Accuracy and safety of an autonomous artificial intelligence clinical assistant conducting telemedicine follow-up assessment for cataract surgery.

Background: Artificial intelligence deployed to triage patients post-cataract surgery could help to identify and prioritise individuals who need clinical input and to expand clinical capacity. This study investigated the accuracy and safety of an autonomous telemedicine call (Dora, version R1) in detecting cataract surgery patients who need further management and compared its performance against ophthalmic specialists. Methods: 225 participants were recruited from two UK public teaching hospitals after routine cataract surgery between 17 September 2021 and 31 January 2022. Eligible patients received a call from Dora R1 to conduct a follow-up assessment approximately 3 weeks post cataract surgery, which was supervised in real-time by an ophthalmologist. The primary analysis compared decisions made independently by Dora R1 and the supervising ophthalmologist about the clinical significance of five symptoms and whether the patient required further review. Secondary analyses used mixed methods to examine Dora R1's usability and acceptability and to assess cost impact compared to standard care. This study is registered with ClinicalTrials.gov (NCT05213390) and ISRCTN (16038063). Findings: 202 patients were included in the analysis, with data collection completed on 23 March 2022. Dora R1 demonstrated an overall outcome sensitivity of 94% and specificity of 86% and showed moderate to strong agreement (kappa: 0.758-0.970) with clinicians in all parameters. Safety was validated by assessing subsequent outcomes: 11 of the 117 patients (9%) recommended for discharge by Dora R1 had unexpected management changes, but all were also recommended for discharge by the supervising clinician. Four patients were recommended for discharge by Dora R1 but not the clinician; none required further review on callback. Acceptability, from interviews with 20 participants, was generally good in routine circumstances but patients were concerned about the lack of a 'human element' in cases with complications. Feasibility was demonstrated by the high proportion of calls completed autonomously (195/202, 96.5%). Staff cost benefits for Dora R1 compared to standard care were £35.18 per patient. Interpretation: The composite of mixed methods analysis provides preliminary evidence for the safety, acceptability, feasibility, and cost benefits for clinical adoption of an artificial intelligence conversational agent, Dora R1, to conduct follow-up assessment post-cataract surgery. Further evaluation in real-world implementation should be conducted to provide additional evidence around safety and effectiveness in a larger sample from a more diverse set of Trusts. Funding: This manuscript is independent research funded by the National Institute for Health Research and NHSX (Artificial Intelligence in Health and Care Award, AI_AWARD01852).

Fournier's gangrene complicated by lower limb necrotising fasciitis and pelvic bone osteomyelitis: A case report with literature review.

INTRODUCTION AND IMPORTANCE: Fournier's gangrene is a urological emergency associated with high mortality and morbidity. Severe gangrene resulting in pelvic bone and lower limb involvement are extremely rare. CASE PRESENTATION: We report a rare case of Fournier's gangrene that is complicated by necrotising fasciitis of the lower limb and osteomyelitis of the pelvic bone, in a patient with previous prostatic adenocarcinoma. The patient was promptly resuscitated, started on broad spectrum antibiotics and then underwent an emergent surgical debridement, followed by multiple relook debridement and definitive reconstruction. Throughout the patient's hospitalisation, he was managed in a multidisciplinary team involving surgeons from different specialities, physicians and allied health staff. CLINICAL DISCUSSION: Extension of Fournier's gangrene into distant structures is rare but serious complications. To date, there is only one other case reported in literature. The relationship between prior prostatic malignancy and Fournier's gangrene can be explored in subsequent studies. CONCLUSION: We present a rare case of Fournier's gangrene with pelvic and distal limb involvement. We highlight the possible yet devastating complications of this disease and discuss treatment options available for the holistic management of patients with Fournier's gangrene.

PICH deficiency limits the progression of MYC-induced B-cell lymphoma.

Plk1-interacting checkpoint helicase (PICH) is a DNA translocase involved in resolving ultrafine anaphase DNA bridges and, therefore, is important to safeguard chromosome segregation and stability. PICH is overexpressed in various human cancers, particularly in lymphomas such as Burkitt lymphoma, which is caused by MYC translocations. To investigate the relevance of PICH in cancer development and progression, we have combined novel PICH-deficient mouse models with the Eµ-Myc transgenic mouse model, which recapitulates B-cell lymphoma development. We have observed that PICH deficiency delays the onset of MYC-induced lymphomas in Pich heterozygous females. Moreover, using a Pich conditional knockout mouse model, we have found that Pich deletion in adult mice improves the survival of Eµ-Myc transgenic mice. Notably, we show that Pich deletion in healthy adult mice is well tolerated, supporting PICH as a suitable target for anticancer therapies. Finally, we have corroborated these findings in two human Burkitt lymphoma cell lines and we have found that the death of cancer cells was accompanied by chromosomal instability. Based on these findings, we propose PICH as a potential therapeutic target for Burkitt lymphoma and for other cancers where PICH is overexpressed.

Feasibility of an artificial intelligence phone call for postoperative care following cataract surgery in a diverse population: two phase prospective study protocol.

INTRODUCTION: Artificial intelligence (AI) development has led to improvements in many areas of medicine. Canada has workforce pressures in delivering cataract care. A potential solution is using AI technology that can automate care delivery, increase effectiveness and decrease burdens placed on patients and the healthcare system. This study assesses the use of 'Dora', an example of an AI assistant that is able to deliver a regulated autonomous, voice-based, natural-language consultation with patients over the telephone. Dora is used in routine practice in the UK, but this study seeks to assess the safety, usability, acceptability and cost-effectiveness of using the technology in Canada. METHODS AND ANALYSIS: This is a two-phase prospective single-centred trial. An expected 250 patients will be recruited for each phase of the study. For Phase I of the study, Dora will phone patients at postoperative week 1 and for Phase II of the study, Dora will phone patients within 24hours of their cataract surgery and again at postoperative week 1. We will evaluate the agreement between Dora and a supervising clinician regarding the need for further review based on the patients' symptoms. A random sample of patients will undergo the System Usability Scale followed by an extended semi-structured interview. The primary outcome of agreement between Dora and the supervisor will be assessed using the kappa statistic. Qualitative data from the interviews will further gauge patient opinions about Dora's usability, appropriateness and level of satisfaction. ETHICS AND DISSEMINATION: Research Ethics Board William Osler Health System (ID: 22-0044) has approved this study and will be conducted by guidelines of Declaration of Helsinki. Master-linking sheet will contain the patient chart identification (ID), full name, date of birth and study ID. Results will be shared through peer-reviewed journals and presentations at conferences.

User-acceptability of an automated telephone call for post-operative follow-up after uncomplicated cataract surgery.

BACKGROUND: Innovative technology is recommended to address the current capacity challenges facing the NHS. This study evaluates the patient acceptability of automated telephone follow-up after routine cataract surgery using Dora (Ufonia Limited, Oxford, United Kingdom), which to our knowledge is the first AI-powered clinical assistant to be used in the NHS. Dora has a natural-language, phone conversation with patients about their symptoms after cataract surgery. METHODS: This is a prospective mixed-methods cohort study that was conducted at Buckinghamshire Healthcare NHS Foundation Trust. All patients who were followed up using Dora were asked to give a Net Promoter Score (NPS), and 24 patients were randomly selected to complete the validated Telephone Usability Questionnaire (TUQ) as well as extended semi-structured interviews that underwent thematic analysis. RESULTS: A total of 170 autonomous calls were completed. The median NPS score was 9 out of 10. The TUQ (scored out of 5) showed high rates of acceptability, with an overall mean score of 4.0. Simplicity, time saving, and ease of use scored the highest with a median of 5, whilst 'speaking to Dora feels the same as speaking to a clinician' scored a median of 3. The main themes extracted from the qualitative data were 'I can see why you're doing it', 'It went quite well actually', 'I just trust human beings I suppose'. CONCLUSION: We found high levels of patient acceptability when using Dora across three acceptability measures. Dora provides a potential solution to reduce pressure on hospital capacity whilst also providing a convenient service for patients.

A Prospective Audit Comparing Optos Widefield Imaging to Fundus Examination for Von Hippel-Lindau Retinal Screening.

Background Von Hippel-Lindau (VHL) disease is an autosomal dominant multisystem disorder caused by germline mutations at chromosome 3p25-26 in the VHLtumour suppressor gene. Retinal manifestations include capillary haemangiomas that develop in up to 80% of gene carriers. Lifelong retinal surveillance involves yearly assessment usually by fundoscopy and often as part of a VHL multidisciplinary clinic. Optos ultra-widefield retinal imaging is now becoming more widely used in virtual retinal screening clinics. We aimed to assess discrepancies in the pickup rate of angioma and angiomatous-associated disease between slit-lamp fundoscopy and Optos ultra-widefield imaging. Methodology A total of 49 patients had both Optos ultra-widefield retinal imaging and slit-lamp fundoscopy over 16 months in VHL retinal surveillance clinics at the John Radcliffe Hospital, Oxford, UK. Optos images were analysed for image quality and presence of angioma(s) by a Consultant Ophthalmologist who was masked to the fundoscopy findings. The pickup rate was compared between slit-lamp fundoscopy and Optos imaging. Results In total, data on 94 eyes were collected. Of the total Optos retinal images, 12.8% were positive for angiomas compared to 11.7% from the slit-lamp examination. There was a discrepancy of 1.1% (one value) where the Optos image analysis suggested a possible angioma, which was not identified on slit-lamp examination. Optos imaging identified all angiomas in this cohort. Conclusions Optos imaging was non-inferior to slit-lamp examination in this sample of 94 eyes. In the current COVID-19 climate, reducing clinician-patient interaction is important. This research supports providing retinal imaging as an acceptable alternative to the yearly slit-lamp fundus examination.

Antisense Peptide Nucleic Acid-Diaminobutanoic Acid Dendron Conjugates with SbmA-Independent Antimicrobial Activity against Gram-Negative Bacteria.

Precision antisense antibacterial agents may be developed into novel antibiotics in the fight against multidrug-resistant Gram-negative bacteria. In this study, a series of diaminobutanoic acid (DAB) dendrons are presented as novel carriers for the delivery of antisense antibacterial peptide nucleic acids (PNAs). The dendron-PNA conjugates targeting the essential acpP gene exhibit specific antisense antimicrobial bactericidal activity against Escherichia coli and Klebsiella pneumoniae at one-digit micromolar concentrations, while showing low toxicity to human cells. One compound selected from a structure-activity relationship series showed high stability in mouse and human serum (t1/2 ≫ 24 h) as well as in vivo activity against a multidrug-resistant, extended spectrum beta-lactamase-producing E. coli in a murine peritonitis model. The compound was also well tolerated in mice upon i.v. administration up to a dose of 20 mg/kg, and in vivo fluorescence imaging indicated clearance via renal excretion with slight accumulation in the kidneys and liver. Thus, DAB-based dendrons constitute a promising new chemistry platform for development of effective delivery agents for antibacterial drugs with possible in vivo use.

Distinguishing Intramedullary Spinal Cord Neoplasms from Non-Neoplastic Conditions by Analyzing the Classic Signs on MRI in the Era of AI.

Intramedullary lesions can be challenging to diagnose, given the wide range of possible pathologies. Each lesion has unique clinical and imaging features, which are best evaluated using magnetic resonance imaging. Radiological imaging is unique with rich, descriptive patterns and classic signs-which are often metaphorical. In this review, we present a collection of classic MRI signs, ranging from neoplastic to non-neoplastic lesions, within the spinal cord. The Differential Diagnosis (DD) of intramedullary lesions can be narrowed down by careful analysis of the classic signs and patterns of involvement in the spinal cord. Furthermore, the signs are illustrated memorably with emphasis on the pathophysiology, mimics, and pitfalls. Artificial Intelligence (AI) algorithms, particularly deep learning, have made remarkable progress in image recognition tasks. The classic signs and related illustrations can enhance a pattern recognition approach in diagnostic radiology. Deep learning can potentially be designed to distinguish neoplastic from non-neoplastic processes by pattern recognition of the classic MRI signs.

Primary intraventricular tumors - Imaging characteristics, post-treatment changes and relapses.

Primary intraventricular neoplasms are rare tumors that originate from the ependymal or subependymal, septum pellucidum, choroid plexus and the supporting arachnoid tissue. Knowledge of the common locations of these tumors within the ventricular system, together with key imaging characteristics and presentation age, can significantly narrow the differential diagnosis. In 2016, the WHO reorganized the classification of several primary CNS tumors by combining histopathological and molecular data. This study highlights the imaging characteristics, histopathological and molecular data, treatment strategies and post-treatment changes of primary intraventricular tumors. Molecular-based diagnosis can not only aid in patient stratification and personalized treatment, but it can also provide prognostic and predictive value independent of WHO classification.

Safety and Acceptability of a Natural Language Artificial Intelligence Assistant to Deliver Clinical Follow-up to Cataract Surgery Patients: Proposal.

BACKGROUND: Due to an aging population, the demand for many services is exceeding the capacity of the clinical workforce. As a result, staff are facing a crisis of burnout from being pressured to deliver high-volume workloads, driving increasing costs for providers. Artificial intelligence (AI), in the form of conversational agents, presents a possible opportunity to enable efficiency in the delivery of care. OBJECTIVE: This study aims to evaluate the effectiveness, usability, and acceptability of Dora agent: Ufonia's autonomous voice conversational agent, an AI-enabled autonomous telemedicine call for the detection of postoperative cataract surgery patients who require further assessment. The objectives of this study are to establish Dora's efficacy in comparison with an expert clinician, determine baseline sensitivity and specificity for the detection of true complications, evaluate patient acceptability, collect evidence for cost-effectiveness, and capture data to support further development and evaluation. METHODS: Using an implementation science construct, the interdisciplinary study will be a mixed methods phase 1 pilot establishing interobserver reliability of the system, usability, and acceptability. This will be done using the following scales and frameworks: the system usability scale; assessment of Health Information Technology Interventions in Evidence-Based Medicine Evaluation Framework; the telehealth usability questionnaire; and the Non-Adoption, Abandonment, and Challenges to the Scale-up, Spread and Suitability framework. RESULTS: The evaluation is expected to show that conversational technology can be used to conduct an accurate assessment and that it is acceptable to different populations with different backgrounds. In addition, the results will demonstrate how successfully the system can be delivered in organizations with different clinical pathways and how it can be integrated with their existing platforms. CONCLUSIONS: The project's key contributions will be evidence of the effectiveness of AI voice conversational agents and their associated usability and acceptability. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/27227.

Fundus Autofluorescence Imaging in Macular Telangiectasia Type 2: MacTel Study Report Number 9.

PURPOSE: To investigate the role of fundus autofluorescence (FAF) imaging in the diagnosis of macular telangiectasia type 2 (MacTel) and to describe disease-associated FAF patterns and their origin. DESIGN: Cross-sectional multicenter study METHODS: FAF images were collected from the multicenter MacTel Natural History Observation and Registry Study. In a first qualitative approach, common FAF phenotypes were defined and correlated with multimodal imaging. We then evaluated how many eyes showed FAF changes, and temporal vs nasal asymmetry of FAF changes was graded. Finally, 100 eyes of MacTel patients and 100 control eyes (50 normal eyes and 50 eyes with other macular diseases) were combined and 2 masked graders assessed the presence of MacTel based on FAF images alone. RESULTS: The study included 807 eyes of 420 patients (33 eyes were excluded owing to poor image quality). Loss of macular pigment, cystoid spaces, pigment plaques, neovascular membranes, and ectatic vascular changes commonly caused characteristic changes on FAF images. All MacTel patients had macular FAF changes in at least 1 eye. In 95% of eyes, these changes were more pronounced temporally than nasally. Common FAF patterns were increased (60%) and mixed/decreased FAF (38%) and/or visibility of vascular changes such as blunted vessels or ectatic capillaries (79%). Based on those features, high diagnostic performance was achieved for detection of the disease based on FAF alone (Youden index up to 0.91). CONCLUSIONS: The study demonstrates that MacTel is consistently associated with disease-specific changes on FAF imaging. Those changes are typically more pronounced in the temporal parafovea.

Multimodality imaging and treatment strategy for malignant scalp neoplasms in adults.

Malignant scalp masses deserve much attention as they have the potential to destroy local structures, recur and metastasize to distant organs. Moreover, malignant scalp lesions are known to be more aggressive in behavior than their counterparts elsewhere in the body. Multimodality imaging is essential in narrowing the differential diagnoses of scalp masses, as well as in differentiating benign from malignant masses. Furthermore, imaging is important in (1) evaluating the extent of tumor invasion in the scalp, (2) staging the disease, (3) guiding surgical biopsy and/or resection of the tumor, (4) preoperative planning and post-treatment surveillance of scalp tumors. An interdisciplinary treatment approach is crucial for the management of scalp malignancies given their complex and aggressive nature. This review seeks to describe the unique clinical and imaging characteristics of various types of malignant scalp masses, as well as to review their current treatment strategies.

Insights From Survival Analyses During 12 Years of Anti-Vascular Endothelial Growth Factor Therapy for Neovascular Age-Related Macular Degeneration.

Importance: Although multiple imputation models for missing data and the use of mixed-effects models generally provide better outcome estimates than using only observed data or last observation carried forward in clinical trials, such approaches usually cannot be applied to visual outcomes from retrospective analyses of clinical practice settings, also called real-world outcomes. Objective: To explore the potential usefulness of survival analysis techniques for retrospective clinical practice visual outcomes. Design, Setting, and Participants: This retrospective cohort study covered a 12-year observation period at a tertiary eye center. Of 10 744 eyes with neovascular age-related macular degeneration receiving anti-vascular endothelial growth factor (VEGF) therapy between October 28, 2008, and February 1, 2020, 7802 eyes met study criteria (treatment-naive, first-treated eyes starting anti-VEGF therapy). Eyes were excluded from the analysis if they received photodynamic therapy or macular laser, any previous anti-VEGF therapy, treatment with anti-VEGF agents other than ranibizumab or aflibercept, or had an unknown date or visual acuity (VA) value at first injection. Main Outcomes and Measures: Kaplan-Meier estimates and Cox proportional hazards modeling were used to consider VA reaching an Early Treatment Diabetic Retinopathy Study (ETDRS) letter score of 70 (Snellen equivalent, 20/40) or better, duration of VA sustained at or better than 70 (20/40), and VA declining to 35 (20/200) or worse. Results: A total of 7802 patients (mean [SD] age, 78.7 [8.8] years; 4776 women [61.2%]; and 4785 White [61.3%]) were included in the study. The median time to attaining a VA letter score greater than or equal to 70 (20/40) was 2.0 years (95% CI, 1.87-2.32) after the first anti-VEGF injection. Predictive features were baseline VA (hazard ratio [HR], 1.43 per 5 ETDRS letter score or 1 line; 95% CI, 1.40-1.46), baseline age (HR, 0.88 per 5 years; 95% CI, 0.86-0.90), and injection number (HR, 1.12; 95% CI, 1.10-1.15). Of the 4439 of 7802 patients (57%) attaining this outcome, median time sustained at an ETDRS letter score of 70 (20/40) or better was 1.1 years (95% CI, 1.1-1.2). Conclusions and Relevance: In this cohort study, patients with neovascular age-related macular degeneration beginning anti-VEGF therapy were more likely to experience positive visual outcomes within the first 2.0 years after treatment, typically maintaining this outcome for 1.1 years but then deteriorating to poor vision within 8.7 years. These findings demonstrate the potential usefulness of the proposed analyses. This data set, combined with the statistical approach for retrospective analyses, may provide long-term prognostic information for patients newly diagnosed with this condition.

Near-Infrared In Vivo Whole-Body Fluorescence Imaging of PNA.

Using near-infrared fluorophore Alexa Fluor 680 labeled peptide nucleic acids (PNAs) the biodistribution of such antisense agents can be analyzed in real time in live mice using in vivo imaging. Using the fluorescence intensity emitted from the mouse at different time points following administration, the systemic distribution and organ accumulation of PNA can be tracked. In addition, an estimation of the body half-life of the compound can be obtained by the change in fluorescence intensity over time. With this technique, the distribution of compounds can be monitored real time, while reducing the number of animals and amount of compounds required.