Identifying Environmental Reservoirs Of A Cystic Fibrosis Epidemic Strain Of Pseudomonas Aeruginosa

Pseudomonas aeruginosa is an important cause of infection, particularly amongst Cystic Fibrosis (CF) patients. While a rare opportunistic pathogen, it is commonly isolated from CF patients as it infects 70% of these individuals [1]. The dogma that was held for many years was that each patient was independently infected by locally acquired non-clonal strains of P. aeruginosa from their own environment.  However, it has been increasingly recognized that many patients attending the same clinic may be infected with genetically related strains, suggesting that infection of these strains may also be achieved through patient-to-patient transmission, such as the Prarie Epidemic Strain concentrated in Southern Alberta [1]. While several strains of P. aeruginosa are 'transmissible', the majority of patients acquire infection with unique isolates [2]. There is a need to understand the relationship between patients living in a particular local and the likelihood of infection with organisms endemic in that local. Determining these pockets is essential as P. aeruginosa is a leading cause of morbidity and mortality in patients with CF. Here we report the results of 309 water samples collected from heavily populated CF regions in Southern Alberta. The data confirms that pockets of P. aeruginosa exist in this region

Synthesizing Diabetic Foot Ulcer Images with Diffusion Model

Diabetic Foot Ulcer (DFU) is a serious skin wound requiring specialized care. However, real DFU datasets are limited, hindering clinical training and research activities. In recent years, generative adversarial networks and diffusion models have emerged as powerful tools for generating synthetic images with remarkable realism and diversity in many applications. This paper explores the potential of diffusion models for synthesizing DFU images and evaluates their authenticity through expert clinician assessments. Additionally, evaluation metrics such as Frechet Inception Distance (FID) and Kernel Inception Distance (KID) are examined to assess the quality of the synthetic DFU images. A dataset of 2,000 DFU images is used for training the diffusion model, and the synthetic images are generated by applying diffusion processes. The results indicate that the diffusion model successfully synthesizes visually indistinguishable DFU images. 70% of the time, clinicians marked synthetic DFU images as real DFUs. However, clinicians demonstrate higher unanimous confidence in rating real images than synthetic ones. The study also reveals that FID and KID metrics do not significantly align with clinicians' assessments, suggesting alternative evaluation approaches are needed. The findings highlight the potential of diffusion models for generating synthetic DFU images and their impact on medical training programs and research in wound detection and classification.Comment: 8 pages, 3 figures, 6th Workshop on AI for Aging, Rehabilitation and Intelligent Assisted Living at European Conference on Machine Learning, Italy, 202

Liver transplantation in the critically ill: a multicenter Canadian retrospective cohort study

Introduction: Critically ill cirrhosis patients awaiting liver transplantation (LT) often receive prioritization for organ allocation. Identification of patients most likely to benefit is essential. The purpose of this study was to examine whether the Sequential Organ Failure Assessment (SOFA) score can predict 90-day mortality in critically ill recipients of LT and whether it can predict receipt of LT among critically ill cirrhosis listed awaiting LT. Methods: We performed a multicenter retrospective cohort study consisting of two datasets: (a) all critically-ill cirrhosis patients requiring intensive care unit (ICU) admission before LT at five transplant centers in Canada from 2000 through 2009 (one site, 1990 through 2009), and (b) critically ill cirrhosis patients receiving LT from ICU (n = 115) and those listed but not receiving LT before death (n = 106) from two centers where complete data were available. Results: In the first dataset, 198 critically ill cirrhosis patients receiving LT (mean (SD) age 53 (10) years, 66% male, median (IQR) model for end-stage liver disease (MELD) 34 (26-39)) were included. Mean (SD) SOFA scores at ICU admission, at 48 hours, and at LT were 12.5 (4), 13.0 (5), and 14.0 (4). Survival at 90 days was 84% (n = 166). In multivariable analysis, only older age was independently associated with reduced 90-day survival (odds ratio (OR), 1.07; 95% CI, 1.01 to 1.14; P = 0.013). SOFA score did not predict 90-day mortality at any time. In the second dataset, 47.9% (n = 106) of cirrhosis patients listed for LT died in the ICU waiting for LT. In multivariable analysis, higher SOFA at 48 hours after admission was independently associated with lower probability of receiving LT (OR, 0.89; 95% CI, 0.82 to 0.97; P = 0.006). When including serum lactate and SOFA at 48 hours in the final model, elevated lactate (at 48 hours) was also significantly associated with lower likelihood of receiving LT (0.32; 0.17 to 0.61; P = 0.001). Conclusions: SOFA appears poor at predicting 90-day survival in critically ill cirrhosis patients after LT, but higher SOFA score and elevated lactate 48 hours after ICU admission are associated with a lower probability receiving LT. Older critically ill cirrhosis patients (older than 60) receiving LT have worse 90-day survival and should be considered for LT with caution

Logically Inferred Tuberculosis Transmission (LITT): A Data Integration Algorithm to Rank Potential Source Cases

Understanding tuberculosis (TB) transmission chains can help public health staff target their resources to prevent further transmission, but currently there are few tools to automate this process. We have developed the Logically Inferred Tuberculosis Transmission (LITT) algorithm to systematize the integration and analysis of whole-genome sequencing, clinical, and epidemiological data. Based on the work typically performed by hand during a cluster investigation, LITT identifies and ranks potential source cases for each case in a TB cluster. We evaluated LITT using a diverse dataset of 534 cases in 56 clusters (size range: 2–69 cases), which were investigated locally in three different U.S. jurisdictions. Investigators and LITT agreed on the most likely source case for 145 (80%) of 181 cases. By reviewing discrepancies, we found that many of the remaining differences resulted from errors in the dataset used for the LITT algorithm. In addition, we developed a graphical user interface, user's manual, and training resources to improve LITT accessibility for frontline staff. While LITT cannot replace thorough field investigation, the algorithm can help investigators systematically analyze and interpret complex data over the course of a TB cluster investigation.Code available at:https://github.com/CDCgov/TB_molecular_epidemiology/tree/1.0; https://zenodo.org/badge/latestdoi/166261171

WHAT CAN ADAPTIVE OPTICS DO FOR A SCANNING LASER OPHTHALMOSCOPE ? MOT-CLÉS

ABSTRACT By compensating for the aberrations in the eye that cause blur, the adaptive optics scanning laser ophthalmoscope (AOSLO) yields high-magnification, high-resolution, real-time images of the living human retina. Features as small as single cone photoreceptors can be resolved, single leukocytes are recorded in real time as they pass through the smallest retinal capillaries, and the optical sectioning capability can be used to visualize independent layers of the retinal tissue ranging from the nerve fiber layer, through the blood vessels to the photoreceptors. The use of AO technology not only enhances the breadth of applications of conventional SLOs, but it facilitates a host of new applications. Here we provide an overview of AOSLO performance and its applications, including two clinical examples. Finally, we preview two novel applications; one where the AOSLO is used to present AO-corrected stimuli directly onto the retina while simultaneously recording their exact retinal position, and a second application where AOSLO videos are used to provide very precise, high-frequency measures of eye movements. KEY WORDS Scanning laser ophthalmoscope, adaptive optics, blood flow, optical sectioning, ocular aberrations, eye movements RÉSUMÉ En compensant les aberrations de l'oeil causant un flou, l'ophthalmoscope laser à balayage à optique adaptative (OLBOA) permet d'obtenir un fort grossissement, une haute résolution, des images en temps réel de la rétine de l'humain vivant. Des éléments aussi petits que de simples photorécepteurs coniques peuvent être visibles, des leucocytes isolés sont enregistrés en temps réel quand ils passent à travers les plus petits capillaires rétiniens, et la capacité de sectionnement optique peut être utilisée pour visualiser des couches indépendantes du tissu rétinien allant de la couche de fibres nerveuses aux photorécepteurs en passant par les vaisseaux sanguins. L'utilisation de la technologie OA n'améliore pas seulement le champ d'application des OLB conventionnels, mais facilite également une multitude de nouvelles applications. Nous fournissons ici une vue d'ensemble de la performance de l'OLBOA et de ses applications, en incluant deux exemples cliniques. Enfin, nous annonçons deux nouvelles applications : une dans laquelle l'OLBOA est utilisé pour présenter des stimuli corrigés par OA directement sur la rétine tout en enregistrant simultanément leur position rétinienne exacte, et une deuxième application dans laquelle des vidéos d'OLBOA sont utilisées pour fournir des mesures à haute fréquence très précises des mouvements oculaires

Randomised clinical trial: palliative long-term abdominal drains vs large-volume paracentesis in refractory ascites due to cirrhosis

Background Palliative care remains suboptimal in end‐stage liver disease. Aim To inform a definitive study, we assessed palliative long‐term abdominal drains in end‐stage liver disease to determine recruitment, attrition, safety/potential effectiveness, questionnaires/interview uptake/completion and make a preliminary cost comparison. Methods A 12‐week feasibility nonblinded randomised controlled trial comparing large‐volume paracentesis vs long‐term abdominal drains in refractory ascites due to end‐stage liver disease with fortnightly home visits for clinical/questionnaire‐based assessments. Study success criteria were attrition not >50%, <10% long‐term abdominal drain removal due to complications, the long‐term abdominal drain group to spend <50% ascites‐related study time in hospital vs large‐volume paracentesis group and 80% questionnaire/interview uptake/completion. Results Of 59 eligible patients, 36 (61%) were randomised, 17 to long‐term abdominal drain and 19 to large‐volume paracentesis. Following randomisation, median number (IQR) of hospital ascitic drains (long‐term abdominal drain group vs large‐volume paracentesis group) were 0 (0‐1) vs 4 (3‐7); week 12 serum albumin (g/L) and serum creatinine (μmol/L) were 29 (26.5‐32.5) vs 30 (25‐35) and 104.5 (81‐115.5) vs 127 (63‐158) respectively. Total attrition was 42% (long‐term abdominal drain group 47%, large‐volume paracentesis group 37%). Median (IQR) fortnightly community/hospital/social care ascites‐related costs and percentage study time in hospital were lower in the long‐term abdominal drain group, £329 (253‐580) vs £843 (603‐1060) and 0% (0‐0.74) vs 2.75% (2.35‐3.84) respectively. Self‐limiting cellulitis/leakage occurred in 41% (7/17) in the long‐term abdominal drain group vs 11% (2/19) in the large‐volume paracentesis group; peritonitis incidence was 6% (1/17) vs 11% (2/19) respectively. Questionnaires/interview uptake/completion were ≥80%; interviews indicated that long‐term abdominal drains could transform the care pathway. Conclusions The REDUCe study demonstrates feasibility with preliminary evidence of long‐term abdominal drain acceptability/effectiveness/safety and reduction in health resource utilisation

Quantitative assessment of expression of cell adhesion molecule (CD44) splice variants: CD44 standard (CD44s) and v5, v6 isoforms in oral leukoplakias: An immunohistochemical study

Aim: The aim of this study was to semiquantitatively analyze the immunohistochemical expression pattern of CD44 standard (CD44s) and variant (CD44v) isoforms in leukoplakias using a panel of monoclonal antibodies recognizing epitopes of CD44s and of the variant exons v5 and v6. Objective: To evaluate the efficacy of CD44s and CD44 v5, v6 immunoexpression as possible molecular markers in detecting high-risk leukoplakias when screening for this oral precancer. Materials and Methods: Samples of oral leukoplakia (40 cases) and of normal mucosa (10 cases) were evaluated. Oral leukoplakia was graded into: hyperkeratosis without dysplastic change (8 cases), mild dysplasia (13 cases), moderate dysplasia (10 cases), and severe dysplasias (9 cases). Expression of CD44s,v5, v6 was analyzed by immunohistochemistry in a semiquantitative manner. Three areas of epithelium were scored B, S, and C, i.e., stratum basale, stratum corneum, and stratum spinosum, respectively in leukoplakias. Scoring of all specimens followed a two-parameter system, which implemented percentage of positive cells and staining intensities. Statistical analyses for each parameter of all groups and normals, mean, and standard deviation were calculated by using computer software package EPISTAT. Results: In normal epithelium CD44s, CD44v5, and CD44v6 were expressed as membranous proteins localized on the surface of epithelial cells. Both basal and spinous layer of epithelia expressed strong positive staining of CD44s, v5, v6 which then gradually faded into the negative staining of the superficial keratin layer. Profile of CD44s and v5 revealed that the mean levels of stratum B, S, and C in normal cases were comparable to the study cases and by Student ′t′ test P>0.05 not significant. There was, however, a statistically significant decrease in the expression of v6 with increasing grades of dysplasias when compared with normal mucosa. Conclusion: Among CD44s and its variant isoforms,v5, v6, in this study, variant isoform v6 may serve as a marker in detecting high-risk leukoplakias