AI assisted reader evaluation in acute CT head interpretation (AI-REACT): protocol for a multireader multicase study.

INTRODUCTION: A non-contrast CT head scan (NCCTH) is the most common cross-sectional imaging investigation requested in the emergency department. Advances in computer vision have led to development of several artificial intelligence (AI) tools to detect abnormalities on NCCTH. These tools are intended to provide clinical decision support for clinicians, rather than stand-alone diagnostic devices. However, validation studies mostly compare AI performance against radiologists, and there is relative paucity of evidence on the impact of AI assistance on other healthcare staff who review NCCTH in their daily clinical practice. METHODS AND ANALYSIS: A retrospective data set of 150 NCCTH will be compiled, to include 60 control cases and 90 cases with intracranial haemorrhage, hypodensities suggestive of infarct, midline shift, mass effect or skull fracture. The intracranial haemorrhage cases will be subclassified into extradural, subdural, subarachnoid, intraparenchymal and intraventricular. 30 readers will be recruited across four National Health Service (NHS) trusts including 10 general radiologists, 15 emergency medicine clinicians and 5 CT radiographers of varying experience. Readers will interpret each scan first without, then with, the assistance of the qER EU 2.0 AI tool, with an intervening 2-week washout period. Using a panel of neuroradiologists as ground truth, the stand-alone performance of qER will be assessed, and its impact on the readers' performance will be analysed as change in accuracy (area under the curve), median review time per scan and self-reported diagnostic confidence. Subgroup analyses will be performed by reader professional group, reader seniority, pathological finding, and neuroradiologist-rated difficulty. ETHICS AND DISSEMINATION: The study has been approved by the UK Healthcare Research Authority (IRAS 310995, approved 13 December 2022). The use of anonymised retrospective NCCTH has been authorised by Oxford University Hospitals. The results will be presented at relevant conferences and published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT06018545.

Counter pressure maneuvers for syncope prevention: A semi-systematic review and meta-analysis.

Physical counter pressure maneuvers (CPM) are movements that are recommended to delay or prevent syncope (fainting) by recruiting the skeletal muscle pump to augment cardiovascular control. However, these recommendations are largely based on theoretical benefit, with limited data evaluating the efficacy of CPM to prevent syncope in the real-world setting. We conducted a semi-systematic literature review and meta-analysis to assess CPM efficacy, identify literature gaps, and highlight future research needs. Articles were identified through a literature search (PubMed, April 2022) of peer-reviewed publications evaluating the use of counter pressure or other lower body maneuvers to prevent syncope. Two team members independently screened records for inclusion and extracted data. From 476 unique records identified by the search, 45 met inclusion criteria. Articles considered various syncopal conditions (vasovagal = 12, orthostatic hypotension = 8, postural orthostatic tachycardia syndrome = 1, familial dysautonomia = 2, spinal cord injury = 1, blood donation = 10, healthy controls = 11). Maneuvers assessed included hand gripping, leg fidgeting, stepping, tiptoeing, marching, calf raises, postural sway, tensing (upper, lower, whole body), leg crossing, squatting, "crash" position, and bending foreword. CPM were assessed in laboratory-based studies (N = 28), the community setting (N = 4), both laboratory and community settings (N = 3), and during blood donation (N = 10). CPM improved standing systolic blood pressure (+ 14.8 ± 0.6 mmHg, p < 0.001) and heart rate (+ 1.4 ± 0.5 bpm, p = 0.006), however, responses of total peripheral resistance, stroke volume, or cerebral blood flow were not widely documented. Most patients experienced symptom improvement following CPM use (laboratory: 60 ± 4%, community: 72 ± 9%). The most prominent barrier to employing CPM in daily living was the inability to recognize an impending faint. Patterns of postural sway may also recruit the skeletal muscle pump to enhance cardiovascular control, and its potential as a discrete, proactive CPM needs further evaluation. Physical CPM were successful in improving syncopal symptoms and producing cardiovascular responses that may bolster against syncope; however, practical limitations may restrict applicability for use in daily living.

Faintly tired: a systematic review of fatigue in patients with orthostatic syncope.

BACKGROUND: Orthostatic syncope (transient loss of conscious when standing-fainting) is common and negatively impacts quality of life. Many patients with syncope report experiencing fatigue, sometimes with "brain fog", which may further impact their quality of life, but the incidence and severity of fatigue in patients with syncope remain unclear. In this systematic review, we report evidence on the associations between fatigue and conditions of orthostatic syncope. METHODS: We performed a comprehensive literature search of four academic databases to identify articles that evaluated the association between orthostatic syncope [postural orthostatic tachycardia syndrome (POTS), vasovagal syncope (VVS), orthostatic hypotension (OH)] and fatigue. Studies were independently screened using a multi-stage approach by two researchers to maintain consistency and limit bias. RESULTS: Our initial search identified 2797 articles, of which 13 met our inclusion criteria (POTS n = 10; VVS n = 1; OH n = 1; VVS and POTS n = 1). Fatigue scores were significantly higher in patients with orthostatic syncope than healthy controls, and were particularly severe in those with POTS. Fatigue associated with orthostatic syncope disorders spanned multiple domains, with each dimension contributing equally to increased fatigue. "Brain fog" was an important symptom of POTS, negatively affecting productivity and cognition. Finally, fatigue was negatively associated with mental health in patients with POTS. CONCLUSION: In conditions of orthostatic syncope, fatigue is prevalent and debilitating, especially in patients with POTS. The consideration of fatigue in patients with orthostatic disorders is essential to improve diagnosis and management of symptoms, thus improving quality of life for affected individuals.

A multicentre study of the relationship between abdominal flap and mastectomy weights in immediate unilateral free flap breast reconstruction and the effect of adjuvant radiotherapy.

Abdominal free flaps are considered the gold standard for post-mastectomy autologous breast reconstruction. A key element of outcome assessment is breast symmetry often achieved by approximating the reconstructed breast dimensions such as weight (wt) to those of the mastectomy. However, the ideal relationship between these two entities remains unclear. 525 immediate unilateral abdominal free flap breast reconstruction (FFBR) patients were enrolled in a multicentre study (UK 141; Italy 384) and subdivided into Group A (flap wt < mastectomy wt, n = 163), Group B (flap wt > mastectomy wt, n = 260) and Group C (flap wt = mastectomy wt, n = 102). Their rates of contralateral balancing and ipsilateral revision surgeries were compared using Chi-Square tests. Radiotherapy influence on these adjustment procedures was also assessed. More contralateral balancing procedures (17%) were performed than ipsilateral revisions (10%). Group A rates of contralateral balancing procedures were three times higher than Group B's with a ratio of 37 to 1 versus Group C (37% vs 11% vs 1% respectively, p < 0.001). Similarly, the ipsilateral breast revision surgery rate in Group A was double that of Group B and almost three times that of Group C (17% vs 8% vs 6% respectively, p = 0.01). Adjuvant radiotherapy disproportionately increased ipsilateral revisions versus contralateral balancing surgeries (p = 0.028). A flap-to-mastectomy weight ratio of less than 1 (Group A) significantly increases subsequent adjustments on both contralateral and reconstructed breasts whilst irradiation predisposes to ipsilateral revisions. This is important in patient counselling and intraoperative flap contouring. Flap weight should ideally approximate or exceed mastectomy weight in unilateral FFBR.

Long-term Outcomes Following Endovascular Aneurysm Repair for Ruptured Abdominal Aortic Aneurysms.

Purpose: To investigate the long-term outcomes of endovascular aneurysm repair (EVAR) for ruptured abdominal aortic aneurysm (rAAA) from a single center over an 11-year period. Materials and Methods: A retrospective analysis was conducted of 121 patients (median age 78 years; 100 men) with rAAA who underwent emergency EVAR at a single tertiary vascular center from January 2006 to December 2016. The study included only ruptures confirmed by evidence of hematoma on preoperative computed tomography; both iliac and aortic aneurysm ruptures were eligible. The primary outcome measures included mortality and reintervention rates. Kaplan-Meier estimates of survival and freedom from reintervention are reported with the 95% confidence interval (CI). Results: In-hospital and 30-day mortality rates for emergency EVAR were 16.5%; 90-day mortality was 24.0%. The mortality estimates were 27.3% (95% CI 20% to 36%) at 1 year and 61.7% (95% CI 51% to 72%) at 5 years. In the observation period to 2017, 63 reinterventions were performed on 37 patients (30.6%). Median time to the first reintervention was 3.2 years. Freedom from reintervention in surviving patients at 1 year was 86% (95% CI 72% to 94%) and 51% (95% CI 26% to 71%) at 5 years. Four patients (3.3%) had a secondary sac rupture over the study period. Conclusion: Emergency EVAR for ruptured AAA can be performed with acceptable short-term outcomes; however, long-term surveillance is necessary, and reintervention is common.

Physiological Roles of DNA Double-Strand Breaks.

Genomic integrity is constantly threatened by sources of DNA damage, internal and external alike. Among the most cytotoxic lesions is the DNA double-strand break (DSB) which arises from the cleavage of both strands of the double helix. Cells boast a considerable set of defences to both prevent and repair these breaks and drugs which derail these processes represent an important category of anticancer therapeutics. And yet, bizarrely, cells deploy this very machinery for the intentional and calculated disruption of genomic integrity, harnessing potentially destructive DSBs in delicate genetic transactions. Under tight spatiotemporal regulation, DSBs serve as a tool for genetic modification, widely used across cellular biology to generate diverse functionalities, ranging from the fundamental upkeep of DNA replication, transcription, and the chromatin landscape to the diversification of immunity and the germline. Growing evidence points to a role of aberrant DSB physiology in human disease and an understanding of these processes may both inform the design of new therapeutic strategies and reduce off-target effects of existing drugs. Here, we review the wide-ranging roles of physiological DSBs and the emerging network of their multilateral regulation to consider how the cell is able to harness DNA breaks as a critical biochemical tool.

Understanding specific functions of PARP-2: new lessons for cancer therapy.

Poly(ADP-ribosyl)ation (PARylation) is a widespread and highly conserved post-translational modification catalysed by a large family of enzymes called poly(ADP-ribose) polymerases (PARPs). PARylation plays an essential role in various cardinal processes of cellular physiology and recent approvals and breakthrough therapy designations for PARP inhibitors in cancer therapy have sparked great interest in pharmacological targeting of PARP proteins. Although, many PARP inhibitors have been developed, existing compounds display promiscuous inhibition across the PARP superfamily which could lead to unwanted off-target effects. Thus the prospect of isoform-selective inhibition is being increasingly explored and research is now focusing on understanding specific roles of PARP family members. PARP-2, alongside PARP-1 and PARP-3 are the only known DNA damage-dependent PARPs and play critical roles in the DNA damage response, DNA metabolism and chromatin architecture. However, growing evidence shows that PARP-2 plays specific and diverse regulatory roles in cellular physiology, ranging from genomic stability and epigenetics to proliferative signalling and inflammation. The emerging network of PARP-2 target proteins has uncovered wide-ranging functions of the molecule in many cellular processes commonly dysregulated in carcinogenesis. Here, we review novel PARP-2-specific functions in the hallmarks of cancer and consider the implications for the development of isoform-selective inhibitors in chemotherapy. By considering the roles of PARP-2 through the lens of tumorigenesis, we propose PARP-2-selective inhibition as a potentially multipronged attack on cancer physiology.