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Background: Due to the shortage of donor organs, an increasing number of transplant organs are harvested after circulatory arrest (donation after circulatory death [DCD]). Using a translational porcine model of DCD, this study developed and evaluated a protocol based on cardioprotection by multidrug postconditioning to optimize resuscitation of DCD hearts during ex situ heart perfusion (ESHP)., Methods: Hearts of female pigs (45.0 ± 4.5 kg) were procured following a clinically identical DCD protocol, consisting of the termination of ventilator support and confirmation of circulatory arrest, followed by a 15-min standoff period. DCD hearts were randomly allocated to ESHP (38.4°C) in the absence (untreated, N = 5) or presence (treated, N = 5) of a postconditioning treatment added to the perfusate, consisting of Intralipid (1%), sevoflurane (2% v/v), and remifentanil (3 nM). All hearts were perfused with blood and Krebs-Henseleit solution (1:1) for 60 min in Langendorff mode and for an additional 300 min in working mode for a total perfusion time of 6 h. Oxidative capacity and detailed left ventricular mechanical function under an increasing workload (left atrial pressure, 6 to 12 mmHg) were assessed hourly. Left ventricular tissue was snap-frozen at the end of ESHP and used for molecular analyses., Results: Left ventricular inotropy (LVdP/dtmax) did not decline over time in treated DCD hearts and was significantly higher at the end of the protocol as compared with untreated DCD hearts (ΔLVdP/dtmax = 440 mmHg/s; P = 0.009). Treated DCD hearts exhibited persistently higher left ventricular stroke work index during the 6-h period of ESHP, whereas untreated DCD hearts displayed a significant decline (change in left ventricular stroke work index = -3.10 ml · mmHg/g; P(time within untreated group) < 0.001). Treated DCD hearts displayed higher metabolic activity as measured by oxygen consumption (ΔO2 = 3.11 ml O2 · min-1 · 100 g-1; P = 0.004) and released lower amounts of cell-free mitochondrial DNA into the perfusate, a marker of potential graft dysfunction. Treated hearts also used fatty acids from Intralipid as an energy source, whereas untreated DCD hearts showed glyceroneogenesis with triglyceride accumulation and depletion of tricarboxylic acid cycle intermediates; reduced mitochondrial complex I, II, and III activities with accumulation of mitochondrial NADH, and signs of ultrastructural damage., Conclusions: A translationally relevant protective ESHP protocol consisting of treatment with Intralipid, sevoflurane, and remifentanil markedly accelerated functional recovery and improved viability of DCD hearts., (Copyright © 2024 American Society of Anesthesiologists. All Rights Reserved.)

This meeting report presents a consensus on the biological aspects of lipid emulsions in parenteral nutrition, emphasizing the unanimous support for the integration of lipid emulsions, particularly those containing fish oil, owing to their many potential benefits beyond caloric provision. Lipid emulsions have evolved from simple energy sources to complex formulations designed to improve safety profiles and offer therapeutic benefits. The consensus highlights the critical role of omega-3 polyunsaturated fatty acids (PUFAs), notably eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), found in fish oil and other marine oils, for their anti-inflammatory properties, muscle mass preservation, and as precursors to the specialized pro-resolving mediators (SPMs). SPMs play a significant role in immune modulation, tissue repair, and the active resolution of inflammation without impairing host defense mechanisms. The panel's agreement underscores the importance of incorporating fish oil within clinical practices to facilitate recovery in conditions like surgery, critical illness, or immobility, while cautioning against therapies that might disrupt natural inflammation resolution processes. This consensus not only reaffirms the role of specific lipid components in enhancing patient outcomes, but also suggests a shift towards nutrition-based therapeutic strategies in clinical settings, advocating for the proactive evidence-based use of lipid emulsions enriched with omega-3 PUFAs. Furthermore, we should seek to apply our knowledge concerning DHA, EPA, and their SPM derivatives, to produce more informative randomized controlled trial protocols, thus allowing more authoritative clinical recommendations., (© 2024 The Author(s). The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.)

Purpose: Depression is associated with low-grade systemic inflammation and impaired intestinal function, both of which may reduce dietary iron absorption. Low iron status has been associated with depression in adults and adolescents. In Swiss adolescents, we determined the associations between paediatric major depressive disorder (pMDD), inflammation, intestinal permeability and iron status., Methods: This is a matched case-control study in 95 adolescents with diagnosed pMDD and 95 healthy controls aged 13-17 years. We assessed depression severity using the Children's Depression Rating Scale-Revised. We measured iron status (serum ferritin (SF) and soluble transferrin receptor (sTfR)), inflammation (C-reactive protein (CRP) and alpha-1-acid-glycoprotein (AGP)), and intestinal permeability (intestinal fatty acid binding protein (I-FABP)). We assessed history of ID diagnosis and treatment with a self-reported questionnaire., Results: SF concentrations did not differ between adolescents with pMDD (median (IQR) SF: 31.2 (20.2, 57.0) μg/L) and controls (32.5 (22.6, 48.3) μg/L, p = 0.4). sTfR was lower among cases than controls (4.50 (4.00, 5.50) mg/L vs 5.20 (4.75, 6.10) mg/L, p < 0.001). CRP, AGP and I-FABP were higher among cases than controls (CRP: 0.16 (0.03, 0.43) mg/L vs 0.04 (0.02, 0.30) mg/L, p = 0.003; AGP: 0.57 (0.44, 0.70) g/L vs 0.52 (0.41, 0.67) g/L, p = 0.024); I-FABP: 307 (17, 515) pg/mL vs 232 (163, 357) pg/mL, p = 0.047). Of cases, 44% reported having a history of ID diagnosis compared to 26% among controls (p = 0.020). Finally, 28% of cases had iron treatment at/close to study inclusion compared to 14% among controls., Conclusion: Cases had significantly higher systemic inflammation and intestinal permeability than controls but did not have lower iron status. Whether this is related to the higher rate of ID diagnosis and iron treatment in adolescents with depression is uncertain., (© 2024. The Author(s).)

Background and Aims: Parenteral nutrition (PN) rich in n-6 and n-3 long-chain fatty acids is used in clinical practice for nourishing patients who are unable to receive adequate nutrition through their digestive systems. In this study, we compare the effect on inflammation of the commonly used lipid emulsions Omegaven (n-3-rich) and Intralipid (n-6-rich) in human peripheral blood mononuclear cells (PBMCs)., Methods: PBMCs were treated with different doses of n-3-rich Omegaven and n-6-rich Intralipid and the immune cells were characterized by flow cytometry., Results: We show that incubation of PBMCs with n-3-rich Omegaven leads to an increase in expression of CD1d and CD86 in CD14+monocytes. At the same time, an increased number of NKT cells expressing cytotoxic T cell antigen 4 is observed, suggesting immunological synapse formation. Both CD14+monocytes and NKT cells showed an increase in IL-10 production and a reduction in the pro-inflammatory cytokines IFN-γ, TNF-α, and IL-4, which led to an increase in the number of FOXP3+T regulatory cells. In addition, we show that n-3-rich Omegaven reduces the expression of TNFα, IFNγ and IL-4 in CD4+T and CD8+T cells independent of the presented interaction between CD14+monocytes and NKT cells. The described mechanism of n-3 rich lipid emulsions was confirmed in PBMCs from patients with inflammatory bowel disease but not in colorectal cancer patients which seem to lack the interaction between CD14+monocytes and NKT cells., Conclusions: These results show a mechanism for the beneficial effect of the n-3-rich Omegaven in patients with inflammatory conditions but questions its use in patients with cancer. Hence, our results may assist in choosing the best lipid emulsion for patients who require PN., Competing Interests: Conflict of interest The authors have declared that no conflict of interest exists., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Observational studies suggest a link between n-3 polyunsaturated fatty acid (PUFA) intake, n-3 PUFA status, and depression in adults, but studies in adolescents are scarce. This study aimed to determine associations of n-3 PUFA status and intake with paediatric major depressive disorder (pMDD) in Swiss adolescents., Methods: We conducted a matched case-control study in 95 adolescents diagnosed with pMDD and 95 healthy controls aged 13 to <18 years. We analysed red blood cell (RBC) fatty acid (FA) composition (% of total FA). n-3 PUFA intake was assessed using a focused food frequency questionnaire and depression severity was assessed by the Children's Depression Rating Scale-Revised (CDRS-R)., Results: Mean RBC eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were lower in cases than controls (EPA: 0.41 ± 0.11 vs 0.46 ± 0.12, p < 0.001; DHA: 4.07 ± 1.04 vs 4.73 ± 1.04, p < 0.001). Subsequently, the mean RBC n-3 index was lower (4.51 ± 1.10 vs 5.20 ± 1.11, p < 0.001) and the n-6/n-3 PUFA ratio higher (5.51 ± 1.25 vs 4.96 ± 1.08, p < 0.001) in cases than controls. Adolescents with a higher n-3 index had lower odds for depression (OR = 0.49 [95% CI: 0.32-0.71]). In contrast, the n-6/n-3 PUFA ratio was associated with higher odds for depression (OR = 1.58 [95% CI: 1.14-2.25]). Intake of alpha-linolenic acid, EPA and DHA did not differ between cases and controls., Conclusion: Our results suggest that a higher RBC n-3 PUFA status during adolescence is associated with a lower risk for pMDD, whereas a higher n-6/n-3 PUFA ratio is associated with a higher risk for pMDD. Differences in n-3 PUFA intake did not explain the observed differences in n-3 PUFA status., Competing Interests: Declaration of competing interest All authors declare that they have no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Recent developments in urological implants have focused on preventive strategies to mitigate encrustation and biofilm formation. Parylene, a conformal, pinhole-free polymer coating, has gained attention due to its high biocompatibility and chemical resistance, excellent barrier properties, and low friction coefficient. This study aims to evaluate the effectiveness of parylene C in comparison to a parylene VT4 grade coating in preventing encrustation on a urinary bladder pressure MEMS sensor system. Additionally, silicon oxide (SiO x ) applied as a finish coating was investigated for further improvements. An in vitro encrustation system mimicking natural urine flow was used to quantify the formation of urinary stones. These stones were subsequently analyzed using Fourier transform infrared spectrometry (FTIR). Encrustation results were then discussed in relation to coating surface chemical properties. Parylene C and VT4 grades demonstrated a very low encrustation mass, making them attractive options for encrustation prevention. The best performance was achieved after the addition of a hydrophilic SiO x finish coating on parylene VT4 grade. Parylene-based encapsulation proved to be an outstanding solution to prevent encrustation for urological implants.

While water vapor transmission rate (WVTR) measurement is standardly used to assess material permeability, a system able to quantify liquid water transmission rate (WTR) measurement is highly desirable for implantable thin film barrier coatings. Indeed, since implantable devices are in contact or immersed in body fluids, liquid WTR was carried out to obtain a more realistic measurement of the barrier performance. Parylene is a well-established polymer which is often the material of choice for biomedical encapsulation applications due to its flexibility, biocompatibility, and attractive barrier properties. Four grades of parylene coatings were tested with a newly developed permeation measurement system based on a quadrupole mass spectrometer (QMS) detection method. Successful measurements of gas and water vapor and the water transmission rates of thin parylene films were performed and validated, comparing the results with a standardized method. In addition, the WTR results allowed for the extraction of an acceleration transmission rate factor from the vapor-to-liquid water measurement mode, which varies from 4 to 4.8 between WVTR and WTR. With a WTR of 72.5 µm g m -2 day -1 , parylene C displayed the most effective barrier performance.

Objectives: To develop a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to quantify 41 different purine and pyrimidine (PuPy) metabolites in human urine to allow detection of most known disorders in this metabolic pathway and to determine reference intervals., Methods: Urine samples were diluted with an aqueous buffer to minimize ion suppression. For detection and quantification, liquid chromatography was combined with electrospray ionization, tandem mass spectrometry and multiple reaction monitoring. Transitions and instrument settings were established to quantify 41 analytes and nine stable-isotope-labeled internal standards (IS)., Results: The established method is precise (intra-day CV: 1.4-6.3%; inter-day CV: 1.3-15.2%), accurate (95.2% external quality control results within ±2 SD and 99.0% within ±3 SD; analyte recoveries: 61-121%), sensitive and has a broad dynamic range to quantify normal and pathological metabolite concentrations within one run. All analytes except aminoimidazole ribonucleoside (AIr) are stable before, during and after sample preparation. Moreover, analytes are not affected by five cycles of freeze-thawing (variation: -5.6 to 7.4%), are stable in thymol (variation: -8.4 to 12.9%) and the lithogenic metabolites also in HCl conserved urine. Age-dependent reference intervals from 3,368 urine samples were determined and used to diagnose 11 new patients within 7 years (total performed tests: 4,206)., Conclusions: The presented method and reference intervals enable the quantification of 41 metabolites and the potential diagnosis of up to 25 disorders of PuPy metabolism., (© 2023 Walter de Gruyter GmbH, Berlin/Boston.)

α-linolenic acid (ALA) is an essential C-18 n-3 polyunsaturated fatty acid (PUFA), which can be elongated to longer n-3 PUFAs, such as eicosapentaenoic acid (EPA). These long-chain n-3 PUFAs have anti-inflammatory and pro-resolution effects either directly or through their oxylipin metabolites. However, there is evidence that the conversion of ALA to the long-chain PUFAs is limited. On the other hand, there is evidence in humans that supplementation of ALA in the diet is associated with an improved lipid profile, a reduction in the inflammatory biomarker C-reactive protein (CRP) and a reduction in cardiovascular diseases (CVDs) and all-cause mortality. Studies investigating the cellular mechanism for these beneficial effects showed that ALA is metabolized to oxylipins through the Lipoxygenase (LOX), the Cyclooxygenase (COX) and the Cytochrome P450 (CYP450) pathways, leading to hydroperoxy-, epoxy-, mono- and dihydroxylated oxylipins. In several mouse and cell models, it has been shown that ALA and some of its oxylipins, including 9- and 13-hydroxy-octadecatrienoic acids (9-HOTrE and 13-HOTrE), have immunomodulating effects. Taken together, the current literature suggests a beneficial role for diets rich in ALA in human CVDs, however, it is not always clear whether the described effects are attributable to ALA, its oxylipins or other substances present in the supplemented diets.

Background: While lipid emulsions in modern formulations for total parenteral nutrition (TPN) provide essential fatty acids and dense calories, they also promote inflammation and immunometabolic disruptions., Objectives: We aimed to develop a novel lipid emulsion for TPN use with superior immunometabolic actions compared with available standard lipid emulsions., Methods: A novel lipid emulsion [Vegaven (VV)] containing 30% of 18-carbon n-3 fatty acids (α-linolenic acid and stearidonic acid) was developed for TPN (VV-TPN) and compared with TPN containing soybean oil-based lipid emulsion (IL-TPN) and fish-oil-based lipid emulsion (OV-TPN). In vivo studies were performed in instrumented male C57BL/6 mice subjected to 7-d TPN prior to analysis of cytokines, indices of whole-body and hepatic glucose metabolism, immune cells, lipid mediators, and mucosal bowel microbiome., Results: IL-6 to IL-10 ratios were significantly lower in liver and skeletal muscle of VV-TPN mice when compared with IL-TPN or OV-TPN mice. VV-TPN and OV-TPN each increased hepatic insulin receptor abundance and resulted in similar HOMA-IR values, whereas only VV-TPN increased hepatic insulin receptor substrate 2 and maintained normal hepatic glycogen content, effects that were IL-10-dependent and mediated by glucokinase activation. The percentages of IFN-γ- and IL-17-expressing CD4+ T cells were increased in livers of VV-TPN mice, and liver macrophages exhibited primed phenotypes when compared with IL-TPN. This immunomodulation was associated with successful elimination of the microinvasive bacterium Akkermansia muciniphila from the bowel mucosa by VV-TPN as opposed to standard lipid emulsions. Assay of hepatic lipid mediators revealed a distinct profile with VV-TPN, including increases in 9(S)-hydroxy-octadecatrienoic acid. When co-administered with IL-TPN, hydroxy-octadecatrienoic acids mimicked the VV-TPN immunometabolic phenotype., Conclusions: We here report the unique anti-inflammatory, insulin-sensitizing, and immunity-enhancing properties of a newly developed lipid emulsion designed for TPN use based on 18-carbon n-3 fatty acids., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Macroenzymes are high-molecular weight forms of enzymes whose presence in human sera can lead to non-pathological, elevated enzyme activities, resulting in further unnecessary clinical evaluation. Precipitation with polyethylene glycol (PEG) is an efficient method for removing macroforms from patient samples and can therefore be used for their identification. Cut-offs (99. Percentiles) for the PEG precipitation activity (%PPA) for eight routine enzyme activities were determined on Abbott's Alinity c, namely: AST (61%), ALT (70%), GGT (41%), LDH (45%), lipase (56%), ALP (17%), CK (36%) and PAMY (45%). Two macroforms (PAMY and CK) were then identified by gel filtration chromatography. We suggest that a %PPA above the enzyme-specific cut-off makes the presence of a macroform possible while a %PPA ≥80%, i.e. markedly above the cut-off, makes it very likely for all enzymes., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Background: Lipid emulsions are a key component of total parenteral nutrition (TPN) and are administered to patients who are unable to ingest their daily required calories orally. Lipid emulsions rich with n-6 (ω-6) PUFAs are known to cause parenteral nutrition-associated liver disease and have inflammatory side effects, whereas n-3 PUFA-rich emulsions have favourable clinical outcomes., Objectives: The present study used targeted lipid mediator analysis to investigate the metabolism of a n-3 PUFA-rich lipid emulsion and a n-6 PUFA-rich lipid emulsion in a mouse model of TPN and in primary human monocyte-derived macrophages (MDMs) and CD4+ T cells., Results: Mice given n-3 PUFA-based TPN for 7 d had a less proinflammatory lipid mediator profile compared with those receiving n-6 PUFA-based TPN. This was characterized by higher concentrations of specialized pro-resolving mediators (SPMs) and endocannabinoids, including resolvin D (RvD) 1, maresin (MaR) 1, MaR2, protectin D1 (PD1), protectin DX (PDX), and the endocannabinoids eicosapentaenoyl ethanolamide (EPEA) and docosahexaenoyl ethanolamide (DHEA) in the liver and RvD1, 17R-RvD1, RvD2, RvD3, RvD5, MaR1, MaR2, PD1, PDX, and EPEA and DHEA in the spleen. The spleen was identified as a source of high lipid mediator and SPM formation as lipid mediator concentrations were on average 25-fold higher than in the liver. Additionally, n-3 PUFA-treated primary human MDMs produced RvD5 and the endocannabinoids EPEA and DHEA, which was associated with an increased IL-10 secretion. In contrast, primary human CD4+ T cells showed only an increase in SPM precursors and an increase in the endocannabinoids EPEA and DHEA, which was associated with reduced cytokine expression., Conclusions: This demonstrates that lipid mediators, particularly SPMs and endocannabinoids from spleen, could play a key role in facilitating the favorable clinical outcomes associated with the use of n-3 PUFA-rich lipid emulsions in TPN., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Lipid emulsions are crucial for life-saving total parenteral nutrition (TPN). Their composition provides a high amount of essential fatty acids and calories for millions of patients with serious diseases. Nevertheless, several TPN-mediated side-effects have been reported in over 90% of patients. This project aimed to investigate the effect of a high amount of ω3 fatty acids (Omegaven ® ) emulsion vs. a high amount of ω6 fatty acids (Intralipid ® ) emulsions on the endothelial barrier function. EA.hy926 cell line was cultured and incubated with 0.01, 0.1, and 1 mM lipid emulsions. The influence of these lipid emulsions on the barrier function was assessed using ECIS technology, immunofluorescent microscopy, viability measurements by flow cytometry, multiplex cytokines analysis, and qRT-PCR. BODIPY staining confirmed the uptake of fatty acids by endothelial cells. ECIS measurements demonstrated that a high concentration of Omegaven ® prevents barrier formation and impairs the barrier function by inducing cell detachment. Moreover, the expression of VE-cadherin and F-actin formation showed a reorganization of the cell structure within 2 h of 1 mM Omegaven ® addition. Interestingly, the study's findings contradict previous studies and revealed that Omegaven ® at high concentration, but not Intralipid, induces cell detachments, impairing endothelial cells' barrier function. In summary, our studies shed new light on the effect of lipid emulsions on the endothelium.

Background & Aims: Total parenteral nutrition (TPN) causes gut atrophy, dysbiosis and leakage of the gut barrier. This study aimed to characterize the gut microbiome in response to different TPNs and tested the hypothesis whether increased gut permeability in TPN would lead to changes in the circulating bacterial DNA ("blood microbiome")., Methods: Male C57BL/6J mice were randomly allocated to the following groups for seven days (1) chow-fed control (C) without jugular vein catheter (JVC, n=6) (2) chow-fed with JVC and infusion of saline (S) (n = 6) (3) Intralipid-based TPN (n-6:n-3 ratio 7:1) (IL, n = 6) (4) Omegaven-based TPN (n-6:n-3 ratio 1:8) (OV, n = 6). Blood was collected by cardiac puncture and feces (stool pellet) were collected from the colon. Blood and stool samples were analyzed by 16S rRNA gene sequencing., Results: TPN administration was associated with a compositional shift in the gut microbial community that involved the expansion of Bacteroidota along with a decrease in gut bacteria belonging to the Firmicutes phylum as compared to chow-fed mice. Gram-negative Verrucomicrobiota and Proteobacteria were also increased in the gut microbiome of mice receiving TPN. Gammaproteobacteria, namely Burkholderiales, were specifically increased in Intralipid-based TPN. On the other hand, Proteobacteria and Actinobacteriota were the dominant taxa in blood samples. The families Comamonadaceae and Burkholderiaceae (both from Burkholderiales order) were increased in the "blood microbiome" of mice with indwelling JVC when compared with chow-fed mice without JVC. The increase in Burkholderiaceae was more pronounced in Intralipid-based TPN., Conclusions: Profound changes in the gut microbiome of mice subjected to TPN occurred, which were not reflected in the "blood microbiome" suggesting that the gut and "blood microbiome" represent two rather distinct separate microbiotic compartments. The parenteral provision of n-3 fatty acids appears to protect against proinflammatory bacteria in the gut and against the increased presence of JVC-associated bacteria as measured by circulating bacterial DNA., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2022 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

Low copeptin levels may indicate inadequate arginine-vasopressin release promoting arterial hypotension, whereas high copeptin concentrations may reflect disease severity. This single-center prospective non-randomized clinical trial analyzed the course of blood copeptin in critically ill normo- and hypotensive children and its association with disease severity. In 164 patients (median age 0.5 years (interquartile range 0.1, 2.9)), the mean copeptin concentration at baseline was 43.5 pmol/L. Though not significantly different after 61 h (primary outcome, mean individual change: −12%, p = 0.36, paired t-test), we detected 1.47-fold higher copeptin concentrations during arterial hypotension when compared to normotension (mixed-effect ANOVA, p = 0.01). In total, 8 out of 34 patients (23.5%) with low copeptin concentrations <10 pmol/L were hypotensive. Copeptin was highest in the adjusted mixed-effect regression analysis within the first day (+20% at 14 h) and decreased significantly at 108 h (−27%) compared to baseline (p = 0.002). Moreover, we found a significant association with vasopressor-inotrope treatment intensity, infancy (1−12 months) and cardiopulmonary bypass (all p ≤ 0.001). In conclusion, high copeptin values were associated with arterial hypotension and severity of disease in critically ill children. This study does not support the hypothesis that low copeptin values might be indicative of arginine-vasopressin deficiency.

Objectives: Pathologic ejection fraction (EF), shortening fraction (FS), and standard heart failure biomarkers (high sensitive troponin T and N-terminal brain natriuretic peptide) during follow-up after childhood cancer have been associated with irreversible cardiac damage. We aimed to evaluate strain imaging values by echocardiography and new biomarkers for heart failure with preserved ejection fraction (HFpEF) as potential more sensitive parameters for cardiac deterioration in childhood cancer survivors (CCS)., Materials and Methods: Prospective study with 50 CCS (median 16.2 y) at a median follow-up of 13 years. In addition to standard echo and laboratory parameters for heart failure, strain measurements and new biomarkers, including myocardial inflammation (interleukin 6), extracellular matrix (ECM) remodeling (C-telopeptide for type I collagen, intact N-terminal propeptide of type III procollagen), and other heart failure biomarkers (galectin 3, solutable ST2, growth differentiation factor 15), were obtained and compared with 50 healthy controls., Results: No significant differences in EF, FS, high sensitive troponin T, N-terminal brain natriuretic peptide, interleukin 6, solutable ST2, and galectin 3 were found between study and control groups. In contrast, strain imaging showed significant differences between both groups (global longitudinal strainGLS -16.1% vs. -20.4%, P<0.0001; global circumferential strain -14.3 vs. -21.4%, P<0.0001), detecting 66% (global longitudinal strain) and 76% (global circumferential strain) of patients with pathologic values in contrast to 6% (EF) and 16% (FS) for standard parameters. Markers for disturbances of ECM remodeling (C-telopeptide for type I collagen, intact N-terminal propeptide of type III procollagen, each P<0.0001) and growth differentiation factor 15 (P<0.0001) were significantly different between the groups., Conclusion: Strain imaging and new cardiac biomarkers used in HFpEF focusing on ECM remodeling appear to be more sensitive in detecting early remodeling processes in CCS than standard echo and laboratory parameters., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: Quantitative measurement of plasma free hemoglobin (fHb) concentrations is essential for monitoring pediatric ECMO patients, since hemolysis has a great impact on the patient's clinical outcome. The aim of this study was to validate the hemolysis index (HI) assay on Abbott's Alinity c system as a quantitative method to measure fHb., Methods: The performance of the HI assay, based on an automated spectrophotometric method recording the absorption at four different wavelength pairs, was evaluated using the 20 × 2 × 2 design according to the CLSI-EP05-A3 guidelines. LLOQ and LLOD were calculated according to CLSI-EP17 guidelines with CVs set to 10% and 20%, respectively. Furthermore, the method was tested for interferences with bilirubin and Intralipid®., Results: Linearity was ensured over an analytical measurement range of 30-7250 mg/L and the calculated LLOQ and LLOD were 80 mg/L and 50 mg/L, respectively. Intra-run and total imprecisions ranged from 0.9-3.4% and 1.0-3.4%, respectively. The HI assay correlated well with the Harboe method (HI (mg/L) = 0.998 * fHb (mg/L) + 28 mg/L, R = 0.998, n = 50) and interference testing showed no impact of bilirubin and Intralipid® up to 709 mg/L and 5580 mg/L, respectively., Conclusions: The HI assay on Abbott's Alinity c system allows a precise and accurate determination of fHb concentrations with no significant interferences in a simple, rapid and cost-effective way., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Obesity leads to chronic inflammation of the adipose tissue which is tightly associated with the metabolic syndrome, type 2 diabetes and cardiovascular disease. Inflammation of the adipose tissue is mainly characterized by the presence of crown-like structures composed of inflammatory macrophages in the neighborhood of adipocytes. Resolvin D1 (RvD1), a potent anti-inflammatory and pro-resolving lipid mediator derived from the omega-3 fatty acid docosahexaenoic acid, has been shown to reduce the inflammatory tone of adipose tissue in animal models but the underlying mechanism is not clear. We investigated the effect of RvD1 on the inflammatory state of a human co-culture system of adipocytes and macrophages. For this, human mesenchymal stem cells were differentiated into mature adipocytes and overlaid with human primary macrophages. In this co-culture, 10-500 nM RvD1 dose-dependently reduced the secretion of the pro-inflammatory cytokine IL-6 (-21%) and its soluble receptor IL-6Rα (-22%), of the chemokine MCP-1 (-13%), and of the adipokine leptin (-22%). Similarly, we observed a reduction in secretion of the soluble receptor IL-6Rα (-20%), and TNF-α (-11%) when macrophages alone were treated with RvD1, while no change of cytokine secretion was observed when adipocytes were treated with RvD1. We conclude that RvD1 polarizes macrophages to an anti-inflammatory phenotype, which in turn modulates inflammation in adipocytes., (Copyright © 2021. Published by Elsevier Ltd.)