Washout Time Research Articles

Targeting the Sphingosine-1-Phosphate Pathway: New Opportunities in Inflammatory Bowel Disease Management.

Inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC) are chronic immune-mediated diseases which primarily target the intestines. In recent years, the development and regulatory approval of various immunotherapies, both biological agents and small molecules, that target specific pathways of the IBD-associated inflammatory cascade have revolutionized the treatment of IBD. Small molecules offer the advantages of oral administration and short wash-out times. Sphingosine-1-phosphate (S1P) is a bioactive metabolite of ceramide, which exerts its functions after binding to five G-protein-coupled receptors (S1PR1-S1PR5). Concerning IBD, S1P participates in the egress of lymphocytes from the secondary lymphoid tissue and their re-circulation to sites of inflammation, mainly through S1PR1 binding. In addition, this system facilitates the differentiation of T-helper cells towards proinflammatory immunophenotypes. Recently, S1P modulators have offered a valuable addition to the IBD treatment armamentarium. They exert their anti-inflammatory function via sequestration of T cell subsets in the lymphoid tissues and prevention of gut homing. In this review, we revisit the role of the S1P/S1PR axis in the pathogenesis of IBD and discuss efficacy and safety data from clinical trials and real-world reports on the two S1PR modulators, ozanimod and etrasimod, that are currently approved for IBD treatment, and comment on their potential positioning in the IBD day-to-day management. We also present recent data on emerging S1P modulators. Finally, based on the successes and failures of S1PR modulators in IBD, we discuss future avenues of IBD treatments targeting the S1P/S1PR axis.

Benchtop Flow Stasis Quantification: In Vitro Methods and In Vivo Possibilities.

Neo-sinus flow stasis has ben correlated with transcatheter heart valve (THV) thrombosis severity and occurrence. Standard benchtop flow field quantification techniques require optical access or modified prosthesis models that may not reflect the true nature of the original valve. En face and fluoroscopic videodensitometry enable visualization of washout in regions otherwise unviewable. This study compares two in vitro methods of assessing flow stasis in scenarios with insufficient optical access for traditional techniques such as particle image velocimetry (PIV). A series of seven paired experiments were conducted using a previously described laser-enhanced video densitometry (LEVD) and fluoroscopic video densitometry (FVD). Both sets of experiments were analyzed to calculate washout time as a measure of flow stasis. A novel flow stasis measure termed contrast attenuation ratio (CAR) is proposed as a viable single measure of flow stasis obtainable from only a small number of cardiac cycles of in vitro or in vivo fluoroscopic data. Retrospective fluoroscopic datasets (n = 72) were analyzed to assess the feasibility of obtaining this metric from routine clinical practice and its ability to stratify results. Neo-sinus flow stasis calculated from in vitro fluoroscopy was well correlated with LEVD (r2 = 0.77, p = 0.009). The newly proposed CAR metric showed good agreement with the commonly used "washout time" measure of flow stasis (r2 = 0.91, p < 0.001) while allowing for assessment with incomplete or truncated data. As a proof of concept, CAR was measured in 72 consecutive retrospective fluoroscopic datasets. CAR averaged 10.6 ± 4.6% with a range of 1.5-20.3% in these patients. This study demonstrates two in vitro methods that can be used to assess relative flow stasis in otherwise optically inaccessible regions surrounding cardiac or vascular implants. In addition, the fluoroscopic benchtop technique was used to validate a metric that allows for extension to routine clinical fluoroscopy. This contrast attenuation ratio (CAR) metric was found to be both accurate and clinically obtainable, and potentially offers a new method for valve thrombosis risk stratification.

PHARMACOKINETIC PROFILES OF ORAL PHENYLBUTAZONE, MELOXICAM, AND FIROCOXIB IN SOUTHERN BLACK RHINOCEROS (DICEROS BICORNIS MINOR).

The pharmacokinetic profile of selected NSAIDs in southern black rhinoceros (Diceros bicornis minor) were studied. Phenylbutazone (PBZ), meloxicam (MEL), and firocoxib (FIR) were administered orally to five captive, black rhinoceros, and blood was collected at predetermined time points for NSAID quantification and noncompartmental pharmacokinetic (PK) analysis. Phenylbutazone 4.0 mg/kg PO q12h for three doses, MEL 0.3 mg/kg PO q24h administered twice, and a single oral dose of FIR 0.1 mg/kg, were tested with a minimum washout time of 2 wk. PBZ reached a median (range) peak concentration (Cmax) of 9.42 (2.74-11.5) g/ml at a mean (range) time (Tmax) of 6.00 (4.00 to >12.00) h, and the median (range) elimination half-life (T1/2) was 6.07 (3.95-6.49) h. Phenylbutazone pharmacokinetic parameters for black rhinoceros in this study were similar to domestic horses. Meloxicam reached a median (range) Cmax of 0.576 (0.357-0.655) µg/ml at a median (range) time (Tmax) of 6.00 (4.00-12.00) h; the median (range) T1/2 of MEL was 14.0 (12.4-17.9) h. These results demonstrate that once-daily administration of MEL at 0.3 mg/kg resulted in a serum concentration of greater than 0.200 µg/ml from 2 to 24 h in four animals, which is within the analgesic range (0.200-0.400 µg/ml) for this drug in other species postulated by other studies. A single dose of firocoxib (0.1 mg/kg) reached a median (range) peak concentration (Cmax) of 15.7 (9.65-17.3) ng/ml at a median (range) Tmax of 4.00 (4.00-6.00) h. The median (range) elimination T1/2 of FIR was 4.96 (4.47-6.51) h, which is faster than in the horse. The data suggest that extrapolation from equine FIR dosage recommendations is inappropriate for black rhinoceros.

Evaluation of the Effects of Punica granatum Flower Tablets on Pain and Healing of Minor Recurrent Aphthous Stomatitis: A Randomized Clinical Trial.

The purpose of this study was to determine the therapeutic effect of the Punica granatum (PG) flower on recurrent aphthous stomatitis in comparison with corticosteroid therapy. This cross-over randomized clinical trial was conductedon the patients who had been referred to Shiraz Dental School for their RAS in 2021. All the participants used both P. granatum flower tablets and Triadent a month apart for wash-out time and all compared themselves. In the experimental group, 30 patients received pomegranate flower tablets, three tablets daily, for 6 days. In the control group, oral paste Triadent has been prescribed three times a day for 6 days. The visual analog scale (VAS) and the size of RAS were evaluated on Days 0-6. Data were analyzed by SPSS version 21. The Wilcoxon test was used. The mean age of participants was 27.8 ± 14.77 years old. In this study, 15 patients (50%) were men and 15 patients (50%) were women. The mean value of VAS after using prescribed treatment in both evaluated groups on all days was significantly different such that the VAS values were lower for PG flower tablets than Triadent (p value < 0.05). The size of oral lesions in participants who used PG flower tablets was significantly less than those who used Triadent on all evaluation days (p value < 0.05) except on Day 1 (p value = 0.29). The descending slope of VAS from Days 1 to 6 for both Triadent and PG flower tablet users was significant and noticeable. (p value < 0.05). According to the result of this study, both P. granatum flower tablet and Triadent are useful in reducing the size, period of healing, and VAS of patients with RAS, but the PG flower tablet is more effective.

Impact of pre-transplant immune checkpoint inhibitor use on post-transplant outcomes in HCC: A systematic review and individual patient data meta-analysis

Treatment with immune checkpoint inhibitors (ICIs) for hepatocellular carcinoma (HCC) prior to liver transplantation (LT) has been reported; however, ICIs may elevate the risk of allograft rejection and impact other clinical outcomes. This study aims to summarize the impact of ICI use on post-LT outcomes. In this individual patient data meta-analysis, we searched databases to identify HCC cases treated with ICIs before LT, detailing allograft rejection, HCC recurrence, and overall survival. We performed Cox regression analysis to identify risk factors for allograft rejection. Among 91 eligible patients, with a median (IQR) follow-up of 690.0 (654.5) days, there were 24 (26.4%) allograft rejections, 9 (9.9%) HCC recurrences, and 9 (9.9%) deaths. Age (adjusted hazard ratio [aHR] per 10 years 0.72, 95% CI 0.53-0.99, p= 0.044) and ICI washout time (aHR per 1 week 0.92, 95% CI 0.86-0.99, p= 0.022) were associated with allograft rejection. The median (IQR) washout period for patients with ≤20% probability of allograft rejection was 94 (196) days. Overall survival did not differ between cases with and without allograft rejection (log-rank test, p= 0.2). Individuals with HCC recurrence had fewer median (IQR) ICI cycles than those without recurrence (4.0 [1.8] vs. 8.0 [9.0]; p= 0.025). The proportion of patients within Milan post-ICI was lower for those with recurrence vs. without (16.7% vs. 65.3%, p= 0.032). Patients have acceptable post-LT outcomes after ICI therapy. Age and ICI washout length relate to the allograft rejection risk, and a 3-month washout may reduce it to that of patients without ICI exposure. Number of ICI cycles and tumor burden may affect recurrence risk. Large prospective studies are necessary to confirm these associations. This systematic review and individual patient data meta-analysis of 91 patients with hepatocellular carcinoma and immune checkpoint inhibitor use prior to liver transplantation suggest acceptable overall post-transplant outcomes. Older age and longer immune checkpoint inhibitor washout period have a significant inverse association with the risk of allograft rejection. A 3-month washout may reduce it to that of patients without immune checkpoint inhibitor exposure. Additionally, a higher number of immune checkpoint inhibitor cycles and tumor burden within Milan criteria at the completion of immunotherapy may predict a decreased risk of hepatocellular carcinoma recurrence, but this observation requires further validation in larger prospective studies.

In Situ Gelling Behavior and Biopharmaceutical Characterization of Nano-Silver-Loaded Poloxamer Matrices Designed for Nasal Drug Delivery.

A combination of Poloxamer 407 (P407) and hydroxypropyl methylcellulose (HPMC) hydrosols is proposed as an in situ thermo-gelling vehicle for the nasal drug delivery of chlorhexidine-silver nanoparticles conjugates (SN-CX). Optimization of the formulation was carried out by applying varying ratios of P407 and HPMC in the presence and absence of SN-CX so that gelation would occur in the temperature range of the nasal cavity (30-34 °C). Mechanisms for the observed gelation phenomena were suggested based on viscosimetry, texture analysis, and dynamic light scattering. Tests were carried out for sprayability, washout time, in vitro drug release, ex vivo permeation, and antimicrobial activity. When applied separately, HPMC was found to lower the P407 gelation temperature (Tg), whereas SN-CX increased it. However, in the presence of HPMC, SN-CX interfered with the P407 micellar organization in a principally contrasting way while leading to an even further decrease in Tg. SN-CX-loaded nasal formulations composed of P407 16% and HPMC 0.1% demonstrated a desired gelation at 31.9 °C, good sprayability (52.95% coverage of the anterior nasal cavity), mucoadhesion for 70 min under simulated nasal clearance, expedient release and permeation, and preserved anti-infective activity against seasonal Influenza virus and beta-coronavirus, Pseudomonas aeruginosa, Klebsiella pneumoniae, Staphylococcus aureus and other pathogens. Our findings suggest that the current development could be considered a potential formulation of a protective nasal spray against respiratory infections.

Multimode Ultrasound Model for Predicting the Early Treatment Response of Anti-VEGF Agents Plus Anti-PD-1 Antibody in Patients with Unresectable Hepatocellular Carcinoma

ObjectiveThe purpose of the study described was to establish prediction models to initially screen the beneficiary patients with unresectable hepatocellular carcinoma (HCC) in the treatment of anti-vascular endothelial growth factor (VEGF) agents plus anti-programmed cell death-1 (PD-1) antibody. MethodsA total of 62 patients were enrolled in this study. All patients underwent ultrasound (US), color ddoppler flowing imaging (CDFI), contrast-enhanced ultrasound (CEUS) and laboratory examinations within 2 wk before the treatment. Tumor response was assessed according to mRECIST criteria. Univariate and multivariate analyses were used to select the independent predictors. US + CDFI, CEUS and FULL models were established. Three models were displayed by nomography. Receiver operating characteristic (ROC) and calibration curves were drawn to evaluate the predictive ability of models. Decision curve analysis (DCA) was used to assess the clinical utility of models. ResultsOn univariate and multivariate analysis, the US boundary (p = 0.037), halo (p = 0.002) and CDFI (p = 0.024) were included in the US + CDFI model. CEUS boundary (p = 0.001) and washout time (p < 0.001) were included in the CEUS model. The number of lesions (p = 0.104), halo on US (p = 0.014), CDFI (p = 0.057) and washout time on CEUS (p = 0.015) were incorporated into the FULL model. The C indices of the US + CDFI, CEUS and FULL models were 0.918, 0.920 and 0.973. CEUS and FULL models yielded a good net benefit for almost all threshold probabilities. ConclusionNomograms based on US, CDFI, CEUS and clinical characteristics could help to non-invasively predict the response to treatment with anti-PD-1 antibodies plus anti-VEGF agents.

Evaluation of dental plaque reduction using microcurrent-emitting toothbrushes in orthodontic patients: a randomized, double-blind, crossover clinical trial

This study aimed to compare the effectiveness of microcurrent-emitting toothbrushes (MCTs) and ordinary toothbrushes in reducing the dental plaque index (PI) and dental caries activity among orthodontic patients. The evaluation was performed using a crossover study design involving 22 orthodontic patients randomly assigned to the MCT or ordinary toothbrush groups. The participants used the designated toothbrush for 4 weeks and had a 1-week wash-out time before crossover to the other toothbrush. PI (Attin’s index) and dental caries activity were measured at baseline and at the end of each 4-week period. Additionally, patients completed questionnaires to assess patient satisfaction for “freshness in mouth” and “cleansing degree.” The results showed that the MCT group had a significant reduction in PI (p = 0.009), whereas the ordinary toothbrush group did not (p = 0.595). There was no significant difference in the dental caries activity between the two groups (p > 0.05). Patient satisfaction assessment revealed that 65% patients in the MCT group had more than “fair” experience of freshness, in contrast to 50% of patients in the ordinary toothbrush group. Satisfaction with cleansing degree was similar in both groups. Overall, these findings suggest that MCTs are more effective in reducing dental PI than ordinary toothbrushes.

Analysis of early response to chemotherapy for non-Hodgkin’s lymphoma by quantitative contrast-enhanced ultrasound: A prospective case-control crossectional study

ObjectiveTo investigate the value of quantitative contrast-enhanced ultrasonography (CEUS) in assessing and predicting early therapy response of non-Hodgkin’s lymphoma (NHL). MethodsFifty-six cases of NHL were studied using CEUS before and after three cycles of R-CHOP / CHOP. Quantitative parameters such as arrival time (ATM), time to peak (TTP), △T = TTP-ATM, area under the gamma curve (Area), curve gradient (Grad), wash-out time (WT), base intensity (BI), peak intensity (PI) and ΔI = PI-BI were compared between the lymphoma and normal lymph nodes before and at mid-treatment, respectively. Changes in quantitative CEUS parameters were also compared between complete response (CR) and incomplete response(non-CR) groups. Besides, the correlation analysis was performed between pretreatment PI and changes in quantitative parameters. ResultsAfter three cycles of R-CHOP/CHOP, S/L (P < 0.001), PI (P = 0.002), ΔI (P < 0.001), Grad (P < 0.001), and Area (P < 0.001) of NHL were significantly decreased. The CR group and non-CR group only differed in ATM before treatment. In contrast, there was no statistical difference in any of the parameters between the two groups at mid-treatment. Finally, a significant correlation was observed between pre-treatment PI and PI△% (r = 0.736, P < 0.001). ConclusionsCEUS is promising for the assessment of response of NHL to R-CHOP/CHOP. Intra-lesion perfusion changes take precedence over morphological changes suggesting treatment efficacy. Pre-treatment ATM values may help to suggest efficacy outcomes and pre-treatment PI values may be a valid predictor of lymphoma perfusion response.

Simulation study of water shut-off treatment for heterogeneous layered oil reservoirs

The purpose of this paper is to develop a hydrodynamic model of two-phase, three-component fluid flow in a heterogeneous layered reservoir, taking into account cross-flow between layers, and to predict the process of oil displacement by water under conditions of water shut-off in the vicinity of injection or production wells. Numerical calculations at different water cuts (38%, 50%, 96%) showed that in the presence of cross-flow between layers, the current oil recovery coefficient of the reservoir at water shut-off in the vicinity of the producing well increases by 0.3254, 0.3067, and 0.0429 respectively, compared to water shut-off in the vicinity of the injection well. In the absence of cross-flow between layers, there is a decrease in oil recovery coefficient by 0.0082 and 0.0072 at 38 and 50% water cut, respectively. Additionally, there is an increase in recovery coefficient by 0.007 at 96% water cut. It was also obtained that in the presence of cross-flow between layers the gel washout period at water shut-off in the vicinity of the injection well is less at different water cut in 1.24–1.81 times than in the vicinity of the production well. In the absence of cross-flow between layers, the washout time at 38 and 50% water cut is almost the same, but increases by 1.084 times at 96% water cut. Comparison of results of water shut-off prediction using proposed hydrodynamic model and real data showed that calculations describe real data with an average error of about 7%.

Dynamic Contrast-Enhanced Ultrasonography Combined With LR-M Classification Criteria for Differentiating Malignant Liver Nodules at High Risk for Hepatocellular Carcinoma

ObjectiveWe aimed to investigate the value of quantitative parameters derived from dynamic contrast-enhanced ultrasonography (DCE-US) and a combination of these quantitative parameters with the LR-M classification criteria in distinguishing hepatocellular carcinoma (HCC) nodules and non-HCC malignancies. MethodsHCC and non-HCC malignant nodules were grouped using pathologic results, and each nodule was classified using CEUS LI-RADS 2017. Quantitative CEUS analysis of each nodule was performed using VueBox, and quantitative parameters were compared between the HCC and non-HCC groups. The diagnostic efficacy of the LR-5 category for HCC was analyzed using the LR-M classification criteria along with time-related quantitative parameters. ResultsOf the 190 malignant liver nodules, 137 and 53 were HCCs and non-HCC malignancies, respectively. The median values of quantitative parameters RT (rise time), TTP (time to peak), mTTl (mean transit time local), and FT (fall time) in the non-HCC malignant group were lower than those in the HCC group, with p < 0.05. There was a statistically significant difference in WiAUC (wash-in area under the curve), WoAUC (wash-out area under the curve), WiWoAUC (wash-in and wash-out area under the curve), and WoR (wash-out rate) values between HCC and non-HCC malignant groups, with p < 0.05. Using LR-M washout time <60 s and FT ≤21.2 s as the new diagnostic standard, the LR-5 category showed a sensitivity of 83.9%, specificity of 96.2%, and positive predictive value of 98.3% for HCC diagnosis. ConclusionDCE-US can facilitate the distinction of HCCs and non-HCC malignancies. Non-HCC malignancies present with earlier peak enhancement and more rapid and marked washout than HCC nodules. The combination of the LR-M classification criteria and FT ≤21.2 s can significantly improve the diagnostic sensitivity of the LR-5 category for HCC.

Evaluation of Washout Periods After Dorsal Root Ganglion Stimulation Trial

ObjectiveDorsal root ganglion stimulation (DRG-S) is a novel therapy to treat chronic pain. It has shown efficacy when delivered intermittently, suggesting a delayed washout effect exists. To measure the washout period, and to determine whether there are differences in washout times among different types of treated pain, we measured the time for pain to return at the end of the patients’ one-week DRG stimulation trials. Materials and MethodsPatients who completed a successful DRG-S trial were included. The times until 25% (t25) and 90% (t90) of baseline pain level returned were recorded. The patients were divided into neuropathic, nociceptive, and mixed pain groups for subgroup comparison. t25 and t90 were plotted in the entire cohort and subgroups using reverse Kaplan-Meier plots (failure curves) and compared using a log-rank test. ResultsIn total, 29 consecutive patients were included. Median t25 and t90 times were 7.1 and 19.5 hours, respectively. Median (interquartile range) times were longest for the nociceptive pain group (n = 17) and shortest for the neuropathic pain group (n = 6), with the mixed-pain group (n = 6) in between (t25: 7.1 [1.7–19.4], 3.40 [1.4–8.4], and 5.7 [0.8–17.6]; t90, 22.0 [10.7–71.0], 7.6 [3.6–19.8], and 20.9 [14.2–31.2], respectively). t90 times differed significantly by pain type (p = 0.040). ConclusionsThis study showed a prolonged washout period after cessation of DRG-S therapy. Washout times vary according to pain type. The observed effects are possibly due to long-term depression of pain signaling and could allow the implementation of alternative stimulation strategies with DRG-S. Further investigations evaluating DRG-S washout times are warranted.

Standard technical specifications for methacholine chloride (Methacholine) bronchial challenge test (2023)

Standard technical specifications for methacholine chloride (Methacholine) bronchial challenge test (2023)

Radiomics-Based Machine Learning Classification Strategy for Characterization of Hepatocellular Carcinoma on Contrast-Enhanced Ultrasound in High-Risk Patients with LI-RADS Category M Nodules.

Objective Accurate differentiation within the LI-RADS category M (LR-M) between hepatocellular carcinoma (HCC) and non-HCC malignancies (mainly intrahepatic cholangiocarcinoma [CCA] and combined hepatocellular and cholangiocarcinoma [cHCC-CCA]) is an area of active investigation. We aimed to use radiomics-based machine learning classification strategy for differentiating HCC from CCA and cHCC-CCA on contrast-enhanced ultrasound (CEUS) images in high-risk patients with LR-M nodules. Methods A total of 159 high-risk patients with LR-M nodules (69 HCC and 90 CCA/cHCC-CCA) who underwent CEUS within 1 month before pathologic confirmation from January 2006 to December 2019 were retrospectively included (111 patients for training set and 48 for test set). The training set was used to build models, while the test set was used to compare models. For each observation, six CEUS images captured at predetermined time points (T1, peak enhancement after contrast injection; T2, 30 seconds; T3, 45 seconds; T4, 60 seconds; T5, 1-2 minutes; and T6, 2-3 minutes) were collected for tumor segmentation and selection of radiomics features, which included seven types of features: first-order statistics, shape (2D), gray-level co-occurrence matrix, gray-level size zone matrix, gray-level run length matrix, neighboring gray tone difference matrix, and gray-level dependence matrix. Clinical data and key radiomics features were employed to develop the clinical model, radiomics signature (RS), and combined RS-clinical (RS-C) model. The RS and RS-C model were built using the machine learning framework. The diagnostic performance of these three models was calculated and compared. Results Alpha-fetoprotein (AFP), CA19-9, enhancement pattern, and time of washout were included as independent factors for clinical model (all p < 0.05). Both the RS and RS-C model performed better than the clinical model in the test set (area under the curve [AUC] of 0.698 [0.571-0.812] for clinical model, 0.903 [0.830-0.970] for RS, and 0.912 [0.838-0.977] for the RS-C model; both p < 0.05). Conclusions Radiomics-based machine learning classifiers may be competent for differentiating HCC from CCA and cHCC-CCA in high-risk patients with LR-M nodules.

Value of high frame rate contrast enhanced ultrasound in gallbladder wall thickening in non-acute setting

BackgroundUltrasound (US) has been widely used in screening and differential diagnosis of gallbladder wall thickening (GWT). However, the sensitivity and specificity for diagnosing wall-thickening type gallbladder cancer are limited, leading to delayed treatment or overtreatment. We aim to explore the value of high frame rate contrast enhanced ultrasound (H-CEUS) in distinguishing wall-thickening type gallbladder cancer (malignant) from GWT mimicking malignancy (benign).MethodsThis retrospective study enrolled consecutive patients with non-acute GWT who underwent US and H-CEUS examination before cholecystectomy. Clinical information, US image and H-CEUS image characteristics between malignant and benign GWT were compared. The independent risk factors for malignant GWT on H-CEUS images were selected by multivariate logistic regression analysis. The diagnostic performance of H-CEUS in determining malignant GWT was compared with that of the gallbladder reporting and data system (GB-RADS) score.ResultsForty-six patients included 30 benign GWTs and 16 malignant GWTs. Only mural layering and interface with liver on US images were significantly different between malignant and benign GWT (P < 0.05). Differences in enhancement direction, vascular morphology, serous layer continuity, wash-out time and mural layering in the venous phase of GWT on H-CEUS images were significant between malignant and benign GWT (P < 0.05). The sensitivity, specificity and accuracy of H-CEUS based on enhancement direction, vascular morphology and wash-out time in the diagnosis of malignant GWT were 93.75%, 90.00%, and 91.30%, respectively. However, the sensitivity, specificity and accuracy of the GB-RADS score were only 68.75%, 73.33% and 71.74%, respectively. The area under ROC curve (AUC) of H-CEUS was significantly higher than that of the GB-RADS score (AUC = 0.965 vs. 0.756).ConclusionsH-CEUS can accurately detect enhancement direction, vascular morphology and wash-out time of GWT, with a higher diagnostic performance than the GB-RADS score in determining wall-thickening type gallbladder cancer. This study provides a novel imaging means with high accuracy for the diagnosis of wall-thickening type gallbladder cancer, thus may be better avoiding delayed treatment or overtreatment.

The effects of hydrolyzed protein on macronutrient digestibility, fecal metabolites and microbiota, oxidative stress and inflammatory biomarkers, and skin and coat quality in adult dogs.

Research on protein hydrolysates has observed various properties and functionalities on ingredients depending on the type of hydrolysate. The objective of this study was to evaluate the effects of hydrolyzed chicken protein that was incorporated into diets on digestibility, gut health, skin and coat health, oxidative stress, and intestinal inflammation markers in healthy adult dogs. Five complete and balanced diets were manufactured: (1) CONd: 25% chicken meal diet; (2) 5% CLHd: 5% chicken liver and heart hydrolysate plus 20% chicken meal diet; (3) CLHd: 25% chicken liver and heart hydrolysate diet; (4) 5% CHd: 5% chicken hydrolysate plus 20% chicken meal diet; (5) CHd: 25% chicken hydrolysate diet. A replicated 5 × 5 Latin square design was used which included 10 neutered adult Beagles. Each of the 5 periods consisted of a 7-d washout time and a 28-d treatment period. All diets were well accepted by the dogs. Fecal butyrate concentration was higher while fecal isovalerate and total phenol/indole were lower in dogs fed CLHd than CONd (P < 0.05). Dogs fed CHd had higher fecal immunoglobulin A concentration when compared with CLHd (P < 0.05); however, both groups were comparable to the CONd. There was no difference among groups in serum cytokine concentrations, serum oxidative stress biomarkers, or skin and coat health analyses (P > 0.05). Fecal microbiota was shifted by CLHd with higher abundance in Ruminococcus gauvreauii group as well as lower Clostridium sensu stricto 1, Sutterella, Fusobacterium, and Bacteroides when compared with CONd (P < 0.05). There was also a difference in beta diversity of fecal microbiota between CLHd and CHd (P < 0.05). In conclusion, chicken protein hydrolysate could be incorporated into canine extruded diets as a comparable source of protein to traditional chicken meal. The test chicken protein hydrolysates showed the potential to support gut health by modulating immune response and microbiota; however, functional properties of protein hydrolysates are dependent on inclusion level and source.

The world anti-doping code – Prohibited List 2024

The List of Prohibited Substances and Methods for the year 2024 has already been published by the World Anti-Doping Agency and came into force on January 1st across the world and for all sports. At the same time, a document was published with changes in relation to the List published for the year 2023. Of particular note is the inclusion of tramadol as drug prohibited in competition. In this text, reference is also made to the corticosteroid washout times, to the monitoring program and the Therapeutic Use Exemption whenever the athlete needs to take a prohibited medication included in the List. Attention is also drawn to the beta-agonists drugs widely used in the treatment of asthma.

Abstract 14220: Establishing Dosing Parameters for the Use of Maternal Hyperoxygenation to Affect Fetal Cardiovascular Physiology

Introduction: Maternal hyperoxygenation (MH) has been used to aid in the prognosis of fetal abnormalities. No data exist on the dose-response relationship or washout time of short-term MH administration related to fetal cardiovascular effects. Hypothesis: There may be a dose-response to MH with effect on pulmonary vascular resistance as measured by pulmonary artery pulsatility index (PAPI) and combined cardiac output (CCO). Aims: The aims of this study were: to determine the appropriate MH dose to obtain a physiologic response (i.e. decrease in PAPI), to evaluate the change in CCO, and to identify the washout period. Methods: Expectant mothers with normal fetal echocardiograms were prospectively recruited from 3/2019 to 6/2023. A research echocardiogram with MH was performed after 31 weeks gestation. Fetal cardiac abnormalities and other comorbidities were excluded. Patients were randomly assigned to either; 2 liters (L) nasal cannula (NC), 4L NC or 8L facemask, all at 100% Fi0 2 . Measurements of PAPI and CCO were performed at baseline, at 1 minute (min) and at 5 min intervals to 20 mins. The same time points were repeated off oxygen. Differences in PAPI were compared between doses and between time points using a mixed effects model. Results: We recruited 29 patients at a mean gestational age of 32.9 (± 0.9 weeks). On oxygen, there was a statistically significant decrease in the PAPI at 8L (-0.18 per min, 95% CI -0.32, -0.05), with the largest decrease occurring between baseline and 5 mins, and PAPI stabilizing after 10 mins (figure). During the washout period, starting at 1 min off oxygen, PAPI values normalized, with no statistically significant changes with 2L, 4L or 8L compared to baseline. No effect on CCO was seen from MH administration. Conclusions: An oxygen dose of 8L is needed for an appropriate PAPI response, with the largest effect occurring before 10 mins. After oxygen is removed, PAPI values normalize by one min. Changes in CCO were not seen with MH in this normal population.

196 The Effect of Hydrolyzed Protein on Fecal Microbiota in Adult Dogs

Abstract Research on protein hydrolysates has observed various properties and functionalities of these ingredients depending on the type of hydrolysate. The objective of this study was to evaluate the effect of hydrolyzed chicken protein that was incorporated into diets on gut health in healthy adult dogs. Five complete and balanced treatment diets were manufactured: 1) CONd: chicken meal diet; 2) 5% CLHd: 5% substitution of chicken liver hydrolysate of chicken meal diet; 3) CLHd: chicken liver hydrolysate diet; 4) 5% CHd: 5% substitution of chicken hydrolysate of chicken meal diet; and 5) CHd: chicken hydrolysate diet. A 5×5 Latin square design was used which included 10 neutered adult beagles. Each of the 5 periods consisted of a 7-d washout time and a 28-d treatment period. All diets were well accepted by the dogs. For fecal metabolites, there was greater fecal butyrate concentration as well as reduced isovalerate, 4-ethylphenol, and indole in dogs fed CLHd than CONd (P &amp;lt; 0.05). Regarding the overall microbiota composition, Firmicutes, Bacteriodota, Fusobacteriota, Actinobacteriota, and Proteobacteria were the top 5 most abundant phyla. At the class level, samples from CHd group had greater relative abundances of Bacteriodia and Fusobacteriia as well as less Bacilli. On the other hand, CLHd group had greater abundances of Bacilli and Actinobacteria with less Fusobacteriia. At the level of order, CHd group had greater Bacteriodales and Fusobacteriales while CLHd group had greater Bifidobacteriales. At the family level, CHd group showed a greater abundance of Muribaculaceae and a decreased abundance of Bifidobacteriaceae when compared with the other groups. Alternatively, CLHd group demonstrated a greater abundance of Bifidobacteriaceae together with reduced abundance of Fusobacteriaceae, Muribaculaceae, Sutterrellaceae, and Ruminococcaceae. Fecal microbiota was shifted by CLHd with greater differential abundance in Ruminococcus gauvreauii group as well as reduced Clostridium sensu stricto 1, Sutterella, Fusobacterium, and Bacteroides compared with CONd (P &amp;lt; 0.05). There was also a difference in beta diversity of fecal microbiota between CLHd and CHd (P &amp;lt; 0.05). However, no difference was observed in alpha diversity among treatment groups (P &amp;lt; 0.05). Fecal butyrate concentration was negatively correlated with the genera Blautia, Phascolarctobacterium, Sutterella, Faecalibacterium, and Bacteriodes. Conversely, Allobaculum and Bifidobacterium were positively correlated with butyrate concentration. In conclusion, the test chicken protein hydrolysates may have potential to support gut health by modulating microbiota.

PSIX-6 The Effects of Hydrolyzed Protein on Macronutrient Digestibility, Fecal Metabolites, Oxidative Stress and Inflammatory Biomarkers, and Skin and Coat Quality in Adult Dogs

Abstract Research on protein hydrolysates has observed various properties and functionalities of these ingredients depending on the type of hydrolysate. The objective of this study was to evaluate the effects of hydrolyzed chicken protein that was incorporated into diets on digestibility, gut health, skin and coat health, oxidative stress, and inflammation in healthy adult dogs. Five complete and balanced treatment diets were manufactured: 1) CONd: chicken meal diet; 2) 5% CLHd: 5% substitution of chicken liver hydrolysate of chicken meal diet; 3) CLHd: chicken liver hydrolysate diet; 4) 5% CHd: 5% substitution of chicken hydrolysate of chicken meal diet; and 5) CHd: chicken hydrolysate diet. A 5×5 Latin square design was used which included 10 neutered adult beagles. Each of the 5 periods consisted of a 7-d washout time and a 28-d treatment period. All diets were well accepted by the dogs. There was greater (P &amp;lt; 0.05) fecal butyrate (226.8 μmol/g DMB) concentration as well as decreasedr isovalerate (6.8 μmol/g DMB), 4-ethylphenol (1.4 μmol/g DMB), and indole (0.7 μmol/g DMB) in dogs fed CLHd than CONd (149.3, 10.8, 2.5, and 1.5 μmol/g DMB, respectively). Doges fed CHd had greater (P &amp;lt; 0.05) fecal immunoglobulin A concentration (2.86 mg/g) when compared with CLHd (0.91 mg/g); however, both groups were comparable to the control. There was no difference among groups in serum cytokine concentrations, serum oxidative stress biomarkers, or skin and coat health analyses (P &amp;gt; 0.05). In conclusion, chicken protein hydrolysate could be incorporated into canine extruded diets as a comparable source of protein to traditional chicken meal. The test chicken protein hydrolysates may have potential to support gut health by modulating immune response and fermentative activity; however, more research is needed to confirm the effect.