Use of a Novel Artificial Intelligence System Leads to the Detection of Significantly Higher Number of Adenomas During Screening and Surveillance Colonoscopy: Results From a Large, Prospective, US Multicenter, Randomized Clinical Trial.

INTRODUCTION: Adenoma per colonoscopy (APC) has recently been proposed as a quality measure for colonoscopy. We evaluated the impact of a novel artificial intelligence (AI) system, compared with standard high-definition colonoscopy, for APC measurement. METHODS: This was a US-based, multicenter, prospective randomized trial examining a novel AI detection system (EW10-EC02) that enables a real-time colorectal polyp detection enabled with the colonoscope (CAD-EYE). Eligible average-risk subjects (45 years or older) undergoing screening or surveillance colonoscopy were randomized to undergo either CAD-EYE-assisted colonoscopy (CAC) or conventional colonoscopy (CC). Modified intention-to-treat analysis was performed for all patients who completed colonoscopy with the primary outcome of APC. Secondary outcomes included positive predictive value (total number of adenomas divided by total polyps removed) and adenoma detection rate. RESULTS: In modified intention-to-treat analysis, of 1,031 subjects (age: 59.1 ± 9.8 years; 49.9% male), 510 underwent CAC vs 523 underwent CC with no significant differences in age, gender, ethnicity, or colonoscopy indication between the 2 groups. CAC led to a significantly higher APC compared with CC: 0.99 ± 1.6 vs 0.85 ± 1.5, P = 0.02, incidence rate ratio 1.17 (1.03-1.33, P = 0.02) with no significant difference in the withdrawal time: 11.28 ± 4.59 minutes vs 10.8 ± 4.81 minutes; P = 0.11 between the 2 groups. Difference in positive predictive value of a polyp being an adenoma among CAC and CC was less than 10% threshold established: 48.6% vs 54%, 95% CI -9.56% to -1.48%. There were no significant differences in adenoma detection rate (46.9% vs 42.8%), advanced adenoma (6.5% vs 6.3%), sessile serrated lesion detection rate (12.9% vs 10.1%), and polyp detection rate (63.9% vs 59.3%) between the 2 groups. There was a higher polyp per colonoscopy with CAC compared with CC: 1.68 ± 2.1 vs 1.33 ± 1.8 (incidence rate ratio 1.27; 1.15-1.4; P < 0.01). DISCUSSION: Use of a novel AI detection system showed to a significantly higher number of adenomas per colonoscopy compared with conventional high-definition colonoscopy without any increase in colonoscopy withdrawal time, thus supporting the use of AI-assisted colonoscopy to improve colonoscopy quality ( ClinicalTrials.gov NCT04979962).

Emergence potential of mosquito-borne arboviruses from the Florida Everglades.

The Greater Everglades Region of South Florida is one of the largest natural wetlands and the only subtropical ecosystem found in the continental United States. Mosquitoes are seasonally abundant in the Everglades where several potentially pathogenic mosquito-borne arboviruses are maintained in natural transmission cycles involving vector-competent mosquitoes and reservoir-competent vertebrate hosts. The fragile nature of this ecosystem is vulnerable to many sources of environmental change, including a wetlands restoration project, climate change, invasive species and residential development. In this study, we obtained baseline data on the distribution and abundance of both mosquitos and arboviruses occurring in the southern Everglades region during the summer months of 2013, when water levels were high, and in 2014, when water levels were low. A total of 367,060 mosquitoes were collected with CO2-baited CDC light traps at 105 collection sites stratified among the major landscape features found in Everglades National Park, Big Cypress National Preserve, Fakahatchee State Park Preserve and Picayune State Forest, an area already undergoing restoration. A total of 2,010 pools of taxonomically identified mosquitoes were cultured for arbovirus isolation and identification. Seven vertebrate arboviruses were isolated: Everglades virus, Tensaw virus, Shark River virus, Gumbo Limbo virus, Mahogany Hammock virus, Keystone virus, and St. Louis encephalitis virus. Except for Tensaw virus, which was absent in 2013, the remaining viruses were found to be most prevalent in hardwood hammocks and in Fakahatchee, less prevalent in mangroves and pinelands, and absent in cypress and sawgrass. In contrast, in the summer of 2014 when water levels were lower, these arboviruses were far less prevalent and only found in hardwood hammocks, but Tensaw virus was present in cypress, sawgrass, pinelands, and a recently burned site. Major environmental changes are anticipated in the Everglades, many of which will result in increased water levels. How these might lead to the emergence of arboviruses potentially pathogenic to both humans and wildlife is discussed.

Patient Release and Instructions for Lutetium Dotatate Radiopharmaceutical Therapy.

ABSTRACT: Lutetium Dotatate radiopharmaceutical therapy (Lutathera) was approved by the United States Food and Drug Administration in 2018 and is used to treat somatostatin receptor positive neuroendocrine tumors. With all new radiopharmaceutical therapies, the radiation exposure to members of the public from the patient who received the therapy must be within regulatory limits and safe. If the patient will expose members of the public to too much radiation, the therapy must be performed on an inpatient basis. This paper shows that the administration of Lutathera can be done on an outpatient basis and provides safety and travel restrictions that should be communicated to the patient prior to leaving. The guidance presented herein serves as a basis for medical institutions looking to use Lutathera to treat patients.

Pairwise comparison locomotion scoring for dairy cattle.

Conventional locomotion scoring is a subjective, absolute, and discrete assessment of locomotion. Here we assess pairwise comparison scoring to improve upon the limited intra- and interobserver consistency typical of conventional locomotion scoring. Five observers performed conventional 4-level locomotion scoring using 50 video recordings of dairy cattle, and also assessed 90 pairs of videos (composed from the same 50 recordings) using relative pairwise scoring. Intra- and interobserver consistency of pairwise scores [intraobserver: percentage agreement (PA) = 82%, κ = 0.63; interobserver: PA = 79%, κ = 0.57] were greater than of 4-level absolute scores (intraobserver: PA = 72%, κw = 0.74; interobserver: PA = 56%, κw = 0.59). Pairwise scores were scaled with an optimization method to obtain the position of the 50 recordings on a continuous locomotion scale. These continuous locomotion scores (CLS) were compared with the conventional mean absolute visual locomotion scores (VLS). Correlation between CLS and VLS was strong (τ = 0.69), and consistency between binarized CLS and binarized VLS was high (PA = 84%, κ = 0.66 for threshold VLS ≥1). Just noticeable difference (JND) for locomotion scoring was 0.3 on a 4-level scale ranging from 0 to 3. Pairwise scoring and scaling had the scoring consistency of binary absolute scoring with finer continuous granularity than 4-level absolute scoring. The pairwise scoring method, and associated scaling, offer a more consistent and informative alternative to conventional absolute multilevel locomotion scoring.

Extrinsic Parameter Calibration for Line Scanning Cameras on Ground Vehicles with Navigation Systems Using a Calibration Pattern.

Line scanning cameras, which capture only a single line of pixels, have been increasingly used in ground based mobile or robotic platforms. In applications where it is advantageous to directly georeference the camera data to world coordinates, an accurate estimate of the camera's 6D pose is required. This paper focuses on the common case where a mobile platform is equipped with a rigidly mounted line scanning camera, whose pose is unknown, and a navigation system providing vehicle body pose estimates. We propose a novel method that estimates the camera's pose relative to the navigation system. The approach involves imaging and manually labelling a calibration pattern with distinctly identifiable points, triangulating these points from camera and navigation system data and reprojecting them in order to compute a likelihood, which is maximised to estimate the 6D camera pose. Additionally, a Markov Chain Monte Carlo (MCMC) algorithm is used to estimate the uncertainty of the offset. Tested on two different platforms, the method was able to estimate the pose to within 0.06 m/1.05 ∘ and 0.18 m/2.39 ∘ . We also propose several approaches to displaying and interpreting the 6D results in a human readable way.

More than meets the eye: the changing face of histopathology.

This personal reflection on trends in histopathology over the past 50 years draws upon experience of professional training and practice in the specialty in the UK. Developments during this period often resulted from new therapies (and their adverse effects) necessitating greater precision in the histopathological classification of disease, for which morphology alone can be insufficient. Conversely, histopathology has contributed to advances in our understanding of disease, leading directly to novel and more effective treatments. New infections, some involving histopathology in their discovery, have also led to fresh diagnostic challenges. Increasingly, patients have benefited from fundamental changes in professionalism in pathology. Through audit, external quality assurance, continuing professional development, standardized reporting, and increasing specialization, the consistency and reliability of histopathological diagnoses have steadily improved. Regarding the specialty's future, some now see rivalry between the morphological and molecular approaches to diagnosis and classification, particularly for neoplastic disease. An integrated strategy led by the specialty is more likely to strengthen histopathology and ultimately to have the greatest benefit for patients.

Image Based Mango Fruit Detection, Localisation and Yield Estimation Using Multiple View Geometry.

This paper presents a novel multi-sensor framework to efficiently identify, track, localise and map every piece of fruit in a commercial mango orchard. A multiple viewpoint approach is used to solve the problem of occlusion, thus avoiding the need for labour-intensive field calibration to estimate actual yield. Fruit are detected in images using a state-of-the-art faster R-CNN detector, and pair-wise correspondences are established between images using trajectory data provided by a navigation system. A novel LiDAR component automatically generates image masks for each canopy, allowing each fruit to be associated with the corresponding tree. The tracked fruit are triangulated to locate them in 3D, enabling a number of spatial statistics per tree, row or orchard block. A total of 522 trees and 71,609 mangoes were scanned on a Calypso mango orchard near Bundaberg, Queensland, Australia, with 16 trees counted by hand for validation, both on the tree and after harvest. The results show that single, dual and multi-view methods can all provide precise yield estimates, but only the proposed multi-view approach can do so without calibration, with an error rate of only 1.36% for individual trees.

Radar Sensing for Intelligent Vehicles in Urban Environments.

Radar overcomes the shortcomings of laser, stereovision, and sonar because it can operate successfully in dusty, foggy, blizzard-blinding, and poorly lit scenarios. This paper presents a novel method for ground and obstacle segmentation based on radar sensing. The algorithm operates directly in the sensor frame, without the need for a separate synchronised navigation source, calibration parameters describing the location of the radar in the vehicle frame, or the geometric restrictions made in the previous main method in the field. Experimental results are presented in various urban scenarios to validate this approach, showing its potential applicability for advanced driving assistance systems and autonomous vehicle operations.

Long-Term Prognostic Significance of Persisting Histological Activity Despite Biochemical Remission in Autoimmune Hepatitis.

OBJECTIVES: Biochemical remission is widely considered a satisfactory treatment end point in autoimmune hepatitis (AIH). The significance of persisting histological activity despite biochemical remission is unknown. We aimed to assess the frequency and prognostic significance of persisting histological inflammation in patients with AIH who had achieved biochemical remission with treatment. METHODS: We studied 120 patients (median age at diagnosis 57 years; 81% female) with AIH by International Criteria (59% definite), who received immunosuppressive treatment and underwent a follow-up liver biopsy after at least 6 months of sustained biochemical remission (defined as normal serum ALT and globulin). RESULTS: Fifty-five patients (46%) had persisting histological activity (Ishak histological activity index (HAI) ≥4). These patients had higher serum ALT (24 vs. 18 IU/l, P=0.003) and AST (27 vs. 23 IU/l, P=0.03) at the time of follow-up biopsy, compared with patients who achieved histological remission (HAI ≤3). They had less frequent regression of fibrosis on follow-up biopsy compared with those achieving histological remission (32 vs. 60%, P=0.004) and had excess mortality (standardized mortality ratio 1.4 vs. 0.7, P<0.05). The excess mortality was due to liver disease. On multivariate analysis, persisting histological activity was independently associated with all-cause death/transplantation (HR 3.1 (95% CI 1.2-8.1); P=0.02); an association with liver-related death/transplantation fell short of significance (HR 9.7 (95% CI 0.84-111.6; P=0.07). CONCLUSIONS: Persisting histological activity, despite biochemical remission, is frequent in patients with treated AIH and is associated with lower rates of fibrosis regression and reduced long-term survival.

Prognostic significance of Akt, phospho-Akt and BAD expression in primary breast cancer.

Apoptotic markers in breast cancer are reported to have prognostic significance. The aim of this study was to assess the prognostic value of Akt, phospho-Akt and BAD expression in primary tumours from breast cancer patients. Expression of phospho-Akt did not correlate with menopausal status, nodal involvement or tumour size, although there was a significant correlation between phospho-Akt and oestrogen receptor status and tumour grade. No association was found between phospho-Akt and BAD. However, a significant correlation was found between Akt and BAD. Akt and phospho-Akt expression did not correlate with either disease-free survival (DFS) or overall survival (OS). Conversely, BAD immunostaining correlated significantly with increasing tumour size and with oestrogen receptor (ER) immunostaining in both frozen and paraffin sections. Expression of BAD appeared to be nucleolar in addition to its cytoplasmic and nuclear staining. Comparison of immunohistochemical staining on frozen sections and paraffin sections showed a reasonable concordance in Akt and BAD immunoreactivity. However, the results showed for the first time that strong BAD expression is related to a favourable prognosis but is not an independent prognostic factor. In conclusion, these results could provide the basis for understanding how Akt, phospho-Akt and BAD expression contributes to the prognosis of invasive breast cancer.

Transmucosal gastric leak induced by proton pump inhibitors.

Despite their remarkable safety profile and lack of clinical side effects, proton pump inhibitors (PPIs) induce a transmucosal gastric leak to non-electrolyte probes of various sizes. The ex vivo addition of PPIs to isolated rat gastric corpus increases transmucosal permeability in a dose-dependent manner, which corresponds with PPIs' dose-dependent inhibition of acid secretion. Upon the addition of omeprazole, lansoprazole, or esomeprazole, a small decrease in transepithelial resistance and the concomitant stimulation of short circuit current was observed. Additionally, transepithelial flux of (14)C-[D]-mannitol (MW 182.17) across the gastric mucosa increased by a mean of 68% immediately following the addition of 200 microM omeprazole. This flux increase was bidirectional. Omeprazole also increased the paracellular permeability to larger radiolabeled probes, including (14)C-sucrose (MW 342.3) and (14)C-polyethylene glycol (MW 4,000) by 118% and 350%, respectively. However, the flux of still larger probes, 10,000 and 70,000 MW dextrans, was not increased. Because PPIs are so widely used and are assumed to be innocuous, this transmucosal gastric leak must be further investigated, as it may carry considerable biomedical implications.

Clinical, educational, and epidemiological value of autopsy.

The autopsy is now often regarded as of marginal use in modern clinical practice. In this Review we contend that the autopsy remains an important procedure with substantial, if largely underused, potential to advance medical knowledge and improve clinical practice. Many doctors lack familiarity with autopsy practices, and are insufficiently aware of the benefits for not only bereaved families but also present and future patients. In this Review, which has an international perspective, we consider the ascent and decline of the autopsy, the legal frameworks that govern its use, the value and potential pitfalls of alternatives to the conventional method, and the autopsy's role in undergraduate medical education. We also draw attention to the continuing ability of autopsies to improve the completeness and reliability of death certification, which is important for public-health strategies and for some bereaved families.

Gorham disease: an intraoperative case study.

Gorham disease is a rare chronic disorder that is characterized by the abnormal proliferation of thin-walled capillaries and small lymphatic vessels that results in the massive osteolysis of adjacent bone. Clinical manifestations are determined by the area of involvement, which may include the chest and ribs. The case presented involves a 47-year-old man with Gorham disease complicated by unilateral chylothorax who was treated with thoracic duct ligation. The anesthetic implications associated with Gorham disease are discussed, and nonsurgical primary and adjunctive treatments for chylothorax are summarized.

Clearance of hepatitis C virus is not associated with single nucleotide polymorphisms in the IL-1, -6, or -10 genes.

Hepatitis C virus (HCV) commonly causes a chronic infection, but a minority of patients are able to clear the virus and do not run the risk of developing HCV-induced organ damage. Genetic associations between immunoregulatory cytokines interleukin (IL)-1, -6, and -10 with clinical features of HCV, including virus clearance, have been inconsistent. We determined cytokine genotypes in 606 patients who had serologic evidence of HCV exposure, 190 (18%) of whom were consistently negative for HCV RNA, indicating successful virus clearance. There was no significant difference in genotype frequencies between HCV clearance and nonclearance groups for IL-1B (-511 and +3954), IL-1A (+4845), IL-1RN (+2018), IL-6 (-174), or IL-10 (-1082). We conclude that these single nucleotide polymorphisms are unlikely to play an important, if any, role in determining the likelihood of clearing HCV infection.

Histopathology training in Europe: a lesson for other specialties?

Critical shortages of trained histopathologists limit the capacity of cancer and other clinical services. A survey of histopathology training in 18 European countries conducted by the European Union of Medical Specialists Section of Pathology/European Board of Pathology revealed a considerable shortage of both trained and trainee histopathologists in several of the responding countries. Demographic data indicate a high preponderance of trained histopathologists over 55 years of age and a notable proportion of part-time personnel. Although the training capacity in some countries has been increased, the immediate future of histopathology and the clinical services dependent on the specialty is worrisome. The histopathology workload is growing, and, in some countries, recruitment of trainees is insufficient for future needs. To avert the serious consequences for dependent clinical specialties and their patients, there should be a concerted European action to promote and expand histopathology training.

Alphastatin, a 24-amino acid fragment of human fibrinogen, is a potent new inhibitor of activated endothelial cells in vitro and in vivo.

Angiogenesis, the development of new blood vessels from existing vasculature, is crucial for the development and metastasis of solid tumors. Here, we show for the first time that a 24-amino acid peptide derived from the amino terminus of the alpha chain of human fibrinogen (termed "alphastatin") has potent antiangiogenic properties, inhibiting both the migration and tubule formation of human dermal microvascular endothelial cells in response to vascular endothelial growth factor (VEGF) or basic fibroblast growth factor (bFGF) in vitro. Moreover, alphastatin markedly inhibits the growth of tumors in a syngeneic murine model. Tumors from mice receiving daily injections of alphastatin for 12 days exhibited large areas of intravascular disruption and thrombosis with substantial cellular necrosis. Importantly, alphastatin administration had no detectable effect on vessels in such normal tissues as liver, lungs, and kidney. Taken together, these data indicate that alphastatin is a potent new antiangiogenic agent in vitro and antivascular agent in vivo.