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BACKGROUND: An accurate, rapid estimate of glomerular filtration rate (GFR) in kidney transplant patients affords early detection of transplant deterioration and timely intervention. This study compared the performance of serum creatinine (Cr) and cystatin C (CysC)-based GFR equations to measured GFR (mGFR) using iohexol among pediatric kidney transplant recipients. METHODS: CysC, Cr, and mGFR were obtained from 45 kidney transplant patients, 1-18 years old. Cr- and CysC-estimated GFR (eGFR) was compared against mGFR using the Cr-based (Bedside Schwartz, U25-Cr), CysC-based (Gentian CysC, CAPA, U25-CysC), and Cr-CysC combination (CKiD Cr-CysC, U25 Cr-CysC) equations in terms of bias, precision, and accuracy. Bland-Altman plots assessed the agreement between eGFR and mGFR. Secondary analyses evaluated the formulas in patients with biopsy-proven histological changes, and K/DOQI CKD staging. RESULTS: Bias was small with Gentian CysC (0.1 ml/min/1.73 m2); 88.9% and 37.8% of U25-CysC estimations were within 30% and 10% of mGFR, respectively. In subjects with histological changes on biopsy, Gentian CysC had a small bias and U25-CysC were more accurate-both with 83.3% of and 41.7% of estimates within 30% and 10% mGFR, respectively. Precision was better with U25-CysC, CKiD Cr-CysC, and U25 Cr-CysC. Bland-Altman plots showed the Bedside Schwartz, Gentian CysC, CAPA, and U25-CysC tend to overestimate GFR when > 100 ml/min/1.72 m2. CAPA misclassified CKD stage the least (whole cohort 24.4%, histological changes on biopsy 33.3%). CONCLUSIONS: In this small cohort, CysC-based equations with or without Cr may have better bias, precision, and accuracy in predicting GFR.

Impaired intestinal integrity in broilers reduces performance and health, highlighting the importance of accurately measuring intestinal permeability (IP) to maintain gut health. The objective of this study was to evaluate the efficiency of iohexol as an IP marker in broilers challenged with Eimeria maxima , Clostridium perfringens , or both during both peak challenge (day [d] 21) and recovery (d 28) periods. One-day-old male Ross 708 birds (n = 56) were distributed into 4 treatment groups: NC (no-challenge control); EM (challenged with 5,000 E. maxima sporulated oocysts/bird on d 15); CP (challenged with 1.0 × 108 CFUs/bird of C. perfringens on d 19 and d 20); and EM + CP (challenged by co-infection of E. maxima and C. perfringens as described). On d 21 and d 28, each bird received an iohexol dose of 64.7 mg/kg body weight via oral gavage. One hour later, blood samples were collected from 14 birds (12 in EM) per group on d 21 and from 7 birds (6 in EM) on d 28. For lesion scoring and ileum collection, 7 birds per group (6 birds in EM) were sampled on each d 21 and d 28. Birds in the EM and EM + CP groups had lower body weight gain (BWG) compared to the NC and CP groups on d 19–21 (P ≤ 0.05). These birds also exhibited significantly greater lesion scores and markedly higher serum iohexol levels on d 21 (P ≤ 0.05). However, no significant differences in serum iohexol levels were observed among treatment groups following recovery on d 28. Moreover, significant differentials were observed in the mRNA abundance of key tight junction proteins (CLDN1, CLDN2, and ZO3), pro-inflammatory cytokines (IL-1β, IFNγ, and IL-22), and gut health markers (GLP2, OLFM4, and MUC2) in the EM and EM + CP groups compared to the NC and CP groups on d 21. In conclusion, this study demonstrates that iohexol is an effective marker for assessing IP in broilers under different enteric challenge conditions. [ABSTRACT FROM AUTHOR]

Abstract Background Current endogenous indicators utilised in avian medicine are not sensitive enough to detect renal disease in its early stages. Alternative markers ought to be examined as a result. The aim is to investigate the accuracy of limited-sampling models for glomerular filtration rate (GFR) in adult seagulls using plasma clearance of iohexol (IOX). Results We compared the GFR estimated from the plasma concentration of IOX at 3 sampling times, known as limited sampling models, with that estimated from the plasma concentration of IOX at 6 sampling times (reference model). The reference model’s mean ± SD for GFR was 6.88 ± 2.46 mL/min/kg and did not considerably differ from the GFR predicted by the limited-sampling models. Model 4, in which GFR was estimated using plasma IOX concentrations at 5, 15, and 90 min after IOX administration, had the smallest GFR bias compared to the reference model. Conclusions The findings revealed that IOX plasma clearance was a reliable, accurate, and clinically applicable approach to calculating seagull GFR. This strategy might help with the validation and subsequent development of clinical renal biomarkers.

To prospectively determine whether extrinsic warming of the low-osmolality CT contrast media (Iohexol 350, Iodixanol 320, Iopromide 300, and Iopamidol 300) to 37°C prior to intravenous administration affects extravasation and allergic-like reaction rates. This large scale prospective case control study of adverse events included all the patients between the age group of 15–80 years undergoing routine contrast–enhanced computed tomographic (CECT) examinations from April 2018 to March 2020 at our institute. Ex vivo experiments were also performed to demonstrate change in contrast viscosity and fluid dynamics in relation to temperature. A total of 24,379 CECTs were conducted during the study period. Extrinsic warming showed a significant decrease in extravasation rates for Iohexol 350 at flow rates <3.5 mL/sec (P=0.037). No significant difference was observed with Iopromide 300 (P=0.432). Overall, a significant decrease in allergic reactions and overall contrast-related reactions (excluding physiologic reactions) was noted (P<0.001), with Iohexol 350. However, no significant difference was found with Iopromide 300. The most common physiological reaction was a sense of warmth, more prevalent in the warmed group, aligning with ex-vivo experiments demonstrating decreased viscosity with contrast warming. Extrinsic warming of contrast helps reduce the incidence of allergic-like reactions and extravasations for Iohexol 350, but no significant difference was noted with Iopromide 300 even at low injection rates (<3.5 mL/sec). • Warming contrast media to 37°C significantly reduces adverse reactions. • Iohexol 350 showed fewer extravasations and allergic reactions when warmed. • No significant difference in reactions for warmed vs. non-warmed Iopromide 300. • Physiologic reactions like nausea are higher with non-warmed contrast media. • Study supports extrinsic warming of CT contrast for reducing adverse effects. [ABSTRACT FROM AUTHOR]

In situ forming implants (ISFIs) composed of biodegradable polymers and biocompatible solvents are generally designed for sustained drug release. In this study, a non-invasive computed tomography (CT) imaging approach is used to achieve real time imaging of ISFIs in vivo and in vitro using leuprolide acetate in situ forming implant as a model drug product. The process of implant formation, inner structure change and their impact on drug release were elucidated. Real-time drug distribution was unveiled by the CT contrast agent, iohexol, where it shows a core-shell structure of the deposition. The incorporation of leuprolide acetate (LA) led to a reduced extent of burst release, prolongated release profile, and extended implant size expansion. LA was found to interact with the solvent and slowed down the polymer phase inversion, thus significantly changed the drug distribution in the implant and reduced the drug release. The implant inner structure identified through SEM, implant size change, and polymer degradation along with the CT real time imaging all consistently support the implant formation differences and their implant on the drug release. Similar patterns of implant size expansion and iohexol distribution in the implants were observed both in vitro and in vivo for the implants with and without LA. The comprehensive understanding of the impact of implant formation on drug release through real time CT imaging facilitates the ISFI product development and evaluation. [Display omitted] [ABSTRACT FROM AUTHOR]

The increase in imaging technologies as well as many disease conditions requiring contrast media for diagnosis makes it important to investigate the effect of contrast media on hepato-renal function and its relation to oxidant and antioxidant status. To achieve this, twenty-five male albino rats were divided into 5 groups and administered with different doses of contrast agents (urografin and iohexol). After 48 hours of administration, 5 ml of blood samples was collected for the assessment of renal function, hepatic function and oxidative stress. The liver and kidneys were also excised for histological analysis. The result showed a significant increase (p=0.003) in the mean serum creatinine and urea in animals treated with either iohexol or urografin at different doses compared to the control. There was a significant increase (p=0.003) in serum malondialdehyde (MDA) level in contrast media group when compared with the control but serum total antioxidant status (TAS) level decreased in the groups administered with contrast media though the difference was not significant (p=0.003). Groups injected with iohexol showed no obvious histopathological alteration in both renal and hepatic tissues. In the groups treated with urografin, especially in higher dose, inflammatory cellular infiltration was observed at the peri-glomerular region and within the medulla in the kidney, while in the liver the portal tract appeared enlarged with infiltration of inflammatory cells. The result suggests that both iohexol and urografin are risk factors of kidney and liver damage as a result of increase in the pro-oxidant MDA and marked histomorphological alteration. [ABSTRACT FROM AUTHOR]

Impaired intestinal integrity in broilers reduces performance and health, highlighting the importance of accurately measuring intestinal permeability (IP) to maintain gut health. The objective of this study was to evaluate the efficiency of iohexol as an IP marker in broilers challenged with Eimeria maxima, Clostridium perfringens, or both during both peak challenge (day [d] 21) and recovery (d 28) periods. One-day-old male Ross 708 birds (n = 56) were distributed into 4 treatment groups: NC (no-challenge control); EM (challenged with 5,000 E. maxima sporulated oocysts/bird on d 15); CP (challenged with 1.0 × 108 CFUs/bird of C. perfringens on d 19 and d 20); and EM + CP (challenged by co-infection of E. maxima and C. perfringens as described). On d 21 and d 28, each bird received an iohexol dose of 64.7 mg/kg body weight via oral gavage. One hour later, blood samples were collected from 14 birds (12 in EM) per group on d 21 and from 7 birds (6 in EM) on d 28. For lesion scoring and ileum collection, 7 birds per group (6 birds in EM) were sampled on each d 21 and d 28. Birds in the EM and EM + CP groups had lower body weight gain (BWG) compared to the NC and CP groups on d 19–21 (P ≤ 0.05). These birds also exhibited significantly greater lesion scores and markedly higher serum iohexol levels on d 21 (P ≤ 0.05). However, no significant differences in serum iohexol levels were observed among treatment groups following recovery on d 28. Moreover, significant differentials were observed in the mRNA abundance of key tight junction proteins (CLDN1, CLDN2, and ZO3), pro-inflammatory cytokines (IL-1β, IFNγ, and IL-22), and gut health markers (GLP2, OLFM4, and MUC2) in the EM and EM + CP groups compared to the NC and CP groups on d 21. In conclusion, this study demonstrates that iohexol is an effective marker for assessing IP in broilers under different enteric challenge conditions.

Purpose This multicenter prospective study aimed to evaluate the quality and diagnostic effectiveness of cerebral angiography images obtained using low-concentration iodinated contrast agents (iohexol 240 mgI/mL, iopamidol 250 mgI/mL, and iodixanol 270 mgI/mL) and to assess the safety thereof. The study addresses the need for safer contrast agent alternatives without compromising the diagnostic quality of identifying cerebrovascular disease. Materials and Methods Conducted in 5 medical centers in South Korea, we enrolled patients aged 19 years or older who were referred for diagnostic cerebral angiography under non-emergency conditions, excluding those with specific health conditions and sensitivities. The study design included a prospective, observational approach with a 1-way analysis of variance (ANOVA) for sample size calculation, aiming for a total sample of 231 participants for adequate power. Image quality was evaluated using a 4-level scale by 2 independent, blinded radiologists, and adverse reactions were monitored both immediately and up to 7 days post-procedure. Statistical analysis involved 1-way ANOVA and Kruskal–Wallis tests to assess the image quality and safety profiles of the contrast agents. Results Among 266 patients screened, 243 were included in the final analysis. The evaluation revealed no statistically significant differences in image quality among the 3 types of low-concentration contrast agents. Adverse events were observed in 28.8% of patients, with 27.2% experiencing acute reactions, primarily mild reactions, and 3.3% experiencing delayed reactions. The overall safety profile showed no significant changes in vital signs or electrocardiogram readings before and after contrast agent injection. Conclusion Using low-concentration iodinated contrast agents for cerebral angiography provides image quality comparable to that of conventional high-concentration agents, with no significant increase in adverse events, suggesting a safer alternative for patients.

Implementing shortened one-compartment iohexol plasma clearance models for GFR measurement is crucial since the gold standard inulin renal clearance technique and the reference two-compartment, 10-hour, 16-samplings iohexol plasma clearance method are clinically unfeasible. Inulin may precipitate anaphylactic shock. Four-hour and 8-hour one-compartment iohexol plasma clearance models with Bröchner-Mortensen correction provide accurate GFR measurements in patients with estimated GFR (eGFR) > or ≤40 mL/min/1.73m2, respectively. We compared the performance of the simplified 5-hour, 4-samplings, two-compartment population pharmacokinetic model (popPK) with the performance of the reference two-compartment 10-hour iohexol method in 16 patients with GFR 15.2 to 56.5 mL/min/1.73 m2. We also compared the performance of shortened (5, 6 and 7-hour) one-compartment models with the performance of the standard 8-hour one-compartment model in 101 patients with eGFR ≤40 mL/min/1.73 m2. The performance of popPK and shortened methods versus reference methods was evaluated by total deviation index (TDI), concordance correlation coefficient (CCC) and coverage probability (CP). TDI <10%, CCC ≥0.9 and CP >90% indicated adequate performance. TDI, CCC and CP of popPK were 11.11%, 0.809 and 54.10%, respectively. All shortened, one-compartment models overestimated the GFR (p <0.0001 for all) as compared to the 8-hour model. TDI, CCC and CP were 7.02%, 0.815, and 75.80% for the 7-hour model, 7.26%, 0.803, and 74.20% for the 6-hour model, and 8.85%, 0.729 and 64.70% for the 5-hour model. The agreement of popPK model was comparable to that obtained with the Chronic-Kidney-Disease-Collaboration-Epidemiology (CKD-Epi) and the Modification-of-Diet-in-Renal-Disease (MDRD) serum-creatinine based equations for GFR estimation. PopPK model is remarkably unreliable for GFR measurement in stage III-IV CKD patients. In patients with eGFR ≤40 mL/min/1.73m2, shortened one-compartment models, in particular the 5-hour model, are less performant than the reference 8-hour model. For accurate GFR measurements, the iohexol plasma clearance should be measured with appropriate protocols. Over-simplified procedures should be avoided. [ABSTRACT FROM AUTHOR]

Creatinine-based estimated glomerular filtration rate (eGFR) is imprecise at individual level, due to non-GFR-related serum creatinine determinants, including atypical muscle mass. Cystatin C has the advantage of being independent of muscle mass, a feature that led to the development of race- and sex-free equations. Yet, cystatin C–based equations do not perform better than creatinine-based equations for estimating GFR unless both variables are included together. The new race-free Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation had slight opposite biases between Black and non-Black subjects in the USA, but has poorer performance than that the previous version in European populations. The European Kidney Function Consortium (EKFC) equation developed in 2021 can be used in both children and adults, is more accurate in young and old adults, and is applicable to non-white European populations, by rescaling the Q factor, i.e. population median creatinine, in a potentially universal way. A sex- and race-free cystatin C–based EKFC, with the same mathematical design, has also be defined. New developments in the field of GFR estimation would be standardization of cystatin C assays, development of creatinine-based eGFR equations that incorporate muscle mass data, implementation of new endogenous biomarkers and the use of artificial intelligence. Standardization of different GFR measurement methods would also be a future challenge, as well as new technologies for measuring GFR. Future research is also needed into discrepancies between cystatin C and creatinine, which is associated with high risk of adverse events: we need to standardize the definition of discrepancy and understand its determinants. [ABSTRACT FROM AUTHOR]

Purpose: This multicenter prospective study aimed to evaluate the quality and diagnostic effectiveness of cerebral angiography images obtained using low-concentration iodinated contrast agents (iohexol 240 mgI/mL, iopamidol 250 mgI/mL, and iodixanol 270 mgI/mL) and to assess the safety thereof. The study addresses the need for safer contrast agent alternatives without compromising the diagnostic quality of identifying cerebrovascular disease. Materials and Methods: Conducted in 5 medical centers in South Korea, we enrolled patients aged 19 years or older who were referred for diagnostic cerebral angiography under non-emergency conditions, excluding those with specific health conditions and sensitivities. The study design included a prospective, observational approach with a 1-way analysis of variance (ANOVA) for sample size calculation, aiming for a total sample of 231 participants for adequate power. Image quality was evaluated using a 4-level scale by 2 independent, blinded radiologists, and adverse reactions were monitored both immediately and up to 7 days post-procedure. Statistical analysis involved 1-way ANOVA and Kruskal–Wallis tests to assess the image quality and safety profiles of the contrast agents. Results: Among 266 patients screened, 243 were included in the final analysis. The evaluation revealed no statistically significant differences in image quality among the 3 types of low-concentration contrast agents. Adverse events were observed in 28.8% of patients, with 27.2% experiencing acute reactions, primarily mild reactions, and 3.3% experiencing delayed reactions. The overall safety profile showed no significant changes in vital signs or electrocardiogram readings before and after contrast agent injection. Conclusion: Using low-concentration iodinated contrast agents for cerebral angiography provides image quality comparable to that of conventional high-concentration agents, with no significant increase in adverse events, suggesting a safer alternative for patients. [ABSTRACT FROM AUTHOR]

Endoplasmic reticulum (ER) stress-associated chaperones trigger a defense mechanism called as unfolded protein response (UPR) which can manage apoptosis and be determinative in cell fate. Both anticancer drug effects and potential toxicity effects of magnetic resonance imaging (MRI) and computed tomography (CT) contrast agents were aimed to be evaluated. For this purpose, we investigated expression profiles of endoplasmic reticulum stress-associated chaperone molecules in human pancreatic tumor lines BxPC-3 and PANC-1 and control human embryonic kidney cells 293 (HEK293) induced with a variety of gadolinium and iohexol contrast agents. Protein expression levels of ER stress-associated chaperones (master regulator: GRP78/Bip and its copartners: Calnexin, Ero1, PDI, CHOP, IRE1α and PERK) were evaluated with Western blotting. Expression levels at mRNA level were also assessed for GRP78/Bip and CHOP with real-time PCR. Induction of cells was carried out with four different Gd-based contrast agents (GBCAs): (Dotarem, Optimark, Primovist and Gadovist) and two different iohexol agents (Omnipol, Omnipaque). CT contrast agents tested in the study did not result in significant ER stress in HEK293 cells. However, they do not seem to have theranostic potential in pancreas cancer through ER pathway. The potential efficiency of macrocyclic MRI contrast agents to provoke apoptosis via ER stress-associated chaperones in BxPC-3 cells lends credibility for their future theranostic use in pancreas cancer as long as undesired toxicity effects were carefully considered. ER stress markers and/or contrast agents seem to have promising potential to be translated into the clinical practice to manage pancreas cancer progression. [ABSTRACT FROM AUTHOR]

Simple Summary: Acute hemorrhagic diarrhea syndrome (AHDS) is characterized by severe gastrointestinal fluid loss and necrotizing enteritis. This indicates an intestinal barrier dysfunction, altered intestinal permeability may indicate disease severity and might represent a risk factor for the development of chronic disorders. Serum iohexol measurement is utilized to assess intestinal permeability in dogs. Our study aimed to correlate intestinal permeability (measured by serum iohexol concentration (SIC)) with clinical severity in dogs with AHDS. We hypothesized increased intestinal permeability in dogs with AHDS, correlating with clinical severity. Fifty-three client-owned dogs, including those with AHDS and healthy controls, were enrolled. Clinical severity was assessed using the AHDS index and criteria for systemic inflammatory response syndrome (SIRS). Simultaneously, dogs were orally administered iohexol, and serum samples were collected for SIC measurement. The findings revealed significantly elevated SIC among dogs with AHDS compared to healthy controls, with a positive correlation between SIC and disease severity indices. These results highlight that dogs with a severe form of AHDS have an especially significant dysfunction of the intestinal barrier. Future studies are necessary to evaluate a potential association between an altered intestinal barrier at the phase of acute enteritis and the development of chronic intestinal disease later in life. Histopathologic examination of intestinal biopsies from dogs with acute hemorrhagic diarrhea syndrome (AHDS) reveals necrotizing enteritis and epithelial integrity loss. Serum iohexol measurement has been utilized to assess intestinal permeability. Our hypothesis is that dogs with AHDS have increased intestinal permeability, which is associated with the severity of clinical signs. In this prospective case–control study, 53 client-owned dogs (28 AHDS, 25 healthy controls) were evaluated. Clinical severity was assessed using the AHDS index and systemic inflammatory response syndrome (SIRS) criteria. Simultaneously, dogs received oral iohexol, and serum iohexol concentrations (SICs) were measured two hours later. Results indicated significantly higher (p = 0.002) SIC in AHDS dogs (median: 51 µg/mL; min–max: 9–246) than in healthy controls (30 µg/mL; 11–57). There was a significant positive correlation between AHDS index and SIC (rS = 0.4; p = 0.03) and a significant negative between SIC and serum albumin concentrations (Pearson r = −0.55; p = 0.01). Dogs with severe AHDS (mean 106 µg/mL; range: 17–246) demonstrated significantly higher (p = 0.002) SIC than those with mild to moderate disease (29 µg/mL; 9–54). These findings underscore the association between intestinal permeability and clinical severity in dogs with AHDS assessed by iohexol. [ABSTRACT FROM AUTHOR]

Patients with kidney disease require frequent blood tests to monitor their kidney function, which is particularly difficult for young children and the elderly. For these people, the standard method is to evaluate serum creatinine or cystatin C or drug levels through venous sampling, but more recently, evaluation using dried blood spots has been used. This narrative review reports information from the literature on the use of dried blood spots to quantify the main markers used to detect kidney diseases. The ScienceDirect and PubMed databases were searched using the keywords: "dried blood on filter paper," "markers of renal function," "renal function," "creatinine," "cystatin C," "urea," "iohexol," and "iotalamate." Studies using animal samples were excluded, and only relevant articles in English or Spanish were considered. Creatinine was the most assessed biomarker in studies using dried blood spots to monitor kidney function, showing good performance in samples whose hematocrit levels were within normal reference values. According to the included studies, dried blood spots are a practical monitoring alternative for kidney disease. Validation parameters, such as sample and card type, volume, storage, internal patterns, and the effects of hematocrit are crucial to improving the reliability of these results.

A survey was conducted among clinical chemists and nephrologists from hospitals in Europe and North America to identify differences in protocols for measuring glomerular filtration rate (GFR) using iohexol clearance. The survey revealed a lack of standardization in pre-analytical, analytical, and post-analytical protocols for iohexol-based GFR measurement. Variations were found in patient instructions, timing of measurements, number of samples collected, measurement methods, and corrections and adjustments used. The study emphasizes the need for standardization in iohexol-based GFR measurement to improve clinical decision-making, patient care, and kidney function research. [Extracted from the article]

Accurate assessment of renal function is of great clinical and scientific importance, as it is an important pharmacokinetic covariate of pivotal drugs. The iohexol clearance is nearly identical to the glomerular filtration rate, but its determination usually requires an intravenous injection and therefore bears intrinsic risks. This motivates to showcase an "en passant" approach to quantification of renal function without additional risk or blood sampling beyond routine care using real-world data. We enrolled 37 intensive care patients who received high doses of iohexol for computed tomography imaging, and quantified series of iohexol plasma concentrations by highperformance liquid chromatography (HPLC-UV). Iohexol clearance was derived by both log-linear regression and nonlinear least squares fitting and compared to glomerular filtration rate estimated by the CKD-EPI-2021 formulas. Nonlinear fitting not only turned out to be more accurate but also more robust in handling the irregularly timed data points. Concordance of iohexol clearance against estimations based on both creatinine and cystatin C showed a slightly higher bias (-3.44 mL/min/1.73 m2) compared to estimations based on creatinine alone (-0.76 mL/min/1.73m2), but considerably narrower limits of agreement (±42.8 vs. 56 mL/min/1.73m2) and higher Lin's correlation (0.84 vs. 0.72). In summary, we have demonstrated the feasibility and performance of the "en passant" variant of the iohexol method in intensive care medicine and described a working protocol for its application in clinical practice and pharmacologic studies. [ABSTRACT FROM AUTHOR]

Patients with kidney disease require frequent blood tests to monitor their kidney function, which is particularly difficult for young children and the elderly. For these people, the standard method is to evaluate serum creatinine or cystatin C or drug levels through venous sampling, but more recently, evaluation using dried blood spots has been used. This narrative review reports information from the literature on the use of dried blood spots to quantify the main markers used to detect kidney diseases. The ScienceDirect and PubMed databases were searched using the keywords: "dried blood on filter paper," "markers of renal function," "renal function," "creatinine," "cystatin C," "urea," "iohexol," and "iotalamate." Studies using animal samples were excluded, and only relevant articles in English or Spanish were considered. Creatinine was the most assessed biomarker in studies using dried blood spots to monitor kidney function, showing good performance in samples whose hematocrit levels were within normal reference values. According to the included studies, dried blood spots are a practical monitoring alternative for kidney disease. Validation parameters, such as sample and card type, volume, storage, internal patterns, and the effects of hematocrit are crucial to improving the reliability of these results. [ABSTRACT FROM AUTHOR]

Sulfate radical (SO4•−)–based advanced oxidation processes (AOPs) from sulfite activation have recently received attention for abatement of microorganic pollutants in the aquatic environments. Trace-level Co(II) has been demonstrated to be effective for promoting sulfite activation (simplified as the Co(II)/sulfite system) and the corresponding radical formation, yet this process is challenged by the limited valence inter-transformation of Co(II)/Co(III). In order to enhance this valence inter-transformation, a novel Co(II)/HPO42−/sulfite system is developed in this work, because HPO42−, as a typical radical scavenging agent, has the advantage of complexing with Co(II) without quenching effect. In this work, complexation of Co(II) with HPO42− can regulate the electronic structure of Co(II), accelerate electron transfer, and promote valence inter-transformation of Co(II)/Co(III) during the sulfite activation process. The Co(II)/HPO42−/sulfite system exhibits superior iohexol abatement performance under circumneutral conditions. For pH 8.0 and Co(II) dose of 1 μM, the iohexol abatement efficiency is as high as 98%, which is considerably higher than that of the Co(II)/sulfite system (50%). SO4•− is identified as the predominant reactive radical contributing to iohexol abatement. The presence of HPO42− broadens the pH adaptability of the Co(II)/sulfite system for iohexol abatement. In addition, the coexisting Cl− exerts an inhibitory effect on iohexol abatement while the other cations and anions show negligible effect. The Co(II)/HPO42−/sulfite system displays good reusability and adaptability towards various organic pollutants. This study highlights the important role of complexation of Co(II) with HPO42− in sulfite activation and provides a feasible idea for abatement of the microorganic pollutants. [ABSTRACT FROM AUTHOR]

This study aimed to develop material for multimodal imaging by means of X‐ray and near‐infrared containing FDA‐ and EMA‐approved iohexol and indocyanine green (ICG). The mentioned contrast agents (CAs) are hydrophilic and amphiphilic, respectively, which creates difficulties in fabrication of functional polymeric composites for fiducial markers (FMs) with usage thereof. Therefore, this study exploited for the first time the possibility of enhancing the radiopacity and introduction of the NIR fluorescence of FMs by adsorption of the CAs on hydroxyapatite (HAp) nanoparticles. The particles were embedded in the poly(L‐lactide‐co‐caprolactone) (P[LAcoCL]) matrix resulting in the composite material for bimodal near‐infrared fluorescence‐ and X‐ray‐based imaging. The applied method of material preparation provided homogenous distribution of both CAs with high iohexol loading efficiency and improved fluorescence signal due to hindered ICG aggregation. The material possessed profound contrasting properties for both imaging modalities. Its stability was evaluated during in vitro experiments in phosphate‐buffered saline (PBS) and foetal bovine serum (FBS) solutions. The addition of HAp nanoparticles had significant effect on the fluorescence signal. The X‐ray radiopacity was stable within minimum 11 weeks, even though the addition of ICG contributed to a faster release of iohexol. The stiffness of the material was not affected by iohexol or ICG, but incorporation of HAp nanoparticles elevated the values of bending modulus by approximately 70%. Moreover, the performed cell study revealed that all tested materials were not cytotoxic. Thus, the developed material can be successfully used for fabrication of FMs. [ABSTRACT FROM AUTHOR]

Barium sulfate and iohexol are commonly used as contrast agents for videofluoroscopic swallowing study (VFSS). This study compared their usefulness as contrast agents in visualizing components of swallowing predictable of subsequent pneumonia and unintentional weight loss after VFSS. This was a randomized, controlled, crossover trial. The two contrast agents were alternately used in the same participants, and the order in which the contrast agent was tested first was randomly assigned. After VFSS, we followed the participants for 3 months and the association between VFSS findings of each contrast agent and the subsequent pneumonia and unintentional weight loss were analyzed. A total of 30 participants were included in the analysis. We recorded 11 cases of subsequent pneumonia and 13 of unintentional weight loss. Regarding the risk of subsequent pneumonia after VFSS, only the oral transit time and number of swallows tested with barium sulfate indicated significant differences between participants with and without subsequent pneumonia. For unintentional weight loss, oral transit time and pharyngeal wall coating after swallowing tested with barium sulfate, as well as oral transit time, nasal penetration, residue in the valleculae, PAS scores, and number of swallows when testing with iohexol demonstrated significant differences between those with and without unintentional weight loss. [ABSTRACT FROM AUTHOR]

(1) Pigs are physiologically very relevant as animal models of human physiology. Radiotracer methods for porcine GFR (glomerular filtration rate) determination exist but require full-curve blood sampling or the application of correction formulas, which vary among studies. (2) We used porcine GFR data (40 datapoints from 20 juvenile pigs) for which the GFR was measured as the plasma clearance of [99mTc]Tc-DTPA. The reference clearance (Cl, GFR; range 41–85 mL/min) was measured from the full curve under the data. For simpler determination, an approximate clearance, Cl1, was based on the last five blood samples (acquired 120–240 min post injection). (3) The following formula for the GFR was developed: Cl = 1.27 · (Cl1)0.92. The spread (SD) was within 4% of the reference GFR. A comparison with the literature data showed that our correction formula was robust in pigs of various breeds, sizes up to approximately 200 kg, and GFRs up to approximately 400 mL/min, with a spread of up to 8%. The formula was also applicable for iohexol as the tracer. (4) A formula was developed that allows porcine GFR to be measured using only 4–5 late blood samples. This new formula can be applied across a wide range of swine breeds, animal sizes, and GFR ranges, allowing for robust determination of the GFR in pigs without full-curve blood sampling and without urine collection. [ABSTRACT FROM AUTHOR]

Rationale and objectiveGlomerular filtration rate (GFR) estimation based on creatinine and cystatin C (eGFRcr-cys) is more accurate than estimated GFR (eGFR) based on creatinine or cystatin C alone (eGFRcr or eGFRcys, respectively), but the inclusion of creatinine in eGFRcr-cys requires specification of a person's race. β2-Microglobulin (B2M) and β-trace protein (BTP) are alternative filtration markers that appear to be less influenced by race than creatinine is.Study designStudy of diagnostic test accuracy.Setting and participantsDevelopment in a pooled population of 7 studies with 5,017 participants with and without chronic kidney disease. External validation in a pooled population of 7 other studies with 2,245 participants.Tests comparedPanel eGFR using B2M and BTP in addition to cystatin C (3-marker panel) or creatinine and cystatin C (4-marker panel) with and without age and sex or race.OutcomesGFR measured as the urinary clearance of iothalamate, plasma clearance of iohexol, or plasma clearance of [51Cr]EDTA.ResultsMean measured GFRs were 58.1 and 83.2 mL/min/1.73 m2, and the proportions of Black participants were 38.6% and 24.0%, in the development and validation populations, respectively. In development, addition of age and sex improved the performance of all equations compared with equations without age and sex, but addition of race did not further improve the performance. In validation, the 4-marker panels were more accurate than the 3-marker panels (P < 0.001). The 3-marker panel without race was more accurate than eGFRcys (percentage of estimates greater than 30% different from measured GFR [1 - P30] of 15.6% vs 17.4%; P = 0.01), and the 4-marker panel without race was as accurate as eGFRcr-cys (1 - P30 of 8.6% vs 9.4%; P = 0.2). Results were generally consistent across subgroups.LimitationsNo representation of participants with severe comorbid illness and from geographic areas outside of North America and Europe.ConclusionsThe 4-marker panel eGFR is as accurate as eGFRcr-cys without requiring specification of race. A more accurate race-free eGFR could be an important advance.

Background: An accurate measurement of the glomerular filtration rate (GFR) is essential for detecting renal insufficiency in living kidney donors. Iohexol is a "near-ideal" exogenous filtration marker for GFR measurements that has attracted increasing interest in clinical practice because it is non-toxic, non-radioactive, readily available, and easy to measure. In this study, we aimed to set up a laboratory test to conveniently assess the plasma clearance of iohexol in living kidney donors. Methods: A workflow was established in the institution's infusion clinic to administer iohexol and to collect three timed blood samples from renal transplant donors. Iohexol was thereafter measured by liquid chromatography–tandem mass spectrometry (LC-MS/MS). The serum proteins were precipitated and the supernatant containing iohexol was diluted prior to the LC-MS/MS analysis. The LC-MS/MS method was developed on a Thermo Vanquish UHPLC coupled with a TSQ Endura triple quadruple mass spectrometer with a total run time of 2.5 min. The analytical performance of the method was assessed. Results: The LC-MS/MS method demonstrated a good analytical performance. To calculate the iohexol clearance rate and the GFR, automated data integration and a result calculation were accomplished by using a custom Python script. Automated result reporting was achieved using a laboratory informatics system (LIS) vendor's direct media interface. Conclusions: We developed and implemented a laboratory test to assess the plasma clearance of iohexol. A workflow was established in the hospital to reliably measure the GFR in living kidney donors, with a potential to be further expanded into other areas where an accurate GFR measurement is needed. [ABSTRACT FROM AUTHOR]

Glomerular filtration rate (GFR) is estimated in clinical practice from equations based on the serum concentration of endogenous biomarkers and demographic data. The 2009 creatinine-based Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI2009) was recommended worldwide until 2021, when it was recalibrated to remove the African-American race factor. The CKD-EPI2009 and CKD-EPIcr2021 equations overestimate GFR of adults aged 18–30 years, with a strong overestimation in estimated GFR (eGFR) at age 18 years. CKD-EPICr2021 does not perform better than CKD-EPI2009 in US population, overestimating GFR in non-Black subjects, and underestimating it in Black subjects with the same magnitude. CKD-EPICr2021 performed worse than the CKD-EPI2009 in White Europeans, and provides no or limited performance gains in Black European and Black African populations. The European Kidney Function Consortium (EKFC) equation, which incorporates median normal value of serum creatinine in healthy population, overcomes the limitations of the CKD-EPI equations: it provides a continuity of eGFR at the transition between pediatric and adult care, and performs reasonably well in diverse populations, assuming dedicated scaling of serum creatinine (Q) values is used. The new EKFC equation based on cystatin C (EKFCCC) shares the same mathematical construction, namely, it incorporates the median cystatin C value in the general population, which is independent of sex and ethnicity. EKFCCC is therefore a sex-free and race-free equation, which performs better than the CKD-EPI equation based on cystatin C. Despite advances in the field of GFR estimation, no equation is perfectly accurate, and GFR measurement by exogenous tracer clearance is still required in specific populations and/or specific clinical situations. [ABSTRACT FROM AUTHOR]

This study was conducted to evaluate the effect of the comparative study of contrast media for gastrography of the mynah bird. This study was conducted on 12 adult male mynah birds. Using different contrast agents, all the birds were studied five times, with a minimum of two days of the time interval between each study. Radiographic tests were performed 1, 5, 15, 30, 60, and 90 minutes after ingesting the contrast agent via using a gavage tract; imaging was performed at a time interval of 30 minutes and continued until the time when the contrast agent reached the cloaca and was excreted. There was a statistically significant difference between the results of digestive system studies using Iodixanol, Iohexol, and barium sulfate in terms of mean scores of the contrast agent’s ability to fill different parts of the gastrointestinal tract, clarity of observations, and observing details of the gastrointestinal tract at all times of radiography (p < 0.05). Iodixanol is less nephrotoxic and is a better contrast agent, however, we do not recommend using Iodixanol and Iohexol diluted by water at a ratio of 1:1.

BACKGROUND: At present, cone-beam computed tomography (CBCT) cannot clearly portray the outline of gingival soft tissue, which is not only easily susceptible to interference from lip tissue and metal restoration artifacts and has poor repeatability, but also is not conducive to accurately measure soft tissue and classify gingival biotypes. OBJECTIVE: To access the feasibility of using CBCT in conjunction with novel radiocontrast agent to develop gingival morphology in a stable and convenient manner, as well as the reliability of classifying gingival biotypes. METHODS: Totally 180 maxillary anterior teeth from 30 healthy volunteers were collected and the gingival thickness 2 mm below the gingival margin and the width of keratinized gingiva were measured directly. The composition of light-cure gingival barrier resin and iohexol injection was applied to the measurement area. Then the positioning wire was set up and CBCT imaging was used to assess the width of keratinized gingiva and gingiva thickness at 2 mm below the gingival margin. RESULTS AND CONCLUSION: In comparison to the direct measurement method, the approach of CBCT in conjunction with the novel radiocontrast agent demonstrated good reproducibility (P > 0.05) and reliability (ICC > 0.9), when measuring the gingival thickness and the width of keratinized gingiva on the labial side. The concordance of two approaches to classify gingival biotypes which was examined using the Kappa concordance test showed good consistency (Kappa=0.882). There were no significant statistical differences between the two approaches (P > 0.05). Overall, CBCT combined with the radiocontrast agent can clearly develop the gingival outline, which shows good feasibility and reliability. [ABSTRACT FROM AUTHOR]

The aim of this prospective study was to compare the diagnostic performance of contrast-enhanced mammography (CEM) versus digital mammography (DM) combined with breast ultrasound (BUS) in women with dense breasts. Between March 2021 and February 2022, patients eligible for CEM with the breast composition category ACR BI-RADS c–d at DM and an abnormal finding (BI-RADS 3-4-5) at DM and/or BUS were considered. During CEM, a nonionic iodinated contrast agent (Iohexol 350 mg I/mL, 1.5 mL/kg) was power-injected intravenously. Images were evaluated independently by two breast radiologists. Findings classified as BI-RADS 1–3 were considered benign, while BI-RADS 4–5 were considered malignant. In case of discrepancies, the higher category was considered for DM+BUS. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were calculated, using histology/≥12-month follow-up as gold standards. In total, 51 patients with 65 breast lesions were included. 59 (90.7%) abnormal findings were detected at DM+BUS, and 65 (100%) at CEM. The inter-reader agreement was excellent (Cohen's k = 0.87 for DM+BUS and 0.97 for CEM). CEM showed a 93.5% sensitivity (vs. 90.3% for DM+BUS), a 79.4–82.4% specificity (vs. 32.4–35.5% for DM+BUS) (McNemar p = 0.006), a 80.6–82.9% PPV (vs. 54.9–56.0% for DM+BUS), a 93.1–93.3% NPV (vs. 78.6–80.0% for DM+BUS), and a 86.1–87.7% accuracy (vs. 60.0–61.5% for DM+BUS). The AUC was higher for CEM than for DM+BUS (0.865 vs. 0.613 for Reader 1, and 0.880 vs. 0.628, for Reader 2) (p < 0.001). In conclusion, CEM had a better diagnostic performance than DM and BUS alone and combined together in patients with dense breasts. [ABSTRACT FROM AUTHOR]

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[Objectives]The aim of this study was to determine the optimal angiography protocol for canine heart and pulmonary artery angiography. [Methods]The variable iohexol concentrations were tested in this study to evaluate the effects on ardiac and pulmonary angiography, while injection duration and injection rate were same for the same size dogs. Iohexol dose(I content)from 100 to 200 mg·mL-1 were used in small dogs for ardiac angiography, 200 to 300 mg·mL-1 in middle dogs and 150 to 200 mg·mL-1 in large dogs. For pulmonary angiography, iohexol concentrations were 50 to 100 mg·mL-1 in small dogs, 50 to 100 mg·mL-1 in middle dogs and 150 to 200 mg·mL-1 in large dogs. Contrast agent was injected intravenously from cephalic veins after anesthesia. Dynamic scanning project was performed to obtain time-density curve of region of interest. Scanning delay time was calculated based on the time-density curve. The time to reach 200 HU aortic sinus was designated as delay time of cardiac angiography. The time to reach the peak enhancement of pulmonary artery trunk was designated as delay time of pulmonary arteriography. Then the images were obtained by volume scanning project. The images quality obtained by different contrast schemes were evaluated quantitatively and qualitatively to determine the optimal contrast scheme. [Results]The optimum cardiac angiography conditions for small dogs were 200 mg·mL-1 of iohexol concentration, 10 mL of iohexol volume, 5 mL of saline dose and 1 mL·s-1 of injection rate. For middle dogs, the optimum conditions were 250 mg·mL-1 of iohexol concentration, 15 mL of iohexol volume, 10 mL of saline dose and 1 mL·s-1 of injection rate. For large dogs, the optimum conditions were 350 mg·mL-1 of iohexol concentration, 30 mL of iohexol volume, 20 mL of saline dose and 1 mL·s-1 of injection rate. The optimum pulmonary arteriography conditions were as follows:75 mg·mL-1 of iohexol concentration, 15 mL of iohexol volume, 15 mL of saline dose and 5 mL·s-1 of injection rate in small dogs. For middle dogs those were 100 mg·mL-1 of iohexol concentration, 20 mL of iohexol volume, 20 mL of saline dose and 5 mL·s-1 of injection rate. And for large dogs those were 175 mg·mL-1 of iohexol concentration, 30 mL of iohexol volume, 30 mL of saline dose and 5 mL·s-1 of injection rate. The higher post-vascular enhancement CT values with good image quality and good contrast effects were obtained when used above conditions. [Conclusions]Through repeated tests, the contrast agent conditions used in this test can obtain satisfactory and clinically diagnostic images and can be applied to CT imaging of cardiac and pulmonary artery diseases in dogs. [ABSTRACT FROM AUTHOR]

Background: Acute kidney injury (AKI) and renal dysfunction after heart transplantation are common and serious complications. Atrial natriuretic peptide (ANP) has been shown to increase glomerular filtration rate (GFR) and exert renoprotective effects when used for the prevention/treatment of AKI in cardiac surgery. We tested the hypothesis that intraoperative and postoperative administration of ANP could prevent a postoperative decrease in renal function early after heart transplantation. Methods: Seventy patients were randomized to receive either ANP (50 ng/kg/min) (n = 33) or placebo (n = 37) starting after induction of anesthesia and continued for 4 days after heart transplantation or until treatment with dialysis was started. The primary end‐point of the present study was measured GFR (mGFR) at day 4, assessed by plasma clearance of a renal filtration marker. Also, the incidence of postoperative AKI and dialysis were assessed. Results: Median (IQR) mGFR at day 4 postoperatively was 60.0 (57.0) and 50.1 (36.3) ml/min/1.72 m2 for the placebo and ANP groups, respectively (p =.705). During ongoing ANP infusion, the need for dialysis was 21.6% and 9.1% for the placebo and ANP groups, respectively (p =.197). The incidences of AKI for the placebo and the ANP groups were 76.5% and 63.6%, respectively (p =.616). The incidences of AKI stage 1 were 32.4% and 21.2% for the placebo and ANP groups, respectively (p =.420) and for AKI stage 2 or 3, 37.8% and 42.4%, respectively (p =.808). Conclusion: The study failed to detect that ANP infusion attenuates renal dysfunction or decreases the incidence of AKI after heart transplantation. [ABSTRACT FROM AUTHOR]

OBJECTIVE To investigate the effect of iohexol on standardized quantitative urine culture results in dogs. The authors hypothesized that the presence of iohexol in inoculated urine samples would result in lower bacterial concentrations (CFU/mL) and, therefore, decrease culture sensitivity. SAMPLE Urine samples were aseptically collected during cystoscopy from a single client-owned dog untreated with antimicrobials. PROCEDURES An experimental controlled study. The urine sample was divided into 38 aliquots (0.5 mL each) that were used as negative controls or inoculated with an equal amount of Escherichia coli (105 CFU/mL). Different volumes (0.1 and 0.5 mL) of contrast or saline were added to the aliquots and quantitative culture results were compared. Two different incubation times between the preparation of aliquots and culture were evaluated (15 minutes and 24 hours). RESULTS All aliquots from samples inoculated with E. coli (positive controls and iohexol-group) had the same reported quantitative result (104 CFU/mL). No growth was reported for the negative controls. Iohexol did not show any anti-E. coli properties in canine urine cultures for dilutions up to 1:2 contrast:urine and concentrations up to 120 mgI/mL. No difference was reported when iohexol was incubated with inoculated urine for 15 minutes or 24 hours. CLINICAL RELEVANCE Based on the experimental in vitro conditions described, administration of iohexol before the collection of urine during urologic procedures does not negatively impact the isolation and growth of E. coli. [ABSTRACT FROM AUTHOR]

Contrast-induced nephropathy (CIN) is one of the most common causes of acute kidney injury (AKI). However, management is still limited, and the cellular response to radiocontrast removal for CIN remains unclear. This study aimed to explore the latent effects of iohexol in cultured renal tubular cells with or without the removal of iohexol by medium replacement. HK2 renal tubular cells were subcultured 24 h before use in CIN experiments. Three treatment groups were established: the control, a radiocontrast (iohexol)-only group at 75 mg I/mL (I-75), and iohexol exposure for 24 h with culture medium replacement (I-75/M). Cell cycle arrest, fibrogenic mediator assays, cell viability, cell function, and cell-cycle-related protein expression were compared between groups. Iohexol induced numerous changes in HK2 renal tubular cells, such as enlarged cell shape, cell cycle arrest, increased apoptosis, and polyploidy. Iohexol inhibited the expression of cyclins, CDKs, ZO-1, and E-cadherin but conversely enhanced the expression of p21 and fibrosis-related genes, including TGF-β1, CTGF, collagen I, collagen III, and HIF-1α within 60 hr after the exposure. Except for the recovery from cell cycle arrest and cell cycle gene expression, notably, the removal of iohexol by medium replacement could not fully recover the renal tubular cells from the formation of polyploid cells, the adhesion or spreading, or the expression of fibrosis-related genes. The present study demonstrates, for the first time, that iohexol exerts latent cytotoxic effects on cultured renal tubular cells after its removal, suggesting that these irreversible cell changes may cause the insufficiency of radiocontrast reduction in CIN, which is worth investigating further. [ABSTRACT FROM AUTHOR]

ObjectivesThe goal of this study was to demonstrate feasibility of measuring extracellular pH in cartilage and meniscus using acidoCEST technique with a 3-dimensional ultrashort echo time readout (acidoCEST-UTE) magnetic resonance imaging (MRI).Materials and methodsMagnetization transfer ratio asymmetry, radiofrequency (RF) power mismatch, and relative saturation transfer were evaluated in liquid phantoms for iopromide, iopamidol, and iohexol over a pH range of 6.2 to 7.8, at various agent concentrations, temperatures, and buffer concentrations. Tissue phantoms containing cartilage and meniscus were evaluated with the same considerations for iopamidol and iohexol. Phantoms were imaged with the acidoCEST-UTE MRI sequence at 3 T. Correlation coefficients and coefficients of variations were calculated. Paired Wilcoxon rank-sum tests were used to evaluate for statistically significant differences.ResultsThe RF power mismatch and relative saturation transfer analyses of liquid phantoms showed iopamidol and iohexol to be the most promising agents for this study. Both these agents appeared to be concentration independent and feasible for use with or without buffer and at physiologic temperature over a pH range of 6.2 to 7.8. Ultimately, RF power mismatch fitting of iohexol showed the strongest correlation coefficients between cartilage, meniscus, and fluid. In addition, ratiometric values for iohexol are similar among liquid as well as different tissue types.ConclusionsMeasuring extracellular pH in cartilage and meniscus using acidoCEST-UTE MRI is feasible.

Yanyan Li,1,2 Junda Wang,2 Dan Huang,2 Chao Yu1 1College of Pharmacy, Chongqing Medical University, Chongqing, People’s Republic of China; 2Chongqing Traditional Chinese Medicine Hospital, Chongqing, People’s Republic of ChinaCorrespondence: Chao Yu, College of Pharmacy, Chongqing Medical University, Yixueyuan Road, Yuzhong District, Chongqing, 400016, People’s Republic of China, Tel +86 23-68485589, Fax +86 23-68486294, Email yuchao@cqmu.edu.cnPurpose: To investigate the effect of baicalin on the reactive oxygen species (ROS)/ NOD-like receptor protein 3 (NLRP3)/Caspase-1/gasdermin-D (GSDMD) inflammasome pathway and its related mechanism in regulating pyroptosis of human renal tubular epithelial cells (HK-2) induced by contrast media.Methods: Iohexol was used to act on HK-2 cells to establish a renal tubular cell pyroptosis model; and the signal pathway genes were silenced, cytokines were detected by enzyme-linked immunosorbent assay (ELISA), and cell viability, gene expression, and protein expression were evaluated by double fluorescence staining and flow cytometry. To assess the cytotoxicity caused by the contrast agent; cells were pretreated with different concentrations of baicalin; and then the cells were exposed to iohexol again, and the relevant indicators were tested again.Results: After HK-2 cells were exposed to iohexol, the NLRP3 inflammasome pathway markers NLRP3, interleukin (IL)-1β, and IL-18 mRNA levels as well as the protein expression levels of NLRP3, ASC, Caspase-1, and GSDMD were up-regulated. In addition, the effect also significantly increased the IL-18, IL-1β, lactate dehydrogenase (LDH), superoxide dismutase (SOD), malondialdehyde (MDA) release, and cellular ROS levels. The results of Annexin V-FITC/PI flow cytometry showed that the level of apoptosis was increased. However, after the intervention of baicalin, the changes in the above indexes caused by iohexol stimulation of HK-2 cells were inhibited.Conclusion: Exposure to iohexol can induce pyroptosis of HK-2 cells through the ROS/NLRP3/Caspase-1/GSDMD signaling pathway. Baicalin ameliorated iohexol-induced pyroptosis in HK-2 cells by regulating the NLRP3 inflammasome pathway.Keywords: pyroptosis, baicalin, iohexol, ROS/NLRP3/Caspase-1/GSDMD pathway, kidney injury

ABSTRACT: Intestinal integrity losses have been identified as a main driver for poor performance in broilers. The oral administration of markers such as iohexol is a major asset for measuring intestinal permeability (IP) alterations. The aim of the current study was to evaluate oral iohexol administration and serum levels as a quantitative measure for IP in Ross 308 broilers and to identify possible associations with histologic measurements. A total of 40, day-old broiler chickens were randomly divided into 4 groups of 10 broilers and a coccidiosis model was used to induce IP. Three challenge groups received a mixture of different field strains and concentrations of Eimeria acervulina and Eimeria maxima at d 16, and 1 group operated as an uninfected control group. On d 20, 5 birds per group were orally administered the permeability marker iohexol at a dose of 64.7 mg/kg body weight and blood was taken 60 min after the oral gavage. On d 21 these 5 birds per group were euthanized. On d 21, 5 other birds per group were given iohexol where after blood was taken. These birds were euthanized on d 22. During necropsy, birds were scored for coccidiosis lesions and a duodenal segment was taken for histology. The Eimeria challenge had a significant impact on the villus length, crypt depth, villus-to-crypt ratio and CD3+ T-lymphocytes area percentage. Challenged birds had a significant higher concentration of serum iohexol on both sampling days, as compared to the uninfected controls. A significant correlation could be found between the serum iohexol concentration and the histologic parameters (villus length, crypt depth and villus-to-crypt ratio) on the first sampling day. This suggests that iohexol may be used as a gut permeability marker in broilers under Eimeria challenge.

Background: Acute kidney injury (AKI) and augmented renal clearance (ARC), both alterations of the glomerular filtration rate (GFR), are prevalent in critically ill children and neonates. AKI and ARC prevalence estimates are based on estimation of GFR (eGFR) using serum creatinine (SCr), which is known to be inaccurate. We aimed to test our hypothesis that AKI prevalence will be higher and ARC prevalence will be lower in critically ill children when using iohexol-based measured GFR (mGFR), rather than using eGFR. Additionally, we aimed to investigate the performance of different SCr-based eGFR methods. Methods: In this single-center prospective study, critically ill term-born neonates and children were included. mGFR was calculated using a plasma disappearance curve after parenteral administration of iohexol. AKI diagnosis was based on the KDIGO criteria, SCr-based eGFR, and creatinine clearance (CrCL). Differences between eGFR and mGFR were determined using Wilcoxon signed-rank tests and by calculating bias and accuracy (percentage of eGFR values within 30% of mGFR values). Results: One hundred five children, including 43 neonates, were included. AKI prevalence was higher based on mGFR (48%), than with KDIGO or eGFR (11–40%). ARC prevalence was lower with mGFR (24%) compared to eGFR (38–51%). eGFR equations significantly overestimated mGFR (60–71 versus 41 ml/min/1.73 m2, p < 0.001–0.002). Accuracy was highest with eGFR equations based on age- and sex-dependent equations (up to 59%). Conclusion: Iohexol-based AKI prevalence was higher and ARC prevalence lower compared to standard SCr-based eGFR methods. Age- and sex-dependent equations for eGFR (eGFR-Smeets for neonates and eGFR-Pierce for children) best approached measured GFR and should preferably be used to optimize diagnosis of AKI and ARC in this population. A higher resolution version of the Graphical abstract is available as Supplementary information [ABSTRACT FROM AUTHOR]

Objectives: Maximum a posteriori Bayesian estimation (MAP-BE) based on a limited sampling strategy and a population pharmacokinetic (POPPK) model is used to estimate individual pharmacokinetic parameters. Recently, we proposed a methodology that combined population pharmacokinetic and machine learning (ML) to decrease the bias and imprecision in individual iohexol clearance prediction. The aim of this study was to confirm the previous results by developing a hybrid algorithm combining POPPK, MAP-BE and ML that accurately predicts isavuconazole clearance. Methods: A total of 1727 isavuconazole rich PK profiles were simulated using a POPPK model from the literature, and MAP-BE was used to estimate the clearance based on: (i) the full PK profiles (refCL); and (ii) C24h only (C24h-CL). Xgboost was trained to correct the error between refCL and C24h-CL in the training dataset (75%). C24h-CL as well as ML-corrected C24h-CL were evaluated in a testing dataset (25%) and then in a set of PK profiles simulated using another published POPPK model. Results: A strong decrease in mean predictive error (MPE%), imprecision (RMSE%) and the number of profiles outside ± 20% MPE% (n-out20%) was observed with the hybrid algorithm (decreased in MPE% by 95.8% and 85.6%; RMSE% by 69.5% and 69.0%; n-out20% by 97.4% and 100% in the training and testing sets, respectively. In the external validation set, the hybrid algorithm decreased MPE% by 96%, RMSE% by 68% and n-out20% by 100%. Conclusion: The hybrid model proposed significantly improved isavuconazole AUC estimation over MAP-BE based on the sole C24h and may improve dose adjustment. [ABSTRACT FROM AUTHOR]

In combination with Bayesian estimates based on a population pharmacokinetic model, limited sampling strategies (LSS) may reduce the number of samples required for individual pharmacokinetic parameter estimations. Such strategies reduce the burden when assessing the area under the concentration versus time curves (AUC) in therapeutic drug monitoring. However, it is not uncommon for the actual sample time to deviate from the optimal one. In this work, we evaluate the robustness of parameter estimations to such deviations in an LSS. A previously developed 4-point LSS for estimation of serum iohexol clearance (i.e., dose/AUC) was used to exemplify the effect of sample time deviations. Two parallel strategies were used: (a) shifting the exact sampling time by an empirical amount of time for each of the four individual sample points, and (b) introducing a random error across all sample points. The investigated iohexol LSS appeared robust to deviations from optimal sample times, both across individual and multiple sample points. The proportion of individuals with a relative error greater than 15% (P15) was 5.3% in the reference run with optimally timed sampling, which increased to a maximum of 8.3% following the introduction of random error in sample time across all four time points. We propose to apply the present method for the validation of LSS developed for clinical use. [ABSTRACT FROM AUTHOR]

The article "Pineal germinoma diagnosed by iohexol CT ventriculography" published in Pediatric Radiology discusses the case of a 9-year-old boy with intermittent headaches and vomiting. A pineal mass was identified using iohexol CT ventriculography, leading to a diagnosis of pineal germinoma. The tumor was successfully resected, and the patient received postoperative chemoradiotherapy with no recurrence during the 12-month follow-up. The article highlights the importance of iohexol CT ventriculography in the accurate diagnosis and treatment of such cases. [Extracted from the article]

Abstract Background A negative oral contrast agent (OCA) has been long sought for, to better delineate the bowel and visualise surrounding structures. Lumentin® 44 (L44) is a new OCA formulated to fill the entire small bowel. The aim of this study was to compare L44 with positive and neutral conventional OCA in abdominal computed tomography (CT). Methods Forty-five oncologic patients were randomised to receive either L44 or one of the two comparators (MoviPrep® or diluted Omnipaque®). Abdominal CT examinations with intravenous contrast agent were acquired according to standard protocols. The studies were read independently by two senior radiologists. Results The mean intraluminal Hounsfield units (HU)-values of regions-of-interest (ROIs) for each subsegment of small bowel and treatment group were -404.0 HU for L44, 166.1 HU for Omnipaque®, and 16.7 HU for MoviPrep® (L44 versus Omnipaque, p

Rationale & Objective: Serum creatinine and cystatin C are used to estimate glomerular filtration rate, but creatinine-based estimated glomerular filtration rate (eGFRcr), cystatin C–based estimated glomerular filtration rate (eGFRcys), and combined creatinine- and cystatin C–based estimated glomerular filtration rate (eGFRcr-cys) are often divergent, particularly in older adults. We investigated which estimated glomerular filtration rate (eGFR) was more accurate and less biased compared with measured glomerular filtration rate (mGFR). Study Design: A diagnostic test study from the Berlin Initiative Study. Setting & Participants: The study population included 657 individuals aged 70 years or older with iohexol plasma clearance (mGFR) and serum creatinine and cystatin C measurements: 567 community-dwelling participants and 90 with a serum creatinine of ≥1.5 mg/dL. Tests Compared: We defined 3 groups on the basis of the difference eGFRcys − eGFRcr: whether < −5 mL/min/1.73 m2 (lower eGFRcys), within 5 mL/min/1.73 m2 (reference), or ≥ 5 mL/min/1.73 m2 (lower eGFRcr). eGFRcr, eGFRcys, and eGFRcr-cys were compared to mGFR to assess bias and accuracy. Outcome: Median bias (eGFR minus mGFR) with 95% CIs and accuracy (percentage of eGFR values within ±30% of mGFR). Results: The mean ± standard deviation age was 78 ± 6 years; the mean eGFRcys, eGFRcr, and eGFRcr-cys were 59 ± 23, 64 ± 20, and 61 ± 22 mL/min/1.73 m2, respectively, and the mean mGFR was 56 ± 19 mL/min. Half of the participants were in the lower eGFRcys group (n=337, 51%). Among them, the median bias for eGFRcys was the lowest (median bias, −2.7; 95% CI, −3.8 to −1.9) compared with the other eGFR equations. Conversely, in the lower eGFRcr group (n=121, 18%), the median bias for eGFRcr was the lowest compared with those for eGFRcys and eGFRcr-cys (2.9; [95% CI, 0.9-4.8] vs 13.8 [95% CI, 11.4-15.6] and 9.5 [95% CI, 7.7-11.0], respectively). Accuracy (percentage of eGFR values within ±30% of mGFR) was 93% for eGFRcr in the lower eGFRcr group and 92% for eGFRcys and 94% for eGFRcr-cys in the lower eGFRcys group. Limitations: Untested generalizability in younger populations. Conclusions: Among older adults, the lower eGFR between eGFRcys and eGFRcr was a more accurate and less biased estimate of mGFR when comparing the groups.

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We sought to assess the feasibility of computed tomography coronary angiography (CTCA) on a 128-slice, dual source scanner in children with acute and convalescent phase Kawasaki disease (KD).A prospective study of 49 children with KD (12 at presentation and 37 in the convalescent phase) was conducted between November 2013 and April 2015. CTCA was performed with either prospective (n = 37) or retrospective (n = 12) electrocardiographic gating. A radiologist blinded to clinical profile and echocardiogram evaluated each scan.Median age (36 boys and 13 girls) was 7 years. Median dose-length product value and median effective CT radiation dose was 32mGycm (interquartile range [IQR]: 21-74) and 0.54 miliSieverts (mSv) (IQR: 0.77-3.2) for all scans, and 27mGycm (IQR: 18.5-33.75) and 0.48mSv (IQR: 0.18-1.17) for prospectively triggered scans (n = 37). Fourteen subjects (30 coronary segments) showed abnormalities by CTCA including aneurysms (n = 27) and stenoses (n = 3). In the acute phase (n = 12), aneurysms were detected in 5 children (18 segments).CTCA allows comprehensive evaluation of coronary arteries in children with KD.