Artificial Intelligence for Real-Time Prediction of the Histology of Colorectal Polyps by General Endoscopists.

BACKGROUND: Real-time prediction of histologic features of small colorectal polyps may prevent resection and/or pathologic evaluation and therefore decrease colonoscopy costs. Previous studies showed that computer-aided diagnosis (CADx) was highly accurate, though it did not outperform expert endoscopists. OBJECTIVE: To assess the diagnostic performance of histologic predictions by general endoscopists before and after assistance from CADx in a real-life setting. DESIGN: Prospective, multicenter, single-group study. (ClinicalTrials.gov: NCT04437615). SETTING: 6 centers across the United States. PARTICIPANTS: 1252 consecutive patients undergoing colonoscopy and 49 general endoscopists with variable experience in real-time prediction of polyp histologic features. INTERVENTION: Real-time use of CADx during routine colonoscopy. MEASUREMENTS: The primary end points were the sensitivity and specificity of CADx-unassisted and CADx-assisted histologic predictions for adenomas measuring 5 mm or less. For clinical purposes, additional estimates according to location and confidence level were provided. RESULTS: The CADx device made a diagnosis for 2695 polyps measuring 5 mm or less (96%) in 1252 patients. There was no difference in sensitivity between the unassisted and assisted groups (90.7% vs. 90.8%; P = 0.52). Specificity was higher in the CADx-assisted group (59.5% vs. 64.7%; P < 0.001). Among all 2695 polyps measuring 5 mm or less, 88.2% and 86.1% (P < 0.001) in the CADx-assisted and unassisted groups, respectively, could be resected and discarded without pathologic evaluation. Among 743 rectosigmoid polyps measuring 5 mm or less, 49.5% and 47.9% (P < 0.001) in the CADx-assisted and unassisted groups, respectively, could be left in situ without resection. LIMITATION: Decision making based on CADx might differ outside a clinical trial. CONCLUSION: CADx assistance did not result in increased sensitivity of optical diagnosis. Despite a slight increase, the specificity of CADx-assisted diagnosis remained suboptimal. PRIMARY FUNDING SOURCE: Olympus America Corporation served as the clinical study sponsor.

Hepatocellular carcinoma after direct-acting antivirals for hepatitis C is associated with KIR-HLA types predicting weak NK cell-mediated immunity.

BACKGROUND AND AIMS: Second-generation direct-acting antivirals (2G DAA) to cure HCV have led to dramatic clinical improvements. HCV-associated hepatocellular carcinoma (HCC), however, remains common. Impaired immune tumor surveillance may play a role in HCC development. Our cohort evaluated the effects of innate immune types and clinical variables on outcomes including HCC. METHODS: Participants underwent full HLA class I/KIR typing and long-term HCV follow-up. RESULTS: A total of 353 HCV+ participants were followed for a mean of 7 years. Cirrhosis: 25% at baseline, developed in 12% during follow-up. 158 participants received 2G DAA therapy. HCC developed without HCV therapy in 20 subjects, 24 HCC after HCV therapy, and 10 of these after 2G DAA. Two predictors of HCC among 2G DAA-treated patients: cirrhosis (OR, 10.0, p = 0.002) and HLA/KIR profiles predicting weak natural killer (NK) cell-mediated immunity (NK cell complementation groups 6, 9, 11, 12, OR of 5.1, p = 0.02). Without 2G DAA therapy: cirrhosis was the main clinical predictor of HCC (OR, 30.8, p < 0.0001), and weak NK-cell-mediated immunity did not predict HCC. CONCLUSION: Cirrhosis is the main risk state predisposing to HCC, but weak NK-cell-mediated immunity may predispose to post-2G DAA HCC more than intermediate or strong NK-cell-mediated immunity.

The role of urology and radiology in prostate biopsy: current trends and future perspectives.

PURPOSE: Prostate biopsy is central to the accurate histological diagnosis of prostate cancer. In current practice, the biopsy procedure can be performed using a transrectal or transperineal route with different technologies available for targeting of lesions within the prostate. Historically, the biopsy procedure was performed solely by urologists, but with the advent of image-guided techniques, the involvement of radiologists in prostate biopsy has become more common. Herein, we discuss the pros, cons and future considerations regarding their ongoing role. METHODS: A narrative review regarding the current evidence was completed. PubMed and Cochrane central register of controlled trials were search until January 2024. All study types were of consideration if published after 2000 and an English language translation was available. RESULTS: There are no published studies that directly compare outcomes of prostate biopsy when performed by a urologist or radiologist. In all published studies regarding the learning curve for prostate biopsy, the procedure was performed by urologists. These studies suggest that the learning curve for prostate biopsy is between 10 and 50 cases to reach proficiency in terms of prostate cancer detection and complications. It is recognised that many urologists are poorly able to accurately interpret multi parametric (mp)-MRI of the prostate. Collaboration between the specialities is of importance with urology offering the advantage of being involved in prior and future care of the patient while radiology has the advantage of being able to expertly interpret preprocedure MRI. CONCLUSION: There is no evidence to suggest that prostate biopsy should be solely performed by a specific specialty. The most important factor remains knowledge of the relevant anatomy and sufficient volume of cases to develop and maintain skills.

An Inclusive Civil Society Dialogue for Successful Implementation of the EU HTA Regulation: Call to Action to Ensure Appropriate Involvement of Stakeholders and Collaborators.

OBJECTIVES: Stakeholder involvement has long been considered a success factor for a joint European health technology assessment (HTA) process, and its relevance is now anchored in the EU HTA Regulation's (EU HTAR) legislative wording. Therefore, we aimed to explore the roles, challenges, and most important activities to increase the level of involvement per stakeholder group. METHODS: At the 2022 Fall Convention of the European Access Academy (EAA), working groups addressed the involvement of patients, clinicians, regulators, health technology developers (HTD), and national HTA bodies and payers within the EU HTA process. Each working group revisited the pre-convention survey results, determined key role characteristics for each stakeholder, and agreed on the most important activities to fulfill the role profile. Finally, the activities suggested per group were prioritized by plenary group. RESULTS: The prioritized actions for patients included training and capacity building, the establishment of a patient involvement committee, and the establishment of a patient unit at the EC secretariat. For clinicians, it included alignment on evidence assessment from a clinical vs. HTA point of view, capacity building, and standardization of processes. The most important actions for regulators are to develop joint regulatory-HTA guidance documents, align processes and interfaces under the regulation, and share discussions on post-licensing evidence generation. HTDs prioritized scientific advice capacity and the review of the scoping process, and further development of the scope of the assessment report fact checks. The top three actions for national HTA bodies and payers included clarification on the early HTD dialogue process, political support and commitment, and clarification on financial support. CONCLUSIONS: Addressing the activities identified as the most important for stakeholders/collaborators in the EU HTA process (e.g., in the implementation of the EU HTA Stakeholder Network and of the guidance documents developed by the EUnetHTA 21 consortium) will be key to starting an "inclusive civil society dialogue", as suggested by the European Commission's Pharmaceutical Strategy.

Erratum to 'Adductor Canal Block vs Liposomal Bupivacaine Periarticular Injection in Total Knee Arthroplasty: A Randomized Controlled Trial' [Arthroplasty Today 9 (2021) 21-28].

[This corrects the article DOI: 10.1016/j.artd.2021.03.008.].

Conservation genetics of Notelaea lloydii (Oleaceae) in south-eastern Queensland, Australia.

Habitat fragmentation can increase the chance of population bottlenecks and inbreeding, and may ultimately lead to reduced fitness and local extinction. Notelaea lloydii is a native olive species endemic to Australia and listed as vulnerable due to its restricted distribution. A recent molecular systematics study has revealed there might be some geographic structuring among N. lloydii populations. Therefore, we undertook a genome-wide single nucleotide polymorphism (SNP) analysis to determine levels and patterns of genetic diversity, inbreeding and gene flow within and among N. lloydii populations in south-eastern Queensland. Furthermore, as the reproductive phase of a plant's life history has a profound influence on genetic diversity, life history reproductive traits were also studied. Our SNP analysis revealed low genetic diversity, inbreeding and significant genetic structuring even among proximate populations. Results of a flower and fruit bagging experiment in two consecutive seasons revealed that N. lloydii produced many flowers but only a few fruits survived to maturity. There were no differences in bagged and un-bagged flowering and fruiting rates, and therefore, we conclude that the high fruit abortion rate was probably due to inbreeding depression and/or suboptimal conditions, rather than pollinator availability and insect attack. Overall, results of this study indicate that the populations of N. lloydii are small, inbred and genetically isolated and represent unique management units that require local conservation management due to ongoing threats associated with urbanisation.

Cost-effectiveness of volume computed tomography in lung cancer screening: a cohort simulation based on Nelson study outcomes.

OBJECTIVES: This study aimed to evaluate the cost-effectiveness of lung cancer screening (LCS) with volume-based low-dose computed tomography (CT) versus no screening for an asymptomatic high-risk population in the United Kingdom (UK), utilising the long-term insights provided by the NELSON study, the largest European randomized control trial investigating LCS. METHODS: A cost-effectiveness analysis was conducted using a decision tree and a state-transition Markov model to simulate the identification, diagnosis, and treatments for a lung cancer high-risk population, from a UK National Health Service (NHS) perspective. Eligible participants underwent annual volume CT screening and were compared to a cohort without the option of screening. Screen-detected lung cancers, costs, quality-adjusted life years (QALYs), and the incremental cost-effectiveness ratio (ICER) were predicted. RESULTS: Annual volume CT screening of 1.3 million eligible participants resulted in 96,474 more lung cancer cases detected in early stage, and 73,825 fewer cases in late stage, leading to 53,732 premature lung cancer deaths averted and 421,647 QALYs gained, compared to no screening. The ICER was £5,455 per QALY. These estimates were robust in sensitivity analyses. LIMITATIONS: Lack of long-term survival data for lung cancer patients; deficiency in rigorous micro-costing studies to establish detailed treatment costs inputs for lung cancer patients. CONCLUSIONS: Annual LCS with volume-based low-dose CT for a high-risk asymptomatic population is cost-effective in the UK, at a threshold of £20,000 per QALY, representing an efficient use of NHS resources with substantially improved outcomes for lung cancer patients, as well as additional societal and economic benefits for society as a whole. These findings advocate evidence-based decisions for the potential implementation of a nationwide LCS in the UK.

Lung dendritic-cell metabolism underlies susceptibility to viral infection in diabetes.

People with diabetes feature a life-risking susceptibility to respiratory viral infection, including influenza and SARS-CoV-2 (ref. 1), whose mechanism remains unknown. In acquired and genetic mouse models of diabetes, induced with an acute pulmonary viral infection, we demonstrate that hyperglycaemia leads to impaired costimulatory molecule expression, antigen transport and T cell priming in distinct lung dendritic cell (DC) subsets, driving a defective antiviral adaptive immune response, delayed viral clearance and enhanced mortality. Mechanistically, hyperglycaemia induces an altered metabolic DC circuitry characterized by increased glucose-to-acetyl-CoA shunting and downstream histone acetylation, leading to global chromatin alterations. These, in turn, drive impaired expression of key DC effectors including central antigen presentation-related genes. Either glucose-lowering treatment or pharmacological modulation of histone acetylation rescues DC function and antiviral immunity. Collectively, we highlight a hyperglycaemia-driven metabolic-immune axis orchestrating DC dysfunction during pulmonary viral infection and identify metabolic checkpoints that may be therapeutically exploited in mitigating exacerbated disease in infected diabetics.

Multiscale landscape genetic analysis identifies major waterways as a barrier to dispersal of feral pigs in north Queensland, Australia.

Feral pigs (Sus scrofa) are a destructive and widespread invasive pest in Australia. An understanding of feral pig movement is required to develop management strategies to control feral pigs in Australia. Because landscape structure can have a strong influence on animal movement, it is important to determine how landscape features facilitate or impede the movement of feral pigs. Consequently, we conducted a landscape genetic analysis of feral pig populations in the Herbert region of far north Queensland, Australia, to determine management units and provide recommendations to better inform feral pig population control strategies. Using microsatellite data obtained from 256 feral pig samples from 44 sites, we examined feral pig population structure at multiple spatial scales for univariate and multivariate landscape resistance surfaces to determine the optimal spatial scale and to identify which of the nine landscape features tested impede or facilitate feral pig gene flow. Only weak genetic structure was found among the 44 sampling sites, but major waterways were identified as a minor barrier to gene flow, and an isolation by distance model was supported. We also found that highways facilitated gene flow across the study area, and this suggests that they may act as movement corridors or indicate translocation of feral pigs. Additionally, incorporating a second spatial scale enhanced the ability of our landscape genetics analysis to detect the influence of landscape structure on gene flow. We identified three management units based on natural barriers to gene flow and future targeted control should be undertaken in these management units to deliver sustained reduction of feral pig populations in the Herbert region. This study demonstrates how a landscape genetic approach can be used to gain insight into the ecology of an invasive pest species and be used to develop population control strategies which utilise natural barriers to movement.

Guiding principles for technical infrastructure to support computable biomedical knowledge.

Over the past 4 years, the authors have participated as members of the Mobilizing Computable Biomedical Knowledge Technical Infrastructure working group and focused on conceptualizing the infrastructure required to use computable biomedical knowledge. Here, we summarize our thoughts and lay the foundation for future work in the development of CBK infrastructure, including: explaining the difference between computable knowledge and data, and contextualizing the conversation with the Learning Health Systems and the FAIR principles. Specifically, we provide three guiding principles to advance the development of CBK infrastructure: (a) Promote interoperable systems for data and knowledge to be findable, accessible, interoperable, and reusable. (b) Enable stable, trustworthy knowledge representations that are human and machine readable. (c) Computable knowledge resources should, when possible, be open. Standards supporting computable knowledge infrastructures must be open.

The role of stakeholder involvement in the evolving EU HTA process: Insights generated through the European Access Academy's multi-stakeholder pre-convention questionnaire.

Involvement of all relevant stakeholders will be of utmost importance for the success of the developing EU HTA harmonization process. A multi-step procedure was applied to develop a survey across stakeholders/collaborators within the EU HTA framework to assess their current level of involvement, determine their suggested future role, identify challenges to contribution, and highlight efficient ways to fulfilling their role. The 'key' stakeholder groups identified and covered by this research included: patients', clinicians', regulatory, and Health Technology Developer representatives. The survey was circulated to a wide expert audience including all relevant stakeholder groups in order to determine self-perception by the 'key' stakeholders regarding involvement in the HTA process (self-rating), and in a second, slightly modified version of the questionnaire, to determine the perception of 'key' stakeholder involvement by HTA bodies, payers, and policymakers (external rating). Predefined analyses were conducted on the submitted responses. Fifty-four responses were received (patients 9; clinicians: 8; regulators: 4; HTDs 14; HTA bodies: 7; Payers: 5; policymakers 3; others 4). The mean self-perceived involvement score was consistently lower for each of the 'key' stakeholder groups than the respective external ratings. Based on the qualitative insights generated in the survey, a RACI Chart (Responsible/Accountable/Consulted/Informed) was developed for each of the stakeholder groups to determine their roles and involvement in the current EU HTA process. Our findings suggest extensive effort and a distinct research agenda are required to ensure adequate involvement of the key stakeholder groups in the evolving EU HTA process.

Growth Rates of Pulmonary Carcinoid Tumors and Hamartomas.

BACKGROUND: Pulmonary nodule growth is often measured by volume doubling time (VDT), which may guide management. Most malignant nodules have a VDT of 20 to 400 days, with longer VDTs typically observed in indolent nodules. We assessed the utility of VDT in differentiating pulmonary carcinoids and hamartomas. METHODS: A review was performed from January 2012 to October 2021 to identify patients with pathologic diagnoses and at least 2 chest computed tomography scans obtained 6 or more months apart. Visualization software was used to segment nodules and calculate diameter and volume. Volume doubling time was calculated for scans with 1-mm slices. For the remainder, estimated nodule volume doubling time (eVDT) was calculated using nodule diameter. Volume doubling times/eVDTs were placed into growth categories: less than 400 days; 400-600 days; and more than 600 days. RESULTS: Sixty nodules were identified, 35 carcinoids and 25 hamartomas. Carcinoids were larger than hamartomas (median diameter, 13.5 vs 11.5 mm; P = 0.05). For carcinoid tumors, median VDT (n = 15) was 1485 days, and median eVDT (n = 32) was 1309 days; for hamartomas, median VDT (n = 8) was 2040 days and median eVDT (n = 25) was 2253 days. Carcinoid tumor eVDT was significantly shorter than hamartomas ( P = 0.03). By growth category, 1 of 25 hamartomas and 5 of 35 carcinoids had eVDT less than 400 days and 24 of 25 hamartomas and 27 of 35 carcinoids had eVDT more than 600 days. Of 4 carcinoid tumors with metastases, 2 had eVDT less than 400 days and 2 had eVDT more than 600 days. CONCLUSIONS: Growth rate was not a reliable differentiator of pulmonary hamartomas and carcinoids. Slow growing carcinoids can metastasize. Radiologists should be cautious when discontinuing computed tomography follow-up based on growth rates alone.

A Prospective Multi-institutional Study Using a Novel Safety Valve for the Prevention of Catheter Balloon Inflation Injury of the Urethra.

PURPOSE: We prospectively assessed the ability of a novel transurethral catheterization safety valve to prevent urethral catheter balloon injury in a multi-institutional clinical setting. MATERIALS AND METHODS: A prospective, multi-institution study was conducted. The safety valve was introduced for urinary catheterization in 6 hospital groups (4 in Ireland; 2 in the UK). The safety valve allows fluid in the catheter system to vent through a pressure relief valve if attempted intraurethral inflation of the catheter's anchoring balloon occurs. Device usage was studied over a 12-month period, with data recorded using a 7-item data sticker containing a scannable QR code. "Venting" through the safety valve during catheterization was indicative of prevention of a urethral injury. An embedded 3-month study was conducted in 3 centers, with any catheter balloon injuries occurring during catheterization without safety valve use referred to the on-call urology team recorded. Health economic analyses were also performed. RESULTS: During the overall 12-month device study phase, 994 urethral catheterizations were performed across study sites. Twenty-two (2.2%) episodes of safety valve venting were recorded. No urethral injuries occurred in these patients. In the embedded 3-month study, 18 catheter balloon injuries were recorded in association with catheterizations performed without the safety valve. Based on confirmed and device-prevented urethral injuries, the injury rate for urethral catheterization without safety valve use was calculated to be 5.5/1,000 catheterizations. CONCLUSIONS: The safety valve has the potential to eliminate catheter balloon injury if widely adopted. It represents a simple, effective, and innovative solution to this recurring problem applicable to all patient cohorts.

Epithelial Nlrp10 inflammasome mediates protection against intestinal autoinflammation.

Unlike other nucleotide oligomerization domain-like receptors, Nlrp10 lacks a canonical leucine-rich repeat domain, suggesting that it is incapable of signal sensing and inflammasome formation. Here we show that mouse Nlrp10 is expressed in distal colonic intestinal epithelial cells (IECs) and modulated by the intestinal microbiome. In vitro, Nlrp10 forms an Apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC)-dependent, m-3M3FBS-activated, polyinosinic:polycytidylic acid-modulated inflammasome driving interleukin-1ß and interleukin-18 secretion. In vivo, Nlrp10 signaling is dispensable during steady state but becomes functional during autoinflammation in antagonizing mucosal damage. Importantly, whole-body or conditional IEC Nlrp10 depletion leads to reduced IEC caspase-1 activation, coupled with enhanced susceptibility to dextran sodium sulfate-induced colitis, mediated by altered inflammatory and healing programs. Collectively, understanding Nlrp10 inflammasome-dependent and independent activity, regulation and possible human relevance might facilitate the development of new innate immune anti-inflammatory interventions.

Coral adaptive capacity insufficient to halt global transition of coral reefs into net erosion under climate change.

Projecting the effects of climate change on net reef calcium carbonate production is critical to understanding the future impacts on ecosystem function, but prior estimates have not included corals' natural adaptive capacity to such change. Here we estimate how the ability of symbionts to evolve tolerance to heat stress, or for coral hosts to shuffle to favourable symbionts, and their combination, may influence responses to the combined impacts of ocean warming and acidification under three representative concentration pathway (RCP) emissions scenarios (RCP2.6, RCP4.5 and RCP8.5). We show that symbiont evolution and shuffling, both individually and when combined, favours persistent positive net reef calcium carbonate production. However, our projections of future net calcium carbonate production (NCCP) under climate change vary both spatially and by RCP. For example, 19%-35% of modelled coral reefs are still projected to have net positive NCCP by 2050 if symbionts can evolve increased thermal tolerance, depending on the RCP. Without symbiont adaptive capacity, the number of coral reefs with positive NCCP drops to 9%-13% by 2050. Accounting for both symbiont evolution and shuffling, we project median positive NCPP of coral reefs will still occur under low greenhouse emissions (RCP2.6) in the Indian Ocean, and even under moderate emissions (RCP4.5) in the Pacific Ocean. However, adaptive capacity will be insufficient to halt the transition of coral reefs globally into erosion by 2050 under severe emissions scenarios (RCP8.5).

The Ability of Patients to Correctly Identify Their Hospitalist on a Patient Satisfaction Survey and the Impact of This Factor on Hospitalist Scores.

Background: Patient evaluations of their physician have been utilized to evaluate physician performance and calculate hospital reimbursement. Despite the routine use of these evaluations, little research has been done to evaluate the accuracy of these evaluations. We assessed patient's ability to correctly identify the hospitalist providing their care and whether identification of the hospitalist affected the cumulative satisfaction scores. Methods: This prospective observational study was conducted at a suburban voluntary hospital. Hospitalists were evaluated anonymously by their patients over a 4-month period on a questionnaire designed to assess patient satisfaction. Results: One hundred fifty-eight patients evaluated 16 hospitalists yielding an average of 9.9 evaluations per hospitalist. Forty Nine (31%) patients were able to identify their hospitalist. The top score (3) accounted for 76% of patient responses across all questions. Significant differences (p = .0007) existed in the distribution of these scores when patients who could identify their hospitalist was compared with those who couldn't. The variables for effective communication and hospitalist introduction were scored significantly higher by patients who could identify their hospitalist (2.77 vs 2.55; p = .027 and 2.90 vs 2.67; p = .005). Patients of younger age and female gender were more likely identify their hospitalist. Conclusions: Less than one-third of patients were able to correctly identify their hospitalist. The variables for effective communication and hospitalist introduction to the patient were scored significantly higher by patients who could identify their hospitalist. The elimination of scores by patients who could not correctly identify their provider resulted in marked changes in the percentile ranking of these providers.

Inequity in smoking cessation clinical trials testing pharmacotherapies: exclusion of smokers with mental health disorders.

OBJECTIVES: People suffering from mental health disorder (MHDs) are often under-represented in clinical research though the reasons for their exclusion are rarely recorded. As they have higher rates of smoking and nicotine dependence, it is crucial that they are adequately represented in clinical trials of established pharmacotherapy interventions for smoking cessation. This review aims to examine the practice of excluding smokers with MHDs and reasons for such exclusion in clinical trials evaluating pharmacotherapy treatments for smoking cessation. DATA SOURCE: The Cochrane database of systematic reviews was searched until September 2020 for reviews on smoking cessation using pharmacotherapies. STUDY SELECTION: Randomised controlled trials (RCTs) within the selected Cochrane reviews were included. DATA EXTRACTION: Conducted by one author and independently verified by three authors. DATA SYNTHESIS: We included 279 RCTs from 13 Cochrane reviews. Of all studies, 51 (18.3%) explicitly excluded participants with any MHDs, 152 (54.5%) conditionally excluded based on certain MHD criteria and 76 (27.2%) provided insufficient information to ascertain either inclusion or exclusion. Studies of antidepressant medications used for smoking cessation were found to be 3.33 times more likely (95% CI 1.38 to 8.01, p=0.007) to conditionally exclude smokers with MHDs than explicitly exclude compared with studies of nicotine replacement therapy. CONCLUSION: Smokers with MHDs are not sufficiently represented in RCTs examining the safety and effectiveness of smoking cessation medications. Greater access to clinical trial participation needs to be facilitated for this group to better address access to appropriate pharmacotherapeutic interventions in this vulnerable population.