responding cell frequencies. In cohort 1, interleukin (IL)-2 dominated the gliadin peptide-stimulated cytokine release profile in whole blood. GC caused systemic IL-2 release acutely and increased gliadin peptide-stimulated IFN-γ ELISPOT and whole blood CRA responses. Whole blood CRA after GC was dominated by IL-2, but also included IFN-γ, C-X-C motif chemokine ligand 10/IFN-γ-induced protein 10 (CXCL10/IP-10), CXCL9/monokine induced by IFN-γ (MIG), IL-10, chemokine (C-C motif) ligand 3/macrophage inflammatory protein 1-alpha (CCL3/MIP-1α), TNF-α and IL-8/CXCL8. In cohorts 2 and 3, gliadin peptide-stimulated whole blood IL-2 release was 100% specific and 92% sensitive for CD patients on a gluten-free diet; the estimated frequency of cells in CD blood secreting IL-2 to α-gliadin peptide was 0·5 to 11 per ml. Whole blood IL-2 release successfully mapped human leucocyte antigen (HLA)-DQ2·5-restricted epitopes in an α-gliadin peptide library using CD blood before and after GC. Whole blood IL-2 release assay using electrochemiluminescence is a sensitive test for rare gliadin-specific T cells in CD, and could aid in monitoring and diagnosis. Larger studies and validation with tetramer-based assays are warranted.

Management of the thrombotic risk associated with COVID-19: guidance for the hemostasis laboratory.

Coronavirus disease 2019 (COVID-19) is associated with extreme inflammatory response, disordered hemostasis and high thrombotic risk. A high incidence of thromboembolic events has been reported despite thromboprophylaxis, raising the question of a more effective anticoagulation. First-line hemostasis tests such as activated partial thromboplastin time, prothrombin time, fibrinogen and D-dimers are proposed for assessing thrombotic risk and monitoring hemostasis, but are vulnerable to many drawbacks affecting their reliability and clinical relevance. Specialized hemostasis-related tests (soluble fibrin complexes, tests assessing fibrinolytic capacity, viscoelastic tests, thrombin generation) may have an interest to assess the thrombotic risk associated with COVID-19. Another challenge for the hemostasis laboratory is the monitoring of heparin treatment, especially unfractionated heparin in the setting of an extreme inflammatory response. This review aimed at evaluating the role of hemostasis tests in the management of COVID-19 and discussing their main limitations.

First Robinsoniella peoriensis aortic cross homograft mycotic pseudoaneurysm: A case report and review of the literature.

Mycotic aortic aneurysm is a rare and challenging complication of aortic homografts caused by an infection and is associated with high morbidity and mortality. We report the first case of an aortic cross homograft mycotic pseudoaneurysm caused by Robinsoniella peoriensis in a 70-year-old man. Our patient underwent surgery for a recurrence of aortic cross mycotic pseudoaneurysm at the level of the aortic homograft he had had 7 years before. A clot-removal of the pseudoaneurysm was surgically carried out and the homograft was completely removed. Anaerobic culture from tissue samples yielded pure growth of a spore-forming Gram-positive rod, identified later as Robinsoniella peoriensis by 16S rRNA gene sequencing. The patient was then discharged with oral clindamycin according to the in vitro susceptibility testing. Identification of R. peoriensis might be challenging in clinical laboratories with no access to molecular methods.

Assessment of risk of peripheral vascular disease and vascular care capacity in low- and middle-income countries.

BACKGROUND: This study aimed to describe national peripheral vascular disease (PVD) risk and health burden, and vascular care capacity in Ghana. The gap between PVD burden and vascular care capacity in low- and middle-income countries was defined, and capacity improvement priorities were identified. METHODS: Data to estimate PVD risk factor burden were obtained from the World Health Organization Study on Global Ageing and Adult Health (SAGE), Ghana, and the Institute of Health Metrics and Evaluation Global Burden of Disease (IHME GBD) database. In addition, a novel nationwide assessment of vascular care capacity was performed, with 20 vascular care items assessed at 40 hospitals in Ghana. Factors contributing to specific item deficiency were described. RESULTS: From the SAGE database, there were 4305 respondents aged at least 50 years with data to estimate PVD risk. Of these, 57·4 per cent were at moderate to risk high of PVD with at least three risk factors; extrapolating nationally, the estimate was 1 654 557 people. Based on IHME GBD data, the estimated disability-adjusted life-years incurred from PVD increased fivefold from 1990 to 2010 (from 6·3 to 31·7 per 100 000 persons respectively). Vascular care capacity assessment demonstrated marked deficiencies in items for diagnosis, and in perioperative and vascular surgical care. Deficiencies were most often due to absence of equipment, lack of training and technology breakage. CONCLUSION: Risk factor reduction and management as well as optimization of current resources are paramount to avoid the large burden of PVD falling on healthcare systems in low- and middle-income countries. These countries are not well equipped to handle vascular surgical care, and rapid development of such capacity would be difficult and expensive.

Ruthenium photoredox-triggered phospholipid membrane formation.

As more methodologies for generating and manipulating biomimetic cellular systems are developed, opportunities arise for combining different methods to create more complex synthetic biological constructs. This necessitates an increasing need for tools to selectively trigger individual methodologies. Here we demonstrate ruthenium tris-bipyridine mediated photoredox triggering of the copper catalyzed alkyne azide cycloaddition reaction (CuAAC), resulting in the synthesis of biomimetic phospholipids in situ, and subsequent membrane assembly. The use of a ruthenium-copper electron transport chain to trigger phospholipid assembly opens up future opportunities for spatiotemporal synthesis of membranes.

Exogenous administration of protease-resistant, non-matrix-binding IGFBP-2 inhibits tumour growth in a murine model of breast cancer.

BACKGROUND: Insulin-like growth factors (IGF-I and IGF-II) signal via the type 1 IGF receptor (IGF-1R) and IGF-II also activates the insulin receptor isoform A (IR-A). Signalling via both receptors promotes tumour growth, survival and metastasis. In some instances IGF-II action via the IR-A also promotes resistance to anti-IGF-1R inhibitors. This study assessed the efficacy of two novel modified IGF-binding protein-2 (IGFBP-2) proteins that were designed to sequester both IGFs. The two modified IGFBP-2 proteins were either protease resistant alone or also lacked the ability to bind extracellular matrix (ECM). METHODS: The modified IGFBP-2 proteins were tested in vitro for their abilities to inhibit cancer cell proliferation and in vivo to inhibit MCF-7 breast tumour xenograft growth. RESULTS: Both mutants retained low nanomolar affinity for IGF-I and IGF-II (0.8-2.1-fold lower than IGFBP-2) and inhibited cancer cell proliferation in vitro. However, the combined protease resistant, non-matrix-binding mutant was more effective in inhibiting MCF-7 tumour xenograft growth and led to inhibition of angiogenesis. CONCLUSIONS: By removing protease cleavage and matrix-binding sites, modified IGFBP-2 was effective in inhibiting tumour growth and reducing tumour angiogenesis.

Kidneys at higher risk of discard: expanding the role of dual kidney transplantation.

Half of the recovered expanded criteria donor (ECD) kidneys are discarded in the United States. A new kidney allocation system offers kidneys at higher risk of discard, Kidney Donor Profile Index (KDPI)>85%, to a wider geographic area to promote broader sharing and expedite utilization. Dual kidney transplantation (DKT) based on the KDPI is a potential option to streamline allocation of kidneys which otherwise would have been discarded. To assess the clinical utility of the KDPI in kidneys at higher risk of discard, we analyzed the OPTN/UNOS Registry that included the deceased donor kidneys recovered between 2002 and 2012. The primary outcomes were allograft survival, patient survival and discard rate based on different KDPI categories (<80%, 80-90% and >90%). Kidneys with KDPI>90% were associated with increased odds of discard (OR=1.99, 95% CI 1.74-2.29) compared to ones with KDPI<80%. DKTs of KDPI>90% were associated with lower overall allograft failure (HR=0.74, 95% CI 0.62-0.89) and better patient survival (HR=0.79, 95% CI 0.64-0.98) compared to single ECD kidneys with KDPI>90%. Kidneys at higher risk of discard may be offered in the up-front allocation system as a DKT. Further modeling and simulation studies are required to determine a reasonable KDPI cutoff percentile.

Ex-vivo whole blood secretion of interferon (IFN)-γ and IFN-γ-inducible protein-10 measured by enzyme-linked immunosorbent assay are as sensitive as IFN-γ enzyme-linked immunospot for the detection of gluten-reactive T cells in human leucocyte antigen (HLA)-DQ2·5(+) -associated coeliac disease.

T cell cytokine release assays are used to diagnose infectious diseases, but not autoimmune or allergic disease. Coeliac disease (CD) is a common T cell-mediated disease diagnosed by the presence of gluten-dependent intestinal inflammation and serology. Many patients cannot be diagnosed with CD because they reduce dietary gluten before medical workup. Oral gluten challenge in CD patients treated with gluten-free diet (GFD) mobilizes gluten-reactive T cells measurable by interferon (IFN)-γ enzyme-linked immunospot (ELISPOT) or major histocompatibility complex (MHC) class II tetramers. Immunodominant peptides are quite consistent in the 90% of patients who possess HLA-DQ2·5. We aimed to develop whole blood assays to detect gluten-specific T cells. Blood was collected before and after gluten challenge from GFD donors confirmed to have CD (n = 27, all HLA-DQ2·5(+) ), GFD donors confirmed not to have CD (n = 6 HLA-DQ2·5(+) , 11 HLA-DQ2·5(-) ) and donors with CD not following GFD (n = 4, all HLA-DQ2·5(+) ). Plasma IFN-γ and IFN-γ inducible protein-10 (IP-10) were measured by enzyme-linked immunosorbent assay (ELISA) after whole blood incubation with peptides or gliadin, and correlated with IFN-γ ELISPOT. No T cell assay could distinguish between CD patients and controls prior to gluten challenge, but after gluten challenge the whole blood IFN-γ ELISA and the ELISPOT were both 85% sensitive and 100% specific for HLA-DQ2·5(+) CD patients; the whole blood IP-10 ELISA was 94% sensitive and 100% specific. We conclude that whole blood cytokine release assays are sensitive and specific for detection of gluten-reactive T cells in CD; further clinical studies addressing the utility of these tests in patients with an uncertain diagnosis of CD is warranted.

What do the revised UK standards of proficiency mean for diagnostic radiography training? A regional radiographer focus group study.

INTRODUCTION: Revisions to the UK Health and Care Professions Council (HCPC) standards of proficiency for diagnostic radiographers came into effect on September 1st 2023. Changes include an increase of proficiencies in CT and extended to MRI imaging. As workforce support the development of learners to meet stage outcomes in practice, this study aimed to understand the radiographers' expectations of future learners' training to meet the new standards of proficiency. METHODS: Snowball sampling was used to invite practice educators/student supervisors and department leads within the 21 NHS Trusts in the North East and Yorkshire region providing diagnostic radiography practice placements. Online focus groups used a semi structured topic guide to explore the expectations of student performance during different stages of their training, and on different types of pre-registration programmes. Participants views were sought on considerations for appropriate assessment. Thematic analysis was supported by NVivo software. RESULTS: Fifteen diagnostic radiographers across 11 NHS trusts participated in 5 focus groups in November 2022. The findings showed consistency in expectations of student performance in projectional radiography, patient care and communication. Participants felt some standards of proficiency were beyond threshold competency, or current practices were a barrier in supporting learning. Participants felt assessment over a period and range of examinations in the clinical environment gave a fairer picture of student performance. CONCLUSION: There is uncertainty and perceived barriers in supporting future diagnostic radiography training in the practice setting. IMPLICATIONS FOR PRACTICE: Further work will be needed to identify and support appropriate learning opportunities and stage outcomes if learners are to meet the breadth of HCPC standards of proficiency with some consistency.

Diagnostic radiography workforce expectations of learners against the 2023 HCPC standards of proficiency: Results of a UK Delphi study.

INTRODUCTION: The UK Health and Care Professions Council revised the Standards of Proficiency for diagnostic radiographers in 2023 to reflect modern practices and service needs. This will impact on the training and assessment of learners throughout their programmes in order to support them to meet the threshold standards. METHODS: A Delphi survey was distributed to UK diagnostic radiographers to ascertain the stage of training in which they expect each standard of proficiency to be demonstrated by the learner. RESULTS: Ninety-four diagnostic radiographers responded to the survey and 58.5% (n = 55) completed the second round of the survey. Participants agreed on the stage of pre-registration training that 74.9% of standards should be met. However, for 19.6% of standards there was no consensus. In 5.5% of standards participants expected these to be met one year post qualification. CONCLUSION: Agreement of when three quarters of the new Standards would be expected to be met during pre-registration training could support practice placement learning and assessment. However, there is some uncertainty around the Standards and the ability to provide appropriate resources, support, and expertise to enable learners to meet them. IMPLICATIONS FOR PRACTICE: The consensus of expectations could inform stage appropriate learning opportunities aligned to the 2023 HCPC Standards within practice placements, and a standardised assessment, should the appetite be established. However, the UK diagnostic radiography profession still has some work to do in aligning expectations with the statutory regulatory body requirements and preparing all staff to support learners to meet all threshold standards at point of qualification.

Developing CT workforce competencies: What knowledge and skills should we expect of an early career radiographer?

INTRODUCTION: Individual professions seek to define their professional practice through competencies which describe the behaviours and technical attributes to perform effectively within role. Professional body and regulatory frameworks define universal standards for radiography but there is limited evidence of the technical competencies expected of the workforce in Computed Tomography (CT). This study aimed to address this gap by agreeing the essential competencies for the early career radiography workforce who have CT as part of their clinical responsibilities. This is the first step in developing a competency framework for CT across all radiography expertise levels. METHODS: A modified e-Delphi study was used to identify and gain agreement on essential practice competencies for this group. Structured surveys over two rounds were completed by an expert panel with CT knowledge and experience. Participants were asked to rate the essentiality of competencies for the novice CT workforce. Structured feedback was provided between surveys for consensus building, defined by the content validity ratio (CVR). RESULTS: Survey responses were received from 34 participants across different diagnostic imaging roles and settings. A total of 56 competency statements were agreed as essential for the early career CT workforce, including some appropriate to assistant radiographer practitioner roles. Competencies could be divided into those that were relevant to diagnostic radiography but could be applied to the CT setting (n = 32) and technical attributes unique to the CT context (n = 24). CONCLUSION: CT competencies for this group centre around understanding technical concepts of image formation and image quality optimisation; patient preparation and contrast media administration. IMPLICATIONS FOR PRACTICE: The competencies presented in this research represent the agreed minimum standards for the workforce in CT. Further work is required to validate competencies in practice.

The Effect of Nb, Ta, and Ti on the Oxidation of a New Polycrystalline Ni-Based Superalloy.

The effect of variations in Nb, Ta, and Ti concentrations in exchange for Al on the oxidation resistance of a new polycrystalline Ni-based superalloy (C19) was studied in air at 800 °C for up to 1000 h. An external scale of Ti-doped Cr2O3 and a sub-scale of discontinuous Al2O3 intrusions formed on the surface of all the studied alloys. Contrary to other reports, increasing the Nb concentration improved the oxidation performance and may have promoted the formation of a CrTaO4 layer, thereby reducing oxygen ingress. The addition of Ta also significantly improved oxidation resistance and reduced the depth of the Al2O3 intrusions. Increasing the Ti concentration did not significantly affect the oxidation performance, potentially due to the relatively low Ti concentrations investigated. Several of the studied alloys with modified Ta and Ti concentrations showed regions of continuous Al2O3 scale formation, suggesting that the compositions are in a transition regime between Cr2O3-forming and Al2O3-forming behaviour. The findings suggested that part of the Ti content in C19 could potentially be replaced with Nb, Ta and/or other elements to further enhance oxidation resistance and other desirable properties. Overall, the insights gained could serve as a guide to optimise the composition of C19 and similar alloys for enhanced oxidation resistance. Supplementary Information: The online version contains supplementary material available at 10.1007/s11085-023-10218-7.

A qualitative analysis of the role of the diagnostic radiographer in child safeguarding.

BACKGROUND: The role of medical imaging in the investigation of suspected child abuse is well documented. However, the role of the radiographer as an instigator of such concerns is less well understood. The fast-paced development of related technology and the evolution of the profession into new areas of work is argued to have impacted upon the traditional interaction between patient and professional; thus requiring a contemporary analysis of current practice. OBJECTIVE: As part of a wider multimethod thesis, this qualitative study sought to fill a gap in the literature with regard the role of the radiographer in child safeguarding by exploring their knowledge of, attitude towards and practical experience of the phenomenon. PARTICIPANTS AND SETTING: Online, semi-structured interviews were conducted with n=12 radiographers from across England between 2020 and 2021. Recruitment occurred via an initial survey and interviews were conducted online. METHODS: Verbatim transcripts were analysed using a framework analysis approach to create initial codes which led to themes for discussion. RESULTS: The framework analysis approach resulted in the identification of three constituent themes: (1) Patient, (2) Examination and (3) Radiographer. Each constituent themes were built from a comprehensive coding of the data. Analysis of these themes are presented in terms of quotes and diagrammatic depiction. CONCLUSION: For radiographers to be able to identify child safeguarding concerns, alignment of these constituent themes is necessary with the radiographer being the theme that can be greater controlled in terms of knowledge and attitude. Conceptually, this analysis could be extended to other professionals. Contemporary practice within medical imaging has made it more challenging to assess some physical and social signs of child safeguarding concern, and thus for the alignment to occur, as compared with previous generations. To maximise the contribution, education needs to account for wider paediatric practice and the imaging modality utilised by the radiographer. A case study approach demonstrating the potential that exists for the profession to contribute would be beneficial. Interprofessionally, greater involvement of radiographers in the assessment and escalation of any concerns could provide benefit to the patient.

The TGF-ß-Smad3 pathway inhibits CD28-dependent cell growth and proliferation of CD4 T cells.

Transforming growth factor-ß (TGF-ß) maintains self-tolerance through a constitutive inhibitory effect on T-cell reactivity. In most physiological situations, the tolerogenic effects of TGF-ß depend on the canonical signaling molecule Smad3. To characterize how TGF-ß/Smad3 signaling contributes to maintenance of T-cell tolerance, we characterized the transcriptional landscape downstream of TGF-ß/Smad3 signaling in resting or activated CD4 T cells. We report that in the presence of TGF-ß, Smad3 modulates the expression of >400 transcripts. Notably, we identified 40 transcripts whose expression showed Smad3 dependence in both resting and activated cells. This 'signature' confirmed the non-redundant role of Smad3 in TGF-ß biology and identified both known and putative immunoregulatory genes. Moreover, we provide genomic and functional evidence that the TGF-ß/Smad3 pathway regulates T-cell activation and metabolism. In particular, we show that TGF-ß/Smad3 signaling dampens the effect of CD28 stimulation on T-cell growth and proliferation. The impact of TGF-ß/Smad3 signals on T-cell activation was similar to that of the mTOR inhibitor Rapamycin. Considering the importance of co-stimulation on the outcome of T-cell activation, we propose that TGF-ß-Smad3 signaling may maintain T-cell tolerance by suppressing co-stimulation-dependent mobilization of anabolic pathways.

Antigen-specific human monoclonal antibodies from mice engineered with human Ig heavy and light chain YACs.

We describe a strategy for producing human monoclonal antibodies in mice by introducing large segments of the human heavy and kappa light chain loci contained on yeast artificial chromosomes into the mouse germline. Such mice produce a diverse repertoire of human heavy and light chains, and upon immunization with tetanus toxin have been used to derive antigen-specific, fully human monoclonal antibodies. Breeding such animals with mice engineered by gene targeting to be deficient in mouse immunoglobulin (Ig) production has led to a mouse strain in which high levels of antibodies are produced, mostly comprised of both human heavy and light chains. These strains should provide insight into the adoptive human antibody response and permit the development of fully human monoclonal antibodies with therapeutic potential.

Awake Craniotomy: A Case Series of Anaesthetic Management using a Combination of Scalp Block, Dexmedetomidine and Remifentanil in Hospital Universiti Sains Malaysia.

Awake craniotomy is a brain surgery in patients who are kept awake when it is indicated for certain intracranial pathologies. The anaesthetic management strategy is very important to achieve the goals of the surgery. We describe a series of our first four cases performed under a combination of scalp block and conscious sedation. Scalp block was performed using a mixture of ropivacaine 0.7% and adrenaline 5 5µg/ ml administered to the nerves that innervate the scalp. Conscious sedation was achieved with a combination of two recently available drugs in our country, dexmedetomidine (selective α 2-agonist) and remifentanil (ultra-short acting opioid). Remifentanil was delivered in a target controlled infusion (TCI) mode.

Evaluating Wagner Oxidation Criteria for Protective Al2O3 Scale Formation in Ni-Based Superalloys.

An assessment is made of the Wagner transition criteria for predicting the formation of a continuous Al2O3 scale in Ni-based superalloys. Predictions are compared with data from an experimental Ni-based superalloy as well as commercial superalloys for which published data are available. The methodology was generally successful in predicting the transition temperature of the commercial superalloys but underpredicted the transition temperature of the experimental superalloy by approximately 50-100 °C. The difference in the transition temperature of the experimental superalloy to form a continuous Al2O3 scale is primarily attributed to a complex oxide subscale that increased the internal volume fraction of oxide and led to reduced oxygen ingress. The sensitivity and limitations of the methodology are discussed, and recommendations are made to refine the methodology to facilitate the interpretation of oxidation behaviour in polycrystalline Ni-based superalloys. Supplementary Information: The online version contains supplementary material available at 10.1007/s11085-023-10163-5.

Evaluating the role of the diagnostic radiographer in identifying child safeguarding concerns: A knowledge, attitude and practice survey approach.

INTRODUCTION: Child safeguarding and the appropriate identification of suspected victims represents a global phenomenon. Diagnostic imaging is acknowledged as a contributory diagnostic service but the role of the radiographer in the identification and escalation process is less well understood. METHOD: A Knowledge, Attitude and Practice (KAP) survey was constructed to evaluate knowledge base in the context of the patient-radiographer interaction, the shaping of attitude towards child safeguarding and attitudes held towards their role plus the actual practical experiences of managing child safeguarding concerns. RESULTS: Respondents demonstrated a inconsistent knowledge base with respect to physical, social and radiographic signs and symptoms of child safeguarding concern. A positive attitude towards the role of the radiographer in child safeguarding was demonstrated but one that was shaped more by experience than pre-registration education. Assessment of concerns was chiefly influenced by clinical history and appreciation of aetiology. Practically, radiographers have infrequent involvement with the identification and escalation of concerns. Whilst some statistically significant relationships between responses and demographics did exist, these were either sporadic or argued to be a result of natural variation. CONCLUSION: Assessment of physical and social signs of child safeguarding concern are argued to be becoming more challenging. Radiological signs continue to be visible to radiographers but with increasing use of other imaging modalities these signs are becoming more varied in nature and are providing new challenges. Radiographers are capable of escalation when required to do so. IMPLICATIONS FOR PRACTICE: To maximise the contribution of the profession, education needs to account for imaging modality worked with, in combination with an understanding of related aetiology. Previously existing concerns with respect to escalating processes are no longer in evidence and radiographers are both willing and able to contribute to that process.

D-dimer testing: A narrative review.

D-dimer containing species are soluble fibrin degradation products derived from plasmin-mediated degradation of cross-linked fibrin, i.e., 'D-dimer'. D-dimer can hence be considered a biomarker of in vivo activation of both coagulation and fibrinolysis, the leading clinical application in daily practice of which is ruling out venous thromboembolism (VTE). D-dimer has been further evaluated for assessing the risk of VTE recurrence and helping define optimal duration of anticoagulation treatment in VTE, for diagnosing disseminated intravascular coagulation (DIC), and for screening those at enhanced risk of VTE. D-dimer assays should however be performed as intended by regulatory agencies, as their use outside these indications might make them a laboratory-developed test (LDT). This narrative review is aimed at: (1) reviewing the definition of D-dimer, (2) discussing preanalytical variables affecting D-dimer measurement, (3) reviewing and comparing the assays performance and some postanalytical variables (e.g., different units and age-adjusted cutoffs), and (4) discussing the interest of D-dimer measurement across different clinical settings, including pregnancy, cancer, and coronavirus disease 2019 (COVID-19).