Natural language processing to automate a web-based model of care and modernize skin cancer multidisciplinary team meetings.

BACKGROUND: Cancer multidisciplinary team (MDT) meetings are under intense pressure to reform given the rapidly rising incidence of cancer and national mandates for protocolized streaming of cases. The aim of this study was to validate a natural language processing (NLP)-based web platform to automate evidence-based MDT decisions for skin cancer with basal cell carcinoma as a use case. METHODS: A novel and validated NLP information extraction model was used to extract perioperative tumour and surgical factors from histopathology reports. A web application with a bespoke application programming interface used data from this model to provide an automated clinical decision support system, mapped to national guidelines and generating a patient letter to communicate ongoing management. Performance was assessed against retrospectively derived recommendations by two independent and blinded expert clinicians. RESULTS: There were 893 patients (1045 lesions) used to internally validate the model. High accuracy was observed when compared against human predictions, with an overall value of 0.92. Across all classifiers the virtual skin MDT was highly specific (0.96), while sensitivity was lower (0.72). CONCLUSION: This study demonstrates the feasibility of a fully automated, virtual, web-based service model to host the skin MDT with good system performance. This platform could be used to support clinical decision-making during MDTs as 'human in the loop' approach to aid protocolized streaming. Future prospective studies are needed to validate the model in tumour types where guidelines are more complex.

Development of the Escalation of Therapy or Intervention (ETI) Calculator for Patients with Ulcerative Colitis Using ePROMs.

BACKGROUND AND AIMS: Digital collection of patient-reported outcome measures [PROMs] is largely unexplored as a basis for follow-up for patients with ulcerative colitis [UC]. Our aim was to develop a model to predict the likelihood of escalation of therapy or intervention at an outpatient appointment that may be used to rationalize follow-up. METHODS: TrueColours-IBD is a web-based, real-time, remote monitoring software that allows longitudinal collection of ePROMs. Data for prediction modelling were derived from a Development Cohort, guided by the TRIPOD statement. Logistic regression modelling used ten candidate items to predict escalation of therapy or intervention. An Escalation of Therapy or Intervention [ETI] calculator was developed, and applied in a Validation Cohort at the same centre. RESULTS: The Development Cohort [n = 66] was recruited in 2016 and followed for 6 months [208 appointments]. From ten items, four significant predictors of ETI were identified: SCCAI, IBD Control-8, faecal calprotectin, and platelets. For practicality, a model with only SCCAI and IBD Control-8, both entered remotely by the patient, without the need for faecal calprotectin or blood tests was selected. Between 2018 and 2020, a Validation Cohort of 538 patients [1188 appointments] was examined. A 5% threshold on the ETI calculator correctly identified 343/388 [88%] escalations and 274/484 [57%] non-escalations. CONCLUSIONS: A calculator based on digital, patient-entered data on symptoms and quality of life can predict whether a patient with UC requires escalation of therapy or intervention at an outpatient appointment. This may be used to streamline outpatient appointments for patients with UC.

Abnormal Cyclic Nucleotide Signaling at the Outer Mitochondrial Membrane In Sympathetic Neurons During the Early Stages of Hypertension.

BACKGROUND: Disruption of cyclic nucleotide signaling in sympathetic postganglionic neurons contributes to impaired intracellular calcium handling (Ca2+) and the development of dysautonomia during the early stages of hypertension, although how this occurs is poorly understood. Emerging evidence supports the uncoupling of signalosomes in distinct cellular compartments involving cyclic nucleotide-sensitive PDEs (phosphodiesterases), which may underpin the autonomic phenotype in stellate neurons. METHODS: Using a combination of single-cell RNA sequencing together with Forster resonance energy transfer-based sensors to monitor cyclic adenosine 3',5'-monophosphate, PKA (protein kinase A)-dependent phosphorylation and cGMP (cyclic guanosine 3',5'-monophosphate), we tested the hypothesis that dysregulation occurs in a sub-family of PDEs in the cytosol and outer mitochondrial membrane of neurons from the stellate ganglion. RESULTS: PDE2A, 6D, 7A, 9A genes were highly expressed in young Wistar neurons and also conserved in neurons from spontaneously hypertensive rats (SHRs). In stellate neurons from prehypertensive SHRs, we found the levels of cyclic adenosine 3',5'-monophosphate and cGMP at the outer mitochondrial membrane were decreased compared with normal neurons. The reduced cyclic adenosine 3',5'-monophosphate response was due to the hydrolytic activity of overexpressed PDE2A2 located at the mitochondria. Normal cyclic adenosine 3',5'-monophosphate levels were re-established by inhibition of PDE2A. There was also a greater PKA-dependent phosphorylation in the cytosol and at the outer mitochondrial membrane in spontaneously hypertensive rat neurons, where this response was regulated by protein phosphatases. The cGMP response was only restored by inhibition of PDE6. CONCLUSIONS: When taken together, these results suggest that site-specific inhibition of PDE2A and PDE6D at the outer mitochondrial membrane may provide a therapeutic target to ameliorate cardiac sympathetic impairment during the onset of hypertension.